Role of the offshore Pedro Banks left-lateral strike-slip fault zone in the plate tectonic evolution of the northern Caribbean

NASA Astrophysics Data System (ADS)

Ott, B.; Mann, P.; Saunders, M.

2013-12-01

Previous workers, mainly mapping onland active faults on Caribbean islands, defined the northern Caribbean plate boundary zone as a 200-km-wide bounded by two active and parallel strike-slip faults: the Oriente fault along the northern edge of the Cayman trough with a GPS rate of 14 mm/yr, and and the Enriquillo-Plaintain Garden fault zone (EPGFZ) with a rate of 5-7 mm/yr. In this study we use 5,000 km of industry and academic data from the Nicaraguan Rise south and southwest of the EPGFZ in the maritime areas of Jamaica, Honduras, and Colombia to define an offshore, 700-km-long, active, left-lateral strike-slip fault in what has previously been considered the stable interior of the Caribbean plate as determined from plate-wide GPS studies. The fault was named by previous workers as the Pedro Banks fault zone because a 100-km-long segment of the fault forms an escarpment along the Pedro carbonate bank of the Nicaraguan Rise. Two fault segments of the PBFZ are defined: the 400-km-long eastern segment that exhibits large negative flower structures 10-50 km in width, with faults segments rupturing the sea floor as defined by high resolution 2D seismic data, and a 300-km-long western segment that is defined by a narrow zone of anomalous seismicity first observed by previous workers. The western end of the PBFZ terminates on a Quaternary rift structure, the San Andres rift, associated with Plio-Pleistocene volcanism and thickening trends indicating initial rifting in the Late Miocene. The southern end of the San Andreas rift terminates on the western Hess fault which also exhibits active strands consistent with left-lateral, strike-slip faults. The total length of the PBFZ-San Andres rift-Southern Hess escarpment fault is 1,200 km and traverses the entire western end of the Caribbean plate. Our interpretation is similar to previous models that have proposed the "stable" western Caribbean plate is broken by this fault whose rate of displacement is less than the threshold recognizable from the current GPS network (~3 mm/yr). The Late Miocene age of the fault indicates it may have activated during the Late Miocene to recent Hispaniola-Bahamas oblique collision event.

Role of IL-9 and STATs in hematological malignancies (Review).

PubMed

Chen, Na; Wang, Xin

2014-03-01

Although interleukin-9 (IL-9) exhibits pleiotropic functions in the immune system, it remains a well-known cytokine in hematological malignancies. Previous cell culture and animal model studies have revealed that the Janus kinase-signal transducer and activator of transcription signaling pathway, which may be activated by a number of cytokines including IL-9, is critical in hematological malignancies. The current review summarizes the characterization of the biological activities of IL-9, highlights the clearly defined roles of the cytokine, and outlines questions with regard to the functions of IL-9 that require further exploration and their downstream signaling proteins, signal transducers and activators of transcription.

shinyGISPA: A web application for characterizing phenotype by gene sets using multiple omics data combinations.

PubMed

Dwivedi, Bhakti; Kowalski, Jeanne

2018-01-01

While many methods exist for integrating multi-omics data or defining gene sets, there is no one single tool that defines gene sets based on merging of multiple omics data sets. We present shinyGISPA, an open-source application with a user-friendly web-based interface to define genes according to their similarity in several molecular changes that are driving a disease phenotype. This tool was developed to help facilitate the usability of a previously published method, Gene Integrated Set Profile Analysis (GISPA), among researchers with limited computer-programming skills. The GISPA method allows the identification of multiple gene sets that may play a role in the characterization, clinical application, or functional relevance of a disease phenotype. The tool provides an automated workflow that is highly scalable and adaptable to applications that go beyond genomic data merging analysis. It is available at http://shinygispa.winship.emory.edu/shinyGISPA/.

shinyGISPA: A web application for characterizing phenotype by gene sets using multiple omics data combinations

PubMed Central

Dwivedi, Bhakti

2018-01-01

While many methods exist for integrating multi-omics data or defining gene sets, there is no one single tool that defines gene sets based on merging of multiple omics data sets. We present shinyGISPA, an open-source application with a user-friendly web-based interface to define genes according to their similarity in several molecular changes that are driving a disease phenotype. This tool was developed to help facilitate the usability of a previously published method, Gene Integrated Set Profile Analysis (GISPA), among researchers with limited computer-programming skills. The GISPA method allows the identification of multiple gene sets that may play a role in the characterization, clinical application, or functional relevance of a disease phenotype. The tool provides an automated workflow that is highly scalable and adaptable to applications that go beyond genomic data merging analysis. It is available at http://shinygispa.winship.emory.edu/shinyGISPA/. PMID:29415010

Refusal skill ability: an examination of adolescent perceptions of effectiveness.

PubMed

Nichols, Tracy R; Birnel, Sara; Graber, Julia A; Brooks-Gunn, Jeanne; Botvin, Gilbert J

2010-06-01

This pilot study examined whether refusal assertion as defined by a proven drug prevention program was associated with adolescent perceptions of effectiveness by comparing two sets of coded responses to adolescent videotaped refusal role-plays (N = 63). The original set of codes was defined by programmatic standards of refusal assertion and the second by a group of high school interns. Consistency with programming criteria was found for interns' ratings of several indicators of verbal and non-verbal assertiveness. However, a strategy previously defined by the program as effective was perceived as ineffective by adolescents while another deemed ineffective and problematic by intervention developers was viewed as effective. Interns endorsed presenting detailed and reasonable arguments as an effective refusal strategy while short, simple statements were deemed ineffective. This study suggests the importance of including adolescent perspectives in the design, delivery, and evaluation of drug prevention strategies.

High-dose etoposide (VP-16)-containing preparatory regimens in allogeneic and autologous bone marrow transplantation for hematologic malignancies.

PubMed

Blume, K G; Forman, S J

1992-12-01

High-dose etoposide has been added to total body irradiation, cyclophosphamide, carmustine, or busulfan in preparatory regimens for allogeneic or autologous bone marrow transplantation for patients with leukemia, Hodgkin's disease, lymphoma, or multiple myeloma. The treatment results are encouraging, indicating that etoposide may be a valuable addition to the previously established regimens. Etoposide should be incorporated into collaborative, prospective trials to define its ultimate role in bone marrow transplantation.

Overweight individuals are at increased risk for thrombotic thrombocytopenic purpura.

PubMed

Nicol, Kathleen K; Shelton, Brent J; Knovich, Mary Ann; Owen, John

2003-11-01

Our understanding of the pathophysiology of thrombotic thrombocytopenic purpura, TTP, has increased dramatically in the past few years with the identification of the role of ADAMTS13. Nonetheless, risk factors for the development of acute TTP are few. Informally, obesity was felt to be common in patients with TTP and so a formal study was undertaken to further define this association. We report our data in 105 patients with classical TTP as defined by thrombocytopenia and microangiopathic hemolytic anemia. We found that marked obesity is a previously unrecognized risk factor with an associated odds ratio of 7.6. Interestingly, despite this increased risk, obesity might well be associated with lower mortality, although this did not reach statistical significance. Copyright 2003 Wiley-Liss, Inc.

Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: a prospective cohort study

PubMed Central

2012-01-01

Introduction Acute deterioration of cirrhosis is associated with high mortality rates particularly in the patients who develop organ failure (OF), a condition that is referred to as acute-on-chronic liver failure (ACLF), which is currently not completely defined. This study aimed to determine the role of predisposing factors, the nature of the precipitating illness and inflammatory response in the progression to OF according to the PIRO (predisposition, injury, response, organ failure) concept to define the risk of in-hospital mortality. Methods A total of 477 patients admitted with acute deterioration of cirrhosis following a defined precipitant over a 5.5-year period were prospectively studied. Baseline clinical, demographic and biochemical data were recorded for all patients and extended serial data from the group that progressed to OF were analysed to define the role of PIRO in determining in-hospital mortality. Results One hundred and fifty-nine (33%) patients developed OF, of whom 93 patients died (58%) compared with 25/318 (8%) deaths in the non-OF group (P < 0.0001). Progression to OF was associated with more severe underlying liver disease and inflammation. In the OF group, previous hospitalisation (P of PIRO); severity of inflammation and lack of its resolution (R of PIRO); and severity of organ failure (O of PIRO) were associated with significantly greater risk of death. In the patients who recovered from OF, mortality at three years was almost universal. Conclusions The results of this prospective study shows that the occurrence of OF alters the natural history of cirrhosis. A classification based on the PIRO concept may allow categorization of patients into distinct pathophysiologic and prognostic groups and allow a multidimensional definition of ACLF. PMID:23186071

The Role of Copy Number Variation in Susceptibility to Amyotrophic Lateral Sclerosis: Genome-Wide Association Study and Comparison with Published Loci

PubMed Central

Wain, Louise V.; Pedroso, Inti; Landers, John E.; Breen, Gerome; Shaw, Christopher E.; Leigh, P. Nigel; Brown, Robert H.

2009-01-01

Background The genetic contribution to sporadic amyotrophic lateral sclerosis (ALS) has not been fully elucidated. There are increasing efforts to characterise the role of copy number variants (CNVs) in human diseases; two previous studies concluded that CNVs may influence risk of sporadic ALS, with multiple rare CNVs more important than common CNVs. A little-explored issue surrounding genome-wide CNV association studies is that of post-calling filtering and merging of raw CNV calls. We undertook simulations to define filter thresholds and considered optimal ways of merging overlapping CNV calls for association testing, taking into consideration possibly overlapping or nested, but distinct, CNVs and boundary estimation uncertainty. Methodology and Principal Findings In this study we screened Illumina 300K SNP genotyping data from 730 ALS cases and 789 controls for copy number variation. Following quality control filters using thresholds defined by simulation, a total of 11321 CNV calls were made across 575 cases and 621 controls. Using region-based and gene-based association analyses, we identified several loci showing nominally significant association. However, the choice of criteria for combining calls for association testing has an impact on the ranking of the results by their significance. Several loci which were previously reported as being associated with ALS were identified here. However, of another 15 genes previously reported as exhibiting ALS-specific copy number variation, only four exhibited copy number variation in this study. Potentially interesting novel loci, including EEF1D, a translation elongation factor involved in the delivery of aminoacyl tRNAs to the ribosome (a process which has previously been implicated in genetic studies of spinal muscular atrophy) were identified but must be treated with caution due to concerns surrounding genomic location and platform suitability. Conclusions and Significance Interpretation of CNV association findings must take into account the effects of filtering and combining CNV calls when based on early genome-wide genotyping platforms and modest study sizes. PMID:19997636

Toward Understanding the Nature of a Partnership Between an Elementary Classroom Teacher and an Informal Science Educator

NASA Astrophysics Data System (ADS)

Weiland, Ingrid S.; Akerson, Valarie L.

2013-12-01

This study explored the nature of the relationship between a fifth-grade teacher and an informal science educator as they planned and implemented a life science unit in the classroom, and sought to define this relationship in order to gain insight into the roles of each educator. In addition, student learning as a result of instruction was assessed. Prior research has predominately examined relationships and roles of groups of teachers and informal educators in the museum setting (Tal et al. in Sci Educ 89:920-935, 2005; Tal and Steiner in Can J Sci Math Technol Educ 6:25-46, 2006; Tran 2007). The current study utilized case study methodology to examine one relationship (between two educators) in more depth and in a different setting—an elementary classroom. The relationship was defined through a framework of cooperation, coordination, and collaboration (Buck 1998; Intriligator 1986, 1992) containing eight dimensions. Findings suggest a relationship of coordination, which requires moderate commitment, risk, negotiation, and involvement, and examined the roles that each educator played and how they negotiated these roles. Consistent with previous examinations in science education of educator roles, the informal educator's role was to provide the students with expertise and resources not readily available to them. The roles played by the classroom teacher included classroom management, making connections to classroom activities and curricula, and clarifying concepts. Both educators' perceptions suggested they were at ease with their roles and that they felt these roles were critical to the optimization of the short time frames (1 h) the informal educator was in the classroom. Pre and posttest tests demonstrated students learned as a result of the programs.

The snake on the caduceus: dimensions of medical and psychiatric responsibility in the Third Reich.

PubMed

Hunter, E

1993-03-01

The literature on the activities of medical professionals during the tumultuous years of the Third Reich has, over the last decade, increased substantially. However, many questions remain unanswered and the subject is likely to receive further attention following recent access to previously restricted archival material in Eastern Europe. In this paper, based on the English language literature, the author explores the role of medicine, and in particular psychiatry, in defining the bio-medical vision that was central to Nazi ideology.

[Therapeutic nursing: a systematic review].

PubMed

Lautenschläger, S; Müller, C; Immenschuh, U; Muser, J; Behrens, J

2014-08-01

For some years therapeutic service catalogues have been established in medical rehabilitation which have broadened our previous understanding of nursing actions. Currently, therapeutic nursing plays a prominent role in neurological early rehabilitation because the operations and procedures coding system (OPS) 8-552 within the DRG-System (Diagnosis Related Groups) states that therapeutic nursing must be carried out by specially trained nursing personnel. This requirement leads to inconsistencies in nursing practice and the medical service of the health insurance (MDK) since a definition of therapeutic nursing is lacking. A previous review of therapeutic nursing in 2003 focused primarily on the development of the therapeutic nursing role, but not on therapeutic nursing itself. The following article contains the first systematic review of the current state of research regarding a definition of therapeutic nursing. For this purpose, a systematic study was conducted to examine if there are, nationally or internationally, any definitions of therapeutic nursing and to identify what the therapeutic aspects of nursing are. The research included following database; Medline, Cinahl and Embase. Additionally, a research by hand of several German journals as well as textbooks and specialized literature was carried out. 5 studies were selected which define the term "therapeutic nursing". Among these are one review, one primary study, one theoretical discussion and one dissertation. Further twenty four studies were identified which do not define the term, but are closely related to the subject, and use or characterize the term in various contexts. The publications examined provided indications of duties, interventions and roles nurses should perform, but not how to carry these out, nor what is therapeutic about the nursing. At the same time, the low number of studies reveals that therapeutic nursing has barely been examined and demonstrates the lack of theoretically grounding through nursing science. © Georg Thieme Verlag KG Stuttgart · New York.

Spatial but not object memory impairments in children with fetal alcohol syndrome.

PubMed

Uecker, A; Nadel, L

1998-07-01

Behavioral dissociations on tests of cognitive abilities are powerful tools that can help define the neuropsychology of developmentally disabling conditions. Animals gestationally exposed to alcohol demonstrate spatial (place) but not object (cue) memory impairments. Whether children with fetal alcohol syndrome demonstrate a similar dissociation has received little attention. In this experiment, 30 Native American children, 15 previously identified with fetal alcohol syndrome and 15 control children, were asked to recall places and objects in a task previously shown to be sensitive to memory skills in individuals with and without mental retardation. As in animal models, children with fetal alcohol syndrome demonstrated a spatial but not an object memory impairment. A possible role for the hippocampus was discussed.

Social Noise: Generating Random Numbers from Twitter Streams

NASA Astrophysics Data System (ADS)

Fernández, Norberto; Quintas, Fernando; Sánchez, Luis; Arias, Jesús

2015-12-01

Due to the multiple applications of random numbers in computer systems (cryptography, online gambling, computer simulation, etc.) it is important to have mechanisms to generate these numbers. True Random Number Generators (TRNGs) are commonly used for this purpose. TRNGs rely on non-deterministic sources to generate randomness. Physical processes (like noise in semiconductors, quantum phenomenon, etc.) play this role in state of the art TRNGs. In this paper, we depart from previous work and explore the possibility of defining social TRNGs using the stream of public messages of the microblogging service Twitter as randomness source. Thus, we define two TRNGs based on Twitter stream information and evaluate them using the National Institute of Standards and Technology (NIST) statistical test suite. The results of the evaluation confirm the feasibility of the proposed approach.

The ROCK isoforms differentially regulate the morphological characteristics of carcinoma cells.

PubMed

Jerrell, Rachel J; Leih, Mitchell J; Parekh, Aron

2017-06-26

Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between 2 modes of migration, mesenchymal and amoeboid. Changes in ROCK activity can cause a switch between these migration phenotypes which are defined by distinct morphologies. However, recent studies have shown that the ROCK isoforms are not functionally redundant as previously thought. Therefore, it is unclear whether the ROCK isoforms play different roles in regulating migration phenotypes. Here, we found that ROCK1 and ROCK2 differentially regulate carcinoma cell morphology resulting in intermediate phenotypes that share some mesenchymal and amoeboid characteristics. These findings suggest that the ROCK isoforms play unique roles in the phenotypic plasticity of mesenchymal carcinoma cells which may have therapeutic implications.

Signal transduction mechanisms in plants: an overview

NASA Technical Reports Server (NTRS)

Clark, G. B.; Thompson, G. Jr; Roux, S. J.

2001-01-01

This article provides an overview on recent advances in some of the basic signalling mechanisms that participate in a wide variety of stimulus-response pathways. The mechanisms include calcium-based signalling, G-protein-mediated-signalling and signalling involving inositol phospholipids, with discussion on the role of protein kinases and phosphatases interspersed. As a further defining feature, the article highlights recent exciting findings on three extracellular components that have not been given coverage in previous reviews of signal transduction in plants, extracellular calmodulin, extracellular ATP, and integrin-like receptors, all of which affect plant growth and development.

Redesigning a risk-management process for tracking injuries.

PubMed

Wenzel, G R

1998-01-01

The changing responsibilities of registered nurses are challenging even the most dedicated professionals. To survive within her newly-defined roles, one nurse used a total quality improvement model to understand, analyze, and improve a medical center's system for tracking inpatient injuries. This process led to the drafting of an original software design that implemented a nursing informatics tracking system. It has resulted in significant savings of time and money and has far surpassed the accuracy, efficiency, and scope of the previous method. This article presents an overview of the design process.

The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

PubMed

Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

2017-04-01

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

Computer analysis of multicircuit shells of revolution by the field method

NASA Technical Reports Server (NTRS)

Cohen, G. A.

1975-01-01

The field method, presented previously for the solution of even-order linear boundary value problems defined on one-dimensional open branch domains, is extended to boundary value problems defined on one-dimensional domains containing circuits. This method converts the boundary value problem into two successive numerically stable initial value problems, which may be solved by standard forward integration techniques. In addition, a new method for the treatment of singular boundary conditions is presented. This method, which amounts to a partial interchange of the roles of force and displacement variables, is problem independent with respect to both accuracy and speed of execution. This method was implemented in a computer program to calculate the static response of ring stiffened orthotropic multicircuit shells of revolution to asymmetric loads. Solutions are presented for sample problems which illustrate the accuracy and efficiency of the method.

Proposing an Operational Definition of Science Teacher Beliefs

NASA Astrophysics Data System (ADS)

Hutner, Todd L.; Markman, Arthur B.

2016-10-01

Much research has shown that a science teacher's beliefs are related to their teaching practice. This line of research has often defined "belief" epistemologically. That is, beliefs are often defined relative to other mental constructs, such as knowledge, dispositions, or attitudes. Left unspecified is the role beliefs play in cognition and how they come to influence science teachers' classroom practice. As such, researchers and science teacher educators have relied on an (at times, implicit) assumption that there is a direct causal relationship between teachers' beliefs and classroom practice. In this paper, we propose an operational, as opposed to epistemological, definition of belief. That is, we are explicit about the role a belief plays in science teachers' cognition and how that leads to classroom practice. We define a belief as a mental representation that influences the practice of a teacher if and only if the belief is active in cognition. We then turn our attention to two limitations in the literature on that have arisen via previous definitions and assumptions regarding science teacher beliefs, showing how defining beliefs operationally helps think about these issues in new ways. The two limitations surround: (1) the difficulty in precisely delineating belief from knowledge; and (2) the interconnectedness of beliefs such that they draw meaning from one another. We then show how our definition of beliefs is congruent with other models of teacher cognition reported in the literature. Finally, we provide implications arising from this definition of belief for both science teacher educators and those who conduct research on the beliefs of both preservice and in-service science teachers.

Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.

PubMed

Alzan, Heba F; Knowles, Donald P; Suarez, Carlos E

2016-11-01

Apicomplexa tick-borne hemoparasites, including Babesia bovis, Babesia microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis, respectively. These parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate and tick hosts. Large gaps in knowledge concerning the mechanisms used by these parasites for gene regulation remain. Regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families are known to play crucial roles as transcription factors. Although the repertoire of Api-AP2 has been defined and a HMG gene was previously identified in the B. bovis genome, these regulatory genes have not been described in detail in B. microti and T. equi. In this study, comparative bioinformatics was used to: (i) identify and map genes encoding for these transcription factors among three parasites' genomes; (ii) identify a previously unreported HMG gene in B. microti; (iii) define a repertoire of eight conserved Myb genes; and (iv) identify AP2 correlates among B. bovis and the better-studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three gene families in B. bovis erythrocyte stage parasites. Sequence comparisons show conservation of functional domains and general architecture in the AP2, Myb, and HMG proteins, which may be significant for the regulation of common critical parasite life cycle transitions in B. bovis, B. microti, and T. equi. A detailed understanding of the role of gene families encoding DNA binding proteins will provide new tools for unraveling regulatory mechanisms involved in B. bovis, B. microti, and T. equi life cycles and environmental adaptive responses and potentially contributes to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis.

Mechanisms of Hypertension: The Expanding Role of Aldosterone

PubMed Central

FREEL, E. MARIE; CONNELL, JOHN M.C.

2005-01-01

Hypertension is a common disorder that affects a large heterogeneous patient population. Subgroups can be identified on the basis of their responses to hormonal and biologic stimuli. These subgroups include low-renin hypertensives and nonmodulators. Aldosterone, the principal human mineralocorticoid, is increasingly recognized as playing a significant role in cardiovascular morbidity, and its role in hypertension has recently been reevaluated with studies that suggest that increased aldosterone biosynthesis (as defined by an elevated aldosterone to renin ratio) is a key phenotype in up to 15% of individuals with hypertension. It was reported previously that a polymorphism of the gene (C to T conversion at position −344) encoding aldosterone synthase is associated with hypertension, particularly in individuals with a high ratio. However, the most consistent association with this variant is a relative impairment of adrenal 11β-hydroxylation. This review explores the evidence for this and provides a hypothesis linking impaired 11β-hydroxylation and hypertension with a raised aldosterone to renin ratio. It is also speculated that there is substantial overlap between this group of patients and previously identified low-renin hypertensives and nonmodulators. Thus, these groups may form a neurohormonal spectrum reflecting different stages of hypertension or indeed form sequential steps in the natural history of hypertension in genetically susceptible individuals. PMID:15284285

CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease.

PubMed

Kadivar, Mohammad; Petersson, Julia; Svensson, Lena; Marsal, Jan

2016-12-15

γδ T cells have been attributed a wide variety of functions, which in some cases may appear as contradictory. To better understand the enigmatic biology of γδ T cells it is crucial to define the constituting subpopulations. γδ T cells have previously been categorized into two subpopulations: CD8αα + and CD8 - cells. In this study we have defined and characterized a novel subset of human γδ T-cells expressing CD8αβ. These CD8αβ + γδ T cells differed from the previously described γδ T cell subsets in several aspects, including the degree of enrichment within the gut mucosa, the activation status in blood, the type of TCRδ variant used in blood, and small but significant differences in their response to IL-2 stimulation. Furthermore, the novel subset expressed cytotoxic mediators and CD69, and produced IFN-γ and TNF-α. In patients with active inflammatory bowel disease the mucosal frequencies of CD8αβ + γδ T cells were significantly lower as compared with healthy controls, correlated negatively with the degree of disease activity, and increased to normal levels as a result of anti-TNF-α therapy. In conclusion, our results demonstrate that CD8αβ + γδ T cells constitute a novel lymphocyte subset, which is strongly enriched within the gut and may play an important role in gut homeostasis and mucosal healing in inflammatory bowel disease. Copyright © 2016 by The American Association of Immunologists, Inc.

The role of regulatory B cells in digestive system diseases.

PubMed

Zhou, Zhenyu; Gong, Lei; Wang, Xiaoyun; Hu, Zhen; Wu, Gaojue; Tang, Xuejun; Peng, Xiaobin; Tang, Shuan; Meng, Miao; Feng, Hui

2017-04-01

The past decade has provided striking insights into a newly identified subset of B cells known as regulatory B cells (Bregs). In addition to producing antibody, Bregs also regulate diseases via cytokine production and antigen presentation. This subset of B cells has protective and potentially therapeutic effects. However, the particularity of Bregs has caused some difficulties in conducting research on their roles. Notably, human B10 cells, which are Bregs that produce interleukin 10, share phenotypic characteristics with other previously defined B cell subsets, and currently, there is no known surface phenotype that is unique to B10 cells. An online search was performed in the PubMed and Web of Science databases for articles published providing evidences on the role of regulatory B cells in digestive system diseases. Abundant evidence has demonstrated that Bregs play a regulatory role in inflammatory, autoimmune, and tumor diseases, and regulatory B cells play different roles in different diseases, but future work needs to determine the mechanisms by which Bregs are activated and how these cells affect their target cells.

Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli

PubMed Central

Scott, Barry; Young, Carolyn A.; Saikia, Sanjay; McMillan, Lisa K.; Monahan, Brendon J.; Koulman, Albert; Astin, Jonathan; Eaton, Carla J.; Bryant, Andrea; Wrenn, Ruth E.; Finch, Sarah C.; Tapper, Brian A.; Parker, Emily J.; Jameson, Geoffrey B.

2013-01-01

The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse). This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis. PMID:23949005

Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle.

PubMed

Vlahovich, Nicole; Kee, Anthony J; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S; Parton, Robert G; Gunning, Peter W; Hardeman, Edna C

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation-contraction coupling in skeletal muscle.

Cytoskeletal Tropomyosin Tm5NM1 Is Required for Normal Excitation–Contraction Coupling in Skeletal Muscle

PubMed Central

Vlahovich, Nicole; Kee, Anthony J.; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S.; Parton, Robert G.; Gunning, Peter W.

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation–contraction coupling in skeletal muscle. PMID:19005216

Retrospective analysis of Bluetongue farm risk profile definition, based on biology, farm management practices and climatic data.

PubMed

Cappai, Stefano; Loi, Federica; Coccollone, Annamaria; Contu, Marino; Capece, Paolo; Fiori, Michele; Canu, Simona; Foxi, Cipriano; Rolesu, Sandro

2018-07-01

Bluetongue (BT) is a vector-borne disease transmitted by species of Culicoides midges (Diptera: Ceratopogonidae). Many studies have contributed to clarifying various aspects of its aetiology, epidemiology and vector dynamic; however, BT remains a disease of epidemiological and economic importance that affects ruminants worldwide. Since 2000, the Sardinia region has been the most affected area of the Mediterranean basin. The region is characterised by wide pastoral areas for sheep and represents the most likely candidate region for the study of Bluetongue virus (BTV) distribution and prevalence in Italy. Furthermore, specific information on the farm level and epidemiological studies needs to be provided to increase the knowledge on the disease's spread and to provide valid mitigation strategies in Sardinia. This study conducted a punctual investigation into the spatial patterns of BTV transmission to define a risk profile for all Sardinian farmsby using a logistic multilevel mixed model that take into account agro-meteorological aspects, as well as farm characteristics and management. Data about animal density (i.e. sheep, goats and cattle), vaccination, previous outbreaks, altitude, land use, rainfall, evapotranspiration, water surface, and farm management practices (i.e. use of repellents, treatment against insect vectors, storage of animals in shelter overnight, cleaning, presence of mud and manure) were collected for 12,277 farms for the years 2011-2015. The logistic multilevel mixed model showed the fundamental role of climatic factors in disease development and the protective role of good management, vaccination, outbreak in the previous year and altitude. Regional BTV risk maps were developed, based on the predictor values of logistic model results, and updated every 10 days. These maps were used to identify, 20 days in advance, the areas at highest risk. The risk farm profile, as defined by the model, would provide specific information about the role of each factor for all Sardinian institutions involved in devising BT prevention and control strategies. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

To Care Is to Coprovide

PubMed Central

Buetow, Stephen A.

2005-01-01

Although primary care, including family medicine, recognizes different types of clinician-patient interaction, I argue that only interactions characterized by coprovision define care. By coprovision I mean that clinicians and patients each provide the expertise in health care that they have the capacity to contribute in any given situation. I argue that paternalism and consumerism cannot signify care in any real sense. Some implications of this analysis include a reconceptualization of family medicine and its defining attributes; support for features of caring relationships, such as mutual responsiveness and responsibility; and an acknowledgment that clinicians and patients need to be self-regarding as well as other-regarding. In a previous issue of the Annals, I called for a new dictionary for family medicine, one that would redefine attributes of family medicine in ways not exclusively clinician-centric. Specifically, it would acknowledge the role of patients and their informal caregivers as coproviding, not merely consuming, health care. PMID:16338920

Understanding Road Usage Patterns in Urban Areas

NASA Astrophysics Data System (ADS)

Wang, Pu; Hunter, Timothy; Bayen, Alexandre M.; Schechtner, Katja; González, Marta C.

2012-12-01

In this paper, we combine the most complete record of daily mobility, based on large-scale mobile phone data, with detailed Geographic Information System (GIS) data, uncovering previously hidden patterns in urban road usage. We find that the major usage of each road segment can be traced to its own - surprisingly few - driver sources. Based on this finding we propose a network of road usage by defining a bipartite network framework, demonstrating that in contrast to traditional approaches, which define road importance solely by topological measures, the role of a road segment depends on both: its betweeness and its degree in the road usage network. Moreover, our ability to pinpoint the few driver sources contributing to the major traffic flow allows us to create a strategy that achieves a significant reduction of the travel time across the entire road system, compared to a benchmark approach.

Skin microbiome changes in patients with interdigital tinea pedis.

PubMed

Wang, R; Song, Y; Du, M; Yang, E; Yu, J; Wan, Z; Li, R

2018-04-28

Tinea pedis is a chronic, recurrent superficial fungal infection that most commonly involves the toe web spaces. 1 Previous culture-based studies have incompletely defined the microbial landscape associated with tinea pedis, which was considered the result of infection with a single fungus. However, the recalcitrant course of the disease suggests that microbial community shifts have a role in disease pathogenesis. 2 This study was conducted to characterize the bacterial and fungal microbiome changes associated with interdigital tinea pedis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Measuring Distance of Fuzzy Numbers by Trapezoidal Fuzzy Numbers

NASA Astrophysics Data System (ADS)

Hajjari, Tayebeh

2010-11-01

Fuzzy numbers and more generally linguistic values are approximate assessments, given by experts and accepted by decision-makers when obtaining value that is more accurate is impossible or unnecessary. Distance between two fuzzy numbers plays an important role in linguistic decision-making. It is reasonable to define a fuzzy distance between fuzzy objects. To achieve this aim, the researcher presents a new distance measure for fuzzy numbers by means of improved centroid distance method. The metric properties are also studied. The advantage is the calculation of the proposed method is far simple than previous approaches.

Tropomyosin 4 defines novel filaments in skeletal muscle associated with muscle remodelling/regeneration in normal and diseased muscle.

PubMed

Vlahovich, Nicole; Schevzov, Galina; Nair-Shaliker, Visalini; Ilkovski, Biljana; Artap, Stanley T; Joya, Josephine E; Kee, Anthony J; North, Kathryn N; Gunning, Peter W; Hardeman, Edna C

2008-01-01

The organisation of structural proteins in muscle into highly ordered sarcomeres occurs during development, regeneration and focal repair of skeletal muscle fibers. The involvement of cytoskeletal proteins in this process has been documented, with nonmuscle gamma-actin found to play a role in sarcomere assembly during muscle differentiation and also shown to be up-regulated in dystrophic muscles which undergo regeneration and repair [Lloyd et al.,2004; Hanft et al.,2006]. Here, we show that a cytoskeletal tropomyosin (Tm), Tm4, defines actin filaments in two novel compartments in muscle fibers: a Z-line associated cytoskeleton (Z-LAC), similar to a structure we have reported previously [Kee et al.,2004], and longitudinal filaments that are orientated parallel to the sarcomeric apparatus, present during myofiber growth and repair/regeneration. Tm4 is upregulated in paradigms of muscle repair including induced regeneration and focal repair and in muscle diseases with repair/regeneration features, muscular dystrophy and nemaline myopathy. Longitudinal Tm4-defined filaments also are present in diseased muscle. Transition of the Tm4-defined filaments from a longitudinal to a Z-LAC orientation is observed during the course of muscle regeneration. This Tm4-defined cytoskeleton is a marker of growth and repair/regeneration in response to injury, disease state and stress in skeletal muscle.

The clinical nurse specialist in New Zealand: how is the role defined?

PubMed

Roberts, Jennifer; Floyd, Sue; Thompson, Shona

2011-07-01

New Zealand, like many countries, is developing new advanced nursing practice roles to meet emerging needs. While much has been written about the Nurse Practitioner (NP), the role of Clinical Nurse Specialist (CNS) remains relatively unexplored and lacks national definition. This paper reports the findings from research designed to investigate the role of the CNS and how it is defined by New Zealand District Health Boards (DHBs). The study sought to identify the current requirements and expectations for the CNS role and how it is defined in practice. In 2008, 15 CNS job descriptions were collected from eight DHBs throughout the country generating data that were treated both quantitatively and qualitatively. Overall, few areas of consensus were found regarding the essential requirements for the CNS role and there were inconsistencies in how the roles were defined, most notably concerning requirements for postgraduate qualifications and Professional Development Recognition Programmes. Thematic analysis of the documents generated four key areas relevant to the CNS role. These described the CNS as a leader, a clinical expert, a co-ordinator and an educator. The findings indicate that the CNS role is inconsistently defined in New Zealand, particularly with respect to the postgraduate qualifications required and what is meant by 'expertise'.

Circuits of Surveillance

PubMed Central

Williams, Robin; Johnson, Paul

2005-01-01

This paper examines the increasing police use of DNA profiling and databasing as a developing instrumentality of modern state surveillance. It briefly notes previously published work on a variety of surveillance technologies and their role in the governance of social action and social order. It then argues that there are important differences amongst the ways in which several such technologies construct and use identificatory artefacts, their orientations to human subjectivity, and their role in the governmentality of citizens and others. The paper then describes the novel and powerful form of bio-surveillance offered by DNA profiling and illustrates this by reference to an ongoing empirical study of the police uses of the UK National DNA Database for the investigation of crime. It is argued that DNA profiling and databasing enable the construction of a ‘closed circuit’ of surveillance of a defined population. PMID:16467920

Emulation as an Integrating Principle for Cognition

PubMed Central

Colder, Brian

2011-01-01

Emulations, defined as ongoing internal representations of potential actions and the futures those actions are expected to produce, play a critical role in directing human bodily activities. Studies of gross motor behavior, perception, allocation of attention, response to errors, interoception, and homeostatic activities, and higher cognitive reasoning suggest that the proper execution of all these functions relies on emulations. Further evidence supports the notion that reinforcement learning in humans is aimed at updating emulations, and that action selection occurs via the advancement of preferred emulations toward realization of their action and environmental prediction. Emulations are hypothesized to exist as distributed active networks of neurons in cortical and sub-cortical structures. This manuscript ties together previously unrelated theories of the role of prediction in different aspects of human information processing to create an integrated framework for cognition. PMID:21660288

Crystal Structure of the N-Terminal Half of the Traffic Controller UL37 from Herpes Simplex Virus 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koenigsberg, Andrea L.; Heldwein, Ekaterina E.; Sandri-Goldin, Rozanne M.

Inner tegument protein UL37 is conserved among all three subfamilies of herpesviruses. Studies of UL37 homologs from two alphaherpesviruses, herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV), have suggested that UL37 plays an essential albeit poorly defined role in intracellular capsid trafficking. At the same time, HSV and PRV homologs cannot be swapped, which suggests that in addition to a conserved function, UL37 homologs also have divergent virus-specific functions. Accurate dissection of UL37 functions requires detailed maps in the form of atomic-resolution structures. Previously, we reported the crystal structure of the N-terminal half of UL37 (UL37N) from PRV. Here,more » we report the crystal structure of HSV-1 UL37N. Comparison of the two structures reveals that UL37 homologs differ in their overall shapes, distributions of surface charges, and locations of projecting loops. In contrast, the previously identified R2 surface region is structurally conserved. We propose that within the N-terminal half of UL37, functional conservation is centered within the R2 surface region, whereas divergent structural elements pinpoint regions mediating virus-specific functions and may engage different binding partners. Together, the two structures can now serve as templates for a structure-guided exploration of both conserved and virus-specific functions of UL37. IMPORTANCEThe ability to move efficiently within host cell cytoplasm is essential for replication in all viruses. It is especially important in the neuroinvasive alphaherpesviruses, such as human herpes simplex virus 1 (HSV-1), HSV-2, and veterinarian pseudorabies virus (PRV), that infect the peripheral nervous system and have to travel long distances along axons. Capsid movement in these viruses is controlled by capsid-associated tegument proteins, yet their specific roles have not yet been defined. Systematic exploration of the roles of tegument proteins in capsid trafficking requires detailed navigational charts in the form of their three-dimensional structures. Here, we determined the crystal structure of the N-terminal half of a conserved tegument protein, UL37, from HSV-1. This structure, along with our previously reported structure of the UL37 homolog from PRV, provides a much needed 3-dimensional template for the dissection of both conserved and virus-specific functions of UL37 in intracellular capsid trafficking.« less

Identification of Independent Streptococcus gordonii SspA and SspB Functions in Coaggregation with Actinomyces naeslundii

PubMed Central

Egland, Paul G.; Dû, Laurence D.; Kolenbrander, Paul E.

2001-01-01

The initial stages of dental plaque formation involve the adherence of early colonizing organisms such as Streptococcus gordonii and Actinomyces naeslundii to the saliva-coated tooth surface and to each other. The S. gordonii surface proteins SspA and SspB are known to play a role in adherence to salivary proteins and mediate coaggregation with other bacteria. Coaggregation is the adhesin receptor-mediated interaction between genetically distinct cell types and appears to be ubiquitous among oral isolates. To define the function of SspA and SspB separately on the surface of their natural host, we constructed and analyzed the coaggregation properties of an isogenic sspB mutant of S. gordonii DL1, an sspAB double mutant, and a previously described sspA mutant. A. naeslundii strains have been previously classified into six coaggregation groups based on the nature of their coaggregations with S. gordonii DL1 and other oral streptococci. Coaggregation assays with the sspA and sspB mutants showed that SspA and SspB are the streptococcal proteins primarily responsible for defining these coaggregation groups and, thus, are highly significant in the establishment of early dental plaque. SspA exhibited two coaggregation-specific functions. It participated in lactose-inhibitable and -noninhibitable interactions, while SspB mediated only lactose-noninhibitable coaggregations. Accordingly, the sspAB double mutant lacked these functions and allowed us to detect a third coaggregation interaction with one of these organisms. These proteins may play an important role in development of S. gordonii-A. naeslundii communities in early dental plaque. Understanding these adhesin proteins will aid investigations of complex microbial communities that characterize periodontal diseases. PMID:11705927

Structural changes in the vascular bundles of light-exposed and shaded spruce needles suffering from Mg deficiency and ozone pollution.

PubMed

Boxler-Baldoma, Carmen; Lütz, Cornelius; Heumann, Hans-Günther; Siefermann-Harms, Dorothea

2006-02-01

The correlation between structural changes of the vascular bundles and needle yellowing was examined for needles of damaged spruce (Picea abies (L.) Karst.) growing at a Mg-deficient and ozone polluted mountain site in the Central Black Forest (840m a.s.l.). In the previous year's sun-exposed needles, the following sequence of events was observed: (1) rapid needle yellowing, (2) hypertrophy and anomalous divisions of cambium cells, (3) phloem collapse, and, (4) production of atypical xylem tracheids. Under defined shade (reduction of the photosynthetically active photon flux density of the ambient light by 85-90%), the needles remained green, while the phloem collapsed completely within the first 6 weeks of shading; subsequently, a reversal of the collapse was observed. Under both light conditions, the content of Mg not bound to chlorophyll (Mg(free)) was in the range of 0.1 mg g(-1) needle dry matter, and hardly changed throughout the investigation period. After Mg fertilization, the Mg(free) level of the previous year's needles increased to 0.2 mg g(-1) dry matter, the light-exposed needles remained green, and the vascular bundles developed no anomalies. The data show that the rapid needle yellowing of ozone-exposed Mg-deficient needles did not depend on the collapse of the phloem. Mg deficiency played a key role in the development of anomalous vascular bundles under light, and also appears to explain the transient changes in sieve cell structure under shade. The role of Mg deficiency, rather than ozone pollution, in the damage of the sieve cells was confirmed in a long-term ozone exposure experiment with young clonal spruce growing under defined conditions.

Alteration textures in terrestrial volcanic glass and the associated bacterial community.

PubMed

Cockell, C S; Olsson-Francis, K; Herrera, A; Meunier, A

2009-01-01

Alteration textures were examined in subglacial (hyaloclastite) deposits at Valafell, Southern Iceland. Pitted and 'elongate' alteration features are observed in the glass similar to granular and tubular features reported previously in deep-ocean basaltic glasses, but elongate features generally did not have a length to width ratio greater than five. Elongate features were found in only 7% of surfaces. Crystalline basalt clasts, which are incorporated into the hyaloclastite, did not display elongate structures. Pitted alteration features were poorly defined in crystalline basalt, comprising only 4% of the surface compared to 47% in the case of basaltic glass. Examination of silica-rich glass (obsidian) and rhyolite similarly showed poorly defined pitted textures that comprised less than 15% of the surface and no elongate features were observed. These data highlight the differences in alteration textures between terrestrial basaltic glass and previously studied deep-ocean and subsurface basaltic glass, and the important role of mineralogy in controlling the type and abundance of alteration features. The hyaloclastite contains a diverse and abundant bacterial population, as determined by 16S rDNA analysis, which could be involved in weathering the glass. Despite the presence of phototrophs, we show that they were not involved in the production of most alteration textures in the basaltic glass materials we examined.

Contribution of volatiles to the antifungal effect of Lactobacillus paracasei in defined medium and yogurt.

PubMed

Aunsbjerg, S D; Honoré, A H; Marcussen, J; Ebrahimi, P; Vogensen, F K; Benfeldt, C; Skov, T; Knøchel, S

2015-02-02

Lactic acid bacteria with antifungal properties can be used to control spoilage of food and feed. Previously, most of the identified metabolites have been isolated from cell-free fermentate of lactic acid bacteria with methods suboptimal for detecting possible contribution from volatiles to the antifungal activity. The role of volatile compounds in the antifungal activity of Lactobacillus paracasei DGCC 2132 in a chemically defined interaction medium (CDIM) and yogurt was therefore investigated with a sampling technique minimizing volatile loss. Diacetyl was identified as the major volatile produced by L. paracasei DGCC 2132 in CDIM. When the strain was added to a yogurt medium diacetyl as well as other volatiles also increased but the metabolome was more complex. Removal of L. paracasei DGCC 2132 cells from CDIM fermentate resulted in loss of both volatiles, including diacetyl, and the antifungal activity towards two strains of Penicillium spp. When adding diacetyl to CDIM or yogurt without L. paracasei DGCC 2132, marked inhibition was observed. Besides diacetyl, the antifungal properties of acetoin were examined, but no antifungal activity was observed. Overall, the results demonstrate the contribution of diacetyl in the antifungal effect of L. paracasei DGCC 2132 and indicate that the importance of volatiles may have been previously underestimated. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and Validation of the Alcohol Identity Implicit Associations Test (AI-IAT)

PubMed Central

Gray, Heather M.; LaPlante, Debi A.; Bannon, Brittany L.; Ambady, Nalini; Shaffer, Howard J.

2011-01-01

Alcohol identity is the extent to which an individual perceives drinking alcohol to be a defining characteristic of his or her self-identity. Although alcohol identity might play an important role in risky college drinking practices, there is currently no easily administered, implicit measure of this concept. Therefore we developed a computerized implicit measure of alcohol identity (the Alcohol Identity Implicit Associations Test; AI-IAT) and assessed its reliability and predictive validity in relation to risky college drinking practices. One hundred forty-one college students completed the AI-IAT. Again 3- and 6-months later, we administered the AI-IAT and indices of engagement in risky college drinking practices. A subset of participants also completed the previously-validated implicit measure of alcohol identity. Scores on the AI-IAT were stable over time, internally consistent, and positively correlated with the previously-validated measure of alcohol identity. Baseline AI-IAT scores predicted future engagement in risky college drinking practices, even after controlling for standard alcohol consumption measures. We conclude that the AI-IAT reliably measures alcohol identity, a concept that appears to play an important role in risky college drinking practices. PMID:21621924

Cyberbullying Among Adolescent Bystanders: Role of Affective Versus Cognitive Empathy in Increasing Prosocial Cyberbystander Behavior

PubMed Central

Barlińska, Julia; Szuster, Anna; Winiewski, Mikołaj

2018-01-01

The purpose of this study was to investigate if affective (vicarious sharing of emotions) and cognitive empathy (mental perspective taking) induction may stimulate adolescent online bystanders’ intervention in cyberbullying cases. The role of reporting the abuse is crucial because it is a form of active support to the victim, initiated by children, to stop the bullying. The effectiveness of empathy activation in decreasing negative cyberbystander reinforcing behavior has been proved in previous studies. The effects of affective and cognitive empathy activation on positive cyberbystander behavior, defined as reporting the bullying online, were explored in two follow-up studies N = 271 and N = 265. The influence of experiencing cyberbullying as perpetrator, victim, and as determined by gender on prosocial cyberbystander behavior was also controlled. The results indicate that only cognitive empathy activation increases the likelihood of intervening bystander behavior. Neither affective empathy induction, previous experience of cyberperpetration, cybervictimization, nor gender affected the engagement in prosocial bystander behavior. The conclusion of the research is that a program consequently activating more reflective cognitive empathy induction can contribute toward the establishment of healthier behavioral patterns among bystanders to cyberbullying, increasing the probability of their reporting the cyberbullying acts. PMID:29899715

Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy

Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murinemore » lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6-8 week mice (adult) identified 928 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. Finally, this multi-omic view provides a unique resource and deeper insight into normal pulmonary development.« less

Cyberbullying Among Adolescent Bystanders: Role of Affective Versus Cognitive Empathy in Increasing Prosocial Cyberbystander Behavior.

PubMed

Barlińska, Julia; Szuster, Anna; Winiewski, Mikołaj

2018-01-01

The purpose of this study was to investigate if affective (vicarious sharing of emotions) and cognitive empathy (mental perspective taking) induction may stimulate adolescent online bystanders' intervention in cyberbullying cases. The role of reporting the abuse is crucial because it is a form of active support to the victim, initiated by children, to stop the bullying. The effectiveness of empathy activation in decreasing negative cyberbystander reinforcing behavior has been proved in previous studies. The effects of affective and cognitive empathy activation on positive cyberbystander behavior, defined as reporting the bullying online, were explored in two follow-up studies N = 271 and N = 265. The influence of experiencing cyberbullying as perpetrator, victim, and as determined by gender on prosocial cyberbystander behavior was also controlled. The results indicate that only cognitive empathy activation increases the likelihood of intervening bystander behavior. Neither affective empathy induction, previous experience of cyberperpetration, cybervictimization, nor gender affected the engagement in prosocial bystander behavior. The conclusion of the research is that a program consequently activating more reflective cognitive empathy induction can contribute toward the establishment of healthier behavioral patterns among bystanders to cyberbullying, increasing the probability of their reporting the cyberbullying acts.

Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

DOE PAGES

Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy; ...

2017-02-01

Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murinemore » lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6-8 week mice (adult) identified 928 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. Finally, this multi-omic view provides a unique resource and deeper insight into normal pulmonary development.« less

Ischaemic memory imaging using metabolic radiopharmaceuticals: overview of clinical settings and ongoing investigations.

PubMed

Yoshinaga, Keiichiro; Naya, Masanao; Shiga, Tohru; Suzuki, Eriko; Tamaki, Nagara

2014-02-01

"Ischaemic memory" is defined as a prolonged functional and/or biochemical alteration remaining after a particular episode of severe myocardial ischaemia. The biochemical alteration has been reported as metabolic stunning. Metabolic imaging has been used to detect the footprint left by previous ischaemic episodes evident due to delayed recovery of myocardial metabolism (persistent dominant glucose utilization with suppression of fatty acid oxidation). β-Methyl-p-[(123)I]iodophenylpentadecanoic acid (BMIPP) is a single-photon emission computed tomography (SPECT) radiotracer widely used for metabolic imaging in clinical settings in Japan. In patients with suspected coronary artery disease but no previous myocardial infarction, BMIPP has shown acceptable diagnostic accuracy. In particular, BMIPP plays an important role in the identification of prior ischaemic insult in patients arriving at emergency departments with acute chest pain syndrome. Recent data also show the usefulness of (123)I-BMIPP SPECT for predicting cardiovascular events in patients undergoing haemodialysis. Similarly, SPECT or PET imaging with (18)F-FDG injected during peak exercise or after exercise under fasting conditions shows an increase in FDG uptake in postischaemic areas. This article will overview the roles of ischaemic memory imaging both under established indications and in ongoing investigations.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, multiple myeloma and skin changes) with cranial vault plasmocytoma and the role of surgery in its management: a case report.

PubMed

Plata Bello, Julio; Garcia-Marin, Victor

2013-10-18

POEMS syndrome (an acronym of polyneuropathy, organomegaly, endocrinopathy, multiple myeloma and skin changes) is a paraneoplastic disorder related to an underlying plasma cell dyscrasia. The development of such a syndrome is rare and its association with calvarial plasmocytoma is even less common, with only two previous reported cases. We describe, in detail, an unusual presentation of cranial plasmocytoma associated with POEMS syndrome and briefly discuss the possible role of surgery in the management of this disease. We present the case of a 45-year-old Caucasian man who was admitted to our department presenting with progressive weakness in his lower limbs, enlarged lymph nodes and a large mass on the scalp with intense bone erosion. POEMS criteria were present and pathological studies confirmed a Castleman's variant plasmocytoma. Clinical status improved noticeably after the excision of the plasmocytoma and the treatment was completed with radiotherapy and steroid pulse therapy. Cranial vault plasmocytoma and its association with POEMS syndrome are rare conditions with few previously reported cases. Although the role of surgery is not clearly defined in POEMS syndrome guidelines, the fact that there seems to be a better prognosis and clinical outcome when surgery is used as a part of the management in POEMS syndrome with cranial vault plasmocytoma is worth discussing.

Pre-existing central nervous system lesions negate cytokine requirements for regional experimental autoimmune encephalomyelitis development.

PubMed

Li, Xin; Lees, Jason R

2013-03-01

In region-specific forms of experimental autoimmune encephalomyelitis (EAE), lesion initiation is regulated by T-cell-produced interferon-γ (IFN-γ) resulting in spinal cord disease in the presence of IFN-γ and cerebellar disease in the absence of IFN-γ. Although this role for IFN-γ in regional disease initiation is well defined, little is known about the consequences of previous tissue inflammation on subsequent regional disease, information vital to the development of therapeutics in established disease states. This study addressed the hypothesis that previous establishment of regional EAE would determine subsequent tissue localization of new T-cell invasion and associated symptoms regardless of the presence or absence of IFN-γ production. Serial transfer of optimal or suboptimal doses of encephalitogenic IFN-γ-sufficient or -deficient T-cell lines was used to examine the development of new clinical responses associated with the spinal cord and cerebellum at various times after EAE initiation. Previous inflammation within either cerebellum or spinal cord allowed subsequent T-cell driven inflammation within that tissue regardless of IFN-γ presence. Further, T-cell IFN-γ production after initial lesion formation exacerbated disease within the cerebellum, suggesting that IFN-γ plays different roles at different stages of cerebellar disease. For the spinal cord, IFN-γ-deficient cells (that are ordinarily cerebellum disease initiators) were capable of driving new spinal-cord-associated clinical symptoms more than 60 days after the initial acute EAE resolution. These data suggest that previous inflammation modulates the molecular requirements for new neuroinflammation development. © 2012 Blackwell Publishing Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mills, Evan; Jones, Richard B.

Large yet infrequent disruptions of electrical power can impact tens of millions of people in a single event, triggering significant economic damages, portions of which are insured. Small and frequent events are also significant in the aggregate. This article explores the role that insurance claims data can play in better defining the broader economic impacts of grid disruptions in the U.S. context. We developed four case studies, using previously unpublished data for specific actual grid disruptions. The cases include the 1977 New York City blackout, the 2003 Northeast blackout, multi-year national annual lightning-related electrical damage and multi-year national line-disturbance events.more » Insured losses represent between 3 and 64 per cent of total loss costs across the case studies. Here, the household sector emerges as a larger locus of costs than indicated in previous studies, and short-lived events emerge as important sources of loss costs.« less

Thalamic amplification of cortical connectivity sustains attentional control

PubMed Central

Schmitt, L. Ian; Wimmer, Ralf D.; Nakajima, Miho; Happ, Michael; Mofakham, Sima; Halassa, Michael M.

2017-01-01

While interactions between the thalamus and cortex are critical for cognitive function1–3, the exact contribution of the thalamus to these interactions is often unclear. Recent studies have shown diverse connectivity patterns across the thalamus 4,5, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions6 is unknown. Here, by investigating prefrontal cortical (PFC) representation of two rules used to guide attention, we find that the mediodorsal thalamus (MD) sustains these representations without relaying categorical information. Specifically, MD input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioral performance, while enhancing MD excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function indicates that the thalamus plays much more central roles in cognition than previously thought. PMID:28467827

An insurance perspective on U.S. electric grid disruption costs

DOE PAGES

Mills, Evan; Jones, Richard B.

2016-10-12

Large yet infrequent disruptions of electrical power can impact tens of millions of people in a single event, triggering significant economic damages, portions of which are insured. Small and frequent events are also significant in the aggregate. This article explores the role that insurance claims data can play in better defining the broader economic impacts of grid disruptions in the U.S. context. We developed four case studies, using previously unpublished data for specific actual grid disruptions. The cases include the 1977 New York City blackout, the 2003 Northeast blackout, multi-year national annual lightning-related electrical damage and multi-year national line-disturbance events.more » Insured losses represent between 3 and 64 per cent of total loss costs across the case studies. Here, the household sector emerges as a larger locus of costs than indicated in previous studies, and short-lived events emerge as important sources of loss costs.« less

[Neural Mechanisms Underlying the Processing of Temporal Information in Episodic Memory and Its Disturbance].

PubMed

Iwata, Saeko; Tsukiura, Takashi

2017-11-01

Episodic memory is defined as memory for personally experienced events, and includes memory content and contextual information of time and space. Previous neuroimaging and neuropsychological studies have demonstrated three possible roles of the temporal context in episodic memory. First, temporal information contributes to the arrangement of temporal order for sequential events in episodic memory, and this process is involved in the lateral prefrontal cortex. The second possible role of temporal information in episodic memory is the segregation between memories of multiple events, which are segregated by cues of different time information. The role of segregation is associated with the orbitofrontal regions including the orbitofrontal cortex and basal forebrain region. Third, temporal information in episodic memory plays an important role in the integration of multiple components into a coherent episodic memory, in which episodic components in the different modalities are combined by temporal information as an index. The role of integration is mediated by the medial temporal lobe including the hippocampus and parahippocampal gyrus. Thus, temporal information in episodic memory could be represented in multiple stages, which are involved in a network of the lateral prefrontal, orbitofrontal, and medial temporal lobe regions.

Convergent, not serial, striatal and pallidal circuits regulate opioid-induced food intake

PubMed Central

Taha, Sharif A.; Katsuura, Yoshihiro; Noorvash, David; Seroussi, Ariel; Fields, Howard L.

2009-01-01

Mu opioid receptor (MOR) signaling in the nucleus accumbens (NAcc) elicits marked increases in the consumption of palatable tastants. However, the mechanism and circuitry underlying this effect are not fully understood. Multiple downstream target regions have been implicated in mediating this effect but the role of the ventral pallidum (VP), a primary target of NAcc efferents, has not been well defined. To probe the mechanisms underlying increased consumption, we identified behavioral changes in licking patterns following NAcc MOR stimulation. Because the temporal structure of licking reflects the physiological substrates modulating consumption, these measures provide a useful tool in dissecting the cause of increased consumption following NAcc MOR stimulation. Next, we used a combination of pharmacological inactivation and lesions to define the role of the VP in hyperphagia following infusion of the MOR-specific agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the NAcc. In agreement with previous studies, results from lick microstructure analysis suggest that NAcc MOR stimulation augments intake through a palatability-driven mechanism. Our results also demonstrate an important role for the VP in normal feeding behavior: pharmacological inactivation of the VP suppresses baseline and NAcc DAMGO-induced consumption. However, this interaction does not occur through a serial circuit requiring direct projections from the NAcc to the VP. Rather, our results indicate that NAcc and VP circuits converge on a common downstream target that regulates food intake. PMID:19336249

[Tool for measuring occupational stress: a nurses' stress inventory].

PubMed

Stacciarini, J M; Tróccoli, B T

2000-12-01

We present an exploratory study aiming at constructing an inventory to measure occupational stress in nurses ("Inventário de Estresse em Enfermeiros"--IEE). A set of items was initially constructed from previously defined categories based on interviews with nurses and then improved through semantic analysis by referees and a pilot-test with nursing students. A sample of 461 nurses--workers from the public services of the Federal District--who answered the IEE was used in the study. Factorial analysis indicated the presence of a second-order global factor and three first-order factors: Interpersonal Relationships, Stressful Career Roles and Intrinsic Job Factors.

Predictors of Positive Treatment Outcome in People With Anorexia Nervosa Treated in a Specialized Inpatient Unit: The Role of Early Response to Treatment.

PubMed

Wales, Jackie; Brewin, Nicola; Cashmore, Rebecca; Haycraft, Emma; Baggott, Jonathan; Cooper, Amy; Arcelus, Jon

2016-09-01

To investigate factors which predict positive treatment outcome in inpatients with anorexia nervosa (AN), particularly the role of early treatment response. 102 patients entering specialist inpatient treatment were assessed for eating disorder history, psychopathology, and motivation to change. Predictive factors assessed were: early treatment response defined as weight increase of at least 0.5-1 kg/week during the first 6 weeks of treatment (n=87), admission body mass index (BMI), onset age, chronicity, motivation to change, diagnosis, and previous hospitalization for AN. Positive treatment outcome was defined as achieving a BMI of 17.5 kg/m(2) within an individual time frame. Logistic regression indicated that patients were 18 times more likely to reach positive treatment outcome if they met the National Institute for Health and Care Excellence weight guidelines within the first 6 weeks of hospitalization. Higher admission BMI was also found to predict positive treatment outcome. Higher entry BMI and early weight gain predict positive treatment outcome in individuals receiving specialist AN inpatient treatment. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Crack Growth Analysis for Arbitrary Spectrum Loading. Volume 1. Results and Discussion

DTIC Science & Technology

1974-10-01

amplitude growth without previous load history effects) the crack growth increments were increased. Many of the specimens were fitted with the Amsler...absolute magnitude of the maximum load.) Further, if S is defined as a function of the previous load history , then c h9 Equation (19) will predict...crack growth interaction effects. It remains then, to define S as a function of stress ratio and previous load history , and anyc other pertinent

Principal Leadership and Reading Specialist Role Understanding in the Era of Test-Based Accountability Policies

ERIC Educational Resources Information Center

Prezyna, Dolores Marie; Garrison, Mark J.; Lockte, Hilary A.; Gold, Carol P.

2017-01-01

This study investigates how the role of the reading specialist (RS) is defined and communicated by principals, and examines to what degree a common understanding of this role exists among teachers, building administrators and reading specialists. The principal's responsibility in defining and communicating role, and the effect these efforts have…

Communication as group process media of aircrew performance

NASA Technical Reports Server (NTRS)

Kanki, B. G.; Foushee, H. C.

1989-01-01

This study of group process was motivated by a high-fidelity flight simulator project in which aircrew performance was found to be better when the crew had recently flown together. Considering recent operating experience as a group-level input factor, aspects of the communication process between crewmembers (Captain and First Officer), were explored as a possible mediator to performance. Communication patterns were defined by a speech act typology adapted for the flightdeck setting and distinguished crews that had previously flown together (FT) from those that had not flown together (NFT). A more open communication channel with respect to information exchange and validation and greater First Officer participation in task-related topics was shown by FT crews while NFT crews engaged in more non-task discourse, a speech mode less structured by roles and probably serving a more interpersonal function. Relationships between the speech categories themselves, representing linguistic, and role-related interdependencies provide guidelines for interpreting the primary findings.

A mixability theory for the role of sex in evolution

PubMed Central

Livnat, Adi; Papadimitriou, Christos; Dushoff, Jonathan; Feldman, Marcus W.

2008-01-01

The question of what role sex plays in evolution is still open despite decades of research. It has often been assumed that sex should facilitate the increase in fitness. Hence, the fact that it may break down highly favorable genetic combinations has been seen as a problem. Here, we consider an alternative approach. We define a measure that represents the ability of alleles to perform well across different combinations and, using numerical iterations within a classical population-genetic framework, show that selection in the presence of sex favors this ability in a highly robust manner. We also show that the mechanism responsible for this effect has been out of the purview of previous theory, because it operates during the evolutionary transient, and that the breaking down of favorable genetic combinations is an integral part of it. Implications of these results and more to evolutionary theory are discussed. PMID:19073912

A mixability theory for the role of sex in evolution.

PubMed

Livnat, Adi; Papadimitriou, Christos; Dushoff, Jonathan; Feldman, Marcus W

2008-12-16

The question of what role sex plays in evolution is still open despite decades of research. It has often been assumed that sex should facilitate the increase in fitness. Hence, the fact that it may break down highly favorable genetic combinations has been seen as a problem. Here, we consider an alternative approach. We define a measure that represents the ability of alleles to perform well across different combinations and, using numerical iterations within a classical population-genetic framework, show that selection in the presence of sex favors this ability in a highly robust manner. We also show that the mechanism responsible for this effect has been out of the purview of previous theory, because it operates during the evolutionary transient, and that the breaking down of favorable genetic combinations is an integral part of it. Implications of these results and more to evolutionary theory are discussed.

Attending to the role of race/ethnicity in family violence research.

PubMed

Malley-Morrison, Kathleen; Hines, Denise A

2007-08-01

Since the 1970s, researchers and public health and/or social policy communities have devoted increasing attention to family violence. Although officially reported crime figures for family violence appear to be declining, rates continue to be high in broadly defined racial and/or ethnic minority groups. More careful assessments of the potential role of race/ethnicity in family violence, and similarities and differences occurring across and within groups categorized based on race/ethnicity, are essential if adequate interventions are to be developed and utilized. This article provides suggestions on conducting better studies on family violence in the United States, particularly with respect to issues of race/ethnicity. The authors begin by considering conceptions and definitions of race/ethnicity and providing a broad definition of family violence. They then suggest issues for consideration at each stage of the research process, from reviewing previous research, to making methodological decisions, selecting samples, choosing measures, and analyzing and interpreting findings.

Mitochondrial and ER Calcium Uptake and Release Fluxes and their Interplay in Intact Nerve Cells

NASA Astrophysics Data System (ADS)

Friel, David D.

Ionized free Ca ( Ca 2+) is a ubiquitous signaling ion that serves as the critical link between a variety of physiological stimuli and their intracellular effectors. Previous studies of reduced in vitro preparations have provided functional characterizations of various Ca 2+ channels, pumps and exchangers that regulate cellular Ca 2+ movements. However, little is known about the functional interplay between transporters that are expressed together in intact cells and orchestrate stimulus-evoked changes in [ Ca 2+]. This review summarizes recent progress in characterizing Ca 2+ transporters in sympathetic neurons, which provide an ideal model for studying Ca 2+ dynamics in neurons. Our results show how the functional interplay between Ca 2+ transport systems that are regulated by Ca 2+ in quantitatively differ-ent ways leads to emergent properties of Ca 2+ signaling that are expected to play a critical role in defining how Ca 2+ serves its role as a signaling ion.

Sucrose accumulation in sweet sorghum stems occurs by apoplasmic phloem unloading and does not involve differential Sucrose transporter expression.

PubMed

Bihmidine, Saadia; Baker, R Frank; Hoffner, Cassandra; Braun, David M

2015-07-30

Sorghum (Sorghum bicolor L. Moench) cultivars store non-structural carbohydrates predominantly as either starch in seeds (grain sorghums) or sugars in stems (sweet sorghums). Previous research determined that sucrose accumulation in sweet sorghum stems was not correlated with the activities of enzymes functioning in sucrose metabolism, and that an apoplasmic transport step may be involved in stem sucrose accumulation. However, the sucrose unloading pathway from stem phloem to storage parenchyma cells remains unelucidated. Sucrose transporters (SUTs) transport sucrose across membranes, and have been proposed to function in sucrose partitioning differences between sweet and grain sorghums. The purpose of this study was to characterize the key differences in carbohydrate accumulation between a sweet and a grain sorghum, to define the path sucrose may follow for accumulation in sorghum stems, and to determine the roles played by sorghum SUTs in stem sucrose accumulation. Dye tracer studies to determine the sucrose transport route revealed that, for both the sweet sorghum cultivar Wray and grain sorghum cultivar Macia, the phloem in the stem veins was symplasmically isolated from surrounding cells, suggesting sucrose was apoplasmically unloaded. Once in the phloem apoplasm, a soluble tracer diffused from the vein to stem parenchyma cell walls, indicating the lignified mestome sheath encompassing the vein did not prevent apoplasmic flux outside of the vein. To characterize carbohydrate partitioning differences between Wray and Macia, we compared the growth, stem juice volume, solute contents, SbSUTs gene expression, and additional traits. Contrary to previous findings, we detected no significant differences in SbSUTs gene expression within stem tissues. Phloem sieve tubes within sweet and grain sorghum stems are symplasmically isolated from surrounding cells; hence, unloading from the phloem likely occurs apoplasmically, thereby defining the location of the previously postulated step for sucrose transport. Additionally, no changes in SbSUTs gene expression were detected in sweet vs. grain sorghum stems, suggesting alterations in SbSUT transcript levels do not account for the carbohydrate partitioning differences between cultivars. A model illustrating sucrose phloem unloading and movement to stem storage parenchyma, and highlighting roles for sucrose transport proteins in sorghum stems is discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bihmidine, Saadia; Baker, R. Frank; Hoffner, Cassandra

Background: Sorghum (Sorghum bicolor L. Moench) cultivars store non-structural carbohydrates predominantly as either starch in seeds (grain sorghums) or sugars in stems (sweet sorghums). Previous research determined that sucrose accumulation in sweet sorghum stems was not correlated with the activities of enzymes functioning in sucrose metabolism, and that an apoplasmic transport step may be involved in stem sucrose accumulation. However, the sucrose unloading pathway from stem phloem to storage parenchyma cells remains unelucidated. Sucrose transporters (SUTs) transport sucrose across membranes, and have been proposed to function in sucrose partitioning differences between sweet and grain sorghums. The purpose of this studymore » was to characterize the key differences in carbohydrate accumulation between a sweet and a grain sorghum, to define the path sucrose may follow for accumulation in sorghum stems, and to determine the roles played by sorghum SUTs in stem sucrose accumulation. Results: Dye tracer studies to determine the sucrose transport route revealed that, for both the sweet sorghum cultivar Wray and grain sorghum cultivar Macia, the phloem in the stem veins was symplasmically isolated from surrounding cells, suggesting sucrose was apoplasmically unloaded. Once in the phloem apoplasm, a soluble tracer diffused from the vein to stem parenchyma cell walls, indicating the lignified mestome sheath encompassing the vein did not prevent apoplasmic flux outside of the vein. To characterize carbohydrate partitioning differences between Wray and Macia, we compared the growth, stem juice volume, solute contents, SbSUTs gene expression, and additional traits. Contrary to previous findings, we detected no significant differences in SbSUTs gene expression within stem tissues. Conclusions: Phloem sieve tubes within sweet and grain sorghum stems are symplasmically isolated from surrounding cells; hence, unloading from the phloem likely occurs apoplasmically, thereby defining the location of the previously postulated step for sucrose transport. Additionally, no changes in SbSUTs gene expression were detected in sweet vs. grain sorghum stems, suggesting alterations in SbSUT transcript levels do not account for the carbohydrate partitioning differences between cultivars. A model illustrating sucrose phloem unloading and movement to stem storage parenchyma, and highlighting roles for sucrose transport proteins in sorghum stems is discussed.« less

Identification and pathway analysis of microRNAs with no previous involvement in breast cancer.

PubMed

Romero-Cordoba, Sandra; Rodriguez-Cuevas, Sergio; Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

2012-01-01

microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described.

The role of maternal elaborative structure and control in children's memory and suggestibility for a past event.

PubMed

Principe, Gabrielle F; Trumbull, Jacqueline; Gardner, Grace; Van Horn, Elizabeth; Dean, Abigail M

2017-11-01

In this investigation, preschool-aged children experienced a staged event about which their mothers received misinformation suggesting that their children witnessed an activity that did not occur. Later, mothers were asked to talk about this event with their children. Consistent with previous research, mothers' provision of structure (defined as elaborative questions and statements) and degree of control (defined in terms of functional control of conversational turns) emerged as separate dimensions of maternal memory sharing style. When later interviewed by an unfamiliar examiner about the event, children whose mothers demonstrated both high structure and high control provided the highest levels of false reports of the activity suggested to mothers and generously embellished their accounts of this activity with nonoccurring details. In contrast, children with mothers who provided low structure, regardless of their degree of control, made few false reports and used sparse narrative detail. The implications of these findings for children's memory and suggestibility are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia.

PubMed

Kaur, Satvinder; Wang, Joshua L; Ferrari, Loris; Thankachan, Stephen; Kroeger, Daniel; Venner, Anne; Lazarus, Michael; Wellman, Andrew; Arrigoni, Elda; Fuller, Patrick M; Saper, Clifford B

2017-12-06

The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBel CGRP neurons caused wakefulness, whereas optogenetic inhibition of PBel CGRP neurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBel CGRP terminals identified a network of forebrain sites under the control of a PBel CGRP switch that is necessary to arouse animals from hypercapnia. Our findings define a novel cellular target for interventions that may prevent sleep fragmentation and the attendant cardiovascular and cognitive consequences seen in obstructive sleep apnea. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

A Study on Governance and Human Resources for Cooperative Road Facilities Management

NASA Astrophysics Data System (ADS)

Ohno, Sachiko; Takagi, Akiyoshi; Kurauchi, Fumitaka; Demura, Yoshifumi

Within today's infrastructure management, Asset Management systems are becoming a mainstream feature. For region where the risk is low, it is necessary to create a "cooperative road facilities management system". This research both examined and suggested what kind of cooperative road facilities management system should be promoted by the regional society. Concretely, this study defines the operational realities of a previous case. It discusses the problem of the road facilities management as a governance. Furthermore, its realization depends on "the cooperation between municipalities", "the private-sector initiative", and "residents participation" .Also, it discusses the problem of human resources for governance. Its realization depends on "the engineers' promotion", and "creation of a voluntary activity of the resident" as a human resources. Moreover, it defines that the intermediary is important because the human resources tied to the governance. As a result, the prospect of the road facilities management is shown by the role of the player and the relation among player.

Chromosome 17: association of a large inversion polymorphism with corticosteroid response in asthma.

PubMed

Tantisira, Kelan G; Lazarus, Ross; Litonjua, Augusto A; Klanderman, Barbara; Weiss, Scott T

2008-08-01

A 900-kb inversion exists within a large region of conserved linkage disequilibrium (LD) on chromosome 17. CRHR1 is located within the inversion region and associated with inhaled corticosteroid response in asthma. We hypothesized that CRHR1 variants are in LD with the inversion, supporting a potential role for natural selection in the genetic response to corticosteroids. We genotyped six single nucleotide polymorphisms (SNPs) spanning chromosome 17: 40,410,565-42,372,240, including four SNPs defining inversion status. Similar allele frequencies and strong LD were noted between the inversion and a CRHR1 SNP previously associated with lung function response to inhaled corticosteroids. Each inversion-defining SNP was strongly associated with inhaled corticosteroid response in adult asthma (P values 0.002-0.005). The CRHR1 response to inhaled corticosteroids may thus be explained by natural selection resulting from inversion status or by long-range LD with another gene. Additional pharmacogenetic investigations into regions of chromosomal diversity, including copy number variation and inversions, are warranted.

Redefinition of rubisco carboxylase reaction reveals origin of water for hydration and new roles for active-site residues.

PubMed

Kannappan, Babu; Gready, Jill E

2008-11-12

Crystallographic, mutagenesis, kinetic, and computational studies on Rubisco over three decades have revealed much about its catalytic mechanism and the role played by several active-site residues. However, key questions remain unanswered. Specific details of the carboxylase and oxygenase mechanisms, required to underpin the rational re-engineering of Rubisco, are still speculative. Here we address critical gaps in knowledge with a definitive comprehensive computational investigation of the mechanism of carboxylase activity at the Rubisco active site. Density functional theory calculations (B3LYP/6-31G(d,p)) were performed on active-site fragment models of a size up to 77 atoms, not previously possible computationally. All amino acid residues suspected to play roles in the acid-base chemistry in the multistep reaction, and interacting directly with the central Mg (2+) atom and the reactive moiety of substrate and intermediates, were included. The results provide a firm basis for us to propose a novel mechanism for the entire sequence of reactions in the carboxylase catalysis and to define precise roles for the active-site residues, singly and in concert. In this mechanism, the carbamylated LYS201 plays a more limited role than previously proposed but is crucial for initiating the reaction by acting as a base in the enolization. We suggest a wider role for HIS294, with involvement in the carboxylation, hydration, and C2-C3 bond-scission steps, consistent with the suggestion of Harpel et al. (1998) but contrary to the consensus view of Cleland et al. (1998). In contrast to the common assumption that the water molecule for the hydration step comes from within the active site, we propose that the Mg-coordinated water is not dissociated at the start of the gas-addition reaction but rather remains coordinated and is used for the hydration of the C3 carbon atom. New roles are also proposed for LYS175, GLU204, and HIS294. The mechanism suggests roles in the gas-addition step for residues in three spatially distinct regions of the active site, HIS294 and LYS334 in the C-terminal domain of the large subunit (LSU), but also hitherto unsuspected roles for a cluster of three residues (ASN123, GLU60, and TYR20) in the N-terminal domain of the partner LSU of the dimer containing the active site. Our new mechanism is supported by existing experimental data, provides new convincing interpretations of previously puzzling data, and allows new insights into mutational strategies for improving Rubisco activity.

Comparison of Satisfaction, Self-Confidence, and Engagement of Baccalaureate Nursing Students Using Defined Observational Roles and Expectations versus Traditional Role Assignments in High Fidelity Simulation and Debriefing

ERIC Educational Resources Information Center

Howard, Sheri

2017-01-01

The purpose of this study is to compare satisfaction, self-confidence, and engagement of baccalaureate nursing students using defined observational roles and expectations versus traditional observer role assignments in high fidelity simulation and debriefing and to evaluate student perceptions of these constructs. The NLN/Jeffries Simulation…

Sex-Role Stereotyping and Male-Female Character Distribution in Popular, Prestigious, and Sex-Role Defining Children's Literature from 1959 to 1972.

ERIC Educational Resources Information Center

Fraad, Harriet

This dissertation explored the extent and kind of sex-role stereotyping in popular, prestigious, and sex-role defining children's picture books printed between 1959 and 1972. The sample consisted of two categories of popular children's picture books, best-selling golden books and "New York Times" children's best-sellers, one category of Caldecott…

Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

PubMed Central

Steain, Megan; Sutherland, Jeremy P.; Rodriguez, Michael; Cunningham, Anthony L.; Slobedman, Barry

2014-01-01

ABSTRACT Varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes latency within the sensory ganglia and can reactivate to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. Ganglia innervating the site of the cutaneous herpes zoster rash showed evidence of necrosis, secondary to vasculitis, or localized hemorrhage. Despite this, there was limited evidence of VZV antigen expression, although a large inflammatory infiltrate was observed. Characterization of the infiltrating T cells showed a large number of infiltrating CD4+ T cells and cytolytic CD8+ T cells. Many of the infiltrating T cells were closely associated with neurons within the reactivated ganglia, yet there was little evidence of T cell-induced neuronal apoptosis. Notably, an upregulation in the expression of major histocompatibility complex class I (MHC-I) and MHC-II molecules was observed on satellite glial cells, implying these cells play an active role in directing the immune response during herpes zoster. This is the first detailed characterization of the interaction between T cells and neuronal cells within ganglia obtained from patients suffering herpes zoster at the time of death and provides evidence that CD4+ and cytolytic CD8+ T cell responses play an important role in controlling VZV replication in ganglia during active herpes zoster. IMPORTANCE VZV is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes a life-long dormant infection within the sensory ganglia and can reawaken to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. We found that specific T cell subsets are likely to play an important role in controlling VZV replication in ganglia during active herpes zoster. PMID:24352459

GPCRs Direct Germline Development and Somatic Gonad Function in Planarians

PubMed Central

Saberi, Amir; Beets, Isabel; Schoofs, Liliane; Newmark, Phillip A.

2016-01-01

Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development. PMID:27163480

GPCRs Direct Germline Development and Somatic Gonad Function in Planarians.

PubMed

Saberi, Amir; Jamal, Ayana; Beets, Isabel; Schoofs, Liliane; Newmark, Phillip A

2016-05-01

Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

PubMed

Rucker, James J H; Tansey, Katherine E; Rivera, Margarita; Pinto, Dalila; Cohen-Woods, Sarah; Uher, Rudolf; Aitchison, Katherine J; Craddock, Nick; Owen, Michael J; Jones, Lisa; Jones, Ian; Korszun, Ania; Barnes, Michael R; Preisig, Martin; Mors, Ole; Maier, Wolfgang; Rice, John; Rietschel, Marcella; Holsboer, Florian; Farmer, Anne E; Craig, Ian W; Scherer, Stephen W; McGuffin, Peter; Breen, Gerome

2016-02-15

Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Natural Variation of Drug Susceptibility in Wild-Type Human Immunodeficiency Virus Type 1

PubMed Central

Parkin, N. T.; Hellmann, N. S.; Whitcomb, J. M.; Kiss, L.; Chappey, C.; Petropoulos, C. J.

2004-01-01

Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or “biological cutoffs,” for the PhenoSense HIV phenotypic drug susceptibility assay. Definition of the natural variation in drug susceptibility in wild-type human immunodeficiency virus (HIV) type 1 isolates is necessary to determine the prevalence of innate drug resistance and to assess the capability of the PhenoSense assay to reliably measure subtle reductions in drug susceptibility. The biological cutoffs for each drug, defined by the 99th percentile of the fold change in the 50% inhibitory concentration distributions or the mean fold change plus 2 standard deviations, were lower than those previously reported for other phenotypic assays and lower than the clinically relevant cutoffs previously defined for the PhenoSense assay. The 99th percentile fold change values ranged from 1.2 (tenofovir) to 1.8 (zidovudine) for nucleoside reverse transcriptase RT inhibitors (RTIs), from 3.0 (efavirenz) to 6.2 (delavirdine) for nonnucleoside RTIs, and from 1.6 (lopinavir) to 3.6 (nelfinavir) for protease inhibitors. To evaluate the potential role of intrinsic assay variability in the observed variations in the drug susceptibilities of wild-type isolates, 10 reference viruses with different drug susceptibility patterns were tested 8 to 30 times each. The median coefficients of variation in fold change for the reference viruses ranged from 12 to 18% for all drugs except zidovudine (32%), strongly suggesting that the observed differences in wild-type virus susceptibility to the different drugs is related to intrinsic virus variability rather than assay variability. The low biological cutoffs and assay variability suggest that the PhenoSense HIV assay may assist in defining clinically relevant susceptibility cutoffs for resistance to antiretroviral drugs. PMID:14742192

Cerebrospinal and Interstitial Fluid Transport via the Glymphatic Pathway Modeled by Optimal Mass Transport

PubMed Central

Ratner, Vadim; Gao, Yi; Lee, Hedok; Elkin, Rena; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

2017-01-01

The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4 min over ∼3 hrs in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins. PMID:28323163

Cerebrospinal and interstitial fluid transport via the glymphatic pathway modeled by optimal mass transport.

PubMed

Ratner, Vadim; Gao, Yi; Lee, Hedok; Elkin, Rena; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

2017-05-15

The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4min over ∼3h in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins. Copyright © 2017. Published by Elsevier Inc.

Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks.

PubMed

Vara, M Isabel; Campo, Celeste

2015-07-20

Service discovery plays an important role in mobile ad hoc networks (MANETs). The lack of central infrastructure, limited resources and high mobility make service discovery a challenging issue for this kind of network. This article proposes a new service discovery mechanism for discovering and advertising services integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2). In previous studies, we demonstrated the validity of a similar service discovery mechanism integrated into the previous version of OLSR (OLSRv1). In order to advertise services, we have added a new type-length-value structure (TLV) to the OLSRv2 protocol, called service discovery message (SDM), according to the Generalized MANET Packet/Message Format defined in Request For Comments (RFC) 5444. Each node in the ad hoc network only advertises its own services. The advertisement frequency is a user-configurable parameter, so that it can be modified depending on the user requirements. Each node maintains two service tables, one to store information about its own services and another one to store information about the services it discovers in the network. We present simulation results, that compare our service discovery integrated into OLSRv2 with the one defined for OLSRv1 and with the integration of service discovery in Ad hoc On-demand Distance Vector (AODV) protocol, in terms of service discovery ratio, service latency and network overhead.

Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells

PubMed Central

Takeda, Norifumi; Jain, Rajan; LeBoeuf, Matthew R.; Padmanabhan, Arun; Wang, Qiaohong; Li, Li; Lu, Min Min; Millar, Sarah E.; Epstein, Jonathan A.

2013-01-01

The mammalian hair follicle relies on adult resident stem cells and their progeny to fuel and maintain hair growth throughout the life of an organism. The cyclical and initially synchronous nature of hair growth makes the hair follicle an ideal system with which to define homeostatic mechanisms of an adult stem cell population. Recently, we demonstrated that Hopx is a specific marker of intestinal stem cells. Here, we show that Hopx specifically labels long-lived hair follicle stem cells residing in the telogen basal bulge. Hopx+ cells contribute to all lineages of the mature hair follicle and to the interfollicular epidermis upon epidermal wounding. Unexpectedly, our analysis identifies a previously unappreciated progenitor population that resides in the lower hair bulb of anagen-phase follicles and expresses Hopx. These cells co-express Lgr5, do not express Shh and escape catagen-induced apoptosis. They ultimately differentiate into the cytokeratin 6-positive (K6) inner bulge cells in telogen, which regulate the quiescence of adjacent hair follicle stem cells. Although previous studies have suggested that K6+ cells arise from Lgr5-expressing lower outer root sheath cells in anagen, our studies indicate an alternative origin, and a novel role for Hopx-expressing lower hair bulb progenitor cells in contributing to stem cell homeostasis. PMID:23487314

Negative Mood Increases Selective Attention to Negatively Valenced Body Parts in Female Adolescents with Anorexia Nervosa.

PubMed

Svaldi, Jennifer; Bender, Caroline; Caffier, Detlef; Ivanova, Viliana; Mies, Nina; Fleischhaker, Christian; Tuschen-Caffier, Brunna

2016-01-01

Previous research has yielded evidence of increased attentional processing of negatively valenced body parts in women with anorexia nervosa (AN), especially for those with high depressive symptomatology. The present study extended previous research by implementing an experimental mood manipulation. In a within-subjects design, female adolescents with AN (n = 12) and an age matched female control group (CG; n = 12) were given a negative and a positive mood induction at a one-week interval. After each mood induction, participants underwent a 3-min mirror exposure, while their eye movements were recorded. After the positive mood induction, both AN and CG participants displayed longer and more frequent gazes towards their self-defined most ugly relative to their self-defined most beautiful body part. However, after the negative mood induction, only females with AN were characterized by increased attention to their most ugly compared to their most beautiful body part, while CG participants' attention distribution was balanced. Furthermore, in the negative (but not in the positive) mood induction condition gaze frequency and duration towards the most ugly body part was significantly stronger in the AN group relative to the CG. The results emphasize the role of negative mood in the maintenance of pathological information processing of the self-body. This increased body-related negativity-bias during negative mood may lead to the persistence and aggravation of AN patients' body image disturbance.

Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks

PubMed Central

Vara, M. Isabel; Campo, Celeste

2015-01-01

Service discovery plays an important role in mobile ad hoc networks (MANETs). The lack of central infrastructure, limited resources and high mobility make service discovery a challenging issue for this kind of network. This article proposes a new service discovery mechanism for discovering and advertising services integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2). In previous studies, we demonstrated the validity of a similar service discovery mechanism integrated into the previous version of OLSR (OLSRv1). In order to advertise services, we have added a new type-length-value structure (TLV) to the OLSRv2 protocol, called service discovery message (SDM), according to the Generalized MANET Packet/Message Format defined in Request For Comments (RFC) 5444. Each node in the ad hoc network only advertises its own services. The advertisement frequency is a user-configurable parameter, so that it can be modified depending on the user requirements. Each node maintains two service tables, one to store information about its own services and another one to store information about the services it discovers in the network. We present simulation results, that compare our service discovery integrated into OLSRv2 with the one defined for OLSRv1 and with the integration of service discovery in Ad hoc On-demand Distance Vector (AODV) protocol, in terms of service discovery ratio, service latency and network overhead. PMID:26205272

The role of strigolactones and ethylene in disease caused by Pythium irregulare.

PubMed

Blake, Sara N; Barry, Karen M; Gill, Warwick M; Reid, James B; Foo, Eloise

2016-06-01

Plant hormones play key roles in defence against pathogen attack. Recent work has begun to extend this role to encompass not just the traditional disease/stress hormones, such as ethylene, but also growth-promoting hormones. Strigolactones (SLs) are the most recently defined group of plant hormones with important roles in plant-microbe interactions, as well as aspects of plant growth and development, although the knowledge of their role in plant-pathogen interactions is extremely limited. The oomycete Pythium irregulare is a poorly controlled pathogen of many crops. Previous work has indicated an important role for ethylene in defence against this oomycete. We examined the role of ethylene and SLs in response to this pathogen in pea (Pisum sativum L.) at the molecular and whole-plant levels using a set of well-characterized hormone mutants, including an ethylene-insensitive ein2 mutant and SL-deficient and insensitive mutants. We identified a key role for ethylene signalling in specific cell types that reduces pathogen invasion, extending the work carried out in other species. However, we found no evidence that SL biosynthesis or response influences the interaction of pea with P. irregulare or that synthetic SL influences the growth or hyphal branching of the oomycete in vitro. Future work should seek to extend our understanding of the role of SLs in other plant interactions, including with other fungal, bacterial and viral pathogens, nematodes and insect pests. © 2015 BSPP AND JOHN WILEY & SONS LTD.

The applicability of the UK Public Health Skills and Knowledge Framework to the practitioner workforce: lessons for competency framework development.

PubMed

Shickle, Darren; Stroud, Laura; Day, Matthew; Smith, Kevin

2018-06-05

Many countries have developed competency frameworks for public health practice. While the number of competencies vary, frameworks cover similar knowledge and skills although they are not explicitly based on competency theory. A total of 15 qualitative group interviews (of up to six people), were conducted with 51 public health practitioners in 8 local authorities to assess the extent to which practitioners utilize competencies defined within the UK Public Health Skills and Knowledge Framework (PHSKF). Framework analysis was applied to the transcribed interviews. The overall framework was seen positively although no participants had previously read or utilized the PHSKF. Most could provide evidence, although some PHSKF competencies required creative thinking to fit expectations of practitioners and to reflect variation across the domains of practice which are impacted by job role and level of seniority. Evidence from previous NHS jobs or education may be needed as some competencies were not regularly utilized within their current local authority role. Further development of the PHSKF is required to provide guidance on how it should be used for practitioners and other members of the public health workforce. Empirical research can help benchmark knowledge/skills for workforce levels so improving the utility of competency frameworks.

The C. elegans histone deacetylase HDA-1 is required for cell migration and axon pathfinding.

PubMed

Zinovyeva, Anna Y; Graham, Serena M; Cloud, Veronica J; Forrester, Wayne C

2006-01-01

Histone proteins play integral roles in chromatin structure and function. Histones are subject to several types of posttranslational modifications, including acetylation, which can produce transcriptional activation. The converse, histone deacetylation, is mediated by histone deacetylases (HDACs) and often is associated with transcriptional silencing. We identified a new mutation, cw2, in the Caenorhabditis elegans hda-1 gene, which encodes a histone deacetylase. Previous studies showed that a mutation in hda-1, e1795, or reduction of hda-1 RNA by RNAi causes defective vulval and gonadal development leading to sterility. The hda-1(cw2) mutation causes defective vulval development and reduced fertility, like hda-1(e1795), albeit with reduced severity. Unlike the previously reported hda-1 mutation, hda-1(cw2) mutants are viable as homozygotes, although many die as embryos or larvae, and are severely uncoordinated. Strikingly, in hda-1(cw2) mutants, axon pathfinding is defective; specific axons often appear to wander randomly or migrate in the wrong direction. In addition, the long range migrations of three neuron types and fasciculation of the ventral nerve cord are defective. Together, our studies define a new role for HDA-1 in nervous system development, and provide the first evidence for HDAC function in regulating neuronal axon guidance.

Protein Kinase Cδ Promotes Transitional B Cell-Negative Selection and Limits Proximal B Cell Receptor Signaling To Enforce Tolerance

PubMed Central

Zikherman, Julie; Lau, Tannia; Leitges, Michael; Weiss, Arthur

2014-01-01

Protein kinase Cδ (PKCδ) deficiency causes autoimmune pathology in humans and mice and is crucial for the maintenance of B cell homeostasis. However, the mechanisms underlying autoimmune disease in PKCδ deficiency remain poorly defined. Here, we address the antigen-dependent and -independent roles of PKCδ in B cell development, repertoire selection, and antigen responsiveness. We demonstrate that PKCδ is rapidly phosphorylated downstream of both the B cell receptor (BCR) and the B cell-activating factor (BAFF) receptor. We found that PKCδ is essential for antigen-dependent negative selection of splenic transitional B cells and is required for activation of the proapoptotic Ca2+-Erk pathway that is selectively activated during B cell-negative selection. Unexpectedly, we also identified a previously unrecognized role for PKCδ as a proximal negative regulator of BCR signaling that substantially impacts survival and proliferation of mature follicular B cells. As a consequence of these distinct roles, PKCδ deficiency leads to the survival and development of a B cell repertoire that is not only aberrantly autoreactive but also hyperresponsive to antigen stimulation. PMID:24515435

An essential and NSF independent role for α-SNAP in store-operated calcium entry.

PubMed

Miao, Yong; Miner, Cathrine; Zhang, Lei; Hanson, Phyllis I; Dani, Adish; Vig, Monika

2013-07-16

Store-operated calcium entry (SOCE) by calcium release activated calcium (CRAC) channels constitutes a primary route of calcium entry in most cells. Orai1 forms the pore subunit of CRAC channels and Stim1 is the endoplasmic reticulum (ER) resident Ca(2+) sensor. Upon store-depletion, Stim1 translocates to domains of ER adjacent to the plasma membrane where it interacts with and clusters Orai1 hexamers to form the CRAC channel complex. Molecular steps enabling activation of SOCE via CRAC channel clusters remain incompletely defined. Here we identify an essential role of α-SNAP in mediating functional coupling of Stim1 and Orai1 molecules to activate SOCE. This role for α-SNAP is direct and independent of its known activity in NSF dependent SNARE complex disassembly. Importantly, Stim1-Orai1 clustering still occurs in the absence of α-SNAP but its inability to support SOCE reveals that a previously unsuspected molecular re-arrangement within CRAC channel clusters is necessary for SOCE. DOI:http://dx.doi.org/10.7554/eLife.00802.001.

Prion protein is essential for diabetic retinopathy-associated neovascularization.

PubMed

Zhu, Lingyan; Xu, Jixiong; Liu, Ying; Gong, Tian; Liu, Jianying; Huang, Qiong; Fischbach, Shane; Zou, Wenquan; Xiao, Xiangwei

2018-05-30

Diabetic retinopathy (DR), a major complication of diabetes caused by vascular damage and pathological proliferation of retinal vessels, often progresses to vision loss. Vascular endothelial growth factor (VEGF) signaling plays a pivotal role in the development of DR, but the exact underlying molecular mechanisms remain ill-defined. Cellular prion protein (PrP c ) is a surface protein expressed by vascular endothelial cells, and the increased expression of PrP c is associated with physiological and pathological vascularization. Nevertheless, a role for PrP c in the development of DR has not been appreciated. Here, we addressed this question. We found that the development of streptozocin (STZ)-induced DR, but not the STZ-induced hyperglycemia/diabetes itself, was significantly attenuated in PrP c -KO mice, compared to control wildtype (WT) mice, evident by measurement of retinal vascular leakage, retinal neovascularization, a retinopathy score and visual acuity assessment. Moreover, the attenuation of DR severity seemingly resulted from attenuation of retinal neovascularization via VEGF/ras/rac signaling. Together, our study suggests a previously unappreciated role for PrP c in the development of DR.

The Role Of Basal Forebrain Cholinergic Neurons In Fear and Extinction Memory

PubMed Central

Knox, Dayan

2016-01-01

Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral amygdala (BLA) is critical for neural function and synaptic plasticity in these brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp), and BLA has also been implicated in fear and extinction memory. This finding raises the possibility that basal forebrain (BF) cholinergic neurons, the predominant source of acetylcholine in these brain regions, have an important role in mediating fear and extinction memory. While empirical studies support this hypothesis, there are interesting inconsistencies among these studies that raise questions about how best to define the role of BF cholinergic neurons in fear and extinction memory. Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA are critical for fear memory and contextual fear extinction memory. NBM cholinergic neurons that project to the neocortex are critical for cued and contextual fear conditioned suppression, but are not critical for fear memory in other behavioral paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear memory formation. Medial septum and diagonal band of Broca cholinergic neurons are critical for contextual fear memory and acquisition of cued fear extinction. Thus, even though the results of previous studies suggest BF cholinergic neurons modulate fear and extinction memory, inconsistent findings among these studies necessitates more research to better define the neural circuits and molecular processes through which BF cholinergic neurons modulate fear and extinction memory. Furthermore, studies determining if BF cholinergic neurons can be manipulated in such a manner so as to treat excessive fear in anxiety disorders are needed. PMID:27264248

Role of Exonic Variation in Chemokine Receptor Genes on AIDS: CCRL2 F167Y Association with Pneumocystis Pneumonia

PubMed Central

An, Ping; Li, Rongling; Wang, Ji Ming; Yoshimura, Teizo; Takahashi, Munehisa; Samudralal, Ram; O'Brien, Stephen J.; Phair, John; Goedert, James J.; Kirk, Gregory D.; Troyer, Jennifer L.; Sezgin, Efe; Buchbinder, Susan P.; Donfield, Sharyne; Nelson, George W.; Winkler, Cheryl A.

2011-01-01

Chromosome 3p21–22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28–6.31) among four major AIDS–defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation. PMID:22046140

Stimulus-Dependent, Promoter-Specific Binding of Transcription Factor WRKY1 to Its Native Promoter and the Defense-Related Gene PcPR1-1 in ParsleyW⃞

PubMed Central

Turck, Franziska; Zhou, Aifen; Somssich, Imre E.

2004-01-01

WRKY transcription factors form a large family that plays a role in plant responses to biotic stress and during senescence. Defining in vivo relevant WRKY/promoter relationships has been hampered by the factors' indiscriminate binding to known W box DNA elements and their possible genetic redundance. Employing chromatin immunoprecipitations (ChIP) of cultured cells, we show that parsley (Petroselinum crispum) WRKY1 protein binds to the W boxes of its native promoter as well as to that of PcWRKY3 and the defense-related PR10-class marker gene Pathogenesis-Related1-1 (PcPR1-1). Although present at low concentrations in resting cells, WRKY1 does not appear to play a role in the immediate early gene response upon elicitation because it does not bind to the promoter at this time. Paradoxically, in vivo binding at the PcWRKY1 promoter correlates more with downregulation of gene expression, whereas previous overexpression studies suggested an activating function of WRKY1 on PcWRKY1 expression. By contrast, PcPR1-1 expression remains strong when its promoter is occupied in vivo by WRKY1. Unexpectedly, ChIP revealed that W boxes at promoter sites are constitutively occupied by other WRKY transcription factors, indicating that site recruitment does not seem to play a major role in their regulation. Rather, WRKY proteins very likely act in a network of mutually competing participants with temporal displacement occurring at defined preoccupied sites by other family members in a stimulus-dependent manner. PMID:15367720

Diagnosis and management of heart failure in the fetus

PubMed Central

DAVEY, B.; SZWAST, A.; RYCHIK, J.

2015-01-01

Heart failure can be defined as the inability of the heart to sufficiently support the circulation. In the fetus, heart failure can be caused by a myriad of factors that include fetal shunting abnormalities, genetic cardiomyopathies, extracardiac malformations, arrhythmias and structural congenital heart disease. With advances in ultrasound has come the ability to characterize many complex conditions, previously poorly understood. Fetal echocardiography provides the tools necessary to evaluate and understand the various physiologies that contribute to heart failure in the fetus. In this review, we will explore the different mechanisms of heart failure in this unique patient population and highlight the role of fetal echocardiography in the current management of these conditions PMID:22992530

Plant - Growth - Apollo 15 - Lunar Material - MSC

NASA Image and Video Library

1971-10-01

S71-51318 (1 Oct. 1971) --- A close view of germ free plants -- lettuce (left), tomato (right center and left center) and citrus (right). This type of testing is a unique effort at the Manned Spacecraft Center (MSC) to grow germ-free plants. By study of the germ-free plants, NASA and the U.S. Department of Agriculture Forest Service hope to establish clearly the exact mineral needs of the plants alone. Previous nutrition studies have measured the needs of a complex of soil:micro-organisms:plants. Results from studies where the role of microbes is not known or defined are difficult to interpret and do not lead to the accumulation of exacting facts on plant nutrition.

Environmental waste site characterization utilizing aerial photographs and satellite imagery: Three sites in New Mexico, USA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Eeckhout, E.; Pope, P.; Becker, N.

1996-04-01

The proper handling and characterization of past hazardous waste sites is becoming more and more important as world population extends into areas previously deemed undesirable. Historical photographs, past records, current aerial satellite imagery can play an important role in characterizing these sites. These data provide clear insight into defining problem areas which can be surface samples for further detail. Three such areas are discussed in this paper: (1) nuclear wastes buried in trenches at Los Alamos National Laboratory, (2) surface dumping at one site at Los Alamos National Laboratory, and (3) the historical development of a municipal landfill near Lasmore » Cruces, New Mexico.« less

An assessment of faculty and dental student decision-making in ethics.

PubMed

Behar-Horenstein, Linda S; Catalanotto, Frank A; Garvan, Cynthia Wilson; Hudson-Vassell, Charisse

2014-01-01

This study reports and compares dental student and dental faculty scores to national norms for the Defining Issues Test 2, a measure of ethical decision-making competency. The findings showed that dental students and faculty tend to make decisions that promote self-interest, paralleling the ethical orientation of business professionals. Differences associated with gender, language, and norms from previous studies were observed. The findings underscore the importance of raising dental faculty and student awareness of their own ethical decision-making approaches. More importantly, the findings highlight the need to ensure that dental faculty have both the knowledge and skills to train dental students about the central role that ethical decision-making must play in patient care.

A cellular and regulatory map of the GABAergic nervous system of C. elegans

PubMed Central

Gendrel, Marie; Atlas, Emily G; Hobert, Oliver

2016-01-01

Neurotransmitter maps are important complements to anatomical maps and represent an invaluable resource to understand nervous system function and development. We report here a comprehensive map of neurons in the C. elegans nervous system that contain the neurotransmitter GABA, revealing twice as many GABA-positive neuron classes as previously reported. We define previously unknown glia-like cells that take up GABA, as well as 'GABA uptake neurons' which do not synthesize GABA but take it up from the extracellular environment, and we map the expression of previously uncharacterized ionotropic GABA receptors. We use the map of GABA-positive neurons for a comprehensive analysis of transcriptional regulators that define the GABA phenotype. We synthesize our findings of specification of GABAergic neurons with previous reports on the specification of glutamatergic and cholinergic neurons into a nervous system-wide regulatory map which defines neurotransmitter specification mechanisms for more than half of all neuron classes in C. elegans. DOI: http://dx.doi.org/10.7554/eLife.17686.001 PMID:27740909

New constraints on the spatial distribution and morphology of the Halimeda bioherms of the Great Barrier Reef, Australia

NASA Astrophysics Data System (ADS)

McNeil, Mardi A.; Webster, Jody M.; Beaman, Robin J.; Graham, Trevor L.

2016-12-01

Halimeda bioherms occur as extensive geological structures on the northern Great Barrier Reef (GBR), Australia. We present the most complete, high-resolution spatial mapping of the northern GBR Halimeda bioherms, based on new airborne lidar and multibeam echosounder bathymetry data. Our analysis reveals that bioherm morphology does not conform to the previous model of parallel ridges and troughs, but is far more complex than previously thought. We define and describe three morphological sub-types: reticulate, annulate, and undulate, which are distributed in a cross-shelf pattern of reduced complexity from east to west. The northern GBR bioherms cover an area of 6095 km2, three times larger than the original estimate, exceeding the area and volume of calcium carbonate in the adjacent modern shelf-edge barrier reefs. We have mapped a 1740 km2 bioherm complex north of Raine Island in the Cape York region not previously recorded, extending the northern limit by more than 1° of latitude. Bioherm formation and distribution are controlled by a complex interaction of outer-shelf geometry, regional and local currents, coupled with the morphology and depth of continental slope submarine canyons determining the delivery of cool, nutrient-rich water upwelling through inter-reef passages. Distribution and mapping of Halimeda bioherms in relation to Great Barrier Reef Marine Park Authority bioregion classifications and management zones are inconsistent and currently poorly defined due to a lack of high-resolution data not available until now. These new estimates of bioherm spatial distribution and morphology have implications for understanding the role these geological features play as structurally complex and productive inter-reef habitats, and as calcium carbonate sinks which record a complete history of the Holocene post-glacial marine transgression in the northern GBR.

Hypoxia-inducible factor-1α in vascular smooth muscle regulates blood pressure homeostasis through a peroxisome proliferator-activated receptor-γ-angiotensin II receptor type 1 axis.

PubMed

Huang, Yan; Di Lorenzo, Annarita; Jiang, Weidong; Cantalupo, Anna; Sessa, William C; Giordano, Frank J

2013-09-01

Hypertension is a major worldwide health issue for which only a small proportion of cases have a known mechanistic pathogenesis. Of the defined causes, none have been directly linked to heightened vasoconstrictor responsiveness, despite the fact that vasomotor tone in resistance vessels is a fundamental determinant of blood pressure. Here, we reported a previously undescribed role for smooth muscle hypoxia-inducible factor-1α (HIF-1α) in controlling blood pressure homeostasis. The lack of HIF-1α in smooth muscle caused hypertension in vivo and hyperresponsiveness of resistance vessels to angiotensin II stimulation ex vivo. These data correlated with an increased expression of angiotensin II receptor type I in the vasculature. Specifically, we show that HIF-1α, through peroxisome proliferator-activated receptor-γ, reciprocally defined angiotensin II receptor type I levels in the vessel wall. Indeed, pharmacological blockade of angiotensin II receptor type I by telmisartan abolished the hypertensive phenotype in smooth muscle cell-HIF-1α-KO mice. These data revealed a determinant role of a smooth muscle HIF-1α/peroxisome proliferator-activated receptor-γ/angiotensin II receptor type I axis in controlling vasomotor responsiveness and highlighted an important pathway, the alterations of which may be critical in a variety of hypertensive-based clinical settings.

The role of magnocellular signals in oculomotor attentional capture

PubMed Central

Leonard, Carly J.; Luck, Steven J.

2011-01-01

While it is known that salient distractors often capture covert and overt attention, it is unclear whether salience signals that stem from magnocellular visual input have a more dominant role in oculomotor capture than those that result from parvocellular input. Because of the direct anatomical connections between the magnocellular pathway and the superior colliculus, salience signals generated from the magnocellular pathway may produce greater oculomotor capture than those from the parvocellular pathway, which could be potentially harder to overcome with “top-down”, goal-directed guidance. Although previous research has addressed this with regard to magnocellular transients, in the current research we investigated whether a static singleton distractor defined along a dimension visible to the magnocellular pathway would also produce enhanced oculomotor capture. In two experiments, we addressed this possibility by comparing a parvo-biased singleton condition, in which the distractor was defined by isoluminant chromatic color contrast, with a magno+parvo singleton condition, in which the distractor also differed in luminance from the surrounding objects. In both experiments, magno+parvo singletons elicited faster eye movements than parvo-only singletons, presumably reflecting faster information transmission in the magnocellular pathway, but magno+parvo singletons were not significantly more likely to produce oculomotor capture. Thus, although magnocellular salience signals are available more rapidly, they have no sizable advantage over parvocellular salience signals in controlling oculomotor orienting when all stimuli have a common onset. PMID:22076486

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Bohyun; Kim, Inki; Nam, Ja-Ae

EFC-1 integrase is a site-specific recombinase that belongs to the large family of serine recombinase. In previously study, we isolated the temperate phage EFC-1, and characterized its genomic sequence. Within its genome, Orf28 was predicted encode a 464 amino acid of a putative integrase gene. In this study, EFC-1 integrase was characterized in vitro and in vivo. In vitro assay was performed using purified His-tag fusion integrase. Also, to identify which serine is involved in the catalytic domain, we used site-directed mutagenesis and analyzed by a recombination assay in vitro. In vivo assay involved PCR and confocal microscopy in HEK293 cells, and determined the minimal lengthsmore » of attP and attB sites. According to our results, the EFC-1 integrase-mediated recombination was site-specific and unidirectional system in vitro and in vivo. Serine 21 of EFC-1 integrase plays a major role in the catalytic domain, and minimal sizes of attB and attP was defined 48 and 54 bp. Our finding may help develop a useful tool for gene therapy and gene delivery system. - Highlights: • EFC-1 integrase-mediated recombination was site-specific and unidirectional system. • Serine 21 of EFC-1 integrase plays a major role in the catalytic domain. • The functional minimal sizes of attB and attP was defined 48 and 54 bp.« less

Quantifying the Sources of Intermodel Spread in Equilibrium Climate Sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caldwell, Peter M.; Zelinka, Mark D.; Taylor, Karl E.

This paper clarifies the causes of intermodel differences in the global-average temperature response to doubled CO 2, commonly known as equilibrium climate sensitivity (ECS). The authors begin by noting several issues with the standard approach for decomposing ECS into a sum of forcing and feedback terms. This leads to a derivation of an alternative method based on linearizing the effect of the net feedback. Consistent with previous studies, the new method identifies shortwave cloud feedback as the dominant source of intermodel spread in ECS. This new approach also reveals that covariances between cloud feedback and forcing, between lapse rate andmore » longwave cloud feedbacks, and between albedo and shortwave cloud feedbacks play an important and previously underappreciated role in determining model differences in ECS. Finally, defining feedbacks based on fixed relative rather than specific humidity (as suggested by Held and Shell) reduces the covariances between processes and leads to more straightforward interpretations of results.« less

Quantifying the Sources of Intermodel Spread in Equilibrium Climate Sensitivity

DOE PAGES

Caldwell, Peter M.; Zelinka, Mark D.; Taylor, Karl E.; ...

2016-01-07

This paper clarifies the causes of intermodel differences in the global-average temperature response to doubled CO 2, commonly known as equilibrium climate sensitivity (ECS). The authors begin by noting several issues with the standard approach for decomposing ECS into a sum of forcing and feedback terms. This leads to a derivation of an alternative method based on linearizing the effect of the net feedback. Consistent with previous studies, the new method identifies shortwave cloud feedback as the dominant source of intermodel spread in ECS. This new approach also reveals that covariances between cloud feedback and forcing, between lapse rate andmore » longwave cloud feedbacks, and between albedo and shortwave cloud feedbacks play an important and previously underappreciated role in determining model differences in ECS. Finally, defining feedbacks based on fixed relative rather than specific humidity (as suggested by Held and Shell) reduces the covariances between processes and leads to more straightforward interpretations of results.« less

The use of thermal capsulorrhaphy in the treatment of multidirectional instability.

PubMed

Fitzgerald, Brian T; Watson, B Thomas; Lapoint, John M

2002-01-01

The purpose of this study is to report on our experience with thermal capsulorrhaphy in the treatment of multidirectional instability of the shoulder. Thirty-three consecutive patients (33 shoulders) with multidirectional instability were treated with arthroscopic thermal capsulorrhaphy. Twelve patients had a history of traumatic dislocation. Three patients had been previously treated with open inferior capsular shift procedures. At a mean follow-up of 36 months (range, 24-40 months), results were available for 30 patients. On the basis of the UCLA rating scale, out of a possible 35 points, the mean preoperative score was 16.7 points and postoperatively it was 30.1 points, with 3 excellent, 20 good, and 7 poor results. Twenty-three patients (76%) were returned to full activity. In our experience the majority of patients with multidirectional instability were able to return to their previous occupations in the armed forces following thermal capsulorrhaphy. More information further defining the biomechanical pathology of capsular laxity and the specific role of electrothermal shrinkage in treating shoulder instability is needed.

A dictionary of behavioral motifs reveals clusters of genes affecting Caenorhabditis elegans locomotion.

PubMed

Brown, André E X; Yemini, Eviatar I; Grundy, Laura J; Jucikas, Tadas; Schafer, William R

2013-01-08

Visible phenotypes based on locomotion and posture have played a critical role in understanding the molecular basis of behavior and development in Caenorhabditis elegans and other model organisms. However, it is not known whether these human-defined features capture the most important aspects of behavior for phenotypic comparison or whether they are sufficient to discover new behaviors. Here we show that four basic shapes, or eigenworms, previously described for wild-type worms, also capture mutant shapes, and that this representation can be used to build a dictionary of repetitive behavioral motifs in an unbiased way. By measuring the distance between each individual's behavior and the elements in the motif dictionary, we create a fingerprint that can be used to compare mutants to wild type and to each other. This analysis has revealed phenotypes not previously detected by real-time observation and has allowed clustering of mutants into related groups. Behavioral motifs provide a compact and intuitive representation of behavioral phenotypes.

Germline mutations and somatic inactivation of TRIM28 in Wilms tumour

PubMed Central

Halliday, Benjamin J.; Markie, David M.; Grundy, Richard G.; Ludgate, Jackie L.; Black, Michael A.; Weeks, Robert J.; Catchpoole, Daniel R.; Reeve, Anthony E.

2018-01-01

Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of TRIM28, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing. TRIM28-mutated tumours had a monomorphic epithelial histology that is uncommon for Wilms tumour. Critically, these tumours were negative for TRIM28 immunohistochemical staining whereas the epithelial component in normal tissue and other Wilms tumours stained positively. These data, together with a characteristic gene expression profile, suggest that inactivation of TRIM28 provides the molecular basis for defining a previously described subtype of Wilms tumour, that has early age of onset and excellent prognosis. PMID:29912901

Biosynthesis and Regulation of Sulfomenaquinone, a Metabolite Associated with Virulence in Mycobacterium tuberculosis.

PubMed

Sogi, Kimberly M; Holsclaw, Cynthia M; Fragiadakis, Gabriela K; Nomura, Daniel K; Leary, Julie A; Bertozzi, Carolyn R

2016-11-11

Sulfomenaquinone (SMK) is a recently identified metabolite that is unique to the Mycobacterium tuberculosis (M. tuberculosis) complex and is shown to modulate its virulence. Here, we report the identification of the SMK biosynthetic operon that, in addition to a previously identified sulfotransferase stf3, includes a putative cytochrome P450 gene (cyp128) and a gene of unknown function, rv2269c. We demonstrate that cyp128 and stf3 are sufficient for the biosynthesis of SMK from menaquinone and rv2269c exhibits promoter activity in M. tuberculosis. Loss of Stf3 expression, but not that of Cyp128, is correlated with elevated levels of menaquinone-9, an essential component in the electron-transport chain in M. tuberculosis. Finally, we showed in a mouse model of infection that the loss of cyp128 exhibits a hypervirulent phenotype similar to that in previous studies of the stf3 mutant. These findings provide a platform for defining the molecular basis of SMK's role in M. tuberculosis pathogenesis.

Problems in Defining the Field of Distance Education.

ERIC Educational Resources Information Center

Keegan, Desmond

1988-01-01

This discussion of definitions of distance education responds to previous articles attempting to define the field. Topics discussed include distance education versus conventional education; group-based distance education; differences between open learning and distance education; and criteria to define distance education. (13 references) (LRW)

Using home buyers' revealed preferences to define the urban rural fringe

NASA Astrophysics Data System (ADS)

Lesage, James P.; Charles, Joni S.

2008-03-01

The location of new homes defines the urban rural fringe and determines many facets of the urban rural interaction set in motion by construction of new homes in previously rural areas. Home, neighborhood and school district characteristics play a crucial role in determining the spatial location of new residential construction, which in turn defines the boundary and spatial extent of the urban rural fringe. We develop and apply a spatial hedonic variant of the Blinder (J Hum Resour 8:436 455, 1973) and Oaxaca (Int Econ Rev 9:693 709, 1973) price decomposition to newer versus older home sales in the Columbus, Ohio metropolitan area during the year 2000. The preferences of buyers of newer homes are compared to those who purchased the nearest neighboring older home located in the same census block group, during the same year. Use of the nearest older home purchased in the same location represents a methodology to control for various neighborhood, social economic-demographic and school district characteristics that influence home prices. Since newer homes reflect current preferences for home characteristics while older homes reflect past preferences for these characteristics, we use the price differentials between newer and older home sales in the Blinder Oaxaca decomposition to assess the relative significance of various house characteristics to home buyers.

Secretome Analysis Defines the Major Role of SecDF in Staphylococcus aureus Virulence

PubMed Central

Quiblier, Chantal; Seidl, Kati; Roschitzki, Bernd; Zinkernagel, Annelies S.; Berger-Bächi, Brigitte; Senn, Maria M.

2013-01-01

The Sec pathway plays a prominent role in protein export and membrane insertion, including the secretion of major bacterial virulence determinants. The accessory Sec constituent SecDF has been proposed to contribute to protein export. Deletion of Staphylococcus aureus secDF has previously been shown to reduce resistance, to alter cell separation, and to change the expression of certain virulence factors. To analyse the impact of the secDF deletion in S. aureus on protein secretion, a quantitative secretome analysis was performed. Numerous Sec signal containing proteins involved in virulence were found to be decreased in the supernatant of the secDF mutant. However, two Sec-dependent hydrolases were increased in comparison to the wild type, suggesting additional indirect, regulatory effects to occur upon deletion of secDF. Adhesion, invasion, and cytotoxicity of the secDF mutant were reduced in human umbilical vein endothelial cells. Virulence was significantly reduced using a Galleria mellonella insect model. Altogether, SecDF is a promising therapeutic target for controlling S. aureus infections. PMID:23658837

The RNA-binding protein repertoire of embryonic stem cells.

PubMed

Kwon, S Chul; Yi, Hyerim; Eichelbaum, Katrin; Föhr, Sophia; Fischer, Bernd; You, Kwon Tae; Castello, Alfredo; Krijgsveld, Jeroen; Hentze, Matthias W; Kim, V Narry

2013-09-01

RNA-binding proteins (RBPs) have essential roles in RNA-mediated gene regulation, and yet annotation of RBPs is limited mainly to those with known RNA-binding domains. To systematically identify the RBPs of embryonic stem cells (ESCs), we here employ interactome capture, which combines UV cross-linking of RBP to RNA in living cells, oligo(dT) capture and MS. From mouse ESCs (mESCs), we have defined 555 proteins constituting the mESC mRNA interactome, including 283 proteins not previously annotated as RBPs. Of these, 68 new RBP candidates are highly expressed in ESCs compared to differentiated cells, implicating a role in stem-cell physiology. Two well-known E3 ubiquitin ligases, Trim25 (also called Efp) and Trim71 (also called Lin41), are validated as RBPs, revealing a potential link between RNA biology and protein-modification pathways. Our study confirms and expands the atlas of RBPs, providing a useful resource for the study of the RNA-RBP network in stem cells.

Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes

PubMed Central

Glennie, Nelson D.; Volk, Susan W.

2017-01-01

Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells. This protection occurs rapidly after challenge, and requires the recruitment and activation of inflammatory monocytes, which limit parasites by production of both reactive oxygen species and nitric oxide. Overall, these data highlight a novel role for tissue-resident memory cells in recruiting and activating inflammatory monocytes, and underscore the central role that skin-resident T cells play in immunity to cutaneous leishmaniasis. PMID:28419151

Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression.

PubMed

Rossi, Giuliana; Antonini, Stefania; Bonfanti, Chiara; Monteverde, Stefania; Vezzali, Chiara; Tajbakhsh, Shahragim; Cossu, Giulio; Messina, Graziella

2016-03-08

Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The core planar cell polarity gene prickle interacts with flamingo to promote sensory axon advance in the Drosophila embryo.

PubMed

Mrkusich, Eli M; Flanagan, Dustin J; Whitington, Paul M

2011-10-01

The atypical cadherin Drosophila protein Flamingo and its vertebrate homologues play widespread roles in the regulation of both dendrite and axon growth. However, little is understood about the molecular mechanisms that underpin these functions. Whereas flamingo interacts with a well-defined group of genes in regulating planar cell polarity, previous studies have uncovered little evidence that the other core planar cell polarity genes are involved in regulation of neurite growth. We present data in this study showing that the planar cell polarity gene prickle interacts with flamingo in regulating sensory axon advance at a key choice point - the transition between the peripheral nervous system and the central nervous system. The cytoplasmic tail of the Flamingo protein is not required for this interaction. Overexpression of another core planar cell polarity gene dishevelled produces a similar phenotype to prickle mutants, suggesting that this gene may also play a role in regulation of sensory axon advance. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Who Supports the Successful Implementation and Sustainability of Evidence-Based Practices? Defining and Understanding the Roles of Intermediary and Purveyor Organizations.

PubMed

Franks, Robert P; Bory, Christopher T

2015-01-01

Research on implementation science has increased significantly over the past decade. In particular, psychologists have looked closely at the value and importance of bridging the gap between science and practice. As evidence-based practices (EBPs) become more prevalent, concrete mechanisms are needed to bring these scientifically supported treatments and interventions to community-based settings. Intermediary and purveyor organizations (IPOs) have emerged in recent years that specialize in bringing research to practice. Using a framework developed by Franks (), this descriptive study surveyed respondents that self-identified as IPOs and focused on identifying shared definitions, functions, and activities. Results indicated that seven descriptive roles previously identified were supported by this survey and many common shared activities, goals, and functions across these organizations were observed. Further, these organizations appear to be influenced by the growing field of implementation science. Limitations and implications of this study are discussed. © 2015 Wiley Periodicals, Inc.

The Nucleus Prepositus Hypoglossi Contributes to Head Direction Cell Stability in Rats

PubMed Central

Butler, William N.

2015-01-01

Head direction (HD) cells in the rat limbic system fire according to the animal's orientation independently of the animal's environmental location or behavior. These HD cells receive strong inputs from the vestibular system, among other areas, as evidenced by disruption of their directional firing after lesions or inactivation of vestibular inputs. Two brainstem nuclei, the supragenual nucleus (SGN) and nucleus prepositus hypoglossi (NPH), are known to project to the HD network and are thought to be possible relays of vestibular information. Previous work has shown that lesioning the SGN leads to a loss of spatial tuning in downstream HD cells, but the NPH has historically been defined as an oculomotor nuclei and therefore its role in contributing to the HD signal is less clear. Here, we investigated this role by recording HD cells in the anterior thalamus after either neurotoxic or electrolytic lesions of the NPH. There was a total loss of direction-specific firing in anterodorsal thalamus cells in animals with complete NPH lesions. However, many cells were identified that fired in bursts unrelated to the animals' directional heading and were similar to cells seen in previous studies that damaged vestibular-associated areas. Some animals with significant but incomplete lesions of the NPH had HD cells that were stable under normal conditions, but were unstable under conditions designed to minimize the use of external cues. These results support the hypothesis that the NPH, beyond its traditional oculomotor function, plays a critical role in conveying vestibular-related information to the HD circuit. PMID:25673848

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila

PubMed Central

Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke HM; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M

2016-01-01

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification. PMID:26757981

Abstract semantics in the motor system? - An event-related fMRI study on passive reading of semantic word categories carrying abstract emotional and mental meaning.

PubMed

Dreyer, Felix R; Pulvermüller, Friedemann

2018-03-01

Previous research showed that modality-preferential sensorimotor areas are relevant for processing concrete words used to speak about actions. However, whether modality-preferential areas also play a role for abstract words is still under debate. Whereas recent functional magnetic resonance imaging (fMRI) studies suggest an involvement of motor cortex in processing the meaning of abstract emotion words as, for example, 'love', other non-emotional abstract words, in particular 'mental words', such as 'thought' or 'logic', are believed to engage 'amodal' semantic systems only. In the present event-related fMRI experiment, subjects passively read abstract emotional and mental nouns along with concrete action related words. Contrary to expectation, the results indicate a specific involvement of face motor areas in the processing of mental nouns, resembling that seen for face related action words. This result was confirmed when subject-specific regions of interest (ROIs) defined by motor localizers were used. We conclude that a role of motor systems in semantic processing is not restricted to concrete words but extends to at least some abstract mental symbols previously thought to be entirely 'disembodied' and divorced from semantically related sensorimotor processing. Implications for neurocognitive theories of semantics and clinical applications will be highlighted, paying specific attention to the role of brain activations as indexes of cognitive processes and their relationships to 'causal' studies addressing lesion and transcranial magnetic stimulation (TMS) effects. Possible implications for clinical practice, in particular speech language therapy, are discussed in closing. Copyright © 2017. Published by Elsevier Ltd.

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila.

PubMed

Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke Hm; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M

2016-08-01

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification.

The Unculturables: targeted isolation of bacterial species associated with canine periodontal health or disease from dental plaque.

PubMed

Davis, Ian J; Bull, Christopher; Horsfall, Alexander; Morley, Ian; Harris, Stephen

2014-08-01

The current inability to culture the entirety of observed bacteria is well known and with the advent of ever more powerful molecular tools, that can survey bacterial communities at previously unattainable depth, the gap in our capacity to culture and define all of these species increases exponentially. This gap has essentially become the rate limiting step in determining how the knowledge of which species are present in a sample can be applied to understand the role of these species in an ecosystem or disease process. A case in point is periodontal disease, which is the most widespread oral disease in dogs. If untreated the disease results in significant pain, eventual loss of the dentition and potentially an increased risk of systemic diseases. Previous molecular based studies have identified the bacterial species associated with periodontal disease in dogs; however without cultured strains from many of these species it has not been possible to study whether they play a role in the disease process. Using a quantitative polymerase chain reaction (qPCR) directed approach a range of microbiological media were screened and optimized to enrich for previously uncultivated target species. A systematic screening methodology was then employed to isolate the species of interest. In cases where the target species were not cultivable in isolation, helper strains grown underneath a nitrocellulose membrane were used to provide the necessary growth factors. This guided media optimization approach enabled the purification of 14 species, 8 of which we had previously been unable to cultivate in isolation. It is also applicable to the targeted isolation of isolates from species that have previously been cultured (for example to study intra-species variation) as demonstrated by the successful isolation of 6 targeted isolates of already cultured species. To our knowledge this is the first time this combination of qPCR guided media optimization, strategic screening and helper strain support has been used successfully to isolate previously uncultured bacteria. This approach can be applied to any uncultured bacterial species where knowledge of their nutritional requirements or low relative abundance impedes their isolation.

A Salute to a Leader: ARL's Assessment Protocol Initiatives

ERIC Educational Resources Information Center

Heath, Fred

2009-01-01

This brief salute to Duane Webster and his defining role over the past several decades at the Association of Research Libraries (ARL) focuses on his formative role in defining and evolving the assessment protocols employed by both the association and the profession. (Contains 8 notes.)

Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients

PubMed Central

2010-01-01

Background Molecular chaperones have been shown to be important in the growth of the malaria parasite Plasmodium falciparum and inhibition of chaperone function by pharmacological agents has been shown to abrogate parasite growth. A recent study has demonstrated that clinical isolates of the parasite have distinct physiological states, one of which resembles environmental stress response showing up-regulation of specific molecular chaperones. Methods Chaperone networks operational in the distinct physiological clusters in clinical malaria parasites were constructed using cytoscape by utilizing their clinical expression profiles. Results Molecular chaperones show distinct profiles in the previously defined physiologically distinct states. Further, expression profiles of the chaperones from different cellular compartments correlate with specific patient clusters. While cluster 1 parasites, representing a starvation response, show up-regulation of organellar chaperones, cluster 2 parasites, which resemble active growth based on glycolysis, show up-regulation of cytoplasmic chaperones. Interestingly, cytoplasmic Hsp90 and its co-chaperones, previously implicated as drug targets in malaria, cluster in the same group. Detailed analysis of chaperone expression in the patient cluster 2 reveals up-regulation of the entire Hsp90-dependent pro-survival circuitries. In addition, cluster 2 also shows up-regulation of Plasmodium export element (PEXEL)-containing Hsp40s thought to have regulatory and host remodeling roles in the infected erythrocyte. Conclusion In all, this study demonstrates an intimate involvement of parasite-encoded chaperones, PfHsp90 in particular, in defining pathogenesis of malaria. PMID:20719001

Representation of action in occipito-temporal cortex.

PubMed

Wiggett, Alison J; Downing, Paul E

2011-07-01

A fundamental question for social cognitive neuroscience is how and where in the brain the identities and actions of others are represented. Here we present a replication and extension of a study by Kable and Chatterjee [Kable, J. W., & Chatterjee, A. Specificity of action representations in the lateral occipito-temporal cortex. Journal of Cognitive Neuroscience, 18, 1498-1517, 2006] examining the role of occipito-temporal cortex in these processes. We presented full-cue movies of actors performing whole-body actions and used fMRI to test for action- and identity-specific adaptation effects. We examined a series of functionally defined regions, including the extrastriate and fusiform body areas, the fusiform face area, the parahippocampal place area, the lateral occipital complex, the right posterior superior temporal sulcus, and motion-selective area hMT+. These regions were analyzed with both standard univariate measures as well as multivoxel pattern analyses. Additionally, we performed whole-brain tests for significant adaptation effects. We found significant action-specific adaptation in many areas, but no evidence for identity-specific adaptation. We argue that this finding could be explained by differences in the familiarity of the stimuli presented: The actions shown were familiar but the actors performing the actions were unfamiliar. However, in contrast to previous findings, we found that the action adaptation effect could not be conclusively tied to specific functionally defined regions. Instead, our results suggest that the adaptation to previously seen actions across identities is a widespread effect, evident across lateral and ventral occipito-temporal cortex.

Negative Mood Increases Selective Attention to Negatively Valenced Body Parts in Female Adolescents with Anorexia Nervosa

PubMed Central

Svaldi, Jennifer; Bender, Caroline; Caffier, Detlef; Ivanova, Viliana; Mies, Nina; Fleischhaker, Christian; Tuschen-Caffier, Brunna

2016-01-01

Objective Previous research has yielded evidence of increased attentional processing of negatively valenced body parts in women with anorexia nervosa (AN), especially for those with high depressive symptomatology. The present study extended previous research by implementing an experimental mood manipulation. Method In a within-subjects design, female adolescents with AN (n = 12) and an age matched female control group (CG; n = 12) were given a negative and a positive mood induction at a one-week interval. After each mood induction, participants underwent a 3-min mirror exposure, while their eye movements were recorded. Results After the positive mood induction, both AN and CG participants displayed longer and more frequent gazes towards their self-defined most ugly relative to their self-defined most beautiful body part. However, after the negative mood induction, only females with AN were characterized by increased attention to their most ugly compared to their most beautiful body part, while CG participants’ attention distribution was balanced. Furthermore, in the negative (but not in the positive) mood induction condition gaze frequency and duration towards the most ugly body part was significantly stronger in the AN group relative to the CG. Discussion The results emphasize the role of negative mood in the maintenance of pathological information processing of the self-body. This increased body-related negativity-bias during negative mood may lead to the persistence and aggravation of AN patients’ body image disturbance. PMID:27123587

Two betweenness centrality measures based on Randomized Shortest Paths

PubMed Central

Kivimäki, Ilkka; Lebichot, Bertrand; Saramäki, Jari; Saerens, Marco

2016-01-01

This paper introduces two new closely related betweenness centrality measures based on the Randomized Shortest Paths (RSP) framework, which fill a gap between traditional network centrality measures based on shortest paths and more recent methods considering random walks or current flows. The framework defines Boltzmann probability distributions over paths of the network which focus on the shortest paths, but also take into account longer paths depending on an inverse temperature parameter. RSP’s have previously proven to be useful in defining distance measures on networks. In this work we study their utility in quantifying the importance of the nodes of a network. The proposed RSP betweenness centralities combine, in an optimal way, the ideas of using the shortest and purely random paths for analysing the roles of network nodes, avoiding issues involving these two paradigms. We present the derivations of these measures and how they can be computed in an efficient way. In addition, we show with real world examples the potential of the RSP betweenness centralities in identifying interesting nodes of a network that more traditional methods might fail to notice. PMID:26838176

The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

PubMed

İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

2017-06-01

The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

Senescence and cancer: an evolving inflammatory paradox

PubMed Central

Ruhland, Megan; Coussens, Lisa M.; Stewart, Sheila

2015-01-01

The senescent phenotype was first describe in 1961 as a phenomenon characterized by the cessation of cellular division. After years of debate as to whether it represented a tissue culture artifact or an important biological process, it is now appreciated that senescence plays an important role in tumorigenesis. Further, senescence is integral to normal biological processes such as embryogenesis and the maintenance of tissue homeostasis. Now with defined roles in development, wound healing, tumor promotion and tumor suppression, it is not surprising that attention has turned to refining our understanding of the mechanisms behind, and consequences of, the induction of senescence. One emerging role for senescence lies in the ability of senescence to orchestrate an inflammatory responses: factors secreted by senescent cells have been identifed in multiple contexts to modulate various aspects of immune response. As with many of the previously described roles for senescence, the type of inflammation established by the senescence phenotype is varied and dependent on context. In this review, we discuss the current state of the field with a focus on the paradoxical outcomes of the senescence-induced inflammatory responses in the context of cancer. A more complete understanding of senescence and an appreciation for its complexities will be important for eventual development of senescence-targeted therapies. PMID:26453912

[Nucleolus transformation in oocytes of mouse antral follicles. Revealing of coilin and RNA polymerase I complex components].

PubMed

Pochukalina, G N; Parfenov, V N

2008-01-01

This study is the continuation of our previous investigation of the nucleolus transformation in growing oocytes from mouse multilayer follicles (Pochukalina, Parfenov, 2006). Here in the present research we have examined the features of organization and molecular composition of nucleolus like body, or postnucleolus, in two groups of oocytes with different chromatin configuration from mouse antral follicles. Using light and electron immunocytochemistry, we have defined the dynamics of ribosomal RNA synthesis and processing molecular component distribution in postnucleolus. Considerable changes in RNA polymerase I distribution and its colocalization with coilin at the periphery of postnucleolus were revealed. Putative role of coilin in formation of complexes with ribosomal RNA synthesis/processing components is discussed.

Normal Untreated Jurkat Cells

NASA Technical Reports Server (NTRS)

2004-01-01

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. The objective of the research was to define a way to differentiate between effects due to microgravity and those due to possible stress from non-optimal spaceflight conditions. These Jurkat cells, a human acute T-cell leukemia was obtained to evaluate three types of potential experimental stressors: a) Temperature elevation; b) Serum starvation; and c) Centrifugal force. The data from previous spaceflight experiments showed that actin filaments and cell shape are significantly different for the control. These normal cells serve as the baseline for future spaceflight experiments.

Microgravity

NASA Image and Video Library

2004-04-15

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. The objective of the research was to define a way to differentiate between effects due to microgravity and those due to possible stress from non-optimal spaceflight conditions. These Jurkat cells, a human acute T-cell leukemia was obtained to evaluate three types of potential experimental stressors: a) Temperature elevation; b) Serum starvation; and c) Centrifugal force. The data from previous spaceflight experiments showed that actin filaments and cell shape are significantly different for the control. These normal cells serve as the baseline for future spaceflight experiments.

Energy and molecules from photochemical/photocatalytic reactions. An overview.

PubMed

Ravelli, Davide; Protti, Stefano; Albini, Angelo

2015-01-16

Photocatalytic reactions have been defined as those processes that require both a (not consumed) catalyst and light. A previous definition was whether such reactions brought a system towards or away from the (thermal) equilibrium. This consideration brings in the question whether a part of the photon energy is incorporated into the photochemical reaction products. Data are provided for representative organic reactions involving or not molecular catalysts and show that energy storage occurs only when a heavily strained structure is generated, and in that case only a minor part of photon energy is actually stored (ΔG up to 25 kcal·mol-1). The green role of photochemistry/photocatalysis is rather that of forming highly reactive intermediates under mild conditions.

The role of basal forebrain cholinergic neurons in fear and extinction memory.

PubMed

Knox, Dayan

2016-09-01

Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral amygdala (BLA) is critical for neural function and synaptic plasticity in these brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp), and BLA has also been implicated in fear and extinction memory. This finding raises the possibility that basal forebrain (BF) cholinergic neurons, the predominant source of acetylcholine in these brain regions, have an important role in mediating fear and extinction memory. While empirical studies support this hypothesis, there are interesting inconsistencies among these studies that raise questions about how best to define the role of BF cholinergic neurons in fear and extinction memory. Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA are critical for fear memory and contextual fear extinction memory. NBM cholinergic neurons that project to the neocortex are critical for cued and contextual fear conditioned suppression, but are not critical for fear memory in other behavioral paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear memory formation. Medial septum and diagonal band of Broca cholinergic neurons are critical for contextual fear memory and acquisition of cued fear extinction. Thus, even though the results of previous studies suggest BF cholinergic neurons modulate fear and extinction memory, inconsistent findings among these studies necessitates more research to better define the neural circuits and molecular processes through which BF cholinergic neurons modulate fear and extinction memory. Furthermore, studies determining if BF cholinergic neurons can be manipulated in such a manner so as to treat excessive fear in anxiety disorders are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

The dual role of fragments in fragment-assembly methods for de novo protein structure prediction

PubMed Central

Handl, Julia; Knowles, Joshua; Vernon, Robert; Baker, David; Lovell, Simon C.

2013-01-01

In fragment-assembly techniques for protein structure prediction, models of protein structure are assembled from fragments of known protein structures. This process is typically guided by a knowledge-based energy function and uses a heuristic optimization method. The fragments play two important roles in this process: they define the set of structural parameters available, and they also assume the role of the main variation operators that are used by the optimiser. Previous analysis has typically focused on the first of these roles. In particular, the relationship between local amino acid sequence and local protein structure has been studied by a range of authors. The correlation between the two has been shown to vary with the window length considered, and the results of these analyses have informed directly the choice of fragment length in state-of-the-art prediction techniques. Here, we focus on the second role of fragments and aim to determine the effect of fragment length from an optimization perspective. We use theoretical analyses to reveal how the size and structure of the search space changes as a function of insertion length. Furthermore, empirical analyses are used to explore additional ways in which the size of the fragment insertion influences the search both in a simulation model and for the fragment-assembly technique, Rosetta. PMID:22095594

Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish

PubMed Central

Monteiro, Diana A.; Taylor, Edwin W.; Sartori, Marina R.; Cruz, André L.; Rantin, Francisco T.; Leite, Cleo A. C.

2018-01-01

The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems. PMID:29507882

Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish.

PubMed

Monteiro, Diana A; Taylor, Edwin W; Sartori, Marina R; Cruz, André L; Rantin, Francisco T; Leite, Cleo A C

2018-02-01

The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems.

Sucrose accumulation in sweet sorghum stems occurs by apoplasmic phloem unloading and does not involve differential Sucrose transporter expression

DOE PAGES

Bihmidine, Saadia; Baker, R. Frank; Hoffner, Cassandra; ...

2015-07-30

Background: Sorghum (Sorghum bicolor L. Moench) cultivars store non-structural carbohydrates predominantly as either starch in seeds (grain sorghums) or sugars in stems (sweet sorghums). Previous research determined that sucrose accumulation in sweet sorghum stems was not correlated with the activities of enzymes functioning in sucrose metabolism, and that an apoplasmic transport step may be involved in stem sucrose accumulation. However, the sucrose unloading pathway from stem phloem to storage parenchyma cells remains unelucidated. Sucrose transporters (SUTs) transport sucrose across membranes, and have been proposed to function in sucrose partitioning differences between sweet and grain sorghums. The purpose of this studymore » was to characterize the key differences in carbohydrate accumulation between a sweet and a grain sorghum, to define the path sucrose may follow for accumulation in sorghum stems, and to determine the roles played by sorghum SUTs in stem sucrose accumulation. Results: Dye tracer studies to determine the sucrose transport route revealed that, for both the sweet sorghum cultivar Wray and grain sorghum cultivar Macia, the phloem in the stem veins was symplasmically isolated from surrounding cells, suggesting sucrose was apoplasmically unloaded. Once in the phloem apoplasm, a soluble tracer diffused from the vein to stem parenchyma cell walls, indicating the lignified mestome sheath encompassing the vein did not prevent apoplasmic flux outside of the vein. To characterize carbohydrate partitioning differences between Wray and Macia, we compared the growth, stem juice volume, solute contents, SbSUTs gene expression, and additional traits. Contrary to previous findings, we detected no significant differences in SbSUTs gene expression within stem tissues. Conclusions: Phloem sieve tubes within sweet and grain sorghum stems are symplasmically isolated from surrounding cells; hence, unloading from the phloem likely occurs apoplasmically, thereby defining the location of the previously postulated step for sucrose transport. Additionally, no changes in SbSUTs gene expression were detected in sweet vs. grain sorghum stems, suggesting alterations in SbSUT transcript levels do not account for the carbohydrate partitioning differences between cultivars. A model illustrating sucrose phloem unloading and movement to stem storage parenchyma, and highlighting roles for sucrose transport proteins in sorghum stems is discussed.« less

A rho-binding protein kinase C-like activity is required for the function of protein kinase N in Drosophila development.

PubMed

Betson, Martha; Settleman, Jeffrey

2007-08-01

The Rho GTPases interact with multiple downstream effectors to exert their biological functions, which include important roles in tissue morphogenesis during the development of multicellular organisms. Among the Rho effectors are the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like kinases that bind activated Rho GTPases. The PKN proteins are well conserved evolutionarily, but their biological role in any organism is poorly understood. We previously determined that the single Drosophila ortholog of mammalian PKN proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development. By performing "rescue" studies with various Pkn mutant constructs, we have defined the domains of Pkn required for its role during Drosophila development. These studies suggested that Rho, but not Rac binding is important for Pkn function in development. In addition, we determined that the kinase domain of PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of Pkn during development, thereby exemplifying the evolutionary strategy of "combining" functional domains to produce proteins with distinct biological activities. Interestingly, we also identified a requirement for Pkn in wing morphogenesis, thereby revealing the first postembryonic function for Pkn.

[Competencies and Role Experiences of Peer Support - A Participatory Research Report].

PubMed

Heumann, Kolja; Schmid, Christine; Wilfer, Antje; Bolkan, Suzan; Mahlke, Candelaria; von Peter, Sebastian

2018-05-25

This study explores the peer support providers' competencies and role experiences. A multiple coding approach has been used to collaboratively analyze and discuss ethnographic material. Compared to other professionals, peer support provider engage with patients in a more open and less classificatory way. Their role is often unclear and defined by both more flexibility and dependencies. It is important to clearly define the competencies and roles of peer support providers and balance them with the expectations of the other professionals. © Georg Thieme Verlag KG Stuttgart · New York.

Universities' expectations of pastoral care: trends, stressors, resource gaps and support needs for teaching staff.

PubMed

Laws, Thomas A; Fiedler, Brenton A

2012-10-01

Since the mid-90s, the university environment has challenged the motivation of academic staff to engage in pastoral care. A literature review revealed five themes that aligned with analysis of interview data from a previous study (Laws and Fiedler, 2010). The key themes were i) staff were often disturbed by unplanned intrusions of students who exhibited behavioural problems or sought emotional support, ii) the management of emotions in face-to-face encounters was stressful, iii) staff felt under-equipped for dealing with Mental Health (MH) issues, iv) standards and control needed updating and v) counselling and disability services did not meet academics' need to know about 'at risk' students. Having identified the incidence of mental health issues among Australian University students, this study aims to locate literature that describes how well current university policies/protocols are supported by Evidence Based Practice in the management of MH problems in the student population. Findings from a content analysis of the literature were triangulated with verbatim comments recorded during a previous study that utilised semi structured interviews with 34 academics at the School of Nursing and Midwifery and the School of Commerce at the University of South Australia (Laws and Fiedler, 2010). Lack of clarity on role boundaries around promotion of students' well-being was not clearly defined. The Higher Education (HE) institutions' slowness in responding to mental health needs of students combined with the increasing expectations of academics' performance monitoring has lead staff to avoid deep investment in their students' well-being. The literature indicates that students are in need of psychological support, but pastoral care remains ill-defined despite enduring expectations held by university administrators. Teacher motivation is diminished by time spent with students in need of emotional support which is not acknowledged in workloads. Staff stress is increased by 'emotion work' requiring a greater integration of resources that guide them toward more appropriate and timely student support. Staff require ongoing professional development on the nature of MH problems among students. There is a need for specific orientation programs that better define pastoral care and identify support services for staff and students. Universities need to focus on what is needed to create a well-being environment. Workload allocations must include 'emotion work', and mental health professionals must be employed to improve intervention and support not only for students but also for University staff. With better defined pastoral care roles, academics can more effectively balance their intrinsic and extrinsic motivations toward both personal and corporate objectives. Further research into the efficacy of university resourcing of programs and services is needed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Leading Charters: How Charter School Administrators Define Their Roles and Their Ability to Lead

ERIC Educational Resources Information Center

Carpenter, Dick Michael, II; Peak, Charity

2013-01-01

Charter schools have been studied from numerous perspectives. One topic that remains under-researched, however, is charter school leadership. Therefore, we examine how charter administrators define their leadership roles and their ability to lead. Results indicate that charter principals see three primary functions in their leadership--building…

Torn in Two: An Examiniation of Elementary School Counselors' Perceptions on Self-Efficacy

ERIC Educational Resources Information Center

Sesto, Casper

2013-01-01

The American School Counselor Association (ASCA; The ASCA National Model: A Framework for School Counseling Programs, 2005) developed the ASCA National Model to define the prescribed roles and functions of the professional school counselor. Although the national model initially defines school counselors' roles, counselors find it difficult to…

The theory of n-scales

NASA Astrophysics Data System (ADS)

Dündar, Furkan Semih

2018-01-01

We provide a theory of n-scales previously called as n dimensional time scales. In previous approaches to the theory of time scales, multi-dimensional scales were taken as product space of two time scales [1, 2]. n-scales make the mathematical structure more flexible and appropriate to real world applications in physics and related fields. Here we define an n-scale as an arbitrary closed subset of ℝn. Modified forward and backward jump operators, Δ-derivatives and Δ-integrals on n-scales are defined.

26 CFR 1.410(b)-3 - Employees and former employees who benefit under a plan.

Code of Federal Regulations, 2013 CFR

2013-04-01

... determining accrual rates under the section 401(a)(4) general test. (C) Defined contribution plans. A defined... basis to all employees in the plan. Thus, for example, if the formula under a defined benefit plan takes... determined under the plan if the benefit previously accrued were disregarded. This could happen, for example...

26 CFR 1.410(b)-3 - Employees and former employees who benefit under a plan.

Code of Federal Regulations, 2010 CFR

2010-04-01

... under the section 401(a)(4) general test. (C) Defined contribution plans. A defined contribution plan is... the plan. Thus, for example, if the formula under a defined benefit plan takes into account only the... benefit previously accrued were disregarded. This could happen, for example, when the plan is applying the...

Defining Sex and Abstinence: Dialogue Is the Key

ERIC Educational Resources Information Center

Hamill, Shelley D.; Chepko, Stevie

2005-01-01

When does abstinence end and sexual activity begin? In previous generations, the continuum of sexual activity was well-defined in the old baseball analogy. Teens, parents, and teachers knew what going to first, second, or third base involved. For the current generation of young people, sex and abstinence are not so well-defined. As parents and…

The role of the public health nurse in a changing society.

PubMed

Nic Philibin, Caitriona Aine; Griffiths, Colin; Byrne, Gobnait; Horan, Paul; Brady, Anne-Marie; Begley, Cecily

2010-04-01

This study is a report of a study to clarify the role of the public health nurse in one Irish community care area in the light of acknowledged problems in defining boundaries of the role. Demographic developments and planned reorientation towards primary care of the health service in Ireland have changed the workload of public health nurses, which is unique compared with other countries. However, there is a lack of clarity and consequent problems in defining the role of the Irish public health nurse. A descriptive qualitative study was conducted with 25 representatives of community nursing from one county in Ireland with a population of 209,077 and a complement of 65 full-time equivalent public health nurses. Purposive sampling was used and 21 public health nurses, two registered general nurses, one assistant director and one school nurse participated. Tape-recorded, individual semi-structured interviews were conducted over a 15-month period from 2002 to 2004. The constant comparative method was used for analysis. Four themes emerged: 'Jack of all trades: the role of the public health nurse defined and described', 'the essence of the role', 'challenges to the role of the public health nurse' and 'communication'. The first theme is discussed in this paper. Public health nurses need to define and redesign their role so that they no longer think that they are the catch-all service in the community. This will enable them to deal with the rapid demographic, sociological and cultural changes in the population, a change that has international resonance.

The ankyrin-3 gene is associated with posttraumatic stress disorder and externalizing comorbidity

PubMed Central

Logue, Mark W.; Solovieff, Nadia; Leussis, Melanie P.; Wolf, Erika J.; Melista, Efi; Baldwin, Clinton; Koenen, Karestan C.; Petryshen, Tracey; Miller, Mark W.

2013-01-01

Background The ankyrin 3 gene (ANK3) produces the ankyrin G protein that plays an integral role in regulating neuronal activity. Previous studies have linked ANK3 to bipolar disorder and schizophrenia. A recent mouse study suggests that ANK3 may regulate behavioral disinhibition and stress reactivity. This led us to hypothesize that ANK3 might also be associated with stress-related psychopathology such as posttraumatic stress disorder (PTSD), as well as disorders of the externalizing spectrum such as antisocial personality disorder and substance-related disorders that are etiologically linked to impulsivity and temperamental disinhibition. Methods We examined the possibility of association between ANK3 SNPs and both PTSD and externalizing (defined by a factor score representing a composite of adult antisociality and substance abuse) in a cohort of white non-Hispanic combat veterans and their intimate partners (N=554). Initially, we focused on rs9804190— a SNP previously reported to be associated with bipolar disorder, schizophrenia, and ankyrin G expression in brain. Then we examined 358 additional ANK3 SNPs utilizing a multiple-testing correction. Results rs9804190 was associated with both externalizing and PTSD (p=0.028 and p=0.042 respectively). Analysis of other ANK3 SNPs identified several that were more strongly associated with either trait. The most significant association with externalizing was observed at rs1049862 (p=0.00040, pcorrected=0.60). The most significant association with PTSD (p=0.00060, pcorrected=0.045) was found with three SNPs in complete linkage disequilibrium (LD)—rs28932171, rs11599164, and rs17208576. Conclusions These findings support a role of ANK3 in risk of stress-related and externalizing disorders, beyond its previous associations with bipolar disorder and schizophrenia. PMID:23796624

Betwixt and between: Role conflict, role ambiguity and role definition in project-based dual-leadership structures.

PubMed

Ebbers, Joris J; Wijnberg, Nachoem M

2017-11-01

Project-based organizations in the film industry usually have a dual-leadership structure, based on a division of tasks between the dual leaders - the director and the producer - in which the former is predominantly responsible for the artistic and the latter for the commercial aspects of the film. These organizations also have a role hierarchically below and between the dual leaders: the 1st assistant director. This organizational constellation is likely to lead to role conflict and role ambiguity experienced by the person occupying that particular role. Although prior studies found negative effects of role conflict and role ambiguity, this study shows they can also have beneficial effects because they create space for defining the role expansively that, in turn, can be facilitated by the dual leaders defining their own roles more narrowly. In a more general sense, this study also shows the usefulness of analyzing the antecedents and consequences of roles, role definition, and role crafting in connection to the behavior of occupants of adjacent roles.

DNA binding mechanism revealed by high resolution crystal structure of Arabidopsis thaliana WRKY1 protein

PubMed Central

Duan, Ming-Rui; Nan, Jie; Liang, Yu-He; Mao, Peng; Lu, Lu; Li, Lanfen; Wei, Chunhong; Lai, Luhua; Li, Yi; Su, Xiao-Dong

2007-01-01

WRKY proteins, defined by the conserved WRKYGQK sequence, are comprised of a large superfamily of transcription factors identified specifically from the plant kingdom. This superfamily plays important roles in plant disease resistance, abiotic stress, senescence as well as in some developmental processes. In this study, the Arabidopsis WRKY1 was shown to be involved in the salicylic acid signaling pathway and partially dependent on NPR1; a C-terminal domain of WRKY1, AtWRKY1-C, was constructed for structural studies. Previous investigations showed that DNA binding of the WRKY proteins was localized at the WRKY domains and these domains may define novel zinc-binding motifs. The crystal structure of the AtWRKY1-C determined at 1.6 Å resolution has revealed that this domain is composed of a globular structure with five β strands, forming an antiparallel β-sheet. A novel zinc-binding site is situated at one end of the β-sheet, between strands β4 and β5. Based on this high-resolution crystal structure and site-directed mutagenesis, we have defined and confirmed that the DNA-binding residues of AtWRKY1-C are located at β2 and β3 strands. These results provided us with structural information to understand the mechanism of transcriptional control and signal transduction events of the WRKY proteins. PMID:17264121

The Urinary Bladder Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling

PubMed Central

Habuka, Masato; Fagerberg, Linn; Hallström, Björn M.; Pontén, Fredrik; Yamamoto, Tadashi; Uhlen, Mathias

2015-01-01

To understand functions and diseases of urinary bladder, it is important to define its molecular constituents and their roles in urinary bladder biology. Here, we performed genome-wide deep RNA sequencing analysis of human urinary bladder samples and identified genes up-regulated in the urinary bladder by comparing the transcriptome data to those of all other major human tissue types. 90 protein-coding genes were elevated in the urinary bladder, either with enhanced expression uniquely in the urinary bladder or elevated expression together with at least one other tissue (group enriched). We further examined the localization of these proteins by immunohistochemistry and tissue microarrays and 20 of these 90 proteins were localized to the whole urothelium with a majority not yet described in the context of the urinary bladder. Four additional proteins were found specifically in the umbrella cells (Uroplakin 1a, 2, 3a, and 3b), and three in the intermediate/basal cells (KRT17, PCP4L1 and ATP1A4). 61 of the 90 elevated genes have not been previously described in the context of urinary bladder and the corresponding proteins are interesting targets for more in-depth studies. In summary, an integrated omics approach using transcriptomics and antibody-based profiling has been used to define a comprehensive list of proteins elevated in the urinary bladder. PMID:26694548

Suppressors of systemin signaling identify genes in the tomato wound response pathway.

PubMed Central

Howe, G A; Ryan, C A

1999-01-01

In tomato plants, systemic induction of defense genes in response to herbivory or mechanical wounding is regulated by an 18-amino-acid peptide signal called systemin. Transgenic plants that overexpress prosystemin, the systemin precursor, from a 35S::prosystemin (35S::prosys) transgene exhibit constitutive expression of wound-inducible defense proteins including proteinase inhibitors and polyphenol oxidase. To study further the role of (pro)systemin in the wound response pathway, we isolated and characterized mutations that suppress 35S::prosys-mediated phenotypes. Ten recessive, extragenic suppressors were identified. Two of these define new alleles of def-1, a previously identified mutation that blocks both wound- and systemin-induced gene expression and renders plants susceptible to herbivory. The remaining mutants defined four loci designated Spr-1, Spr-2, Spr-3, and Spr-4 (for Suppressed in 35S::prosystemin-mediated responses). spr-3 and spr-4 mutants were not significantly affected in their response to either systemin or mechanical wounding. In contrast, spr-1 and spr-2 plants lacked systemic wound responses and were insensitive to systemin. These results confirm the function of (pro)systemin in the transduction of systemic wound signals and further establish that wounding, systemin, and 35S::prosys induce defensive gene expression through a common signaling pathway defined by at least three genes (Def-1, Spr-1, and Spr-2). PMID:10545469

Ultrasound-enhanced thrombolysis using Definity as a cavitation nucleation agent.

PubMed

Datta, Saurabh; Coussios, Constantin-C; Ammi, Azzdine Y; Mast, T Douglas; de Courten-Myers, Gabrielle M; Holland, Christy K

2008-09-01

Ultrasound has been shown previously to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity, was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and used to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual-antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120-kHz ultrasound (0.32-MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity. A significant correlation was observed between mass loss and ultraharmonic signals (r = 0.85, p < 0.0001, n = 24). The largest mean penetration depth of rt-PA (222 microm) and plasminogen (241 microm) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment.

Interaction between blood-brain barrier and glymphatic system in solute clearance.

PubMed

Verheggen, I C M; Van Boxtel, M P J; Verhey, F R J; Jansen, J F A; Backes, W H

2018-03-30

Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-β, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-β accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Extending the Borders of Community and Learning with Electronic Mail Discussion Lists.

ERIC Educational Resources Information Center

Yungbluth, Stephen C.; Bertino, Sissy

A qualitative study determined the impact electronic mail (e-mail) discussion lists can have on a college classroom. The theoretical concepts explored are "community" and "roles." Community is defined by the boundaries it possesses, the dialogue exchanged, and the people interacting in the community. Roles may be defined by the interactions among…

"Newbies" and "Celebrities": Detecting Social Roles in an Online Network of Teachers via Participation Patterns

ERIC Educational Resources Information Center

Smith Risser, H.; Bottoms, SueAnn

2014-01-01

The advent of social networking tools allows teachers to create online networks and share information. While some virtual networks have a formal structure and defined boundaries, many do not. These unstructured virtual networks are difficult to study because they lack defined boundaries and a formal structure governing leadership roles and the…

Sensitivity analysis as an aid in modelling and control of (poorly-defined) ecological systems. [closed ecological systems

NASA Technical Reports Server (NTRS)

Hornberger, G. M.; Rastetter, E. B.

1982-01-01

A literature review of the use of sensitivity analyses in modelling nonlinear, ill-defined systems, such as ecological interactions is presented. Discussions of previous work, and a proposed scheme for generalized sensitivity analysis applicable to ill-defined systems are included. This scheme considers classes of mathematical models, problem-defining behavior, analysis procedures (especially the use of Monte-Carlo methods), sensitivity ranking of parameters, and extension to control system design.

Fine needle aspiration cytology of hepatic metastasis from a meningeal hemangiopericytoma. A case report.

PubMed

Ghaffar, Hasan; Parwani, Anil; Rosenthal, Dorothy L

2003-01-01

Hemangiopericytomas (HPCs) are rare spindle cell tumors, constituting 2.5% of soft tissue neoplasms. Few reports have addressed the fine needle aspiration (FNA) cytology of HPC. We describe the FNA biopsy (FNAB) findings in a 44-year-old patient with a previously resected meningeal hemangiopericytoma. The patient underwent ultrasound-guided FNAB of a 16.0-cm, radiographically heterogeneous density in the liver. The FNA smear showed crowded, ovoid to spindle-shaped cells with poorly defined, scant cytoplasm. The neoplastic cells were positive for CD34 and negative for CD31, factor VIII, glial fibrillary acid protein and cytokeratin AE1/AE3, supporting a diagnosis of HPC and compatible with metastasis from the patient's cerebral tumor. This case documents the role of FNA cytology in confirming HPC.

Structural correlation between lipophilicity and lipopolysaccharide-sequestering activity in spermine-sulfonamide analogs.

PubMed

Burns, Mark R; Jenkins, Scott A; Vermeulen, Nicolas M; Balakrishna, Rajalakshmi; Nguyen, Thuan B; Kimbrell, Matthew R; David, Sunil A

2006-12-15

Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria, and play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. We had previously defined the pharmacophore necessary for small molecules to specifically bind and neutralize this complex carbohydrate. A series of aryl and aliphatic spermine-sulfonamide analogs were synthesized and tested in a series of binding and cell-based assays in order to probe the effect of lipophilicity on sequestration ability. A strong correlation was indeed found, supporting the hypothesis that endotoxin-neutralizing ability involves a lipophilic or membrane attachment event. The research discussed herein may be useful for the design of additional carbohydrate recognizing molecules and endotoxin-neutralizing drugs.

Amantadine in the Treatment of Pathological Gambling: A Case Report

PubMed Central

Pettorruso, Mauro; Martinotti, Giovanni; Di Nicola, Marco; Onofrj, Marco; Di Giannantonio, Massimo; Conte, Gianluigi; Janiri, Luigi

2012-01-01

Despite almost a decade of intense research, effective treatment strategies for Pathological Gambling (PG) remain very challenging. This paper details a case report suggesting that the treatment of PG may benefit from the use of the non-specific glutamate blocker amantadine. The drug was well-tolerated and effective, leading to a 43–64% reduction in severity of gambling symptoms (as measured with G-SAS). Our result is discussed in the context of the glutamatergic hypothesis of addiction and in light of previous observations on the potential impact of glutamatergic agents in the treatment of PG. The role of the dopaminergic system, and its interaction with the glutamatergic system, is also explored. Further studies are required to define the true benefits of amantadine for the treatment of PG. PMID:23205015

Teasing in hierarchical and intimate relations.

PubMed

Keltner, D; Young, R C; Heerey, E A; Oemig, C; Monarch, N D

1998-11-01

Following E. Goffman's (1967) face threat analysis of social interaction, it was hypothesized that the aggressive, playful content of teasing would vary according to social status and relational satisfaction, personality, role as teaser or target, and gender. These 4 hypotheses were tested in analyses of the teasing among fraternity members (Study 1) and romantic couples (Study 2). Consistent with a face threat analysis of teasing, low-status fraternity members and satisfied romantic partners teased in more prosocial ways, defined by reduced face threat and increased redressive action. Some findings indicate that disagreeable individuals teased in less prosocial ways, consistent with studies of bullying. Targets reported more negative emotion than teasers. Although female and male romantic partners teased each other in similar ways, women found being the target of teasing more aversive, consistent with previous speculation.

Neuroethics: a modern context for ethics in neuroscience

PubMed Central

Illes, Judy; Bird, Stephanie J.

2006-01-01

Neuroethics, a recently modernized field at the intersection of bioethics and neuroscience, is founded on centuries of discussion of the ethical issues associated with mind and behavior. Broadly defined, neuroethics is concerned with ethical, legal and social policy implications of neuroscience, and with aspects of neuroscience research itself. Advances in neuroscience increasingly challenge long-held views of the self and the individual's relationship to society. Neuroscience also has led to innovations in clinical medicine that have not only therapeutic but also non-therapeutic dimensions that extend well beyond previously charted boundaries. The exponential increase in cross-disciplinary research, the commercialization of cognitive neuroscience, the impetus for training in ethics, and the increased attention being paid to public understanding of science all illuminate the important role of neuroethics in neuroscience. PMID:16859760

Recommendations for breast imaging follow-up of women with a previous history of breast cancer: position paper from the Italian Group for Mammography Screening (GISMa) and the Italian College of Breast Radiologists (ICBR) by SIRM.

PubMed

Bucchi, Lauro; Belli, Paolo; Benelli, Eva; Bernardi, Daniela; Brancato, Beniamino; Calabrese, Massimo; Carbonaro, Luca A; Caumo, Francesca; Cavallo-Marincola, Beatrice; Clauser, Paola; Fedato, Chiara; Frigerio, Alfonso; Galli, Vania; Giordano, Livia; Golinelli, Paola; Mariscotti, Giovanna; Martincich, Laura; Montemezzi, Stefania; Morrone, Doralba; Naldoni, Carlo; Paduos, Adriana; Panizza, Pietro; Pediconi, Federica; Querci, Fiammetta; Rizzo, Antonio; Saguatti, Gianni; Tagliafico, Alberto; Trimboli, Rubina M; Zuiani, Chiara; Sardanelli, Francesco

2016-12-01

Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0-1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15-20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient's age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness.

Sutures, Sinkers, Shear zones and Sills: Cryptic Targets and Explicit Strategies for EARTHSCOPE FlexArray in the East

NASA Astrophysics Data System (ADS)

Brown, L. D.

2006-05-01

Given the 3D framework represented by EarthScope's USArray as it scans eastward, the strategic challenge falls to defining cost-effective deployments of FlexArray to address specific lithospheric targets. Previous deep geophysical surveys (e.g. COCORP, USGS, GLIMPCE, et al.) provide guidance not only in framing the geological issues involved, but in designing field experiments that overcome the limitations of previous work. Opportunities highlighted by these precursor studies include: a) Collisional sutures (e.g. Brunswick Anomaly/Suwannee terrane) which lie buried beneath overthrust terranes/ younger sedimentary covers. Signal penetration in previous controlled source surveys has been insufficient. High resolution passive surveys designed to map intralithospheric detachments, Moho, and mantle subduction scars is needed to validate the extrapolations of the existing upper crustal information; b) Intracratonic basins and domes (e.g. Michigan Basin, Adirondack Dome) are perhaps the greatest geological mystery hosted in the east. Previous geophysical studies have lacked the resolution or penetration needed to identify the buoyancy drivers presumed to be responsible for such structures. It is likely that these drivers lie in the upper mantle and will require detailed velocity imaging to recognized. c) Distributed shear fabrics are a defining characteristic of the deep crust in many deformation zones (e.g. Grenville Front). Detailed mapping of crustal anisotropy associated with such shear zones should help delineate ductile flow directions associated with the orogenies that accreted the eastern U.S. 3 component, 3D active+passive surveys are needed to obtain definitive remote measures of such vector characteristics in the deep crust. d) Extensive reflectors in the central U.S. may mark important buried Precambrian basins and/or sill complexes. If the latter, the magmatic roots of those systems remain unrecognized, as does their volumetric contribution to crustal growth. 3C expanding spreads to resolve lithology in the upper crust, coupled with passive imaging of potential mantle sources, are needed to evaluate the role of these sequences in mid Proterozoic continental evolution. Effective experiments must build upon existing data, be strategic in the selection of the various FlexArray tools available, and link operationally with the Bigfoot deployments in an appropriately staged fashion.

Beta Atomic Contacts: Identifying Critical Specific Contacts in Protein Binding Interfaces

PubMed Central

Liu, Qian; Kwoh, Chee Keong; Hoi, Steven C. H.

2013-01-01

Specific binding between proteins plays a crucial role in molecular functions and biological processes. Protein binding interfaces and their atomic contacts are typically defined by simple criteria, such as distance-based definitions that only use some threshold of spatial distance in previous studies. These definitions neglect the nearby atomic organization of contact atoms, and thus detect predominant contacts which are interrupted by other atoms. It is questionable whether such kinds of interrupted contacts are as important as other contacts in protein binding. To tackle this challenge, we propose a new definition called beta (β) atomic contacts. Our definition, founded on the β-skeletons in computational geometry, requires that there is no other atom in the contact spheres defined by two contact atoms; this sphere is similar to the van der Waals spheres of atoms. The statistical analysis on a large dataset shows that β contacts are only a small fraction of conventional distance-based contacts. To empirically quantify the importance of β contacts, we design βACV, an SVM classifier with β contacts as input, to classify homodimers from crystal packing. We found that our βACV is able to achieve the state-of-the-art classification performance superior to SVM classifiers with distance-based contacts as input. Our βACV also outperforms several existing methods when being evaluated on several datasets in previous works. The promising empirical performance suggests that β contacts can truly identify critical specific contacts in protein binding interfaces. β contacts thus provide a new model for more precise description of atomic organization in protein quaternary structures than distance-based contacts. PMID:23630569

Transfer matrix computation of generalized critical polynomials in percolation

DOE PAGES

Scullard, Christian R.; Jacobsen, Jesper Lykke

2012-09-27

Percolation thresholds have recently been studied by means of a graph polynomial PB(p), henceforth referred to as the critical polynomial, that may be defined on any periodic lattice. The polynomial depends on a finite subgraph B, called the basis, and the way in which the basis is tiled to form the lattice. The unique root of P B(p) in [0, 1] either gives the exact percolation threshold for the lattice, or provides an approximation that becomes more accurate with appropriately increasing size of B. Initially P B(p) was defined by a contraction-deletion identity, similar to that satisfied by the Tuttemore » polynomial. Here, we give an alternative probabilistic definition of P B(p), which allows for much more efficient computations, by using the transfer matrix, than was previously possible with contraction-deletion. We present bond percolation polynomials for the (4, 82), kagome, and (3, 122) lattices for bases of up to respectively 96, 162, and 243 edges, much larger than the previous limit of 36 edges using contraction-deletion. We discuss in detail the role of the symmetries and the embedding of B. For the largest bases, we obtain the thresholds p c(4, 82) = 0.676 803 329 · · ·, p c(kagome) = 0.524 404 998 · · ·, p c(3, 122) = 0.740 420 798 · · ·, comparable to the best simulation results. We also show that the alternative definition of P B(p) can be applied to study site percolation problems.« less

Role of resting cysts in Chilean Alexandrium catenella dinoflagellate blooms revisited.

PubMed

Mardones, Jorge I; Bolch, Chris; Guzmán, Leonardo; Paredes, Javier; Varela, Daniel; Hallegraeff, Gustaaf M

2016-05-01

The detection of sparse Alexandrium catenella-resting cysts in sediments of southern Chilean fjords has cast doubts on their importance in the recurrence of massive toxic dinoflagellate blooms in the region. The role of resting cysts and the existence of different regional Chilean populations was studied by culturing and genetic approaches to define: (1) cyst production; (2) dormancy period; (3) excystment success; (4) offspring viability and (5) strain mating compatibility. This study newly revealed a short cyst dormancy (minimum 69 days), the role of key abiotic factors (in decreasing order salinity, irradiance, temperature and nutrients) controlling cyst germination (max. 60%) and germling growth rates (up to 0.36-0.52div.day -1 ). Amplified fragment length polymorphism (AFLP) characterization showed significant differences in genetic distances (GD) among A. catenella populations that were primarily determined by the geographical origin of isolates and most likely driven by oceanographic dispersal barriers. A complex heterothallic mating system pointed to variable reproductive compatibility (RCs) among Chilean strains that was high among northern (Los Lagos/North Aysén) and southern populations (Magallanes), but limited among the genetically differentiated central (South Aysén) populations. Field cyst surveys after a massive 2009 bloom event revealed the existence of exceptional high cyst densities in particular areas of the fjords (max. 14.627cystscm -3 ), which contrast with low cyst concentrations (<221.3cystscm -3 ) detected by previous oceanographic campaigns. In conclusion, the present study suggests that A. catenella resting cysts play a more important role in the success of this species in Chilean fjords than previously thought. Results from in vitro experiments suggest that pelagic-benthic processes can maintain year-round low vegetative cell concentrations in the water column, but also can explain the detection of high cysts aggregations after the 2009-bloom event. Regional drivers that lead to massive outbreaks, however, are still unknown but potential scenarios are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of metadata in managing large environmental science datasets. Proceedings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melton, R.B.; DeVaney, D.M.; French, J. C.

1995-06-01

The purpose of this workshop was to bring together computer science researchers and environmental sciences data management practitioners to consider the role of metadata in managing large environmental sciences datasets. The objectives included: establishing a common definition of metadata; identifying categories of metadata; defining problems in managing metadata; and defining problems related to linking metadata with primary data.

National Agricultural-Based Lubricants (NABL) Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honary, Lou

2013-09-30

This project, while defined as a one year project from September 30, 2012 – September 30, 2013, was a continuation of a number of tasks that were defined in previous years. Those tasks were performed and were finalized in this period. The UNI-NABL Center, which has been in operation in various forms since 1991, has closed its facilities since September 2013 and will be phasing out in June 2014. This report covers the individual tasks that were identified in the previous reports and provides closure to each task in its final stage.

On Displacement Height, from Classical to Practical Formulation: Stress, Turbulent Transport and Vorticity Considerations

NASA Astrophysics Data System (ADS)

Sogachev, Andrey; Kelly, Mark

2016-03-01

Displacement height ( d) is an important parameter in the simple modelling of wind speed and vertical fluxes above vegetative canopies, such as forests. Here we show that, aside from implicit definition through a (displaced) logarithmic profile, accepted formulations for d do not consistently predict flow properties above a forest. Turbulent transport can affect the displacement height, and is an integral part of what is called the roughness sublayer. We develop a more general approach for estimation of d, through production of turbulent kinetic energy and turbulent transport, and show how previous stress-based formulations for displacement height can be seen as simplified cases of a more general definition including turbulent transport. Further, we also give a simplified and practical form for d that is in agreement with the general approach, exploiting the concept of vortex thickness scale from mixing-layer theory. We assess the new and previous displacement height formulations by using flow statistics derived from the atmospheric boundary-layer Reynolds-averaged Navier-Stokes model SCADIS as well as from wind-tunnel observations, for different vegetation types and flow regimes in neutral conditions. The new formulations tend to produce smaller d than stress-based forms, falling closer to the classic logarithmically-defined displacement height. The new, more generally defined, displacement height appears to be more compatible with profiles of components of the turbulent kinetic energy budget, accounting for the combined effects of turbulent transport and shear production. The Coriolis force also plays a role, introducing wind-speed dependence into the behaviour of the roughness sublayer; this affects the turbulent transport, shear production, stress, and wind speed, as well as the displacement height, depending on the character of the forest. We further show how our practical (`mixing-layer') form for d matches the new turbulence-based relation, as well as correspondence to previous (stress-based) formulations.

A description of the "event manager" role in resuscitations: A qualitative study of interviews and focus groups of resuscitation participants.

PubMed

Taylor, Katherine L; Parshuram, Christopher S; Ferri, Susan; Mema, Briseida

2017-06-01

Communication during resuscitation is essential for the provision of coordinated, effective care. Previously, we observed 44% of resuscitation communication originated from participants other than the physician team leader; 65% of which was directed to the team, exclusive of the team leader. We called this outer-loop communication. This institutional review board-approved qualitative study used grounded theory analysis of focus groups and interviews to describe and define outer-loop communication and the role of "event manager" as an additional "leader." Participants were health care staff involved in the medical management of resuscitations in a quaternary pediatric academic hospital. The following 3 domains were identified: the existence and rationale of outer-loop communication; the functions fulfilled by outer-loop communication; and the leadership and learning of event manager skills. The role was recognized by all team members and evolved organically as resuscitation complexity increased. A "good" manager has similar qualities to a "good team leader" with strong nontechnical skills. Event managers were not formally identified and no specific training had occurred. "Outer-loop" communication supports resuscitation activities. An event manager gives direction to the team, coordinates activities, and supports the team leader. We describe a new role in resuscitation in light of structural organizational theory and cognitive load with a view to incorporating this structure into resuscitation training. Copyright © 2017 Elsevier Inc. All rights reserved.

A Role for USP7 in DNA Replication

PubMed Central

Jagannathan, Madhav; Nguyen, Tin; Gallo, David; Luthra, Niharika; Brown, Grant W.; Saridakis, Vivian

2014-01-01

The minichromosome maintenance (MCM) complex, which plays multiple important roles in DNA replication, is loaded onto chromatin following mitosis, remains on chromatin until the completion of DNA synthesis, and then is unloaded by a poorly defined mechanism that involves the MCM binding protein (MCM-BP). Here we show that MCM-BP directly interacts with the ubiquitin-specific protease USP7, that this interaction occurs predominantly on chromatin, and that MCM-BP can tether USP7 to MCM proteins. Detailed biochemical and structure analyses of the USP7–MCM-BP interaction showed that the 155PSTS158 MCM-BP sequence mediates critical interactions with the TRAF domain binding pocket of USP7. Analysis of the effects of USP7 knockout on DNA replication revealed that lack of USP7 results in slowed progression through late S phase without globally affecting the fork rate or origin usage. Lack of USP7 also resulted in increased levels of MCM proteins on chromatin, and investigation of the cause of this increase revealed a defect in the dissociation of MCM proteins from chromatin in mid- to late S phase. This role of USP7 mirrors the previously described role for MCM-BP in MCM complex unloading and suggests that USP7 works with MCM-BP to unload MCM complexes from chromatin at the end of S phase. PMID:24190967

Analysis of Cisco Open Network Environment (ONE) OpenFlow Controller Implementation

DTIC Science & Technology

2014-08-01

Software - Defined Networking ( SDN ), when fully realized, offer many improvements over the current rigid and...functionalities like handshake, connection setup, switch management, and security. 15. SUBJECT TERMS OpenFlow, software - defined networking , Cisco ONE, SDN ...innovating packet-forwarding technologies. Network device roles are strictly defined with little or no flexibility. In Software - Defined Networks ( SDNs ),

Quantification of Urban Environment's Role in Slope Stability for Landslide Events.

NASA Astrophysics Data System (ADS)

Bozzolan, E.; Holcombe, E.; Wagener, T.; Pianosi, F.

2017-12-01

The combination of a rapid and unplanned urban development with a likely future climate change could significantly affect landslide occurrences in the humid tropics, where rainfall events of high intensity and duration are the dominant trigger for landslide risk. The attention of current landslide hazard studies is largely focussed on natural slope processes based on combinations of environmental factors, excluding the role of urbanisation on slope stability. This project aims to understand the relative influence of urbanisation features on local slope stability and to translate the findings to a wider region. Individual slopes are firstly analysed with the software CHASM, a physically based model which combines soil hydrology and slope stability assessment. Instead of relying on existing records, generally lacking for landslides, ranges of plausible preparatory (such as slope, cohesion, friction angles), triggering (rainfall) and aggravating factors (deforestation, house density and water network) are defined and possible combinations of these factors are created by sampling from those ranges. The influence of urban features on site hydrology and stability mechanisms are evaluated and then implemented in denser urban contexts, characteristic of unplanned settlements. The results of CHASMS can be transferred to regional maps in order to identify the areas belonging to the triggering combinations of factors previously found. In this way, areas susceptible to landslides can be detected not only in terms of natural factors but also in relation to the degree of urbanisation. Realistic scenarios can be extrapolated from the areas considered and then analysed again with CHASM. This permits to adapt (and improve) the initial variability ranges of the factors, creating a general-specific cycle able to identify the landslide susceptibility regions and outline a hazard map. Once the triggers are understood, possible consequences can be assessed and mitigation strategies can be evaluated. The ability to define local urban rainfall threshold for landslide slope stability helps the decision-making process to prioritize the areas of interest and locally define the main causes of instability.

Betwixt and between: Role conflict, role ambiguity and role definition in project-based dual-leadership structures

PubMed Central

Ebbers, Joris J; Wijnberg, Nachoem M

2017-01-01

Project-based organizations in the film industry usually have a dual-leadership structure, based on a division of tasks between the dual leaders – the director and the producer – in which the former is predominantly responsible for the artistic and the latter for the commercial aspects of the film. These organizations also have a role hierarchically below and between the dual leaders: the 1st assistant director. This organizational constellation is likely to lead to role conflict and role ambiguity experienced by the person occupying that particular role. Although prior studies found negative effects of role conflict and role ambiguity, this study shows they can also have beneficial effects because they create space for defining the role expansively that, in turn, can be facilitated by the dual leaders defining their own roles more narrowly. In a more general sense, this study also shows the usefulness of analyzing the antecedents and consequences of roles, role definition, and role crafting in connection to the behavior of occupants of adjacent roles. PMID:29081536

A cross-sectional survey on consequences of nurses' burnout: moderating role of organizational politics.

PubMed

Basar, Ufuk; Basim, Nejat

2016-08-01

The aim of the study was to assess whether perceptions of organizational politics (defined as self-serving behaviours at the expense of others) influence the prospective associations between nurses' burnout and its consequences, namely, intention to quit and neglect of work. Researchers have previously investigated relationships between nurses' burnout, intention to quit, neglect of work and perceptions of organizational politics in different research models and from different perspectives. As far as we know, no studies have considered whether nurses' perceptions of organizational politics moderate the influence of burnout. A cross-sectional survey using self-report questionnaires. Data were collected by questionnaire from a sample of 456 nurses from six private hospitals in Ankara, Turkey in March 2015. Four different previously designed scales were used to measure research variables (burnout, intention to quit, neglect of work and perceptions of organizational politics). Following confirmatory validity and reliability analyses of data collection instruments, descriptive statistics for each research variable were analysed. Structural regression models were created to assess relationships among variables. Burnout resulted in intention to quit and neglect. Intention to quit partially mediated the association between burnout and neglect. Burnout gave rise to intention to quit slightly more strongly in nurses who had greater perceptions of organizational politics. This study uncovers and emphasizes the moderating role of perceptions of organizational politics in consequences of burnout. This may help hospital managers and nurses to improve costs, efficiency, satisfaction and productivity. © 2016 John Wiley & Sons Ltd.

The Escherichia coli O157:H7 cattle immuno-proteome includes outer membrane protein A (OmpA), a modulator of adherence to bovine recto-anal junction squamous epithelial (RSE) cells

PubMed Central

Kudva, Indira T.; Krastins, Bryan; Torres, Alfredo G.; Griffin, Robert W.; Sheng, Haiqing; Sarracino, David A.; Hovde, Carolyn J.; Calderwood, Stephen B.; John, Manohar

2015-01-01

SUMMARY Building on previous studies, we defined the repertoire of proteins comprising the immuno-proteome of E. coli O157:H7 (O157) cultured in DMEM supplemented with norepinephrine (NE; O157 immuno-proteome), a β-adrenergic hormone that regulates E. coli O157 gene expression in the gastrointestinal tract, using a variation of a novel proteomics-based platform proteome mining tool for antigen discovery, called Proteomics-based Expression Library Screening (PELS; Kudva et al., 2006). The E. coli O157 immuno-proteome (O157-IP) comprised 91 proteins, and included those identified previously using PELS, and also proteins comprising DMEM- and bovine rumen fluid- proteomes. Outer membrane protein A (OmpA), a common component of the above proteomes, and reportedly a contributor to E. coli O157 adherence to cultured Hep-2 epithelial cells, was interestingly found to be a modulator rather than a contributor to E. coli O157 adherence to bovine recto-anal junction squamous epithelial (RSE) cells. Our results point to a role for yet to be identified members of the O157-IP in E. coli O157 adherence to RSE-cells, and additionally implicate a possible role for the OmpA regulator, TdcA, in the expression of such adhesins. Our observations have implications for development of efficacious vaccines for preventing E. coli O157 colonization of the bovine gastrointestinal tract. PMID:25643951

KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin

PubMed Central

Richardson, Gavin D.; Bazzi, Hisham; Fantauzzo, Katherine A.; Waters, James M.; Crawford, Heather; Hynd, Phil; Christiano, Angela M.; Jahoda, Colin A. B.

2009-01-01

Summary A key initial event in hair follicle morphogenesis is the localised thickening of the skin epithelium to form a placode, partitioning future hair follicle epithelium from interfollicular epidermis. Although many developmental signalling pathways are implicated in follicle morphogenesis, the role of epidermal growth factor (EGF) and keratinocyte growth factor (KGF, also known as FGF7) receptors are not defined. EGF receptor (EGFR) ligands have previously been shown to inhibit developing hair follicles; however, the underlying mechanisms have not been characterised. Here we show that receptors for EGF and KGF undergo marked downregulation in hair follicle placodes from multiple body sites, whereas the expression of endogenous ligands persist throughout hair follicle initiation. Using embryonic skin organ culture, we show that when skin from the sites of primary pelage and whisker follicle development is exposed to increased levels of two ectopic EGFR ligands (HBEGF and amphiregulin) and the FGFR2(IIIb) receptor ligand KGF, follicle formation is inhibited in a time- and dose-dependent manner. We then used downstream molecular markers and microarray profiling to provide evidence that, in response to KGF and EGF signalling, epidermal differentiation is promoted at the expense of hair follicle fate. We propose that hair follicle initiation in placodes requires downregulation of the two pathways in question, both of which are crucial for the ongoing development of the interfollicular epidermis. We have also uncovered a previously unrecognised role for KGF signalling in the formation of hair follicles in the mouse. PMID:19474150

Impacts of Topographic Shading on Surface Energy Balance of High Mountain Asia Glaciers

NASA Astrophysics Data System (ADS)

Olson, M.; Rupper, S.

2016-12-01

Topographic shading plays an important role in the energy balance of valley glaciers. While previous studies incorporate shading of varying complexity in surface energy balance models, to date, no large-scale studies have explored in depth the effects of topographic shading on glacier surface energy balance, and how these vary geographically within High Mountain Asia (HMA). Here we develop a model to examine the variability in potential insolation during the summer melt season using the ASTER GDEM and multi-hour solar geometry to simulate topographic shading on an idealized glacier. Shading is calculated in simulations utilizing a range of slopes, aspects, and latitudes. We test glacier mass balance sensitivity to these parameters for a suite of glaciers throughout HMA. Our results show that shading impacts on glaciers in HMA are highly variable across different geographic regions, but that they are largely predictable based on topographic characteristics such as slope and aspect. For example, we find in regions with steep topography and high relief that shading frequently dominates in the ablation zone rather than the accumulation zone, contrary to the findings of some previous studies. In these regions, topographic shading may play a more significant role in glacier energy balance. These results will better define the effects of topographic shading on surface energy balance, and improve model accuracy within HMA. Additionally, this topographic shading model provides a framework to quantify how shading effects vary for advancing or retreating glaciers as they respond to fluctuations in climate across HMA.

Characterization of Sulfolobus islandicus rod-shaped virus 2 gp19, a single-strand specific endonuclease.

PubMed

Gardner, Andrew F; Prangishvili, David; Jack, William E

2011-09-01

The hyperthermophilic Sulfolobus islandicus rod-shaped virus 2 (SIRV2) encodes a 25-kDa protein (SIRV2gp19) annotated as a hypothetical protein with sequence homology to the RecB nuclease superfamily. Even though SIRV2gp19 homologs are conserved throughout the rudivirus family and presumably play a role in the viral life cycle, SIRV2gp19 has not been functionally characterized. To define the minimal requirements for activity, SIRV2gp19 was purified and tested under varying conditions. SIRV2gp19 is a single-strand specific endonuclease that requires Mg(2+) for activity and is inactive on double-stranded DNA. A conserved aspartic acid in RecB nuclease superfamily Motif II (D89) is also essential for SIRV2gp19 activity and mutation to alanine (D89A) abolishes activity. Therefore, the SIRV2gp19 cleavage mechanism is similar to previously described RecB nucleases. Finally, SIRV2gp19 single-stranded DNA endonuclease activity could play a role in host chromosome degradation during SIRV2 lytic infection.

Glia initiate brain assembly through non-canonical Chimaerin/Furin axon guidance in C. elegans

PubMed Central

Rapti, Georgia; Li, Chang; Shan, Alan; Lu, Yun; Shaham, Shai

2017-01-01

Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions, are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals. Pioneer sublateral neurons, with unique growth properties, anatomy, and innervation, cooperate with glia to mediate follower-axon guidance. We further identify a CHIN-1/Chimaerin-KPC-1/Furin double mutant that severely disrupts assembly. CHIN-1/Chimaerin and KPC-1/Furin function non-canonically in glia and pioneer neurons for guidance-cue trafficking. We exploit this bottleneck to define roles for glial Netrin and Semaphorin in pioneer- and follower-axon guidance, respectively, and for glial and pioneer-neuron Flamingo/CELSR in follower-axon navigation. Altogether, our studies reveal previously-unknown glial roles in pioneer-axon guidance, suggesting conserved brain-assembly principles. PMID:28846083

A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans.

PubMed

Neal, Scott J; Park, JiSoo; DiTirro, Danielle; Yoon, Jason; Shibuya, Mayumi; Choi, Woochan; Schroeder, Frank C; Butcher, Rebecca A; Kim, Kyuhyung; Sengupta, Piali

2016-05-03

Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation. Copyright © 2016 Neal et al.

Induction Based on Circumscription

NASA Astrophysics Data System (ADS)

Saito, Haruka; Inoue, Katsumi

We investigate induction from the viewpoint of nonmonotonic reasoning. Induction we consider in this paper is descriptive induction. Hypotheses from descriptive induction have the weak property that they only describe rules with respect to the observations and do not realize an inductive leap. In this paper, we define a new form of descriptive induction with circumscription and the idea of explanation and show two procedures for computing it. The new descriptive induction is called circumscriptive induction. By deciding the roles of predicates in circumscription, we can intentionally minimize models of a given inductive problem. By adopting the idea of explanation, we can distinguish between background knowledge and observations. Additionally, we consider the relationship between the way of choosing the roles of predicates in computing circumscription and the property of hypotheses obtained by circumscriptive induction. It is shown that hypotheses from circumscriptive induction reflect a difference between background knowledge and observations and do not realize an inductive leap. We also investigate revision of hypotheses which is as important as generation of hypotheses. In a process of hypothesis revision, a difference between previous induction and circumscriptive induction is clearly characterised.

CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction

PubMed Central

Gri, Giorgia; Piconese, Silvia; Frossi, Barbara; Manfroi, Vanessa; Merluzzi, Sonia; Tripodo, Claudio; Viola, Antonella; Odom, Sandra; Rivera, Juan; Colombo, Mario P.; Pucillo, Carlo E.

2008-01-01

Summary CD4+CD25+ T regulatory cells (Tregs) play a central role in the suppression of immune responses thus serving to induce tolerance and to control persistent immune responses that can lead to autoimmunity. Here we explore if Tregs also play a role in controlling the immediate hypersensitivity response of mast cells (MCs). Tregs directly inhibit the FcεRI-dependent degranulation of MCs through cell-cell contact involving OX40-OX40L interactions between Tregs and MCs, respectively. MCs show increased cAMP levels and reduced Ca2+ influx, independent of PLC-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reverses the inhibitory effects of Tregs restoring normal Ca2+ responses and degranulation. Importantly, the in vivo depletion or inactivation of Tregs causes enhancement of the anaphylactic response. The demonstrated cross-talk between Tregs and MCs defines a previously unrecognized mechanism controlling MCs degranulation. Loss of this interaction may contribute to the severity of allergic responses. PMID:18993084

Regulation of myeloid cell phagocytosis by LRRK2 via WAVE2 complex stabilization is altered in Parkinson's disease.

PubMed

Kim, Kwang Soo; Marcogliese, Paul C; Yang, Jungwoo; Callaghan, Steve M; Resende, Virginia; Abdel-Messih, Elizabeth; Marras, Connie; Visanji, Naomi P; Huang, Jana; Schlossmacher, Michael G; Trinkle-Mulcahy, Laura; Slack, Ruth S; Lang, Anthony E; Park, David S

2018-05-14

Leucine-rich repeat kinase 2 ( LRRK2 ) has been implicated in both familial and sporadic Parkinson's disease (PD), yet its pathogenic role remains unclear. A previous screen in Drosophila identified Scar/WAVE (Wiskott-Aldrich syndrome protein-family verproline) proteins as potential genetic interactors of LRRK2 Here, we provide evidence that LRRK2 modulates the phagocytic response of myeloid cells via specific modulation of the actin-cytoskeletal regulator, WAVE2. We demonstrate that macrophages and microglia from LRRK2-G2019S PD patients and mice display a WAVE2-mediated increase in phagocytic response, respectively. Lrrk2 loss results in the opposite effect. LRRK2 binds and phosphorylates Wave2 at Thr470, stabilizing and preventing its proteasomal degradation. Finally, we show that Wave2 also mediates Lrrk2 - G2019S-induced dopaminergic neuronal death in both macrophage-midbrain cocultures and in vivo. Taken together, a LRRK2-WAVE2 pathway, which modulates the phagocytic response in mice and human leukocytes, may define an important role for altered immune function in PD.

21st century pharmacovigilance: efforts, roles, and responsibilities.

PubMed

Pitts, Peter J; Louet, Hervé Le; Moride, Yola; Conti, Rena M

2016-11-01

In an era when the number of expedited and conditional review pathways for newly available brand-name drugs and biosimilar medicines to treat serious and life-threatening diseases is increasing, defining pharmacovigilance has never been more crucial. 21st century pharmacovigilance is not merely about uncovering, reporting, and addressing adverse events associated with already approved and marketed agents, but can be described as the systematic monitoring of the process of pre-market review and post-market surveillance, which includes the use of medicines in everyday practice. Pharmacovigilance identifies previously unrecognised adverse events or changes in the patterns of these effects, the quality and adequacy of drug supply, and should ensure effective communication with the public, health-care professionals, and patients about the optimum safety and effective use of medicines. In this paper, the first in a Series of three about drug safety in oncology, we discuss evolving challenges in the purview, roles, and responsibilities of the US Food and Drug Administration and the European Medicines Agency with respect to pharmacovigilance efforts, with a special emphasis on oncology treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Methodology for studying discrimination based on sexual orientation and social sex-role stereotypes.

PubMed

De Cecco, J P; Figliulo, M C

1978-01-01

This article presents the methodology used in collecting data for the study of the relationship of sexual orientation and social sex-role to the protection of civil liberties. The methodology is designed to determine how departures in sexual orientation and social sex-role are the basis for the abridgment of civil liberties. Departure in sexual orientation is defined as physical sexual activity involving individuals of the same sex. Departure in social sex-role stereotypes is defined as departing from or conforming to the feminine stereotype for men, the feminine stereotype for women, the masculine sterotype for men, and the masculine stereotype for women.

The role of lightness, hue and saturation in feature-based visual attention.

PubMed

Stuart, Geoffrey W; Barsdell, Wendy N; Day, Ross H

2014-03-01

Visual attention is used to select part of the visual array for higher-level processing. Visual selection can be based on spatial location, but it has also been demonstrated that multiple locations can be selected simultaneously on the basis of a visual feature such as color. One task that has been used to demonstrate feature-based attention is the judgement of the symmetry of simple four-color displays. In a typical task, when symmetry is violated, four squares on either side of the display do not match. When four colors are involved, symmetry judgements are made more quickly than when only two of the four colors are involved. This indicates that symmetry judgements are made one color at a time. Previous studies have confounded lightness, hue, and saturation when defining the colors used in such displays. In three experiments, symmetry was defined by lightness alone, lightness plus hue, or by hue or saturation alone, with lightness levels randomised. The difference between judgements of two- and four-color asymmetry was maintained, showing that hue and saturation can provide the sole basis for feature-based attentional selection. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Defining the Stimulus - A Memoir

PubMed Central

Terrace, Herbert

2010-01-01

The eminent psychophysicist, S. S. Stevens, once remarked that, “the basic problem of psychology was the definition of the stimulus” (Stevens, 1951, p. 46). By expanding the traditional definition of the stimulus, the study of animal learning has metamorphosed into animal cognition. The main impetus for that change was the recognition that it is often necessary to postulate a representation between the traditional S and R of learning theory. Representations allow a subject to re-present a stimulus it learned previously that is currently absent. Thus, in delayed-matching-to-sample, one has to assume that a subject responds to a representation of the sample during test if it responds correctly. Other examples, to name but a few, include concept formation, spatial memory, serial memory, learning a numerical rule, imitation and metacognition. Whereas a representation used to be regarded as a mentalistic phenomenon that was unworthy of scientific inquiry, it can now be operationally defined. To accommodate representations, the traditional discriminative stimulus has to be expanded to allow for the role of representations. The resulting composite can account for a significantly larger portion of the variance of performance measures than the exteroceptive stimulus could by itself. PMID:19969047

The crystal structure of a bacterial Sufu-like protein defines a novel group of bacterial proteins that are similar to the N-terminal domain of human Sufu

PubMed Central

Das, Debanu; Finn, Robert D; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L; Bakolitsa, Constantina; Cai, Xiaohui; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Chiu, Michelle; Clayton, Thomas; Deller, Marc C; Duan, Lian; Ellrott, Kyle; Farr, Carol L; Feuerhelm, Julie; Grant, Joanna C; Grzechnik, Anna; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K; Klock, Heath E; Knuth, Mark W; Kozbial, Piotr; Sri Krishna, S; Kumar, Abhinav; Lam, Winnie W; Marciano, David; Miller, Mitchell D; Morse, Andrew T; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Puckett, Christina; Reyes, Ron; Tien, Henry J; Trame, Christine B; van den Bedem, Henry; Weekes, Dana; Wooten, Tiffany; Xu, Qingping; Yeh, Andrew; Zhou, Jiadong; Hodgson, Keith O; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M; Godzik, Adam; Lesley, Scott A; Wilson, Ian A

2010-01-01

Sufu (Suppressor of Fused), a two-domain protein, plays a critical role in regulating Hedgehog signaling and is conserved from flies to humans. A few bacterial Sufu-like proteins have previously been identified based on sequence similarity to the N-terminal domain of eukaryotic Sufu proteins, but none have been structurally or biochemically characterized and their function in bacteria is unknown. We have determined the crystal structure of a more distantly related Sufu-like homolog, NGO1391 from Neisseria gonorrhoeae, at 1.4 Å resolution, which provides the first biophysical characterization of a bacterial Sufu-like protein. The structure revealed a striking similarity to the N-terminal domain of human Sufu (r.m.s.d. of 2.6 Å over 93% of the NGO1391 protein), despite an extremely low sequence identity of ∼15%. Subsequent sequence analysis revealed that NGO1391 defines a new subset of smaller, Sufu-like proteins that are present in ∼200 bacterial species and has resulted in expansion of the SUFU (PF05076) family in Pfam. PMID:20836087

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions.

PubMed

Wuchty, S; Rajagopala, S V; Blazie, S M; Parrish, J R; Khuri, S; Finley, R L; Uetz, P

2017-01-01

The functions of roughly a third of all proteins in Streptococcus pneumoniae , a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein's function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae . We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae , the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins.

Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor.

PubMed

Wang, H B; Zhang, Y

2001-06-15

Dynamic changes in chromatin structure play an important role in transcription regulation. Recent studies have revealed two mechanisms that alter chromatin structure. One involves ATP-dependent chromatin remodeling, and the other involves acetylation of the core histone tails. We have previously purified and characterized a multi-subunit protein complex, NuRD, which possesses both nucleosome remodeling and histone deacetylase activities. Despite extensive biochemical characterization of the complex, little is known about the functions of its individual components. In this study, we focused on Mi2, a component of the NuRD complex. We found that, similar to the native NuRD complex, recombinant Mi2 is a DNA-dependent, nucleosome-stimulated ATPase. Kinetic analysis of the ATP hydrolysis reaction indicated that the differential stimulation of the Mi2 ATPase by DNA and nucleosomes were primarily due to their differential effects on the turnover number of the reaction. Furthermore, we demonstrated that recombinant Mi2 is an efficient nucleosome remodeling factor when compared to that of the native NuRD complex. Our results define the biochemical function of Mi2 and set the stage for understanding the mechanism of nucleosome remodeling in a defined reconstituted system.

Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor

PubMed Central

Wang, Heng-Bin; Zhang, Yi

2001-01-01

Dynamic changes in chromatin structure play an important role in transcription regulation. Recent studies have revealed two mechanisms that alter chromatin structure. One involves ATP-dependent chromatin remodeling, and the other involves acetylation of the core histone tails. We have previously purified and characterized a multi-subunit protein complex, NuRD, which possesses both nucleosome remodeling and histone deacetylase activities. Despite extensive biochemical characterization of the complex, little is known about the functions of its individual components. In this study, we focused on Mi2, a component of the NuRD complex. We found that, similar to the native NuRD complex, recombinant Mi2 is a DNA-dependent, nucleosome-stimulated ATPase. Kinetic analysis of the ATP hydrolysis reaction indicated that the differential stimulation of the Mi2 ATPase by DNA and nucleosomes were primarily due to their differential effects on the turnover number of the reaction. Furthermore, we demonstrated that recombinant Mi2 is an efficient nucleosome remodeling factor when compared to that of the native NuRD complex. Our results define the biochemical function of Mi2 and set the stage for understanding the mechanism of nucleosome remodeling in a defined reconstituted system. PMID:11410659

Tcf21 regulates the specification and maturation of proepicardial cells

PubMed Central

Tandon, Panna; Miteva, Yana V.; Kuchenbrod, Lauren M.; Cristea, Ileana M.; Conlon, Frank L.

2013-01-01

The epicardium is a mesothelial cell layer essential for vertebrate heart development and pertinent for cardiac repair post-injury in the adult. The epicardium initially forms from a dynamic precursor structure, the proepicardial organ, from which cells migrate onto the heart surface. During the initial stage of epicardial development crucial epicardial-derived cell lineages are thought to be determined. Here, we define an essential requirement for transcription factor Tcf21 during early stages of epicardial development in Xenopus, and show that depletion of Tcf21 results in a disruption in proepicardial cell specification and failure to form a mature epithelial epicardium. Using a mass spectrometry-based approach we defined Tcf21 interactions and established its association with proteins that function as transcriptional co-repressors. Furthermore, using an in vivo systems-based approach, we identified a panel of previously unreported proepicardial precursor genes that are persistently expressed in the epicardial layer upon Tcf21 depletion, thereby confirming a primary role for Tcf21 in the correct determination of the proepicardial lineage. Collectively, these studies lead us to propose that Tcf21 functions as a transcriptional repressor to regulate proepicardial cell specification and the correct formation of a mature epithelial epicardium. PMID:23637334

Defining Supports Geometry

ERIC Educational Resources Information Center

Stephan, Michelle L.; McManus, George E.; Dickey, Ashley L.; Arb, Maxwell S.

2012-01-01

The process of developing definitions is underemphasized in most mathematics instruction. Investing time in constructing meaning is well worth the return in terms of the knowledge it imparts. In this article, the authors present a third approach to "defining," called "constructive." It involves modifying students' previous understanding of a term…

Defining and Differentiating the Makerspace

ERIC Educational Resources Information Center

Dousay, Tonia A.

2017-01-01

Many resources now punctuate the maker movement landscape. However, some schools and communities still struggle to understand this burgeoning movement. How do we define these spaces and differentiate them from previous labs and shops? Through a multidimensional framework, stakeholders should consider how the structure, access, staffing, and tools…

Effects and safety of granulocyte colony-stimulating factor in healthy volunteers

PubMed Central

Anderlini, Paolo

2015-01-01

Purpose of Review Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now widely used in normal donors for collection of peripheral blood progenitor cells (PBPCs) for allogeneic transplantation and granulocytes for transfusion. Currently available data on biologic and molecular effects, and safety of rhG-CSF in normal healthy volunteers are reviewed. Recent Findings In addition to its known activating role on neutrophil kinetics and functional status, rhG-CSF administration can affect monocytes, lymphocytes and the hemostatic system. G-CSF receptors were identified in a variety of non-myeloid tissues, although their role and functional activity have not always been well defined. Moreover, rhG-CSF is capable of modulating complex cytokine networks and can impact the inflammatory response. In addition to its known mobilizing role for PBPCs, rhG-CSF can mobilize dendritic and endothelial progenitor cells as well. On a clinical level, serious rhG-CSF-related adverse events are well described (e.g. splenic rupture) but remain rare. Summary rhG-CSF effects in healthy volunteers, while normally transient and self-limiting, are now believed to be more complex and heterogeneous that previously thought. While rhG-CSF administration to healthy volunteers continues to have a favorable risk-benefit profile, these new findings have implications for safeguarding the safety of normal individuals. PMID:19057203

APRIL modulates B and T cell immunity

PubMed Central

Stein, Jens V.; López-Fraga, Marta; Elustondo, Fernando A.; Carvalho-Pinto, Carla E.; Rodríguez, Dolores; Gómez-Caro, Ruth; de Jong, Joan; Martínez-A, Carlos; Medema, Jan Paul; Hahne, Michael

2002-01-01

The TNF-like ligands APRIL and BLyS are close relatives and share the capacity to bind the receptors TACI and BCMA. BLyS has been shown to play an important role in B cell homeostasis and autoimmunity, but the biological role of APRIL remains less well defined. Analysis of T cells revealed an activation-dependent increase in APRIL mRNA expression. We therefore generated mice expressing APRIL as a transgene in T cells. These mice appeared normal and showed no signs of B cell hyperplasia. Transgenic T cells revealed a greatly enhanced survival in vitro as well as enhanced survival of staphylococcal enterotoxin B–reactive CD4+ T cells in vivo, which both directly correlate with elevated Bcl-2 levels. Analysis of humoral responses to T cell–dependent antigens in the transgenic mice indicated that APRIL affects only IgM but not IgG responses. In contrast, T cell–independent type 2 (TI-2) humoral response was enhanced in APRIL transgenic mice. As TACI was previously reported to be indispensable for TI-2 antibody formation, these results suggest a role for APRIL/TACI interactions in the generation of this response. Taken together, our data indicate that APRIL is involved in the induction and/or maintenance of T and B cell responses. PMID:12070306

The role of the medial prefrontal cortex in trace fear extinction

PubMed Central

Kwapis, Janine L.; Jarome, Timothy J.

2015-01-01

The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that supports extinction of this memory has received very little attention. Recent research has indicated that trace fear extinction requires a different neural circuit than delay extinction; trace extinction requires the participation of the retrosplenial cortex, but not the amygdala, as noted in a previous study. Here, we tested the roles of the prelimbic and infralimbic regions of the medial prefrontal cortex in trace and delay fear extinction by blocking NMDA receptors during extinction learning. We found that the prelimbic cortex is necessary for trace, but not for delay fear extinction, whereas the infralimbic cortex is involved in both types of extinction. These results are consistent with the idea that trace fear associations require plasticity in multiple cortical areas for successful extinction. Further, the infralimbic cortex appears to play a role in extinction regardless of whether the animal was initially trained in trace or delay conditioning. Together, our results provide new information about how the neural circuits supporting trace and delay fear extinction differ. PMID:25512576

Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis.

PubMed

Lévêque, Manuella; Penna, Aubin; Le Trionnaire, Sophie; Belleguic, Chantal; Desrues, Benoît; Brinchault, Graziella; Jouneau, Stéphane; Lagadic-Gossmann, Dominique; Martin-Chouly, Corinne

2018-03-09

Whereas many phagocytosis steps involve ionic fluxes, the underlying ion channels remain poorly defined. As reported in mice, the calcium conducting TRPV2 channel impacts the phagocytic process. Macrophage phagocytosis is critical for defense against pathogens. In cystic fibrosis (CF), macrophages have lost their capacity to act as suppressor cells and thus play a significant role in the initiating stages leading to chronic inflammation/infection. In a previous study, we demonstrated that impaired function of CF macrophages is due to a deficient phagocytosis. The aim of the present study was to investigate TRPV2 role in the phagocytosis capacity of healthy primary human macrophage by studying its activity, its membrane localization and its recruitment in lipid rafts. In primary human macrophages, we showed that P. aeruginosa recruits TRPV2 channels at the cell surface and induced a calcium influx required for bacterial phagocytosis. We presently demonstrate that to be functional and play a role in phagocytosis, TRPV2 might require a preferential localization in lipid rafts. Furthermore, CF macrophage displays a perturbed calcium homeostasis due to a defect in TRPV2. In this context, deregulated TRPV2-signaling in CF macrophages could explain their defective phagocytosis capacity that contribute to the maintenance of chronic infection.

Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity

PubMed Central

Shabalina, Svetlana A.; Spiridonov, Nikolay A.; Kashina, Anna

2013-01-01

Messenger RNA is a key component of an intricate regulatory network of its own. It accommodates numerous nucleotide signals that overlap protein coding sequences and are responsible for multiple levels of regulation and generation of biological complexity. A wealth of structural and regulatory information, which mRNA carries in addition to the encoded amino acid sequence, raises the question of how these signals and overlapping codes are delineated along non-synonymous and synonymous positions in protein coding regions, especially in eukaryotes. Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides. The RNA level selection is acting on synonymous sites in both prokaryotes and eukaryotes and is more common than previously thought. Selection pressure on the coding gene regions follows three-nucleotide periodic pattern of nucleotide base-pairing in mRNA, which is imposed by the genetic code. Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles. Recent experimental evidence and analysis of mRNA structure and interspecies conservation suggest that there is an evolutionary tradeoff between selective pressure acting at the RNA and protein levels. Here we provide a comprehensive overview of the studies that define the role of silent positions in regulating RNA structure and processing that exert downstream effects on proteins and their functions. PMID:23293005

Time series regression-based pairs trading in the Korean equities market

NASA Astrophysics Data System (ADS)

Kim, Saejoon; Heo, Jun

2017-07-01

Pairs trading is an instance of statistical arbitrage that relies on heavy quantitative data analysis to profit by capitalising low-risk trading opportunities provided by anomalies of related assets. A key element in pairs trading is the rule by which open and close trading triggers are defined. This paper investigates the use of time series regression to define the rule which has previously been identified with fixed threshold-based approaches. Empirical results indicate that our approach may yield significantly increased excess returns compared to ones obtained by previous approaches on large capitalisation stocks in the Korean equities market.

Genome-scale analysis of the high-efficient protein secretion system of Aspergillus oryzae

PubMed Central

2014-01-01

Background The koji mold, Aspergillus oryzae is widely used for the production of industrial enzymes due to its particularly high protein secretion capacity and ability to perform post-translational modifications. However, systemic analysis of its secretion system is lacking, generally due to the poorly annotated proteome. Results Here we defined a functional protein secretory component list of A. oryzae using a previously reported secretory model of S. cerevisiae as scaffold. Additional secretory components were obtained by blast search with the functional components reported in other closely related fungal species such as Aspergillus nidulans and Aspergillus niger. To evaluate the defined component list, we performed transcriptome analysis on three α-amylase over-producing strains with varying levels of secretion capacities. Specifically, secretory components involved in the ER-associated processes (including components involved in the regulation of transport between ER and Golgi) were significantly up-regulated, with many of them never been identified for A. oryzae before. Furthermore, we defined a complete list of the putative A. oryzae secretome and monitored how it was affected by overproducing amylase. Conclusion In combination with the transcriptome data, the most complete secretory component list and the putative secretome, we improved the systemic understanding of the secretory machinery of A. oryzae in response to high levels of protein secretion. The roles of many newly predicted secretory components were experimentally validated and the enriched component list provides a better platform for driving more mechanistic studies of the protein secretory pathway in this industrially important fungus. PMID:24961398

Genome-scale analysis of the high-efficient protein secretion system of Aspergillus oryzae.

PubMed

Liu, Lifang; Feizi, Amir; Österlund, Tobias; Hjort, Carsten; Nielsen, Jens

2014-06-24

The koji mold, Aspergillus oryzae is widely used for the production of industrial enzymes due to its particularly high protein secretion capacity and ability to perform post-translational modifications. However, systemic analysis of its secretion system is lacking, generally due to the poorly annotated proteome. Here we defined a functional protein secretory component list of A. oryzae using a previously reported secretory model of S. cerevisiae as scaffold. Additional secretory components were obtained by blast search with the functional components reported in other closely related fungal species such as Aspergillus nidulans and Aspergillus niger. To evaluate the defined component list, we performed transcriptome analysis on three α-amylase over-producing strains with varying levels of secretion capacities. Specifically, secretory components involved in the ER-associated processes (including components involved in the regulation of transport between ER and Golgi) were significantly up-regulated, with many of them never been identified for A. oryzae before. Furthermore, we defined a complete list of the putative A. oryzae secretome and monitored how it was affected by overproducing amylase. In combination with the transcriptome data, the most complete secretory component list and the putative secretome, we improved the systemic understanding of the secretory machinery of A. oryzae in response to high levels of protein secretion. The roles of many newly predicted secretory components were experimentally validated and the enriched component list provides a better platform for driving more mechanistic studies of the protein secretory pathway in this industrially important fungus.

The Ia.2 Epitope Defines a Subset of Lipid Raft Resident MHC Class II Molecules Crucial to Effective Antigen Presentation1

PubMed Central

Busman-Sahay, Kathleen; Sargent, Elizabeth; Harton, Jonathan A.; Drake, James R.

2016-01-01

Previous work has established that binding of the 11-5.2 anti-I-Ak mAb, which recognizes the Ia.2 epitope on I-Ak class II molecules, elicits MHC class II signaling, whereas binding of two other anti-I-Ak mAb that recognize the Ia.17 epitope fail to elicit signaling. Using a biochemical approach, we establish that the Ia.2 epitope recognized by the widely used 11-5.2 mAb defines a subset of cell surface I-Ak molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2 bearing subset of I-Ak class II molecules is critically necessary for effective B cell–T cell interactions especially at low antigen doses, a finding consistent with published studies on the role of raft-resident class II molecules in CD4 T cell activation. Interestingly, B cells expressing recombinant I-Ak class II molecules possessing a β chain-tethered HEL peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.2 negative tethered peptide-class II molecules are severely impaired in their ability to present both tethered peptide or peptide derived from exogenous antigen to CD4 T cells. These results establish the Ia.2 epitope as defining a lipid raft-resident MHC class II confomer vital to the initiation of MHC class II restricted B cell–T cell interactions. PMID:21543648

The Managerial Roles of Community College Chief Academic Officers.

ERIC Educational Resources Information Center

Anderson, Philip Wayne

This study utilized Mintzberg's taxonomy of managerial roles to examine the roles performed by community college chief academic officers (CAOs). Mintzberg's taxonomy defines managerial roles as a set of behaviors and identifies 10 distinct roles: (1) figurehead; (2) leader; (3) liaison; (4) monitor; (5) disseminator; (6) spokesperson; (7)…

Defined three-dimensional microenvironments boost induction of pluripotency

NASA Astrophysics Data System (ADS)

Caiazzo, Massimiliano; Okawa, Yuya; Ranga, Adrian; Piersigilli, Alessandra; Tabata, Yoji; Lutolf, Matthias P.

2016-03-01

Since the discovery of induced pluripotent stem cells (iPSCs), numerous approaches have been explored to improve the original protocol, which is based on a two-dimensional (2D) cell-culture system. Surprisingly, nothing is known about the effect of a more biologically faithful 3D environment on somatic-cell reprogramming. Here, we report a systematic analysis of how reprogramming of somatic cells occurs within engineered 3D extracellular matrices. By modulating microenvironmental stiffness, degradability and biochemical composition, we have identified a previously unknown role for biophysical effectors in the promotion of iPSC generation. We find that the physical cell confinement imposed by the 3D microenvironment boosts reprogramming through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodelling. We conclude that 3D microenvironmental signals act synergistically with reprogramming transcription factors to increase somatic plasticity.

The StarD4 subfamily of steroidogenic acute regulatory-related lipid transfer (START) domain proteins: new players in cholesterol metabolism

PubMed Central

Calderon-Dominguez, Maria; Gil, Gregorio; Medina, Miguel Angel; Pandak, William M.; Rodríguez-Agudo, Daniel

2014-01-01

Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, synthesis, distribution, storage and efflux. However, the way cholesterol is sorted within cells remains poorly defined. The discovery of the newly described StarD4 subfamily, part of the steroidogenic acute regulatory lipid transfer (START) domain family of proteins, affords an opportunity for the study of intracellular cholesterol movement, metabolism and its disorders. The three members of this intracelular subfamily of proteins (StarD4, StarD5 and StarD6) have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization. The ability to bind and transport cholesterol through a non-vesicular mean suggests that they play a previously unappreciated role in cholesterol homeostasis. PMID:24440759

Statistical ensembles for money and debt

NASA Astrophysics Data System (ADS)

Viaggiu, Stefano; Lionetto, Andrea; Bargigli, Leonardo; Longo, Michele

2012-10-01

We build a statistical ensemble representation of two economic models describing respectively, in simplified terms, a payment system and a credit market. To this purpose we adopt the Boltzmann-Gibbs distribution where the role of the Hamiltonian is taken by the total money supply (i.e. including money created from debt) of a set of interacting economic agents. As a result, we can read the main thermodynamic quantities in terms of monetary ones. In particular, we define for the credit market model a work term which is related to the impact of monetary policy on credit creation. Furthermore, with our formalism we recover and extend some results concerning the temperature of an economic system, previously presented in the literature by considering only the monetary base as a conserved quantity. Finally, we study the statistical ensemble for the Pareto distribution.

Structures of Saccharomyces cerevisiae D-arabinose dehydrogenase Ara1 and its complex with NADPH: implications for cofactor-assisted substrate recognition.

PubMed

Hu, Xiao-Qian; Guo, Peng-Chao; Ma, Jin-Di; Li, Wei-Fang

2013-11-01

The primary role of yeast Ara1, previously mis-annotated as a D-arabinose dehydrogenase, is to catalyze the reduction of a variety of toxic α,β-dicarbonyl compounds using NADPH as a cofactor at physiological pH levels. Here, crystal structures of Ara1 in apo and NADPH-complexed forms are presented at 2.10 and 2.00 Å resolution, respectively. Ara1 exists as a homodimer, each subunit of which adopts an (α/β)8-barrel structure and has a highly conserved cofactor-binding pocket. Structural comparison revealed that induced fit upon NADPH binding yielded an intact active-site pocket that recognizes the substrate. Moreover, the crystal structures combined with computational simulation defined an open substrate-binding site to accommodate various substrates that possess a dicarbonyl group.

Mechanisms for cytoplasmic organization: an overview.

PubMed

Pagliaro, L

2000-01-01

One of the basic characteristics of life is the intrinsic organization of cytoplasm, yet we know surprisingly little about the manner in which cytoplasmic macromolecules are arranged. It is clear that cytoplasm is not the homogeneous "soup" it was once envisioned to be, but a comprehensive model for cytoplasmic organization is not available in modern cell biology. The premise of this volume is that phase separation in cytoplasm may play a role in organization at the subcellular level. Other mechanisms for non-membrane-bounded intracellular organization have previously been proposed. Some of these will be reviewed in this chapter. Multiple mechanisms, involving phase separation, specific intracellular targeting, formation of macromolecular complexes, and channeling, all could well contribute to cytoplasmic organization. Temporal and spatial organization, as well as composition, are likely to be important in defining the characteristics of cytoplasm.

Effect of moisture content on dowel-bearing strength

Treesearch

Douglas R. Rammer; Steve G. Winistorfer

2001-01-01

Dowel bearing strength (embedment strength) is a critical component of wood connection design. Previous tests have concentrated on defining the relationship between dowel-bearing strength, specific gravity, and fastener characteristics such as diameter. However, because adoption of yield theory in defining connection strength is relatively new in the United States, few...

Innovation 101: Promoting Undergraduate Innovation through a Two-Day Boot Camp

ERIC Educational Resources Information Center

West, Richard E.; Tateishi, Isaku; Wright, Geoffrey A.; Fonoimoana, Melia

2012-01-01

Over the years, many training methods for creativity and innovation have been developed. Despite these programs and research, further improvement is necessary, particularly in schools of technology and engineering education, where previous efforts have focused on developing solutions to defined problems, not in identifying and defining the…

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

PubMed

Braido, F; Scichilone, N; Lavorini, F; Usmani, O S; Dubuske, L; Boulet, L P; Mosges, R; Nunes, C; Sanchez-Borges, M; Ansotegui, I J; Ebisawa, M; Levi-Schaffer, F; Rosenwasser, L J; Bousquet, J; Zuberbier, T; Canonica, G Walter; Cruz, A; Yanez, A; Yorgancioglu, A; Deleanu, D; Rodrigo, G; Berstein, J; Ohta, K; Vichyanond, P; Pawankar, R; Gonzalez-Diaz, S N; Nakajima, S; Slavyanskaya, T; Fink-Wagner, A; Loyola, C Baez; Ryan, D; Passalacqua, G; Celedon, J; Ivancevich, J C; Dobashi, K; Zernotti, M; Akdis, M; Benjaponpitak, S; Bonini, S; Burks, W; Caraballo, L; El-Sayed, Z Awad; Fineman, S; Greenberger, P; Hossny, E; Ortega-Martell, J A; Saito, H; Tang, M; Zhang, L

2016-01-01

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA 2 LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

3D surface perception from motion involves a temporal–parietal network

PubMed Central

Beer, Anton L.; Watanabe, Takeo; Ni, Rui; Sasaki, Yuka; Andersen, George J.

2010-01-01

Previous research has suggested that three-dimensional (3D) structure-from-motion (SFM) perception in humans involves several motion-sensitive occipital and parietal brain areas. By contrast, SFM perception in nonhuman primates seems to involve the temporal lobe including areas MT, MST and FST. The present functional magnetic resonance imaging study compared several motion-sensitive regions of interest including the superior temporal sulcus (STS) while human observers viewed horizontally moving dots that defined either a 3D corrugated surface or a 3D random volume. Low-level stimulus features such as dot density and velocity vectors as well as attention were tightly controlled. Consistent with previous research we found that 3D corrugated surfaces elicited stronger responses than random motion in occipital and parietal brain areas including area V3A, the ventral and dorsal intraparietal sulcus, the lateral occipital sulcus and the fusiform gyrus. Additionally, 3D corrugated surfaces elicited stronger activity in area MT and the STS but not in area MST. Brain activity in the STS but not in area MT correlated with interindividual differences in 3D surface perception. Our findings suggest that area MT is involved in the analysis of optic flow patterns such as speed gradients and that the STS in humans plays a greater role in the analysis of 3D SFM than previously thought. PMID:19674088

Inference for Environmental Intervention Studies using Principal Stratification

PubMed Central

Hackstadt, A. J.; Butz, Arlene M.; Williams, D’Ann L.; Diette, Gregory B.; Breysse, Patrick N.; Matsui, Elizabeth C.; Peng, Roger D.

2014-01-01

Previous research has found evidence of an association between indoor air pollution and asthma morbidity in children. Environmental intervention studies have been performed to examine the role of household environmental interventions in altering indoor air pollution concentrations and improving health. Previous environmental intervention studies have found only modest effects on health outcomes and it is unclear if the health benefits provided by environmental modification are comparable to those provided by medication. Traditionally, the statistical analysis of environmental intervention studies has involved performing two intention-to-treat analyses that separately estimate the effect of the environmental intervention on health and the effect of the environmental intervention on indoor air pollution concentrations. We propose a principal stratification (PS) approach to examine the extent to which an environmental intervention’s effect on health outcomes coincides with its effect on indoor air pollution. We apply this approach to data from a randomized air cleaner intervention trial conducted in a population of asthmatic children living in Baltimore, Maryland, USA. We find that amongst children for whom the air cleaner reduced indoor particulate matter concentrations, the intervention resulted in a meaningful improvement of asthma symptoms with an effect generally larger than previous studies have shown. A key benefit of using principal stratification in environmental intervention studies is that it allows investigators to estimate causal effects of the intervention for sub-groups defined by changes in the indoor air pollution concentration. PMID:25164949

Inference for environmental intervention studies using principal stratification.

PubMed

Hackstadt, Amber J; Matsui, Elizabeth C; Williams, D'Ann L; Diette, Gregory B; Breysse, Patrick N; Butz, Arlene M; Peng, Roger D

2014-12-10

Previous research has found evidence of an association between indoor air pollution and asthma morbidity in children. Environmental intervention studies have been performed to examine the role of household environmental interventions in altering indoor air pollution concentrations and improving health. Previous environmental intervention studies have found only modest effects on health outcomes and it is unclear if the health benefits provided by environmental modification are comparable with those provided by medication. Traditionally, the statistical analysis of environmental intervention studies has involved performing two intention-to-treat analyses that separately estimate the effect of the environmental intervention on health and the effect of the environmental intervention on indoor air pollution concentrations. We propose a principal stratification approach to examine the extent to which an environmental intervention's effect on health outcomes coincides with its effect on indoor air pollution. We apply this approach to data from a randomized air cleaner intervention trial conducted in a population of asthmatic children living in Baltimore, Maryland, USA. We find that among children for whom the air cleaner reduced indoor particulate matter concentrations, the intervention resulted in a meaningful improvement of asthma symptoms with an effect generally larger than previous studies have shown. A key benefit of using principal stratification in environmental intervention studies is that it allows investigators to estimate causal effects of the intervention for sub-groups defined by changes in the indoor air pollution concentration. Copyright © 2014 John Wiley & Sons, Ltd.

Impact of pathogen-directed antimicrobial therapy for ventilator-associated pneumonia in trauma patients on charges and recurrence.

PubMed

Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Swanson, Joseph M; Wood, G Christopher; Fabian, Timothy C; Croce, Martin A

2015-04-01

Ventilator-associated pneumonia (VAP) represents one of the driving forces behind antibiotic use in the ICU. In a previous study, we established a defined algorithm for treatment of hospital-acquired VAP dictated by the causative pathogen. The purpose of the current study was to evaluate the impact of this algorithm for hospital-acquired VAP on recurrence and charges in trauma patients. Patients with VAP secondary to MRSA, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or Enterobacteriaceae during 5 years subsequent to the previous study were evaluated. All VAP were diagnosed using quantitative cultures of the bronchoalveolar lavage effluent. Duration of antimicrobial therapy was dictated by the causative pathogen. If microbiologic resolution, defined as <10(3) colony-forming units/mL, was achieved, therapy was stopped by day 10. The remainder received 14 days of therapy. Recurrence was defined as >10(5) colony-forming units/mL on subsequent bronchoalveolar lavage performed within 2 weeks after completion of appropriate therapy. Five hundred and twenty-nine VAP episodes were identified in 381 patients. Overall recurrence was unchanged compared with the previous study (1.5% vs 2%; p = 0.3). There was a decrease in the number of bronchoalveolar lavages performed per patient compared with the previous study (1.6 vs 2.3; p = 0.24) and a reduction of 4.8 antibiotic days per VAP episode compared with the previous study. Both changes resulted in a cumulative reduction of $3,535.04 per patient, for a savings of $1.35 million during the study period. Hospital-acquired VAP can be managed effectively by a defined course of therapy dictated by the causative pathogen. Adherence to an established algorithm simplified the management of VAP and contributed to a cumulative reduction in patient charges without impacting recurrence. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

GlyCAM1 negatively regulates monocyte entry into the optic nerve head and contributes to radiation-based protection in glaucoma.

PubMed

Williams, Pete A; Braine, Catherine E; Foxworth, Nicole E; Cochran, Kelly E; John, Simon W M

2017-04-26

We previously reported a profound long-term neuroprotection subsequent to a single radiation-therapy in the DBA/2J mouse model of glaucoma. This neuroprotection prevents entry of monocyte-like immune cells into the optic nerve head during glaucoma. Gene expression studies in radiation-treated mice implicated Glycam1 in this protection. Glycam1 encodes a proteoglycan ligand for L-selectin and is an excellent candidate to modulate immune cell entry into the eye. Here, we experimentally test the hypothesis that radiation-induced over-expression of Glycam1 is a key component of the neuroprotection. We generated a null allele of Glycam1 on a DBA/2J background. Gene and protein expression of Glycam1, monocyte entry into the optic nerve head, retinal ganglion cell death, and axon loss in the optic nerve were assessed. Radiation therapy potently inhibits monocyte entry into the optic nerve head and prevents retinal ganglion cell death and axon loss. DBA/2J mice carrying a null allele of Glycam1 show increased monocyte entry and increased retinal ganglion cell death and axon loss following radiation therapy, but the majority of optic nerves were still protected by radiation therapy. Although GlyCAM1 is an L-selectin ligand, its roles in immunity are not yet fully defined. The current study demonstrates a partial role for GlyCAM1 in radiation-mediated protection. Furthermore, our results clearly show that GlyCAM1 levels modulate immune cell entry from the vasculature into neural tissues. As Glycam1 deficiency has a more profound effect on cell entry than on neurodegeneration, further experiments are needed to precisely define the role of monocyte entry in DBA/2J glaucoma. Nevertheless, GlyCAM1's function as a negative regulator of extravasation may lead to novel therapeutic strategies for an array of common conditions involving inflammation.

Lineage-Specific Differences between the gp120 Inner Domain Layer 3 of Human Immunodeficiency Virus and That of Simian Immunodeficiency Virus

PubMed Central

Ding, Shilei; Medjahed, Halima; Prévost, Jérémie; Coutu, Mathieu; Xiang, Shi-Hua

2016-01-01

ABSTRACT Binding of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological layers (layer 1, layer 2, and layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to layer 1 of HIV-1 gp120, the SIVmac239 gp120 layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could be explained by the existence of a well-conserved tryptophan at position 375 (Trp 375) in HIV-2/SIVsmm. In this study, we investigated the role of SIV layer 3 in viral entry, cell-to-cell fusion, and CD4 binding. We observed that a network of interactions involving some residues of the β8-α5 region in SIVmac239 layer 3 may contribute to CD4 binding by helping shape the nearby Phe 43 cavity, which directly contacts CD4. In summary, our results suggest that layer 3 in SIV has a greater impact on CD4 binding than in HIV-1. This work defines lineage-specific differences in layer 3 from HIV-1 and that from SIV. IMPORTANCE CD4-induced conformational changes in the gp120 inner domain involve rearrangements between three topological layers. While the role of layers 1 to 3 for HIV-1 and layers 1 and 2 for SIV on gp120 transition to the CD4-bound conformation has been reported, the role of SIV layer 3 remains unknown. Here we report that SIV layer 3 has a greater impact on CD4 binding than does layer 3 in HIV-1 gp120. This work defines lineage-specific differences in layer 3 from HIV-1 and SIV. PMID:27535053

Reverse Engineering Field Isolates of Myxoma Virus Demonstrates that Some Gene Disruptions or Losses of Function Do Not Explain Virulence Changes Observed in the Field

PubMed Central

Liu, June; Cattadori, Isabella M.; Sim, Derek G.; Eden, John-Sebastian; Read, Andrew F.

2017-01-01

ABSTRACT The coevolution of myxoma virus (MYXV) and wild European rabbits in Australia and Europe is a paradigm for the evolution of a pathogen in a new host species. Genomic analyses have identified the mutations that have characterized this evolutionary process, but defining causal mutations in the pathways from virulence to attenuation and back to virulence has not been possible. Using reverse genetics, we examined the roles of six selected mutations found in Australian field isolates of MYXV that fall in known or potential virulence genes. Several of these mutations occurred in genes previously identified as virulence genes in whole-gene knockout studies. Strikingly, no single or double mutation among the mutations tested had an appreciable impact on virulence. This suggests either that virulence evolution was defined by amino acid changes other than those analyzed here or that combinations of multiple mutations, possibly involving epistatic interactions or noncoding sequences, have been critical in the ongoing evolution of MYXV virulence. In sum, our results show that single-gene knockout studies of a progenitor virus can have little power to predict the impact of individual mutations seen in the field. The genetic determinants responsible for this canonical case of virulence evolution remain to be determined. IMPORTANCE The species jump of myxoma virus (MYXV) from the South American tapeti to the European rabbit populations of Australia and Europe is a canonical example of host-pathogen coevolution. Detailed molecular studies have identified multiple genes in MYXV that are critical for virulence, and genome sequencing has revealed the evolutionary history of MYXV in Australia and Europe. However, it has not been possible to categorically identify the key mutations responsible for the attenuation of or reversion to virulence during this evolutionary process. Here we use reverse genetics to examine the role of mutations in viruses isolated early and late in the Australian radiation of MYXV. Surprisingly, none of the candidate mutations that we identified as likely having roles in attenuation proved to be important for virulence. This indicates that considerable caution is warranted when interpreting the possible role of individual mutations during virulence evolution. PMID:28768866

Conceptualizing Autism: The Role for Emergence

ERIC Educational Resources Information Center

Anderson, George M.

2009-01-01

The establishment of a criterion for operationally defining emergent phenomena in autism is needed. Key initial questions for autism researchers include how to define emergent phenomena in order to better diagnosis the condition.

Rivastigmine in moderately severe-to-severe Alzheimer’s disease: Severe Impairment Battery factor analysis

PubMed Central

2013-01-01

Introduction The Severe Impairment Battery (SIB) is validated for assessing cognition in patients with severe dementia. The current analysis aimed to further investigate the cognitive efficacy of rivastigmine capsules, as assessed by SIB factor scores, in patients with moderately severe-to-severe Alzheimer’s disease (AD). Methods This was a retrospective analysis of a 26-week, multicenter, randomized, double-blind, placebo-controlled study of oral rivastigmine conducted in Spain. Previously reported outcome measures included the full SIB. Current analyses examined calculated scores and effect sizes for the change from baseline at Week 26 on: newly defined SIB subscales (derived by a factor analysis of the 40 SIB items, using the PROC FACTOR function (SAS)); previously defined memory, language and praxis subscales (derived by previous analysis of the nine SIB domains); and the individual SIB items. Treatment differences were assessed. Results SIB data were provided by 104 rivastigmine-treated patients and 106 patients receiving placebo (Intent-To-Treat Last Observation Carried Forward population). Significantly less decline was observed on the previously defined memory and language subscales, and the newly defined working memory/memory subscale in rivastigmine-treated patients (all P < 0.05 versus placebo). Calculation of effect sizes demonstrated numerically greater efficacy of rivastigmine versus placebo on each of the subscales, and a broad range of SIB items; greatest effect sizes were observed on SIB items assessing the current month (effect size = 0.30) and digit span series (effect size = 0.33). Conclusions These data suggest the observed efficacy of rivastigmine in moderately severe-to-severe AD is likely a cumulative effect across a range of tasks. Rivastigmine demonstrates broad cognitive efficacy in this patient population. PMID:24351447

On the Application of an Enthalpy Method to the Evolution of Fluvial Deltas Under Sea-Level Changes

NASA Astrophysics Data System (ADS)

Anderson, W.; Lorenzo-Trueba, J.; Voller, V. R.

2017-12-01

Fluvial deltas are composites of two primary sedimentary environments: a depositional fluvial region and an offshore region. The fluvial region is defined by two geomorphic moving boundaries: an alluvial-bedrock transition (ABT), which separates the sediment prism from the non-erodible bedrock basement, and the shoreline (SH), where the delta meets the ocean. The trajectories of these boundaries in time and space define the evolution of the shape of the sedimentary prism, and are often used as stratigraphic indicators, particularly in seismic studies, of changes in relative sea level and the identification of stratigraphic sequences. In order to better understand the relative role of sea-level variations, tectonics, and sediment supply on the evolution of these boundaries, we develop a forward stratigraphic model that captures the dynamic behavior of the fluvial surface and treats the SH and ABT as moving boundaries (i.e., internal boundaries whose location must be determined as part of the solution to the overall morphological evolution problem). This forward model extends a numerical technique from heat transfer (i.e., enthalpy method), previously applied to the evolution of sedimentary basins, to account for sea-level changes. The mathematics of the approach are verified by comparing predictions from the numerical model with both existing and newly developed closed form analytical solutions. Model results support previous work, which suggests that the migration of the ABT can respond very differently to the sea-level signal. This response depends on factors such as sediment supply and delta length, which can vary greatly between basins. These results can have important implications for the reconstruction of past sea-level changes from the stratigraphic record of sedimentary basins.

OpT2mise: a randomized controlled trial to compare insulin pump therapy with multiple daily injections in the treatment of type 2 diabetes-research design and methods.

PubMed

Aronson, Ronnie; Cohen, Ohad; Conget, Ignacio; Runzis, Sarah; Castaneda, Javier; de Portu, Simona; Lee, Scott; Reznik, Yves

2014-07-01

In insulin-requiring type 2 diabetes patients, current insulin therapy approaches such as basal-alone or basal-bolus multiple daily injections (MDI) have not consistently provided achievement of optimal glycemic control. Previous studies have suggested a potential benefit of continuous subcutaneous insulin infusion (CSII) in these patients. The OpT2mise study is a multicenter, randomized, trial comparing CSII with MDI in a large cohort of subjects with evidence of persistent hyperglycemia despite previous MDI therapy. Subjects were enrolled into a run-in period for optimization of their MDI insulin regimen. Subjects showing persistent hyperglycemia (glycated hemoglobin [HbA1c] ≥8% and ≤12%) were then randomly assigned to CSII or continuing an MDI regimen for a 6-month phase followed by a single crossover of the MDI arm, switching to CSII. The primary end point is the between-group difference in mean change in HbA1c from baseline to 6 months. Secondary end points include change in mean 24-h glucose values, area under the curve and time spent in hypoglycemia and hyperglycemia, measures of glycemic excursions, change in postprandial hyperglycemia, and evaluation of treatment satisfaction. Safety end points include hypoglycemia, hospital admissions, and emergency room visits. When subject enrollment was completed in May 2013, 495 subjects had been enrolled in the study. The study completion for the primary end point is expected in January 2014. OpT2mise will represent the largest studied homogeneous cohort of type 2 diabetes patients with persistent hyperglycemia despite optimized MDI therapy. OpT2mise will help define the role of CSII in insulin intensification and define its safety, rate of hypoglycemia, patient adherence, and patient satisfaction.

Whose interests do lay people represent? Towards an understanding of the role of lay people as members of committees

PubMed Central

Hogg, Christine; Williamson, Charlotte

2008-01-01

Increasingly, lay people are appointed as members to health service committees. The term ‘lay’ is used loosely and the reasons for involving lay people are seldom clearly defined. This paper argues that the different roles that lay people play need to be explicitly defined in order for their contributions to be realized. Although lay members of health service committees are generally assumed to be working for patients’ interests, our observations lead us to think that some lay people tend to support professionals’ or managers’ interests rather than patients’ interests as patients would define them. We suggest that lay people fall into three broad categories: supporters of dominant (professional) interests, supporters of challenging (managerial) interests and supporters of repressed (patient) interests. These alignments should be taken into account in appointments to health service bodies. Further research is needed on the alignments and roles of lay members. PMID:11286594

The Prevalence of Undiagnosed Concussions in Athletes

PubMed Central

Meehan, William P.; Mannix, Rebekah C.; O'Brien, Michael J.; Collins, Michael W.

2013-01-01

Objective Previous studies suggest athletes underreport concussions. We sought to determine whether athletes in our clinics have sustained previous concussions that went undiagnosed. Design Multi-centered, cross sectional study. Setting Two sport concussion clinics. Patients Patients diagnosed with sport-related concussions or concussions with injury mechanisms and forces similar to those observed in sports were included. Main Outcome Measures The proportion of patients that answered “yes” to the following question were defined as having a previously undiagnosed concussion: “Have you ever sustained a blow to the head which was NOT diagnosed as a concussion but was followed by one or more of the signs and symptoms listed in the Post Concussion Symptom Scale.” Results Of the 486 patients included in the final analysis, 148 (30.5%) reported a previously undiagnosed concussion. Athletes reporting previously undiagnosed concussions had a higher mean Post Concussion Symptom Scale score (33 v. 25; p < 0.004) and were more likely to have lost consciousness (31% v. 22%; p = 0.038) with their current injury than athletes without previously undiagnosed concussions. Conclusions Nearly one third of athletes have sustained previously undiagnosed concussions, defined as a blow to the head followed by the signs and symptoms included in the post concussion symptom scale. Furthermore, these previously undiagnosed concussions are associated with higher post concussion symptom scale scores and higher loss of consciousness rates when future concussions occur. PMID:23727697

Unprecedented Abundance of Protein Tyrosine Phosphorylation Modulates Shigella flexneri Virulence.

PubMed

Standish, Alistair James; Teh, Min Yan; Tran, Elizabeth Ngoc Hoa; Doyle, Matthew Thomas; Baker, Paul J; Morona, Renato

2016-10-09

Evidence is accumulating that protein tyrosine phosphorylation plays a crucial role in the ability of important human bacterial pathogens to cause disease. While most works have concentrated on its role in the regulation of a major bacterial virulence factor, the polysaccharide capsule, recent studies have suggested a much broader role for this post-translational modification. This prompted us to investigate protein tyrosine phosphorylation in the human pathogen Shigella flexneri. We first completed a tyrosine phosphoproteome, identifying 905 unique tyrosine phosphorylation sites on at least 573 proteins (approximately 15% of all proteins). This is the most tyrosine-phosphorylated sites and proteins in a single bacterium identified to date, substantially more than the level seen in eukaryotic cells. Most had not previously been identified and included proteins encoded by the virulence plasmid, which is essential for S. flexneri to invade cells and cause disease. In order to investigate the function of these phosphorylation sites in important virulence factors, phosphomimetic and ablative mutations were constructed in the type 3 secretion system ATPase Spa47 and the master virulence regulator VirB. This revealed that tyrosine residues phosphorylated in our study are critical for Spa47 and VirB activity, and tyrosine phosphorylation likely regulates their functional activity and subsequently the virulence of this major human pathogen. This study suggests that tyrosine phosphorylation plays a critical role in regulating a wide variety of virulence factors in the human pathogen S. flexneri and serves as a base for future studies defining its complete role. Copyright © 2016 Elsevier Ltd. All rights reserved.

Problem Solving in the Natural Sciences and Early Adolescent Girls' Gender Roles and Self-Esteem a Qualitative and Quantitative Analysis from AN Ecological Perspective

NASA Astrophysics Data System (ADS)

Slavkin, Michael

What impact do gender roles and self-esteem have on early adolescent girls' abilities to solve problems when participating in natural science-related activities? Bronfenbrenner's human ecology model and Barker's behavior setting theory were used to assess how environmental contexts relate to problem solving in scientific contexts. These models also provided improved methodology and increased understanding of these constructs when compared with prior research. Early adolescent girls gender roles and self-esteem were found to relate to differences in problem solving in science-related groups. Specifically, early adolescent girls' gender roles were associated with levels of verbal expression, expression of positive affect, dominance, and supportive behavior during science experiments. Also, levels of early adolescent girls self-esteem were related to verbal expression and dominance in peer groups. Girls with high self-esteem also were more verbally expressive and had higher levels of dominance during science experiments. The dominant model of a masculine-typed and feminine-typed dichotomy of problem solving based on previous literature was not effective in Identifying differences within girls' problem solving. Such differences in the results of these studies may be the result of this study's use of observational measures and analysis of the behavior settings in which group members participated. Group behavior and problem-solving approaches of early adolescent girls seemed most likely to be defined by environmental contexts, not governed solely by the personalities of participants. A discussion for the examination of environmental factors when assessing early adolescent girls' gender roles and self-esteem follows this discussion.

The emotional eating and negative food relationship experiences of obese and overweight adults.

PubMed

Ford, Tasha; Lee, HeeSoon; Jeon, MinJeong

2017-07-01

Overweight and obesity pose serious public health problems, affecting 68.8% of Americans. Previous research indicated that psychological factors played important roles in an individual's motivation to consume food. In particular, emotional eating, defined as overeating in response to negative affect, has received particular attention as a risk factor for obesity. This study explored and addressed the emotional factors involved in the development of emotional eating. A total of 10 Midwestern American male and female adults, previously diagnosed as medically overweight and obese, were recruited via online and print advertisement using maximum variation and snowball sampling methods. Using a semi-structured, face-to-face interview format, participants shared their perspectives about the development and persistence of emotional eating. The interviews were transcribed and Atlas.ti software was used to assist in thematic analysis of emotional eating. Study results yielded themes, such as emotional triggers, food cravings, comfort from foods, mindless eating, and childhood experiences. Findings indicated that participants generally lacked emotional self-care, but desired to decrease their emotional eating behaviors. Implications are discussed to construct creative, evidence-based treatments for the overweight and obese emotional eaters.

Direct TFIIA-TFIID Protein Contacts Drive Budding Yeast Ribosomal Protein Gene Transcription*

PubMed Central

Layer, Justin H.; Weil, P. Anthony

2013-01-01

We have previously shown that yeast TFIID provides coactivator function on the promoters of ribosomal protein-encoding genes (RPGs) by making direct contact with the transactivator repressor activator protein 1 (Rap1). Further, our structural studies of assemblies generated with purified Rap1, TFIID, and TFIIA on RPG enhancer-promoter DNA indicate that Rap1-TFIID interaction induces dramatic conformational rearrangements of enhancer-promoter DNA and TFIID-bound TFIIA. These data indicate a previously unknown yet critical role for yeast TFIIA in the integration of activator-TFIID contacts with promoter conformation and downstream preinitiation complex formation and/or function. Here we describe the use of systematic mutagenesis to define how specific TFIIA contacts contribute to these processes. We have verified that TFIIA is required for RPG transcription in vivo and in vitro, consistent with the existence of a critical Rap1-TFIIA-TFIID interaction network. We also identified essential points of contact for TFIIA and Rap1 within the Rap1 binding domain of the Taf4 subunit of TFIID. These data suggest a mechanism for how interactions between TFIID, TFIIA, and Rap1 contribute to the high rate of transcription initiation seen on RPGs in vivo. PMID:23814059

Complete theory of symmetry-based indicators of band topology.

PubMed

Po, Hoi Chun; Vishwanath, Ashvin; Watanabe, Haruki

2017-06-30

The interplay between symmetry and topology leads to a rich variety of electronic topological phases, protecting states such as the topological insulators and Dirac semimetals. Previous results, like the Fu-Kane parity criterion for inversion-symmetric topological insulators, demonstrate that symmetry labels can sometimes unambiguously indicate underlying band topology. Here we develop a systematic approach to expose all such symmetry-based indicators of band topology in all the 230 space groups. This is achieved by first developing an efficient way to represent band structures in terms of elementary basis states, and then isolating the topological ones by removing the subset of atomic insulators, defined by the existence of localized symmetric Wannier functions. Aside from encompassing all earlier results on such indicators, including in particular the notion of filling-enforced quantum band insulators, our theory identifies symmetry settings with previously hidden forms of band topology, and can be applied to the search for topological materials.Understanding the role of topology in determining electronic structure can lead to the discovery, or appreciation, of materials with exotic properties such as protected surface states. Here, the authors present a framework for identifying topologically distinct band-structures for all 3D space groups.

The Rab-binding Profiles of Bacterial Virulence Factors during Infection*

PubMed Central

So, Ernest C.; Schroeder, Gunnar N.; Carson, Danielle; Mattheis, Corinna; Mousnier, Aurélie; Broncel, Malgorzata; Tate, Edward W.; Frankel, Gad

2016-01-01

Legionella pneumophila, the causative agent of Legionnaire's disease, uses its type IV secretion system to translocate over 300 effector proteins into host cells. These effectors subvert host cell signaling pathways to ensure bacterial proliferation. Despite their importance for pathogenesis, the roles of most of the effectors are yet to be characterized. Key to understanding the function of effectors is the identification of host proteins they bind during infection. We previously developed a novel tandem-affinity purification (TAP) approach using hexahistidine and BirA-specific biotinylation tags for isolating translocated effector complexes from infected cells whose composition were subsequently deciphered by mass spectrometry. Here we further advanced the workflow for the TAP approach and determined the infection-dependent interactomes of the effectors SidM and LidA, which were previously reported to promiscuously bind multiple Rab GTPases in vitro. In this study we defined a stringent subset of Rab GTPases targeted by SidM and LidA during infection, comprising of Rab1A, 1B, 6, and 10; in addition, LidA targets Rab14 and 18. Taken together, this study illustrates the power of this approach to profile the intracellular interactomes of bacterial effectors during infection. PMID:26755725

Quantifying the role of forest soil and bedrock in the acid neutralization of surface water in steep hillslopes.

PubMed

Asano, Yuko; Uchida, Taro

2005-02-01

The role of soil and bedrock in acid neutralizing processes has been difficult to quantify because of hydrological and biogeochemical uncertainties. To quantify those roles, hydrochemical observations were conducted at two hydrologically well-defined, steep granitic hillslopes in the Tanakami Mountains of Japan. These paired hillslopes are similar except for their soils; Fudoji is leached of base cations (base saturation <6%), while Rachidani is covered with fresh soil (base saturation >30%), because the erosion rate is 100-1000 times greater. The results showed that (1) soil solution pH at the soil-bedrock interface at Fudoji (4.3) was significantly lower than that of Rachidani (5.5), (2) the hillslope discharge pH in both hillslopes was similar (6.7-6.8), and (3) at Fudoji, 60% of the base cations leaching from the hillslope were derived from bedrock, whereas only 20% were derived from bedrock in Rachidani. Further, previously published results showed that the stream pH could not be predicted from the acid deposition rate and soil base saturation status. These results demonstrate that bedrock plays an especially important role when the overlying soil has been leached of base cations. These results indicate that while the status of soil acidification is a first-order control on vulnerability to surface water acidification, in some cases such as at Fudoji, subsurface interaction with the bedrock determines the sensitivity of surface water to acidic deposition.

Larval Settlement: The Role of Surface Topography for Sessile Coral Reef Invertebrates

PubMed Central

Whalan, Steve; Abdul Wahab, Muhammad A.; Sprungala, Susanne; Poole, Andrew J.; de Nys, Rocky

2015-01-01

For sessile marine invertebrates with complex life cycles, habitat choice is directed by the larval phase. Defining which habitat-linked cues are implicated in sessile invertebrate larval settlement has largely concentrated on chemical cues which are thought to signal optimal habitat. There has been less effort establishing physical settlement cues, including the role of surface microtopography. This laboratory based study tested whether surface microtopography alone (without chemical cues) plays an important contributing role in the settlement of larvae of coral reef sessile invertebrates. We measured settlement to tiles, engineered with surface microtopography (holes) that closely matched the sizes (width) of larvae of a range of corals and sponges, in addition to surfaces with holes that were markedly larger than larvae. Larvae from two species of scleractinian corals (Acropora millepora and Ctenactis crassa) and three species of coral reef sponges (Luffariella variabilis, Carteriospongia foliascens and Ircinia sp.,) were used in experiments. L. variabilis, A. millepora and C. crassa showed markedly higher settlement to surface microtopography that closely matched their larval width. C. foliascens and Ircinia sp., showed no specificity to surface microtopography, settling just as often to microtopography as to flat surfaces. The findings of this study question the sole reliance on chemical based larval settlement cues, previously established for some coral and sponge species, and demonstrate that specific physical cues (surface complexity) can also play an important role in larval settlement of coral reef sessile invertebrates. PMID:25671562

Larval settlement: the role of surface topography for sessile coral reef invertebrates.

PubMed

Whalan, Steve; Wahab, Muhammad A Abdul; Sprungala, Susanne; Poole, Andrew J; de Nys, Rocky

2015-01-01

For sessile marine invertebrates with complex life cycles, habitat choice is directed by the larval phase. Defining which habitat-linked cues are implicated in sessile invertebrate larval settlement has largely concentrated on chemical cues which are thought to signal optimal habitat. There has been less effort establishing physical settlement cues, including the role of surface microtopography. This laboratory based study tested whether surface microtopography alone (without chemical cues) plays an important contributing role in the settlement of larvae of coral reef sessile invertebrates. We measured settlement to tiles, engineered with surface microtopography (holes) that closely matched the sizes (width) of larvae of a range of corals and sponges, in addition to surfaces with holes that were markedly larger than larvae. Larvae from two species of scleractinian corals (Acropora millepora and Ctenactis crassa) and three species of coral reef sponges (Luffariella variabilis, Carteriospongia foliascens and Ircinia sp.,) were used in experiments. L. variabilis, A. millepora and C. crassa showed markedly higher settlement to surface microtopography that closely matched their larval width. C. foliascens and Ircinia sp., showed no specificity to surface microtopography, settling just as often to microtopography as to flat surfaces. The findings of this study question the sole reliance on chemical based larval settlement cues, previously established for some coral and sponge species, and demonstrate that specific physical cues (surface complexity) can also play an important role in larval settlement of coral reef sessile invertebrates.

75 FR 61797 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-06

... amending Section 11 to include a definition of ``System routing table,'' defined as the proprietary process... Locked and Crossed Market Rules. \\3\\ Nasdaq has previously defined the term ``System routing table'' in... better value is the essence of a well-functioning competitive marketplace. The Exchange also believes...

THE RADICAL OF A JORDAN ALGEBRA

PubMed Central

McCrimmon, Kevin

1969-01-01

In this paper we define a Jacobson radical for Jordan algebras analogous to that for associative algebras and show that it enjoys many of the properties of the associative radical. We then relate the corresponding notion of “semisimplicity” to the previously defined notion of “nondegeneracy” (Jacobson, N., these Proceedings, 55, 243-251 (1966)). PMID:16591736

Vertical integration and diversification of acute care hospitals: conceptual definitions.

PubMed

Clement, J P

1988-01-01

The terms vertical integration and diversification, although used quite frequently, are ill-defined for use in the health care field. In this article, the concepts are defined--specifically for nonuniversity acute care hospitals. The resulting definitions are more useful than previous ones for predicting the effects of vertical integration and diversification.

Is It Time for Entrustable Professional Activities for Residency Program Directors?

PubMed

Bing-You, Robert G; Holmboe, Eric; Varaklis, Kalli; Linder, Jo

2017-06-01

Residency program directors (PDs) play an important role in establishing and leading high-quality graduate medical education programs. However, medical educators have failed to codify the position on a national level, and PDs are often not recognized for the significant role they play. The authors of this Commentary argue that the core entrustable professional activities (EPAs) framework may be a mechanism to further this work and define the roles and responsibilities of the PD position. Based on personal observations as PDs and communications with others in the academic medicine community, the authors used work in competency-based medical education to define a list of potential EPAs for PDs. The benefits of developing these EPAs include being able to define competencies for PDs using a deconstructive process, highlighting the increasingly important role PDs play in leading high-quality graduate medical education programs, using EPAs as a framework to assess PD performance and provide feedback, allowing PDs to focus their professional development efforts on the most important areas for their work, and helping guide the PD recruitment and selection processes.

Adolescent Reasoning about Advertisements: Preliminary Investigations.

ERIC Educational Resources Information Center

Linn, Marcia C.; And Others

1982-01-01

Three studies investigate the role of competence factors (defined as acquisition of Piagetian formal reasoning) and performance factors (defined as influences from content and expectations) with respect to adolescents' reasoning about advertisements reporting product tests. (Author/MP)

Role of collateral paths in long-range diffusion in lungs

PubMed Central

Bartel, Seth-Emil T.; Haywood, Susan E.; Woods, Jason C.; Chang, Yulin V.; Menard, Christopher; Yablonskiy, Dmitriy A.; Gierada, David S.; Conradi, Mark S.

2010-01-01

The long-range apparent diffusion coefficient (LRADC) of 3He gas in lungs, measured over times of several seconds and distances of 1–3 cm, probes the connections between the airways. Previous work has shown the LRADC to be small in health and substantially elevated in emphysema, reflecting tissue destruction, which is known to create collateral pathways. To better understand what controls LRADC, we report computer simulations and measurements of 3He gas diffusion in healthy lungs. The lung is generated with a random algorithm using well-defined rules, yielding a three-dimensional set of nodes or junctions, each connected by airways to one parent node and two daughters; airway dimensions are taken from published values. Spin magnetization in the simulated lung is modulated sinusoidally, and the diffusion equation is solved to 1,000 s. The modulated magnetization decays with a time constant corresponding to an LRADC of ~0.001 cm2/s, which is smaller by a factor of ~20 than the values in healthy lungs measured here and previously in vivo and in explanted lungs. It appears that collateral gas pathways, not present in the simulations, are functional in healthy lungs; they provide additional and more direct routes for long-range motion than the canonical airway tree. This is surprising, inasmuch as collateral ventilation is believed to be physiologically insignificant in healthy lungs. We discuss the effect on LRADC of small collateral connections through airway walls and rule out other possible mechanisms. The role of collateral paths is supported by measurements of smaller LRADC in pigs, where collateral ventilation is known to be smaller. PMID:18292298

The Endocytic Recycling Regulatory Protein EHD1 Is Required for Ocular Lens Development

PubMed Central

Arya, Priyanka; Rainey, Mark A.; Bhattacharyya, Sohinee; Mohapatra, Bhopal; George, Manju; Kuracha, Murali R; Storck, Matthew D.; Band, Vimla; Govindarajan, Venkatesh; Band, Hamid

2015-01-01

The C-terminal Eps15 homology domain-containing (EHD) proteins play a key role in endocytic recycling, a fundamental cellular process that ensures the return of endocytosed membrane components and receptors back to the cell surface. To define the in vivo biological functions of EHD1, we have generated Ehd1 knockout mice and previously reported a requirement of EHD1 for spermatogenesis. Here, we show that approximately 56% of the Ehd1-null mice displayed gross ocular abnormalities, including anophthalmia, aphakia, microphthalmia and congenital cataracts. Histological characterization of ocular abnormalities showed pleiotropic defects that include a smaller or absent lens, persistence of lens stalk and hyaloid vasculature, and deformed optic cups. To test whether these profound ocular defects resulted from the loss of EHD1 in the lens or in non-lenticular tissues, we deleted the Ehd1 gene selectively in the presumptive lens ectoderm using Le-Cre. Conditional Ehd1 deletion in the lens resulted in developmental defects that included thin epithelial layers, small lenses and absence of corneal endothelium. Ehd1 deletion in the lens also resulted in reduced lens epithelial proliferation, survival and expression of junctional proteins E-cadherin and ZO-1. Finally, Le-Cre-mediated deletion of Ehd1 in the lens led to defects in corneal endothelial differentiation. Taken together, these data reveal a unique role for EHD1 in early lens development and suggest a previously unknown link between the endocytic recycling pathway and regulation of key developmental processes including proliferation, differentiation and morphogenesis. PMID:26455409

Proteomic analysis of human aqueous humor using multidimensional protein identification technology

PubMed Central

Richardson, Matthew R.; Price, Marianne O.; Price, Francis W.; Pardo, Jennifer C.; Grandin, Juan C.; You, Jinsam; Wang, Mu

2009-01-01

Aqueous humor (AH) supports avascular tissues in the anterior segment of the eye, maintains intraocular pressure, and potentially influences the pathogenesis of ocular diseases. Nevertheless, the AH proteome is still poorly defined despite several previous efforts, which were hindered by interfering high abundance proteins, inadequate animal models, and limited proteomic technologies. To facilitate future investigations into AH function, the AH proteome was extensively characterized using an advanced proteomic approach. Samples from patients undergoing cataract surgery were pooled and depleted of interfering abundant proteins and thereby divided into two fractions: albumin-bound and albumin-depleted. Multidimensional Protein Identification Technology (MudPIT) was utilized for each fraction; this incorporates strong cation exchange chromatography to reduce sample complexity before reversed-phase liquid chromatography and tandem mass spectrometric analysis. Twelve proteins had multi-peptide, high confidence identifications in the albumin-bound fraction and 50 proteins had multi-peptide, high confidence identifications in the albumin-depleted fraction. Gene ontological analyses were performed to determine which cellular components and functions were enriched. Many proteins were previously identified in the AH and for several their potential role in the AH has been investigated; however, the majority of identified proteins were novel and only speculative roles can be suggested. The AH was abundant in anti-oxidant and immunoregulatory proteins as well as anti-angiogenic proteins, which may be involved in maintaining the avascular tissues. This is the first known report to extensively characterize and describe the human AH proteome and lays the foundation for future work regarding its function in homeostatic and pathologic states. PMID:20019884

Is there a role for anterior zone sampling as part of saturation trans-rectal ultrasound guided prostate biopsy?

PubMed

Cole, Eric; Margel, David; Greenspan, Michael; Shayegan, Bobby; Matsumoto, Edward; Fischer, Marc A; Patlas, Michael; Daya, Dean; Pinthus, Jehonathan H

2014-05-03

The prostatic anterior zone (AZ) is not targeted routinely by TRUS guided prostate biopsy (TRUS-Pbx). MRI is an accurate diagnostic tool for AZ tumors, but is often unavailable due to cost or system restrictions. We examined the diagnostic yield of office based AZ TRUS-Pbx. 127 men at risk for AZ tumors were studied: Patients with elevated PSA and previous extended negative TRUS-Pbx (group 1, n = 78) and actively surveyed low risk prostate cancer patients (group 2, n = 49). None of the participants had a previous AZ biopsy. Biopsy template included suspicious ultrasonic areas, 16 peripheral zone (PZ), 4 transitional zone (TZ) and 6 AZ cores. All biopsies were performed by a single urologist under local peri-prostatic anaesthetic, using the B-K Medical US System, an end-firing probe 4-12 MHZ and 18 ga/25 cm needle. All samples were reviewed by a single specialized uro-pathologist. Multivariate analysis was used to detect predictors for AZ tumors accounting for age, PSA, PSA density, prostate volume, BMI, and number of previous biopsies. Median PSA was 10.4 (group 1) and 7.3 (group 2). Age (63.9, 64.5), number of previous biopsies (1.5) and cores (17.8, 21.3) and prostate volume (56.4 cc, 51 cc) were similar for both groups. The overall diagnostic yield was 34.6% (group 1) and 85.7% (group 2). AZ cancers were detected in 21.8% (group 1) and 34.7% (group 2) but were rarely the only zone involved (1.3% and 4.1% respectively). Gleason ≥ 7 AZ cancers were often accompanied by equal grade PZ tumors. In multivariate analysis only prostate volume predicted for AZ tumors. Patients detected with AZ tumors had significantly smaller prostates (36.9 cc vs. 61.1 cc p < 0.001). Suspicious AZ ultrasonic findings were uncommon (6.3%). TRUS-Pbx AZ sampling rarely improves the diagnostic yield of extended PZ sampling in patients with elevated PSA and previous negative biopsies. In low risk prostate cancer patients who are followed by active surveillance, AZ sampling changes risk stratification in 6% but larger studies are needed to define the role of AZ sampling in this population and its correlation with prostatectomy final pathological specimens.

Academic-industry partnerships in addressing nutrition--[infection-immunity-inflammation] interactions.

PubMed

Uauy, Ricardo

2007-10-01

The interaction between nutrition and infection is a key determinant of human health. Traditionally the interaction has centered on the role of nutrients in defining host defenses and the impact of infection in defining nutritional needs and status. Over the past decades the interaction has expanded its scope to encompass the role of specific nutrients in defining acquired immune function, in the modulation of inflammatory processes and on the virulence of the infectious agent itself. More recently the role of micronutrients and fatty acids on the response of cells and tissues to hypoxic and toxic damage has been recognized suggesting a fourth dimension to the interaction. The list of nutrients affecting infection, immunity, inflammation and cell injury has expanded from traditional protein-energy supply to several vitamins, multiple minerals and more recently specific lipid components of the diet. The promise of nutrition in the defense against infection, inflammation and tissue injury has spawned a thriving pharma-nutritional supplement industry and the development of novel foods that require appropriate evaluation of efficacy, safety and effectiveness relative to costs. Academics need to aware of the ethics and the pitfalls in the interaction with industry; conversely industry has to define its role in the process of bringing new knowledge to useful products. The process needs to be interactive, transparent and clearly place public interest above all other considerations.

Molecular Determinants of Peptide Binding to Two Common Rhesus Macaque Major Histocompatibility Complex Class II Molecules

PubMed Central

Dzuris, John L.; Sidney, John; Horton, Helen; Correa, Rose; Carter, Donald; Chesnut, Robert W.; Watkins, David I.; Sette, Alessandro

2001-01-01

Major histocompatibility complex class II molecules encoded by two common rhesus macaque alleles Mamu-DRB1*0406 and Mamu-DRB*w201 have been purified, and quantitative binding assays have been established. The structural requirements for peptide binding to each molecule were characterized by testing panels of single-substitution analogs of the two previously defined epitopes HIV Env242 (Mamu-DRB1*0406 restricted) and HIV Env482 (Mamu-DRB*w201 restricted). Anchor positions of both macaque DR molecules were spaced following a position 1 (P1), P4, P6, P7, and P9 pattern. The specific binding motif associated with each molecule was distinct, but largely overlapping, and was based on crucial roles of aromatic and/or hydrophobic residues at P1, P6, and P9. Based on these results, a tentative Mamu class II DR supermotif was defined. This pattern is remarkably similar to a previously defined human HLA-DR supermotif. Similarities in binding motifs between human HLA and macaque Mamu-DR molecules were further illustrated by testing a panel of more than 60 different single-substitution analogs of the HLA-DR-restricted HA 307–319 epitope for binding to Mamu-DRB*w201 and HLA-DRB1*0101. The Mamu-DRB1*0406 and -DRB*w201 binding capacity of a set of 311 overlapping peptides spanning the entire simian immunodeficiency virus (SIV) genome was also evaluated. Ten peptides capable of binding both molecules were identified, together with 19 DRB1*0406 and 43 DRB*w201 selective binders. The Mamu-DR supermotif was found to be present in about 75% of the good binders and in 50% of peptides binding with intermediate affinity but only in approximately 25% of the peptides which did not bind either Mamu class II molecule. Finally, using flow cytometric detection of antigen-induced intracellular gamma interferon, we identify a new CD4+ T-lymphocyte epitope encoded within the Rev protein of SIV. PMID:11602736

N terminus of Swr1 binds to histone H2AZ and provides a platform for subunit assembly in the chromatin remodeling complex.

PubMed

Wu, Wei-Hua; Wu, Chwen-Huey; Ladurner, Andreas; Mizuguchi, Gaku; Wei, Debbie; Xiao, Hua; Luk, Ed; Ranjan, Anand; Wu, Carl

2009-03-06

Variant histone H2AZ-containing nucleosomes are involved in the regulation of gene expression. In Saccharomyces cerevisiae, chromatin deposition of histone H2AZ is mediated by the fourteen-subunit SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ. Previous work defined the role of seven SWR1 subunits (Swr1 ATPase, Swc2, Swc3, Arp6, Swc5, Yaf9, and Swc6) in maintaining complex integrity and H2AZ histone replacement activity. Here we examined the function of three additional SWR1 subunits, bromodomain containing Bdf1, actin-related protein Arp4 and Swc7, by analyzing affinity-purified mutant SWR1 complexes. We observed that depletion of Arp4 (arp4-td) substantially impaired the association of Bdf1, Yaf9, and Swc4. In contrast, loss of either Bdf1 or Swc7 had minimal effects on overall complex integrity. Furthermore, the basic H2AZ histone replacement activity of SWR1 in vitro required Arp4, but not Bdf1 or Swc7. Thus, three out of fourteen SWR1 subunits, Bdf1, Swc7, and previously noted Swc3, appear to have roles auxiliary to the basic histone replacement activity. The N-terminal region of the Swr1 ATPase subunit is necessary and sufficient to direct association of Bdf1 and Swc7, as well as Arp4, Act1, Yaf9 and Swc4. This same region contains an additional H2AZ-H2B specific binding site, distinct from the previously identified Swc2 subunit. These findings suggest that one SWR1 enzyme might be capable of binding two H2AZ-H2B dimers, and provide further insight on the hierarchy and interdependency of molecular interactions within the SWR1 complex.

Plasminogen Activator Inhibitor-2 Polymorphism Associates with Recurrent Coronary Event Risk in Patients with High HDL and C-Reactive Protein Levels

PubMed Central

Corsetti, James P.; Salzman, Peter; Ryan, Dan; Moss, Arthur J.; Zareba, Wojciech; Sparks, Charles E.

2013-01-01

The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2) were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1), a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095) and LRP-1 (LRP1, rs1800156) as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272), p22phox (CYBA, rs4673), and thrombospondin-4 (THBS4, rs1866389). Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014) along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked to key actions involved in the fibrinolytic process. PMID:23874812

[Biodiversity and civil liability: the role of assessment].

PubMed

Boutonnet, Mathilde

2014-03-01

The purpose of this paper is to make the link between expertise and biodiversity through the civil liability Law. Indeed, since Erika Case (Cour de Cassation, Crim. 25 septembre 2012), this Law recognised the ecological damage. This one is defined as an damage caused to Nature and especially Biodiversity. Thus, the expertise has to play a major role. In this paper, two roles are studied: first all all, the expertise allows to assess the damage of Biodiversity itself, to define and to prove it. Secondly, the expertise is an instrument which is very important for prescribing the measures of compensation, in kind or pecuniary compensation.

User-defined Material Model for Thermo-mechanical Progressive Failure Analysis

NASA Technical Reports Server (NTRS)

Knight, Norman F., Jr.

2008-01-01

Previously a user-defined material model for orthotropic bimodulus materials was developed for linear and nonlinear stress analysis of composite structures using either shell or solid finite elements within a nonlinear finite element analysis tool. Extensions of this user-defined material model to thermo-mechanical progressive failure analysis are described, and the required input data are documented. The extensions include providing for temperature-dependent material properties, archival of the elastic strains, and a thermal strain calculation for materials exhibiting a stress-free temperature.

Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs.

PubMed

Ardesjö-Lundgren, Brita; Tengvall, Katarina; Bergvall, Kerstin; Farias, Fabiana H G; Wang, Liya; Hedhammar, Åke; Lindblad-Toh, Kerstin; Andersson, Göran

2017-08-01

Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome-wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin-2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities. The main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD-affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location. Skin biopsies were collected from nine CAD-affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology. We observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding-partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed. Plakophilin-2 protein in dog skin is expressed in both epithelial and immune cells; based on its subcellular location its functional role is implicated in both nuclear and structural processes. © 2017 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and ACVD.

Higher-order corrections to the effective potential close to the jamming transition in the perceptron model

NASA Astrophysics Data System (ADS)

Altieri, Ada

2018-01-01

In view of the results achieved in a previously related work [A. Altieri, S. Franz, and G. Parisi, J. Stat. Mech. (2016) 093301], 10.1088/1742-5468/2016/09/093301, regarding a Plefka-like expansion of the free energy up to the second order in the perceptron model, we improve the computation here focusing on the role of third-order corrections. The perceptron model is a simple example of constraint satisfaction problem, falling in the same universality class as hard spheres near jamming and hence allowing us to get exact results in high dimensions for more complex settings. Our method enables to define an effective potential (or Thouless-Anderson-Palmer free energy), namely a coarse-grained functional, which depends on the generalized forces and the effective gaps between particles. The analysis of the third-order corrections to the effective potential reveals that, albeit irrelevant in a mean-field framework in the thermodynamic limit, they might instead play a fundamental role in considering finite-size effects. We also study the typical behavior of generalized forces and we show that two kinds of corrections can occur. The first contribution arises since the system is analyzed at a finite distance from jamming, while the second one is due to finite-size corrections. We nevertheless show that third-order corrections in the perturbative expansion vanish in the jamming limit both for the potential and the generalized forces, in agreement with the isostaticity argument proposed by Wyart and coworkers. Finally, we analyze the relevant scaling solutions emerging close to the jamming line, which define a crossover regime connecting the control parameters of the model to an effective temperature.

Higher-order corrections to the effective potential close to the jamming transition in the perceptron model.

PubMed

Altieri, Ada

2018-01-01

In view of the results achieved in a previously related work [A. Altieri, S. Franz, and G. Parisi, J. Stat. Mech. (2016) 093301]10.1088/1742-5468/2016/09/093301, regarding a Plefka-like expansion of the free energy up to the second order in the perceptron model, we improve the computation here focusing on the role of third-order corrections. The perceptron model is a simple example of constraint satisfaction problem, falling in the same universality class as hard spheres near jamming and hence allowing us to get exact results in high dimensions for more complex settings. Our method enables to define an effective potential (or Thouless-Anderson-Palmer free energy), namely a coarse-grained functional, which depends on the generalized forces and the effective gaps between particles. The analysis of the third-order corrections to the effective potential reveals that, albeit irrelevant in a mean-field framework in the thermodynamic limit, they might instead play a fundamental role in considering finite-size effects. We also study the typical behavior of generalized forces and we show that two kinds of corrections can occur. The first contribution arises since the system is analyzed at a finite distance from jamming, while the second one is due to finite-size corrections. We nevertheless show that third-order corrections in the perturbative expansion vanish in the jamming limit both for the potential and the generalized forces, in agreement with the isostaticity argument proposed by Wyart and coworkers. Finally, we analyze the relevant scaling solutions emerging close to the jamming line, which define a crossover regime connecting the control parameters of the model to an effective temperature.

Identification of the Kelch Family Protein Nd1-L as a Novel Molecular Interactor of KRIT1

PubMed Central

Cutano, Valentina; Martino, Chiara

2012-01-01

Loss-of-function mutations of the KRIT1 gene (CCM1) have been associated with the Cerebral Cavernous Malformation (CCM) disease, which is characterized by serious alterations of brain capillary architecture. The KRIT1 protein contains multiple interaction domains and motifs, suggesting that it might act as a scaffold for the assembly of functional protein complexes involved in signaling networks. In previous work, we defined structure-function relationships underlying KRIT1 intramolecular and intermolecular interactions and nucleocytoplasmic shuttling, and found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. Here we report the identification of the Kelch family protein Nd1-L as a novel molecular interactor of KRIT1. This interaction was discovered through yeast two-hybrid screening of a mouse embryo cDNA library, and confirmed by pull-down and co-immunoprecipitation assays of recombinant proteins, as well as by co-immunoprecipitation of endogenous proteins in human endothelial cells. Furthermore, using distinct KRIT1 isoforms and mutants, we defined the role of KRIT1 domains in the Nd1-L/KRIT1 interaction. Finally, functional assays showed that Nd1-L may contribute to the regulation of KRIT1 nucleocytoplasmic shuttling and cooperate with KRIT1 in modulating the expression levels of the antioxidant protein SOD2, opening a novel avenue for future mechanistic studies. The identification of Nd1-L as a novel KRIT1 interacting protein provides a novel piece of the molecular puzzle involving KRIT1 and suggests a potential functional cooperation in cellular responses to oxidative stress, thus expanding the framework of molecular complexes and mechanisms that may underlie the pathogenesis of CCM disease. PMID:22970292

Family History of Peripheral Artery Disease is associated with Prevalence and Severity of Peripheral Artery Disease: The San Diego Population Study (SDPS)

PubMed Central

Wassel, Christina L.; Loomba, Rohit; Ix, Joachim H.; Allison, Matthew A.; Denenberg, Julie O.; Criqui, Michael H.

2011-01-01

Objective To determine the association of family history of peripheral artery disease (PAD) with PAD prevalence and severity. Background PAD is a significant public health problem. Shared genetic and environmental factors may play an important role in the development of PAD. However, family history of PAD has not been adequately investigated. Methods The San Diego Population Study (SDPS) enrolled 2404 ethnically diverse men and women aged 29–91 who attended a baseline visit from 1994–98 to assess PAD and venous disease. Ankle brachial index (ABI) measurement was performed at the baseline clinic examination and family history of PAD was obtained via questionnaire. Family history of PAD was primarily defined as having any 1st degree relative with PAD. Prevalent PAD was defined as ABI ≤ 0.90 and severe prevalent PAD as ABI ≤ 0.70, with both definitions also including any previous leg revascularization. Logistic regression was used to evaluate the association of family history of PAD with prevalent PAD. Results The mean (SD) age was 59 (11) years, 66% were women, and 58% were Caucasian with 42% comprising other racial/ethnic groups. Prevalence of PAD was 3.6%, and severe prevalent PAD was 1.9%. In fully adjusted models, family history of PAD was associated with a 1.83-fold higher odds of PAD (95% CI (1.03, 3.26), p=0.04), an association which was stronger for severe prevalent PAD (OR 2.42, 95% CI (1.13, 5.23), p=0.02). Conclusions Family history of PAD is independently strongly associated with PAD prevalence and severity. This indicates a role for genetic factors and/or other shared environmental factors contributing to PAD. PMID:21920269

The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes.

PubMed

Wang, Hong-Mei; Xu, Yun-Fei; Ning, Shang-Lei; Yang, Du-Xiao; Li, Yi; Du, Yu-Jie; Yang, Fan; Zhang, Ya; Liang, Nan; Yao, Wei; Zhang, Ling-Li; Gu, Li-Chuan; Gao, Cheng-Jiang; Pang, Qi; Chen, Yu-Xin; Xiao, Kun-Hong; Ma, Rong; Yu, Xiao; Sun, Jin-Peng

2014-09-01

The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes. Enzymologic characterization and three crystal structures of PTPN18 in complex with HER2 phospho-peptides revealed the molecular basis for the recognition between PTPN18 and specific HER2 phosphorylation sites, which assumes two distinct conformations. Unique structural properties of PTPN18 contribute to the regulation of sub-cellular phosphorylation networks downstream of HER2, which are required for inhibition of HER2-mediated cell growth and migration. Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY(1112), the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop. In agreement with the negative regulatory role of PTPN18 in HER2 signaling, the HER2/PTPN18 ratio was correlated with breast cancer stage. Taken together, our study presents a structural basis for selective HER2 dephosphorylation, a previously uncharacterized mechanism for HER2 degradation and a novel function for the PTPN18 PEST domain. The new regulatory role of the PEST domain in the ubiquitination pathway will broaden our understanding of the functions of other important PEST domain-containing phosphatases, such as LYP and PTPN12.

Matrix metalloproteinase-10/TIMP-2 structure and analyses define conserved core interactions and diverse exosite interactions in MMP/TIMP complexes.

PubMed

Batra, Jyotica; Soares, Alexei S; Mehner, Christine; Radisky, Evette S

2013-01-01

Matrix metalloproteinases (MMPs) play central roles in vertebrate tissue development, remodeling, and repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) regulate proteolytic activity by binding tightly to the MMP active site. While each of the four TIMPs can inhibit most MMPs, binding data reveal tremendous heterogeneity in affinities of different TIMP/MMP pairs, and the structural features that differentiate stronger from weaker complexes are poorly understood. Here we report the crystal structure of the comparatively weakly bound human MMP-10/TIMP-2 complex at 2.1 Å resolution. Comparison with previously reported structures of MMP-3/TIMP-1, MT1-MMP/TIMP-2, MMP-13/TIMP-2, and MMP-10/TIMP-1 complexes offers insights into the structural basis of binding selectivity. Our analyses identify a group of highly conserved contacts at the heart of MMP/TIMP complexes that define the conserved mechanism of inhibition, as well as a second category of diverse adventitious contacts at the periphery of the interfaces. The AB loop of the TIMP N-terminal domain and the contact loops of the TIMP C-terminal domain form highly variable peripheral contacts that can be considered as separate exosite interactions. In some complexes these exosite contacts are extensive, while in other complexes the AB loop or C-terminal domain contacts are greatly reduced and appear to contribute little to complex stability. Our data suggest that exosite interactions can enhance MMP/TIMP binding, although in the relatively weakly bound MMP-10/TIMP-2 complex they are not well optimized to do so. Formation of highly variable exosite interactions may provide a general mechanism by which TIMPs are fine-tuned for distinct regulatory roles in biology.

ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation

PubMed Central

Schumacher, Michael A; Hedl, Matija; Abraham, Clara; Bernard, Jessica K; Lozano, Patricia R; Hsieh, Jonathan J; Almohazey, Dana; Bucar, Edie B; Punit, Shivesh; Dempsey, Peter J; Frey, Mark R

2017-01-01

Efficient clearance of pro-inflammatory macrophages from tissues after resolution of a challenge is critical to prevent prolonged inflammation. Defects in clearance can contribute to conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination of pro-inflammatory macrophages are incompletely defined. We tested whether the ErbB4 receptor tyrosine kinase, previously not known to have role in macrophage biology, is involved in this process. In vitro, pro-inflammatory activation of cultured murine and human macrophages induced ErbB4 expression; in contrast, other ErbB family members were not induced in pro-inflammatory cells, and other innate immune lineages (dendritic cells, neutrophils) did not express detectable ErbB4 levels. Treatment of activated pro-inflammatory macrophages with the ErbB4 ligand neuregulin-4 (NRG4) induced apoptosis. ErbB4 localized to the mitochondria in these cells. Apoptosis was accompanied by loss of mitochondrial membrane potential, and was dependent upon the proteases that generate the cleaved ErbB4 intracellular domain fragment, suggesting a requirement for this fragment and mitochondrial pathway apoptosis. In vivo, ErbB4 was highly expressed on pro-inflammatory macrophages but not neutrophils during experimental DSS colitis in C57Bl/6 mice. Active inflammation in this model suppressed NRG4 expression, which may allow for macrophage persistence and ongoing inflammation. Consistent with this notion, NRG4 levels rebounded during the recovery phase, and administration of exogenous NRG4 during colitis reduced colonic macrophage numbers and ameliorated inflammation. These data define a novel role for ErbB4 in macrophage apoptosis, and outline a mechanism of feedback inhibition that may promote resolution of colitis. PMID:28230865

Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

PubMed Central

Tamburini, Beth A.; Trapp, Susan; Phang, Tzu Lip; Schappa, Jill T.; Hunter, Lawrence E.; Modiano, Jaime F.

2009-01-01

The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors. PMID:19461996

Global geological mapping of Ganymede

NASA Astrophysics Data System (ADS)

Patterson, G. Wesley; Collins, Geoffrey C.; Head, James W.; Pappalardo, Robert T.; Prockter, Louise M.; Lucchitta, Baerbel K.; Kay, Jonathan P.

2010-06-01

We have compiled a global geological map of Ganymede that represents the most recent understanding of the satellite based on Galileo mission results. This contribution builds on important previous accomplishments in the study of Ganymede utilizing Voyager data and incorporates the many new discoveries that were brought about by examination of Galileo data. We discuss the material properties of geological units defined utilizing a global mosaic of the surface with a nominal resolution of 1 km/pixel assembled by the USGS with the best available Voyager and Galileo regional coverage and high resolution imagery (100-200 m/pixel) of characteristic features and terrain types obtained by the Galileo spacecraft. We also use crater density measurements obtained from our mapping efforts to examine age relationships amongst the various defined units. These efforts have resulted in a more complete understanding of the major geological processes operating on Ganymede, especially the roles of cryovolcanic and tectonic processes in the formation of might materials. They have also clarified the characteristics of the geological units that comprise the satellite's surface, the stratigraphic relationships of those geological units and structures, and the geological history inferred from those relationships. For instance, the characteristics and stratigraphic relationships of dark lineated material and reticulate material suggest they represent an intermediate stage between dark cratered material and light material units.

Pyrosequencing the Manduca sexta larval midgut transcriptome: messages for digestion, detoxification and defence.

PubMed

Pauchet, Y; Wilkinson, P; Vogel, H; Nelson, D R; Reynolds, S E; Heckel, D G; ffrench-Constant, R H

2010-02-01

The tobacco hornworm Manduca sexta is an important model for insect physiology but genomic and transcriptomic data are currently lacking. Following a recent pyrosequencing study generating immune related expressed sequence tags (ESTs), here we use this new technology to define the M. sexta larval midgut transcriptome. We generated over 387,000 midgut ESTs, using a combination of Sanger and 454 sequencing, and classified predicted proteins into those involved in digestion, detoxification and immunity. In many cases the depth of 454 pyrosequencing coverage allowed us to define the entire cDNA sequence of a particular gene. Many new M. sexta genes are described including up to 36 new cytochrome P450s, some of which have been implicated in the metabolism of host plant-derived nicotine. New lepidopteran gene families such as the beta-fructofuranosidases, previously thought to be restricted to Bombyx mori, are also described. An unexpectedly high number of ESTs were involved in immunity, for example 39 contigs encoding serpins, and the increasingly appreciated role of the midgut in insect immunity is discussed. Similar studies of other tissues will allow for a tissue by tissue description of the M. sexta transcriptome and will form an essential complimentary step on the road to genome sequencing and annotation.

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions

PubMed Central

Rajagopala, S. V.; Blazie, S. M.; Parrish, J. R.; Khuri, S.; Finley, R. L.

2017-01-01

ABSTRACT The functions of roughly a third of all proteins in Streptococcus pneumoniae, a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein’s function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae. We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae, the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins. PMID:28744484

Spatial scale and sampling resolution affect measures of gap disturbance in a lowland tropical forest: implications for understanding forest regeneration and carbon storage.

PubMed

Lobo, Elena; Dalling, James W

2014-03-07

Treefall gaps play an important role in tropical forest dynamics and in determining above-ground biomass (AGB). However, our understanding of gap disturbance regimes is largely based either on surveys of forest plots that are small relative to spatial variation in gap disturbance, or on satellite imagery, which cannot accurately detect small gaps. We used high-resolution light detection and ranging data from a 1500 ha forest in Panama to: (i) determine how gap disturbance parameters are influenced by study area size, and the criteria used to define gaps; and (ii) to evaluate how accurately previous ground-based canopy height sampling can determine the size and location of gaps. We found that plot-scale disturbance parameters frequently differed significantly from those measured at the landscape-level, and that canopy height thresholds used to define gaps strongly influenced the gap-size distribution, an important metric influencing AGB. Furthermore, simulated ground surveys of canopy height frequently misrepresented the true location of gaps, which may affect conclusions about how relatively small canopy gaps affect successional processes and contribute to the maintenance of diversity. Across site comparisons need to consider how gap definition, scale and spatial resolution affect characterizations of gap disturbance, and its inferred importance for carbon storage and community composition.

The role of internal reference prices in consumers' willingness to pay judgments: Thaler's Beer Pricing Task revisited.

PubMed

Ranyard, R; Charlton, J P; Williamson, J

2001-02-01

Alternative reference prices, either displayed in the environment (external) or recalled from memory (internal) are known to influence consumer judgments and decisions. In one line of previous research, internal reference prices have been defined in terms of general price expectations. However, Thaler (Marketing Science 4 (1985) 199; Journal of Behavioral Decision Making 12 (1999) 183) defined them as fair prices expected from specific types of seller. Using a Beer Pricing Task, he found that seller context had a substantial effect on willingness to pay, and concluded that this was due to specific internal reference prices evoked by specific contexts. In a think aloud study using the same task (N = 48), we found only a marginal effect of seller context. In a second study using the Beer Pricing Task and seven analogous ones (N = 144), general internal reference prices were estimated by asking people what they normally paid for various commodities. Both general internal reference prices and seller context influenced willingness to pay, although the effect of the latter was again rather small. We conclude that general internal reference prices have a greater impact in these scenarios than specific ones, because of the lower cognitive load involved in their storage and retrieval.

First case report of M1 macrophage polarization in an untreated symptomatic patient with toxoplasmosis.

PubMed

De Luca, Graziano; Di Lisio, Chiara; Lattanzio, Giuseppe; D'Antuono, Tommaso; Liberatore, Marcella; Aiello, Francesca Bianca

2018-03-27

In immunocompetent patients, acute toxoplasmosis is usually asymptomatic. We identified M1 macrophages in a case of symptomatic acute Toxoplasma gondii infection that resolved without treatment. M1 macrophages have been demonstrated in animal models of toxoplasmosis, but not in humans. A 63-year-old woman presented with laterocervical and axillary bilateral lymphadenopathy. Her anamnesis defined an episode of high fever and prolonged asthenia 4 months previously, which suggested an infectious disease. Following laboratory, radiological, and pathological analyses, she was diagnosed with toxoplasmosis. Immunohistochemical analyses were performed on lymph node sections. More than 50% of the macrophages in the lymph node microgranulomas were M1 macrophages, defined by CD68 + /p-Stat1 + staining, and the presence of T helper 1 lymphocytes indicated an immune response known to induce M1 macrophage polarization. Activated endothelial cells were found only in inflamed areas. No therapy was administered before or after diagnosis, and the lymphadenopathy resolved after a follow-up of 5 months. This is the first report to demonstrate the presence of M1 macrophages in human toxoplasmosis. Our findings contribute to the understanding of the pathogenesis of toxoplasmosis, and encourage further studies on the role of macrophage polarization in human toxoplasmosis.

FcgammaRIIa genotype predicts progression of HIV infection.

PubMed

Forthal, Donald N; Landucci, Gary; Bream, Jay; Jacobson, Lisa P; Phan, Tran B; Montoya, Benjamin

2007-12-01

Polymorphisms in FcgammaR genes are associated with susceptibility to or severity of a number of autoimmune and infectious diseases. We found that HIV-infected men in the Multicenter AIDS Cohort Study with the FcgammaRIIa RR genotype progressed to a CD4(+) cell count of <200/mm(3) at a faster rate than individuals with the RH or HH genotypes (relative hazard = 1.6; p = 0.0001). However, progression to AIDS (using the broad definition of either a CD4(+) cell count <200/mm(3) or development of an AIDS-defining illness) was less impacted by FcgammaRIIa genotype, largely because HH homozygotes had an increased risk of Pneumocystis jiroveci pneumonia as an AIDS-defining illness. We also showed that chronically infected subjects develop a substantial anti-gp120-specific IgG2 response. Moreover, HIV-1 immune complexes are more efficiently internalized by monocytes from HH subjects compared with RR subjects, likely because of the presence of IgG2 in the complexes. Finally, the FcgammaRIIIa F/V gene polymorphism was not associated with progression of HIV infection, but, as demonstrated previously, did predict the risk of Kaposi's sarcoma. These results demonstrate the importance of FcgammaRs in AIDS pathogenesis and point toward a critical role for interactions between FcgammaRs and immune complexes in disease progression.

Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line.

PubMed

Qiang, Weiguang; Wu, Qinqin; Zhou, Fuxiang; Xie, Conghua; Wu, Changping; Zhou, Yunfeng

2014-03-07

Mammalian telomeres are protected by the shelterin complex that contains the six core proteins POT1, TPP1, TIN2, TRF1, TRF2 and RAP1. TPP1, formerly known as TINT1, PTOP, and PIP1, is a key factor that regulates telomerase recruitment and activity. In addition to this, TPP1 is required to mediate the shelterin assembly and stabilize telomere. Previous work has found that TPP1 expression was elevated in radioresistant cells and that overexpression of TPP1 led to radioresistance and telomere lengthening in telomerase-positive cells. However, the exact effects and mechanism of TPP1 on radiosensitivity are yet to be precisely defined in the ALT cells. Here we report on the phenotypes of the conditional deletion of TPP1 from the human osteosarcoma U2OS cells using ALT pathway to extend the telomeres.TPP1 deletion resulted in telomere shortening, increased apoptosis and radiation sensitivity enhancement. Together, our findings show that TPP1 plays a vital role in telomere maintenance and protection and establish an intimate relationship between TPP1, telomere and cellular response to ionizing radiation, but likely has the specific mechanism yet to be defined. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore.

PubMed

Davidson, Sean M; Foote, Kirsty; Kunuthur, Suma; Gosain, Raj; Tan, Noah; Tyser, Richard; Zhao, Yong Juan; Graeff, Richard; Ganesan, A; Duchen, Michael R; Patel, Sandip; Yellon, Derek M

2015-12-01

In the heart, a period of ischaemia followed by reperfusion evokes powerful cytosolic Ca(2+) oscillations that can cause lethal cell injury. These signals represent attractive cardioprotective targets, but the underlying mechanisms of genesis are ill-defined. Here, we investigated the role of the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), which is known in several cell types to induce Ca(2+) oscillations that initiate from acidic stores such as lysosomes, likely via two-pore channels (TPCs, TPC1 and 2). An NAADP antagonist called Ned-K was developed by rational design based on a previously existing scaffold. Ned-K suppressed Ca(2+) oscillations and dramatically protected cardiomyocytes from cell death in vitro after ischaemia and reoxygenation, preventing opening of the mitochondrial permeability transition pore. Ned-K profoundly decreased infarct size in mice in vivo. Transgenic mice lacking the endo-lysosomal TPC1 were also protected from injury. NAADP signalling plays a major role in reperfusion-induced cell death and represents a potent pathway for protection against reperfusion injury. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore

PubMed Central

Davidson, Sean M.; Foote, Kirsty; Kunuthur, Suma; Gosain, Raj; Tan, Noah; Tyser, Richard; Zhao, Yong Juan; Graeff, Richard; Ganesan, A.; Duchen, Michael R.; Patel, Sandip; Yellon, Derek M.

2015-01-01

Aims In the heart, a period of ischaemia followed by reperfusion evokes powerful cytosolic Ca2+ oscillations that can cause lethal cell injury. These signals represent attractive cardioprotective targets, but the underlying mechanisms of genesis are ill-defined. Here, we investigated the role of the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), which is known in several cell types to induce Ca2+ oscillations that initiate from acidic stores such as lysosomes, likely via two-pore channels (TPCs, TPC1 and 2). Methods and results An NAADP antagonist called Ned-K was developed by rational design based on a previously existing scaffold. Ned-K suppressed Ca2+ oscillations and dramatically protected cardiomyocytes from cell death in vitro after ischaemia and reoxygenation, preventing opening of the mitochondrial permeability transition pore. Ned-K profoundly decreased infarct size in mice in vivo. Transgenic mice lacking the endo-lysosomal TPC1 were also protected from injury. Conclusion NAADP signalling plays a major role in reperfusion-induced cell death and represents a potent pathway for protection against reperfusion injury. PMID:26395965

CCR7 Plays No Appreciable Role in Trafficking of Central Memory CD4 T Cells to Lymph Nodes

PubMed Central

Lugt, Bryan Vander; Tubo, Noah J.; Nizza, Suzanne T.; Boes, Marianne; Malissen, Bernard; Fuhlbrigge, Robert C.; Kupper, Thomas S.; Campbell, James J.

2013-01-01

CCR7−/− mice exhibit profound anomalies in LN and spleen architecture, which complicates the study of CCR7-mediated T cell trafficking in vivo. To circumvent this problem, we established in vivo models in which WT and CCR7−/− populations coexist within mice possessing normal lymphoid organs, and must compete for developmental niches within the tissues of these mice. Under the conditions we have created in vivo, we find the entry of memory CD4 T cells into LN from the blood to be independent of CCR7. Thus, the central memory CD4 T cells that traffic though LN, which are often defined by their expression of CCR7, do not appear to gain any competitive homing advantage by expressing this receptor. Furthermore, in contrast to cutaneous DC populations, we found that CCR7 deficiency had no appreciable effect on the exit of CD4 T cells from inflamed skin. Finally, we found that WT and CCR7−/− precursors were equally represented within the major thymic subpopulations, despite previous findings that CCR7 plays a role in seeding the thymus from bone marrow-derived T cell precursors. PMID:23935190

Lamins in the nuclear interior - life outside the lamina.

PubMed

Naetar, Nana; Ferraioli, Simona; Foisner, Roland

2017-07-01

Nuclear lamins are components of the peripheral lamina that define the mechanical properties of nuclei and tether heterochromatin to the periphery. A-type lamins localize also to the nuclear interior, but the regulation and specific functions of this nucleoplasmic lamin pool are poorly understood. In this Commentary, we summarize known pathways that are potentially involved in the localization and dynamic behavior of intranuclear lamins, including their post-translational modifications and interactions with nucleoplasmic proteins, such as lamina-associated polypeptide 2α (LAP2α; encoded by TMPO ). In addition, new data suggest that lamins in the nuclear interior have an important role in chromatin regulation and gene expression through dynamic binding to both hetero- and euchromatic genomic regions and promoter subdomains, thereby affecting epigenetic pathways and chromatin accessibility. Nucleoplasmic lamins also have a role in spatial chromatin organization and may be involved in mechanosignaling. In view of this newly emerging concept, we propose that the previously reported cellular phenotypes in lamin-linked diseases are, at least in part, rooted in an impaired regulation and/or function of the nucleoplasmic lamin A/C pool. © 2017. Published by The Company of Biologists Ltd.

Evaluating Changes in Tendon Crimp with Fatigue Loading as an ex vivo Structural Assessment of Tendon Damage

PubMed Central

Freedman, Benjamin R.; Zuskov, Andrey; Sarver, Joseph J.; Buckley, Mark R.; Soslowsky, Louis J.

2015-01-01

The complex structure of tendons relates to their mechanical properties. Previous research has associated the waviness of collagen fibers (crimp) during quasi-static tensile loading to tensile mechanics, but less is known about the role of fatigue loading on crimp properties. In this study (IACUC approved), mouse patellar tendons were fatigue loaded while an integrated plane polariscope simultaneously assessed crimp properties. We demonstrate a novel structural mechanism whereby tendon crimp amplitude and frequency are altered with fatigue loading. In particular, fatigue loading increased the crimp amplitude across the tendon width and length, and these structural alterations were shown to be both region and load dependent. The change in crimp amplitude was strongly correlated to mechanical tissue laxity (defined as the ratio of displacement and gauge length relative to the first cycle of fatigue loading assessed at constant load throughout testing), at all loads and regions evaluated. Together, this study highlights the role of fatigue loading on tendon crimp properties as a function of load applied and region evaluated, and offers an additional structural mechanism for mechanical alterations that may lead to ultimate tendon failure. PMID:25773654

Quantitative trait loci and metabolic pathways

PubMed Central

McMullen, M. D.; Byrne, P. F.; Snook, M. E.; Wiseman, B. R.; Lee, E. A.; Widstrom, N. W.; Coe, E. H.

1998-01-01

The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for “channeling” of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits. PMID:9482823

The Role for Virtual Patients in the Future of Medical Education.

PubMed

Berman, Norman B; Durning, Steven J; Fischer, Martin R; Huwendiek, Soren; Triola, Marc M

2016-09-01

The medical education community is working-across disciplines and across the continuum-to address the current challenges facing the medical education system and to implement strategies to improve educational outcomes. Educational technology offers the promise of addressing these important challenges in ways not previously possible. The authors propose a role for virtual patients (VPs), which they define as multimedia, screen-based interactive patient scenarios. They believe VPs offer capabilities and benefits particularly well suited to addressing the challenges facing medical education. Well-designed, interactive VP-based learning activities can promote the deep learning that is needed to handle the rapid growth in medical knowledge. Clinically oriented learning from VPs can capture intrinsic motivation and promote mastery learning. VPs can also enhance trainees' application of foundational knowledge to promote the development of clinical reasoning, the foundation of medical practice. Although not the entire solution, VPs can support competency-based education. The data created by the use of VPs can serve as the basis for multi-institutional research that will enable the medical education community both to better understand the effectiveness of educational interventions and to measure progress toward an improved system of medical education.

Development of a mental health smartphone app: perspectives of mental health service users.

PubMed

Goodwin, John; Cummins, John; Behan, Laura; O'Brien, Sinead M

2016-10-01

Current mental health policy emphasises the importance of service user involvement in the delivery of care. Information Technology can have an effect on quality and efficiency of care. The aim of this study is to gain the viewpoint of service users from a local mental health service in developing a mental health app. A qualitative descriptive approach was used. Eight volunteers aged 18-49 years were interviewed with the aid of a semi-structured questionnaire. Interviewees defined a good app by its ease of use. Common themes included availability of contact information, identifying triggers, the ability to rate mood/anxiety levels on a scale, guided relaxation techniques, and the option to personalise the app. The researchers will aim to produce an app that is easily accessible, highly personalisable and will include functions highlighted as important (i.e. contact information, etc.). This research will assist in the development of an easy-to-use app that could increase access to services, and allow service users to take an active role in their care. In previous studies, apps were developed without the involvement of service users. This study recognises the important role of service users in this area.

A common biological mechanism in cancer and Alzheimer’s disease?

PubMed Central

Behrens, Maria I; Lendon, Corinne; Roe, Catherine M.

2009-01-01

Cancer and Alzheimer’s disease (AD) are two common disorders for which the final pathophysiological mechanism is not yet clearly defined. In a prospective longitudinal study we have previously shown an inverse association between AD and cancer, such that the rate of developing cancer in general with time was significantly slower in participants with AD, while participants with a history of cancer had a slower rate of developing AD. In cancer, cell regulation mechanisms are disrupted with augmentation of cell survival and/or proliferation, whereas conversely, AD is associated with increased neuronal death, either caused by, or concomitant with, beta amyloid (Aβ) and tau deposition. The possibility that perturbations of mechanisms involved in cell survival/death regulation could be involved in both disorders is discussed. Genetic polymorphisms, DNA methylation or other mechanisms that induce changes in activity of molecules with key roles in determining the decision to “repair and live”- or “die” could be involved in the pathogenesis of the two disorders. As examples, the role of p53, Pin1 and the Wnt signaling pathway are discussed as potential candidates that, speculatively, may explain inverse associations between AD and cancer. PMID:19519301

Learning from dying patients during their final days: life reflections gleaned from dignity therapy.

PubMed

Hack, Thomas F; McClement, Susan E; Chochinov, Harvey M; Cann, Beverley J; Hassard, Thomas H; Kristjanson, Linda J; Harlos, Mike

2010-10-01

Dignity therapy is a novel therapeutic approach designed to decrease suffering, enhance quality of life and bolster a sense of dignity for patients approaching death. The benefits of dignity therapy were previously documented in a sample of 100 terminally ill patients. One of the products of dignity therapy is a transcript of the edited therapy session(s). In this qualitative study, 50 of the 100 (17 from Winnipeg, Manitoba, Canada, and 33 from Perth, Australia) dignity therapy transcripts were randomly drawn, and independently coded and analysed by three investigators using a grounded theory approach. The transcripts revealed that dignity therapy serves to provide a safe, therapeutic environment for patients to review the most meaningful aspects of their lives in such a manner that their core values become apparent. The most common values expressed by the patients included 'Family', 'Pleasure', 'Caring', 'A Sense of Accomplishment', 'True Friendship', and 'Rich Experience'. Exemplars of each of these values illustrate the pervasive, defining role of values in our lives. The findings are discussed in terms of values theory, the role of dignity therapy, and consideration of values clarification in clinicians' efforts to enhance the dignity of terminally ill patients.

Flux-lattice melting, anisotropy, and the role of interlayer coupling in Bi-Sr-Ca-Cu-O single crystals

NASA Astrophysics Data System (ADS)

Duran, C.; Yazyi, J.; de La Cruz, F.; Bishop, D. J.; Mitzi, D. B.; Kapitulnik, A.

1991-10-01

We have used the high-Q mechanical-oscillator technique to probe the vortex-lattice structure in high-quality Bi-Sr-Ca-Cu-O single crystals over a wide range of magnetic fields (200 Oe to 40 kOe), and relative orientations θ between the magnetic field and the crystalline c^ axis. In addition to the large softening and dissipation peak previously observed and interpreted as due to flux-lattice melting, another distinctly different peak at higher temperatures is seen. The temperatures where the dissipation peaks take place are solely defined by the parallel component of the field cosθ, while the restoring force on the oscillator is due to both field components. We suggest that the two peaks are due to the softening of interplanar coupling at the low-temperature peak, and melting or depinning of the two-dimensional pancake vortices at the higher-temperature peak.

Application of chemical biology in target identification and drug discovery.

PubMed

Zhu, Yue; Xiao, Ting; Lei, Saifei; Zhou, Fulai; Wang, Ming-Wei

2015-09-01

Drug discovery and development is vital to the well-being of mankind and sustainability of the pharmaceutical industry. Using chemical biology approaches to discover drug leads has become a widely accepted path partially because of the completion of the Human Genome Project. Chemical biology mainly solves biological problems through searching previously unknown targets for pharmacologically active small molecules or finding ligands for well-defined drug targets. It is a powerful tool to study how these small molecules interact with their respective targets, as well as their roles in signal transduction, molecular recognition and cell functions. There have been an increasing number of new therapeutic targets being identified and subsequently validated as a result of advances in functional genomics, which in turn led to the discovery of numerous active small molecules via a variety of high-throughput screening initiatives. In this review, we highlight some applications of chemical biology in the context of drug discovery.

Population dynamics of Lutzomyia shannoni (Diptera: Psychodidae) in relation to the epizootiology of vesicular stomatitis virus on Ossabaw Island, Georgia.

PubMed

Comer, J A; Kavanaugh, D M; Stallknecht, D E; Corn, J L

1994-11-01

Population dynamics of Lutzomyia shannoni Dyar were studied on Ossabaw Island, GA, to define further the role of this species in the epizootiology of the New Jersey serotype of vesicular stomatitis (VSNJ) virus. Bimonthly collections of sand flies egressing from hollow trees from April to November 1991 indicated that there were three generations of sand flies. Data from light trap collections from 1986 through 1989 indicated that similar seasonal cycles occurred during previous years. At this site, we hypothesize that L. shannoni undergoes facultative diapause. Two isolates of VSNJ virus were obtained from female sand flies collected in May and June of 1991. We believe that the virus overwinters in immature L. shannoni and that transovarially infected sand flies emerging each spring initiate a summer amplification cycle in swine on Ossabaw Island.

[Arterial media calcification in patients with type 2 diabetes mellitus].

PubMed

Belovici, Maria Isabela; Pandele, G I

2008-01-01

Arterial calcification was previously viewed as an inevitable, passive, and degenerative process that occurred at the end stages of atherosclerosis. Recent studies, however, have demonstrated that calcification of arteries is a complex and regulated process. It may occur in conjunction with atherosclerosis or in an isolated form that is commonly associated with diabetes and renal failure. Higher artery calcium scores are associated with increased cardiovascular events, and some aspects of arterial calcification are similar to the biology of forming bone. Arterial calcification can thus be viewed as a distinct inflammatory arteriopathy, much like atherosclerosis and aneurysms, with its own contribution to cardiovascular morbidity and mortality. Current research involves efforts to define the complex interactions between cellular and molecular mediators of arterial calcification and, in particular, the role of endogenous calcification inhibitors. This review discusses the clinical relevance, cellular events, and suspected molecular pathways that control arterial calcification.

A commentary on the role of molecular technology and automation in clinical diagnostics

PubMed Central

O’Connor, Ciara; Fitzgibbon, Marie; Powell, James; Barron, Denis; O’Mahony, Jim; Power, Lorraine; O’Connell, Nuala H; Dunne, Colum

2014-01-01

Historically, the identification of bacterial or yeast isolates has been based on phenotypic characteristics such as growth on defined media, colony morphology, Gram stain, and various biochemical reactions, with significant delay in diagnosis. Clinical microbiology as a medical specialty has embraced advances in molecular technology for rapid species identification with broad-range 16S rDNA polymerase chain reaction (PCR) and matrix-assisted laser desorption and/or ionization time of flight (MALDI-TOF) mass spectrometry demonstrated as accurate, rapid, and cost-effective methods for the identification of most, but not all, bacteria and yeasts. Protracted conventional incubation times previously necessary to identify certain species have been mitigated, affording patients quicker diagnosis with associated reduction in exposure to empiric broad-spectrum antimicrobial therapy and shortened hospital stay. This short commentary details such molecular advances and their implications in the clinical microbiology setting. PMID:24658184

[Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors].

PubMed

Massardo, Teresa; Jofré, María Josefina; Sierralta, María Paulina; Canessa, José; Castro, Gabriel; Berrocal, Isabel; Gallegos, Iván

2012-09-01

The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control.

DQE analysis for CCD imaging arrays

NASA Astrophysics Data System (ADS)

Shaw, Rodney

1997-05-01

By consideration of the statistical interaction between exposure quanta and the mechanisms of image detection, the signal-to-noise limitations of a variety of image acquisition technologies are now well understood. However in spite of the growing fields of application for CCD imaging- arrays and the obvious advantages of their multi-level mode of quantum detection, only limited and largely empirical approaches have been made to quantify these advantages on an absolute basis. Here an extension is made of a previous model for noise-free sequential photon-counting to the more general case involving both count-noise and arbitrary separation functions between count levels. This allows a basic model to be developed for the DQE associated with devices which approximate to the CCD mode of operation, and conclusions to be made concerning the roles of the separation-function and count-noise in defining the departure from the ideal photon counter.

Numeracy moderates the influence of task-irrelevant affect on probability weighting.

PubMed

Traczyk, Jakub; Fulawka, Kamil

2016-06-01

Statistical numeracy, defined as the ability to understand and process statistical and probability information, plays a significant role in superior decision making. However, recent research has demonstrated that statistical numeracy goes beyond simple comprehension of numbers and mathematical operations. On the contrary to previous studies that were focused on emotions integral to risky prospects, we hypothesized that highly numerate individuals would exhibit more linear probability weighting because they would be less biased by incidental and decision-irrelevant affect. Participants were instructed to make a series of insurance decisions preceded by negative (i.e., fear-inducing) or neutral stimuli. We found that incidental negative affect increased the curvature of the probability weighting function (PWF). Interestingly, this effect was significant only for less numerate individuals, while probability weighting in more numerate people was not altered by decision-irrelevant affect. We propose two candidate mechanisms for the observed effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic Characterization and Physiological Role of Endopeptidase O from Lactobacillus helveticus CNRZ32

PubMed Central

Chen, Yo-Shen; Steele, James L.

1998-01-01

A previously identified insert expressing an endopeptidase from a Lactobacillus helveticus CNRZ32 genomic library was characterized. Nucleotide sequence analysis revealed an open reading frame of 1,941 bp encoding a putative protein of 71.2 kDa which contained a zinc-protease motif. Protein homology searches revealed that this enzyme has 40% similarity with endopeptidase O (PepO) from Lactococcus lactis P8-2-47. Northern hybridization revealed that pepO is monocistronic and is expressed throughout the growth phase. CNRZ32 derivatives lacking PepO activity were constructed via gene replacement. Enzyme assays revealed that the PepO mutant had significantly reduced endopeptidase activity when compared to CNRZ32 with two of the three substrates examined. Growth studies indicated that PepO has no detectable effect on growth rate or acid production by Lactobacillus helveticus CNRZ32 in amino acid defined or skim milk medium. PMID:9726890

The relationship between social deprivation and the incidence of adult fractures.

PubMed

Court-Brown, Charles M; Aitken, Stuart A; Duckworth, Andrew D; Clement, Nicholas D; McQueen, Margaret M

2013-03-20

Social deprivation is associated with many diseases. To our knowledge, there has been no previous investigation of its role in the epidemiology and incidence of fractures in adults. We analyzed 6872 consecutive fractures in patients fifteen years of age or older over a one-year period. Social deprivation was analyzed using the Carstairs score, which is derived from patients' postal codes and accurately defines social deprivation in our population. Social deprivation is associated with an increasing fracture incidence. The effect is not linear, and the most deprived 10% of society are affected. The odds ratios of the most deprived 10% of society having an increased incidence of fractures are 3.7 in males and 3.1 in females. Social deprivation is associated with a significant increase in the incidence of fractures in the most deprived 10% of the population. Most fracture types are affected.

Social-ecological resilience and social conflict: institutions and strategic adaptation in Swedish water management.

PubMed

Galaz, Victor

2005-11-01

Dealing with uncertainty and complexity in social-ecological systems is profoundly dependent on the ability of natural resource users to learn and adapt from ecological surprises and crises. This paper analyzes why and how learning processes are affected by strategic behavior among natural resource users and how social conflict is affected by social and ecological uncertainty. The claim is that social conflict among natural resource users seriously inhibits the possibilities of learning and adaptation in social-ecological systems. This is done combining insights from political science, experimental economics, and social-psychology and an analytical case study elaborating social conflict and institutional change in Swedish water management institutions. This paper also discusses the crucial role the institutional context plays in defining the outcome of learning processes in Swedish water management institutions and hence highlights previously poorly elaborated political aspects of learning processes and institutional change in social-ecological systems.

Oscillatory Dynamics of One-Dimensional Homogeneous Granular Chains

NASA Astrophysics Data System (ADS)

Starosvetsky, Yuli; Jayaprakash, K. R.; Hasan, Md. Arif; Vakakis, Alexander F.

The acoustics of the homogeneous granular chains has been studied extensively both numerically and experimentally in the references cited in the previous chapters. This chapter focuses on the oscillatory behavior of finite dimensional homogeneous granular chains. It is well known that normal vibration modes are the building blocks of the vibrations of linear systems due to the applicability of the principle of superposition. One the other hand, nonlinear theory is deprived of such a general superposition principle (although special cases of nonlinear superpositions do exist), but nonlinear normal modes ‒ NNMs still play an important role in the forced and resonance dynamics of these systems. In their basic definition [1], NNMs were defined as time-periodic nonlinear oscillations of discrete or continuous dynamical systems where all coordinates (degrees-of-freedom) oscillate in-unison with the same frequency; further extensions of this definition have been considered to account for NNMs of systems with internal resonances [2]...

Are corticothalamic 'up' states fragments of wakefulness?

PubMed

Destexhe, Alain; Hughes, Stuart W; Rudolph, Michelle; Crunelli, Vincenzo

2007-07-01

The slow (<1 Hz) oscillation, with its alternating 'up' and 'down' states in individual neurons, is a defining feature of the electroencephalogram (EEG) during slow-wave sleep (SWS). Although this oscillation is well preserved across mammalian species, its physiological role is unclear. Electrophysiological and computational evidence from the cortex and thalamus now indicates that slow-oscillation 'up' states and the 'activated' state of wakefulness are remarkably similar dynamic entities. This is consistent with behavioural experiments suggesting that slow-oscillation 'up' states provide a context for the replay, and possible consolidation, of previous experience. In this scenario, the T-type Ca(2+) channel-dependent bursts of action potentials that initiate each 'up' state in thalamocortical (TC) neurons might function as triggers for synaptic and cellular plasticity in corticothalamic networks. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).

Lignin‐Derived Thioacidolysis Dimers: Reevaluation, New Products, Authentication, and Quantification

PubMed Central

Yue, Fengxia; Regner, Matt; Sun, Runcang

2017-01-01

Abstract Lignin structural studies play an essential role both in understanding the development of plant cell walls and for valorizing lignocellulosics as renewable biomaterials. Dimeric products released by selectively cleaving β–aryl ether linkages between lignin units reflect the distribution of recalcitrant lignin units, but have been neither absolutely defined nor quantitatively determined. Here, 12 guaiacyl‐type thioacidolysis dimers were identified and quantified using newly synthesized standards. One product previously attributed to deriving from β–1‐coupled units was established as resulting from β–5 units, correcting an analytical quandary. Another longstanding dilemma, that no β–β dimers were recognized in thioacidolysis products from gymnosperms, was resolved with the discovery of two such authenticated compounds. Individual GC response factors for each standard compound allowed rigorous quantification of dimeric products released from softwood lignins, affording insight into the various interunit‐linkage distributions in lignins and thereby guiding the valorization of lignocellulosics. PMID:28125766

Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18

PubMed Central

Guo, Peng-Chao; Dong, Zhaoming; Zhao, Ping; Zhang, Yan; He, Huawei; Tan, Xiang; Zhang, Weiwei; Xia, Qingyou

2015-01-01

Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development. PMID:26148664

A commentary on the role of molecular technology and automation in clinical diagnostics.

PubMed

O'Connor, Ciara; Fitzgibbon, Marie; Powell, James; Barron, Denis; O'Mahony, Jim; Power, Lorraine; O'Connell, Nuala H; Dunne, Colum

2014-01-01

Historically, the identification of bacterial or yeast isolates has been based on phenotypic characteristics such as growth on defined media, colony morphology, Gram stain, and various biochemical reactions, with significant delay in diagnosis. Clinical microbiology as a medical specialty has embraced advances in molecular technology for rapid species identification with broad-range 16S rDNA polymerase chain reaction (PCR) and matrix-assisted laser desorption and/or ionization time of flight (MALDI-TOF) mass spectrometry demonstrated as accurate, rapid, and cost-effective methods for the identification of most, but not all, bacteria and yeasts. Protracted conventional incubation times previously necessary to identify certain species have been mitigated, affording patients quicker diagnosis with associated reduction in exposure to empiric broad-spectrum antimicrobial therapy and shortened hospital stay. This short commentary details such molecular advances and their implications in the clinical microbiology setting.

Regional 3D Numerical Modeling of the Lithosphere-Mantle System: Implications for Continental Rift-Parallel Surface Velocities

NASA Astrophysics Data System (ADS)

Stamps, S.; Bangerth, W.; Hager, B. H.

2014-12-01

The East African Rift System (EARS) is an active divergent plate boundary with slow, approximately E-W extension rates ranging from <1-6 mm/yr. Previous work using thin-sheet modeling indicates lithospheric buoyancy dominates the force balance driving large-scale Nubia-Somalia divergence, however GPS observations within the Western Branch of the EARS show along-rift motions that contradict this simple model. Here, we test the role of mantle flow at the rift-scale using our new, regional 3D numerical model based on the open-source code ASPECT. We define a thermal lithosphere with thicknesses that are systematically changed for generic models or based on geophysical constraints in the Western branch (e.g. melting depths, xenoliths, seismic tomography). Preliminary results suggest existing variations in lithospheric thicknesses along-rift in the Western Branch can drive upper mantle flow that is consistent with geodetic observations.

On the closed form mechanistic modeling of milling: Specific cutting energy, torque, and power

NASA Astrophysics Data System (ADS)

Bayoumi, A. E.; Yücesan, G.; Hutton, D. V.

1994-02-01

Specific energy in metal cutting, defined as the energy expended in removing a unit volume of workpiece material, is formulated and determined using a previously developed closed form mechanistic force model for milling operations. Cutting power is computed from the cutting torque, cutting force, kinematics of the cutter, and the volumetric material removal rate. Closed form expressions for specific cutting energy were formulated and found to be functions of the process parameters: pressure and friction for both rake and flank surfaces and chip flow angle at the rake face of the tool. Friction is found to play a very important role in cutting torque and power. Experiments were carried out to determine the effects of feedrate, cutting speed, workpiece material, and flank wear land width on specific cutting energy. It was found that the specific cutting energy increases with a decrease in the chip thickness and with an increase in flank wear land.

Heterotopic pancreas in excluded stomach diagnosed after gastric bypass surgery

PubMed Central

2013-01-01

Background Heterotopic pancreas is defined as finding of pancreatic tissue without anatomic and vascular continuity with the normal pancreas. Heterotopic pancreas is a rare condition difficult to diagnose and with controversial clinical management. Case presentation We describe a 43 year old female patient previously submitted to laparoscopic gastric bypass for primary treatment of morbid obesity; 5 years later, the patient was discovered to have a mass in the antrum of the excluded stomach that was found to be heterotopic pancreatic tissue. Before gastric bypass surgery, the presence of the pancreatic mass in the gastric wall was unnoticed in the imagiologic records. Conclusion This is the first reported case of pancreatic heterotopy diagnosed in the excluded stomach after gastric bypass. A putative role of incretin hormones in mediating pancreatic cell hyperplasia of heterotopic pancreatic remnants should be considered an additional hypothesis that requires further research. PMID:24267291

Common variants in ZMIZ1 and near NGF confer risk for primary dysmenorrhoea

PubMed Central

Li, Zhiqiang; Chen, Jianhua; Zhao, Ying; Wang, Yujiong; Xu, Jinrui; Ji, Jue; Shen, Jingyi; Zhang, Weiping; Chen, Zuosong; Sun, Qilin; Mao, Lijuan; Cheng, Shulin; Yang, Bo; Zhang, Dongtao; Xu, Yufeng; Zhao, Yingying; Liu, Danping; Shen, Yinhuan; Zhang, Weijie; Li, Changgui; Shen, Jiawei; Shi, Yongyong

2017-01-01

Primary dysmenorrhoea, defined as painful menstrual cramps in the absence of pelvic pathology, is a common problem in women of reproductive age. Its aetiology and pathophysiology remain largely unknown. Here we performed a two-stage genome-wide association study and subsequent replication study to identify genetic factors associated with primary dysmenorrhoea in a total of 6,770 Chinese individuals. Our analysis provided evidence of a significant (P<5 × 10−8) association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF. ZMIZ1 has previously been associated with several autoimmune diseases, and NGF plays a key role in the generation of pain and hyperalgesia and has been associated with migraine. These findings provide future directions for research on susceptibility mechanisms for primary dysmenorrhoea. Furthermore, our genetic architecture analysis provides molecular support for the heritability and polygenic nature of this condition. PMID:28447608

Gravity modulates Listing's plane orientation during both pursuit and saccades

NASA Technical Reports Server (NTRS)

Hess, Bernhard J M.; Angelaki, Dora E.

2003-01-01

Previous studies have shown that the spatial organization of all eye orientations during visually guided saccadic eye movements (Listing's plane) varies systematically as a function of static and dynamic head orientation in space. Here we tested if a similar organization also applies to the spatial orientation of eye positions during smooth pursuit eye movements. Specifically, we characterized the three-dimensional distribution of eye positions during horizontal and vertical pursuit (0.1 Hz, +/-15 degrees and 0.5 Hz, +/-8 degrees) at different eccentricities and elevations while rhesus monkeys were sitting upright or being statically tilted in different roll and pitch positions. We found that the spatial organization of eye positions during smooth pursuit depends on static orientation in space, similarly as during visually guided saccades and fixations. In support of recent modeling studies, these results are consistent with a role of gravity on defining the parameters of Listing's law.

Natural neural projection dynamics underlying social behavior

PubMed Central

Gunaydin, Lisa A.; Grosenick, Logan; Finkelstein, Joel C.; Kauvar, Isaac V.; Fenno, Lief E.; Adhikari, Avishek; Lammel, Stephan; Mirzabekov, Julie J.; Airan, Raag D.; Zalocusky, Kelly A.; Tye, Kay M.; Anikeeva, Polina; Malenka, Robert C.; Deisseroth, Karl

2014-01-01

Social interaction is a complex behavior essential for many species, and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically- and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social but not novel-object interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type-1 dopamine receptor signaling downstream in the NAc. Direct observation of projection-specific activity in this way captures a fundamental and previously inaccessible dimension of circuit dynamics. PMID:24949967

Conformational changes of the N-terminal part of Mason-Pfizer monkey virus p12 protein during multimerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knejzlik, Zdenek; Ulbrich, Pavel; Strohalm, Martin

2009-10-10

The Mason-Pfizer monkey virus is a prototype Betaretrovirus with the defining characteristic that it assembles spherical immature particles from Gag-related polyprotein precursors within the cytoplasm of the infected cell. It was shown previously that the N-terminal part of the Gag p12 domain (wt-Np12) is required for efficient assembly. However, the precise role for p12 in mediating Gag-Gag interaction is still poorly understood. In this study we employed detailed circular dichroism spectroscopy, electron microscopy and ultracentrifugation analyses of recombinant wt-Np12 prepared by in vitro transcription and translation. The wt-Np12 domain fragment forms fibrillar structures in a concentration-dependent manner. Assembly into fibersmore » is linked to a conformational transition from unfolded or another non-periodical state to alpha-helix during multimerization.« less

Machismo and Mexican American men: an empirical understanding using a gay sample.

PubMed

Estrada, Fernando; Rigali-Oiler, Marybeth; Arciniega, G Miguel; Tracey, Terence J G

2011-07-01

Machismo continues to be a defining aspect of Mexican American men that informs a wide array of psychological and behavioral dimensions. Although strides have been made in this area of research, understanding of the role of this construct in the lives of gay men remains incomplete. Our purpose in this study was to gain a deeper understanding of machismo using a sample of Mexican American gay men. This study examined for the first time whether a 2-factor model of machismo previously validated with heterosexual, Mexican American men generalized to a sample of 152 gay men of similar ethnic background. Relations between machismo, sexual risk, and internalized homophobia were also explored. Confirmatory factor analysis supported the 2-factor model with the current sample. Results also indicated machismo as predicting internalized homophobia and as an index of risky sex. Limitations are presented and implications are discussed.

Outer satellite atmospheres: Their nature and planetary interactions

NASA Technical Reports Server (NTRS)

Smyth, W. H.; Combi, M. R.

1982-01-01

Significant progress is reported in early modeling analysis of observed sodium cloud images with our new model which includes the oscillating Io plasma torus ionization sink. Both the general w-D morphology of the region B cloud as well as the large spatial gradient seen between the region A and B clouds are found to be consistent with an isotropic flux of sodium atoms from Io. Model analysis of the spatially extended high velocity directional features provided substantial evidence for a magnetospheric wind driven gas escape mechanism from Io. In our efforts to define the source(s) of hydrogen atoms in the Saturn system, major steps were taken in order to understand the role of Titan. We have completed the comparison of the Voyager UVS data with previous Titan model results, as well as the update of the old model computer code to handle the spatially varying ionization sink for H atoms.

Adding and Removing Web Area Users, and Changing User Roles

EPA Pesticide Factsheets

Webmasters can add users to a web area, and assign or change roles, which define the actions a user is able to take in the web area. Non-webmasters must use a request form to add users and change roles.

The Power of Possibility. Defining Moments: How IDRA and Its Partners Are Changing Public Education. IDRA Annual Report 2014

ERIC Educational Resources Information Center

Intercultural Development Research Association, 2014

2014-01-01

Intercultural Development Research Association's (IDRA) 2014 Annual Report highlights seven defining moments in the work of the previous year: (1) Securing Opportunity; (2) Defending Children's Educational and Civil Rights; (3) Building a National Grassroots Family Model; (4) Putting Quality Early Education at the Forefront; (5) Empowering…

In vitro fertilization (IVF) from low or high antral follicle count pubertal beef heifers using semi-defined culture conditions

USDA-ARS?s Scientific Manuscript database

Antral follicle counts (AFC) vary among pubertal beef heifers. Our objective was to compare the in vitro maturation and fertilization of oocytes collected from low and high AFC heifers. Previously we reported results using serum-based IVF media and in this study report results using semi-defined m...

Mobile Device Impairment ... Similar Problems, Similar Solutions?

ERIC Educational Resources Information Center

Harper, Simon; Yesilada, Yeliz; Chen, Tianyi

2011-01-01

Previous studies have defined a new type of impairment in which an able-bodied user's behaviour is impaired by both the characteristics of a device and the environment in which it is used. This behavioural change is defined as a situationally-induced impairment and is often associated with small devices used in a mobile setting or constrained…

Vps26B-retromer negatively regulates plasma membrane resensitization of PAR-2.

PubMed

Bugarcic, Andrea; Vetter, Irina; Chalmers, Silke; Kinna, Genevieve; Collins, Brett M; Teasdale, Rohan D

2015-11-01

Retromer is a trimeric complex composed of Vps26, Vps29, and Vps35 and has been shown to be involved in trafficking and sorting of transmembrane proteins within the endosome. The Vps26 paralog, Vps26B, defines a distinct retromer complex (Vps26B-retromer) in vivo and in vitro. Although endosomally associated, Vps26B-retromer does not bind the established retromer transmembrane cargo protein, cation-independent mannose 6-phosphate receptor (CI-M6PR), indicating it has a distinct role to retromer containing the Vps26A paralog. In the present study we use the previously established Vps26B-expressing HEK293 cell model to address the role of Vps26B-retromer in trafficking of the protease activated G-protein coupled receptor PAR-2 to the plasma membrane. In these cells there is no apparent defect in the initial activation of the receptor, as evidenced by release of intracellular calcium, ERK1/2 signaling and endocytosis of activated receptor PAR-2 into degradative organelles. However, we observe a significant delay in plasma membrane repopulation of the protease activated G protein-coupled receptor PAR-2 following stimulation, resulting in a defect in PAR-2 activation after resensitization. Here we propose that PAR-2 plasma membrane repopulation is regulated by Vps26B-retromer, describing a potential novel role for this complex. © 2015 International Federation for Cell Biology.

Packaging signals in single-stranded RNA viruses: nature's alternative to a purely electrostatic assembly mechanism.

PubMed

Stockley, Peter G; Twarock, Reidun; Bakker, Saskia E; Barker, Amy M; Borodavka, Alexander; Dykeman, Eric; Ford, Robert J; Pearson, Arwen R; Phillips, Simon E V; Ranson, Neil A; Tuma, Roman

2013-03-01

The formation of a protective protein container is an essential step in the life-cycle of most viruses. In the case of single-stranded (ss)RNA viruses, this step occurs in parallel with genome packaging in a co-assembly process. Previously, it had been thought that this process can be explained entirely by electrostatics. Inspired by recent single-molecule fluorescence experiments that recapitulate the RNA packaging specificity seen in vivo for two model viruses, we present an alternative theory, which recognizes the important cooperative roles played by RNA-coat protein interactions, at sites we have termed packaging signals. The hypothesis is that multiple copies of packaging signals, repeated according to capsid symmetry, aid formation of the required capsid protein conformers at defined positions, resulting in significantly enhanced assembly efficiency. The precise mechanistic roles of packaging signal interactions may vary between viruses, as we have demonstrated for MS2 and STNV. We quantify the impact of packaging signals on capsid assembly efficiency using a dodecahedral model system, showing that heterogeneous affinity distributions of packaging signals for capsid protein out-compete those of homogeneous affinities. These insights pave the way to a new anti-viral therapy, reducing capsid assembly efficiency by targeting of the vital roles of the packaging signals, and opens up new avenues for the efficient construction of protein nanocontainers in bionanotechnology.

Rationale in support of the use of selective dopamine D₃ receptor antagonists for the pharmacotherapeutic management of substance use disorders.

PubMed

Heidbreder, Christian

2013-02-01

Growing evidence indicates that dopamine (DA) D(3) receptors are involved in the control of drug-seeking behavior and may play an important role in the pathophysiology of substance use disorders. First, DA D(3) receptors are distributed in strategic areas belonging to the mesolimbic DA system such as the ventral striatum, midbrain, and pallidum, which have been associated with behaviors controlled by the presentation of drug-associated cues. Second, repeated exposure to drugs of abuse has been shown to produce neuroadaptations in the DA D(3) system. Third, the synthesis and characterization of highly potent and selective DA D(3) receptor antagonists has permitted to further define the role of the DA D(3) receptor in drug addiction. Provided that the available preclinical and preliminary clinical evidence can be translated into clinical proof of concept in human, selective DA D(3) receptor antagonists show promise for the treatment of substance use disorders as reflected by their potential to (1) regulate the motivation to self-administered drugs under schedules of reinforcement that require an increase in work demand and (2) disrupt the responsiveness to drug-associated stimuli that play a key role in the reinstatement of drug-seeking behavior triggered by re-exposure to the drug itself, re-exposure to environmental cues that had been previously associated with drug-taking behavior, or stress.

Role Sequencing: Does Order Matter for Mental Health?

ERIC Educational Resources Information Center

Jackson, Pamela Braboy

2004-01-01

Role sequencing refers to the ordering of social roles. According to the normative order hypothesis, adults who follow a certain sequencing of their social roles will be better adjusted than their peers who follow other life course patterns. The normative order is defined as first entering the paid labor force, getting married, and later having…

Defining role models for staff orientation.

PubMed

Kinley, H

This article examines the need for a formal role model to help integrate new staff within a unit. While acknowledging the range of titles and functions ascribed to such a role in the literature, the author suggests that the essence of the role and its formal recognition has benefits for experienced staff and orientees alike.

Nursing faculty roles in international service-learning projects.

PubMed

Kohlbry, Pamela; Daugherty, JoAnn

2013-01-01

The purpose of this article is to describe faculty roles related to the design and implementation of an international nursing service-learning project. The impetus for this project was the 2008 American Association of Colleges of Nursing (AACN) recommendations for using service-learning and immersion of students in diverse communities to improve nursing education in the area of cultural competency (American Association of Colleges of Nursing, 2008a). We define service-learning as a learning experience engaging students in meeting community needs in an international setting so as to offer a different perspective into community health practices and to promote cultural competency. Based on our experience with service-learning, we identified four faculty roles in developing these types of projects. We define these roles as initiator, collaborator, facilitator, and advocate. This article will discuss the application of these faculty roles in developing service-learning opportunities with students. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of habitat choice in micro-evolutionary dynamics: An experimental study on the Mediterranean killifish Aphanius fasciatus (Cyprinodontidae).

PubMed

Angeletti, Dario; Sebbio, Claudia; Carlini, Alessandro; Strinati, Claudia; Nascetti, Giuseppe; Carere, Claudio; Cimmaruta, Roberta

2017-12-01

Habitat choice is defined as a nonrandom distribution of genotypes in different microhabitats. Therefore, it could exert a great impact on the genetic variance of natural populations by promoting genetic divergence, local adaptation, and may even lead to sympatric speciation. Despite this potential role in micro- and macro-evolutionary processes, there is little empirical evidence that the various genotypes within a population may differ in habitat choice-related behaviors. Here, we tested whether habitat choice may have contributed to genetic divergence within a local population of the Mediterranean killifish Aphanius fasciatus , which emerged between groups inhabiting microhabitats with different oxygen concentrations during previous field studies. In a first experiment, we studied the distribution of individuals in conditions of hypoxia and normoxia to test whether they had a different ability to shy away from a hypoxic environment; in a second experiment, we analyzed the individual behavior of fish separately in the two conditions, to verify whether they showed peculiar behavioral responses linked to a possible differential distribution. We then analyzed the six allozyme loci, whose allelic and genotypic frequencies were significantly divergent in the previous studies. In the first test, we found that the distribution of the two homozygote genotypes of the glucose-6-phosphate isomerase-1 locus (GPI-1) was significantly different between the hypoxic and the normoxic conditions. During the second test, all individuals were more active in hypoxic conditions, but the two GPI-1 homozygotes showed a significant difference in time spent performing surface breathing, which was consistent with their distribution observed in the first experiment. These results provide evidence that individual behavioral traits, related to genetic features, may lead to a nonrandom distribution of genotypes in heterogeneous although contiguous microhabitats and, consequently, that habitat choice can play a significant role in driving the micro-evolutionary dynamics of this species.

Role Clarification Processes for Better Integration of Nurse Practitioners into Primary Healthcare Teams: A Multiple-Case Study

PubMed Central

D'Amour, Danielle; Contandriopoulos, Damien; Chouinard, Véronique; Dubois, Carl-Ardy

2014-01-01

Role clarity is a crucial issue for effective interprofessional collaboration. Poorly defined roles can become a source of conflict in clinical teams and reduce the effectiveness of care and services delivered to the population. Our objective in this paper is to outline processes for clarifying professional roles when a new role is introduced into clinical teams, that of the primary healthcare nurse practitioner (PHCNP). To support our empirical analysis we used the Canadian National Interprofessional Competency Framework, which defines the essential components for role clarification among professionals. A qualitative multiple-case study was conducted on six cases in which the PHCNP role was introduced into primary care teams. Data collection included 34 semistructured interviews with key informants involved in the implementation of the PHCNP role. Our results revealed that the best performing primary care teams were those that used a variety of organizational and individual strategies to carry out role clarification processes. From this study, we conclude that role clarification is both an organizational process to be developed and a competency that each member of the primary care team must mobilize to ensure effective interprofessional collaboration. PMID:25692039

Role clarification processes for better integration of nurse practitioners into primary healthcare teams: a multiple-case study.

PubMed

Brault, Isabelle; Kilpatrick, Kelley; D'Amour, Danielle; Contandriopoulos, Damien; Chouinard, Véronique; Dubois, Carl-Ardy; Perroux, Mélanie; Beaulieu, Marie-Dominique

2014-01-01

Role clarity is a crucial issue for effective interprofessional collaboration. Poorly defined roles can become a source of conflict in clinical teams and reduce the effectiveness of care and services delivered to the population. Our objective in this paper is to outline processes for clarifying professional roles when a new role is introduced into clinical teams, that of the primary healthcare nurse practitioner (PHCNP). To support our empirical analysis we used the Canadian National Interprofessional Competency Framework, which defines the essential components for role clarification among professionals. A qualitative multiple-case study was conducted on six cases in which the PHCNP role was introduced into primary care teams. Data collection included 34 semistructured interviews with key informants involved in the implementation of the PHCNP role. Our results revealed that the best performing primary care teams were those that used a variety of organizational and individual strategies to carry out role clarification processes. From this study, we conclude that role clarification is both an organizational process to be developed and a competency that each member of the primary care team must mobilize to ensure effective interprofessional collaboration.

A Parameterized Model of Amylopectin Synthesis Provides Key Insights into the Synthesis of Granular Starch

PubMed Central

Wu, Alex Chi; Morell, Matthew K.; Gilbert, Robert G.

2013-01-01

A core set of genes involved in starch synthesis has been defined by genetic studies, but the complexity of starch biosynthesis has frustrated attempts to elucidate the precise functional roles of the enzymes encoded. The chain-length distribution (CLD) of amylopectin in cereal endosperm is modeled here on the basis that the CLD is produced by concerted actions of three enzyme types: starch synthases, branching and debranching enzymes, including their respective isoforms. The model, together with fitting to experiment, provides four key insights. (1) To generate crystalline starch, defined restrictions on particular ratios of enzymatic activities apply. (2) An independent confirmation of the conclusion, previously reached solely from genetic studies, of the absolute requirement for debranching enzyme in crystalline amylopectin synthesis. (3) The model provides a mechanistic basis for understanding how successive arrays of crystalline lamellae are formed, based on the identification of two independent types of long amylopectin chains, one type remaining in the amorphous lamella, while the other propagates into, and is integral to the formation of, an adjacent crystalline lamella. (4) The model provides a means by which a small number of key parameters defining the core enzymatic activities can be derived from the amylopectin CLD, providing the basis for focusing studies on the enzymatic requirements for generating starches of a particular structure. The modeling approach provides both a new tool to accelerate efforts to understand granular starch biosynthesis and a basis for focusing efforts to manipulate starch structure and functionality using a series of testable predictions based on a robust mechanistic framework. PMID:23762422

Exploring the factors that influence the perception of risk: The case of Volcán de Colima, Mexico

NASA Astrophysics Data System (ADS)

Gavilanes-Ruiz, Juan Carlos; Cuevas-Muñiz, Alicia; Varley, Nick; Gwynne, Gemma; Stevenson, John; Saucedo-Girón, Ricardo; Pérez-Pérez, Anaid; Aboukhalil, Mary; Cortés-Cortés, Abel

2009-10-01

Volcán de Colima has increased its activity considerably since 1998 with four periods of effusion and since 2003, daily Vulcanian explosions. During 2005 the magnitude of the explosivity increased, producing many pyroclastic flows, two of which reached over 5 km from the volcano, making them the largest events since the last Plinian eruption in 1913. A significant risk is also presented by the lahar hazard, with various examples of damage to infrastructure during the last few years and 23 people killed in 1955. Nearly 5000 people live in small settlements within 15 km of the volcano. Since 1997 six studies have been carried out in the region in an attempt to define the relationship that exists between the population and its neighbour. Although the methodologies used were different, each study considered the results of the previous and attempted to contribute further data to define geographical variation in the perception of risk. The results of the studies highlight the minor role of increasing activity on risk perception, and distance from the volcano was shown to not directly influence risk perception. In most cases it is the combination of various socio-cultural, historical and political factors that defines the perception of volcanic risk within these villages. By studying the social representation of the risk, such complexity could be better understood. The 1997-2000 information campaign evidently improved risk perception; however, it is clear that this type of program needs to be continued to achieve a long lasting impact. Increased knowledge, however, does not guarantee willing participation in official risk mitigation strategies.

Sex in public and private settings among Latino MSM

PubMed Central

Reisen, Carol A; Iracheta, Miguel A.; Zea, Maria Cecilia; Bianchi, Fernanda T.; Poppen, Paul J.

2009-01-01

Latino men who have sex with men (MSM) constitute a group at high risk for HIV. Recent approaches to understanding sexual risk have emphasized the role that contextual factors can play in shaping behavior. This study examined sexual behavior of Latino MSM in private and public settings. First, a within-person comparison of behaviors performed in sexual encounters that occurred in public and private settings was conducted. Unprotected anal intercourse and other sexual behaviors involving anal stimulation were more common in private settings; group sex was more likely in public settings. Second, a between-person analysis compared sexual behaviors of MSM who went to three different types of public sex settings during the previous six months. The types were: 1) commercial sex venues (CSVs), which were defined as businesses with the function of providing a space where MSM can go to have sexual encounters, such as gay bathhouses; 2) commercial sex environments (CSEs), which were defined as businesses with another apparent function, but in which MSM sometimes have sexual encounters, such as gay bars or pornographic movie houses; and 3) public sex environments (PSEs), which were defined as free public areas where MSM can go to find partners for anonymous sex, such as parks or public restrooms. Results indicated that anal sexual behavior was most likely to occur in CSVs and least likely in PSEs, but the probability of unprotected anal intercourse was not found to differ among the three types of settings. Behavioral differences were discussed in terms of structural conditions related to privacy and safety, and psychological factors related to intimacy. PMID:20461575

Attitudes and concerns of Canadian animal health technologists toward postoperative pain management in dogs and cats.

PubMed

Dohoo, S E; Dohoo, I R

1998-08-01

Three hundred and twenty-two Canadian animal health technologists (AHTs) were surveyed to determine their attitudes toward postoperative pain management in dogs and cats following 6 surgical procedures, their concerns regarding the use of opioid analgesics, and their role within veterinary practices with respect to postoperative pain control. Two hundred and sixty-four (82%) returned the questionnaire. Pain perception was defined as the average of pain rankings for dogs and cats (on a scale of 1 to 10) following abdominal surgery, or the value for dogs or cats if the AHT worked with only 1 of the 2 species. Maximum concern about the risks associated with the postoperative use of morphine or oxymorphone was defined as the highest rating assigned to any of the 6 risks evaluated in either dogs or cats. Animal health technologists reported significantly higher pain perception scores than did veterinarians who completed a similar survey 2 years previously. Higher pain perception scores were associated with decreased satisfaction with the adequacy of analgesic therapy in their practice, higher pain control goals, and attendance at continuing education within the previous 12 months. The majority of AHTs (55%) agreed that one or more risks associated with the use of morphine or oxymorphone outweighed the benefits. The 3 issues that were perceived to pose the greatest risk were respiratory depression, bradycardia, and sedation and excitement, for dogs and cats, respectively. Most AHTs (68%) considered their knowledge related to the recognition and control of pain to be adequate, compared with 24% of veterinarians who responded to a similar previous survey. As for veterinarians, experience gained while in practice was ranked as the most important source of knowledge, while the technical program attended was ranked as least important. Over 88% of the AHTs provided nursing care during the postoperative period, monitored animals for side effects of postoperative analgesic therapy, informed veterinarians when animals were in pain, recommended analgesic therapy when they believed it was warranted, reported that animals received analgesics when they believed it was warranted, administered analgesics under the instruction of a veterinarian, and believed they were part of a team working to provide adequate postoperative pain control.

The prevalence of undiagnosed concussions in athletes.

PubMed

Meehan, William P; Mannix, Rebekah C; O'Brien, Michael J; Collins, Michael W

2013-09-01

Previous studies suggest athletes underreport concussions. We sought to determine whether athletes in our clinics have sustained previous concussions that went undiagnosed. Multicentered cross sectional study. Two sport concussion clinics. Patients diagnosed with sport-related concussions or concussions with injury mechanisms and forces similar to those observed in sports were included. The proportion of patients who answered "yes" to the following question were defined as having a previously undiagnosed concussion: "Have you ever sustained a blow to the head which was NOT diagnosed as a concussion but was followed by one or more of the signs and symptoms listed in the Post Concussion Symptom Scale?" Of the 486 patients included in the final analysis, 148 (30.5%) patients reported a previously undiagnosed concussion. Athletes reporting previously undiagnosed concussions had a higher mean Post Concussion Symptom Scale (PCSS) score (33 vs 25; P < 0.004) and were more likely to have lost consciousness (31% vs 22%; P = 0.038) with their current injury than athletes without previously undiagnosed concussions. Nearly one-third of athletes have sustained previously undiagnosed concussions, defined as a blow to the head followed by the signs and symptoms included in the PCSS. Furthermore, these previously undiagnosed concussions are associated with higher PCSS scores and higher loss of consciousness rates when future concussions occur. Many athletes have sustained previous blows to the head that result in the signs and symptoms of concussion but have not been diagnosed with a concussion. These injuries are associated with increased rates of loss of consciousness and higher symptom scale scores with future concussions.

Understanding gender roles in teen pregnancy prevention among American Indian youth.

PubMed

Hanson, Jessica D; McMahon, Tracey R; Griese, Emily R; Kenyon, DenYelle Baete

2014-11-01

To examine the impact of gender norms on American Indian (AI) adolescents' sexual health behavior. The project collected qualitative data at a reservation site and an urban site through 24 focus groups and 20 key informant interviews. The reasons that AI youth choose to abstain or engage in sexual intercourse and utilize contraception vary based on gender ideologies defined by the adolescent's environment. These include social expectations from family and peers, defined roles within relationships, and gender empowerment gaps. Gender ideology plays a large role in decisions about contraception and sexual activity for AI adolescents, and it is vital to include redefinitions of gender norms within AI teen pregnancy prevention program.

Dragon (repulsive guidance molecule RGMb) inhibits E-cadherin expression and induces apoptosis in renal tubular epithelial cells.

PubMed

Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y; Xia, Yin

2013-11-01

Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45-66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo.

The role of stabilizing and communicating symptoms given overlapping communities in psychopathology networks.

PubMed

Blanken, Tessa F; Deserno, Marie K; Dalege, Jonas; Borsboom, Denny; Blanken, Peter; Kerkhof, Gerard A; Cramer, Angélique O J

2018-04-11

Network theory, as a theoretical and methodological framework, is energizing many research fields, among which clinical psychology and psychiatry. Fundamental to the network theory of psychopathology is the role of specific symptoms and their interactions. Current statistical tools, however, fail to fully capture this constitutional property. We propose community detection tools as a means to evaluate the complex network structure of psychopathology, free from its original boundaries of distinct disorders. Unique to this approach is that symptoms can belong to multiple communities. Using a large community sample and spanning a broad range of symptoms (Symptom Checklist-90-Revised), we identified 18 communities of interconnected symptoms. The differential role of symptoms within and between communities offers a framework to study the clinical concepts of comorbidity, heterogeneity and hallmark symptoms. Symptoms with many and strong connections within a community, defined as stabilizing symptoms, could be thought of as the core of a community, whereas symptoms that belong to multiple communities, defined as communicating symptoms, facilitate the communication between problem areas. We propose that defining symptoms on their stabilizing and/or communicating role within and across communities accelerates our understanding of these clinical phenomena, central to research and treatment of psychopathology.

The contribution of tumour-derived exosomes to the hallmarks of cancer.

PubMed

Meehan, Katie; Vella, Laura J

2016-01-01

Exosomes are small, biologically active extracellular vesicles and over the last decade, both stromal and tumour-derived exosomes (TDE) have been implicated in cancer onset, progression and metastases. Cancer is a complex disease that is underpinned by several "cancer hallmarks", originally described by Hanahan and Weinberg in 2000 and then revised in 2011. The hallmarks of cancer comprise six biological capabilities, along with two emerging hallmarks and two enabling characteristics that facilitate tumour growth and metastatic dissemination. Ample evidence supports a clear role for TDE in four of the original biological hallmarks (sustaining proliferative signalling, resisting cell death, inducing angiogenesis and activating invasion and metastases). A less-defined role exists for TDE in evading growth suppressors, and currently, there is no evidence to suggest a role for TDE in enabling replicative immortality. TDE are intimately involved in the newly defined hallmarks of cancer and enabling characteristics, most evidently in immune inhibition and tumour-promoting inflammation, which ultimately enable escape from immune destruction and tumour progression. Herein, we discuss the role of TDE in the context of the hallmarks and enabling characteristics of cancer as defined by Hanahan and Weinberg.

Entry Points When Undergraduate Research Mentors Reflect on Their Role: A Qualitative Case Study

ERIC Educational Resources Information Center

Wallin, Patric; Adawi, Tom

2018-01-01

Graduate students and postdoctoral researchers are increasingly taking on mentoring roles in undergraduate research (UR). There is, however, a paucity of research focusing on how they conceptualize their mentoring role. In this qualitative interview study, we identified three entry points that mentors reflect on to define their role: (1) What are…

Motivation within Role-Playing as a Means to Intensify College Students' Educational Activity

ERIC Educational Resources Information Center

Burenkova, Olga Mikhailovna; Arkhipova, Irina Vladimirovna; Semenov, Sergei Aleksandrovich; Samarenkina, Saniya Zakirzyanovna

2015-01-01

This article covers college students' educational activity issues while studying a foreign language; analyzes special aspects of motivation introduction, their specific features. It also defines role and structure of role-playing. The authors come to the conclusion that introduction of role-playing in an educational process will bring it closer to…

Idiographic Roles of Cooperating Teachers as Mentors in Pre-Service Distance Teacher Education

ERIC Educational Resources Information Center

Koc, Ebru Melek

2012-01-01

This study aims to define the roles of cooperating teachers as mentors in the context of distance-learning teacher education. The participants included 358 cooperating teachers who mentored 4th-year student teachers in a Distance English Language Teacher Training Program in Turkey. To determine the roles that were perceived as mentoring roles by…

Coming in from the Margins: Faculty Development's Emerging Organizational Development Role in Institutional Change

ERIC Educational Resources Information Center

Schroeder, Connie

2010-01-01

Recognizing that a necessary and significant role change is underway in faculty development, this book calls for centers to merge their traditional responsibilities and services with a leadership role as organizational developers. Failing to define and outline the dimensions and expertise of this new role puts centers at risk of not only…

Isopermutation group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muktibodh, A. S.

2015-03-10

The concept of ‘Isotopy’ as formulated by Ruggero Maria Santilli [1, 2, 3] plays a vital role in the development of Iso mathematics. Santilli defined iso-fields of characteristic zero. In this paper we extend this definition to define Iso-Galois fields [4] which are essentially of non-zero characteristic. Isotopically isomorphic realizations of a group define isopermutation group which gives a clear cut distinction between automorphic groups and isotopic groups.

Defining as a Mathematical Activity: A Framework for Characterizing Progress from Informal to More Formal Ways of Reasoning

ERIC Educational Resources Information Center

Zandieh, Michelle; Rasmussen, Chris

2010-01-01

The purpose of this paper is to further the notion of defining as a mathematical activity by elaborating a framework that structures the role of defining in student progress from informal to more formal ways of reasoning. The framework is the result of a retrospective account of a significant learning experience that occurred in an undergraduate…

The ULT trxG Fatcors play a role in Arabidopsis Fertilization

USDA-ARS?s Scientific Manuscript database

Trithorax group (trxG) and Polycomb group (PcG) proteins are epigenetic modifiers that play key roles in eukaryotic development by promoting active or repressive gene expression states, respectively. Although PcG proteins have well-defined roles in controlling developmental transitions, cell fate de...

Nrk2b-mediated NAD+ production regulates cell adhesion and is required for muscle morphogenesis in vivo

PubMed Central

Goody, Michelle F.; Kelly, Meghan W.; Lessard, Kevin N.; Khalil, Andre; Henry, Clarissa A.

2010-01-01

Cell-matrix adhesion complexes (CMACs) play fundamental roles during morphogenesis. Given the ubiquitous nature of CMACs and their roles in many cellular processes, one question is how specificity of CMAC function is modulated. The clearly defined cell behaviors that generate segmentally reiterated axial skeletal muscle during zebrafish development comprise an ideal system with which to investigate CMAC function during morphogenesis. We found that Nicotinamide riboside kinase 2b (Nrk2b) cell autonomously modulates the molecular composition of CMACs in vivo. Nrk2b is required for normal Laminin polymerization at the myotendinous junction (MTJ). In Nrk2b-deficient embryos, at MTJ loci where Laminin is not properly polymerized, muscle fibers elongate into adjacent myotomes and are abnormally long. In yeast and human cells, Nrk2 phosphorylates Nicotinamide Riboside and generates NAD+ through an alternative salvage pathway. Exogenous NAD+ treatment rescues MTJ development in Nrk2b-deficient embryos, but not in laminin mutant embryos. Both Nrk2b and Laminin are required for localization of Paxillin, but not β-Dystroglycan, to CMACs at the MTJ. Overexpression of Paxillin in Nrk2b-deficient embryos is sufficient to rescue MTJ integrity. Taken together, these data show that Nrk2b plays a specific role in modulating subcellular localization of discrete CMAC components that in turn play roles in musculoskeletal development. Furthermore, these data suggest that Nrk2b-mediated synthesis of NAD+ is functionally upstream of Laminin adhesion and Paxillin subcellular localization during MTJ development. These results indicate a previously unrecognized complexity to CMAC assembly in vivo and also elucidate a novel role for NAD+ during morphogenesis. PMID:20566368

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

PubMed

Nguyen, Quan Dong; De Falco, Sandro; Behar-Cohen, Francine; Lam, Wai-Ching; Li, Xuri; Reichhart, Nadine; Ricci, Federico; Pluim, Jennifer; Li, William W

2018-02-01

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

49 CFR 195.446 - Control room management.

Code of Federal Regulations, 2010 CFR

2010-10-01

... written control room management procedures that implement the requirements of this section. The procedures... define the roles and responsibilities of a controller during normal, abnormal, and emergency operating... operator must define each of the following: (1) A controller's authority and responsibility to make...

Mapping variable width riparian buffers

Treesearch

Sinan Abood

2016-01-01

Riparian buffers are dynamic, transitional ecosystems between aquatic and terrestrial ecosystems with well-defined vegetation and soil characteristics. Previous approaches to riparian buffer delineation have...

Forest Plantations

Treesearch

D. Zhang; J.A. Stanturf

2008-01-01

Between the extremes of afforestation and unaided naturalregeneration of natural forests, there is a range offorest conditions in which human intervention occurs.Previously, forest plantations were defined as...

Intranasal oxytocin and a polymorphism in the oxytocin receptor gene are associated with human-directed social behavior in golden retriever dogs.

PubMed

Persson, Mia E; Trottier, Agaia J; Bélteky, Johan; Roth, Lina S V; Jensen, Per

2017-09-01

The oxytocin system may play an important role in dog domestication from the wolf. Dogs have evolved unique human analogue social skills enabling them to communicate and cooperate efficiently with people. Genomic differences in the region surrounding the oxytocin receptor (OXTR) gene have previously been associated with variation in dogs' communicative skills. Here we have utilized the unsolvable problem paradigm to investigate the effects of oxytocin and OXTR polymorphisms on human-directed contact seeking behavior in 60 golden retriever dogs. Human-oriented behavior was quantified employing a previously defined unsolvable problem paradigm. Behaviors were tested twice in a repeated, counterbalanced design, where dogs received a nasal dose of either oxytocin or saline 45min before each test occasion. Buccal DNA was analysed for genotype on three previously identified SNP-markers associated with OXTR. The same polymorphisms were also genotyped in 21 wolf blood samples to explore potential genomic differences between the species. Results showed that oxytocin treatment decreased physical contact seeking with the experimenter and one of the three polymorphisms was associated with degree of physical contact seeking with the owner. Dogs with the AA-genotype at this locus increased owner physical contact seeking in response to oxytocin while the opposite effect was found in GG-genotype individuals. Hence, intranasal oxytocin treatment, an OXTR polymorphism and their interaction are associated with dogs' human-directed social skills, which can explain previously described breed differences in oxytocin response. Genotypic variation at the studied locus was also found in wolves indicating that it was present even at the start of dog domestication. Copyright © 2017 Elsevier Inc. All rights reserved.

[Leaders as intermediates between economic incentive models and professional motivation].

PubMed

Korlén, Sara; Essén, Anna; Lindgren, Peter; Amer-Wåhlin, Isis; von Thiele Schwarz, Ulrica

2018-05-24

The application of economic incentives to providers in health care governance is debated. Advocates argue that it drives efficiency and improvement, opponents claim that it leads to unintended consequences for patients and professionals. Research shows that incentives can increase well-defined activities and targets, but there is a lack of substantial evidence that applications in health care lead to desired outcomes. The motivational literature acknowledges internal sources of motivation as important determinants of behavior, and the literature about professions suggests that professional values of serving patient needs is a key motivator. The management literature identifies the important role of leaders in aligning external demands and rewards to staff preferences, using their own management and leadership skills. Findings in health services research confirm the vital role of leaders for successful implementation and improvement work. In sum, internal motivators and the role of leaders are important to acknowledge also when understanding how economic governance models are put into practice.Our recently published qualitative case study provides empirical examples of how clinical leaders function as intermediaries between a local care choice model, including financial incentives, and the motivation of staff. The strategies deployed by the leaders aimed to align the economic logics of the model to the professional focus on increasing patient value. The main conclusion from these empirical examples, as well as previous research, is that health care managers play a key role in aligning economic incentive models with professional values and in translating such models in to feasible tasks related to the provision of high quality care.

The underestimated role of temperature-oxygen relationship in large-scale studies on size-to-temperature response.

PubMed

Walczyńska, Aleksandra; Sobczyk, Łukasz

2017-09-01

The observation that ectotherm size decreases with increasing temperature (temperature-size rule; TSR) has been widely supported. This phenomenon intrigues researchers because neither its adaptive role nor the conditions under which it is realized are well defined. In light of recent theoretical and empirical studies, oxygen availability is an important candidate for understanding the adaptive role behind TSR. However, this hypothesis is still undervalued in TSR studies at the geographical level. We reanalyzed previously published data about the TSR pattern in diatoms sampled from Icelandic geothermal streams, which concluded that diatoms were an exception to the TSR. Our goal was to incorporate oxygen as a factor in the analysis and to examine whether this approach would change the results. Specifically, we expected that the strength of size response to cold temperatures would be different than the strength of response to hot temperatures, where the oxygen limitation is strongest. By conducting a regression analysis for size response at the community level, we found that diatoms from cold, well-oxygenated streams showed no size-to-temperature response, those from intermediate temperature and oxygen conditions showed reverse TSR, and diatoms from warm, poorly oxygenated streams showed significant TSR. We also distinguished the roles of oxygen and nutrition in TSR. Oxygen is a driving factor, while nutrition is an important factor that should be controlled for. Our results show that if the geographical or global patterns of TSR are to be understood, oxygen should be included in the studies. This argument is important especially for predicting the size response of ectotherms facing climate warming.

The Changing Job of the President.

ERIC Educational Resources Information Center

McPhail, Irving P.

The multiple roles of a contemporary Black college president are discussed and defined, focusing on the changing role of the president. Like their White counterparts, presidents of the nation's 117 historically Black colleges have seen their roles evolve as they have become savvy promoters, competing aggressively for students and philanthropic…

Individualizing Education: A Guide for Tutors.

ERIC Educational Resources Information Center

Linder, Steven; Gordon, Rhonda Ellen

A background manual for tutors explains and defines their role in a system of individualized education in some detail. Differences between the role of teacher and the role of tutor are analyzed. Methods of forestalling cheating and other "black-market operations" are discussed. Tutoring procedures are outlined and individualized education manuals…

Scientist | Center for Cancer Research

Cancer.gov

KEY ROLES/RESPONSIBILITIES The Scientist I will support research efforts to define the role of transcriptional regulators in myeloid cell development, and their potential role in leukemogenesis.  This work will be accomplished performing both molecular and stem cell biology techniques, cloning and construction of retroviral vectors, quantitative RT-PCR, cloning of conditional

The Imperative of Service in the Professor's Role.

ERIC Educational Resources Information Center

Achilles, C. M.; Achilles, Susan H.

In the professorial role's traditional triad of teaching, research, and service, research (publishing) and teaching get more attention than service. If professors are to be part of improving education in America's schools, they must define service more broadly, and they must give greater attention to the service role. Education should be…

Lay food and health worker involvement in community nutrition and dietetics in England: roles, responsibilities and relationship with professionals.

PubMed

Kennedy, L A; Milton, B; Bundred, P

2008-06-01

Community-based food initiatives have developed in recent years with the aim of engaging previously 'hard to reach' groups. Lay workers engaged in community nutrition activities are promoted as a cost-effective mechanism for reaching underserved groups. The main objective of the study was to explore perceptions and definitions of lay food and health worker (LFHW) helping roles within the context of National Health Service (NHS) community nutrition and dietetic services in order to define the conceptual and practical elements of this new role and examine the interface with professional roles. Interpretive qualitative inquiry; semi-structured interviews with LFHW and NHS professionals employed by community-based programmes, serving 'hard-to-reach' neighbourhoods, across England. A total sampling framework was used to capture all existing and 'fully operational' lay food initiatives in England at the commencement of fieldwork (January 2002). In total, 29 professionals and 53 LFHWs were interviewed across 15 of the 18 projects identified. Although all 15 projects shared a universal goal, to promote healthy eating, this was achieved through a limited range of approaches, characterized by a narrow, individualistic focus. Lay roles spanned three broad areas: nutrition education; health promotion; and administration and personal development. Narratives from both professionals and LFHWs indicated that the primary role for LFHWs was to encourage dietary change by translating complex messages into credible and culturally appropriate advice. This research confirms the emerging discipline involving lay helping within the NHS and community dietetics. The primary role of LFHWs in the 15 projects involved was to support existing NHS services to promote healthy eating amongst 'hard to reach' communities. The activities undertaken by LFHWs are strongly influenced by professionals and the NHS. Inherent to this is a fairly narrow interpretation of health, resulting in a limited range of practice.

A defining aspect of human resilience in the workplace: a structural modeling approach.

PubMed

Everly, George S; Davy, Jeanettte A; Smith, Kenneth J; Lating, Jeffrey M; Nucifora, Frederick C

2011-06-01

It has been estimated that up to 90% of the US population is exposed to at least 1 traumatic event during their lifetime. Although there is growing evidence that most people are resilient, meaning that they have the ability to adapt to or rebound from adversity, between 5% and 10% of individuals exposed to traumatic events meet criteria for posttraumatic stress disorder. Therefore, identifying the elements of resilience could lead to interventions or training programs designed to enhance resilience. In this article, we test the hypothesis that the effects of stressor conditions on outcomes such as job-related variables may be mediated through the cognitive and affective registrations of those events, conceptualized as subjective stress arousal. The subjects were 491 individuals employed in public accounting, who were sampled from a mailing list provided by the American Institute of Certified Public Accountants. The stressors used in this study were role ambiguity, role conflict, and role overload and the outcome measures were performance, turnover intentions, job satisfaction, and burnout. Stress arousal was measured using a previously developed stress arousal scale. We conducted a series of 2 EQS structural modeling analyses to assess the impact of stress arousal. The first model examined only the direct effects from the role stressors to the outcome constructs. The second model inserted stress arousal as a mediator in the relations between the role stressors and the outcomes. The results of our investigation supported the notion that subjective stress arousal provides greater explanatory clarity by mediating the effects of stressors upon job-related outcome. Including stress arousal in the model provided a much more comprehensive understanding of the relation between stressor and outcomes, and the contribution of role ambiguity and role conflict were better explained. By understanding these relations, anticipatory guidance and crisis intervention programs can be designed and implemented to enhance human resilience. These data could serve to improve training programs for these "at risk" professional groups or even the population as a whole.

Defining quality in radiology.

PubMed

Blackmore, C Craig

2007-04-01

The introduction of pay for performance in medicine represents an opportunity for radiologists to define quality in radiology. Radiology quality can be defined on the basis of the production model that currently drives reimbursement, codifying the role of radiologists as being limited to the production of timely and accurate radiology reports produced in conditions of maximum patient safety and communicated in a timely manner. Alternately, quality in radiology can also encompass the professional role of radiologists as diagnostic imaging specialists responsible for the appropriate use, selection, interpretation, and application of imaging. Although potentially challenging to implement, the professional model for radiology quality is a comprehensive assessment of the ways in which radiologists add value to patient care. This essay is a discussion of the definition of radiology quality and the implications of that definition.

46 CFR 38.01-2 - Transportation of portable cylinders or portable tanks containing or having previously contained...

Code of Federal Regulations, 2012 CFR

2012-10-01

..., as defined in 49 CFR 173.50. (ii) Flammable solids. (iii) Oxidizing materials. (iv) Corrosive liquids... containing or having previously contained liquefied flammable gases in dry cargo spaces-TB/ALL. 38.01-2 Section 38.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS LIQUEFIED FLAMMABLE...

46 CFR 38.01-2 - Transportation of portable cylinders or portable tanks containing or having previously contained...

Code of Federal Regulations, 2011 CFR

2011-10-01

..., as defined in 49 CFR 173.50. (ii) Flammable solids. (iii) Oxidizing materials. (iv) Corrosive liquids... containing or having previously contained liquefied flammable gases in dry cargo spaces-TB/ALL. 38.01-2 Section 38.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS LIQUEFIED FLAMMABLE...

46 CFR 38.01-2 - Transportation of portable cylinders or portable tanks containing or having previously contained...

Code of Federal Regulations, 2013 CFR

2013-10-01

..., as defined in 49 CFR 173.50. (ii) Flammable solids. (iii) Oxidizing materials. (iv) Corrosive liquids... containing or having previously contained liquefied flammable gases in dry cargo spaces-TB/ALL. 38.01-2 Section 38.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS LIQUEFIED FLAMMABLE...

46 CFR 38.01-2 - Transportation of portable cylinders or portable tanks containing or having previously contained...

Code of Federal Regulations, 2014 CFR

2014-10-01

..., as defined in 49 CFR 173.50. (ii) Flammable solids. (iii) Oxidizing materials. (iv) Corrosive liquids... containing or having previously contained liquefied flammable gases in dry cargo spaces-TB/ALL. 38.01-2 Section 38.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS LIQUEFIED FLAMMABLE...

Facilitation of Taste Memory Acquisition by Experiencing Previous Novel Taste Is Protein-Synthesis Dependent

ERIC Educational Resources Information Center

Merhav, Maayan; Rosenblum, Kobi

2008-01-01

Very little is known about the biological and molecular mechanisms that determine the effect of previous experience on implicit learning tasks. In the present study, we first defined weak and strong taste inputs according to measurements in the behavioral paradigm known as latent inhibition of conditioned taste aversion. We then demonstrated that…

Managing across levels of government: evaluation of federal-state roles and responsibilities involving nonfederal forests in the United States

Treesearch

Paul V. Ellefson; Calder M. Hibbard; Michael A. Kilgore

2006-01-01

With the assistance of state foresters and federal agency executives, an evaluation was made of federal and state government roles and responsibilities focused nonfederal forests in the United States. The evaluation involved an inventory of legally (and administratively) defined federal roles, identification bf federal programs supporting accomplishment of such roles,...

CCK response in bulimia nervosa and following remission

PubMed Central

Hannon-Engel, Sandra L.; Filin, Evgeniy E.; Wolfe, Barbara E.

2013-01-01

The core defining features of bulimia nervosa (BN) are repeated binge eating episodes and inappropriate compensatory (e.g. purging) behavior. Previous studies suggest an abnormal postprandial response in the satiety-signaling peptide cholecystokinin (CCK) in persons with BN. It is unknown whether this altered response persists following remission or if it may be a potential target for the development of clinical treatment strategies. To examine the nature of this altered response, this study assessed whether CCK normalizes following remission from BN (RBN). This study prospectively evaluated the plasma CCK response and corresponding eating behavior-related ratings (e.g. satiety, fullness, hunger, urge to binge and vomit) in individuals with BN-purging subtype (n=10), RBN-purging subtype (n =14), and healthy controls (CON, n=13) at baseline, +15, +30, and +60 minutes following the ingestion of a standardized liquid test meal. Subject groups did not significantly differ in CCK response to the test meal. A significant relationship between CCK response and satiety ratings was observed in the RBN group (r=.59, p<.05 two-tailed). A new and unanticipated finding in the BN group was a significant relationship between CCK response and ratings of “urge to vomit” (r=.86, p < .01, two-tailed). Unlike previous investigations CCK response did not differ in BN and CON groups. Thus the role of symptom severity remains an area of further investigation. Additionally, findings suggest that in this sample, CCK functioning following remission from BN-purging subtype is not different from controls. It remains unknown whether or not CCK functioning may be a protective or liability factor in the stabilization and recovery process. Replication studies utilizing a larger sample size are needed to further elucidate the role of CCK in recovery from BN and its potential target of related novel treatment strategies. PMID:23988345

Genome-Wide Mutant Fitness Profiling Identifies Nutritional Requirements for Optimal Growth of Yersinia pestis in Deep Tissue

PubMed Central

Palace, Samantha G.; Proulx, Megan K.; Lu, Shan; Baker, Richard E.

2014-01-01

ABSTRACT Rapid growth in deep tissue is essential to the high virulence of Yersinia pestis, causative agent of plague. To better understand the mechanisms underlying this unusual ability, we used transposon mutagenesis and high-throughput sequencing (Tn-seq) to systematically probe the Y. pestis genome for elements contributing to fitness during infection. More than a million independent insertion mutants representing nearly 200,000 unique genotypes were generated in fully virulent Y. pestis. Each mutant in the library was assayed for its ability to proliferate in vitro on rich medium and in mice following intravenous injection. Virtually all genes previously established to contribute to virulence following intravenous infection showed significant fitness defects, with the exception of genes for yersiniabactin biosynthesis, which were masked by strong intercellular complementation effects. We also identified more than 30 genes with roles in nutrient acquisition and metabolism as experiencing strong selection during infection. Many of these genes had not previously been implicated in Y. pestis virulence. We further examined the fitness defects of strains carrying mutations in two such genes—encoding a branched-chain amino acid importer (brnQ) and a glucose importer (ptsG)—both in vivo and in a novel defined synthetic growth medium with nutrient concentrations matching those in serum. Our findings suggest that diverse nutrient limitations in deep tissue play a more important role in controlling bacterial infection than has heretofore been appreciated. Because much is known about Y. pestis pathogenesis, this study also serves as a test case that assesses the ability of Tn-seq to detect virulence genes. PMID:25139902

Analysis of the arabinoxylan arabinofuranohydrolase gene family in barley does not support their involvement in the remodelling of endosperm cell walls during development.

PubMed

Laidlaw, Hunter K C; Lahnstein, Jelle; Burton, Rachel A; Fincher, Geoffrey B; Jobling, Stephen A

2012-05-01

Arabinoxylan arabinofuranohydrolases (AXAHs) are family GH51 enzymes that have been implicated in the removal of arabinofuranosyl residues from the (1,4)-β-xylan backbone of heteroxylans. Five genes encoding barley AXAHs range in size from 4.6 kb to 7.1 kb and each contains 16 introns. The barley HvAXAH genes map to chromosomes 2H, 4H, and 5H. A small cluster of three HvAXAH genes is located on chromosome 4H and there is evidence for gene duplication and the presence of pseudogenes in barley. The cDNAs corresponding to barley and wheat AXAH genes were cloned, and transcript levels of the genes were profiled across a range of tissues at different developmental stages. Two HvAXAH cDNAs that were successfully expressed in Nicotiana benthamiana leaves exhibited similar activities against 4-nitrophenyl α-L-arabinofuranoside, but HvAXAH2 activity was significantly higher against wheat flour arabinoxylan, compared with HvAXAH1. HvAXAH2 also displayed activity against (1,5)-α-L-arabinopentaose and debranched arabinan. Western blotting with an anti-HvAXAH antibody was used to define further the locations of the AXAH enzymes in developing barley grain, where high levels were detected in the outer layers of the grain but little or no protein was detected in the endosperm. The chromosomal locations of the genes do not correspond to any previously identified genomic regions shown to influence heteroxylan structure. The data are therefore consistent with a role for AXAH in depolymerizing arabinoxylans in maternal tissues during grain development, but do not provide compelling evidence for a role in remodelling arabinoxylans during endosperm or coleoptile development in barley as previously proposed.

Enhanced sequential reaction time task performance in a rat model of mesial temporal lobe epilepsy with classic hippocampal sclerosis.

PubMed

Will, Johanna L; Eckart, Moritz T; Rosenow, Felix; Bauer, Sebastian; Oertel, Wolfgang H; Schwarting, Rainer K W; Norwood, Braxton A

2013-06-15

The human serial reaction time task (SRTT) has widely been used to study the neural basis of implicit learning. It is well documented, in both human and animal studies, that striatal dopaminergic processes play a major role in this task. However, findings on the role of the hippocampus - which is mainly associated with declarative memory - in implicit learning and performance are less univocal. We used a SRTT to evaluate implicit learning and performance in rats with perforant pathway stimulation-induced hippocampal neuron loss; a clinically-relevant animal model of mesial temporal lobe epilepsy (MTLS-HS). As has been previously reported for the Sprague-Dawley strain, 8h of continuous stimulation in male Wistar rats reliably induced widespread neuron loss in areas CA3 and CA1 with a characteristic sparing of CA2 and the granule cells. Histological analysis revealed that hippocampal volume was reduced by an average of 44%. Despite this severe hippocampal injury, rats showed superior performance in our instrumental SRTT, namely shorter reaction times, and without a loss in accuracy, especially during the second half of our 16-days testing period. These results demonstrate that a hippocampal lesion can improve performance in a rat SRTT, which is probably due to enhanced instrumental performance. In line with our previous findings based on ibotenic-acid induced hippocampal lesion, these data support the hypothesis that loss or impairment of hippocampal function can enhance specific task performance, especially when it is dependent on procedural (striatum-dependent) mechanisms with minimal spatial requirements. As the animal model used here exhibits the defining characteristics of MTLE-HS, these findings may have implications for the study and management of patients with MTLE. Copyright © 2013 Elsevier B.V. All rights reserved.

Immune complex-induced human monocyte procoagulant activity. I. a rapid unidirectional lymphocyte-instructed pathway.

PubMed

Schwartz, B S; Edgington, T S

1981-09-01

It has previously been described that soluble antigen:antibody complexes in antigen excess can induce an increase in the procoagulant activity of human peripheral blood mononuclear cells. It has been proposed that this response may explain the presence of fibrin in immune complex-mediated tissue lesions. In the present study we define cellular participants and their roles in the procoagulant response to soluble immune complexes. Monocytes were shown by cell fractionation and by a direct cytologic assay to be the cell of origin of the procoagulant activity; and virtually all monocytes were able to participate in the response. Monocytes, however, required the presence of lymphocytes to respond. The procoagulant response required cell cooperation, and this collaborative interaction between lymphocytes and monocytes appeared to be unidirectional. Lymphocytes once triggered by immune complexes induced monocytes to synthesize the procoagulant product. Intact viable lymphocytes were required to present instructions to monocytes; no soluble mediator could be found to subserve this function. Indeed, all that appeared necessary to induce monocytes to produce procoagulant activity was an encounter with lymphocytes that had previously been in contact with soluble immune complexes. The optimum cellular ratio for this interaction was four lymphocytes per monocyte, about half the ratio in peripheral blood. The procoagulant response was rapid, reaching a maximum within 6 h after exposure to antigen:antibody complexes. The procoagulant activity was consistent with tissue factor because Factors VII and X and prothrombin were required for clotting of fibrinogen. WE propose that this pathway differs from a number of others involving cells of the immune system. Elucidation of the pathway may clarify the role of this lymphocyte-instructed monocyte response in the Shwartzman phenomenon and other thrombohemorrhagic events associated with immune cell function and the formation of immune complexes.

Characterization of cucumber fermentation spoilage bacteria by enrichment culture and 16S rDNA cloning.

PubMed

Breidt, Fred; Medina, Eduardo; Wafa, Doria; Pérez-Díaz, Ilenys; Franco, Wendy; Huang, Hsin-Yu; Johanningsmeier, Suzanne D; Kim, Jae Ho

2013-03-01

Commercial cucumber fermentations are typically carried out in 40000 L fermentation tanks. A secondary fermentation can occur after sugars are consumed that results in the formation of acetic, propionic, and butyric acids, concomitantly with the loss of lactic acid and an increase in pH. Spoilage fermentations can result in significant economic loss for industrial producers. The microbiota that result in spoilage remain incompletely defined. Previous studies have implicated yeasts, lactic acid bacteria, enterobacteriaceae, and Clostridia as having a role in spoilage fermentations. We report that Propionibacterium and Pectinatus isolates from cucumber fermentation spoilage converted lactic acid to propionic acid, increasing pH. The analysis of 16S rDNA cloning libraries confirmed and expanded the knowledge gained from previous studies using classical microbiological methods. Our data show that Gram-negative anaerobic bacteria supersede Gram-positive Fermincutes species after the pH rises from around 3.2 to pH 5, and propionic and butyric acids are produced. Characterization of the spoilage microbiota is an important first step in efforts to prevent cucumber fermentation spoilage. An understanding of the microorganisms that cause commercial cucumber fermentation spoilage may aid in developing methods to prevent the spoilage from occurring. © 2013 Institute of Food Technologists®

Segmentation of cortical bone using fast level sets

NASA Astrophysics Data System (ADS)

Chowdhury, Manish; Jörgens, Daniel; Wang, Chunliang; Smedby, Årjan; Moreno, Rodrigo

2017-02-01

Cortical bone plays a big role in the mechanical competence of bone. The analysis of cortical bone requires accurate segmentation methods. Level set methods are usually in the state-of-the-art for segmenting medical images. However, traditional implementations of this method are computationally expensive. This drawback was recently tackled through the so-called coherent propagation extension of the classical algorithm which has decreased computation times dramatically. In this study, we assess the potential of this technique for segmenting cortical bone in interactive time in 3D images acquired through High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The obtained segmentations are used to estimate cortical thickness and cortical porosity of the investigated images. Cortical thickness and Cortical porosity is computed using sphere fitting and mathematical morphological operations respectively. Qualitative comparison between the segmentations of our proposed algorithm and a previously published approach on six images volumes reveals superior smoothness properties of the level set approach. While the proposed method yields similar results to previous approaches in regions where the boundary between trabecular and cortical bone is well defined, it yields more stable segmentations in challenging regions. This results in more stable estimation of parameters of cortical bone. The proposed technique takes few seconds to compute, which makes it suitable for clinical settings.

The Functional Landscape of Hsp27 Reveals New Cellular Processes such as DNA Repair and Alternative Splicing and Proposes Novel Anticancer Targets*

PubMed Central

Katsogiannou, Maria; Andrieu, Claudia; Baylot, Virginie; Baudot, Anaïs; Dusetti, Nelson J.; Gayet, Odile; Finetti, Pascal; Garrido, Carmen; Birnbaum, Daniel; Bertucci, François; Brun, Christine; Rocchi, Palma

2014-01-01

Previously, we identified the stress-induced chaperone, Hsp27, as highly overexpressed in castration-resistant prostate cancer and developed an Hsp27 inhibitor (OGX-427) currently tested in phase I/II clinical trials as a chemosensitizing agent in different cancers. To better understand the Hsp27 poorly-defined cytoprotective functions in cancers and increase the OGX-427 pharmacological safety, we established the Hsp27-protein interaction network using a yeast two-hybrid approach and identified 226 interaction partners. As an example, we showed that targeting Hsp27 interaction with TCTP, a partner protein identified in our screen increases therapy sensitivity, opening a new promising field of research for therapeutic approaches that could decrease or abolish toxicity for normal cells. Results of an in-depth bioinformatics network analysis allying the Hsp27 interaction map into the human interactome underlined the multifunctional character of this protein. We identified interactions of Hsp27 with proteins involved in eight well known functions previously related to Hsp27 and uncovered 17 potential new ones, such as DNA repair and RNA splicing. Validation of Hsp27 involvement in both processes in human prostate cancer cells supports our system biology-predicted functions and provides new insights into Hsp27 roles in cancer cells. PMID:25277244

Ten years of major equestrian injury: are we addressing functional outcomes?

PubMed Central

Ball, Jill E; Ball, Chad G; Mulloy, Robert H; Datta, Indraneel; Kirkpatrick, Andrew W

2009-01-01

Background Horseback riding is considered more dangerous than motorcycle riding, skiing, automobile racing, football and rugby. The integral role of rehabilitation therapy in the recovery of patients who have sustained a major horse-related injury is previously not described. The goals of this paper were to (1) define the incidence and pattern of severe equestrian trauma, (2) identify the current level of in-patient rehabilitation services, (3) describe functional outcomes for patients, and (4) discuss methods for increasing rehabilitation therapy in this unique population. Methods and results A retrospective review of the trauma registry at a level 1 center (1995–2005) was completed in conjunction with a patient survey outlining formal in-hospital therapy. Forty-nine percent of patients underwent in-patient rehabilitation therapy. Injuries predictive of receiving therapy included musculoskeletal and spinal cord trauma. Previous injury while horseback riding was predictive of not receiving therapy. The majority (55%) of respondents had chronic physical difficulties following their accident. Conclusion Rehabilitation therapy is significantly underutilized following severe equestrian trauma. Increased therapy services should target patients with brain, neck and skull injuries. Improvements in the initial provision, and follow-up of rehabilitation therapy could enhance functional outcomes in the treatment resistant Western equestrian population. PMID:19228424

Filling cystoureterography facilitates stone visualization in patients with previously inserted double-J ureteral stents.

PubMed

Kravchick, Sergey George; Shumalinsky, Dmitry; Jeshurun-Koren, Michael; Stepnov, Eugen; Cytron, Shmuel

2005-06-01

In our study, we assessed the ability of a filling cystogram to induce vesicoureteral reflux (VUR) and to evaluate its role in stone targeting during ESWL in the presence of a double-J ureteral stent (JJ-S). Filling cystoureterography was performed during ESWL in 17 patients with previously inserted 4.7 F JJ-S. The examination ended with stone localization. In every procedure, 3,500 shock waves were delivered with an energy range of 18-23 kV. Patients were evaluated 4 weeks after ESWL. A stone-free result was defined as no evidence of calculi in the first or second visits. Because contrast material was employed in this study, we also evaluated its possible interference with the results of lithotripsy. All radiolucent or poorly calcified stones were successfully localized. In four patients, rhythmic suprapubic manual pressure was performed to initiate VUR. Reflux was low grade in 35% and high grade in 65% of renal units. The efficiency quotient reached 59%. In vitro artificial stones were successfully disintegrated both in water and solutions of Ultravist. In the presence of a JJ-S, filling cystography can easily localize radiolucent stones during SWL. No special catheters or stents are required for this technique. Ultravist in particular does not affect the results of ESWL unfavorably.

Different gene-specific mechanisms determine the 'revised-response' memory transcription patterns of a subset of A. thaliana dehydration stress responding genes.

PubMed

Liu, Ning; Ding, Yong; Fromm, Michael; Avramova, Zoya

2014-05-01

Plants that have experienced several exposures to dehydration stress show increased resistance to future exposures by producing faster and/or stronger reactions, while many dehydration stress responding genes in Arabidopsis thaliana super-induce their transcription as a 'memory' from the previous encounter. A previously unknown, rather unusual, memory response pattern is displayed by a subset of the dehydration stress response genes. Despite robustly responding to a first stress, these genes return to their initial, pre-stressed, transcript levels during the watered recovery; surprisingly, they do not respond further to subsequent stresses of similar magnitude and duration. This transcriptional behavior defines the 'revised-response' memory genes. Here, we investigate the molecular mechanisms regulating this transcription memory behavior. Potential roles of abscisic acid (ABA), of transcription factors (TFs) from the ABA signaling pathways (ABF2/3/4 and MYC2), and of histone modifications (H3K4me3 and H3K27me3) as factors in the revised-response transcription memory patterns are elucidated. We identify the TF MYC2 as the critical component for the memory behavior of a specific subset of MYC2-dependent genes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Redefining the modular organization of the core Mediator complex.

PubMed

Wang, Xuejuan; Sun, Qianqian; Ding, Zhenrui; Ji, Jinhua; Wang, Jianye; Kong, Xiao; Yang, Jianghong; Cai, Gang

2014-07-01

The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation.

Redefining the modular organization of the core Mediator complex

PubMed Central

Wang, Xuejuan; Sun, Qianqian; Ding, Zhenrui; Ji, Jinhua; Wang, Jianye; Kong, Xiao; Yang, Jianghong; Cai, Gang

2014-01-01

The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation. PMID:24810298

Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Dong, E-mail: austhudong@126.com; Wu, Jing, E-mail: wujing8008@126.com; Wang, Wan

The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domainmore » and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy.« less

The Rab-binding Profiles of Bacterial Virulence Factors during Infection.

PubMed

So, Ernest C; Schroeder, Gunnar N; Carson, Danielle; Mattheis, Corinna; Mousnier, Aurélie; Broncel, Malgorzata; Tate, Edward W; Frankel, Gad

2016-03-11

Legionella pneumophila, the causative agent of Legionnaire's disease, uses its type IV secretion system to translocate over 300 effector proteins into host cells. These effectors subvert host cell signaling pathways to ensure bacterial proliferation. Despite their importance for pathogenesis, the roles of most of the effectors are yet to be characterized. Key to understanding the function of effectors is the identification of host proteins they bind during infection. We previously developed a novel tandem-affinity purification (TAP) approach using hexahistidine and BirA-specific biotinylation tags for isolating translocated effector complexes from infected cells whose composition were subsequently deciphered by mass spectrometry. Here we further advanced the workflow for the TAP approach and determined the infection-dependent interactomes of the effectors SidM and LidA, which were previously reported to promiscuously bind multiple Rab GTPases in vitro. In this study we defined a stringent subset of Rab GTPases targeted by SidM and LidA during infection, comprising of Rab1A, 1B, 6, and 10; in addition, LidA targets Rab14 and 18. Taken together, this study illustrates the power of this approach to profile the intracellular interactomes of bacterial effectors during infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Evolution of Genome Size and Complexity in Pinus

PubMed Central

Morse, Alison M.; Peterson, Daniel G.; Islam-Faridi, M. Nurul; Smith, Katherine E.; Magbanua, Zenaida; Garcia, Saul A.; Kubisiak, Thomas L.; Amerson, Henry V.; Carlson, John E.; Nelson, C. Dana; Davis, John M.

2009-01-01

Background Genome evolution in the gymnosperm lineage of seed plants has given rise to many of the most complex and largest plant genomes, however the elements involved are poorly understood. Methodology/Principal Findings Gymny is a previously undescribed retrotransposon family in Pinus that is related to Athila elements in Arabidopsis. Gymny elements are dispersed throughout the modern Pinus genome and occupy a physical space at least the size of the Arabidopsis thaliana genome. In contrast to previously described retroelements in Pinus, the Gymny family was amplified or introduced after the divergence of pine and spruce (Picea). If retrotransposon expansions are responsible for genome size differences within the Pinaceae, as they are in angiosperms, then they have yet to be identified. In contrast, molecular divergence of Gymny retrotransposons together with other families of retrotransposons can account for the large genome complexity of pines along with protein-coding genic DNA, as revealed by massively parallel DNA sequence analysis of Cot fractionated genomic DNA. Conclusions/Significance Most of the enormous genome complexity of pines can be explained by divergence of retrotransposons, however the elements responsible for genome size variation are yet to be identified. Genomic resources for Pinus including those reported here should assist in further defining whether and how the roles of retrotransposons differ in the evolution of angiosperm and gymnosperm genomes. PMID:19194510

Employer involvement in defined contribution investment education.

PubMed

Blau, G; VanDerhei, J L

2000-01-01

In this paper the authors consider the personnel problems that may arise for defined contribution plan sponsors if major market corrections cause older employees to delay retirement beyond previous expectations. We move from that basic premise to argue that, given the continued evolution from defined benefit (DB) to defined contribution (DC) retirement plans, employers need to be more "proactive" in educating their employees about their retirement planning. A human resources perspective is used to support this argument, apart from and in addition to legal considerations such as ERISA Section 404(c). Specifics of employer involvement and its place as a component of an organization's culture are discussed. Finally, recommendations are given for employers to consider.

Understanding Gender Roles in Teen Pregnancy Prevention among American Indian Youth

PubMed Central

Hanson, Jessica D.; McMahon, Tracey R.; Griese, Emily R.; Kenyon, DenYelle Baete

2014-01-01

Objectives To examine the impact of gender norms on American Indian (AI) adolescents' sexual health behavior. Methods The project collected qualitative data at a reservation site and an urban site through 24 focus groups and 20 key informant interviews. Results The reasons that AI youth choose to abstain or engage in sexual intercourse and utilize contraception vary based on gender ideologies defined by the adolescent's environment. These include social expectations from family and peers, defined roles within relationships, and gender empowerment gaps. Conclusions Gender ideology plays a large role in decisions about contraception and sexual activity for AI adolescents, and it is vital to include re-definitions of gender norms within AI teen pregnancy prevention program. PMID:25207506

The shape parameter and its modification for defining coastal profiles

NASA Astrophysics Data System (ADS)

Türker, Umut; Kabdaşli, M. Sedat

2009-03-01

The shape parameter is important for the theoretical description of the sandy coastal profiles. This parameter has previously been defined as a function of the sediment-settling velocity. However, the settling velocity cannot be characterized over a wide range of sediment grains. This, in turn, limits the calculation of the shape parameter over a wide range. This paper provides a simpler and faster analytical equation to describe the shape parameter. The validity of the equation has been tested and compared with the previously estimated values given in both graphical and tabular forms. The results of this study indicate that the analytical solutions of the shape parameter improved the usability of profile better than graphical solutions, predicting better results both at the surf zone and offshore.

Community-acquired Pseudomonas aeruginosa urinary tract infections in children hospitalized in a tertiary center: relative frequency, risk factors, antimicrobial resistance and treatment.

PubMed

Marcus, N; Ashkenazi, S; Samra, Z; Cohen, A; Livni, G

2008-10-01

The practice of antibiotic prophylaxis against recurrent urinary tract infection (UTI), with hospitalization reserved for severe or complicated cases, has led to changes in the nature and culprit uropathogens of community-acquired (CA), hospital-treated UTI. Characterization of subgroups that need special considerations is crucial. To elucidate the trends and characteristics of CA Pseudomonas UTI in hospitalized children; define the antibiotic susceptibility; determine the appropriateness of the empiric antibiotics used; compare to other causes of UTI in this population; and thereby define predictors for Pseudomonas UTI. A prospective clinical and laboratory study from 2001 through 2005. Children with P. aeruginosa UTI were characterized and compared with non-Pseudomonas UTI. Of 351 episodes of culture-proven CA UTI, 28 (8%) were caused by Pseudomonas, representing a 2.8-fold increase from our previous study. Pseudomonas UTI was more common in children > 5 years (p < 0.01), with urinary abnormalities (p < 0.01) and with previous antibiotic use in the previous month (p < 0.001). Pseudomonas UTI was often resistant to antibiotics usually recommended for empiric therapy; 25% was initially treated with inappropriate IV antibiotics (4.6% in the non-Pseudomonas group, p < 0.001) with 1.3 days longer IV antibiotics. On multivariate analysis, risk factors for Pseudomonas UTI were previous antibiotic therapy and underlying urinary pathology. Pseudomonas UTI seems to increase in CA, hospital-treated children and is often treated inappropriately according to current treatment protocols. Awareness of this trend and knowledge of the defined risk factors of Pseudomonas UTI might improve the empiric antibiotic therapy.

Defining quantitative stream disturbance gradients and the additive role of habitat variation to explain macroinvertebrate taxa richness

EPA Science Inventory

Most studies dealing with the use of ecological indicators and other applied ecological research relies on some definition or concept of what constitutes least-, intermediate- and most-disturbed condition. Currently, most rigorous methodologies designed to define those conditions...

Introduction and historical perspective.

PubMed

Gunning, Peter

2008-01-01

Tropomyosin is a coiled coil dimer which forms a polymer along the major groove of the majority of actin filaments. It is therefore one of the two primary components of the actin filament. Our understanding of the biological function of tropomyosin has been driven almost entirely by its role in striated muscle. This reflects both its original discovery as part of the thin filament in skeletal muscle and its pivotal role in regulating muscle contraction. In contrast, its role in the function of the cytoskeleton of all cells has been poorly understood due, at least in part, to the technical challenge of deciphering the function of a large number of isoforms. This book has brought together many of the leading researchers who have defined the function of tropomyosin in both normal and pathological conditions. Each author brings their own perspective in a series of stand alone reviews of the areas of tropomyosin research they have played a major role in defining.

Ethics in psychiatry and psychoanalysis.

PubMed

Lothane, Z

1999-01-01

Ethics plays a dual role in psychiatry. The extrinsic role is in defining the rules of ethical conduct for the psychiatrist as a professional dealing with patients, peers and society at large. The intrinsic role is in defining ethical or moral conflict as a determining component in the construction of symptoms of mental disorder. Ethical considerations play a role in the truthful description of the disorder, diagnosis, dynamic formulation and the doctor-patient relationship in treatment. In treatment, there is a need to acknowledge 2 dimensions of psychological conflict: (1) an appraisal of the actual realistic moral conflicts due to symptomatic unethical conduct that goes against one's normative conscience, and (2) resolution of past conflicts arising from unconscious or repressed aspects of the neurotic conscience or superego, i.e. a holdover of unreflected obedience to parental authority. The resolution of past and ongoing conflicts promotes growth toward autonomy of moral judgment, free choice and moral responsibility.

Rural Hispanic Counselor and Student Perspectives and Their Roles in Providing Improved Secondary Guidance Counseling

ERIC Educational Resources Information Center

Friesenhahn-Soliz, Grace; Bain, Steve; Maxwell, Gerri

2015-01-01

School counselors can serve as agents of change in our nation's schools, particularly for marginalized students whose voices are frequently not heard. Historically, the role of the school counselor has been under-utilized and inaccurately defined. Research available on counselor role definition has been primarily quantitative. Research on…

Strategic planning--the role of the chief executive.

PubMed

Daniel, A L

1992-04-01

Failure to see strategic planning as a process and ineffective CEO involvement are two reasons for failures in strategic planning. This article outlines the stages in an effective strategic planning process, discusses the appropriate role or roles for the CEO or leader in each stage, and defines the expected results from effective strategic planning.

What Students Need: Exploring Teachers' Views via Imagined Role-Playing

ERIC Educational Resources Information Center

Zazkis, Rina; Nejad, Masomeh Jamshid

2014-01-01

Role-playing is an unscripted dramatic technique that encourages participants to improvise behaviors that illustrate expected actions of persons involved in defined situations. However, among various uses in developing professionals, the use of role-playing in teacher education is rather rare. To give all students the opportunity to participate in…

Reaffirming the Role of Faculty in Academic Advising. Monograph Series, No. 1.

ERIC Educational Resources Information Center

Kramer, Gary L., Ed.

The six papers of this monograph discuss the role of faculty in campus academic advising programs in discussions of training, accountability, evaluation, and recognition and reward. The first paper, "Redefining Faculty Roles for Academic Advising" (Gary L. Kramer) defines three attributes of successful advising programs: as an integral component…

Civic Engagement as a Retirement Role for Aging Americans

ERIC Educational Resources Information Center

Kaskie, Brian; Imhof, Sara; Cavanaugh, Joseph; Culp, Kennith

2008-01-01

Purpose: Public attention directed toward the civic engagement of retired Americans has increased considerably. The purpose of this research was to define civic engagement as a retirement role and differentiate individuals who met this role definition from other retirees. Design and Methods: Retirees who met our definition of civic engagement were…

The Evolving Identity of School Counselors as Defined by the Stakeholders

ERIC Educational Resources Information Center

Perkins, Gerra; Oescher, Jeffrey; Ballard, Mary B.

2010-01-01

To better understand the evolving identity of school counselors, this article examines the value stakeholders place on the roles of elementary school counselors. The School Counselor Role Survey (SCRS) was administered to assess stakeholders' perceptions of the importance of the school counselor roles advocated by The Education Trust and the…

The Importance of Being Human: Instructors' Personal Presence in Distance Programs

ERIC Educational Resources Information Center

Reupert, Andrea; Maybery, Darryl; Patrick, Kent; Chittleborough, Philip

2009-01-01

Literature on the role of higher education distance instructors mostly focuses on their teaching role, involving tasks such as curriculum design, instruction, and facilitating student learning. What is missing is the role of the "person" of the instructor, defined as his or her personality, identity, integrity, emotions, thoughts, beliefs, and…

Roles and Structures for Participation in Higher Education Governance: A Rationale.

ERIC Educational Resources Information Center

Ikenberry, Stanley O.

It is obvious that the roles for participation of faculty, students and administrators in campus governance are inadequately defined and that the organizational structure through which these roles might be performed is deficient. This paper considers the rationale for such faculty and student organizations and examines some issues that have to be…

Ethnic Variations in Family Power Relations: Part I--Jewish American Families.

ERIC Educational Resources Information Center

Victor, Jeffrey S.

Roles in the Jewish-American family system tend to be flexible, without a clearly defined division of labor or hierarchy of authority. Husband-father and wife-mother roles tend to be somewhat interchangeable and androgynous. Because role expectations constantly change to fit changing circumstances, ambiguity in each member's perception of…

The Microcosm within: An interview with William B. Miller, Jr., on the Extended Hologenome theory of evolution.

PubMed

Hunt, Tam

2015-01-01

There is a singular unifying reality underlying every biologic interaction on our planet. In immunology, that which does not kill you makes you different. -William B. Miller, Jr. We are experiencing a revolution in our understanding of inner space on a par with our exponentially increasing understanding of outer space. In biology, we are learning that the genetic and epigenetic complexity within organisms is far deeper than suspected. This is a key theme in William B. Miller Jr.'s book, The Microcosm Within: Evolution and Extinction in the Hologenome. We are learning also that a focus on the human genome alone is misleading when it comes to who we really are as biological entities, and in terms of how we and other creatures have evolved. Rather than being defined by the human genome alone, we are instead defined by the "hologenome," the sum of the human genome and the far larger genetic endowment of the microbiome and symbiotic communities that reside within and around us. Miller is a medical doctor previously in private practice in Pennsylvania and Phoenix, Arizona. This book is his first foray into evolutionary theory. His book could have been titled "The Origin of Variation" because this is his primary focus. He accepts that natural selection plays a role in evolution, but he demotes this mechanism to a less important role than the Modern Synthesis suggests. His main gripe, however, concerns random variation. He argues that random variation is unable to explain the origin and evolution of biological forms that we see in the world around us and in the historical record. Miller suggests that, rather than random variation as the engine of novelty, there is a creative impulse at the heart of cellular life, and even at the level of the genetic aggregate, that generates novelty on a regular basis. I probe this assertion in the interview below. He also highlights the strong role of "exogenous genetic assault" in variation and in his immunological model of evolution.

Developing a modern standard to define and assess professionalism in trainees.

PubMed

Schwartz, Ann C; Kotwicki, Raymond J; McDonald, William M

2009-01-01

Assessing professionalism in medical education poses many challenges. The authors discuss common themes and principles in managing professionalism in medical education. The authors review the development of standards of professionalism in medical education. They define educational goals for professionalism and also discuss the practical problems with assessing professionalism and addressing it with the trainees. Strategies for remediation of unprofessional conduct are outlined. Given the importance of role models in the development of professional behavior, maintaining an environment that fosters professionalism is an implicit feature of teaching professionalism. Professionalism should be a part of the objectives for each course and clinical rotation, using clearly defined goals and objectives. Assessment of professionalism should begin early and be conducted frequently, giving trainees the opportunity to change. A formal mentoring system can be an effective mechanism to develop role models and teach professionalism. Teaching professionalism through formal curricula is paramount in helping develop new generations of compassionate and responsible physicians. Additional strategies such as consistent role modeling of professional behaviors are also needed to encourage the development of professional physicians.

Scientific misconduct and research integrity for the bench scientist.

PubMed

Pascal, C B

2000-09-01

This paper describes the role of the Office of Research Integrity (ORI), a component of the Public Health Service (PHS), in defining scientific misconduct in research supported with PHS funds and in establishing standards for responding to allegations of misconduct. The principal methods by which ORI exercises its responsibilities in this area are defining what types of behaviors undertaken by research investigators constitute misconduct, overseeing institutional efforts to investigate and report misconduct, and recommending to the Assistant Secretary for Health (ASH) PHS administrative actions when misconduct is identified. ORI also takes affirmative steps to promote research integrity through education, training, and other initiatives. The role of the research institution in responding to misconduct and promoting research integrity is complementary and overlapping with ORI's efforts but, as the employer of research investigators and front-line manager of the research, the institution has a greater opportunity to promote the highest standards of integrity in the day-to-day conduct of research. Finally, legal precedent established through civil litigation has played an important role in defining the standards that apply in determining when a breach of research integrity has occurred.

Mentoring Nurse Practitioners in a Hospital Setting.

PubMed

Pop, Rodica S

2017-08-01

Nursing philosophy is the foundation of nurse practitioner (NP) training. However, NP practice is based on the medical care model. Thus, the necessity of mediating between these two approaches is often problematic for new NPs who are transitioning into their new roles. Mentoring has been used successfully to facilitate role transition and role understanding for nurses, NPs, and physicians. However, mentoring has been rarely studied in NPs. The purpose of this study was to develop a theory of mentoring for new NPs in a hospital setting. Grounded theory methodology was used. The sampling approach was initially purposive and was then shifted to theoretical to ensure the collection of meaningful data. Semistructuredinterviews were recorded and transcribed into Word documents for analysis. The three-phase analysis developed by Corbin and Strauss was initiated after the second interview. Sixteen participants (eight mentors and eight mentees) were interviewed between February and June 2011. The core category that emerged from the data was "defining self," and the main categories were forming the relationship, developing the relationship, and mentoring outcomes. A well-designed formal mentoring program may greatly improve the transition of NPs into a new role. The theory generated by the data from these study participants provides clearly defined categories that may be operationally defined and utilized to develop evaluation tools for mentoring programs.

Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association.

PubMed

Gorelick, Philip B; Furie, Karen L; Iadecola, Costantino; Smith, Eric E; Waddy, Salina P; Lloyd-Jones, Donald M; Bae, Hee-Joon; Bauman, Mary Ann; Dichgans, Martin; Duncan, Pamela W; Girgus, Meighan; Howard, Virginia J; Lazar, Ronald M; Seshadri, Sudha; Testai, Fernando D; van Gaal, Stephen; Yaffe, Kristine; Wasiak, Hank; Zerna, Charlotte

2017-10-01

Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA's Life's Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index <25 kg/m 2 ) and 3 ideal health factors (untreated blood pressure <120/<80 mm Hg, untreated total cholesterol <200 mg/dL, and fasting blood glucose <100 mg/dL). In addition, in relation to maintenance of cognitive health, we recommend following previously published guidance from the AHA/American Stroke Association, Institute of Medicine, and Alzheimer's Association that incorporates control of cardiovascular risks and suggest social engagement and other related strategies. We define optimal brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA's Life's Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA's Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health promotion and disease prevention. © 2017 American Heart Association, Inc.

Defining Optimal Brain Health in Adults

PubMed Central

Gorelick, Philip B.; Furie, Karen L.; Iadecola, Costantino; Smith, Eric E.; Waddy, Salina P.; Lloyd-Jones, Donald M.; Bae, Hee-Joon; Bauman, Mary Ann; Dichgans, Martin; Duncan, Pamela W.; Girgus, Meighan; Howard, Virginia J.; Lazar, Ronald M.; Seshadri, Sudha; Testai, Fernando D.; van Gaal, Stephen; Yaffe, Kristine; Wasiak, Hank; Zerna, Charlotte

2017-01-01

Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA’s Life’s Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index <25 kg/m2) and 3 ideal health factors (untreated blood pressure <120/<80 mm Hg, untreated total cholesterol <200 mg/dL, and fasting blood glucose <100 mg/dL). In addition, in relation to maintenance of cognitive health, we recommend following previously published guidance from the AHA/American Stroke Association, Institute of Medicine, and Alzheimer’s Association that incorporates control of cardiovascular risks and suggest social engagement and other related strategies. We define optimal brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA’s Life’s Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA’s Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health promotion and disease prevention. PMID:28883125

A Father's Role in His Child's Development. Unit for Child Studies. Selected Papers Number 20.

ERIC Educational Resources Information Center

Patterson, Ross

By considering three historical stages of the father's role in the development of his child (father of the past, present, and future), one may perceive a pattern. The father of the past had a clearly defined role; however, this role did not take into account the emotional well-being of family members. Consequently, all in the family lost out,…

Clarifying the role of the mental health peer specialist in Massachusetts, USA: insights from peer specialists, supervisors and clients.

PubMed

Cabral, Linda; Strother, Heather; Muhr, Kathy; Sefton, Laura; Savageau, Judith

2014-01-01

Mental health peer specialists develop peer-to-peer relationships of trust with clients to improve their health and well-being, functioning in ways similar to community health workers. Although the number of peer specialists in use has been increasing, their role in care teams is less defined than that of the community health worker. This qualitative study explored how the peer specialist role is defined across different stakeholder groups, the expectations for this role and how the peer specialist is utilised and integrated across different types of mental health services. Data were collected through interviews and focus groups conducted in Massachusetts with peer specialists (N = 44), their supervisors (N = 14) and clients (N = 10) between September 2009 and January 2011. A consensus coding approach was used and all data outputs were reviewed by the entire team to identify themes. Peer specialists reported that their most important role is to develop relationships with clients and that having lived mental health experience is a key element in creating that bond. They also indicated that educating staff about the recovery model and peer role is another important function. However, they often felt a lack of clarity about their role within their organisation and care team. Supervisors valued the unique experience that peer specialists bring to an organisation. However, without a defined set of expectations for this role, they struggled with training, guiding and evaluating their peer specialist staff. Clients reported that the shared lived experience is important for the relationship and that working with a peer specialist has improved their mental health. With increasing support for person-centred integrated healthcare delivery models, the demand for mental health peer specialist services will probably increase. Therefore, clearer role definition, as well as workforce development focused on team orientation, is necessary for peer specialists to be fully integrated and supported in care teams. © 2013 John Wiley & Sons Ltd.

Self-Control and Impulsiveness in Nondieting Adult Human Females: Effects of Visual Food Cues and Food Deprivation

ERIC Educational Resources Information Center

Forzano, Lori-Ann B.; Chelonis, John J.; Casey, Caitlin; Forward, Marion; Stachowiak, Jacqueline A.; Wood, Jennifer

2010-01-01

Self-control can be defined as the choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer, and impulsiveness as the opposite. Previous research suggests that exposure to visual food cues affects adult humans' self-control. Previous research also suggests that food deprivation decreases adult humans' self-control. The…

20 CFR 1002.264 - Is the employee allowed to repay a previous distribution from a pension benefits plan upon being...

Code of Federal Regulations, 2010 CFR

2010-04-01

... distribution from a pension benefits plan upon being reemployed? 1002.264 Section 1002.264 Employees' Benefits... and Benefits Pension Plan Benefits § 1002.264 Is the employee allowed to repay a previous distribution from a pension benefits plan upon being reemployed? Yes, provided the plan is a defined benefit plan...

Identification of novel protein domains required for the expression of an active dehydratase fragment from a polyunsaturated fatty acid synthase.

PubMed

Oyola-Robles, Delise; Gay, Darren C; Trujillo, Uldaeliz; Sánchez-Parés, John M; Bermúdez, Mei-Ling; Rivera-Díaz, Mónica; Carballeira, Néstor M; Baerga-Ortiz, Abel

2013-07-01

Polyunsaturated fatty acids (PUFAs) are made in some strains of deep-sea bacteria by multidomain proteins that catalyze condensation, ketoreduction, dehydration, and enoyl-reduction. In this work, we have used the Udwary-Merski Algorithm sequence analysis tool to define the boundaries that enclose the dehydratase (DH) domains in a PUFA multienzyme. Sequence analysis revealed the presence of four areas of high structure in a region that was previously thought to contain only two DH domains as defined by FabA-homology. The expression of the protein fragment containing all four protein domains resulted in an active enzyme, while shorter protein fragments were not soluble. The tetradomain fragment was capable of catalyzing the conversion of crotonyl-CoA to β-hydroxybutyryl-CoA efficiently, as shown by UV absorbance change as well as by chromatographic retention of reaction products. Sequence alignments showed that the two novel domains contain as much sequence conservation as the FabA-homology domains, suggesting that they too may play a functional role in the overall reaction. Structure predictions revealed that all domains belong to the hotdog protein family: two of them contain the active site His70 residue present in FabA-like DHs, while the remaining two do not. Replacing the active site His residues in both FabA domains for Ala abolished the activity of the tetradomain fragment, indicating that the DH activity is contained within the FabA-homology regions. Taken together, these results provide a first glimpse into a rare arrangement of DH domains which constitute a defining feature of the PUFA synthases. Copyright © 2013 The Protein Society.

A global solution to the Schrödinger equation: From Henstock to Feynman

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nathanson, Ekaterina S., E-mail: enathanson@ggc.edu; Jørgensen, Palle E. T., E-mail: palle-jorgensen@uiowa.edu

2015-09-15

One of the key elements of Feynman’s formulation of non-relativistic quantum mechanics is a so-called Feynman path integral. It plays an important role in the theory, but it appears as a postulate based on intuition, rather than a well-defined object. All previous attempts to supply Feynman’s theory with rigorous mathematics underpinning, based on the physical requirements, have not been satisfactory. The difficulty comes from the need to define a measure on the infinite dimensional space of paths and to create an integral that would possess all of the properties requested by Feynman. In the present paper, we consider a newmore » approach to defining the Feynman path integral, based on the theory developed by Muldowney [A Modern Theory of Random Variable: With Applications in Stochastic Calcolus, Financial Mathematics, and Feynman Integration (John Wiley & Sons, Inc., New Jersey, 2012)]. Muldowney uses the Henstock integration technique and deals with non-absolute integrability of the Fresnel integrals, in order to obtain a representation of the Feynman path integral as a functional. This approach offers a mathematically rigorous definition supporting Feynman’s intuitive derivations. But in his work, Muldowney gives only local in space-time solutions. A physical solution to the non-relativistic Schrödinger equation must be global, and it must be given in the form of a unitary one-parameter group in L{sup 2}(ℝ{sup n}). The purpose of this paper is to show that a system of one-dimensional local Muldowney’s solutions may be extended to yield a global solution. Moreover, the global extension can be represented by a unitary one-parameter group acting in L{sup 2}(ℝ{sup n})« less

Use of a dynamic in vitro attachment and invasion system (DIVAS) to determine influence of growth rate on invasion of respiratory epithelial cells by group B Streptococcus.

PubMed

Malin, G; Paoletti, L C

2001-11-06

Expression of capsular polysaccharide (CPS) and some surface proteins by group B Streptococcus (GBS) is regulated by growth rate. We hypothesized that precise control of GBS growth, and thus surface-expressed components, could modulate the ability of GBS to invade eukaryotic cells. To test this hypothesis, a dynamic in vitro attachment and invasion system (DIVAS) was developed that combines the advantages of bacterial growth in continuous culture with tissue culture. Tissue culture flasks were modified with inlet and outlet ports to permit perfusion of GBS. Encapsulated type III GBS strains M781 and COH1 and strains COH1-11 and COH1-13 (transposon mutants of COH1 that express an asialo CPS or are acapsular, respectively) were grown in continuous culture in a chemically defined medium at fast mass doubling time (t(d) = 1.8 h) and slow (t(d) = 11 h) growth rates, conditions previously shown to induce and repress, respectively, type III CPS expression. Encapsulated GBS strains invaded A549 respiratory epithelial cells 20- to 700-fold better at the fast than at the slow growth rate, suggesting a role for CPS. However, unencapsulated GBS were also invasive but only when cultured at the fast growth rate, which indicates that GBS invasion is independent of CPS expression and can be regulated by growth rate. Growth rate-dependent invasion occurred when GBS was grown in continuous culture under glucose-defined, thiamine-defined, and undefined nutrient limitations. These results suggest a growth rate-dependent regulation of GBS pathogenesis and demonstrate the usefulness of DIVAS as a tool in studies of host-microbe interactions.

Naturally Occurring Structural Isomers in Serum IgA1 O-Glycosylation

PubMed Central

Takahashi, Kazuo; Smith, Archer D.; Poulsen, Knud; Kilian, Mogens; Julian, Bruce A.; Mestecky, Jiri; Novak, Jan; Renfrow, Matthew B.

2013-01-01

IgA is the most abundantly produced antibody and plays an important role in the mucosal immune system. Human IgA is represented by two isotypes, IgA1 and IgA2. The major structural difference between these two subclasses is the presence of nine potential sites of O-glycosylation in the hinge region between the first and second constant region domains of the heavy chain. Thr225, Thr228, Ser230, Ser232 and Thr236 have been identified as the predominant sites of O-glycan attachment. The range and distribution of O-glycan chains at each site within the context of adjacent sites in this clustered region create a complex heterogeneity of surface epitopes that is incompletely defined. We previously described the analysis of IgA1 O-glycan heterogeneity by use of high resolution LC/MS and electron capture dissociation tandem MS to unambiguously localize all amino acid attachment sites in IgA1 (Ale) myeloma protein. Here, we report the identification and elucidation of IgA1 O-glycopeptide structural isomers that occur based on amino acid position of the attached glycans (positional isomers) and the structure of the O-glycan chains at individual sites (glycan isomers). These isomers are present in a model IgA1 (Mce1) myeloma protein and occur naturally in normal human serum IgA1. Variable O-glycan chains attached to Ser230, Thr233 or Thr236 produce the predominant positional isomers, including O-glycans composed of a single GalNAc residue. These findings represent the first definitive identification of structural isomeric IgA1 O-glycoforms, define the single-site heterogeneity for all O-glycan sites in a single sample, and have implications for defining epitopes based on clustered O-glycan variability. PMID:22067045

Investigation of Crohn’s Disease Risk Loci in Ulcerative Colitis Further Defines Their Molecular Relationship

PubMed Central

ANDERSON, CARL A.; MASSEY, DUNECAN C. O.; BARRETT, JEFFREY C.; PRESCOTT, NATALIE J.; TREMELLING, MARK; FISHER, SHEILA A.; GWILLIAM, RHIAN; JACOB, JEMIMA; NIMMO, ELAINE R.; DRUMMOND, HAZEL; LEES, CHARLIE W.; ONNIE, CLIVE M.; HANSON, CATHERINE; BLASZCZYK, KATARZYNA; RAVINDRARAJAH, RADHI; HUNT, SARAH; VARMA, DHIRAJ; HAMMOND, NAOMI; LEWIS, GREGORY; ATTLESEY, HEATHER; WATKINS, NICK; OUWEHAND, WILLEM; STRACHAN, DAVID; MCARDLE, WENDY; LEWIS, CATHRYN M.; LOBO, ALAN; SANDERSON, JEREMY; JEWELL, DEREK P.; DELOUKAS, PANOS; MANSFIELD, JOHN C.; MATHEW, CHRISTOPHER G.; SATSANGI, JACK; PARKES, MILES

2009-01-01

Background & Aims Identifying shared and disease-specific susceptibility loci for Crohn’s disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD. Methods We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls. Results Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 × 10-8; odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD. Conclusions Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis. PMID:19068216

Identification of novel protein domains required for the expression of an active dehydratase fragment from a polyunsaturated fatty acid synthase

PubMed Central

Oyola-Robles, Delise; Gay, Darren C; Trujillo, Uldaeliz; Sánchez-Parés, John M; Bermúdez, Mei-Ling; Rivera-Díaz, Mónica; Carballeira, Néstor M; Baerga-Ortiz, Abel

2013-01-01

Polyunsaturated fatty acids (PUFAs) are made in some strains of deep-sea bacteria by multidomain proteins that catalyze condensation, ketoreduction, dehydration, and enoyl-reduction. In this work, we have used the Udwary-Merski Algorithm sequence analysis tool to define the boundaries that enclose the dehydratase (DH) domains in a PUFA multienzyme. Sequence analysis revealed the presence of four areas of high structure in a region that was previously thought to contain only two DH domains as defined by FabA-homology. The expression of the protein fragment containing all four protein domains resulted in an active enzyme, while shorter protein fragments were not soluble. The tetradomain fragment was capable of catalyzing the conversion of crotonyl-CoA to β-hydroxybutyryl-CoA efficiently, as shown by UV absorbance change as well as by chromatographic retention of reaction products. Sequence alignments showed that the two novel domains contain as much sequence conservation as the FabA-homology domains, suggesting that they too may play a functional role in the overall reaction. Structure predictions revealed that all domains belong to the hotdog protein family: two of them contain the active site His70 residue present in FabA-like DHs, while the remaining two do not. Replacing the active site His residues in both FabA domains for Ala abolished the activity of the tetradomain fragment, indicating that the DH activity is contained within the FabA-homology regions. Taken together, these results provide a first glimpse into a rare arrangement of DH domains which constitute a defining feature of the PUFA synthases. PMID:23696301

Self-Concept: An Operational Model for Educators.

ERIC Educational Resources Information Center

Obiakor, Festus

This document begins by discussing the important role self-concept plays in a student's academic achievement, social adjustment, and physical capability. A perceptual notion of self-concept is defined as awareness through senses. An operational notion of self-concept is defined as self-descriptive behaviors. Literature is reviewed which defines…

UV RADIATION EFFECTS ON MICROBES AND MICROBIAL PROCESSES

EPA Science Inventory

The ultraviolet (UV) region of solar radiation is defined as wavelengths in the range of 200 to 400 nm. In contrast to visible radiation (400 - 800 nm), which has a well-defined role as the energy source for most of the Earth's primary production, the effects of UV radiation on b...

Myth #10: Business Can Define Workplace Literacy.

ERIC Educational Resources Information Center

Literacy Beat, 1989

1989-01-01

Representatives of the business community define workplace literacy according to how well informed are the spokespersons for business, how expansive is their view of the role of literacy, and the extent to which literacy bears on their firms' productivity. These elements affect business people's understanding of what constitutes workplace…

Plurilingual Ethos: A Peep into the Sociology of Language.

ERIC Educational Resources Information Center

Khubchandani, Lachman M.

1998-01-01

Issues in the study of bilingualism and multilingualism in India and Pakistan are examined, including the delineation of linguistic boundaries, defining a society that is multicultural and yet has developed a "communication ethos" based on a core of common experience, the difficulty in interpreting language role and defining language…

Design of a Course on the Medical Consequences of Nuclear War.

ERIC Educational Resources Information Center

Cassel, Christine; And Others

1982-01-01

A course is described in which students were to: learn about nuclear weapons and their medical, social, and ecological consequences; identify principles of social ethics defining health professionals' roles; and define professional activities consistent with these principles. Student attitudes toward the course and its content were measured. (MSE)

Proposing an Operational Definition of Science Teacher Beliefs

ERIC Educational Resources Information Center

Hutner, Todd L.; Markman, Arthur B.

2016-01-01

Much research has shown that a science teacher's beliefs are related to their teaching practice. This line of research has often defined "belief" epistemologically. That is, beliefs are often defined relative to other mental constructs, such as knowledge, dispositions, or attitudes. Left unspecified is the role beliefs play in cognition…

History of Medford School District Library Media Centers.

ERIC Educational Resources Information Center

Wisely, Steve

2002-01-01

Describes the development of library media centers, programs, and staff at the Medford School District (Oregon). Information from the standards and research used to define roles and responsibilities is summarized, and relevant Oregon state educational organizations are listed. Some of the results of the district's well-defined library programs and…

Defining the Terms of Go-between Process.

ERIC Educational Resources Information Center

Bambrick, Andrew F.

1980-01-01

Defines terms and operations of Zuk's Go-between Process, in which the therapist manages roles of go-between, side-taker, or celebrant in family therapy interviews. This technique is contrasted with Structural-Strategic Family Therapy in which supervisors phone instructions to trainees while observing through a one-way mirror. (JAC)

The music of your emotions: neural substrates involved in detection of emotional correspondence between auditory and visual music actions.

PubMed

Petrini, Karin; Crabbe, Frances; Sheridan, Carol; Pollick, Frank E

2011-04-29

In humans, emotions from music serve important communicative roles. Despite a growing interest in the neural basis of music perception, action and emotion, the majority of previous studies in this area have focused on the auditory aspects of music performances. Here we investigate how the brain processes the emotions elicited by audiovisual music performances. We used event-related functional magnetic resonance imaging, and in Experiment 1 we defined the areas responding to audiovisual (musician's movements with music), visual (musician's movements only), and auditory emotional (music only) displays. Subsequently a region of interest analysis was performed to examine if any of the areas detected in Experiment 1 showed greater activation for emotionally mismatching performances (combining the musician's movements with mismatching emotional sound) than for emotionally matching music performances (combining the musician's movements with matching emotional sound) as presented in Experiment 2 to the same participants. The insula and the left thalamus were found to respond consistently to visual, auditory and audiovisual emotional information and to have increased activation for emotionally mismatching displays in comparison with emotionally matching displays. In contrast, the right thalamus was found to respond to audiovisual emotional displays and to have similar activation for emotionally matching and mismatching displays. These results suggest that the insula and left thalamus have an active role in detecting emotional correspondence between auditory and visual information during music performances, whereas the right thalamus has a different role.

Understanding the roles of nonstructural carbohydrates in forest trees - from what we can measure to what we want to know.

PubMed

Hartmann, Henrik; Trumbore, Susan

2016-07-01

Contents 386 I. 386 II. 388 III. 392 IV. 392 V. 396 VI. 399 399 References 399 SUMMARY: Carbohydrates provide the building blocks for plant structures as well as versatile resources for metabolic processes. The nonstructural carbohydrates (NSC), mainly sugars and starch, fulfil distinct functional roles, including transport, energy metabolism and osmoregulation, and provide substrates for the synthesis of defence compounds or exchange with symbionts involved in nutrient acquisition or defence. At the whole-plant level, NSC storage buffers the asynchrony of supply and demand on diel, seasonal or decadal temporal scales and across plant organs. Despite its central role in plant function and in stand-level carbon cycling, our understanding of storage dynamics, its controls and response to environmental stresses is very limited, even after a century of research. This reflects the fact that often storage is defined by what we can measure, that is, NSC concentrations, and the interpretation of these as a proxy for a single function, storage, rather than the outcome of a range of NSC source and sink functions. New isotopic tools allow direct quantification of timescales involved in NSC dynamics, and show that NSC-C fixed years to decades previously is used to support tree functions. Here we review recent advances, with emphasis on the context of the interactions between NSC, drought and tree mortality. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Antibody Responses to Marburg Virus in Egyptian Rousette Bats and Their Role in Protection against Infection.

PubMed

Storm, Nadia; Jansen Van Vuren, Petrus; Markotter, Wanda; Paweska, Janusz T

2018-02-10

Egyptian rousette bats (ERBs) are reservoir hosts for the Marburg virus (MARV). The immune dynamics and responses to MARV infection in ERBs are poorly understood, and limited information exists on the role of antibodies in protection of ERBs against MARV infection. Here, we determine the duration of maternal immunity to MARV in juvenile ERBs, and evaluate the duration of the antibody response to MARV in bats naturally or experimentally infected with the virus. We further explore whether antibodies in previously naturally exposed bats is fully protective against experimental reinfection with MARV. Maternal immunity was lost in juvenile ERBs by 5 months of age. Antibodies to MARV remained detectable in 67% of experimentally infected bats approximately 4 months post inoculation (p.i.), while antibodies to MARV remained present in 84% of naturally exposed bats at least 11 months after capture. Reinfection of seropositive ERBs with MARV produced an anamnestic response from day 5 p.i. Although PCR-defined viremia was present in 73.3% of reinfected ERBs, replicating virus was recovered from the serum of only one bat on day 3 p.i. The negative PCR results in the salivary glands, intestines, bladders and reproductive tracts of reinfected bats, and the apparent absence of MARV in the majority of swabs collected from these bats suggest that reinfection may only play a minor role in the transmission and maintenance of MARV amongst ERBs in nature.

Towards an explicit account of implicit learning.

PubMed

Forkstam, Christian; Petersson, Karl Magnus

2005-08-01

The human brain supports acquisition mechanisms that can extract structural regularities implicitly from experience without the induction of an explicit model. Reber defined the process by which an individual comes to respond appropriately to the statistical structure of the input ensemble as implicit learning. He argued that the capacity to generalize to new input is based on the acquisition of abstract representations that reflect underlying structural regularities in the acquisition input. We focus this review of the implicit learning literature on studies published during 2004 and 2005. We will not review studies of repetition priming ('implicit memory'). Instead we focus on two commonly used experimental paradigms: the serial reaction time task and artificial grammar learning. Previous comprehensive reviews can be found in Seger's 1994 article and the Handbook of Implicit Learning. Emerging themes include the interaction between implicit and explicit processes, the role of the medial temporal lobe, developmental aspects of implicit learning, age-dependence, the role of sleep and consolidation. The attempts to characterize the interaction between implicit and explicit learning are promising although not well understood. The same can be said about the role of sleep and consolidation. Despite the fact that lesion studies have relatively consistently suggested that the medial temporal lobe memory system is not necessary for implicit learning, a number of functional magnetic resonance studies have reported medial temporal lobe activation in implicit learning. This issue merits further research. Finally, the clinical relevance of implicit learning remains to be determined.

Genome-wide DNA methylation patterns in LSH mutant reveals de-repression of repeat elements and redundant epigenetic silencing pathways

PubMed Central

Yu, Weishi; McIntosh, Carl; Lister, Ryan; Zhu, Iris; Han, Yixing; Ren, Jianke; Landsman, David; Lee, Eunice; Briones, Victorino; Terashima, Minoru; Leighty, Robert; Ecker, Joseph R.

2014-01-01

Cytosine methylation is critical in mammalian development and plays a role in diverse biologic processes such as genomic imprinting, X chromosome inactivation, and silencing of repeat elements. Several factors regulate DNA methylation in early embryogenesis, but their precise role in the establishment of DNA methylation at a given site remains unclear. We have generated a comprehensive methylation map in fibroblasts derived from the murine DNA methylation mutant Hells−/− (helicase, lymphoid specific, also known as LSH). It has been previously shown that HELLS can influence de novo methylation of retroviral sequences and endogenous genes. Here, we describe that HELLS controls cytosine methylation in a nuclear compartment that is in part defined by lamin B1 attachment regions. Despite widespread loss of cytosine methylation at regulatory sequences, including promoter regions of protein-coding genes and noncoding RNA genes, overall relative transcript abundance levels in the absence of HELLS are similar to those in wild-type cells. A subset of promoter regions shows increases of the histone modification H3K27me3, suggesting redundancy of epigenetic silencing mechanisms. Furthermore, HELLS modulates CG methylation at all classes of repeat elements and is critical for repression of a subset of repeat elements. Overall, we provide a detailed analysis of gene expression changes in relation to DNA methylation alterations, which contributes to our understanding of the biological role of cytosine methylation. PMID:25170028

The default mode network in chimpanzees (Pan troglodytes) is similar to that of humans.

PubMed

Barks, Sarah K; Parr, Lisa A; Rilling, James K

2015-02-01

The human default mode network (DMN), comprising medial prefrontal cortex, precuneus, posterior cingulate cortex, lateral parietal cortex, and medial temporal cortex, is highly metabolically active at rest but deactivates during most focused cognitive tasks. The DMN and social cognitive networks overlap significantly in humans. We previously demonstrated that chimpanzees (Pan troglodytes) show highest resting metabolic brain activity in the cortical midline areas of the human DMN. Human DMN is defined by task-induced deactivations, not absolute resting metabolic levels; ergo, resting activity is insufficient to define a DMN in chimpanzees. Here, we assessed the chimpanzee DMN's deactivations relative to rest during cognitive tasks and the effect of social content on these areas' activity. Chimpanzees performed a match-to-sample task with conspecific behavioral stimuli of varying sociality. Using [(18)F]-FDG PET, brain activity during these tasks was compared with activity during a nonsocial task and at rest. Cortical midline areas in chimpanzees deactivated in these tasks relative to rest, suggesting a chimpanzee DMN anatomically and functionally similar to humans. Furthermore, when chimpanzees make social discriminations, these same areas (particularly precuneus) are highly active relative to nonsocial tasks, suggesting that, as in humans, the chimpanzee DMN may play a role in social cognition. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Steric interactions determine side-chain conformations in protein cores.

PubMed

Caballero, D; Virrueta, A; O'Hern, C S; Regan, L

2016-09-01

We investigate the role of steric interactions in defining side-chain conformations in protein cores. Previously, we explored the strengths and limitations of hard-sphere dipeptide models in defining sterically allowed side-chain conformations and recapitulating key features of the side-chain dihedral angle distributions observed in high-resolution protein structures. Here, we show that modeling residues in the context of a particular protein environment, with both intra- and inter-residue steric interactions, is sufficient to specify which of the allowed side-chain conformations is adopted. This model predicts 97% of the side-chain conformations of Leu, Ile, Val, Phe, Tyr, Trp and Thr core residues to within 20°. Although the hard-sphere dipeptide model predicts the observed side-chain dihedral angle distributions for both Thr and Ser, the model including the protein environment predicts side-chain conformations to within 20° for only 60% of core Ser residues. Thus, this approach can identify the amino acids for which hard-sphere interactions alone are sufficient and those for which additional interactions are necessary to accurately predict side-chain conformations in protein cores. We also show that our approach can predict alternate side-chain conformations of core residues, which are supported by the observed electron density. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease.

PubMed

Malerba, Mario; Radaeli, Alessandro; Santini, Giuseppe; Morjaria, Jaymin; Mores, Nadia; Mondino, Chiara; Macis, Giuseppe; Montuschi, Paolo

2018-06-01

Bronchodilators, including long-acting muscarinic receptor antagonists (LAMAs), are a mainstay of the pharmacological treatment of chronic obstructive pulmonary disease (COPD). LAMAs act as bronchodilators principally by antagonizing airway smooth muscle cells M 3 muscarinic receptors. Aclidinium bromide is a twice-daily LAMA which was developed to improve on the efficacy and/or safety of previous LAMAs. Area covered: Herein, the authors present the pharmacotherapeutic role of aclidinium in COPD and point out unmet need in this research area. The following aspects are covered: a) the discovery and medicinal chemistry of aclidinium bromide; b) an overview of the market; c) its mechanism of action; d) its pharmacokinetic/pharmacodynamic profile derived from pre-clinical studies; e) the clinical studies which led to its licensing; f) the evidence from meta-analyses; g) the aclidinium/formoterol fixed dose combination for COPD and h) priorities in this area of research. Expert opinion: Aclidinium bromide has the pharmacological properties, safety and efficacy profile and inhaler characteristics which makes it a valuable therapeutic option for pharmacological management of patients with COPD. Due to its rapid biotransformation into inactive metabolites, aclidinium is potentially one of the safest LAMAs. Further head-to-head randomized clinical trials are required to define efficacy and safety of aclidinium when compared to once-daily LAMAs. The clinical relevance of airway anti-remodeling effects of aclidinium has to be defined.

Molecular signatures of plastic phenotypes in two eusocial insect species with simple societies.

PubMed

Patalano, Solenn; Vlasova, Anna; Wyatt, Chris; Ewels, Philip; Camara, Francisco; Ferreira, Pedro G; Asher, Claire L; Jurkowski, Tomasz P; Segonds-Pichon, Anne; Bachman, Martin; González-Navarrete, Irene; Minoche, André E; Krueger, Felix; Lowy, Ernesto; Marcet-Houben, Marina; Rodriguez-Ales, Jose Luis; Nascimento, Fabio S; Balasubramanian, Shankar; Gabaldon, Toni; Tarver, James E; Andrews, Simon; Himmelbauer, Heinz; Hughes, William O H; Guigó, Roderic; Reik, Wolf; Sumner, Seirian

2015-11-10

Phenotypic plasticity is important in adaptation and shapes the evolution of organisms. However, we understand little about what aspects of the genome are important in facilitating plasticity. Eusocial insect societies produce plastic phenotypes from the same genome, as reproductives (queens) and nonreproductives (workers). The greatest plasticity is found in the simple eusocial insect societies in which individuals retain the ability to switch between reproductive and nonreproductive phenotypes as adults. We lack comprehensive data on the molecular basis of plastic phenotypes. Here, we sequenced genomes, microRNAs (miRNAs), and multiple transcriptomes and methylomes from individual brains in a wasp (Polistes canadensis) and an ant (Dinoponera quadriceps) that live in simple eusocial societies. In both species, we found few differences between phenotypes at the transcriptional level, with little functional specialization, and no evidence that phenotype-specific gene expression is driven by DNA methylation or miRNAs. Instead, phenotypic differentiation was defined more subtly by nonrandom transcriptional network organization, with roles in these networks for both conserved and taxon-restricted genes. The general lack of highly methylated regions or methylome patterning in both species may be an important mechanism for achieving plasticity among phenotypes during adulthood. These findings define previously unidentified hypotheses on the genomic processes that facilitate plasticity and suggest that the molecular hallmarks of social behavior are likely to differ with the level of social complexity.

Spatial scale and sampling resolution affect measures of gap disturbance in a lowland tropical forest: implications for understanding forest regeneration and carbon storage

PubMed Central

Lobo, Elena; Dalling, James W.

2014-01-01

Treefall gaps play an important role in tropical forest dynamics and in determining above-ground biomass (AGB). However, our understanding of gap disturbance regimes is largely based either on surveys of forest plots that are small relative to spatial variation in gap disturbance, or on satellite imagery, which cannot accurately detect small gaps. We used high-resolution light detection and ranging data from a 1500 ha forest in Panama to: (i) determine how gap disturbance parameters are influenced by study area size, and the criteria used to define gaps; and (ii) to evaluate how accurately previous ground-based canopy height sampling can determine the size and location of gaps. We found that plot-scale disturbance parameters frequently differed significantly from those measured at the landscape-level, and that canopy height thresholds used to define gaps strongly influenced the gap-size distribution, an important metric influencing AGB. Furthermore, simulated ground surveys of canopy height frequently misrepresented the true location of gaps, which may affect conclusions about how relatively small canopy gaps affect successional processes and contribute to the maintenance of diversity. Across site comparisons need to consider how gap definition, scale and spatial resolution affect characterizations of gap disturbance, and its inferred importance for carbon storage and community composition. PMID:24452032

Association of tamoxifen with meningioma: a population-based study in Sweden

PubMed Central

Sundquist, Jan; Sundquist, Kristina

2016-01-01

Previous studies suggest that hormone therapy may play an important role in the development of meningioma. However, it is unclear whether medication with tamoxifen can prevent meningioma. Our study cohort included all women who were diagnosed with breast cancer between 1961 and 2010, and a total of 227 535 women were identified with breast cancer with a median age at diagnosis of 63 years. Women diagnosed with breast cancer after 1987 were defined as tamoxifen exposed; those diagnosed with breast cancer before or during 1987 were defined as not exposed to tamoxifen. Standardized incidence ratios (SIRs) were used to calculate the risk of subsequent meningioma. Of these women, 223 developed meningioma. For women without tamoxifen exposure, the risk of meningioma was significantly increased, with an SIR of 1.54 (95% confidence interval 1.30–1.81); the risk was not increased in those with tamoxifen exposure (SIR=1.06, 95% confidence interval 0.84–1.32). The increased risk of meningioma in women without tamoxifen exposure persisted during 10 years of follow-up. In this historical cohort study, we found that women diagnosed with breast cancer but not treated with tamoxifen had an increased incidence of meningioma, whereas the incidence was close to that of the general population in patients treated with tamoxifen. This suggests that tamoxifen may prevent the development of meningioma. PMID:25642792

Molecular signatures of plastic phenotypes in two eusocial insect species with simple societies

PubMed Central

Patalano, Solenn; Vlasova, Anna; Wyatt, Chris; Ewels, Philip; Camara, Francisco; Ferreira, Pedro G.; Asher, Claire L.; Jurkowski, Tomasz P.; Segonds-Pichon, Anne; Bachman, Martin; González-Navarrete, Irene; Minoche, André E.; Krueger, Felix; Lowy, Ernesto; Marcet-Houben, Marina; Rodriguez-Ales, Jose Luis; Nascimento, Fabio S.; Balasubramanian, Shankar; Gabaldon, Toni; Tarver, James E.; Andrews, Simon; Himmelbauer, Heinz; Hughes, William O. H.; Guigó, Roderic; Reik, Wolf; Sumner, Seirian

2015-01-01

Phenotypic plasticity is important in adaptation and shapes the evolution of organisms. However, we understand little about what aspects of the genome are important in facilitating plasticity. Eusocial insect societies produce plastic phenotypes from the same genome, as reproductives (queens) and nonreproductives (workers). The greatest plasticity is found in the simple eusocial insect societies in which individuals retain the ability to switch between reproductive and nonreproductive phenotypes as adults. We lack comprehensive data on the molecular basis of plastic phenotypes. Here, we sequenced genomes, microRNAs (miRNAs), and multiple transcriptomes and methylomes from individual brains in a wasp (Polistes canadensis) and an ant (Dinoponera quadriceps) that live in simple eusocial societies. In both species, we found few differences between phenotypes at the transcriptional level, with little functional specialization, and no evidence that phenotype-specific gene expression is driven by DNA methylation or miRNAs. Instead, phenotypic differentiation was defined more subtly by nonrandom transcriptional network organization, with roles in these networks for both conserved and taxon-restricted genes. The general lack of highly methylated regions or methylome patterning in both species may be an important mechanism for achieving plasticity among phenotypes during adulthood. These findings define previously unidentified hypotheses on the genomic processes that facilitate plasticity and suggest that the molecular hallmarks of social behavior are likely to differ with the level of social complexity. PMID:26483466

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome.

PubMed

Swanson, Larry W; Sporns, Olaf; Hahn, Joel D

2016-10-04

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules. The modules form four topographically distinct longitudinal columns that only partly correspond to previous interpretations of cerebral nuclei structure-function organization. The network of connections within and between modules in one hemisphere or the other is quite dense (about 40% of all possible connections), whereas the network of connections between hemispheres is weak and sparse (only about 5% of all possible connections). Particularly highly interconnected regions (rich club and hubs within it) form a topologically continuous band extending through two of the modules. Connection path lengths among numerous pairs of regions, and among some of the network's modules, are relatively long, thus accounting for low global efficiency in network communication. These results provide a starting point for reexamining the connectional organization of the cerebral hemispheres as a whole (right and left cerebral cortex and cerebral nuclei together) and their relation to the rest of the nervous system.

The moderating role of job resources in the relationship between job demands and interleukin-6 in an Italian healthcare organization.

PubMed

Falco, Alessandra; Dal Corso, Laura; Girardi, Damiano; De Carlo, Alessandro; Comar, Manola

2018-02-01

In this study we examined the association between job demands (JD), job resources (JR), and serum levels of a possible biomarker of stress, the pro-inflammatory cytokine interleukin-6 (IL-6). According to the buffer hypothesis of the Job Demands-Resources (JD-R) model, we expected that job resources-defined as job autonomy and social support from supervisor-might buffer the relationship between job demands, defined as emotional demands and interpersonal conflict with colleagues, and IL-6. Data from 119 employees in an Italian public healthcare organization (acute care hospital) were analyzed using multiple regression. In predicting IL-6, the interactions between emotional demands and JR and between interpersonal conflict with colleagues and job autonomy (but not social support) were significant, after controlling for the effect of age and gender. The association between JD and IL-6 was stronger for individuals with low levels of JR, so that levels of IL-6 were highest when JD were high and JR were low. Overall, these results are consistent with the buffer hypothesis of the JD-R model and also extend previous research, showing that the exposure to stressful situations at work, measured as high JD and low JR, is associated with higher levels of IL-6 in hospital employees. © 2017 Wiley Periodicals, Inc.

A conceptual model of the role of complexity in the care of patients with multiple chronic conditions.

PubMed

Grembowski, David; Schaefer, Judith; Johnson, Karin E; Fischer, Henry; Moore, Susan L; Tai-Seale, Ming; Ricciardi, Richard; Fraser, James R; Miller, Donald; LeRoy, Lisa

2014-03-01

Effective healthcare for people with multiple chronic conditions (MCC) is a US priority, but the inherent complexity makes both research and delivery of care particularly challenging. As part of AHRQ Multiple Chronic Conditions Research Network (MCCRN) efforts, the Network developed a conceptual model to guide research in this area. To synthesize methodological and topical issues relevant to MCC patient care into a framework that can improve the delivery of care and advance future research about caring for patients with MCC. The Network synthesized essential constructs for MCC research identified from roundtable discussion, input from expert advisors, and previously published models. The AHRQ MCCRN conceptual model defines complexity as the gap between patient needs and healthcare services, taking into account both the multiple considerations that affect the needs of MCC patients, as well as the contextual factors that influence service delivery. The model reframes processes and outcomes to include not only clinical care quality and experience, but also patient health, well being, and quality of life. The single-condition paradigm for treating needs one-by-one falls apart and highlights the need for care systems to address dynamic patient needs. Defining complexity in terms of the misalignment between patient needs and services offers new insights in how to research and develop solutions to patient care needs.

3D Printing Polymers with Supramolecular Functionality for Biological Applications.

PubMed

Pekkanen, Allison M; Mondschein, Ryan J; Williams, Christopher B; Long, Timothy E

2017-09-11

Supramolecular chemistry continues to experience widespread growth, as fine-tuned chemical structures lead to well-defined bulk materials. Previous literature described the roles of hydrogen bonding, ionic aggregation, guest/host interactions, and π-π stacking to tune mechanical, viscoelastic, and processing performance. The versatility of reversible interactions enables the more facile manufacturing of molded parts with tailored hierarchical structures such as tissue engineered scaffolds for biological applications. Recently, supramolecular polymers and additive manufacturing processes merged to provide parts with control of the molecular, macromolecular, and feature length scales. Additive manufacturing, or 3D printing, generates customizable constructs desirable for many applications, and the introduction of supramolecular interactions will potentially increase production speed, offer a tunable surface structure for controlling cell/scaffold interactions, and impart desired mechanical properties through reinforcing interlayer adhesion and introducing gradients or self-assembled structures. This review details the synthesis and characterization of supramolecular polymers suitable for additive manufacture and biomedical applications as well as the use of supramolecular polymers in additive manufacturing for drug delivery and complex tissue scaffold formation. The effect of supramolecular assembly and its dynamic behavior offers potential for controlling the anisotropy of the printed objects with exquisite geometrical control. The potential for supramolecular polymers to generate well-defined parts, hierarchical structures, and scaffolds with gradient properties/tuned surfaces provides an avenue for developing next-generation biomedical devices and tissue scaffolds.

The Dying Role: Its Relevance to Improved Patient Care.

PubMed

Noyes, Russell; Clancy, John

2016-01-01

SOCIETY is failing to meet the obligation it has to its dying members. Persons with terminal illnesses suffer isolation and neglect in hospitals, receive overzealous treatment by physicians, and are kept in ignorance of their situation by families and medical personnel. Evidence for these statements has come from observers of the medical care system and from dying patients themselves (Kübler-Ross, 1969; Reynolds and Kalish, 1974; Sudnow, 1967). In the nineteenth century it was common for persons to die in the familiar environs of their homes, surrounded by grieving families from whom they parted in a meaningful manner (Blauner, 1966). Dying persons of today no longer fill a well-defined social role. Instead, the distinction between the roles of sick and dying persons has been lost and, in the resulting confusion, the care of dying people has suffered. The purpose of this article is to clarify the distinction between the dying and sick roles, identify the signs of existing role confusion, suggest ways in which this confusion may be corrected, and show how reestablishment of the dying role can result in improved care of dying people. The important part physicians play in defining sick and dying roles will be emphasized.

Managerial Discretion.

ERIC Educational Resources Information Center

May, William J.

1983-01-01

Defines the principal's role as educational leader. Shows how the status of principals and the bureaucracy of public schools in Canada limit the principal's role. Explains the Canadian school budgeting process and its disadvantages. Suggests that school-based management can overcome educational centralization. (SB)

Determinants of underdiagnosis of COPD in national and international surveys.

PubMed

Lamprecht, Bernd; Soriano, Joan B; Studnicka, Michael; Kaiser, Bernhard; Vanfleteren, Lowie E; Gnatiuc, Louisa; Burney, Peter; Miravitlles, Marc; García-Rio, Francisco; Akbari, Kaveh; Ancochea, Julio; Menezes, Ana M; Perez-Padilla, Rogelio; Montes de Oca, Maria; Torres-Duque, Carlos A; Caballero, Andres; González-García, Mauricio; Buist, Sonia

2015-10-01

COPD ranks within the top three causes of mortality in the global burden of disease, yet it remains largely underdiagnosed. We assessed the underdiagnosis of COPD and its determinants in national and international surveys of general populations. We analyzed representative samples of adults aged ≥ 40 years randomly selected from well-defined administrative areas worldwide (44 sites from 27 countries). Postbronchodilator FEV1/FVC < lower limit of normal (LLN) was used to define chronic airflow limitation consistent with COPD. Undiagnosed COPD was considered when participants had postbronchodilator FEV1/FVC < LLN but were not given a diagnosis of COPD. Among 30,874 participants with a mean age of 56 years, 55.8% were women, and 22.9% were current smokers. Population prevalence of (spirometrically defined) COPD ranged from 3.6% in Barranquilla, Colombia, to 19.0% in Cape Town, South Africa. Only 26.4% reported a previous lung function test, and only 5.0% reported a previous diagnosis of COPD, whereas 9.7% had a postbronchodilator FEV1/FVC < LLN. Overall, 81.4% of (spirometrically defined) COPD cases were undiagnosed, with the highest rate in Ile-Ife, Nigeria (98.3%) and the lowest rate in Lexington, Kentucky (50.0%). In multivariate analysis, a greater probability of underdiagnosis of COPD was associated with male sex, younger age, never and current smoking, lower education, no previous spirometry, and less severe airflow limitation. Even with substantial heterogeneity in COPD prevalence, COPD underdiagnosis is universally high. Because effective management strategies are available for COPD, spirometry can help in the diagnosis of COPD at a stage when treatment will lead to better outcomes and improved quality of life.

The Impact of High School Science Teachers' Beliefs, Curricular Enactments and Experience on Student Learning During an Inquiry-based Urban Ecology Curriculum

NASA Astrophysics Data System (ADS)

McNeill, Katherine L.; Silva Pimentel, Diane; Strauss, Eric G.

2013-10-01

Inquiry-based curricula are an essential tool for reforming science education yet the role of the teacher is often overlooked in terms of the impact of the curriculum on student achievement. Our research focuses on 22 teachers' use of a year-long high school urban ecology curriculum and how teachers' self-efficacy, instructional practices, curricular enactments and previous experience impacted student learning. Data sources included teacher belief surveys, teacher enactment surveys, a student multiple-choice assessment focused on defining and identifying science concepts and a student open-ended assessment focused on scientific inquiry. Results from the two hierarchical linear models indicate that there was significant variation between teachers in terms of student achievement. For the multiple-choice assessment, teachers who spent a larger percentage of time on group work and a smaller percentage of time lecturing had greater student learning. For the open-ended assessment, teachers who reported a higher frequency of students engaging in argument and sharing ideas had greater student learning while teachers who adapted the curriculum more had lower student learning. These results suggest the importance of supporting the active role of students in instruction, emphasising argumentation, and considering the types of adaptations teachers make to curriculum.

Do Multiple Forms of Social Capital Mediate the Relationship Between Parental Violence and Children's Maladaptive Behaviors?

PubMed

Kim, Sangwon; Lee, Yanghee

2018-03-01

Many things can harm children's well-being. Among them, exposure to parental violence makes children vulnerable and often leads to aggression and/or depression. However, not all children who have suffered parental violence show aggressive behavior or depressive mood. Social capital, defined as resources accruing from interpersonal relationships, was proposed to significantly mediate the relationships among adverse experiences and their negative impacts. In previous studies, social capital accrued from parents played a positive role for children in violent situations, but children exposed to parental violence need alternative sources of social capital. This study targeted fourth-grade Korean children and aimed to identify and test the role of various forms of social capital to help children overcome negative consequences from parental violence. Siblings, friends, teachers, neighbors, and online acquaintances were sources of social capital, and the results showed that social capital from siblings, teachers, neighbors, or online acquaintances mediated in the relationships between parental violence and aggressive behavior. In addition, social capital from siblings and online acquaintances mediated in the relationships between parental violence and depressive mood. The findings have implications in terms of intervention. It is suggested that multiple forms of social capital from children's immediate environments are helpful in their adaptation from exposure to parental violence, and thus, relationship-based interventions are recommended.

A Multifaceted Mathematical Approach for Complex Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexander, F.; Anitescu, M.; Bell, J.

2012-03-07

Applied mathematics has an important role to play in developing the tools needed for the analysis, simulation, and optimization of complex problems. These efforts require the development of the mathematical foundations for scientific discovery, engineering design, and risk analysis based on a sound integrated approach for the understanding of complex systems. However, maximizing the impact of applied mathematics on these challenges requires a novel perspective on approaching the mathematical enterprise. Previous reports that have surveyed the DOE's research needs in applied mathematics have played a key role in defining research directions with the community. Although these reports have had significantmore » impact, accurately assessing current research needs requires an evaluation of today's challenges against the backdrop of recent advances in applied mathematics and computing. To address these needs, the DOE Applied Mathematics Program sponsored a Workshop for Mathematics for the Analysis, Simulation and Optimization of Complex Systems on September 13-14, 2011. The workshop had approximately 50 participants from both the national labs and academia. The goal of the workshop was to identify new research areas in applied mathematics that will complement and enhance the existing DOE ASCR Applied Mathematics Program efforts that are needed to address problems associated with complex systems. This report describes recommendations from the workshop and subsequent analysis of the workshop findings by the organizing committee.« less

In vitro evidence for the participation of Drosophila melanogaster sperm β-N-acetylglucosaminidases in the interactions with glycans carrying terminal N-acetylglucosamine residues on the egg's envelopes.

PubMed

Intra, Jari; Veltri, Concetta; De Caro, Daniela; Perotti, Maria Elisa; Pasini, Maria Enrica

2017-09-01

Fertilization is a complex and multiphasic process, consisting of several steps, where egg-coating envelope's glycoproteins and sperm surface receptors play a critical role. Sperm-associated β-N-acetylglucosaminidases, also known as hexosaminidases, have been identified in a variety of organisms. Previously, two isoforms of hexosaminidases, named here DmHEXA and DmHEXB, were found as intrinsic proteins in the sperm plasma membrane of Drosophila melanogaster. In the present work, we carried out different approaches using solid-phase assays in order to analyze the oligosaccharide recognition ability of D. melanogaster sperm hexosaminidases to interact with well-defined carbohydrate chains that might functionally mimic egg glycoconjugates. Our results showed that Drosophila hexosaminidases prefer glycans carrying terminal β-N-acetylglucosamine, but not core β-N-acetylglucosamine residues. The capacity of sperm β-N-acetylhexosaminidases to bind micropylar chorion and vitelline envelope was examined in vitro assays. Binding was completely blocked when β-N-acetylhexosaminidases were preincubated with the glycoproteins ovalbumin and transferrin, and the monosaccharide β-N-acetylglucosamine. Overall, these data support the hypothesis of the potential role of these glycosidases in sperm-egg interactions in Drosophila. © 2017 Wiley Periodicals, Inc.

Side effects, adherence self-efficacy, and adherence to antiretroviral treatment: a mediation analysis in a Chinese sample.

PubMed

Zhang, Liying; Li, Xiaoming; Lin, Zhenping; Jacques-Tiura, Angela J; Xu, Jinping; Zhou, Yuejiao; Qiao, Shan; Shen, Zhiyong; Stanton, Bonita

2016-07-01

Antiretroviral therapy (ART) is a lifelong treatment. To date, ART adherence is suboptimal for most patients in resource-poor settings. Previous research indicates that medication side effects are perceived to be a significant barrier of high ART adherence. Data regarding the role of adherence self-efficacy in mediating the relationship between side effects from ART and adherence to ART are limited; thus, this study examines this potential mediational role of self-efficacy. A cross-sectional survey of 2987 people living with HIV aged ≥18 years was conducted in 2012-2013 in Guangxi Autonomous Region (Guangxi) which has one of the fastest-growing HIV rates in China. Of the total sample, 2146 (72.1%) participants had initiated ART. Participants reported the number of days of completing the daily dose of ART in the past month; adherence was defined as completing the daily dose at least 28 days in the last month (≥90%). Side effects were significantly negatively related to adherence to ART. Mediation analyses indicated that adherence self-efficacy significantly mediated the side effects-adherence relationship. Future interventions to increase adherence self-efficacy and effective coping with side effects among HIV patients are needed in order to improve their ART adherence.

Material-Model-Based Determination of the Shock-Hugoniot Relations in Nanosegregated Polyurea

NASA Astrophysics Data System (ADS)

Grujicic, Mica; Snipes, J. S.; Galgalikar, R.; Ramaswami, S.

2014-02-01

Previous experimental investigations reported in the open literature have indicated that applying polyurea external coatings and/or internal linings can substantially improve ballistic penetration resistance and blast survivability of buildings, vehicles, and laboratory/field test-plates, as well as the blast-mitigation capacity of combat helmets. The protective role of polyurea coatings/linings has been linked to polyurea microstructure, which consists of discrete hard-domains distributed randomly within a compliant/soft matrix. When this protective role is investigated computationally, the availability of reliable, high-fidelity constitutive models for polyurea is vitally important. In the present work, a comprehensive overview and a critical assessment of a polyurea material constitutive model, recently proposed by Shim and Mohr (Int J Plast 27:868-886, 2011), are carried out. The review revealed that this model can accurately account for the experimentally measured uniaxial-stress versus strain data obtained under monotonic and multistep compressive loading/unloading conditions, as well as under stress relaxation conditions. On the other hand, by combining analytical and finite-element procedures with the material model in order to define the basic shock-Hugoniot relations for this material, it was found that the computed shock-Hugoniot relations differ significantly from their experimental counterparts. Potential reasons for the disagreement between the computed and experimental shock-Hugoniot relations are identified.

Sucrose breakdown within guard cells provides substrates for glycolysis and glutamine biosynthesis during light-induced stomatal opening.

PubMed

Medeiros, David B; Perez Souza, Leonardo; Antunes, Werner C; Araújo, Wagner L; Daloso, Danilo M; Fernie, Alisdair R

2018-05-01

Sucrose has long been thought to play an osmolytic role in stomatal opening. However, recent evidence supports the idea that the role of sucrose in this process is primarily energetic. Here we used a combination of stomatal aperture assays and kinetic [U- 13 C]-sucrose isotope labelling experiments to confirm that sucrose is degraded during light-induced stomatal opening and to define the fate of the C released from sucrose breakdown. We additionally show that addition of sucrose to the medium did not enhance light-induced stomatal opening. The isotope experiment showed a consistent 13 C enrichment in fructose and glucose, indicating that during light-induced stomatal opening sucrose is indeed degraded. We also observed a clear 13 C enrichment in glutamate and glutamine (Gln), suggesting a concerted activation of sucrose degradation, glycolysis and the tricarboxylic acid cycle. This is in contrast to the situation for Gln biosynthesis in leaves under light, which has been demonstrated to rely on previously stored C. Our results thus collectively allow us to redraw current models concerning the influence of sucrose during light-induced stomatal opening, in which, instead of being accumulated, sucrose is degraded providing C skeletons for Gln biosynthesis. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3.

PubMed

Pérez-Schindler, Joaquín; Esparza, Mary C; McKendry, James; Breen, Leigh; Philp, Andrew; Schenk, Simon

2017-09-01

Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth. In contrast to previous work, two different resistance exercise protocols did not change STAT3 phosphorylation in human skeletal muscle. To directly address the role of STAT3 in load-induced (i.e., adaptive) growth, we studied the anabolic effects of 14 days of synergist ablation (SA) in skeletal muscle-specific STAT3 knockout (mKO) mice and their floxed, wild-type (WT) littermates. Plantaris muscle weight and fiber area in the nonoperated leg (control; CON) was comparable between genotypes. As expected, SA significantly increased plantaris weight, muscle fiber cross-sectional area, and anabolic signaling in WT mice, although interestingly, this induction was not impaired in STAT3 mKO mice. Collectively, these data demonstrate that STAT3 is not required for overload-mediated hypertrophy in mouse skeletal muscle. Copyright © 2017 the American Physiological Society.

The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway

PubMed Central

Roboti, Peristera; Sato, Keisuke; Lowe, Martin

2015-01-01

Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and found that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) and Golgi complex during anterograde trafficking, and is also required for retrograde trafficking to the ER. Using co-depletion experiments, we also found that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER–Golgi interface, some of which are partially redundant with another golgin, namely GM130 (also known as GOLGA2). PMID:25717001

Pros, cons, and current indications of open craniotomy versus gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization.

PubMed

Surdell, Daniel L; Bhattacharjee, Sumon; Loftus, Christopher M

2002-06-01

The successful treatment of an intracranial arteriovenous malformation poses both technical and conceptual problems to the neurosurgeon. Treatment decisions are made in light of current understanding of the natural history of these lesions. It is important to understand the pros, cons and current indication of open craniotomy vs. gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization. Surgical removal of an arteriovenous malformation is indicated when the operative risk is less than the morbidity and mortality associated with its natural history. The treatment goal of complete angiographic obliteration of arteriovenous malformations is achieved most effectively by microneurosurgery in low-grade lesions. Large lesions frequently require a combination of embolization and microsurgery. Although recent advances in technology and medical management have allowed previously inoperable arteriovenous malformations to be surgically excised, there is still a small group of arteriovenous malformations that cannot be excised safely due to their size and location. Stereotactic radiosurgery is clearly an important adjunct in the multimodality treatment approach for large arteriovenous malformations. Endovascular embolization can potentially increase safety and efficacy in the treatment of arteriovenous malformations when applied to selective cases with well-defined treatment goals.

Nuclear pore complex evolution: a trypanosome Mlp analogue functions in chromosomal segregation but lacks transcriptional barrier activity

PubMed Central

Holden, Jennifer M.; Koreny, Ludek; Obado, Samson; Ratushny, Alexander V.; Chen, Wei-Ming; Chiang, Jung-Hsien; Kelly, Steven; Chait, Brian T.; Aitchison, John D.; Rout, Michael P.; Field, Mark C.

2014-01-01

The nuclear pore complex (NPC) has dual roles in nucleocytoplasmic transport and chromatin organization. In many eukaryotes the coiled-coil Mlp/Tpr proteins of the NPC nuclear basket have specific functions in interactions with chromatin and defining specialized regions of active transcription, whereas Mlp2 associates with the mitotic spindle/NPC in a cell cycle–dependent manner. We previously identified two putative Mlp-related proteins in African trypanosomes, TbNup110 and TbNup92, the latter of which associates with the spindle. We now provide evidence for independent ancestry for TbNup92/TbNup110 and Mlp/Tpr proteins. However, TbNup92 is required for correct chromosome segregation, with knockout cells exhibiting microaneuploidy and lowered fidelity of telomere segregation. Further, TbNup92 is intimately associated with the mitotic spindle and spindle anchor site but apparently has minimal roles in control of gene transcription, indicating that TbNup92 lacks major barrier activity. TbNup92 therefore acts as a functional analogue of Mlp/Tpr proteins, and, together with the lamina analogue NUP-1, represents a cohort of novel proteins operating at the nuclear periphery of trypanosomes, uncovering complex evolutionary trajectories for the NPC and nuclear lamina. PMID:24600046

The Ca2+-induced methyltransferase xPRMT1b controls neural fate in amphibian embryo.

PubMed

Batut, Julie; Vandel, Laurence; Leclerc, Catherine; Daguzan, Christiane; Moreau, Marc; Néant, Isabelle

2005-10-18

We have previously shown that an increase in intracellular Ca2+ is both necessary and sufficient to commit ectoderm to a neural fate in Xenopus embryos. However, the relationship between this Ca2+ increase and the expression of early neural genes has yet to be defined. Using a subtractive cDNA library between untreated and caffeine-treated animal caps, i.e., control ectoderm and ectoderm induced toward a neural fate by a release of Ca2+, we have isolated the arginine N-methyltransferase, xPRMT1b, a Ca2+-induced target gene, which plays a pivotal role in this process. First, we show in embryo and in animal cap that xPRMT1b expression is Ca2+-regulated. Second, overexpression of xPRMT1b induces the expression of early neural genes such as Zic3. Finally, in the whole embryo, antisense approach with morpholino oligonucleotide against xPRMT1b impairs neural development and in animal caps blocks the expression of neural markers induced by a release of internal Ca2+. Our results implicate an instructive role of an enzyme, an arginine methyltransferase protein, in the embryonic choice of determination between epidermal and neural fate. The results presented provide insights by which a Ca2+ increase induces neural fate.

Intermediate-filaments: from disordered building blocks to well-ordered cells

NASA Astrophysics Data System (ADS)

Kornreich, Micha; Malka-Gibor, Eti; Laser-Azogui, Adi; Doron, Ofer; Avinery, Ram; Herrmann, Harald; Beck, Roy

In the past decade it was found that ~50% of human proteins contain long disordered regions, which play significant functional roles. As these regions lack a defined 3D folded structure, their ensemble conformations can be studied using polymer physics statistical-mechanics arguments. We measure the structure and mechanical response of hydrogels composed of neuronal intermediate filaments proteins. In the nervous system, these proteins provide cells with their mechanical support and shape, via interactions of their long, highly charged and disordered protein chains. We employ synchrotron small-angle X-ray scattering and various microscopy techniques to investigate such hydrogels from the nano- to the macro-scale. In contrast to previous polymer physics theories and experiments, we find that shorter and less charged chains can promote network expansion. The results are explained by intricate interactions between specific domains on the interacting chains, and also suggest a novel structural justification for the changing protein compositions observed during neuronal development. We address the following questions: Can protein disorder have an important role in cellular architecture? Can structural disorder in the micro-scale induce orientational and translational order on the macro-scale? How do the physical properties of disordered protein regions, such as charge, length, and hydrophobicity, modulate the cellular super-structure?

Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation

PubMed Central

2017-01-01

The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations) that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed. PMID:29073146

A nitric oxide/cysteine interaction mediates the activation of soluble guanylate cyclase

PubMed Central

Fernhoff, Nathaniel B.; Derbyshire, Emily R.; Marletta, Michael A.

2009-01-01

Nitric oxide (NO) regulates a number of essential physiological processes by activating soluble guanylate cyclase (sGC) to produce the second messenger cGMP. The mechanism of NO sensing was previously thought to result exclusively from NO binding to the sGC heme; however, recent studies indicate that heme-bound NO only partially activates sGC and additional NO is involved in the mechanism of maximal NO activation. Furthermore, thiol oxidation of sGC cysteines results in the loss of enzyme activity. Herein the role of cysteines in NO-stimulated sGC activity investigated. We find that the thiol modifying reagent methyl methanethiosulfonate specifically inhibits NO activation of sGC by blocking a non-heme site, which defines a role for sGC cysteine(s) in mediating NO binding. The nature of the NO/cysteine interaction was probed by examining the effects of redox active reagents on NO-stimulated activity. These results show that NO binding to, and dissociation from, the critical cysteine(s) does not involve a change in the thiol redox state. Evidence is provided for non-heme NO in the physiological activation of sGC in context of a primary cell culture of human umbilical vein endothelial cells. These findings have relevance to diseases involving the NO/cGMP signaling pathway. PMID:20007374

Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1.

PubMed

Svensson, Katrin J; Christianson, Helena C; Wittrup, Anders; Bourseau-Guilmain, Erika; Lindqvist, Eva; Svensson, Lena M; Mörgelin, Matthias; Belting, Mattias

2013-06-14

The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signaling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signaling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft-associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signaling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signaling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.

The role of the illusion in the construction of erotic desire: narratives from heterosexual men who have occasional sex with transgender women.

PubMed

Reback, Cathy J; Kaplan, Rachel L; Bettcher, Talia M; Larkins, Sherry

2016-08-01

Little is known about men's sexual desire for and erotic attraction to male-to-female transgender women. To better understand how erotic desire is constructed, this study examined the narratives of a sample of heterosexual men who had had an occasional sexual encounter with a transgender woman. Open-ended qualitative interviews were conducted with 16 heterosexual men who reported at least one sexual encounter with a transgender woman in the previous 12 months. Using principles of Grounded Theory, three themes emerged: (1) the erotic desire that transpired from a transgender woman's construction of her femininity, (2) the sexual act that dictated the specific navigation of a transgender woman's penis and (3) the sexual dissonance that resulted from being a heterosexually identified man having sex with a partner who had a penis. These themes reflected how the participants defined and negotiated their sexual encounters, both psychologically through their understanding of sex with a transgender woman with a penis, and physically through the navigation of specific sex acts. The role of the 'illusion' was central to the meaning and construction of erotic desire. These narratives provided another framework for continuing discourse on the complexity of erotic desire.

The Role of the Illusion in the Construction of Erotic Desire: Narratives from Heterosexual Men Who Have Occasional Sex with Transgender Women

PubMed Central

Reback, Cathy J.; Kaplan, Rachel L.; Bettcher, Talia M.; Larkins, Sherry

2016-01-01

Little is known about men’s sexual desire for and erotic attraction to male-to-female transgender women. This study examined the narratives of a sample of heterosexual men who had an occasional sexual encounter with a transgender woman to better understand how erotic desire was constructed. Open-ended qualitative interviews were conducted with 16 heterosexual men who reported at least one sexual encounter with a transgender woman in the previous 12 months. Using the principles of Grounded Theory, three themes emerged: (1) the erotic desire that transpired from a transgender woman’s construction of her femininity; (2) the sexual act that dictated specific navigation of a transgender woman’s penis; and, (3) the sexual dissonance that resulted from being a heterosexually identified man having sex with a partner who had a penis. These themes reflected how the participants defined and negotiated their sexual encounters, both psychologically through their understanding of sex with a transgender woman with a penis, and physically through the navigation of specific sex acts. The role of the ‘illusion’ was central in the meaning and construction of erotic desire. These narratives provided another framework for the continuing discourse on the complexity of erotic desire. PMID:26967172

Exploring Maps with Greedy Navigators

NASA Astrophysics Data System (ADS)

Lee, Sang Hoon; Holme, Petter

2012-03-01

During the last decade of network research focusing on structural and dynamical properties of networks, the role of network users has been more or less underestimated from the bird’s-eye view of global perspective. In this era of global positioning system equipped smartphones, however, a user’s ability to access local geometric information and find efficient pathways on networks plays a crucial role, rather than the globally optimal pathways. We present a simple greedy spatial navigation strategy as a probe to explore spatial networks. These greedy navigators use directional information in every move they take, without being trapped in a dead end based on their memory about previous routes. We suggest that the centralities measures have to be modified to incorporate the navigators’ behavior, and present the intriguing effect of navigators’ greediness where removing some edges may actually enhance the routing efficiency, which is reminiscent of Braess’s paradox. In addition, using samples of road structures in large cities around the world, it is shown that the navigability measure we define reflects unique structural properties, which are not easy to predict from other topological characteristics. In this respect, we believe that our routing scheme significantly moves the routing problem on networks one step closer to reality, incorporating the inevitable incompleteness of navigators’ information.

The Role of the Central Noradrenergic System in Behavioral Inhibition

PubMed Central

Stone, Eric A.; Lin, Yan; Sarfraz, Yasmeen; Quartermain, David

2011-01-01

Although the central noradrenergic system has been shown to be involved in a number of behavioral and neurophysiological processes, the relation of these to its role in depressive illness has been difficult to define. The present review discusses the hypothesis that one of its chief functions that may be related to affective illness is the inhibition of behavioral activation, a prominent symptom of the disorder. This hypothesis is found to be consistent with most previous neuropsychopharmacological and immunohistochemical experiments on active behavior in rodents in a variety of experimental conditions using manipulation of neurotransmission at both locus coeruleus and forebrain adrenergic receptors. The findings support a mechanism in which high rates of noradrenergic neural activity suppress the neural activity of principal neurons in forebrain regions mediating active behavior. The suppression may be mediated through postsynaptic galaninergic and adrenergic receptors, and via the release of corticotrophin-releasing hormone. The hypothesis is consistent with clinical evidence for central noradrenergic system hyperactivity in depressives and with the view that this hyperactivity is a contributing etiological factor in the disorder. A similar mechanism may underlie the ability of the noradrenergic system to suppress seizure activity suggesting that inhibition of the spread of neural activation may be a unifying function. PMID:21315760

Examining the relationship between socio-economic status, WASH practices and wasting

PubMed Central

Raihan, Mohammad Jyoti; Farzana, Fahmida Dil; Sultana, Sabiha; Haque, Md Ahshanul; Rahman, Ahmed Shafiqur; Waid, Jillian L.; McCormick, Ben; Choudhury, Nuzhat; Ahmed, Tahmeed

2017-01-01

Childhood wasting is a global problem and is significantly more pronounced in low and middle income countries like Bangladesh. Socio Economic Status (SES) and Water, Sanitation and Hygiene (WASH) practices may be significantly associated with wasting. Most previous research is consistent about the role of SES, but the significance of WASH in the context of wasting remains ambiguous. The effect of SES and WASH on weight for length (WHZ) is examined using a Structural Equation Model (SEM) to explicitly describe the direct and indirect role of WASH in the context of SES.A nationally representative survey of 10,478 Bangladeshi children under 5 were examined. An expert defined SEM was used to construct latent variables for SES and WASH. The SEM included a direct pathway from SES to WHZ and an indirect pathway from SES to WHZ via WASH along with regression of relevant covariates on the outcome WHZ and the latent variables. Both SES (p<0.01) and WASH (p<0.05) significantly affect WHZ. SES (p<0.01) also significantly affects WASH. Other structural components showed that child’s age (p<0.01) affects WHZ and types of residence (p<0.01) affects SES. WASH practices at least partially mediate the association between SES and wasting status. WASH and SES are both significantly associated with WHZ. PMID:28278161

The pharmacists' role in improving guideline compliance for thyroid function testing in patients with heart failure.

PubMed

Ziman, Melanie E; Bui, Hien T; Smith, Craig S; Tsukiji, Lori A; Asmatey, Veda M; Chu, Steven B; Miano, John S

2012-04-01

This single-center retrospective pilot program's objective was to utilize outpatient pharmacists to improve laboratory test adherence in chronic heart failure (CHF) patients overdue for thyroid function testing, thereby demonstrating the value of the outpatient pharmacist and justifying possible clinical role expansion. Thyroid disorders may contribute to CHF development, progression, and exacerbation. Testing is the standard of care in CHF patients per American Heart Association's 2009 Guidelines. Delinquency was defined as labs not conducted within 1 year in patients with euthyroid history, within 6 months in patients with thyroid dysfunction, abnormal labs at any time without follow-up, or lab absence after thyroid medication initiation, adjustment, or discontinuation. Targeted 80 nonpregnant adult CHF patients with delinquent thyroid function tests were counseled to get thyroid labs at point of sale, via telephone, e-mail, or letter. In collaboration with physicians, pharmacists ordered thyroid-stimulating hormone (TSH) and free T4 (FT4) labs. For patients with abnormal laboratory results, pharmacists coordinated drug therapy and follow-up labs. Data were collected from November 1, 2009 to March 30, 2010. Seventy-two patients (90%) previously delinquent for thyroid function testing received relevant thyroid labs. Ten patients (12.5%) with abnormal thyroid function tests not on prior drug therapy received treatment.

DNA-PKcs is critical for telomere capping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilley, David; Tanaka, Hiromi; Hande, M. Prakash

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is critical for DNA repair via the non-homologous end joining (NHEJ) pathway. Previously, it was reported that bone marrow cells and spontaneously transformed fibroblasts from SCID (severe combined immunodeficiency) mice have defects in telomere maintenance. The genetically defective SCID mouse arose spontaneously from its parental strain CB17. One known genomic alteration in SCID mice is a truncation of the extreme carboxyl-terminus of DNA-PKcs, but other as yet unidentified alterations may also exist. We have used a defined system, the DNA-PKcs knockout mouse, to investigate specifically the role DNA-PKcs specifically plays in telomere maintenance.more » We report that primary mouse embryonic fibroblasts (MEFs) and primary cultured kidney cells from 6-8 month old DNA-PKcs deficient mice accumulate a large number of telomere fusions, yet still retain wildtype telomere length. Thus, the phenotype of this defect separates the two-telomere related phenotypes, capping and length maintenance. DNA-PKcs deficient MEFs also exhibit elevated levels of chromosome fragments and breaks, which correlate with increased telomere fusions. Based on the high levels of telomere fusions observed in DNA-PKcs deficient cells, we conclude that DNA-PKcs plays an important capping role at the mammalian telomere.« less

Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus.

PubMed

Pardos de la Gandara, Maria; Borges, Vitor; Chung, Marilyn; Milheiriço, Catarina; Gomes, João Paulo; de Lencastre, Herminia; Tomasz, Alexander

2018-06-01

Methicillin-resistant Staphylococcus aureus (MRSA) strains carry either a mecA - or a mecC -mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the mecC -carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes ( fruB , gmk , hpt , purB , prsA , and relA ), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA. Copyright © 2018 American Society for Microbiology.

Chronic Pain: Content Validation of Nursing Diagnosis in Slovakia and the Czech Republic.

PubMed

Zeleníková, Renáta; Maniaková, Lenka

2015-10-01

The main purpose of the study was to validate the defining characteristics and related factors of the nursing diagnosis "chronic pain" in Slovakia and the Czech Republic. This is a descriptive study. The validation process involved was based on Fehring's Diagnostic Content Validity Model. Three defining characteristics (reports pain, altered ability to continue previous activities, and depression) were classified as major by Slovak nurses, and one defining characteristic (reports pain) was classified as major by Czech nurses. The results of the study provide guidance in devising strategies of pain assessment and can aid in the formulation of accurate nursing diagnoses. The defining characteristic "reports pain" is important for arriving at the nursing diagnosis "chronic pain." © 2014 NANDA International, Inc.

Role of man in flight experiment payloads, phase 1. [Spacelab mission planning

NASA Technical Reports Server (NTRS)

Malone, T. B.; Kirkpatrick, M.

1974-01-01

The identification of required data for studies of Spacelab experiment functional allocation, the development of an approach to collecting these data from the payload community, and the specification of analytical methods necessary to quantitatively determine the role of man in specific Spacelab experiments are presented. A generalized Spacelab experiment operation sequence was developed, and the parameters necessary to describe each signle function in the sequence were identified. A set of functional descriptor worksheets were also drawn up. The methodological approach to defining the role of man was defined as a series of trade studies using a digial simulation technique. The tradeoff variables identified include scientific crew size, skill mix, and location. An existing digital simulation program suitable for the required analyses was identified and obtained.

Selective small-molecule inhibitors as chemical tools to define the roles of matrix metalloproteinases in disease.

PubMed

Meisel, Jayda E; Chang, Mayland

2017-11-01

The focus of this article is to highlight novel inhibitors and current examples where the use of selective small-molecule inhibitors has been critical in defining the roles of matrix metalloproteinases (MMPs) in disease. Selective small-molecule inhibitors are surgical chemical tools that can inhibit the targeted enzyme; they are the method of choice to ascertain the roles of MMPs and complement studies with knockout animals. This strategy can identify targets for therapeutic development as exemplified by the use of selective small-molecule MMP inhibitors in diabetic wound healing, spinal cord injury, stroke, traumatic brain injury, cancer metastasis, and viral infection. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

Rural Hispanic Counselor and Student Perspectives and Their Roles in Providing Improved Secondary Guidance Counseling

ERIC Educational Resources Information Center

Friesenhahn-Soliz, Grace

2012-01-01

School counselors can serve as agents of change in our nation's schools, particularly for marginalized students whose voices are frequently not heard. Historically, the role of the school counselor has been under-utilized and inaccurately defined. Research available on counselor role definition has been primarily quantitative. Research on…

The Role of Parentification and Family Climate in Adaptation among Immigrant Adolescents in Israel

ERIC Educational Resources Information Center

Walsh, Sophie; Shulman, Shmuel; Bar-On, Zvulun; Tsur, Antal

2006-01-01

Parentification has been defined as the familial interactional pattern in which children and adolescents are assigned or assume roles and responsibilities normally the province of adults. Two studies were conducted to examine the role that parentification takes in the context of immigration with regard to its impact on adolescent adaptation. In…

Caring About Kids: The Importance of Play.

ERIC Educational Resources Information Center

National Inst. of Mental Health (DHHS), Rockville, MD. Div. of Scientific and Public Information.

In several brief sections, this pamphlet defines play, discusses how play helps a child develop, and how play changes as a child grows older, indicates the role of toys and certain play activities in promoting sex stereotypes, and identifies the role of fantasy and imagination in children's play. A discussion of the role of parents in fostering…

ACHP | News | The ACHP Announces New Director ...

Science.gov Websites

Section 106 cases that have defined the shape of the Section 106 process and the ACHP's role in it have ;we are looking forward to Reid assuming this important role, and we are delighted to be able to . Additionally, the ACHP has a key role in administering the Administration's Preserve America Initiative

The Role of International Service-Learning in Facilitating Undergraduate Students' Self-Exploration

ERIC Educational Resources Information Center

Yang, Min; Luk, Lillian Yun Yung; Webster, Beverley Joyce; Chau, Albert Wai-lap; Ma, Carol Hok Ka

2016-01-01

This article examines the role of international service-learning (ISL) in facilitating undergraduates' exploration of their conceptions of self (i.e., self-exploration). Conception of self refers to the use of values to define one's role in a social/cultural group or organization and in society, and to determine current actions and future…

School-Age Care from the Perspective of Social Role Theory.

ERIC Educational Resources Information Center

Ollhoff, Jim; Ollhoff, Laurie

Within the literature of social psychology, there exists a body of information that deals with role theory, defined as the expectations persons have at any given time and the norms that govern their behavior. This paper discusses role theory as it applies to school-age child caregivers and as part of the process of professionalism.…

Thinking Complexly about Men, Gender Role Conflict, and Counseling Psychology

ERIC Educational Resources Information Center

Wester, Stephen R.

2008-01-01

O'Neil (2008) defines male gender role conflict (GRC) as a psychological state in which the socialized male gender role has negative consequences for the person or others. Building on this, many now realize that the mechanisms through which these negative consequences occur, rather than being global, are instead contextual. That is, different men…

Predicting Negative Discipline in Traditional Families: A Multi-Dimensional Stress Model.

ERIC Educational Resources Information Center

Fisher, Philip A.

An attempt is made to integrate existing theories of family violence by introducing the concept of family role stress. Role stressors may be defined as factors inhibiting the enactment of family roles. Multiple regression analyses were performed on data from 190 families to test a hypothesis involving the prediction of negative discipline at…

Exploring the Supervisor Role as a Facilitator of Knowledge Sharing in Teams

ERIC Educational Resources Information Center

MacNeil, Christina Mary

2004-01-01

This paper explores the themes and implications, concerning the role of the supervisor as a facilitator of knowledge sharing in teams. After describing the strategic context for devolving human resource responsibilities to line managers, the paper defines and discusses the line manager/supervisor role. The barriers to learning in the workplace are…

The Hidden Roles of the School Librarian

ERIC Educational Resources Information Center

Novotny, Rebecca Maria

2017-01-01

Purpose: The purpose of this mixed methods study was to define the roles of school librarians as perceived by librarians and principals in regard to the ALA/AASL Standards for the Initial Preparation of School Librarians (2010). This study was designed to explore the perceptions of librarians and principals on the role of the librarian in the…

Defining the Role of the Pharmacy Technician and Identifying Their Future Role in Medicines Optimisation

PubMed Central

Boughen, Melanie; Sutton, Jane; Fenn, Tess

2017-01-01

Background: Traditionally, pharmacy technicians have worked alongside pharmacists in community and hospital pharmacy. Changes within pharmacy provide opportunity for role expansion and with no apparent career pathway, there is a need to define the current pharmacy technician role and role in medicines optimisation. Aim: To capture the current roles of pharmacy technicians and identify how their future role will contribute to medicines optimisation. Methods: Following ethical approval and piloting, an online survey to ascertain pharmacy technicians’ views about their roles was undertaken. Recruitment took place in collaboration with the Association of Pharmacy Technicians UK. Data were exported to SPSS, data screened and descriptive statistics produced. Free text responses were analysed and tasks collated into categories reflecting the type of work involved in each task. Results: Responses received were 393 (28%, n = 1380). Results were organised into five groups: i.e., hospital, community, primary care, General Practitioner (GP) practice and other (which included HM Prison Service). Thirty tasks were reported as commonly undertaken in three or more settings and 206 (84.7%, n = 243) pharmacy technicians reported they would like to expand their role. Conclusions: Tasks core to hospital and community pharmacy should be considered for inclusion to initial education standards to reflect current practice. Post qualification, pharmacy technicians indicate a significant desire to expand clinically and managerially allowing pharmacists more time in patient-facing/clinical roles. PMID:28970452

Defining the Role of the Pharmacy Technician and Identifying Their Future Role in Medicines Optimisation.

PubMed

Boughen, Melanie; Sutton, Jane; Fenn, Tess; Wright, David

2017-07-15

Traditionally, pharmacy technicians have worked alongside pharmacists in community and hospital pharmacy. Changes within pharmacy provide opportunity for role expansion and with no apparent career pathway, there is a need to define the current pharmacy technician role and role in medicines optimisation. To capture the current roles of pharmacy technicians and identify how their future role will contribute to medicines optimisation. Following ethical approval and piloting, an online survey to ascertain pharmacy technicians' views about their roles was undertaken. Recruitment took place in collaboration with the Association of Pharmacy Technicians UK. Data were exported to SPSS, data screened and descriptive statistics produced. Free text responses were analysed and tasks collated into categories reflecting the type of work involved in each task. Responses received were 393 (28%, n = 1380). Results were organised into five groups: i.e., hospital, community, primary care, General Practitioner (GP) practice and other (which included HM Prison Service). Thirty tasks were reported as commonly undertaken in three or more settings and 206 (84.7%, n = 243) pharmacy technicians reported they would like to expand their role. Tasks core to hospital and community pharmacy should be considered for inclusion to initial education standards to reflect current practice. Post qualification, pharmacy technicians indicate a significant desire to expand clinically and managerially allowing pharmacists more time in patient-facing/clinical roles.

How evidence from observing attending physicians links to a competency-based framework.

PubMed

Bacchus, Maria; Ward, David R; de Grood, Jill; Lemaire, Jane B

2017-06-01

Competency-based medical education frameworks are often founded on a combination of existing research, educational principles and expert consensus. Our objective was to examine how components of the attending physician role, as determined by observing preceptors during their real-world work, link to the CanMEDS Physician Competency Framework. This is a sub-study of a broader study exploring the role of the attending physician by observing these doctors during their working day. The parent study revealed three overarching elements of the role that emerged from 14 themes and 123 sub-themes: (i) Competence, defined as the execution of traditional physician competencies; (ii) Context, defined as the environment in which the role is carried out, and (iii) Conduct, defined as the manner of acting, or behaviours and attitudes in the role that helped to negotiate the complex environment. In this sub-study, each sub-theme, or 'role-related component', was mapped to the competencies described in the CanMEDS 2005 and 2015 frameworks. Many role-related components from the Competence element were represented in the 2015 CanMEDS framework. No role-related components from the Context element were represented. Some role-related components from the Conduct element were represented. These Conduct role-related components were better represented in the 2015 CanMEDS framework than in the 2005 framework. This study shows how the real-world work of attending physicians links to the CanMEDS framework and provides empirical data identifying disconnects between espoused and observed behaviours. There is a conceptual gap where the contextual influences of physicians' work and the competencies required to adjust to these influences are missing from the framework. These concepts should be incorporated into learning both broadly, such as through an emphasis on context within curriculum development for the workplace (e.g. entrustable professional activities), and explicitly, through the introduction of novel competencies (e.g. the Conduct role-related components described in this study). © 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Characterization of Ferroplasma acidiphilum growing in pure and mixed culture with Leptospirillum ferriphilum.

PubMed

Merino, M P; Andrews, B A; Parada, P; Asenjo, J A

2016-11-01

Biomining is defined as biotechnology for metal recovery from minerals, and is promoted by the concerted effort of a consortium of acidophile prokaryotes, comprised of members of the Bacteria and Archaea domains. Ferroplasma acidiphilum and Leptospirillum ferriphilum are the dominant species in extremely acid environments and have great use in bioleaching applications; however, the role of each species in this consortia is still a subject of research. The hypothesis of this work is that F. acidiphilum uses the organic matter secreted by L. ferriphilum for growth, maintaining low levels of organic compounds in the culture medium, preventing their toxic effects on L. ferriphilum. To test this hypothesis, a characterization of Ferroplasma acidiphilum strain BRL-115 was made with the objective of determining its optimal growth conditions. Subsequently, under the optimal conditions, L. ferriphilum and F. acidiphilum were tested growing in each other's supernatant, in order to define if there was exchange of metabolites between the species. With these results, a mixed culture in batch cyclic operation was performed to obtain main specific growth rates, which were used to evaluate a mixed metabolic model previously developed by our group. It was observed that F. acidiphilum, strain BRL-115 is a chemomixotrophic organism, and its growth is maximized with yeast extract at a concentration of 0.04% wt/vol. From the experiments of L. ferriphilum growing on F. acidiphilum supernatant and vice versa, it was observed that in both cases cell growth is favorably affected by the presence of the filtered medium of the other microorganism, proving a synergistic interaction between these species. Specific growth rates were obtained in cyclic batch operation of the mixed culture and were used as input data for a Flux Balance Analysis of the mixed metabolic model, obtaining a reasonable behavior of the metabolic fluxes and the system as a whole, therefore consolidating the model previously developed. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1390-1396, 2016. © 2016 American Institute of Chemical Engineers.

Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study.

PubMed

Lidbury, Brett A; Kita, Badia; Lewis, Donald P; Hayward, Susan; Ludlow, Helen; Hedger, Mark P; de Kretser, David M

2017-03-16

Investigations of activin family proteins as serum biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). CFS/ME is a disease with complex, wide-ranging symptoms, featuring persistent fatigue of 6 months or longer, particularly post exertion. No definitive biomarkers are available. A cross-sectional, observational study of CFS/ME patients fulfilling the 2003 Canadian Consensus Criteria, in parallel with healthy non-fatigued controls, was conducted. Comparisons with a previously defined activin reference population were also performed. For the total study cohort the age range was 18-65 years with a female: male participant ratio of greater than 3:1. All participants were assessed via a primary care community clinic. Blood samples were collected for pathology testing after physical examination and orthostatic intolerance assessment. Cytokines, activin A, activin B and follistatin were also measured in sera from these samples. All data were compared between the CFS/ME and control cohorts, with the activins and follistatin also compared with previously defined reference intervals. Serum activin B levels for CFS/ME participants were significantly elevated when compared to the study controls, as well as the established reference interval. Serum activin A and follistatin were within their normal ranges. All routine and special pathology markers were within the normal laboratory reference intervals for the total study cohort, with no significant differences detected between CFS/ME and control groups. Also, no significant differences were detected for IL-2, IL-4, IL-6, IL-10, IL-17A, TNF or IFN-gamma. Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.

Streptococcus pneumoniae Endohexosaminidase D, Structural and Mechanistic Insight into Substrate-Assisted Catalysis in Family 85 Glycoside Hydrolases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbott, D.; Macauley, M; Vocadlo, D

2009-01-01

Endo-?-d-glucosaminidases from family 85 of glycoside hydrolases (GH85 endohexosaminidases) act to cleave the glycosidic linkage between the two N-acetylglucosamine units that make up the chitobiose core of N-glycans. Endohexosaminidase D (Endo-D), produced by Streptococcus pneumoniae, is believed to contribute to the virulence of this organism by playing a role in the deglycosylation of IgG antibodies. Endohexosaminidases have received significant attention for this reason and, moreover, because they are powerful tools for chemoenzymatic synthesis of proteins having defined glycoforms. Here we describe mechanistic and structural studies of the catalytic domain (SpGH85) of Endo-D that provide compelling support for GH85 enzymes usingmore » a catalytic mechanism involving substrate-assisted catalysis. Furthermore, the structure of SpGH85 in complex with the mechanism-based competitive inhibitor NAG-thiazoline (Kd = 28 ?m) provides a coherent rationale for previous mutagenesis studies of Endo-D and other related GH85 enzymes. We also find GH85, GH56, and GH18 enzymes have a similar configuration of catalytic residues. Notably, GH85 enzymes have an asparagine in place of the aspartate residue found in these other families of glycosidases. We propose that this residue, as the imidic acid tautomer, acts analogously to the key catalytic aspartate of GH56 and GH18 enzymes. This topographically conserved arrangement of the asparagine residue and a conserved glutamic acid, coupled with previous kinetic studies, suggests these enzymes may use an unusual proton shuttle to coordinate effective general acid and base catalysis to aid cleavage of the glycosidic bond. These results collectively provide a blueprint that may be used to facilitate protein engineering of these enzymes to improve their function as biocatalysts for synthesizing glycoproteins having defined glycoforms and also may serve as a guide for generating inhibitors of GH85 enzymes.« less

Transfer matrix computation of critical polynomials for two-dimensional Potts models

DOE PAGES

Jacobsen, Jesper Lykke; Scullard, Christian R.

2013-02-04

We showed, In our previous work, that critical manifolds of the q-state Potts model can be studied by means of a graph polynomial P B(q, v), henceforth referred to as the critical polynomial. This polynomial may be defined on any periodic two-dimensional lattice. It depends on a finite subgraph B, called the basis, and the manner in which B is tiled to construct the lattice. The real roots v = e K — 1 of P B(q, v) either give the exact critical points for the lattice, or provide approximations that, in principle, can be made arbitrarily accurate by increasingmore » the size of B in an appropriate way. In earlier work, P B(q, v) was defined by a contraction-deletion identity, similar to that satisfied by the Tutte polynomial. Here, we give a probabilistic definition of P B(q, v), which facilitates its computation, using the transfer matrix, on much larger B than was previously possible.We present results for the critical polynomial on the (4, 8 2), kagome, and (3, 12 2) lattices for bases of up to respectively 96, 162, and 243 edges, compared to the limit of 36 edges with contraction-deletion. We discuss in detail the role of the symmetries and the embedding of B. The critical temperatures v c obtained for ferromagnetic (v > 0) Potts models are at least as precise as the best available results from Monte Carlo simulations or series expansions. For instance, with q = 3 we obtain v c(4, 8 2) = 3.742 489 (4), v c(kagome) = 1.876 459 7 (2), and v c(3, 12 2) = 5.033 078 49 (4), the precision being comparable or superior to the best simulation results. More generally, we trace the critical manifolds in the real (q, v) plane and discuss the intricate structure of the phase diagram in the antiferromagnetic (v < 0) region.« less

Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munira A Kadhim

2010-03-05

To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry andmore » risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim to uncover protein mediators of the bystander responses using advanced proteomic screening of factors released from irradiated, bystander and unstable cells. Integral to these studies will be an assessment of the role of genetic susceptibility in these responses, using CBA/H and C57BL/6J mice. The relevance of in vivo interactions between stem cells and the stem cell niche will be explored in the future by re-implantation techniques of previously irradiated cells. The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program.« less

One amino acid in mouse activated factor VII defines its endothelial protein C receptor (EPCR) binding and modulates its EPCR-dependent hemostatic activity in vivo.

PubMed

Pavani, G; Zintner, S M; Ivanciu, L; Small, J C; Stafford, K A; Szeto, J H; Margaritis, P

2017-03-01

Essentials The lack of factor (F) VIIa-endothelial protein C receptor (EPCR) binding in mice is unresolved. A single substitution of Leu4 to Phe in mouse FVIIa (mFVIIa) enables its interaction with EPCR. mFVIIa with a Phe4 shows EPCR binding-dependent enhanced hemostatic function in vivo vs. mFVIIa. Defining the FVIIa-EPCR interaction in mice allows for further investigating its biology in vivo. Background Human activated factor VII (hFVIIa), which is used in hemophilia treatment, binds to the endothelial protein C (PC) receptor (EPCR) with unclear hemostatic consequences. Interestingly, mice lack the activated FVII (FVIIa)-EPCR interaction. Therefore, to investigate the hemostatic consequences of this interaction in hemophilia, we previously engineered a mouse FVIIa (mFVIIa) molecule that bound mouse EPCR (mEPCR) by using three substitutions from mouse PC (mPC), i.e. Leu4→Phe, Leu8→Met, and Trp9→Arg. The resulting molecule, mFVIIa-FMR, modeled the EPCR-binding properties of hFVIIa and showed enhanced hemostatic capacity in hemophilic mice versus mFVIIa. These data implied a role of EPCR in the action of hFVIIa in hemophilia treatment. However, the substitutions in mFVIIa-FMR only broadly defined the sequence determinants for its mEPCR interaction and enhanced function in vivo. Objectives To determine the individual contributions of mPC Phe4, Met8 and Arg9 to the in vitro/in vivo properties of mFVIIa-FMR. Methods The mEPCR-binding properties of single amino acid variants of mFVIIa or mPC at position 4, 8 or 9 were investigated. Results and conclusions Phe4 in mFVIIa or mPC was solely critical for interaction with mEPCR. In hemophilic mice, administration of mFVIIa harboring a Phe4 resulted in a 1.9-2.5-fold increased hemostatic capacity versus mFVIIa that was EPCR binding-dependent. This recapitulated previous observations made with triple-mutant mFVIIa-FMR. As Leu8 is crucial for hFVIIa-EPCR binding, we describe the sequence divergence of this interaction in mice, now allowing its further characterization in vivo. We also illustrate that modulation of the EPCR-FVIIa interaction may lead to improved FVIIa therapeutics. © 2016 International Society on Thrombosis and Haemostasis.

The Inverse Relation Between Risks and Benefits: The Role of Affect and Expertise.

PubMed

Sokolowska, Joanna; Sleboda, Patrycja

2015-07-01

Although risk and benefits of risky activities are positively correlated in the real world, empirical results indicate that people perceive them as negatively correlated. The common explanation is that confounding benefits and losses stems from affect. In this article, we address the issue that has not been clearly established in studies on the affect heuristic: to what extent boundary conditions, such as judgments' generality and expertise, influence the presence of the inverse relation in judgments of hazards. These conditions were examined in four studies in which respondents evaluated general or specific benefits and risks of "affect-rich" and "affect-poor" hazards (ranging from investments to applications of stem cell research). In line with previous research, affect is defined as good or bad feelings integral to a stimulus. In contrast to previous research, affect is considered as related both to personal feelings and to social controversies associated with a hazard. Expertise is related to personal knowledge (laypersons vs. experts) as well as to objective knowledge (targets well vs. poorly known to science). The direct comparison of the input from personal and objective ignorance into the inverse relation has not been investigated previously. It was found that affect invoked by a hazard guides general but not specific judgments of its benefits and risks. Technical expertise helps to avoid simplified evaluations of consequences as long as they are well known to science. For new, poorly understood hazards (e.g., stem cell research), expertise does not protect from the perception of the inverse relation between benefits and risks. © 2015 Society for Risk Analysis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Richard; Brigham and Women's Hospital, Boston, Massachusetts; Polishchuk, Alexei

Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse inmore » initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.« less

Dragon (Repulsive Guidance Molecule RGMb) Inhibits E-cadherin Expression and Induces Apoptosis in Renal Tubular Epithelial Cells*

PubMed Central

Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y.; Xia, Yin

2013-01-01

Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45–66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo. PMID:24052264

Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implications for drug design

PubMed Central

Omari, Kamel EL; Bronckaers, Annelies; Liekens, Sandra; Pérez-Pérez, Maria-Jésus; Balzarini, Jan; Stammers, David K.

2006-01-01

HTP (human thymidine phosphorylase), also known as PD-ECGF (platelet-derived endothelial cell growth factor) or gliostatin, has an important role in nucleoside metabolism. HTP is implicated in angiogenesis and apoptosis and therefore is a prime target for drug design, including antitumour therapies. An HTP structure in a closed conformation complexed with an inhibitor has previously been solved. Earlier kinetic studies revealed an ordered release of thymine followed by ribose phosphate and product inhibition by both ligands. We have determined the structure of HTP from crystals grown in the presence of thymidine, which, surprisingly, resulted in bound thymine with HTP in a closed dead-end com-plex. Thus thymine appears to be able to reassociate with HTP after its initial ordered release before ribose phosphate and induces the closed conformation, hence explaining the mechanism of non-competitive product inhibition. In the active site in one of the four HTP molecules within the crystal asymmetric unit, additional electron density is present. This density has not been previously seen in any pyrimidine nucleoside phosphorylase and it defines a subsite that may be exploitable in drug design. Finally, because our crystals did not require proteolysed HTP to grow, the structure reveals a loop (residues 406–415), disordered in the previous HTP structure. This loop extends across the active-site cleft and appears to stabilize the dimer interface and the closed conformation by hydrogen-bonding. The present study will assist in the design of HTP inhibitors that could lead to drugs for anti-angiogenesis as well as for the potentiation of other nucleoside drugs. PMID:16803458

Review of historical unusual mortality events (UMEs) in the Gulf of Mexico (1990-2009): providing context for the multi-year northern Gulf of Mexico cetacean UME declared in 2010.

PubMed

Litz, Jenny A; Baran, Melody A; Bowen-Stevens, Sabrina R; Carmichael, Ruth H; Colegrove, Kathleen M; Garrison, Lance P; Fire, Spencer E; Fougeres, Erin M; Hardy, Ron; Holmes, Secret; Jones, Wanda; Mase-Guthrie, Blair E; Odell, Daniel K; Rosel, Patricia E; Saliki, Jeremiah T; Shannon, Delphine K; Shippee, Steve F; Smith, Suzanne M; Stratton, Elizabeth M; Tumlin, Mandy C; Whitehead, Heidi R; Worthy, Graham A J; Rowles, Teresa K

2014-12-02

An unusual mortality event (UME) was declared for cetaceans in the northern Gulf of Mexico (GoM) for Franklin County, Florida, west through Louisiana, USA, beginning in February 2010 and was ongoing as of September 2014. The 'Deepwater Horizon' (DWH) oil spill began on 20 April 2010 in the GoM, raising questions regarding the potential role of the oil spill in the UME. The present study reviews cetacean mortality events that occurred in the GoM prior to 2010 (n = 11), including causes, durations, and some specific test results, to provide a historical context for the current event. The average duration of GoM cetacean UMEs prior to 2010 was 6 mo, and the longest was 17 mo (2005-2006). The highest number of cetacean mortalities recorded during a previous GoM event was 344 (in 1990). In most previous events, dolphin morbillivirus or brevetoxicosis was confirmed or suspected as a causal factor. In contrast, the current northern GoM UME has lasted more than 48 mo and has had more than 1000 reported mortalities within the currently defined spatial and temporal boundaries of the event. Initial results from the current UME do not support either morbillivirus or brevetoxin as primary causes of this event. This review is the first summary of cetacean UMEs in the GoM and provides evidence that the most common causes of previous UMEs are unlikely to be associated with the current UME.

Structural and functional role of bases 32 and 33 in the anticodon loop of yeast mitochondrial tRNAIle

PubMed Central

Montanari, Arianna; De Luca, Cristina; Di Micco, Patrizio; Morea, Veronica; Frontali, Laura; Francisci, Silvia

2011-01-01

Previous work has demonstrated the usefulness of the yeast model to investigate the molecular mechanisms underlying defects due to base substitutions in mitochondrial tRNA genes, and to identify suppressing molecules endowed with potential clinical relevance. The present paper extends these investigations to two human equivalent yeast mutations located at positions 32 and 33 in the anticodon loop of tRNAIle. Notwithstanding the proximity of the two T>C base substitutions, the effects of these mutations have been found to be quite different in yeast, as they are in human. The T32C substitution has a very severe effect in yeast, consisting in a complete inhibition of growth on nonfermentable substrates. Conversely, respiratory defects caused by the T33C mutation could only be observed in a defined genetic context. Analyses of available sequences and selected tRNA three-dimensional structures were performed to provide explanations for the different behavior of these adjacent mutations. Examination of the effects of previously identified suppressors demonstrated that overexpression of the TUF1 gene did not rescue the defective phenotypes determined by either mutation, possibly as a consequence of the lack of interactions between EF-Tu and the tRNA anticodon arm in known structures. On the contrary, both the cognate IleRS and the noncognate LeuRS and ValRS are endowed with suppressing activities toward both mutations. This allows us to extend to the tRNAIle mutants the cross-suppression activity of aminoacyl-tRNA synthetases previously demonstrated for tRNALeu and tRNAVal mutants. PMID:21914842