Rapid, Optimized Interactomic Screening
Hakhverdyan, Zhanna; Domanski, Michal; Hough, Loren; Oroskar, Asha A.; Oroskar, Anil R.; Keegan, Sarah; Dilworth, David J.; Molloy, Kelly R.; Sherman, Vadim; Aitchison, John D.; Fenyö, David; Chait, Brian T.; Jensen, Torben Heick; Rout, Michael P.; LaCava, John
2015-01-01
We must reliably map the interactomes of cellular macromolecular complexes in order to fully explore and understand biological systems. However, there are no methods to accurately predict how to capture a given macromolecular complex with its physiological binding partners. Here, we present a screen that comprehensively explores the parameters affecting the stability of interactions in affinity-captured complexes, enabling the discovery of physiological binding partners and the elucidation of their functional interactions in unparalleled detail. We have implemented this screen on several macromolecular complexes from a variety of organisms, revealing novel profiles even for well-studied proteins. Our approach is robust, economical and automatable, providing an inroad to the rigorous, systematic dissection of cellular interactomes. PMID:25938370
Rönnberg, Tuomas; Jääskeläinen, Kirsi; Blot, Guillaume; Parviainen, Ville; Vaheri, Antti; Renkonen, Risto; Bouloy, Michele; Plyusnin, Alexander
2012-01-01
Hantaviruses (Bunyaviridae) are negative-strand RNA viruses with a tripartite genome. The small (S) segment encodes the nucleocapsid protein and, in some hantaviruses, also the nonstructural protein (NSs). The aim of this study was to find potential cellular partners for the hantaviral NSs protein. Toward this aim, yeast two-hybrid (Y2H) screening of mouse cDNA library was performed followed by a search for potential NSs protein counterparts via analyzing a cellular interactome. The resulting interaction network was shown to form logical, clustered structures. Furthermore, several potential binding partners for the NSs protein, for instance ACBD3, were identified and, to prove the principle, interaction between NSs and ACBD3 proteins was demonstrated biochemically.
Functional advantages of dynamic protein disorder.
Berlow, Rebecca B; Dyson, H Jane; Wright, Peter E
2015-09-14
Intrinsically disordered proteins participate in many important cellular regulatory processes. The absence of a well-defined structure in the free state of a disordered domain, and even on occasion when it is bound to physiological partners, is fundamental to its function. Disordered domains are frequently the location of multiple sites for post-translational modification, the key element of metabolic control in the cell. When a disordered domain folds upon binding to a partner, the resulting complex buries a far greater surface area than in an interaction of comparably-sized folded proteins, thus maximizing specificity at modest protein size. Disorder also maintains accessibility of sites for post-translational modification. Because of their inherent plasticity, disordered domains frequently adopt entirely different structures when bound to different partners, increasing the repertoire of available interactions without the necessity for expression of many different proteins. This feature also adds to the faithfulness of cellular regulation, as the availability of a given disordered domain depends on competition between various partners relevant to different cellular processes. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Huang, Bill X.; Kim, Hee-Yong
2013-01-01
Akt is a critical protein for cell survival and known to interact with various proteins. However, Akt binding partners that modulate or regulate Akt activation have not been fully elucidated. Identification of Akt-interacting proteins has been customarily achieved by co-immunoprecipitation combined with western blot and/or MS analysis. An intrinsic problem of the method is loss of interacting proteins during procedures to remove non-specific proteins. Moreover, antibody contamination often interferes with the detection of less abundant proteins. Here, we developed a novel two-step chemical crosslinking strategy to overcome these problems which resulted in a dramatic improvement in identifying Akt interacting partners. Akt antibody was first immobilized on protein A/G beads using disuccinimidyl suberate and allowed to bind to cellular Akt along with its interacting proteins. Subsequently, dithiobis[succinimidylpropionate], a cleavable crosslinker, was introduced to produce stable complexes between Akt and binding partners prior to the SDS-PAGE and nanoLC-MS/MS analysis. This approach enabled identification of ten Akt partners from cell lysates containing as low as 1.5 mg proteins, including two new potential Akt interacting partners. None of these but one protein was detectable without crosslinking procedures. The present method provides a sensitive and effective tool to probe Akt-interacting proteins. This strategy should also prove useful for other protein interactions, particularly those involving less abundant or weakly associating partners. PMID:23613850
Prugh, Amber M; Cole, Stephanie D; Glaros, Trevor; Angelini, Daniel J
2017-03-25
Mesenchymal stem cells (MSCs) are multipotent cells located within various adult tissues. Recent literature has reported that human bone marrow-derived MSCs express active acetylcholinesterase (AChE) and that disruption of AChE activity by organophosphate (OP) chemicals decreases the ability of MSCs to differentiate into osteoblasts. The potential role of AChE in regulating MSC proliferation and differentiation is currently unknown. In the present study, we demonstrate that MSCs exposed to OPs have both decreased AChE activity and abundance. In addition, exposure to these OPs induced cellular death while decreasing cellular proliferation. Exposures to these compounds also reduced the adipogenic/osteogenic differentiation potentials of the MSCs. To elucidate the possible role of AChE in MSCs signaling following OP exposure, we captured potential AChE binding partners by performing polyhistidine (His 8 )-tagged AChE pulldowns, followed by protein identification using liquid chromatography mass spectrometry (LC-MS). Using this method, we determined that the focal adhesion protein, vinculin, is a potential binding partner with AChE in MSCs and these initial findings were confirmed with follow-up co-immunoprecipitation experiments. Identifying AChE binding partners helps to determine potential pathways associated with MSC proliferation and differentiation, and this understanding could lead to the development of future MSC-based tissue repair therapies. Published by Elsevier B.V.
Compartmentalized partnered replication for the directed evolution of genetic parts and circuits.
Abil, Zhanar; Ellefson, Jared W; Gollihar, Jimmy D; Watkins, Ella; Ellington, Andrew D
2017-12-01
Compartmentalized partnered replication (CPR) is an emulsion-based directed evolution method based on a robust and modular phenotype-genotype linkage. In contrast to other in vivo directed evolution approaches, CPR largely mitigates host fitness effects due to a relatively short expression time of the gene of interest. CPR is based on gene circuits in which the selection of a 'partner' function from a library leads to the production of a thermostable polymerase. After library preparation, bacteria produce partner proteins that can potentially lead to enhancement of transcription, translation, gene regulation, and other aspects of cellular metabolism that reinforce thermostable polymerase production. Individual cells are then trapped in water-in-oil emulsion droplets in the presence of primers and dNTPs, followed by the recovery of the partner genes via emulsion PCR. In this step, droplets with cells expressing partner proteins that promote polymerase production will produce higher copy numbers of the improved partner gene. The resulting partner genes can subsequently be recloned for the next round of selection. Here, we present a step-by-step guideline for the procedure by providing examples of (i) selection of T7 RNA polymerases that recognize orthogonal promoters and (ii) selection of tRNA for enhanced amber codon suppression. A single round of CPR should take ∼3-5 d, whereas a whole directed evolution can be performed in 3-10 rounds, depending on selection efficiency.
Yang, Hui; Li, Jing-Jing; Liu, Shuai; Zhao, Jian; Jiang, Ya-Jun; Song, Ai-Xin; Hu, Hong-Yu
2014-01-01
Expansion of polyglutamine (polyQ) tract may cause protein misfolding and aggregation that lead to cytotoxicity and neurodegeneration, but the underlying mechanism remains to be elucidated. We applied ataxin-3 (Atx3), a polyQ tract-containing protein, as a model to study sequestration of normal cellular proteins. We found that the aggregates formed by polyQ-expanded Atx3 sequester its interacting partners, such as P97/VCP and ubiquitin conjugates, into the protein inclusions through specific interactions both in vitro and in cells. Moreover, this specific sequestration impairs the normal cellular function of P97 in down-regulating neddylation. However, expansion of polyQ tract in Atx3 does not alter the conformation of its surrounding regions and the interaction affinities with the interacting partners, although it indeed facilitates misfolding and aggregation of the Atx3 protein. Thus, we propose a loss-of-function pathology for polyQ diseases that sequestration of the cellular essential proteins via specific interactions into inclusions by the polyQ aggregates causes dysfunction of the corresponding proteins, and consequently leads to neurodegeneration. PMID:25231079
Rai, Vandna; Sharma, Naveen Kumar; Rai, Ashwani K
2006-09-01
Salinity, at a concentration of 10 mM NaCl affected the growth of Azolla pinnata-Anabaena azollae association and became lethal at 40 mM. Plants exposed up to 30 mM NaCl exhibited longer roots than the control, especially during the beginning of incubation. Average root number in plants exposed to 10 and 20 mM NaCl remained almost the same as in control. A further rise in NaCl concentration to 30 mM reduced the root number, and roots shed off at 40 mM NaCl. Presence of NaCl in the nutrient solution increased the cellular Na+ of the intact association exhibiting differential accumulation by individual partners, while it reduced the cellular Ca2+ level. However, cellular K+ content did not show significant change. Cellular Na+ based on fresh weight of respective individual partners (host tissues and cyanobiont) remained higher in the host tissues than the cyanobiont, while reverse was true for K+ and Ca2+ contents. The contribution of A. azollae in the total cellular ion content of the association was a little because of meagre contribution of the cyanobiont mass (19-21%). High salt sensitivity of Azolla-Anabaena complex is due to an inability of the association to maintain low Na+ and high Ca2+ cellular level.
Changing partners at the dance
Kallal, Lara E.; Biron, Christine A.
2013-01-01
Differential use of cellular and molecular components shapes immune responses, but understanding of how these are regulated to promote defense and health during infections is still incomplete. Examples include signaling from members of the Janus activated kinase-signal transducer and activator of transcription (JAK-STAT) cytokine family. Following receptor stimulation, individual JAK-STAT cytokines have preferences for particular key STAT molecules to lead to specific cellular responses. Certain of these cytokines, however, can conditionally activate alternative STATs as well as elicit pleiotropic and paradoxical effects. Studies examining basal and infection conditions are revealing intrinsic and induced cellular differences in various intracellular STAT concentrations to control the biological consequences of cytokine exposure. The system can be likened to changing partners at a dance based on competition and relative availability, and sets a framework for understanding the particular conditions promoting subset biological functions of cytokines as needed during evolving immune responses to infections. PMID:24058795
NASA Astrophysics Data System (ADS)
Herling, Therese; Linse, Sara; Knowles, Tuomas
2015-03-01
Non-covalent and transient protein-ligand interactions are integral to cellular function and malfunction. Key steps in signalling and regulatory pathways rely on reversible non-covalent protein-protein binding or ion chelation. Here we present a microfluidic free-flow electrophoresis method for detecting and characterising protein-ligand interactions in solution. We apply this method to probe the binding equilibria of calmodulin, a central protein to calcium signalling pathways. In this study we characterise the specific binding of calmodulin to phosphorylase kinase, a known target, and creatine kinase, which we identify as a putative binding partner through a protein array screen and surface plasmon resonance experiments. We verify the interaction between calmodulin and creatine kinase in solution using free-flow electrophoresis and investigate the effect of calcium and sodium chloride on the calmodulin-ligand binding affinity in free solution without the presence of a potentially interfering surface. Our results demonstrate the general applicability of quantitative microfluidic electrophoresis to characterise binding equilibria between biomolecules in solution.
Giss, Dominic; Kemmerling, Simon; Dandey, Venkata; Stahlberg, Henning; Braun, Thomas
2014-05-20
Multimolecular protein complexes are important for many cellular processes. However, the stochastic nature of the cellular interactome makes the experimental detection of complex protein assemblies difficult and quantitative analysis at the single molecule level essential. Here, we present a fast and simple microfluidic method for (i) the quantitative isolation of endogenous levels of untagged protein complexes from minute volumes of cell lysates under close to physiological conditions and (ii) the labeling of specific components constituting these complexes. The method presented uses specific antibodies that are conjugated via a photocleavable linker to magnetic beads that are trapped in microcapillaries to immobilize the target proteins. Proteins are released by photocleavage, eluted, and subsequently analyzed by quantitative transmission electron microscopy at the single molecule level. Additionally, before photocleavage, immunogold can be employed to label proteins that interact with the primary target protein. Thus, the presented method provides a new way to study the interactome and, in combination with single molecule transmission electron microscopy, to structurally characterize the large, dynamic, heterogeneous multimolecular protein complexes formed.
Intimate partner violence, technology, and stalking.
Southworth, Cynthia; Finn, Jerry; Dawson, Shawndell; Fraser, Cynthia; Tucker, Sarah
2007-08-01
This research note describes the use of a broad range of technologies in intimate partner stalking, including cordless and cellular telephones, fax machines, e-mail, Internet-based harassment, global positioning systems, spy ware, video cameras, and online databases. The concept of "stalking with technology" is reviewed, and the need for an expanded definition of cyberstalking is presented. Legal issues and advocacy-centered responses, including training, legal remedies, public policy issues, and technology industry practices, are discussed.
Action mechanisms of Liver X Receptors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gabbi, Chiara; Warner, Margaret; Gustafsson, Jan-Åke, E-mail: jgustafs@central.uh.edu
2014-04-11
Highlights: • LXRα and LXRβ are ligand-activated nuclear receptors. • They share oxysterol ligands and the same heterodimerization partner, RXR. • LXRs regulate lipid and glucose metabolism, CNS and immune functions, and water transport. - Abstract: The two Liver X Receptors, LXRα and LXRβ, are nuclear receptors belonging to the superfamily of ligand-activated transcription factors. They share more than 78% homology in amino acid sequence, a common profile of oxysterol ligands and the same heterodimerization partner, Retinoid X Receptor. LXRs play crucial roles in several metabolic pathways: lipid metabolism, in particular in preventing cellular cholesterol accumulation; glucose homeostasis; inflammation; centralmore » nervous system functions and water transport. As with all nuclear receptors, the transcriptional activity of LXR is the result of an orchestration of numerous cellular factors including ligand bioavailability, presence of corepressors and coactivators and cellular context i.e., what other pathways are activated in the cell at the time the receptor recognizes its ligand. In this mini-review we summarize the factors regulating the transcriptional activity and the mechanisms of action of these two receptors.« less
Regulation of ROCK Activity in Cancer
Morgan-Fisher, Marie; Wewer, Ulla M.
2013-01-01
Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)–loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer. PMID:23204112
Prediction of physical protein protein interactions
NASA Astrophysics Data System (ADS)
Szilágyi, András; Grimm, Vera; Arakaki, Adrián K.; Skolnick, Jeffrey
2005-06-01
Many essential cellular processes such as signal transduction, transport, cellular motion and most regulatory mechanisms are mediated by protein-protein interactions. In recent years, new experimental techniques have been developed to discover the protein-protein interaction networks of several organisms. However, the accuracy and coverage of these techniques have proven to be limited, and computational approaches remain essential both to assist in the design and validation of experimental studies and for the prediction of interaction partners and detailed structures of protein complexes. Here, we provide a critical overview of existing structure-independent and structure-based computational methods. Although these techniques have significantly advanced in the past few years, we find that most of them are still in their infancy. We also provide an overview of experimental techniques for the detection of protein-protein interactions. Although the developments are promising, false positive and false negative results are common, and reliable detection is possible only by taking a consensus of different experimental approaches. The shortcomings of experimental techniques affect both the further development and the fair evaluation of computational prediction methods. For an adequate comparative evaluation of prediction and high-throughput experimental methods, an appropriately large benchmark set of biophysically characterized protein complexes would be needed, but is sorely lacking.
Interaction between Herpes Simplex Virus Type 1 IE63 Protein and Cellular Protein p32
Bryant, Helen E.; Matthews, David A.; Wadd, Sarah; Scott, James E.; Kean, Joy; Graham, Susan; Russell, William C.; Clements, J. Barklie
2000-01-01
The herpes simplex virus type 1 (HSV-1) immediate-early gene IE63 (ICP27), the only HSV-1 regulatory gene with a homologue in every mammalian and avian herpesvirus sequenced so far, is a multifunctional protein which regulates transcriptional and posttranscriptional processes. One of its posttranscriptional effects is the inhibition of splicing of viral and cellular transcripts. We previously identified heterogeneous nuclear ribonucleoprotein (hnRNP) K and casein kinase 2 (CK2) as two protein partners of IE63 (H. Bryant et al., J. Biol. Chem. 274:28991–28998, 1999). Here, using a yeast two-hybrid assay, we identify another partner of IE63, the cellular protein p32. Confirmation of this interaction was provided by coimmunoprecipitation from virus-infected cells and recombinant p32 binding assays. A p32-hnRNP K-CK2 complex, which required IE63 to form, was isolated from HSV-1-infected cells, and coimmunoprecipitating p32 was phosphorylated by CK2. Expression of IE63 altered the cytoplasmic distribution of p32, with some now colocalizing with IE63 in the nuclei of infected and transfected cells. As p32 copurifies with splicing factors and can inhibit splicing, we propose that IE63 together with p32, possibly with other IE63 partner proteins, acts to disrupt or regulate pre-mRNA splicing. As well as contributing to host cell shutoff, this effect could facilitate splicing-independent nuclear export of viral transcripts. PMID:11070032
Interaction between herpes simplex virus type 1 IE63 protein and cellular protein p32.
Bryant, H E; Matthews, D A; Wadd, S; Scott, J E; Kean, J; Graham, S; Russell, W C; Clements, J B
2000-12-01
The herpes simplex virus type 1 (HSV-1) immediate-early gene IE63 (ICP27), the only HSV-1 regulatory gene with a homologue in every mammalian and avian herpesvirus sequenced so far, is a multifunctional protein which regulates transcriptional and posttranscriptional processes. One of its posttranscriptional effects is the inhibition of splicing of viral and cellular transcripts. We previously identified heterogeneous nuclear ribonucleoprotein (hnRNP) K and casein kinase 2 (CK2) as two protein partners of IE63 (H. Bryant et al., J. Biol. Chem. 274:28991-28998, 1999). Here, using a yeast two-hybrid assay, we identify another partner of IE63, the cellular protein p32. Confirmation of this interaction was provided by coimmunoprecipitation from virus-infected cells and recombinant p32 binding assays. A p32-hnRNP K-CK2 complex, which required IE63 to form, was isolated from HSV-1-infected cells, and coimmunoprecipitating p32 was phosphorylated by CK2. Expression of IE63 altered the cytoplasmic distribution of p32, with some now colocalizing with IE63 in the nuclei of infected and transfected cells. As p32 copurifies with splicing factors and can inhibit splicing, we propose that IE63 together with p32, possibly with other IE63 partner proteins, acts to disrupt or regulate pre-mRNA splicing. As well as contributing to host cell shutoff, this effect could facilitate splicing-independent nuclear export of viral transcripts.
Hacker, Benedikt; Schultheiß, Christoph; Döring, Michael; Kurzik-Dumke, Ursula
2018-06-01
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1. We disclose the building of hNOT/ALG3 homodimers and provide experimental evidence for its in vivo interaction with the functionally linked proteins OSBP, OSBPL9 and LRP1, the SYPL1 protein and the transcription factor CREB3. Regarding the latter, we show that the 55 kDa N-glycosylated hNOT-1/ALG3-1 molecule binds the N-glycosylated CREB3 precursor but does not interact with CREB3's proteolytic products specific to the endoplasmic reticulum and to the nucleus. The interaction between the two partners is a prerequisite for the proteolytic activation of CREB3. In case of the further binding partners, our data suggest that hNOT-1/ALG3-1 interacts with both OSBPs and with their direct targets LRP1 and VAMP/VAP-A. Moreover, our results show that various partners of hNOT-1/ALG3-1 interact with its diverse post translationally processed products destined to distinct cellular compartments. Generally, our data suggest the involvement of hNOT-1/ALG3-1 in various molecular contexts determining essential processes associated with distinct cellular machineries and related to various pathologies, such as cancer, viral infections, neuronal and immunological disorders and CDG.
Ligand-promoted protein folding by biased kinetic partitioning.
Hingorani, Karan S; Metcalf, Matthew C; Deming, Derrick T; Garman, Scott C; Powers, Evan T; Gierasch, Lila M
2017-04-01
Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems.
Ligand-Promoted Protein Folding by Biased Kinetic Partitioning
Hingorani, Karan S.; Metcalf, Matthew C.; Deming, Derrick T.; Garman, Scott C.; Powers, Evan T.; Gierasch, Lila M.
2017-01-01
Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems. PMID:28218913
Nogales, Eva; Kellogg, Elizabeth H
2017-10-01
As non-crystallizable polymers, microtubules have been the target of cryo-electron microscopy (cryo-EM) studies since the technique was first established. Over the years, image processing strategies have been developed that take care of the unique, pseudo-helical symmetry of the microtubule. With recent progress in data quality and data processing, cryo-EM reconstructions are now reaching resolutions that allow the generation of atomic models of microtubules and the factors that bind them. These include cellular partners that contribute to microtubule cellular functions, or small ligands that interfere with those functions in the treatment of cancer. The stage is set to generate a family portrait for all identified microtubule interacting proteins and to use cryo-EM as a drug development tool in the targeting of tubulin. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Deformable L-shaped microwell array for trapping pairs of heterogeneous cells
NASA Astrophysics Data System (ADS)
Lee, Gi-Hun; Kim, Sung-Hwan; Kang, AhRan; Takayama, Shuichi; Lee, Sang-Hoon; Park, Joong Yull
2015-03-01
To study cell-to-cell interactions, there has been a continuous demand on developing microsystems for trapping pairs of two different cells in microwell arrays. Here, we propose an L-shaped microwell (L-microwell) array that relies on the elasticity of a polydimethylsiloxane (PDMS) substrate for trapping and pairing heterogeneous cells. We designed an L-microwell suitable for trapping single cell in each branch via stretching/releasing the PDMS substrate, and also performed 3D time-dependent diffusion simulations to visualize how cell-secreted molecules diffuse in the L-microwell and communicate with the partner cell. The computational results showed that the secreted molecule first contacted the partner cell after 35 min, and the secreted molecule fully covered the partner cell in 4 h (when referenced to 10% of the secreted molecular concentration). The molecules that diffused to the outside of the L-microwell were significantly diluted by the bulk solution, which prevented unwanted cellular communication between neighboring L-microwells. We produced over 5000 cell pairs in one 2.25 cm2 array with about 30 000 L-microwells. The proposed L-microwell array offers a versatile and convenient cell pairing method to investigate cell-to-cell interactions in, for example, cell fusion, immune reactions, and cancer metastasis.
Song, Tao; Fang, Liurong; Wang, Dang; Zhang, Ruoxi; Zeng, Songlin; An, Kang; Chen, Huanchun; Xiao, Shaobo
2016-06-16
Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has heavily impacted the global swine industry. The PRRSV nonstructural protein 2 (nsp2) plays crucial roles in viral replication and host immune regulation, most likely by interacting with viral or cellular proteins that have not yet been identified. In this study, a quantitative interactome approach based on immunoprecipitation and stable isotope labeling with amino acids in cell culture (SILAC) was performed to identify nsp2-interacting proteins in PRRSV-infected cells with an nsp2-specific monoclonal antibody. Nine viral proteins and 62 cellular proteins were identified as potential nsp2-interacting partners. Our data demonstrate that the PRRSV nsp1α, nsp1β, and nucleocapsid proteins all interact directly with nsp2. Nsp2-interacting cellular proteins were classified into different functional groups and an interactome network of nsp2 was generated. Interestingly, cellular vimentin, a known receptor for PRRSV, forms a complex with nsp2 by using viral nucleocapsid protein as an intermediate. Taken together, the nsp2 interactome under the condition of virus infection clarifies a role of nsp2 in PRRSV replication and immune evasion. Viral proteins must interact with other virus-encoded proteins and/or host cellular proteins to function, and interactome analysis is an ideal approach for identifying such interacting proteins. In this study, we used the quantitative interactome methodology to identify the viral and cellular proteins that potentially interact with the nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) under virus infection conditions, thus providing a rich source of potential viral and cellular interaction partners for PRRSV nsp2. Based on the interactome data, we further demonstrated that PRRSV nsp2 and nucleocapsid protein together with cellular vimentin, form a complex that may be essential for viral attachment and replication, which partly explains the role of nsp2 in PRRSV replication and immune evasion. Copyright © 2016 Elsevier B.V. All rights reserved.
Hsiao, Hao-Ching; Gonzalez, Kim L.; Catanese, Daniel J.; Jordy, Kristopher E.; Matthews, Kathleen S.; Bondos, Sarah E.
2014-01-01
Interactions between structured proteins require a complementary topology and surface chemistry to form sufficient contacts for stable binding. However, approximately one third of protein interactions are estimated to involve intrinsically disordered regions of proteins. The dynamic nature of disordered regions before and, in some cases, after binding calls into question the role of partner topology in forming protein interactions. To understand how intrinsically disordered proteins identify the correct interacting partner proteins, we evaluated interactions formed by the Drosophila melanogaster Hox transcription factor Ultrabithorax (Ubx), which contains both structured and disordered regions. Ubx binding proteins are enriched in specific folds: 23 of its 39 partners include one of 7 folds, out of the 1195 folds recognized by SCOP. For the proteins harboring the two most populated folds, DNA-RNA binding 3-helical bundles and α-α superhelices, the regions of the partner proteins that exhibit these preferred folds are sufficient for Ubx binding. Three disorder-containing regions in Ubx are required to bind these partners. These regions are either alternatively spliced or multiply phosphorylated, providing a mechanism for cellular processes to regulate Ubx-partner interactions. Indeed, partner topology correlates with the ability of individual partner proteins to bind Ubx spliceoforms. Partners bind different disordered regions within Ubx to varying extents, creating the potential for competition between partners and cooperative binding by partners. The ability of partners to bind regions of Ubx that activate transcription and regulate DNA binding provides a mechanism for partners to modulate transcription regulation by Ubx, and suggests that one role of disorder in Ubx is to coordinate multiple molecular functions in response to tissue-specific cues. PMID:25286318
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Ji-sun; Choi, Dong-Ki; Park, Seong-wook
Considering the number of cytosolic proteins associated with many diseases, development of cytosol-penetrating molecules from outside of living cells is highly in demand. To gain access to the cytosol after cellular uptake, cell-penetrating molecules should be released from intermediate endosomes prior to the lysosomal degradation. However, it is very challenging to distinguish the pool of cytosolic-released molecules from those trapped in the endocytic vesicles. Here we describe a method to directly demonstrate the cytosolic localization and quantification of cytosolic amount of a cytosol-penetrating IgG antibody, TMab4, based on enhanced split GFP complementation system. We generated TMab4 genetically fused with onemore » GFP fragment and separately established HeLa cells expressing the other GFP fragment in the cytosol such that the complemented GFP fluorescence is observed only when extracellular-treated TMab4 reaches the cytosol after cellular internalization. The high affinity interactions between streptavidin-binding peptide 2 and streptavidin was employed as respective fusion partners of GFP fragments to enhance the sensitivity of GFP complementation. With this method, cytosolic concentration of TMab4 was estimated to be about 170 nM after extracellular treatment of HeLa cells with 1 μM TMab4 for 6 h. We also found that after cellular internalization into living cells, nearly 1.3–4.3% of the internalized TMab4 molecules escaped into the cytosol from the endocytic vesicles. Our enhanced split GFP complementation assay provides a useful tool to directly quantify cytosolic amount of cytosol-penetrating agents and allows cell-based high-throughput screening for cytosol-penetrating agents with increased endosomal-escaping activity.« less
Kim, Ji-sun; Choi, Dong-Ki; Park, Seong-wook; Shin, Seung-Min; Bae, Jeomil; Kim, Dong-Myung; Yoo, Tae Hyeon; Kim, Yong-Sung
2015-11-27
Considering the number of cytosolic proteins associated with many diseases, development of cytosol-penetrating molecules from outside of living cells is highly in demand. To gain access to the cytosol after cellular uptake, cell-penetrating molecules should be released from intermediate endosomes prior to the lysosomal degradation. However, it is very challenging to distinguish the pool of cytosolic-released molecules from those trapped in the endocytic vesicles. Here we describe a method to directly demonstrate the cytosolic localization and quantification of cytosolic amount of a cytosol-penetrating IgG antibody, TMab4, based on enhanced split GFP complementation system. We generated TMab4 genetically fused with one GFP fragment and separately established HeLa cells expressing the other GFP fragment in the cytosol such that the complemented GFP fluorescence is observed only when extracellular-treated TMab4 reaches the cytosol after cellular internalization. The high affinity interactions between streptavidin-binding peptide 2 and streptavidin was employed as respective fusion partners of GFP fragments to enhance the sensitivity of GFP complementation. With this method, cytosolic concentration of TMab4 was estimated to be about 170 nM after extracellular treatment of HeLa cells with 1 μM TMab4 for 6 h. We also found that after cellular internalization into living cells, nearly 1.3-4.3% of the internalized TMab4 molecules escaped into the cytosol from the endocytic vesicles. Our enhanced split GFP complementation assay provides a useful tool to directly quantify cytosolic amount of cytosol-penetrating agents and allows cell-based high-throughput screening for cytosol-penetrating agents with increased endosomal-escaping activity. Copyright © 2015 Elsevier Inc. All rights reserved.
Manuel, Sharrón L; Johnson, Brian W; Frevert, Charles W; Duncan, Francesca E
2018-04-21
Immunohistochemistry (IHC) is a robust scientific tool whereby cellular components are visualized within a tissue, and this method has been and continues to be a mainstay for many reproductive biologists. IHC is highly informative if performed and interpreted correctly, but studies have shown that the general use and reporting of appropriate controls in IHC experiments is low. This omission of the scientific method can result in data that lacks rigor and reproducibility. In this editorial, we highlight key concepts in IHC controls and describe an opportunity for our field to partner with the Histochemical Society to adopt their IHC guidelines broadly as researchers, authors, ad hoc reviewers, editorial board members, and editors-in-chief. Such cross-professional society interactions will ensure that we produce the highest quality data as new technologies emerge that still rely upon the foundations of classic histological and immunohistochemical principles.
Johannessen, Mona; Walquist, Mari; Gerits, Nancy; Dragset, Marte; Spang, Anne; Moens, Ugo
2011-01-01
Background The human polyomavirus BK (BKV) infects humans worldwide and establishes a persistent infection in the kidney. The BK virus genome encodes three regulatory proteins, large and small tumor-antigen and the agnoprotein, as well as the capsid proteins VP1 to VP3. Agnoprotein is conserved among BKV, JC virus (JCV) and SV40, and agnoprotein-deficient mutants reveal reduced viral propagation. Studies with JCV and SV40 indicate that their agnoproteins may be involved in transcription, replication and/or nuclear and cellular release of the virus. However, the exact function(s) of agnoprotein of BK virus remains elusive. Principal Findings As a strategy of exploring the functions of BKV agnoprotein, we decided to look for cellular interaction partners for the viral protein. Several partners were identified by yeast two-hybrid assay, among them α-SNAP which is involved in disassembly of vesicles during secretion. BKV agnoprotein and α-SNAP were found to partially co-localize in cells, and a complex consisting of agnoprotein and α-SNAP could be co-immunoprecipitated from cells ectopically expressing the proteins as well as from BKV-transfected cells. The N-terminal part of the agnoprotein was sufficient for the interaction with α-SNAP. Finally, we could show that BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter suggesting that agnoprotein may modulate exocytosis. Conclusions We have identified the first cellular interaction partner for BKV agnoprotein. The most N-terminal part of BKV agnoprotein is involved in the interaction with α-SNAP. Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter. PMID:21931730
Evolutionary game theory: cells as players.
Hummert, Sabine; Bohl, Katrin; Basanta, David; Deutsch, Andreas; Werner, Sarah; Theissen, Günter; Schroeter, Anja; Schuster, Stefan
2014-12-01
In two papers we review game theory applications in biology below the level of cognitive living beings. It can be seen that evolution and natural selection replace the rationality of the actors appropriately. Even in these micro worlds, competing situations and cooperative relationships can be found and modeled by evolutionary game theory. Also those units of the lowest levels of life show different strategies for different environmental situations or different partners. We give a wide overview of evolutionary game theory applications to microscopic units. In this first review situations on the cellular level are tackled. In particular metabolic problems are discussed, such as ATP-producing pathways, secretion of public goods and cross-feeding. Further topics are cyclic competition among more than two partners, intra- and inter-cellular signalling, the struggle between pathogens and the immune system, and the interactions of cancer cells. Moreover, we introduce the theoretical basics to encourage scientists to investigate problems in cell biology and molecular biology by evolutionary game theory.
[Detection of protein-protein interactions by FRET and BRET methods].
Matoulková, E; Vojtěšek, B
2014-01-01
Nowadays, in vivo protein-protein interaction studies have become preferable detecting meth-ods that enable to show or specify (already known) protein interactions and discover their inhibitors. They also facilitate detection of protein conformational changes and discovery or specification of signaling pathways in living cells. One group of in vivo methods enabling these findings is based on fluorescent resonance energy transfer (FRET) and its bio-luminescent modification (BRET). They are based on visualization of protein-protein interactions via light or enzymatic excitation of fluorescent or bio-luminescent proteins. These methods allow not only protein localization within the cell or its organelles (or small animals) but they also allow us to quantify fluorescent signals and to discover weak or strong interaction partners. In this review, we explain the principles of FRET and BRET, their applications in the characterization of protein-protein interactions and we describe several findings using these two methods that clarify molecular and cellular mechanisms and signals related to cancer biology.
Structure and functions of the chaperone-like p97/CDC48 in plants.
Bègue, Hervé; Jeandroz, Sylvain; Blanchard, Cécile; Wendehenne, David; Rosnoblet, Claire
2017-01-01
The chaperone-like p97 is a member of the AAA+ ATPase enzyme family that contributes to numerous cellular activities. P97 has been broadly studied in mammals (VCP/p97) and yeasts (CDC48: Cell Division Cycle 48/p97) and numerous investigations highlighted that this protein is post-translationally regulated, is structured in homohexamer and interacts with partners and cofactors that direct it to distinct cellular signalization pathway including protein quality control and degradation, cell cycle regulation, genome stability, vesicular trafficking, autophagy and immunity. p97 is also conserved in plants (CDC48) but its functions are less understood. In the present review we intended to present the state of the art of the structure, regulation and functions of CDC48 in plants. Evidence accumulated underline that CDC48 plays a crucial role in development, cell cycle regulation and protein turnover in plants. Furthermore, its involvement in plant immunity has recently emerged and first interacting partners have been identified, shedding light on its putative cellular activities. Identification of emerging functions of CDC48 in plants opens new roads of research in immunity and provides new insights into the mechanisms of protein quality control. Copyright © 2016 Elsevier B.V. All rights reserved.
Patient preferences for partner notification.
Apoola, A; Radcliffe, K W; Das, S; Robshaw, V; Gilleran, G; Kumari, B S; Boothby, M; Rajakumar, R
2006-08-01
To identify patient preferences for notification of sexual contacts when a sexually transmitted infection (STI) is diagnosed. A questionnaire survey of 2544 patients attending three large genitourinary clinics at Derby, Birmingham, and Coventry in the United Kingdom. The median age of the respondents was 24 with 1474 (57.9%) women, 1835 (72.1%) white, 1826 (71.8%) single. The most favoured method of partner notification was patient referral, which was rated a "good" method by 65.8% when they had to be contacted because a sexual partner has an STI. Notifying contacts by letter as a method of provider partner notification is more acceptable than phoning, text messaging, or email. Respondents with access to mobile telephones, private emails, and private letters were more likely to rate a method of partner notification using that mode of communication as "good" compared to those without. With provider referral methods of partner notification respondents preferred to receive a letter, email, or text message asking them to contact the clinic rather than a letter, email or text message informing them that they may have an STI. Most respondents think that being informed directly by a partner is the best method of being notified of the risk of an STI. Some of the newer methods may not be acceptable to all but a significant minority of respondents prefer these methods of partner notification. The wording of letters, emails, or text messages when used for partner notification has an influence on the acceptability of the method and may influence success of the partner notification method. Services should be flexible enough to utilise the patients' preferred method of partner notification.
Wise retained in the endoplasmic reticulum inhibits Wnt signaling by reducing cell surface LRP6.
Guidato, Sonia; Itasaki, Nobue
2007-10-15
The Wnt signaling pathway is tightly regulated by extracellular and intracellular modulators. Wise was isolated as a secreted protein capable of interacting with the Wnt co-receptor LRP6. Studies in Xenopus embryos revealed that Wise either enhances or inhibits the Wnt pathway depending on the cellular context. Here we show that the cellular localization of Wise has distinct effects on the Wnt pathway readout. While secreted Wise either synergizes or inhibits the Wnt signals depending on the partner ligand, ER-retained Wise consistently blocks the Wnt pathway. ER-retained Wise reduces LRP6 on the cell surface, making cells less susceptible to the Wnt signal. This study provides a cellular mechanism for the action of Wise and introduces the modulation of cellular susceptibility to Wnt signals as a novel mechanism of the regulation of the Wnt pathway.
Apoola, A; Radcliffe, K W; Das, S; Robshaw, V; Gilleran, G; Kumari, B S; Boothby, M; Rajakumar, R
2007-07-01
There have been very few studies focusing on what form of communication patients would find acceptable from a clinic. This study looks at the differences in preferences for various partner notification methods when the respondents were index patients compared with when they had to be contacted because a partner had a sexually transmitted infection (STI). There were 2544 respondents. When the clinic had to notify partners, respondents were more likely to report the method as good when a partner had an STI and they were being contacted compared with when the respondents had an infection and the partner was being contacted. The opposite was true for patient referral partner notification. Therefore, there are variations in the preferences of respondents for partner notification method, which depend on whether they see themselves as index patients or contacts.
Mertz, Joseph; Tan, Haiyan; Pagala, Vishwajeeth; Bai, Bing; Chen, Ping-Chung; Li, Yuxin; Cho, Ji-Hoon; Shaw, Timothy; Wang, Xusheng; Peng, Junmin
2015-01-01
The mind bomb 1 (Mib1) ubiquitin ligase is essential for controlling metazoan development by Notch signaling and possibly the Wnt pathway. It is also expressed in postmitotic neurons and regulates neuronal morphogenesis and synaptic activity by mechanisms that are largely unknown. We sought to comprehensively characterize the Mib1 interactome and study its potential function in neuron development utilizing a novel sequential elution strategy for affinity purification, in which Mib1 binding proteins were eluted under different stringency and then quantified by the isobaric labeling method. The strategy identified the Mib1 interactome with both deep coverage and the ability to distinguish high-affinity partners from low-affinity partners. A total of 817 proteins were identified during the Mib1 affinity purification, including 56 high-affinity partners and 335 low-affinity partners, whereas the remaining 426 proteins are likely copurified contaminants or extremely weak binding proteins. The analysis detected all previously known Mib1-interacting proteins and revealed a large number of novel components involved in Notch and Wnt pathways, endocytosis and vesicle transport, the ubiquitin-proteasome system, cellular morphogenesis, and synaptic activities. Immunofluorescence studies further showed colocalization of Mib1 with five selected proteins: the Usp9x (FAM) deubiquitinating enzyme, alpha-, beta-, and delta-catenins, and CDKL5. Mutations of CDKL5 are associated with early infantile epileptic encephalopathy-2 (EIEE2), a severe form of mental retardation. We found that the expression of Mib1 down-regulated the protein level of CDKL5 by ubiquitination, and antagonized CDKL5 function during the formation of dendritic spines. Thus, the sequential elution strategy enables biochemical characterization of protein interactomes; and Mib1 analysis provides a comprehensive interactome for investigating its role in signaling networks and neuronal development. PMID:25931508
Plakins: a family of versatile cytolinker proteins.
Leung, Conrad L; Green, Kathleen J; Liem, Ronald K H
2002-01-01
By connecting cytoskeletal elements to each other and to junctional complexes, the plakin family of cytolinkers plays a crucial role in orchestrating cellular development and maintaining tissue integrity. Plakins are built from combinations of interacting domains that bind to microfilaments, microtubules, intermediate filaments, cell-adhesion molecules and members of the armadillo family. Plakins are involved in both inherited and autoimmune diseases that affect the skin, neuronal tissue, and cardiac and skeletal muscle. Here, we describe the members of the plakin family and their interaction partners, and give examples of the cellular defects that result from their dysfunction.
21 CFR 1271.15 - Are there any exceptions from the requirements of this part?
Code of Federal Regulations, 2010 CFR
2010-04-01
... ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS General Provisions § 1271.15 Are... only recovers reproductive cells or tissue and immediately transfers them into a sexually intimate partner of the cell or tissue donor. (f) You are not required to register or list your HCT/P's...
21 CFR 1271.15 - Are there any exceptions from the requirements of this part?
Code of Federal Regulations, 2011 CFR
2011-04-01
... ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS General Provisions § 1271.15 Are... only recovers reproductive cells or tissue and immediately transfers them into a sexually intimate partner of the cell or tissue donor. (f) You are not required to register or list your HCT/P's...
21 CFR 1271.15 - Are there any exceptions from the requirements of this part?
Code of Federal Regulations, 2014 CFR
2014-04-01
... ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS General Provisions § 1271.15 Are... only recovers reproductive cells or tissue and immediately transfers them into a sexually intimate partner of the cell or tissue donor. (f) You are not required to register or list your HCT/P's...
The nuclear DEK interactome supports multi-functionality.
Smith, Eric A; Krumpelbeck, Eric F; Jegga, Anil G; Prell, Malte; Matrka, Marie M; Kappes, Ferdinand; Greis, Kenneth D; Ali, Abdullah M; Meetei, Amom R; Wells, Susanne I
2018-01-01
DEK is an oncoprotein that is overexpressed in many forms of cancer and participates in numerous cellular pathways. Of these different pathways, relevant interacting partners and functions of DEK are well described in regard to the regulation of chromatin structure, epigenetic marks, and transcription. Most of this understanding was derived by investigating DNA-binding and chromatin processing capabilities of the oncoprotein. To facilitate the generation of mechanism-driven hypotheses regarding DEK activities in underexplored areas, we have developed the first DEK interactome model using tandem-affinity purification and mass spectrometry. With this approach, we identify IMPDH2, DDX21, and RPL7a as novel DEK binding partners, hinting at new roles for the oncogene in de novo nucleotide biosynthesis and ribosome formation. Additionally, a hydroxyurea-specific interaction with replication protein A (RPA) was observed, suggesting that a DEK-RPA complex may form in response to DNA replication fork stalling. Taken together, these findings highlight diverse activities for DEK across cellular pathways and support a model wherein this molecule performs a plethora of functions. © 2017 Wiley Periodicals, Inc.
Cortactin Branches Out: Roles in Regulating Protrusive Actin Dynamics
Ammer, Amanda Gatesman; Weed, Scott A.
2008-01-01
Since its discovery in the early 1990’s, cortactin has emerged as a key signaling protein in many cellular processes, including cell adhesion, migration, endocytosis, and tumor invasion. While the list of cellular functions influenced by cortactin grows, the ability of cortactin to interact with and alter the cortical actin network is central to its role in regulating these processes. Recently, several advances have been made in our understanding of the interaction between actin and cortactin, providing insight into how these two proteins work together to provide a framework for normal and altered cellular function. This review examines how regulation of cortactin through post-translational modifications and interactions with multiple binding partners elicits changes in cortical actin cytoskeletal organization, impacting the regulation and formation of actin-rich motility structures. PMID:18615630
NASA Astrophysics Data System (ADS)
Geetha, Thangiah; Langlais, Paul; Luo, Moulun; Mapes, Rebekka; Lefort, Natalie; Chen, Shu-Chuan; Mandarino, Lawrence J.; Yi, Zhengping
2011-03-01
Protein-protein interactions are key to most cellular processes. Tandem mass spectrometry (MS/MS)-based proteomics combined with co-immunoprecipitation (CO-IP) has emerged as a powerful approach for studying protein complexes. However, a majority of systematic proteomics studies on protein-protein interactions involve the use of protein overexpression and/or epitope-tagged bait proteins, which might affect binding stoichiometry and lead to higher false positives. Here, we report an application of a straightforward, label-free CO-IP-MS/MS method, without the use of protein overexpression or protein tags, to the investigation of changes in the abundance of endogenous proteins associated with a bait protein, which is in this case insulin receptor substrate-1 (IRS-1), under basal and insulin stimulated conditions. IRS-1 plays a central role in the insulin signaling cascade. Defects in the protein-protein interactions involving IRS-1 may lead to the development of insulin resistance and type 2 diabetes. HPLC-ESI-MS/MS analyses identified eleven novel endogenous insulin-stimulated IRS-1 interaction partners in L6 myotubes reproducibly, including proteins play an important role in protein dephosphorylation [protein phosphatase 1 regulatory subunit 12A, (PPP1R12A)], muscle contraction and actin cytoskeleton rearrangement, endoplasmic reticulum stress, and protein folding, as well as protein synthesis. This novel application of label-free CO-IP-MS/MS quantification to assess endogenous interaction partners of a specific protein will prove useful for understanding how various cell stimuli regulate insulin signal transduction.
NASA Astrophysics Data System (ADS)
Nathalia Wea, Kristiana; Suparmi, A.; Cari, C.; Wahyulianti
2017-11-01
The solution of the Schrodinger equation with physical potential is the important part in quantum physics. Many methods have been developed to resolve the Schrodinger equation. The Nikiforov-Uvarov method and supersymmetric method are the most methods that interesting to be explored. The supersymmetric method not only used to solve the Schrodinger equation but also used to construct the partner potential from a general potential. In this study, the Nikiforov-Uvarov method was used to solve the Schrodinger equation while the supersymmetric method was used to construction partner potential. The study about the construction of the partner potential from general potential Rosen-Morse and Manning Rosen in D-dimensional Schrodinger system has been done. The partner potential was obtained are solvable. By using the Nikiforov-Uvarov method the eigenfunction of the Schrodinger equation in D-dimensional system with general potential Rosen-Morse and Manning Rosen and the Schrodinger equation in D-dimensional system with partner potential Rosen-Morse and Manning Rosen are determined. The eigenfunctions are different between the Schrodinger equation with general potential and the Schrodinger potential with the partner potential.
Plant Abiotic Stress Proteomics: The Major Factors Determining Alterations in Cellular Proteome
Kosová, Klára; Vítámvás, Pavel; Urban, Milan O.; Prášil, Ilja T.; Renaut, Jenny
2018-01-01
HIGHLIGHTS: Major environmental and genetic factors determining stress-related protein abundance are discussed.Major aspects of protein biological function including protein isoforms and PTMs, cellular localization and protein interactions are discussed.Functional diversity of protein isoforms and PTMs is discussed. Abiotic stresses reveal profound impacts on plant proteomes including alterations in protein relative abundance, cellular localization, post-transcriptional and post-translational modifications (PTMs), protein interactions with other protein partners, and, finally, protein biological functions. The main aim of the present review is to discuss the major factors determining stress-related protein accumulation and their final biological functions. A dynamics of stress response including stress acclimation to altered ambient conditions and recovery after the stress treatment is discussed. The results of proteomic studies aimed at a comparison of stress response in plant genotypes differing in stress adaptability reveal constitutively enhanced levels of several stress-related proteins (protective proteins, chaperones, ROS scavenging- and detoxification-related enzymes) in the tolerant genotypes with respect to the susceptible ones. Tolerant genotypes can efficiently adjust energy metabolism to enhanced needs during stress acclimation. Stress tolerance vs. stress susceptibility are relative terms which can reflect different stress-coping strategies depending on the given stress treatment. The role of differential protein isoforms and PTMs with respect to their biological functions in different physiological constraints (cellular compartments and interacting partners) is discussed. The importance of protein functional studies following high-throughput proteome analyses is presented in a broader context of plant biology. In summary, the manuscript tries to provide an overview of the major factors which have to be considered when interpreting data from proteomic studies on stress-treated plants. PMID:29472941
Broadening the functionality of a J-protein/Hsp70 molecular chaperone system.
Schilke, Brenda A; Ciesielski, Szymon J; Ziegelhoffer, Thomas; Kamiya, Erina; Tonelli, Marco; Lee, Woonghee; Cornilescu, Gabriel; Hines, Justin K; Markley, John L; Craig, Elizabeth A
2017-10-01
By binding to a multitude of polypeptide substrates, Hsp70-based molecular chaperone systems perform a range of cellular functions. All J-protein co-chaperones play the essential role, via action of their J-domains, of stimulating the ATPase activity of Hsp70, thereby stabilizing its interaction with substrate. In addition, J-proteins drive the functional diversity of Hsp70 chaperone systems through action of regions outside their J-domains. Targeting to specific locations within a cellular compartment and binding of specific substrates for delivery to Hsp70 have been identified as modes of J-protein specialization. To better understand J-protein specialization, we concentrated on Saccharomyces cerevisiae SIS1, which encodes an essential J-protein of the cytosol/nucleus. We selected suppressors that allowed cells lacking SIS1 to form colonies. Substitutions changing single residues in Ydj1, a J-protein, which, like Sis1, partners with Hsp70 Ssa1, were isolated. These gain-of-function substitutions were located at the end of the J-domain, suggesting that suppression was connected to interaction with its partner Hsp70, rather than substrate binding or subcellular localization. Reasoning that, if YDJ1 suppressors affect Ssa1 function, substitutions in Hsp70 itself might also be able to overcome the cellular requirement for Sis1, we carried out a selection for SSA1 suppressor mutations. Suppressing substitutions were isolated that altered sites in Ssa1 affecting the cycle of substrate interaction. Together, our results point to a third, additional means by which J-proteins can drive Hsp70's ability to function in a wide range of cellular processes-modulating the Hsp70-substrate interaction cycle.
Synaptic vesicle recycling: steps and principles.
Rizzoli, Silvio O
2014-04-16
Synaptic vesicle recycling is one of the best-studied cellular pathways. Many of the proteins involved are known, and their interactions are becoming increasingly clear. However, as for many other pathways, it is still difficult to understand synaptic vesicle recycling as a whole. While it is generally possible to point out how synaptic reactions take place, it is not always easy to understand what triggers or controls them. Also, it is often difficult to understand how the availability of the reaction partners is controlled: how the reaction partners manage to find each other in the right place, at the right time. I present here an overview of synaptic vesicle recycling, discussing the mechanisms that trigger different reactions, and those that ensure the availability of reaction partners. A central argument is that synaptic vesicles bind soluble cofactor proteins, with low affinity, and thus control their availability in the synapse, forming a buffer for cofactor proteins. The availability of cofactor proteins, in turn, regulates the different synaptic reactions. Similar mechanisms, in which one of the reaction partners buffers another, may apply to many other processes, from the biogenesis to the degradation of the synaptic vesicle.
Evidence for dynamically organized modularity in the yeast protein-protein interaction network
NASA Astrophysics Data System (ADS)
Han, Jing-Dong J.; Bertin, Nicolas; Hao, Tong; Goldberg, Debra S.; Berriz, Gabriel F.; Zhang, Lan V.; Dupuy, Denis; Walhout, Albertha J. M.; Cusick, Michael E.; Roth, Frederick P.; Vidal, Marc
2004-07-01
In apparently scale-free protein-protein interaction networks, or `interactome' networks, most proteins interact with few partners, whereas a small but significant proportion of proteins, the `hubs', interact with many partners. Both biological and non-biological scale-free networks are particularly resistant to random node removal but are extremely sensitive to the targeted removal of hubs. A link between the potential scale-free topology of interactome networks and genetic robustness seems to exist, because knockouts of yeast genes encoding hubs are approximately threefold more likely to confer lethality than those of non-hubs. Here we investigate how hubs might contribute to robustness and other cellular properties for protein-protein interactions dynamically regulated both in time and in space. We uncovered two types of hub: `party' hubs, which interact with most of their partners simultaneously, and `date' hubs, which bind their different partners at different times or locations. Both in silico studies of network connectivity and genetic interactions described in vivo support a model of organized modularity in which date hubs organize the proteome, connecting biological processes-or modules -to each other, whereas party hubs function inside modules.
Endocytosis and membrane receptor internalization: implication of F-BAR protein Carom.
Xu, Yanjie; Xia, Jixiang; Liu, Suxuan; Stein, Sam; Ramon, Cueto; Xi, Hang; Wang, Luqiao; Xiong, Xinyu; Zhang, Lixiao; He, Dingwen; Yang, William; Zhao, Xianxian; Cheng, Xiaoshu; Yang, Xiaofeng; Wang, Hong
2017-03-01
Endocytosis is a cellular process mostly responsible for membrane receptor internalization. Cell membrane receptors bind to their ligands and form a complex which can be internalized. We previously proposed that F-BAR protein initiates membrane curvature and mediates endocytosis via its binding partners. However, F-BAR protein partners involved in membrane receptor endocytosis and the regulatory mechanism remain unknown. In this study, we established database mining strategies to explore mechanisms underlying receptor-related endocytosis. We identified 34 endocytic membrane receptors and 10 regulating proteins in clathrin-dependent endocytosis (CDE), a major process of membrane receptor internalization. We found that F-BAR protein FCHSD2 (Carom) may facilitate endocytosis via 9 endocytic partners. Carom is highly expressed, along with highly expressed endocytic membrane receptors and partners, in endothelial cells and macrophages. We established 3 models of Carom-receptor complexes and their intracellular trafficking based on protein interaction and subcellular localization. We conclude that Carom may mediate receptor endocytosis and transport endocytic receptors to the cytoplasm for receptor signaling and lysosome/proteasome degradation, or to the nucleus for RNA processing, gene transcription and DNA repair.
Henne, Melina; König, Nicolas; Triulzi, Tiziana; Baroni, Sara; Forlani, Fabio; Scheibe, Renate; Papenbrock, Jutta
2015-01-01
Sulfurtransferases (Strs) and thioredoxins (Trxs) are members of large protein families. Trxs are disulfide reductases and play an important role in redox-related cellular processes. They interact with a broad range of proteins. Strs catalyze the transfer of a sulfur atom from a suitable sulfur donor to nucleophilic sulfur acceptors in vitro, but the physiological roles of these enzymes are not well defined. Several studies in different organisms demonstrate protein-protein interactions of Strs with members of the Trx family. We are interested in investigating the specificity of the interaction between Str and Trx isoforms. In order to use the bimolecular fluorescence complementation (BiFC), several Str and Trx sequences from Arabidopsis thaliana were cloned into the pUC-SPYNE and pUC-SPYCE split-YFP vectors, respectively. Each couple of plasmids containing the sequences for the putative interaction partners were transformed into Arabidopsis protoplasts and screened using a confocal laser scanning microscope. Compartment- and partner-specific interactions could be observed in transformed protoplasts. Replacement of cysteine residues in the redox-active site of Trxs abolished the interaction signal. Therefore, the redox site is not only involved in the redox reaction but also responsible for the interaction with partner proteins. Biochemical assays support a specific interaction among Strs and certain Trxs. Based on the results obtained, the interaction of Strs and Trxs indicates a role of Strs in the maintenance of the cellular redox homeostasis.
Protein social behavior makes a stronger signal for partner identification than surface geometry
Laine, Elodie
2016-01-01
ABSTRACT Cells are interactive living systems where proteins movements, interactions and regulation are substantially free from centralized management. How protein physico‐chemical and geometrical properties determine who interact with whom remains far from fully understood. We show that characterizing how a protein behaves with many potential interactors in a complete cross‐docking study leads to a sharp identification of its cellular/true/native partner(s). We define a sociability index, or S‐index, reflecting whether a protein likes or not to pair with other proteins. Formally, we propose a suitable normalization function that accounts for protein sociability and we combine it with a simple interface‐based (ranking) score to discriminate partners from non‐interactors. We show that sociability is an important factor and that the normalization permits to reach a much higher discriminative power than shape complementarity docking scores. The social effect is also observed with more sophisticated docking algorithms. Docking conformations are evaluated using experimental binding sites. These latter approximate in the best possible way binding sites predictions, which have reached high accuracy in recent years. This makes our analysis helpful for a global understanding of partner identification and for suggesting discriminating strategies. These results contradict previous findings claiming the partner identification problem being solvable solely with geometrical docking. Proteins 2016; 85:137–154. © 2016 Wiley Periodicals, Inc. PMID:27802579
Protein social behavior makes a stronger signal for partner identification than surface geometry.
Laine, Elodie; Carbone, Alessandra
2017-01-01
Cells are interactive living systems where proteins movements, interactions and regulation are substantially free from centralized management. How protein physico-chemical and geometrical properties determine who interact with whom remains far from fully understood. We show that characterizing how a protein behaves with many potential interactors in a complete cross-docking study leads to a sharp identification of its cellular/true/native partner(s). We define a sociability index, or S-index, reflecting whether a protein likes or not to pair with other proteins. Formally, we propose a suitable normalization function that accounts for protein sociability and we combine it with a simple interface-based (ranking) score to discriminate partners from non-interactors. We show that sociability is an important factor and that the normalization permits to reach a much higher discriminative power than shape complementarity docking scores. The social effect is also observed with more sophisticated docking algorithms. Docking conformations are evaluated using experimental binding sites. These latter approximate in the best possible way binding sites predictions, which have reached high accuracy in recent years. This makes our analysis helpful for a global understanding of partner identification and for suggesting discriminating strategies. These results contradict previous findings claiming the partner identification problem being solvable solely with geometrical docking. Proteins 2016; 85:137-154. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976.
Hofmann-Winkler, Heike; Gnirß, Kerstin; Wrensch, Florian; Pöhlmann, Stefan
2015-10-01
The ongoing Ebola virus (EBOV) disease (EVD) epidemic in Western Africa is the largest EVD outbreak recorded to date and requires the rapid development and deployment of antiviral measures. The viral glycoprotein (GP) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention. However, it is unknown whether the GPs of the currently and previously circulating EBOVs use the same mechanisms for cellular entry and are thus susceptible to inhibition by the same antivirals and cellular defenses. Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. Thus, the viruses responsible for the ongoing EVD epidemic should be fully susceptible to established antiviral strategies targeting GP and cellular entry factors. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Dual Contraceptive Method Use Among Youth in Alternative Schools.
Coyle, Karin K; Peterson, Amy J; Franks, Heather M; Anderson, Pamela M; Glassman, Jill R
2016-12-01
Dual contraceptive method use, or using a highly effective contraceptive method plus a barrier method like condoms, is gaining attention as a strategy for preventing unplanned pregnancy and sexually transmitted diseases. We investigated rates of dual method use among a sample of youth in urban alternative schools, and explored the relationship between dual method use and sexual partner type. The study analyzed data from 765 students enrolled in 11 district-run continuation high schools in northern California. We explored the association between dual method use and sexual partner type (steady only, a mix of steady and non-steady, and non-steady only) using logistic regression. Differences in dual rates by partner type were statistically significant, with higher rates of dual methods use reported among young people reporting non-steady sexual partners only, as compared to those with steady partners only. The data illustrate that young people in alternative school settings could gain from further intervention on the benefits, skills, and challenges of using two methods of contraception as opposed to one with both steady and non-steady sexual partners.
Partner roles in contraceptive use: what do adolescent mothers say?
Lewis, Dinah A; Martins, Summer L; Gilliam, Melissa L
2012-12-01
To examine the role of sexual partners in adolescent mothers' use of non-coital dependent contraceptive methods in the postpartum period. 40 African American adolescent mothers completed surveys and qualitative interviews during the first postpartum year as part of a larger longitudinal study in Chicago, Illinois. Themes related to contraception and sexual partners were analyzed. Adolescent mothers' reports of partners' roles in the use of non-coital dependent contraceptive methods (i.e., oral contraceptives, intrauterine contraception, and depot medroxyprogesterone acetate). Partners largely supported the use of non-coital dependent contraceptive methods, yet mechanisms of support varied greatly, from advocating for specific methods to facilitating participants' continuation of their chosen method. Unsupportive partners either expressed concerns about the safety and side effects of specific methods or desired another child in the near future. Participants valued these preferences to different degrees when making their contraceptive decisions. Partners of adolescent mothers play varying roles in postpartum contraceptive decisions. They thus have the potential both to inhibit and to facilitate the use of non-coital dependent contraception. Quantitative research is needed to further evaluate how partner attitudes and support behaviors, among other factors, affect contraceptive initiation and continuation among adolescent mothers. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.
Jewkes, Rachel; Dunkle, Kristin; Jama-Shai, Nwabisa; Gray, Glenda
2015-01-01
Intimate partner violence (IPV) is a risk factor for HIV acquisition in many settings, but little is known about its impact on cellular immunity especially in HIV infected women, and if any impact differs according to the form of IPV. We tested hypotheses that exposure to IPV, non-partner rape, hunger, pregnancy, depression and substance abuse predicted change in CD4+ and CD8+ T-cell count in a dataset of 103 HIV infected young women aged 15-26 enrolled in a cluster randomised controlled trial. Multiple regression models were fitted to measure rate of change in CD4 and CD8 and including terms for age, person years of CD4+/CD8+ T-cell observation, HIV positivity at baseline, and stratum. Exposure variables included drug use, emotional, physical or sexual IPV exposure, non-partner rape, pregnancy and food insecurity. Mean CD4+ T cell count at baseline (or first HIV+ test) was 567.6 (range 1121-114). Participants were followed for an average of 1.3 years. The magnitude of change in CD4 T-cells was significantly associated with having ever experienced emotional abuse from a current partner at baseline or first HIV+ test (Coeff -132.9 95% CI -196.4, -69.4 p<0.0001) and drug use (Coeff -129.9 95% CI -238.7, -21.2 p=0.02). It was not associated with other measures. The change in CD8 T-cells was associated with having ever experienced emotional abuse at baseline or prior to the first HIV+ test (Coeff -178.4 95%CI -330.2, -26.5 p=0.02). In young ART-naive HIV positive women gender-based violence exposure in the form of emotional abuse is associated with a faster rate of decline in markers of cellular immunity. This highlights the importance of attending to emotional abuse when studying the physiological impact of IPV experience and the mechanisms of its impact on women's health.
Guo, Deyin; Spetz, Carl; Saarma, Mart; Valkonen, Jari P T
2003-05-01
Potyviral helper-component proteinase (HCpro) is a multifunctional protein exerting its cellular functions in interaction with putative host proteins. In this study, cellular protein partners of the HCpro encoded by Potato virus A (PVA) (genus Potyvirus) were screened in a potato leaf cDNA library using a yeast two-hybrid system. Two cellular proteins were obtained that interact specifically with PVA HCpro in yeast and in the two in vitro binding assays used. Both proteins are encoded by single-copy genes in the potato genome. Analysis of the deduced amino acid sequences revealed that one (HIP1) of the two HCpro interactors is a novel RING finger protein. The sequence of the other protein (HIP2) showed no resemblance to the protein sequences available from databanks and has known biological functions.
Willett, Jaime A; Johnson, Ashlyn G; Vogel, Andrea R; Patisaul, Heather B; McGraw, Lisa A; Meitzen, John
2018-04-01
Medium spiny neurons (MSNs) in the nucleus accumbens have long been implicated in the neurobiological mechanisms that underlie numerous social and motivated behaviors as studied in rodents such as rats. Recently, the prairie vole has emerged as an important model animal for studying social behaviors, particularly regarding monogamy because of its ability to form pair bonds. However, to our knowledge, no study has assessed intrinsic vole MSN electrophysiological properties or tested how these properties vary with the strength of the pair bond between partnered voles. Here we performed whole cell patch-clamp recordings of MSNs in acute brain slices of the nucleus accumbens core (NAc) of adult male voles exhibiting strong and weak preferences for their respective partnered females. We first document vole MSN electrophysiological properties and provide comparison to rat MSNs. Vole MSNs demonstrated many canonical electrophysiological attributes shared across species but exhibited notable differences in excitability compared with rat MSNs. Second, we assessed male vole partner preference behavior and tested whether MSN electrophysiological properties varied with partner preference strength. Male vole partner preference showed extensive variability. We found that decreases in miniature excitatory postsynaptic current amplitude and the slope of the evoked action potential firing rate to depolarizing current injection weakly associated with increased preference for the partnered female. This suggests that excitatory synaptic strength and neuronal excitability may be decreased in MSNs in males exhibiting stronger preference for a partnered female. Overall, these data provide extensive documentation of MSN electrophysiological characteristics and their relationship to social behavior in the prairie vole. NEW & NOTEWORTHY This research represents the first assessment of prairie vole nucleus accumbens core medium spiny neuron intrinsic electrophysiological properties and probes the relationship between cellular excitability and social behavior.
Photoactivatable protein labeling by singlet oxygen mediated reactions.
To, Tsz-Leung; Medzihradszky, Katalin F; Burlingame, Alma L; DeGrado, William F; Jo, Hyunil; Shu, Xiaokun
2016-07-15
Protein-protein interactions regulate many biological processes. Identification of interacting proteins is thus an important step toward molecular understanding of cell signaling. The aim of this study was to investigate the use of photo-generated singlet oxygen and a small molecule for proximity labeling of interacting proteins in cellular environment. The protein of interest (POI) was fused with a small singlet oxygen photosensitizer (miniSOG), which generates singlet oxygen ((1)O2) upon irradiation. The locally generated singlet oxygen then activated a biotin-conjugated thiol molecule to form a covalent bond with the proteins nearby. The labeled proteins can then be separated and subsequently identified by mass spectrometry. To demonstrate the applicability of this labeling technology, we fused the miniSOG to Skp2, an F-box protein of the SCF ubiquitin ligase, and expressed the fusion protein in mammalian cells and identified that the surface cysteine of its interacting partner Skp1 was labeled by the biotin-thiol molecule. This photoactivatable protein labeling method may find important applications including identification of weak and transient protein-protein interactions in the native cellular context, as well as spatial and temporal control of protein labeling. Copyright © 2016 Elsevier Ltd. All rights reserved.
Code of Federal Regulations, 2010 CFR
2010-04-01
... CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND... donor screening or testing under §§ 1271.75, 1271.80 and 1271.85 for: (1) Cells and tissues for autologous use; or (2) Reproductive cells or tissue donated by a sexually intimate partner of the recipient...
Code of Federal Regulations, 2014 CFR
2014-04-01
... CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND... donor screening or testing under §§ 1271.75, 1271.80 and 1271.85 for: (1) Cells and tissues for autologous use; or (2) Reproductive cells or tissue donated by a sexually intimate partner of the recipient...
SSC San Diego Biennial Review 2003. Vol 2: Communication and Information Systems
2003-01-01
University, Department of Electrical and Computer Engineering) Michael Jablecki (Science and Technology Corporation) Stochastic Unified Multiple...wearable computers and cellular phones. The technology-transfer process involved a coalition of government and industrial partners, each providing...the design and fabrication of the coupler. SSC San Diego developed a computer -controlled fused fiber fabrication station to achieve the required
Monothiol CGFS Glutaredoxins and BolA-like Proteins: [2Fe-2S] Binding Partners in Iron Homeostasis
Li, Haoran; Outten, Caryn E.
2012-01-01
Monothiol glutaredoxins (Grxs) with a signature CGFS active site and BolA-like proteins have recently emerged as novel players in iron homeostasis. Elegant genetic and biochemical studies examining the functional and physical interactions of CGFS Grxs in the fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe have unveiled their essential roles in intracellular iron signaling, iron trafficking, and the maturation of Fe-S cluster proteins. Biophysical and biochemical analyses of the [2Fe-2S]-bridging interaction between CGFS Grxs and a BolA-like protein in S. cerevisiae provided the first molecular-level understanding of the iron regulation mechanism in this model eukaryote, and established the ubiquitous CGFS Grxs and BolA-like proteins as novel Fe-S cluster-binding regulatory partners. Parallel studies focused on E. coli and human homologues for CGFS Grxs and BolA-like proteins have supported the studies in yeast and provided additional clues to their involvement in cellular iron metabolism. Herein we review recent progress in uncovering the cellular and molecular mechanisms by which CGFS Grxs and BolA-like proteins help regulate iron metabolism in both eukaryotic and prokaryotic organisms. PMID:22583368
Du, Pufeng; Wang, Lusheng
2014-01-01
One of the fundamental tasks in biology is to identify the functions of all proteins to reveal the primary machinery of a cell. Knowledge of the subcellular locations of proteins will provide key hints to reveal their functions and to understand the intricate pathways that regulate biological processes at the cellular level. Protein subcellular location prediction has been extensively studied in the past two decades. A lot of methods have been developed based on protein primary sequences as well as protein-protein interaction network. In this paper, we propose to use the protein-protein interaction network as an infrastructure to integrate existing sequence based predictors. When predicting the subcellular locations of a given protein, not only the protein itself, but also all its interacting partners were considered. Unlike existing methods, our method requires neither the comprehensive knowledge of the protein-protein interaction network nor the experimentally annotated subcellular locations of most proteins in the protein-protein interaction network. Besides, our method can be used as a framework to integrate multiple predictors. Our method achieved 56% on human proteome in absolute-true rate, which is higher than the state-of-the-art methods. PMID:24466278
Sexually Transmitted Disease Partner Notification among African-American, Adolescent Women
Buchsbaum, Anna; Gallo, Maria F.; Whiteman, Maura K.; Cwiak, Carrie; Goedken, Peggy; Kraft, Joan Marie; Jamieson, Denise J.; Kottke, Melissa
2014-01-01
Objective. To better understand preferences and practices regarding partner notification of sexually transmitted infection (STI) among female, African-American adolescents. Methods. Participants completed a questionnaire and STI testing at baseline. Those diagnosed with Chlamydia or gonorrhea were recruited for a follow-up study, involving another questionnaire and repeat STI testing after three months. Results. At baseline, most participants (85.1%) preferred to tell their partner about an STI diagnosis themselves instead of having a health care provider inform him, and 71.0% preferred to bring their partner for clinic treatment instead of giving him pills or a prescription. Two-thirds of participants were classified as having high self-efficacy for partner notification of a positive STI diagnosis. In the multivariable analysis, older participants and those with fewer lifetime sexual partners were more likely to have high self-efficacy. Ninety-three participants (26.6%) had Chlamydia or gonorrhea and, of this subset, 55 participated in the follow-up study. Most adolescents in the follow-up study (76.4%) notified their partner about their infection. Conclusion. Although participants were willing to use most methods of partner notification, most preferred to tell partners themselves and few preferred expedited partner therapy. Traditional methods for partner notification and treatment may not be adequate for all adolescents in this population. PMID:25609905
Endocytosis and membrane receptor internalization: implication of F-BAR protein Carom
Xu, Yanjie; Liu, Suxuan; Xia, Jixiang; Stein, Sam; Ramon, Cueto; Xi, Hang; Wang, Luqiao; Xiong, Xinyu; Zhang, Lixiao; He, Dingwen; Yang, William; Zhao, Xianxian; Cheng, Xiaoshu; Yang, Xiaofeng; Wang, Hong
2016-01-01
Endocytosis is a cellular process mostly responsible for membrane receptor internalization. Cell membrane receptors bind to their ligands and form a complex which can be internalized. We previously proposed that F-BAR protein initiates membrane curvature and mediates endocytosis via their binding partners. However, F-BAR protein partners involved in membrane receptor endocytosis and the regulatory mechanism remain unknown. In this study, we established a group of database mining strategies to explore mechanisms underlying receptor-related endocytosis. We identified 34 endocytic membrane receptors and 10 regulating proteins for vesicle formation in clathrin-dependent endocytosis (CDE), a major process of membrane receptor internalization. We found that F-BAR protein FCHSD2 (Carom) may facilitate endocytosis via 9 endocytic partners. Carom is highly expressed, along with highly expressed endocytic membrane receptors and partners, in endothelial cells and macrophages. We established 3 models of Carom-receptor complex and their intracellular trafficking based on protein-protein interaction and subcellular localization. We conclude that Carom may mediate receptor endocytosis and transport endocytic receptors to the cytoplasm for receptor signaling and lysosome/proteasome degradation, or to the nucleus for RNA processing, gene transcription and DNA repair. PMID:28199211
Synaptic vesicle recycling: steps and principles
Rizzoli, Silvio O
2014-01-01
Synaptic vesicle recycling is one of the best-studied cellular pathways. Many of the proteins involved are known, and their interactions are becoming increasingly clear. However, as for many other pathways, it is still difficult to understand synaptic vesicle recycling as a whole. While it is generally possible to point out how synaptic reactions take place, it is not always easy to understand what triggers or controls them. Also, it is often difficult to understand how the availability of the reaction partners is controlled: how the reaction partners manage to find each other in the right place, at the right time. I present here an overview of synaptic vesicle recycling, discussing the mechanisms that trigger different reactions, and those that ensure the availability of reaction partners. A central argument is that synaptic vesicles bind soluble cofactor proteins, with low affinity, and thus control their availability in the synapse, forming a buffer for cofactor proteins. The availability of cofactor proteins, in turn, regulates the different synaptic reactions. Similar mechanisms, in which one of the reaction partners buffers another, may apply to many other processes, from the biogenesis to the degradation of the synaptic vesicle. PMID:24596248
NASA Astrophysics Data System (ADS)
Basu, Sankar; Söderquist, Fredrik; Wallner, Björn
2017-05-01
The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of a disorder-to-order transitioning code embedded in the amino acid sequences of IDPs/IDPRs. Disordered proteins are characterized by an enormous amount of structural plasticity which makes them promiscuous in binding to different partners, multi-functional in cellular activity and atypical in folding energy landscapes resembling partially folded molten globules. Also, their involvement in several deadly human diseases (e.g. cancer, cardiovascular and neurodegenerative diseases) makes them attractive drug targets, and important for a biochemical understanding of the disease(s). The study of the structural ensemble of IDPs is rather difficult, in particular for transient interactions. When bound to a structured partner, an IDPR adapts an ordered conformation in the complex. The residues that undergo this disorder-to-order transition are called protean residues, generally found in short contiguous stretches and the first step in understanding the modus operandi of an IDP/IDPR would be to predict these residues. There are a few available methods which predict these protean segments from their amino acid sequences; however, their performance reported in the literature leaves clear room for improvement. With this background, the current study presents `Proteus', a random forest classifier that predicts the likelihood of a residue undergoing a disorder-to-order transition upon binding to a potential partner protein. The prediction is based on features that can be calculated using the amino acid sequence alone. Proteus compares favorably with existing methods predicting twice as many true positives as the second best method (55 vs. 27%) with a much higher precision on an independent data set. The current study also sheds some light on a possible `disorder-to-order' transitioning consensus, untangled, yet embedded in the amino acid sequence of IDPs. Some guidelines have also been suggested for proceeding with a real-life structural modeling involving an IDPR using Proteus.
Computational Methods to Predict Protein Interaction Partners
NASA Astrophysics Data System (ADS)
Valencia, Alfonso; Pazos, Florencio
In the new paradigm for studying biological phenomena represented by Systems Biology, cellular components are not considered in isolation but as forming complex networks of relationships. Protein interaction networks are among the first objects studied from this new point of view. Deciphering the interactome (the whole network of interactions for a given proteome) has been shown to be a very complex task. Computational techniques for detecting protein interactions have become standard tools for dealing with this problem, helping and complementing their experimental counterparts. Most of these techniques use genomic or sequence features intuitively related with protein interactions and are based on "first principles" in the sense that they do not involve training with examples. There are also other computational techniques that use other sources of information (i.e. structural information or even experimental data) or are based on training with examples.
Integrative, Dynamic Structural Biology at Atomic Resolution—It’s About Time
van den Bedem, Henry; Fraser, James S.
2015-01-01
Biomolecules adopt a dynamic ensemble of conformations, each with the potential to interact with binding partners or perform the chemical reactions required for a multitude of cellular functions. Recent advances in X-ray crystallography, Nuclear Magnetic Resonance (NMR) spectroscopy, and other techniques are helping us realize the dream of seeing—in atomic detail—how different parts of biomolecules exchange between functional sub-states using concerted motions. Integrative structural biology has advanced our understanding of the formation of large macromolecular complexes and how their components interact in assemblies by leveraging data from many low-resolution methods. Here, we review the growing opportunities for integrative, dynamic structural biology at the atomic scale, contending there is increasing synergistic potential between X-ray crystallography, NMR, and computer simulations to reveal a structural basis for protein conformational dynamics at high resolution. PMID:25825836
Hull, Peter; Mao, Limin; Prestage, Garrett; Zablotska, Iryna; de Wit, John; Holt, Martin
2016-04-19
Mobile phone apps are now the most popular method that Australian gay men use to find sex partners. Partner-seeking mobile phone apps use location functions to identify like-minded men and display their proximity. This study examines whether meeting partners via mobile apps is associated with a greater risk of HIV and sexually transmitted infections (STIs) than with other ways of meeting partners. Data were analysed from the Gay Community Periodic Surveys, community-based, cross-sectional surveys conducted in Australian state capital cities between 2010 and 2014. χ 2 tests and multinomial logistic regression were used to analyse differences in risk profiles of men who used different methods to meet partners. Data were analysed from 36 428 men who participated in the Gay Community Periodic Surveys between 2010 and 2014. In 2014, 4116 men reported meeting sex partners with the use of mobile apps, increasing from 23.9% in 2011 to 42.5% in 2014. Men who used a combination of online and offline methods reported a greater number of sex partners and were more likely to report a recent STI than men who used online methods only or offline methods only. There has been a steep increase in the use of mobile phone apps by gay men in Australia to meet male partners. However, men who use a combination of mobile phone apps, internet websites and offline places to meet partners appear to be at increased risk of STIs or HIV compared with men who use a narrower range of online and offline methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Montgomery, Elizabeth T; van der Straten, Ariane; Chidanyika, Agnes; Chipato, Tsungai; Jaffar, Shabbar; Padian, Nancy
2011-07-01
Enlisting male partner involvement is perceived as an important component of women's successful uptake of female-initiated HIV prevention methods. We conducted a longitudinal study among a cohort of 955 Zimbabwean women participating in a clinical trial of the effectiveness of a female-initiated HIV prevention method (the diaphragm and lubricant gel) to: (a) describe the extent to which women involved their male partners in the decision to use the study products, and (b) measure the effect perceived male partner support had on their acceptability and consistent use of these methods. Reported levels of male partner involvement in discussions and decisions regarding: joining the study, study activities, the outcome of HIV/STI test results, and product use were very high. In multivariate analyses, regular disclosure of study product use and partner approval for the diaphragm and gel were significantly associated with women's acceptability and consistent use of the products; an essential component for determining efficacy of investigational prevention methods. These results support the need for more sophisticated measurement of how couples interact to make decisions that impact study participation and investigational product use as well as more rigorous adaptations and evaluations of existing strategies to involve male partners in female-initiated HIV prevention trials.
NASA Astrophysics Data System (ADS)
Suparmi; Cari, C.; Wea, K. N.; Wahyulianti
2018-03-01
The Schrodinger equation is the fundamental equation in quantum physics. The characteristic of the particle in physics potential field can be explained by using the Schrodinger equation. In this study, the solution of 4 dimensional Schrodinger equation for the anharmonic potential and the anharmonic partner potential have done. The method that used to solve the Schrodinger equation was the ansatz wave method, while to construction the partner potential was the supersymmetric method. The construction of partner potential used to explain the experiment result that cannot be explained by the original potential. The eigenvalue for anharmonic potential and the anharmonic partner potential have the same characteristic. Every increase of quantum orbital number the eigenvalue getting smaller. This result corresponds to Bohrn’s atomic theory that the eigenvalue is inversely proportional to the atomic shell. But the eigenvalue for the anharmonic partner potential higher than the eigenvalue for the anharmonic original potential.
Fowler, Katherine A.; Niolon, Phyllis H.
2014-01-01
Objectives. We estimated the frequency and examined the characteristics of intimate partner homicide and related deaths in 16 US states participating in the National Violent Death Reporting System (NVDRS), a state-based surveillance system. Methods. We used a combination of quantitative and qualitative methods to analyze NVDRS data from 2003 to 2009. We selected deaths linked to intimate partner violence for analysis. Results. Our sample comprised 4470 persons who died in the course of 3350 intimate partner violence–related homicide incidents. Intimate partners and corollary victims represented 80% and 20% of homicide victims, respectively. Corollary homicide victims included family members, new intimate partners, friends, acquaintances, police officers, and strangers. Conclusions. Our findings, from the first multiple-state study of intimate partner homicide and corollary homicides, demonstrate that the burden of intimate partner violence extends beyond the couple involved. Systems (e.g., criminal justice, medical care, and shelters) whose representatives routinely interact with victims of intimate partner violence can help assess the potential for lethal danger, which may prevent intimate partner and corollary victims from harm. PMID:24432943
The prion-ZIP connection: From cousins to partners in iron uptake
Singh, Neena; Asthana, Abhishek; Baksi, Shounak; Desai, Vilok; Haldar, Swati; Hari, Sahi; Tripathi, Ajai K
2015-01-01
ABSTRACT Converging observations from disparate lines of inquiry are beginning to clarify the cause of brain iron dyshomeostasis in sporadic Creutzfeldt-Jakob disease (sCJD), a neurodegenerative condition associated with the conversion of prion protein (PrPC), a plasma membrane glycoprotein, from α-helical to a β-sheet rich PrP-scrapie (PrPSc) isoform. Biochemical evidence indicates that PrPC facilitates cellular iron uptake by functioning as a membrane-bound ferrireductase (FR), an activity necessary for the transport of iron across biological membranes through metal transporters. An entirely different experimental approach reveals an evolutionary link between PrPC and the Zrt, Irt-like protein (ZIP) family, a group of proteins involved in the transport of zinc, iron, and manganese across the plasma membrane. Close physical proximity of PrPC with certain members of the ZIP family on the plasma membrane and increased uptake of extracellular iron by cells that co-express PrPC and ZIP14 suggest that PrPC functions as a FR partner for certain members of this family. The connection between PrPC and ZIP proteins therefore extends beyond common ancestry to that of functional cooperation. Here, we summarize evidence supporting the facilitative role of PrPC in cellular iron uptake, and implications of this activity on iron metabolism in sCJD brains. PMID:26689487
Bartholomeeusen, Koen; Christ, Frauke; Hendrix, Jelle; Rain, Jean-Christophe; Emiliani, Stéphane; Benarous, Richard; Debyser, Zeger; Gijsbers, Rik; De Rijck, Jan
2009-01-01
Lens epithelium-derived growth factor/p75 (LEDGF/p75) is a prominent cellular interaction partner of human immunodeficiency virus-1 (HIV-1) integrase, tethering the preintegration complex to the host chromosome. In light of the development of LEDGF/p75-integrase interaction inhibitors, it is essential to understand the cell biology of LEDGF/p75. We identified pogZ as new cellular interaction partner of LEDGF/p75. Analogous to lentiviral integrase, pogZ, a domesticated transposase, carries a DDE domain, the major determinant for LEDGF/p75 interaction. Using different in vitro and in vivo approaches, we corroborated the interaction between the C terminus of LEDGF/p75 and the DDE domain of pogZ, revealing an overlap in the binding of pogZ and HIV-1 integrase. Competition experiments showed that integrase is efficient in displacing pogZ from LEDGF/p75. Moreover, pogZ does not seem to play a role as a restriction factor of HIV. The finding that LEDGF/p75 is capable of interacting with a DDE domain protein that is not a lentiviral integrase points to a profound role of LEDGF/p75 in DDE domain protein function. PMID:19244240
Yazicioglu, Mustafa N.; Monaldini, Luca; Chu, Kirk; Khazi, Fayaz R.; Murphy, Samuel L.; Huang, Heshu; Margaritis, Paris; High, Katherine A.
2013-01-01
The genes encoding a family of proteins termed proline-rich γ-carboxyglutamic acid (PRRG) proteins were identified and characterized more than a decade ago, but their functions remain unknown. These novel membrane proteins have an extracellular γ-carboxyglutamic acid (Gla) protein domain and cytosolic WW binding motifs. We screened WW domain arrays for cytosolic binding partners for PRRG4 and identified novel protein-protein interactions for the protein. We also uncovered a new WW binding motif in PRRG4 that is essential for these newly found protein-protein interactions. Several of the PRRG-interacting proteins we identified are essential for a variety of physiologic processes. Our findings indicate possible novel and previously unidentified functions for PRRG proteins. PMID:23873930
Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk
Oladimeji, Peter; Cui, Hongmei; Zhang, Chen; Chen, Taosheng
2016-01-01
Introduction Protein-protein interaction and signaling crosstalk contribute to the regulation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) and broaden their cellular function. Area covered This review covers key historic discoveries and recent advances in our understanding of the broad function of PXR and CAR and their regulation by protein-protein interaction and signaling crosstalk. Expert opinion PXR and CAR were first discovered as xenobiotic receptors. However, it is clear that PXR and CAR perform a much broader range of cellular functions through protein-protein interaction and signaling crosstalk, which typically mutually affect the function of all the partners involved. Future research on PXR and CAR should, therefore, look beyond their xenobiotic function. PMID:27295009
Insights in connecting phenotypes in bacteria to coevolutionary information
NASA Astrophysics Data System (ADS)
Cheng, Ryan; Morcos, Faruck; Hayes, Ryan; Helm, Rodney; Levine, Herbert; Onuchic, Jose
It has long been known that protein sequences are far from random. These sequences have been evolutionarily selected to maintain their ability to fold into stable, three-dimensional folded structures as well as their ability to form macromolecular assemblies, perform catalytic functions, etc. For these reasons, there exist quantifiable mutational patterns in the collection of sequence data for a protein family arising from the need to maintain favorable residue-residue interactions to facilitate folding as well as cellular function. Here, we focus on studying the correlated mutational patterns that give rise to interaction specificity in bacterial two-component signaling (TCS) systems. TCS proteins have evolved to be able to preferentially bind and transfer a phosphate group to their signaling partner while avoiding phosphotransfer with non-partners. We infer a Potts model Hamiltonian governing the correlated mutational patterns that are observed in the sequence data of TCS partners and apply this model to recently published in vivo mutational data. Our findings further support the notion that statistical models built from sequence data can be used to predict bacterial phenotypes as well as engineer interaction specificity between non-partner TCS proteins. This research has been supported by the NSF INSPIRE Award (MCB-1241332) and by the CTBP sponsored by the NSF (Grant PHY- 1427654).
Kamanga, G; Brown, L; Jawati, P; Chiwanda, D; Nyirenda, N
2015-12-01
HIV testing and counselling (HTC) is important to effect positive sexual behaviour change and is an entry point to treatment, care, and psychosocial support. One of the most practical initiatives to increase HTC is to encourage sexual partners of HIV-infected persons to test for HIV. However, partner notification strategies must be feasible in the healthcare setting and acceptable to the population. We conducted a qualitative study during the pilot phase of an HIV partner notification trial to complement its assessment of feasibility and acceptability of methods of partner notification. We performed in-depth interviews with 16 consecutive HIV-positive index participants who consented and their 12 identifiable sexual partners. We also conducted two focus group discussions with healthcare workers to supplement the patient perspectives. In the main study, newly diagnosed HIV cases (index cases) were randomized to one of three methods of partner notification: passive, contract, and provider referral. Clients in the passive referral group were responsible for notifying their sexual partners themselves. Individuals in the contract referral group were given seven days to notify their partners, after which a healthcare provider contacted partners who had not reported for counselling and testing. In the provider group, a healthcare provider notified partners directly. Although most index participants and partners expressed a preference for passive notification, they also highlighted benefits for provider-assisted notification and the universal right for all HIV-exposed persons to know their HIV exposure and benefit from HIV testing and access antiretroviral treatment. Several participants mentioned couples counselling as a way to diffuse tension and get accurate information. All mentioned benefits to HIV testing, including the opportunity to change behaviour. Provider-assisted partner notification is not preferred, but it is acceptable and may complement the passive method of notification. Couples counselling should also be encouraged.
ERIC Educational Resources Information Center
van Rhijn, Tricia M.; Murray, Sarah H.; Mizzi, Robert C.
2015-01-01
Through the use of mixed qualitative and quantitative methods, the current study explored the impact of postsecondary study on the intimate relationships and school experiences of partnered mature students. Quantitative regression analyses indicated that parental status, family support, partner support, and sexual desire significantly predicted…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weger, Stefan; Hammer, Eva; Goetz, Anne
2007-05-25
Through yeast two-hybrid analysis and coimmunoprecipitation studies, we have identified a novel cellular AAV-2 Rep78/Rep68 interaction partner located predominantly in the cytoplasm. In public databases, it has been assigned as KCTD5, because of a region of high similarity to the cytoplasmic tetramerization domain of voltage-gated potassium channels. Whereas Rep/KCTD5 interaction relied on the region surrounding the Rep nuclear localization signal, nuclear accumulation of Rep was not required. Wildtype Rep78/Rep68 proteins induced the translocation of large portions of KCTD5 into the nucleus pointing to functional interactions both in the cytoplasm and the nucleus. In line with an anticipated functional interference inmore » the cytoplasm, KCTD5 overexpression completely abrogated Rep68-mediated posttranscriptional activation of a HIV-LTR driven luciferase reporter gene. Our study expands the panel of already identified nuclear Rep interaction partners to a cytoplasmic protein, which raises the awareness that important steps in the AAV life cycle may be regulated in this compartment.« less
Delineating the Tes Interaction Site in Zyxin and Studying Cellular Effects of Its Disruption.
Hadzic, Ermin; Catillon, Marie; Halavatyi, Aliaksandr; Medves, Sandrine; Van Troys, Marleen; Moes, Michèle; Baird, Michelle A; Davidson, Michael W; Schaffner-Reckinger, Elisabeth; Ampe, Christophe; Friederich, Evelyne
2015-01-01
Focal adhesions are integrin-based structures that link the actin cytoskeleton and the extracellular matrix. They play an important role in various cellular functions such as cell signaling, cell motility and cell shape. To ensure and fine tune these different cellular functions, adhesions are regulated by a large number of proteins. The LIM domain protein zyxin localizes to focal adhesions where it participates in the regulation of the actin cytoskeleton. Because of its interactions with a variety of binding partners, zyxin has been proposed to act as a molecular scaffold. Here, we studied the interaction of zyxin with such a partner: Tes. Similar to zyxin, Tes harbors three highly conserved LIM domains of which the LIM1 domain directly interacts with zyxin. Using different zyxin variants in pull-down assays and ectopic recruitment experiments, we identified the Tes binding site in zyxin and showed that four highly conserved amino acids are crucial for its interaction with Tes. Based upon these findings, we used a zyxin mutant defective in Tes-binding to assess the functional consequences of abrogating the zyxin-Tes interaction in focal adhesions. Performing fluorescence recovery after photobleaching, we showed that zyxin recruits Tes to focal adhesions and modulates its turnover in these structures. However, we also provide evidence for zyxin-independent localization of Tes to focal adhesions. Zyxin increases focal adhesion numbers and reduces focal adhesion lifetimes, but does so independent of Tes. Quantitative analysis showed that the loss of interaction between zyxin and Tes affects the process of cell spreading. We conclude that zyxin influences focal adhesion dynamics, that it recruits Tes and that this interaction is functional in regulating cell spreading.
Delineating the Tes Interaction Site in Zyxin and Studying Cellular Effects of Its Disruption
Hadzic, Ermin; Catillon, Marie; Halavatyi, Aliaksandr; Medves, Sandrine; Van Troys, Marleen; Moes, Michèle; Baird, Michelle A.; Davidson, Michael W.; Schaffner-Reckinger, Elisabeth; Ampe, Christophe; Friederich, Evelyne
2015-01-01
Focal adhesions are integrin-based structures that link the actin cytoskeleton and the extracellular matrix. They play an important role in various cellular functions such as cell signaling, cell motility and cell shape. To ensure and fine tune these different cellular functions, adhesions are regulated by a large number of proteins. The LIM domain protein zyxin localizes to focal adhesions where it participates in the regulation of the actin cytoskeleton. Because of its interactions with a variety of binding partners, zyxin has been proposed to act as a molecular scaffold. Here, we studied the interaction of zyxin with such a partner: Tes. Similar to zyxin, Tes harbors three highly conserved LIM domains of which the LIM1 domain directly interacts with zyxin. Using different zyxin variants in pull-down assays and ectopic recruitment experiments, we identified the Tes binding site in zyxin and showed that four highly conserved amino acids are crucial for its interaction with Tes. Based upon these findings, we used a zyxin mutant defective in Tes-binding to assess the functional consequences of abrogating the zyxin-Tes interaction in focal adhesions. Performing fluorescence recovery after photobleaching, we showed that zyxin recruits Tes to focal adhesions and modulates its turnover in these structures. However, we also provide evidence for zyxin-independent localization of Tes to focal adhesions. Zyxin increases focal adhesion numbers and reduces focal adhesion lifetimes, but does so independent of Tes. Quantitative analysis showed that the loss of interaction between zyxin and Tes affects the process of cell spreading. We conclude that zyxin influences focal adhesion dynamics, that it recruits Tes and that this interaction is functional in regulating cell spreading. PMID:26509500
ToxCast HTS Assay Development and Retrofitting: Strategies ...
A presentation to EC JRC partners on new ToxCast HTS assay methods and strategies to address current limitations to HTS methods Slide presentation to EC JRC partners on new ToxCast HTS assay methods and strategies to address current limitations to HTS methods.
Sexually transmitted disease partner notification among African-American, adolescent women.
Buchsbaum, Anna; Gallo, Maria F; Whiteman, Maura K; Cwiak, Carrie; Goedken, Peggy; Kraft, Joan Marie; Jamieson, Denise J; Kottke, Melissa
2014-01-01
To better understand preferences and practices regarding partner notification of sexually transmitted infection (STI) among female, African-American adolescents. Participants completed a questionnaire and STI testing at baseline. Those diagnosed with Chlamydia or gonorrhea were recruited for a follow-up study, involving another questionnaire and repeat STI testing after three months. At baseline, most participants (85.1%) preferred to tell their partner about an STI diagnosis themselves instead of having a health care provider inform him, and 71.0% preferred to bring their partner for clinic treatment instead of giving him pills or a prescription. Two-thirds of participants were classified as having high self-efficacy for partner notification of a positive STI diagnosis. In the multivariable analysis, older participants and those with fewer lifetime sexual partners were more likely to have high self-efficacy. Ninety-three participants (26.6%) had Chlamydia or gonorrhea and, of this subset, 55 participated in the follow-up study. Most adolescents in the follow-up study (76.4%) notified their partner about their infection. Although participants were willing to use most methods of partner notification, most preferred to tell partners themselves and few preferred expedited partner therapy. Traditional methods for partner notification and treatment may not be adequate for all adolescents in this population.
Background | Office of Cancer Clinical Proteomics Research
The term "proteomics" refers to a large-scale comprehensive study of a specific proteome resulting from its genome, including abundances of proteins, their variations and modifications, and interacting partners and networks in order to understand cellular processes involved. Similarly, “Cancer proteomics” refers to comprehensive analyses of proteins and their derivatives translated from a specific cancer genome using a human biospecimen or a preclinical model (e.g., cultured cell or animal model).
ERIC Educational Resources Information Center
Pinkerton, Steven D.; Galletly, Carol L.; McAuliffe, Timothy L.; DiFranceisco, Wayne; Raymond, H. Fisher; Chesson, Harrell W.
2010-01-01
The sexual behaviors of HIV/sexually transmitted infection (STI) prevention intervention participants can be assessed on a partner-by-partner basis: in aggregate (i.e., total numbers of sex acts, collapsed across partners) or using a combination of these two methods (e.g., assessing five partners in detail and any remaining partners in aggregate).…
Drosophila as a genetic and cellular model for studies on axonal growth
Sánchez-Soriano, Natalia; Tear, Guy; Whitington, Paul; Prokop, Andreas
2007-01-01
One of the most fascinating processes during nervous system development is the establishment of stereotypic neuronal networks. An essential step in this process is the outgrowth and precise navigation (pathfinding) of axons and dendrites towards their synaptic partner cells. This phenomenon was first described more than a century ago and, over the past decades, increasing insights have been gained into the cellular and molecular mechanisms regulating neuronal growth and navigation. Progress in this area has been greatly assisted by the use of simple and genetically tractable invertebrate model systems, such as the fruit fly Drosophila melanogaster. This review is dedicated to Drosophila as a genetic and cellular model to study axonal growth and demonstrates how it can and has been used for this research. We describe the various cellular systems of Drosophila used for such studies, insights into axonal growth cones and their cytoskeletal dynamics, and summarise identified molecular signalling pathways required for growth cone navigation, with particular focus on pathfinding decisions in the ventral nerve cord of Drosophila embryos. These Drosophila-specific aspects are viewed in the general context of our current knowledge about neuronal growth. PMID:17475018
Assessment of Trading Partners for China's Rare Earth Exports Using a Decision Analytic Approach
He, Chunyan; Lei, Yalin; Ge, Jianping
2014-01-01
Chinese rare earth export policies currently result in accelerating its depletion. Thus adopting an optimal export trade selection strategy is crucial to determining and ultimately identifying the ideal trading partners. This paper introduces a multi-attribute decision-making methodology which is then used to select the optimal trading partner. In the method, an evaluation criteria system is established to assess the seven top trading partners based on three dimensions: political relationships, economic benefits and industrial security. Specifically, a simple additive weighing model derived from an additive utility function is utilized to calculate, rank and select alternatives. Results show that Japan would be the optimal trading partner for Chinese rare earths. The criteria evaluation method of trading partners for China's rare earth exports provides the Chinese government with a tool to enhance rare earth industrial policies. PMID:25051534
Assessment of trading partners for China's rare earth exports using a decision analytic approach.
He, Chunyan; Lei, Yalin; Ge, Jianping
2014-01-01
Chinese rare earth export policies currently result in accelerating its depletion. Thus adopting an optimal export trade selection strategy is crucial to determining and ultimately identifying the ideal trading partners. This paper introduces a multi-attribute decision-making methodology which is then used to select the optimal trading partner. In the method, an evaluation criteria system is established to assess the seven top trading partners based on three dimensions: political relationships, economic benefits and industrial security. Specifically, a simple additive weighing model derived from an additive utility function is utilized to calculate, rank and select alternatives. Results show that Japan would be the optimal trading partner for Chinese rare earths. The criteria evaluation method of trading partners for China's rare earth exports provides the Chinese government with a tool to enhance rare earth industrial policies.
HSRP and HSRP Partner Analytical Methods and Protocols
HSRP has worked with various partners to develop and test analytical methods and protocols for use by laboratories charged with analyzing environmental and/or buildling material samples following contamination incident.
FK506-Binding Proteins and Their Diverse Functions.
Tong, Mingming; Jiang, Yu
2015-01-01
FK506 binding proteins (FKBPs) are a family of highly conserved proteins in eukaryotes. The prototype of this protein family, FKBP12, is the binding partner for immunosuppressive drugs FK506 and rapamycin. FKBP12 functions as a cis/trans peptidyl prolyl isomerase (PPIase) that catalyzes interconversion between prolyl cis/trans conformations. Members of the FKBP family contain one or several PPIase domains, which do not always exhibit PPIase activity yet are all essential for their function. FKBPs are involved in diverse cellular functions including protein folding, cellular signaling, apoptosis and transcription. They elicit their function through direct binding and altering conformation of their target proteins, hence acting as molecular switches. In this review, we provide a general summary for the structures and diverse functions of FKBPs found in mammalian cells.
Caveolin-1 and Caveolin-2 Can Be Antagonistic Partners in Inflammation and Beyond
de Almeida, Cecília Jacques Gonçalves
2017-01-01
Caveolins, encoded by the CAV gene family, are the main protein components of caveolae. In most tissues, caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are co-expressed, and Cav-2 targeting to caveolae depends on the formation of heterooligomers with Cav-1. Notwithstanding, Cav-2 has unpredictable activities, opposing Cav-1 in the regulation of some cellular processes. While the major roles of Cav-1 as a modulator of cell signaling in inflammatory processes and in immune responses have been extensively discussed elsewhere, the aim of this review is to focus on data revealing the distinct activity of Cav-1 and Cav-2, which suggest that these proteins act antagonistically to fine-tune a variety of cellular processes relevant to inflammation. PMID:29250058
ERIC Educational Resources Information Center
Wallace, Cara L.
2013-01-01
Nurses in all areas of healthcare are exposed to patients who are suspected or actual victims of intimate partner violence. Many times nurses report a general lack of knowledge in regard to the topic. Therefore, it is paramount for nursing educators to identify effective methods to teach their students about intimate partner violence in an effort…
van Manen, Mirjam J.G.; Kreuter, Michael; van den Blink, Bernt; Oltmanns, Ute; Palmowski, Karin; Brunnemer, Eva; Hummler, Simone; Tak, Nelleke C.; van den Toorn, Leon; Miedema, Jelle; Hoogsteden, Henk C.
2017-01-01
Pulmonary fibrosis greatly impacts patients and their partners. Unmet needs of patients are increasingly acknowledged; the needs of partners often remain unnoticed. Little is known about the best way to educate patients and partners. We investigated pulmonary fibrosis patients' and partners' perspectives and preferences in care, and the differences in these between the Netherlands and Germany. Additionally, we evaluated whether interactive interviewing could be a novel education method in this population. Patients and partners were interviewed during pulmonary fibrosis patient information meetings. In the Netherlands, voting boxes were used and results were projected directly. In Germany, questionnaires were used. In the Netherlands, 278 patients and partners participated; in Germany, 51. Many participants experienced anxiety. Almost all experienced misunderstanding, because people do not know what pulmonary fibrosis is. All expressed a need for information, psychological support and care for partners. Use of the interactive voting system was found to be pleasant (70%) and informative (94%). This study improves the knowledge of care needs of patients with pulmonary fibrosis and their partners. There were no major differences between the Netherlands and Germany. Interactive interviewing could be an attractive method to acquire insights into the needs and preferences of patients and partners, while providing them with information at the same time. PMID:28229083
van Manen, Mirjam J G; Kreuter, Michael; van den Blink, Bernt; Oltmanns, Ute; Palmowski, Karin; Brunnemer, Eva; Hummler, Simone; Tak, Nelleke C; van den Toorn, Leon; Miedema, Jelle; Hoogsteden, Henk C; Wijsenbeek, Marlies S
2017-01-01
Pulmonary fibrosis greatly impacts patients and their partners. Unmet needs of patients are increasingly acknowledged; the needs of partners often remain unnoticed. Little is known about the best way to educate patients and partners. We investigated pulmonary fibrosis patients' and partners' perspectives and preferences in care, and the differences in these between the Netherlands and Germany. Additionally, we evaluated whether interactive interviewing could be a novel education method in this population. Patients and partners were interviewed during pulmonary fibrosis patient information meetings. In the Netherlands, voting boxes were used and results were projected directly. In Germany, questionnaires were used. In the Netherlands, 278 patients and partners participated; in Germany, 51. Many participants experienced anxiety. Almost all experienced misunderstanding, because people do not know what pulmonary fibrosis is. All expressed a need for information, psychological support and care for partners. Use of the interactive voting system was found to be pleasant (70%) and informative (94%). This study improves the knowledge of care needs of patients with pulmonary fibrosis and their partners. There were no major differences between the Netherlands and Germany. Interactive interviewing could be an attractive method to acquire insights into the needs and preferences of patients and partners, while providing them with information at the same time.
Beyond Antibodies as Binding Partners: The Role of Antibody Mimetics in Bioanalysis.
Yu, Xiaowen; Yang, Yu-Ping; Dikici, Emre; Deo, Sapna K; Daunert, Sylvia
2017-06-12
The emergence of novel binding proteins or antibody mimetics capable of binding to ligand analytes in a manner analogous to that of the antigen-antibody interaction has spurred increased interest in the biotechnology and bioanalytical communities. The goal is to produce antibody mimetics designed to outperform antibodies with regard to binding affinities, cellular and tumor penetration, large-scale production, and temperature and pH stability. The generation of antibody mimetics with tailored characteristics involves the identification of a naturally occurring protein scaffold as a template that binds to a desired ligand. This scaffold is then engineered to create a superior binder by first creating a library that is then subjected to a series of selection steps. Antibody mimetics have been successfully used in the development of binding assays for the detection of analytes in biological samples, as well as in separation methods, cancer therapy, targeted drug delivery, and in vivo imaging. This review describes recent advances in the field of antibody mimetics and their applications in bioanalytical chemistry, specifically in diagnostics and other analytical methods.
Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer
2007-03-01
nucleus. To confirm the staining is indeed specific, another antibody specific for CrkII is being tested. Furthermore, cytoplasmic and nuclear...the endogenous CrkL binding partner, Gab1 , which is enhanced upon HGF stimulation (Appendix 16). One final experiment, showing that the CrkLV5 tag...receptor tyrosine kinases, and a docking protein Gab1 , involved in epithelial dispersal and morphogenesis (5, 11, 12). The NH2-terminal SH3 domain of
hEcd, A Novel Regulator of Mammary Epithelial Cell Survival
2009-09-01
theYeast Two hybrid analysis with human papilloma virus oncogene E6 (the most efficient oncogene to immortalize hMECs in vitro) as a bait and mammary...transformation. We have identified a novel protein us ing the Yeast Two hybrid analysis with human papilloma virus oncogene E6 (the most efficient...epithelial cell cDNA library, we identified hEcd ( human orthologue of Drosophila Ecdysoneless) as a novel E6 binding partner. To study the cellular
Acceptance of routine or case-based inquiry for intimate partner violence: a mixed method study
2013-01-01
Background The prevalence and detrimental health effects of intimate partner violence have resulted in international discussions and recommendations that health care professionals should screen women for intimate partner violence during general and antenatal health care visits. Due to the lack of discussion on routine or case-based inquiry for intimate partner violence during antenatal care in Germany, this study seeks to explore its acceptability among pregnant German women. Methods A mixed methods approach was used, utilizing a self-administered survey on the acceptability of routine or case-based inquiry for intimate partner violence in a university hospital’s maternity ward in Munich and in-depth interviews with seven women who experienced violence during pregnancy. Results Of the 401 women who participated in the survey, 92 percent were in favor of routine or case-based inquiry for intimate partner violence during antenatal care. Acceptance of routine or case-based inquiry for intimate partner violence during antenatal care was significantly associated with women’s experiences of child sexual abuse, being young, less educated, single or divorced and smoking during pregnancy. Open-ended survey questions and in-depth interviews stressed adequate training for screening, sufficient time and provision of referral information as important conditions for routine or case-based inquiry for intimate partner violence. Conclusions Women in this study showed an overwhelming support for routine or case-based screening for intimate partner violence in antenatal care in Germany. Until adequate training is in place to allow providers to inquire for intimate partner violence in a professional manner, this study recommends that health care providers are made aware of the prevalence and health consequences of violence during pregnancy. PMID:23531127
Inforna 2.0: A Platform for the Sequence-Based Design of Small Molecules Targeting Structured RNAs.
Disney, Matthew D; Winkelsas, Audrey M; Velagapudi, Sai Pradeep; Southern, Mark; Fallahi, Mohammad; Childs-Disney, Jessica L
2016-06-17
The development of small molecules that target RNA is challenging yet, if successful, could advance the development of chemical probes to study RNA function or precision therapeutics to treat RNA-mediated disease. Previously, we described Inforna, an approach that can mine motifs (secondary structures) within target RNAs, which is deduced from the RNA sequence, and compare them to a database of known RNA motif-small molecule binding partners. Output generated by Inforna includes the motif found in both the database and the desired RNA target, lead small molecules for that target, and other related meta-data. Lead small molecules can then be tested for binding and affecting cellular (dys)function. Herein, we describe Inforna 2.0, which incorporates all known RNA motif-small molecule binding partners reported in the scientific literature, a chemical similarity searching feature, and an improved user interface and is freely available via an online web server. By incorporation of interactions identified by other laboratories, the database has been doubled, containing 1936 RNA motif-small molecule interactions, including 244 unique small molecules and 1331 motifs. Interestingly, chemotype analysis of the compounds that bind RNA in the database reveals features in small molecule chemotypes that are privileged for binding. Further, this updated database expanded the number of cellular RNAs to which lead compounds can be identified.
Nitric-oxide Synthase Forms N-NO-pterin and S-NO-Cys
Rosenfeld, Robin J.; Bonaventura, Joseph; Szymczyna, Blair R.; MacCoss, Michael J.; Arvai, Andrew S.; Yates, John R.; Tainer, John A.; Getzoff, Elizabeth D.
2010-01-01
Inducible nitric-oxide synthase (iNOS) produces biologically stressful levels of nitric oxide (NO) as a potent mediator of cellular cytotoxicity or signaling. Yet, how this nitrosative stress affects iNOS function in vivo is poorly understood. Here we define two specific non-heme iNOS nitrosation sites discovered by combining UV-visible spectroscopy, chemiluminescence, mass spectrometry, and x-ray crystallography. We detected auto-S-nitrosylation during enzymatic turnover by using chemiluminescence. Selective S-nitrosylation of the ZnS4 site, which bridges the dimer interface, promoted a dimer-destabilizing order-to-disorder transition. The nitrosated iNOS crystal structure revealed an unexpected N-NO modification on the pterin cofactor. Furthermore, the structurally defined N-NO moiety is solvent-exposed and available to transfer NO to a partner. We investigated glutathione (GSH) as a potential transnitrosation partner because the intracellular GSH concentration is high and NOS can form S-nitrosoglutathione. Our computational results predicted a GSH binding site adjacent to the N-NO-pterin. Moreover, we detected GSH binding to iNOS with saturation transfer difference NMR spectroscopy. Collectively, these observations resolve previous paradoxes regarding this uncommon pterin cofactor in NOS and suggest means for regulating iNOS activity via N-NO-pterin and S-NO-Cys modifications. The iNOS self-nitrosation characterized here appears appropriate to help control NO production in response to cellular conditions. PMID:20659888
ERIC Educational Resources Information Center
Murphy, Sharon; Lemire, Lynne; Wisman, Mindi
2009-01-01
This qualitative case study explores one American Indian (AI) woman's experience of intimate partner violence and the subsequent murder of her abusive partner. The lens of complex personhood (Gordon, 1997) has been applied as a method for understanding "Annie's" multiple identities of AI woman, victim of intimate partner violence, mother, and…
McCarraher, Donna R; Martin, Sandra L; Bailey, Patricia E
2006-03-01
Intimate partner violence is widespread worldwide. While assumed to impact women's ability to use contraceptive methods, few data are available to support this claim. In this study, eight focus group discussions were conducted to guide questionnaire development and to provide contextual information. Participants were women who were currently using the pill and women who had used the pill previously. In addition, 300 women were interviewed who initiated oral contraceptive pill use between December 1995 and April 1996. Participants were interviewed 3-6 months later to investigate the role intimate partner violence played in covert pill use and pill discontinuation. Special study procedures for asking women questions about violence were employed. Nineteen per cent of the women interviewed were using the pill covertly. The odds of covert pill use were four times higher in El Alto and La Paz than in Santa Cruz. Women who used the pill covertly were more likely to have experienced method-related partner violence (OR = 21.27) than women whose partners knew of their pill use. One-third of the women had discontinued pill use at the time of the interview. In the final multivariate analysis, having experienced side-effects (OR = 2.37) was a significant predictor of pill discontinuation and method-related partner violence was marginally predictive (OR = 1.91; 95% CI 1.0-3.66). While efforts are ongoing to incorporate men into family planning programmes, some male partners oppose, and in some situations violently oppose, contraceptive use. The needs of women with these types of partners must not be overlooked.
Partner Dependence and Sexual Risk Behavior Among STI Clinic Patients
Senn, Theresa E.; Carey, Michael P.; Vanable, Peter A.; Coury-Doniger, Patricia
2010-01-01
Objectives To investigate the relation between partner dependence and sexual risk behavior in the context of the information-motivation-behavioral skills (IMB) model. Methods STI clinic patients (n = 1432) completed a computerized interview assessing partner dependence, condom use, and IMB variables. Results Men had higher partner-dependence scores than women did. Patients reporting greater dependence reported less condom use. Gender did not moderate the partner dependence-condom-use relationship. Partner dependence did not moderate the relation between IMB constructs and condom use. Conclusions Further research is needed to determine how partner dependence can be incorporated into conceptual models of safer sex behaviors. PMID:20001183
Older adults' acceptance of a robot for partner dance-based exercise.
Chen, Tiffany L; Bhattacharjee, Tapomayukh; Beer, Jenay M; Ting, Lena H; Hackney, Madeleine E; Rogers, Wendy A; Kemp, Charles C
2017-01-01
Partner dance has been shown to be beneficial for the health of older adults. Robots could potentially facilitate healthy aging by engaging older adults in partner dance-based exercise. However, partner dance involves physical contact between the dancers, and older adults would need to be accepting of partner dancing with a robot. Using methods from the technology acceptance literature, we conducted a study with 16 healthy older adults to investigate their acceptance of robots for partner dance-based exercise. Participants successfully led a human-scale wheeled robot with arms (i.e., a mobile manipulator) in a simple, which we refer to as the Partnered Stepping Task (PST). Participants led the robot by maintaining physical contact and applying forces to the robot's end effectors. According to questionnaires, participants were generally accepting of the robot for partner dance-based exercise, tending to perceive it as useful, easy to use, and enjoyable. Participants tended to perceive the robot as easier to use after performing the PST with it. Through a qualitative data analysis of structured interview data, we also identified facilitators and barriers to acceptance of robots for partner dance-based exercise. Throughout the study, our robot used admittance control to successfully dance with older adults, demonstrating the feasibility of this method. Overall, our results suggest that robots could successfully engage older adults in partner dance-based exercise.
Older adults’ acceptance of a robot for partner dance-based exercise
Chen, Tiffany L.; Beer, Jenay M.; Ting, Lena H.; Hackney, Madeleine E.; Rogers, Wendy A.; Kemp, Charles C.
2017-01-01
Partner dance has been shown to be beneficial for the health of older adults. Robots could potentially facilitate healthy aging by engaging older adults in partner dance-based exercise. However, partner dance involves physical contact between the dancers, and older adults would need to be accepting of partner dancing with a robot. Using methods from the technology acceptance literature, we conducted a study with 16 healthy older adults to investigate their acceptance of robots for partner dance-based exercise. Participants successfully led a human-scale wheeled robot with arms (i.e., a mobile manipulator) in a simple, which we refer to as the Partnered Stepping Task (PST). Participants led the robot by maintaining physical contact and applying forces to the robot’s end effectors. According to questionnaires, participants were generally accepting of the robot for partner dance-based exercise, tending to perceive it as useful, easy to use, and enjoyable. Participants tended to perceive the robot as easier to use after performing the PST with it. Through a qualitative data analysis of structured interview data, we also identified facilitators and barriers to acceptance of robots for partner dance-based exercise. Throughout the study, our robot used admittance control to successfully dance with older adults, demonstrating the feasibility of this method. Overall, our results suggest that robots could successfully engage older adults in partner dance-based exercise. PMID:29045408
Tracking Image Correlation: Combining Single-Particle Tracking and Image Correlation
Dupont, A.; Stirnnagel, K.; Lindemann, D.; Lamb, D.C.
2013-01-01
The interactions and coordination of biomolecules are crucial for most cellular functions. The observation of protein interactions in live cells may provide a better understanding of the underlying mechanisms. After fluorescent labeling of the interacting partners and live-cell microscopy, the colocalization is generally analyzed by quantitative global methods. Recent studies have addressed questions regarding the individual colocalization of moving biomolecules, usually by using single-particle tracking (SPT) and comparing the fluorescent intensities in both color channels. Here, we introduce a new method that combines SPT and correlation methods to obtain a dynamical 3D colocalization analysis along single trajectories of dual-colored particles. After 3D tracking, the colocalization is computed at each particle’s position via the local 3D image cross correlation of the two detection channels. For every particle analyzed, the output consists of the 3D trajectory, the time-resolved 3D colocalization information, and the fluorescence intensity in both channels. In addition, the cross-correlation analysis shows the 3D relative movement of the two fluorescent labels with an accuracy of 30 nm. We apply this method to the tracking of viral fusion events in live cells and demonstrate its capacity to obtain the time-resolved colocalization status of single particles in dense and noisy environments. PMID:23746509
Kleinman, Lawrence C.; Lutz, David; Plumb, Ellen J.; Barkley, Pearl; Nazario, Hector R.; Ramos, Michelle A.; Horowitz, Carol R.
2012-01-01
Background The Communities IMPACT Diabetes Center uses partnered methods to address diabetes-related conditions among African Americans and Latinos in East Harlem, New York. Objectives To describe a novel, partnered approach that integrates simultaneous structured observation by community and academic partners with “on-the-spot” resolution of differences to collect baseline data regarding the built and food environments in a two census tract area of East Harlem and present select findings. Methods We designed an environmental assessment to explore characteristics of the environment related to walking and eating. We paired community and academic partners to assess each block, resolve any differences, and report results. Nearly one year later, we surveyed the data collectors and analyzed responses using standard qualitative methods. Results Key themes included connection to and characteristics of the community; interactions with partners; surprises and learning, and aspects of data collection. All but the first were common to academic and community partners. Relationships between partners were generally amiable. Both community—“I think it was very helpful, we made sure neither of us made mistakes, and helped each other when we could”—and academic–“I really enjoyed it … I learned a lot about the areas I surveyed”—partners were complimentary. Community partners’ strengths included local knowledge of the community, whereas academic partners’ focus on adherence to the specifications was critical. Structured observation identified many sidewalks in disrepair or obstructed, few benches, and highly variable times allocated for pedestrians to cross at cross walks. Conclusions The partnered data collection was both successful and formative, building additional relationships and further capacity for ongoing partnership. Community partners saw their community in a new way, seeing, “little things that are important but people don’t pay attention to.” Structured observations added to our understanding of how an environment may contribute to diabetes. PMID:22080773
Stockman, Jamila K.; Syvertsen, Jennifer L.; Robertson, Angela M.; Ludwig-Barron, Natasha T.; Bergmann, Julie N.; Palinkas, Lawrence A.
2014-01-01
BACKGROUND Female-initiated barrier methods for the prevention of HIV may be an effective alternative for drug-using women who are unable to negotiate safe sex, often as a result of physical and/or sexual partner violence. METHODS Utilizing a SAVA (substance abuse, violence, and AIDS) syndemic framework, we qualitatively examined perspectives on female condoms and vaginal microbicides among 18 women with histories of methamphetamine abuse and partner violence in San Diego, CA, USA. FINDINGS Most women were not interested in female condoms due to perceived discomfort, difficulty of insertion, time-intensive effort, and unappealing appearance. Alternatively, most women viewed vaginal microbicides as a useful method. Positive aspects included convenience, ability to disguise as a lubricant, and a sense of control and empowerment. Concerns included possible side effects, timing of application, and unfavorable characteristics of the gel. Acceptability of female-initiated barrier methods was context dependent (i.e., partner type, level of drug use and violence that characterized the sexual relationship). CONCLUSIONS Findings indicate that efforts are needed to address barriers identified for vaginal microbicides to increase its uptake in future HIV prevention trials and marketing of future FDA-approved products. Strategies should address gender-based inequalities (e.g., partner violence) experienced by drug-using women and promote female empowerment. Education on female-initiated barrier methods is also needed for women who use drugs, as well as health care providers and other professionals providing sexual health care and contraception to women with histories of drug use and partner violence. PMID:24837396
Kleinman, Lawrence C; Lutz, David; Plumb, Ellen J; Barkley, Pearl; Nazario, Hector R; Ramos, Michelle A; Horowitz, Carol R
2011-01-01
The Communities IMPACT Diabetes Center uses partnered methods to address diabetes-related conditions among African Americans and Latinos in East Harlem, New York. To describe a novel, partnered approach that integrates simultaneous structured observation by community and academic partners with "on-the-spot" resolution of differences to collect baseline data regarding the built and food environments in a two census tract area of East Harlem and present select findings. We designed an environmental assessment to explore characteristics of the environment related to walking and eating. We paired community and academic partners to assess each block, resolve any differences, and report results. Nearly one year later, we surveyed the data collectors and analyzed responses using standard qualitative methods. Key themes included connection to and characteristics of the community; interactions with partners; surprises and learning, and aspects of data collection. All but the first were common to academic and community partners. Relationships between partners were generally amiable. Both community-"I think it was very helpful, we made sure neither of us made mistakes, and helped each other when we could"-and academic-"I really enjoyed it . . . I learned a lot about the areas I surveyed"-partners were complimentary. Community partners' strengths included local knowledge of the community, whereas academic partners' focus on adherence to the specifications was critical. Structured observation identified many sidewalks in disrepair or obstructed, few benches, and highly variable times allocated for pedestrians to cross at cross walks. The partnered data collection was both successful and formative, building additional relationships and further capacity for ongoing partnership. Community partners saw their community in a new way, seeing, "little things that are important but people don't pay attention to." Structured observations added to our understanding of how an environment may contribute to diabetes.
Gordon, B R; Martin, D E; Bambery, K R; Motti, C A
2018-04-01
The symbiotic relationship between corals and Symbiodinium spp. is the key to the success and survival of coral reef ecosystems the world over. Nutrient exchange and chemical communication between the two partners provides the foundation of this key relationship, yet we are far from a complete understanding of these processes. This is due, in part, to the difficulties associated with studying an intracellular symbiosis at the small spatial scales required to elucidate metabolic interactions between the two partners. This feasibility study, which accompanied a more extensive investigation of fixed Symbiodinium cells (data unpublished), examines the potential of using synchrotron radiation infrared microspectroscopy (SR-IRM) for exploring metabolite localisation within a single Symbiodinium cell. In doing so, three chemically distinct subcellular regions of a single Symbiodinium cell were established and correlated to cellular function based on assignment of diagnostic chemical classes. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.
Intrinsically Disordered Energy Landscapes
Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.
2015-01-01
Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium. PMID:25999294
Histone chaperones: an escort network regulating histone traffic.
De Koning, Leanne; Corpet, Armelle; Haber, James E; Almouzni, Geneviève
2007-11-01
In eukaryotes, DNA is organized into chromatin in a dynamic manner that enables it to be accessed for processes such as transcription and repair. Histones, the chief protein component of chromatin, must be assembled, replaced or exchanged to preserve or change this organization according to cellular needs. Histone chaperones are key actors during histone metabolism. Here we classify known histone chaperones and discuss how they build a network to escort histone proteins. Molecular interactions with histones and their potential specificity or redundancy are also discussed in light of chaperone structural properties. The multiplicity of histone chaperone partners, including histone modifiers, nucleosome remodelers and cell-cycle regulators, is relevant to their coordination with key cellular processes. Given the current interest in chromatin as a source of epigenetic marks, we address the potential contributions of histone chaperones to epigenetic memory and genome stability.
Emerging role of the Jun N-terminal kinase interactome in human health.
Guo, Xiao-Xi; An, Su; Yang, Yang; Liu, Ying; Hao, Qian; Tang, Tao; Xu, Tian-Rui
2018-02-08
The c-Jun N-terminal kinases (JNKs) are located downstream of Ras-mitogen activated protein kinase signaling cascades. More than 20 years of study has shown that JNKs control cell fate and many cellular functions. JNKs and their interacting proteins form a complicated network with diverse biological functions and physiological effects. Members of the JNK interactome include Jun, amyloid precursor protein, and insulin receptor substrate. Recent studies have shown that the JNK interactome is involved in tumorigenesis, neuron development, and insulin resistance. In this review, we summarize the features of the JNK interactome and classify its members into three groups: upstream regulators, downstream effectors, and scaffold partners. We also highlight the unique cellular signaling mechanisms of JNKs and provide more insights into the roles of the JNK interactome in human diseases. © 2018 International Federation for Cell Biology.
Synthesis, Delivery and Regulation of Eukaryotic Heme and Fe-S Cluster Cofactors
Barupala, Dulmini P.; Dzul, Stephen P.; Riggs-Gelasco, Pamela Jo; Stemmler, Timothy L.
2016-01-01
In humans, the bulk of iron in the body (over 75%) is directed towards heme- or Fe-S cluster cofactor synthesis, and the complex, highly regulated pathways in place to accomplish biosynthesis have evolved to safely assemble and load these cofactors into apoprotein partners. In eukaryotes, heme biosynthesis is both initiated and finalized within the mitochondria, while cellular Fe-S cluster assembly is controlled by correlated pathways both within the mitochondria and within the cytosol. Iron plays a vital role in a wide array of metabolic processes and defects in iron cofactor assembly leads to human diseases. This review describes progress towards our molecular-level understanding of cellular heme and Fe-S cluster biosynthesis, focusing on the regulation and mechanistic details that are essential for understanding human disorders related to the breakdown in these essential pathways. PMID:26785297
Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer
2008-03-01
interact with the endogenous CrkL binding partner, Gab1 , which is enhanced upon HGF stimulation. The over- expression of CrkL and Gab1 leads to Rac...transgenic line in both virgin and lactating mice (Figure 1C). Moreover, although the antibody recognizes endogenous protein, it is clearly evident that...found equal levels in both the nucleus and cytoplasm using two different antibodies targeting CrkI/II or specifically CrkII (7). Furthermore, we have
2013-10-01
IDPs have flexibility, thereby providing the plasticity to enable interactions with multiple partners where high-specificity and low-affinity...block protein-protein interactions is a rapidly evolving field, as the importance of these proteins in disease becomes established. The plasticity of...closest to the structure of EPI-002 — did not bind an abundance of other cellular proteins (Figure 3D , top). Only 3 bands between 200 and 75 kDa were
Verma, Amit K; Diwan, Danish; Raut, Sandeep; Dobriyal, Neha; Brown, Rebecca E; Gowda, Vinita; Hines, Justin K; Sahi, Chandan
2017-06-07
Heat shock proteins of 70 kDa (Hsp70s) partner with structurally diverse Hsp40s (J proteins), generating distinct chaperone networks in various cellular compartments that perform myriad housekeeping and stress-associated functions in all organisms. Plants, being sessile, need to constantly maintain their cellular proteostasis in response to external environmental cues. In these situations, the Hsp70:J protein machines may play an important role in fine-tuning cellular protein quality control. Although ubiquitous, the functional specificity and complexity of the plant Hsp70:J protein network has not been studied. Here, we analyzed the J protein network in the cytosol of Arabidopsis thaliana and, using yeast genetics, show that the functional specificities of most plant J proteins in fundamental chaperone functions are conserved across long evolutionary timescales. Detailed phylogenetic and functional analysis revealed that increased number, regulatory differences, and neofunctionalization in J proteins together contribute to the emerging functional diversity and complexity in the Hsp70:J protein network in higher plants. Based on the data presented, we propose that higher plants have orchestrated their "chaperome," especially their J protein complement, according to their specialized cellular and physiological stipulations. Copyright © 2017 Verma et al.
Accurate prediction of protein–protein interactions from sequence alignments using a Bayesian method
Burger, Lukas; van Nimwegen, Erik
2008-01-01
Accurate and large-scale prediction of protein–protein interactions directly from amino-acid sequences is one of the great challenges in computational biology. Here we present a new Bayesian network method that predicts interaction partners using only multiple alignments of amino-acid sequences of interacting protein domains, without tunable parameters, and without the need for any training examples. We first apply the method to bacterial two-component systems and comprehensively reconstruct two-component signaling networks across all sequenced bacteria. Comparisons of our predictions with known interactions show that our method infers interaction partners genome-wide with high accuracy. To demonstrate the general applicability of our method we show that it also accurately predicts interaction partners in a recent dataset of polyketide synthases. Analysis of the predicted genome-wide two-component signaling networks shows that cognates (interacting kinase/regulator pairs, which lie adjacent on the genome) and orphans (which lie isolated) form two relatively independent components of the signaling network in each genome. In addition, while most genes are predicted to have only a small number of interaction partners, we find that 10% of orphans form a separate class of ‘hub' nodes that distribute and integrate signals to and from up to tens of different interaction partners. PMID:18277381
Laborde, Nicole D; Pleasants, Elizabeth; Reddy, Krishnaveni; Atujuna, Millicent; Nakyanzi, Teopista; Chitukuta, Miria; Naidoo, Sarita; Palanee-Phillips, Thesla; Baeten, Jared M; Montgomery, Elizabeth T
2018-02-01
Vaginally-inserted HIV prevention methods have been reported to impact the sexual experience for women and their partners, and hence impacts acceptability of and adherence to the method. We analyzed in-depth interviews and focus group discussions about participants' sexual experiences while wearing the ring, collected during the MTN-020/ASPIRE phase 3 safety and effectiveness trial of a dapivirine vaginal ring for HIV prevention in Malawi, South Africa, Uganda, and Zimbabwe. Most women reported that partners did not feel the ring during sex, however, women felt they had to manage their partners' interaction with or reaction to the ring. In maintaining positive relationships, women were concerned about partners' discovering ring use and about ensuring that partners had a good sexual experience with them. Finally women were concerned about how they themselves experienced sex with the ring. Some found that the ring made the vaginal environment more desirable for their partners and themselves.
Alcohol Consumption, Drug Use, and Condom Use Among STD Clinic Patients*
Scott-Sheldon, Lori A. J.; Carey, Michael P.; Vanable, Peter A.; Senn, Theresa E.; Coury-Doniger, Patricia; Urban, Marguerite A.
2009-01-01
Objective: Research on the association between substance use and sexual risk behavior has yielded a complex pattern of findings. Such inconsistent findings may reflect method variance, including factors such as gender of the participant, nature of the sexual event, partner characteristics, and type of substance used. The purpose of this study was to investigate the association between substance use and unprotected sex independently for alcohol, drugs, or combined substance use and to examine partner characteristics as a moderator of this association. Method: Participants (N = 1,419; 48% women) were recruited from a publicly funded sexually transmitted disease clinic and were asked to complete an audio computer-assisted self-interview regarding their most recent sexual experience, including nature of the event, substance use, and partner characteristics. Results: Analyses showed that alcohol use was related to condom use when gender and partner type were considered; thus, for women, but not for men, partner type interacted with alcohol consumption such that condom use was less likely when alcohol consumption preceded sex with nonprimary partners (drinking was unrelated to condom use with primary partners). Subsequent analyses examining partner substance use showed that women, but not men, who reported both they and their nonprimary partners were drinking during sex were less likely to use a condom. Conclusions: At the event level, alcohol consumption among sexually transmitted disease clinic patients is associated with condom use, but this association differs by gender and partner characteristics. Findings suggest the need to strengthen substance-use components in sexual risk reduction interventions for women and their partners. PMID:19737501
Exploring partners' perspectives on participation in heart failure home care: a mixed-method design.
Näsström, Lena; Luttik, Marie Louise; Idvall, Ewa; Strömberg, Anna
2017-05-01
To describe the partners' perspectives on participation in the care for patients with heart failure receiving home care. Partners are often involved in care of patients with heart failure and have an important role in improving patients' well-being and self-care. Partners have described both negative and positive experiences of involvement, but knowledge of how partners of patients with heart failure view participation in care when the patient receives home care is lacking. A convergent parallel mixed-method design was used, including data from interviews and questionnaires. A purposeful sample of 15 partners was used. Data collection lasted between February 2010 - December 2011. Interviews were analysed with content analysis and data from questionnaires (participation, caregiving, health-related quality of life, depressive symptoms) were analysed statistically. Finally, results were merged, interpreted and labelled as comparable and convergent or as being inconsistent. Partners were satisfied with most aspects of participation, information and contact. Qualitative findings revealed four different aspects of participation: adapting to the caring needs and illness trajectory, coping with caregiving demands, interacting with healthcare providers and need for knowledge to comprehend the health situation. Results showed confirmatory results that were convergent and expanded knowledge that gave a broader understanding of partner participation in this context. The results revealed different levels of partner participation. Heart failure home care included good opportunities for both participation and contact during home visits, necessary to meet partners' ongoing need for information to comprehend the situation. © 2016 John Wiley & Sons Ltd.
Crane, Cory A
2018-03-07
Efforts designed to investigate the effects of recent alcohol use on the perception of intimate partner aggression have been stultified by significant financial and logistical barriers that warrant the development of supplemental research methods that may result in more prolific investigation of the phenomenon. The current study explored the viability of using online crowdsourcing to assess the effects of recent alcohol use on the perception of partner aggression. Mechanical Turk was used to recruit a convenience sample of 60 males who were asked to provide information on their own use of partner aggression, their most recent episode of alcohol use, and their perception of the behaviors and characters depicted in a written partner aggression vignette. Data were evaluated using five separate hierarchical multiple regression models predicting participant perception. Analyses revealed that 35% of the sample had used partner aggression in the past year and that 22% of the sample had consumed alcohol in the past day. Nonviolent participants perceived the aggressor and the behavior more negatively than partner violent participants. Some indicators revealed that recent alcohol use was associated with more positive perceptions of partner aggression. Expected associations among prior partner aggression, recent alcohol use, and perception of partner aggression vignettes were observed. Crowdsourcing may represent a source for data evaluating the effects of recent alcohol use on perceptions of aggression. Methodological refinement will benefit research and, ultimately, clinical prevention and intervention.
Zhang, Chengxin; Zheng, Wei; Freddolino, Peter L; Zhang, Yang
2018-03-10
Homology-based transferal remains the major approach to computational protein function annotations, but it becomes increasingly unreliable when the sequence identity between query and template decreases below 30%. We propose a novel pipeline, MetaGO, to deduce Gene Ontology attributes of proteins by combining sequence homology-based annotation with low-resolution structure prediction and comparison, and partner's homology-based protein-protein network mapping. The pipeline was tested on a large-scale set of 1000 non-redundant proteins from the CAFA3 experiment. Under the stringent benchmark conditions where templates with >30% sequence identity to the query are excluded, MetaGO achieves average F-measures of 0.487, 0.408, and 0.598, for Molecular Function, Biological Process, and Cellular Component, respectively, which are significantly higher than those achieved by other state-of-the-art function annotations methods. Detailed data analysis shows that the major advantage of the MetaGO lies in the new functional homolog detections from partner's homology-based network mapping and structure-based local and global structure alignments, the confidence scores of which can be optimally combined through logistic regression. These data demonstrate the power of using a hybrid model incorporating protein structure and interaction networks to deduce new functional insights beyond traditional sequence homology-based referrals, especially for proteins that lack homologous function templates. The MetaGO pipeline is available at http://zhanglab.ccmb.med.umich.edu/MetaGO/. Copyright © 2018. Published by Elsevier Ltd.
Risk Factors for Intimate Partner Violence During Pregnancy and Postpartum
Hellmuth, Julianne C.; Gordon, Kristina Coop; Stuart, Gregory L.; Moore, Todd M.
2012-01-01
Purpose This longitudinal investigation examined potential risk factors for intimate partner violence (IPV) among women during pregnancy and 6 weeks postpartum. Methods A sample of 180 pregnant women was collected in order to investigate 1) whether associations between partner alcohol misuse, partner jealousy, partner suspicion of infidelity, and stress were associated with IPV victimization, 2) the indirect effects of alcohol misuse on these relationships, and 3) factors related to changes in IPV victimization over time. Results At baseline, partner alcohol misuse was associated with each type of IPV victimization and the combination of partner alcohol misuse, partner jealousy, and partner suspicion of infidelity was most strongly associated with severe physical victimization. Partner alcohol misuse mediated the relationship between partner jealousy and psychological and severe physical victimization. At follow-up, partner jealousy and stress were related to women’s psychological victimization and partner alcohol misuse was related to women’s severe physical victimization. Conclusions Findings suggest that partner alcohol misuse is a risk factor for women’s IPV victimization during pregnancy and jealousy and stress may increase risk for some types of IPV. Findings also suggest that intervention should target parents early in pregnancy in order to reduce the risk for future IPV. PMID:23053216
Zencir, Sevil; Banerjee, Monimoy; Dobson, Melanie J.; Ayaydin, Ferhan; Fodor, Elfrieda Ayaydin; Topcu, Zeki; Mohanty, Smita
2013-01-01
Regulation of gene expression in cells is mediated by protein-protein, DNA-protein and receptor-ligand interactions. PDZ (PSD-95/Discs-large/ZO-1) domains are protein–protein interaction modules. PDZ-containing proteins function in the organization of multi-protein complexes controlling spatial and temporal fidelity of intracellular signaling pathways. In general, PDZ proteins possess multiple domains facilitating distinct interactions. The human Glutaminase Interacting Protein (hGIP) is an unusual PDZ protein comprising entirely of a single PDZ domain and plays pivotal roles in many cellular processes through its interaction with the C-terminus of partner proteins. Here, we report the identification by yeast two-hybrid screening of two new hGIP-interacting partners, DTX1 and STAU1. Both proteins lack the typical C-terminal PDZ recognition motif but contain a novel internal hGIP recognition motif recently identified in a phage display library screen. Fluorescence resonance energy transfer and confocal microscopy analysis confirmed the in vivo association of hGIP with DTX1 and STAU1 in mammalian cells validating the previous discovery of S/T-X-V/L-D as a consensus internal motif for hGIP recognition. Similar to hGIP, DTX1 and STAU1 have been implicated in neuronal function. Identification of these new interacting partners furthers our understanding of GIP-regulated signaling cascades and these interactions may represent potential new drug targets in humans. PMID:23395680
Correlated preferences for facial masculinity and ideal or actual partner's masculinity
DeBruine, Lisa M; Jones, Benedict C; Little, Anthony C; Boothroyd, Lynda G; Perrett, David I; Penton-Voak, Ian S; Cooper, Philip A; Penke, Lars; Feinberg, David R; Tiddeman, Bernard P
2006-01-01
Studies of women's preferences for male faces have variously reported preferences for masculine faces, preferences for feminine faces and no effect of masculinity–femininity on male facial attractiveness. It has been suggested that these apparently inconsistent findings are, at least partly, due to differences in the methods used to manipulate the masculinity of face images or individual differences in attraction to facial cues associated with youth. Here, however, we show that women's preferences for masculinity manipulated in male faces using techniques similar to the three most widely used methods are positively inter-related. We also show that women's preferences for masculine male faces are positively related to ratings of the masculinity of their actual partner and their ideal partner. Correlations with partner masculinity were independent of real and ideal partner age, which were not associated with facial masculinity preference. Collectively, these findings suggest that variability among studies in their findings for women's masculinity preferences reflects individual differences in attraction to masculinity rather than differences in the methods used to manufacture stimuli, and are important for the interpretation of previous and future studies of facial masculinity. PMID:16777723
Hicks, Sarah; Duran, Bonnie; Wallerstein, Nina; Avila, Magdalena; Belone, Lorenda; Lucero, Julie; Magarati, Maya; Mainer, Elana; Martin, Diane; Muhammad, Michael; Oetzel, John; Pearson, Cynthia; Sahota, Puneet; Simonds, Vanessa; Sussman, Andrew; Tafoya, Greg; Hat, Emily White
2013-01-01
Background Since 2007, the National Congress of American Indians (NCAI) Policy Research Center (PRC) has partnered with the Universities of New Mexico and Washington to study the science of community-based participatory research (CBPR). Our goal is to identify facilitators and barriers to effective community–academic partnerships in American Indian and other communities, which face health disparities. Objectives We have described herein the scientific design of our National Institutes of Health (NIH)-funded study (2009–2013) and lessons learned by having a strong community partner leading the research efforts. Methods The research team is implementing a mixed-methods study involving a survey of principal investigators (PIs) and partners across the nation and in-depth case studies of CBPR projects. Results We present preliminary findings on methods and measures for community-engaged research and eight lessons learned thus far regarding partnership evaluation, advisory councils, historical trust, research capacity development of community partner, advocacy, honoring each other, messaging, and funding. Conclusions Study methodologies and lessons learned can help community–academic research partnerships translate research in communities. PMID:22982842
Protein intrinsic disorder in plants.
Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto
2013-09-12
To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.
Protein intrinsic disorder in plants
Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A.; Solano, Roberto
2013-01-01
To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks. PMID:24062761
Morgan, Sarah V; Garwood, Claire J; Jennings, Luke; Simpson, Julie E; Castelli, Lydia M; Heath, Paul R; Mihaylov, Simeon R; Vaquéz-Villaseñor, Irina; Minshull, Thomas C; Ince, Paul G; Dickman, Mark J; Hautbergue, Guillaume M; Wharton, Stephen B
2018-05-08
Occludin is a component of tight junctions, which are essential structural components of the blood-brain barrier. However, occludin is expressed in cells without tight junctions, implying additional functions. We determined the expression and localisation of occludin in astrocytes in cell culture and in human brain tissue, and sought novel binding partners using a proteomic approach. Expression was investigated by immunocytochemistry and immunoblotting in the 1321N1 astrocytoma cell line and ScienCell human primary astrocytes, and by immunohistochemistry in human autopsy brain tissue. Recombinant N- and C-terminal occludin was used to pull-down proteins from 1321N1 cell lysates and protein-binding partners identified by mass spectrometry analysis. Occludin was expressed in both the cytoplasm and nucleus of astrocytes in vitro and in vivo. Mass spectrometry identified binding to nuclear and cytoplasmic proteins, particularly those related to RNA metabolism and nuclear function. Occludin is expressed in several subcellular compartments of brain cell-types that do not form tight junctions and the expression patterns in cell culture reflect those in human brain tissue, indicating they are suitable model systems. Proteomic analysis suggests that occludin has novel functions in neuroepithelial cells that are unrelated to tight junction formation. Further research will establish the roles of these functions in both cellular physiology and in disease states. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Njengele, Zikhona; Kleynhans, Ronel; Sayed, Yasien; Mosebi, Salerwe
2016-12-01
Vpu is one of four accessory proteins encoded by human immunodeficiency virus type I (HIV-1). Vpu modulates the expression of several cellular restriction factors within the HIV-1 infected cell including CD4, CD74, the bone marrow stromal antigen 2 (BST-2) and NK-T-and-B antigen. The interaction of HIV-1 Vpu with these proteins interferes with the innate immune response directed against HIV-1; thereby promoting viral persistence. The involvement of HIV-1 Vpu in manipulating the cellular environment in ways that favor viral replication makes it an attractive target for anti-HIV drug intervention. This paper describes the over-expression and purification of a soluble HIV-1 Vpu from inclusion bodies by ion-exchange chromatography, allowing production of 6 mg of highly purified protein (>95% purity) per 10 mg of pelleted cells obtained from 1 L of bacterial culture. Far-UV circular dichroism showed that the recombinant protein is folded and retained its secondary structure. Moreover, using ELISA, known HIV-1 Vpu binding partners, BST-2 and CD74, showed that the refolded purified protein is functional or at least assumes a conformation that is capable of binding these putative binding partners. To our knowledge, this is the first report of the purification and successful solubilization of full-length, wild-type HIV-1 Vpu from inclusion bodies in Escherichia coli. Copyright © 2016 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Hillyer, Katie E.; Dias, Daniel A.; Lutz, Adrian; Wilkinson, Shaun P.; Roessner, Ute; Davy, Simon K.
2017-03-01
Rising seawater temperatures pose a significant threat to the persistence of coral reefs. Despite the importance of these systems, major gaps remain in our understanding of how thermal stress and bleaching affect the metabolic networks that underpin holobiont function. We applied gas chromatography-mass spectrometry (GC-MS) metabolomics to detect changes in the intracellular free metabolite pools (polar and semi-polar compounds) of in hospite dinoflagellate symbionts and their coral hosts (and any associated microorganisms) during early- and late-stage thermal bleaching (a reduction of approximately 50 and 70% in symbiont density, respectively). We detected characteristic changes to the metabolite profiles of each symbiotic partner associated with individual cellular responses to thermal, oxidative and osmotic stress, which progressed with the severity of bleaching. Alterations were also indicative of changes to energy-generating and biosynthesis pathways in both partners, with a shift to the increased catabolism of lipid stores. Specifically, in symbiont intracellular metabolite pools, we observed accumulations of multiple free fatty acids, plus the chloroplast-associated antioxidant alpha-tocopherol. In the host, we detected a decline in the abundance of pools of multiple carbohydrates, amino acids and intermediates, in addition to the antioxidant ascorbate. These findings further our understanding of the metabolic changes that occur to symbiont and host (and its associated microorganisms) during thermal bleaching. These findings also provide further insight into the largely undescribed roles of free metabolite pools in cellular homeostasis, signalling and acclimation to thermal stress in the cnidarian-dinoflagellate symbiosis.
Huggins, Christopher J.; Mayekar, Manasi K.; Martin, Nancy; Saylor, Karen L.; Gonit, Mesfin; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C.; Quiñones, Octavio A.
2015-01-01
The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPγ:ATF4 heterodimers, but not C/EBPβ:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPγ and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPβ and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg−/− mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg−/− mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPγ-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg−/− mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPγ as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells. PMID:26667036
Redox-regulated growth factor survival signaling.
Woolley, John F; Corcoran, Aoife; Groeger, Gillian; Landry, William D; Cotter, Thomas G
2013-11-20
Once the thought of as unwanted byproducts of cellular respiration in eukaryotes, reactive oxygen species (ROS) have been shown to facilitate essential physiological roles. It is now understood that ROS are critical mediators of intracellular signaling. Control of signal transduction downstream of growth factor receptors by ROS is a complex process whose details are only recently coming to light. Indeed, recent evidence points to control of signal propagation by ROS at multiple levels in the typical cascade. Growth factor stimulation activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Noxs) at the membrane, producing superoxide in the extracellular matrix, which is catalyzed to the membrane-permeable hydrogen peroxide (H2O2) that mediates intracellular signaling events. The potential for H2O2, however, to disrupt cellular functions by damaging proteins and nucleic acids demands that its levels are kept in check by receptor-associated peroxiredoxins. This interplay of Nox and peroxiredoxin activity moderates levels of H2O2 sufficiently to modify signaling partners locally. Among the best studied of these partners are redox-controlled phosphatases that are inactivated by H2O2. Phosphatases regulate signal propagation downstream of receptors, and thus their inactivation allows a further level of control. Transmission of information further downstream to targets such as transcription factors, themselves regulated by ROS, completes this pathway. Thus, signal propagation or attenuation can be dictated by ROS at multiple points. Given the complex nature of these processes, we envisage the emerging trends in the field of redox signaling in the context of growth factor stimulation.
Huber, Roland G.; Bond, Peter J.
2017-01-01
An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners. PMID:29016650
Ivanov, Stefan M; Cawley, Andrew; Huber, Roland G; Bond, Peter J; Warwicker, Jim
2017-01-01
An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.
Tsutakawa, Susan E; Yan, Chunli; Xu, Xiaojun; Weinacht, Christopher P; Freudenthal, Bret D; Yang, Kun; Zhuang, Zhihao; Washington, M Todd; Tainer, John A; Ivanov, Ivaylo
2015-04-07
Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which also controls cellular responses to DNA damage. Posttranslational modification of PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA-dependent DNA repair and damage tolerance pathways is largely unknown. We used hybrid methods to identify atomic models of PCNAK107-Ub and PCNAK164-SUMO consistent with small-angle X-ray scattering data of these complexes in solution. We show that SUMO and ubiquitin have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations. These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. The unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.
Bioengineering Solutions for Manufacturing Challenges in CAR T Cells
Piscopo, Nicole J.; Mueller, Katherine P.; Das, Amritava; Hematti, Peiman; Murphy, William L.; Palecek, Sean P.; Capitini, Christian M.
2017-01-01
The next generation of therapeutic products to be approved for the clinic is anticipated to be cell therapies, termed “living drugs” for their capacity to dynamically and temporally respond to changes during their production ex vivo and after their administration in vivo. Genetically engineered chimeric antigen receptor (CAR) T cells have rapidly developed into powerful tools to harness the power of immune system manipulation against cancer. Regulatory agencies are beginning to approve CAR T cell therapies due to their striking efficacy in treating some hematological malignancies. However, the engineering and manufacturing of such cells remains a challenge for widespread adoption of this technology. Bioengineering approaches including biomaterials, synthetic biology, metabolic engineering, process control and automation, and in vitro disease modeling could offer promising methods to overcome some of these challenges. Here, we describe the manufacturing process of CAR T cells, highlighting potential roles for bioengineers to partner with biologists and clinicians to advance the manufacture of these complex cellular products under rigorous regulatory and quality control. PMID:28840981
Tsutakawa, Susan E.; Yan, Chunli; Xu, Xiaojun; ...
2015-03-12
Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which also controls cellular responses to DNA damage. Posttranslational modification of PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA-dependent DNA repair and damage tolerance pathways is largely unknown. Here, we used hybrid methods to identify atomic models of PCNA K107-Ub and PCNA K164-SUMO consistent with small-angle X-ray scattering data of these complexes in solution. We show that SUMO and ubiquitin have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations.more » These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. In conclusion, the unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation.« less
Noel, Eric A; Kang, Ming; Adamec, Jiri; Van Etten, James L; Oyler, George A
2014-12-01
The ubiquitin-proteasome system is targeted by many viruses that have evolved strategies to redirect host ubiquitination machinery. Members of the genus Chlorovirus are proposed to share an ancestral lineage with a broader group of related viruses, nucleo-cytoplasmic large DNA viruses (NCLDV). Chloroviruses encode an Skp1 homolog and ankyrin repeat (ANK) proteins. Several chlorovirus-encoded ANK repeats contain C-terminal domains characteristic of cellular F-boxes or related NCLDV chordopox PRANC (pox protein repeats of ankyrin at C-terminal) domains. These observations suggested that this unique combination of Skp1 and ANK repeat proteins might form complexes analogous to the cellular Skp1-Cul1-F-box (SCF) ubiquitin ligase complex. We identified two ANK proteins from the prototypic chlorovirus Paramecium bursaria chlorella virus-1 (PBCV-1) that functioned as binding partners for the virus-encoded Skp1, proteins A682L and A607R. These ANK proteins had a C-terminal Skp1 interactional motif that functioned similarly to cellular F-box domains. A C-terminal motif of ANK protein A682L binds Skp1 proteins from widely divergent species. Yeast two-hybrid analyses using serial domain deletion constructs confirmed the C-terminal localization of the Skp1 interactional motif in PBCV-1 A682L. ANK protein A607R represents an ANK family with one member present in all 41 sequenced chloroviruses. A comprehensive phylogenetic analysis of these related ANK and viral Skp1 proteins suggested partnered function tailored to the host alga or common ancestral heritage. Here, we show protein-protein interaction between corresponding family clusters of virus-encoded ANK and Skp1 proteins from three chlorovirus types. Collectively, our results indicate that chloroviruses have evolved complementing Skp1 and ANK proteins that mimic cellular SCF-associated proteins. Viruses have evolved ways to direct ubiquitination events in order to create environments conducive to their replication. As reported in the manuscript, the large chloroviruses encode several components involved in the SCF ubiquitin ligase complex including a viral Skp1 homolog. Studies on how chloroviruses manipulate their host algal ubiquitination system will provide insights toward viral protein mimicry, substrate recognition, and key interactive domains controlling selective protein degradation. These findings may also further understanding of the evolution of other large DNA viruses, like poxviruses, that are reported to share the same monophyly lineage as chloroviruses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Winer, Rachel L.; Hughes, James P.; Feng, Qinghua; Stern, Joshua E.; Xi, Long Fu; Koutsky, Laura A.
2016-01-01
Background. The risk of incident high-risk human papillomavirus (HR-HPV) infection associated with recent sexual behaviors is undefined in mid-adult women (defined as women aged 25–65 years). Methods. Triannually, 420 female online daters aged 25–65 years submitted vaginal specimens for HPV testing and completed health and sexual behavior questionnaires. The cumulative incidence of and risk factors for incident HR-HPV detection were estimated by Kaplan–Meier and Cox proportional hazards methods. Results. The 12-month cumulative incidence of HR-HPV detection was 25.4% (95% confidence interval [CI], 21.3%–30.1%). Current hormonal contraceptive use was positively associated with incident HR-HPV detection. Lifetime number of male sex partners was also positively associated but only among women not recently sexually active with male partners. In analysis that adjusted for hormonal contraceptive use and marital status, women reporting multiple male partners or male partners who were new, casual, or had ≥1 concurrent partnership had a hazard of incident HR-HPV detection that was 2.81 times (95% CI, 1.38–5.69 times) that for women who reported no male sex partners in the past 6 months. Thus, among women with multiple male partners or male partners who were new, casual, or had ≥1 concurrent partnership, approximately 64% of incident HR-HPV infections were attributable to one of those partners. Conclusions. Among high-risk mid-adult women with recent new male partners, multiple male partners, or male partners who were casual or had ≥1 concurrent partnership, about two thirds of incident HR-HPV detections are likely new acquisitions, whereas about one third of cases are likely redetections of prior infections. PMID:27009602
Contraceptive knowledge, perceptions, and concerns among men in Uganda.
Thummalachetty, Nityanjali; Mathur, Sanyukta; Mullinax, Margo; DeCosta, Kelsea; Nakyanjo, Neema; Lutalo, Tom; Brahmbhatt, Heena; Santelli, John S
2017-10-10
Low contraceptive uptake and high unmet need for contraception remain significant issues in Uganda compared to neighboring countries such as Kenya, Ethiopia, and Rwanda. Although prior research on contraceptive uptake has indicated that male partners strongly influence women's decisions around contraceptive use, there is limited in-depth qualitative research on knowledge and concerns regarding modern contraceptive methods among Ugandan men. Using in-depth interviews (N = 41), this qualitative study investigated major sources of knowledge about contraception and perceptions of contraceptive side effects among married Ugandan men. Men primarily reported knowledge of contraceptives based on partner's experience of side effects, partner's knowledge from health providers and mass media campaigns, and partner's knowledge from her peers. Men were less likely to report contraceptive knowledge from health care providers, mass media campaigns, or peers. Men's concerns about various contraceptive methods were broadly associated with failure of the method to work properly, adverse health effects on women, and severe adverse health effects on children. Own or partner's human immunodeficiency virus (HIV) status did not impact on contraceptive knowledge. Overall, we found limited accurate knowledge about contraceptive methods among men in Uganda. Moreover, fears about the side effects of modern contraceptive methods appeared to be common among men. Family planning services in Uganda could be significantly strengthened by renewed efforts to focus on men's knowledge, fears, and misconceptions.
Detection of Protein SUMOylation In Situ by Proximity Ligation Assays.
Sahin, Umut; Jollivet, Florence; Berthier, Caroline; de Thé, Hugues; Lallemand-Breitenbach, Valérie
2016-01-01
Sumoylation is a posttranslational process essential for life and concerns a growing number of crucial proteins. Understanding the influence of this phenomenon on individual proteins or on cellular pathways in which they function has become an intense area of research. A critical step in studying protein sumoylation is to detect sumoylated forms of a particular protein. This has proven to be a challenging task for a number of reasons, especially in the case of endogenous proteins and in vivo studies or when studying rare cells such as stem cells. Proximity ligation assays that allow detection of closely interacting protein partners can be adapted for initial detection of endogenous sumoylation or ubiquitination in a rapid, ultrasensitive, and cheap manner. In addition, modified forms of a given protein can be detected in situ in various cellular compartments. Finally, the flexibility of this technique may allow rapid screening of drugs and stress signals that may modulate protein sumoylation.
Caudron, Fabrice; Barral, Yves
2013-12-05
Cellular behavior is frequently influenced by the cell's history, indicating that single cells may memorize past events. We report that budding yeast permanently escape pheromone-induced cell-cycle arrest when experiencing a deceptive mating attempt, i.e., not reaching their putative partner within reasonable time. This acquired behavior depends on super-assembly and inactivation of the G1/S inhibitor Whi3, which liberates the G1 cyclin Cln3 from translational inhibition. Super-assembly of Whi3 is a slow response to pheromone, driven by polyQ and polyN domains, counteracted by Hsp70, and stable over generations. Unlike prion aggregates, Whi3 super-assemblies are not inherited mitotically but segregate to the mother cell. We propose that such polyQ- and polyN-based elements, termed here mnemons, act as cellular memory devices to encode previous environmental conditions. Copyright © 2013 Elsevier Inc. All rights reserved.
Synthesis, delivery and regulation of eukaryotic heme and Fe-S cluster cofactors.
Barupala, Dulmini P; Dzul, Stephen P; Riggs-Gelasco, Pamela Jo; Stemmler, Timothy L
2016-02-15
In humans, the bulk of iron in the body (over 75%) is directed towards heme- or Fe-S cluster cofactor synthesis, and the complex, highly regulated pathways in place to accomplish biosynthesis have evolved to safely assemble and load these cofactors into apoprotein partners. In eukaryotes, heme biosynthesis is both initiated and finalized within the mitochondria, while cellular Fe-S cluster assembly is controlled by correlated pathways both within the mitochondria and within the cytosol. Iron plays a vital role in a wide array of metabolic processes and defects in iron cofactor assembly leads to human diseases. This review describes progress towards our molecular-level understanding of cellular heme and Fe-S cluster biosynthesis, focusing on the regulation and mechanistic details that are essential for understanding human disorders related to the breakdown in these essential pathways. Copyright © 2016 Elsevier Inc. All rights reserved.
Poly(A)-binding proteins and mRNA localization: who rules the roost?
Gray, Nicola K; Hrabálková, Lenka; Scanlon, Jessica P; Smith, Richard W P
2015-12-01
RNA-binding proteins are often multifunctional, interact with a variety of protein partners and display complex localizations within cells. Mammalian cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins that regulate multiple aspects of mRNA translation and stability. Although predominantly diffusely cytoplasmic at steady state, they shuttle through the nucleus and can be localized to a variety of cytoplasmic foci, including those associated with mRNA storage and localized translation. Intriguingly, PABP sub-cellular distribution can alter dramatically in response to cellular stress or viral infection, becoming predominantly nuclear and/or being enriched in induced cytoplasmic foci. However, relatively little is known about the mechanisms that govern this distribution/relocalization and in many cases PABP functions within specific sites remain unclear. Here we discuss the emerging evidence with respect to these questions in mammals. © 2015 Authors; published by Portland Press Limited.
Yugandhar, K; Gromiha, M Michael
2014-09-01
Protein-protein interactions are intrinsic to virtually every cellular process. Predicting the binding affinity of protein-protein complexes is one of the challenging problems in computational and molecular biology. In this work, we related sequence features of protein-protein complexes with their binding affinities using machine learning approaches. We set up a database of 185 protein-protein complexes for which the interacting pairs are heterodimers and their experimental binding affinities are available. On the other hand, we have developed a set of 610 features from the sequences of protein complexes and utilized Ranker search method, which is the combination of Attribute evaluator and Ranker method for selecting specific features. We have analyzed several machine learning algorithms to discriminate protein-protein complexes into high and low affinity groups based on their Kd values. Our results showed a 10-fold cross-validation accuracy of 76.1% with the combination of nine features using support vector machines. Further, we observed accuracy of 83.3% on an independent test set of 30 complexes. We suggest that our method would serve as an effective tool for identifying the interacting partners in protein-protein interaction networks and human-pathogen interactions based on the strength of interactions. © 2014 Wiley Periodicals, Inc.
David Parker, R; Regier, Michael D; Widmeyer, Joseph; Honaker, John; Rüütel, Kristi
2015-10-01
Limited research exists on sexually transmitted infection (STI) and risk behaviour among military personnel. Published research on condom use and types of contraceptives used yield mixed results, yet, the perception that military members are at higher risk for STIs remains. The objectives of this cross-sectional study were to measure factors such as condom use, contraceptive methods, and risky behaviours (i.e. drug use and sex with commercial sex workers) and investigate differences between ethnic groups, where culture could influence behaviour. Data were collected from a recruited population of 584 male, military conscripts in northeastern Europe. Using multinomial logistic regression models, statistically significant findings include an interaction between the use of contraceptive methods of Russians with casual partners and ethnicity, with higher odds of effective methods used among Estonians with regular partners (OR = 8.13) or casual partners (OR = 11.58) and Russians with regular partners (OR = 4.98). Effective contraceptive methods used less frequently with casual partners by ethnic Russians is important in providing education and risk reduction services to young, male conscripts. These findings may be used as a baseline to inform health education and STI prevention programmes tailored to military members in Eastern Europe in the absence of other published studies. © The Author(s) 2015.
Intimate Partner Violence in Older Women
ERIC Educational Resources Information Center
Bonomi, Amy E.; Anderson, Melissa L.; Reid, Robert J.; Carrell, David; Fishman, Paul A.; Rivara, Frederick P.; Thompson, Robert S.
2007-01-01
Purpose: We describe the prevalence, types, duration, frequency, and severity of intimate partner violence ("partner violence") in older women. Design and Methods: We randomly sampled a total of 370 English-speaking women (65 years of age and older) from a health care system to participate in a cross-sectional telephone interview. Using 5…
ERIC Educational Resources Information Center
Renner, Lynette M.; Slack, Kristen Shook
2006-01-01
Objective: The purpose of this study is to assess the extent to which intimate partner violence and different forms of child maltreatment occur within and across childhood and adulthood for a high-risk group of women. Method: Low-income adult women were interviewed, retrospectively, regarding their experiences with intimate partner violence and…
Care Partner Responses to the Onset of Mild Cognitive Impairment
ERIC Educational Resources Information Center
Blieszner, Rosemary; Roberto, Karen A.
2010-01-01
Purpose: We examined characteristics, responses, and psychological well-being of care partners who support and assist older adults recently diagnosed with mild cognitive impairment (MCI). Design and Methods: Based on a sample of 106 care partners of community residents diagnosed with MCI at memory clinics, we conducted face-to-face interviews…
From Parents to Partners: Building a Family-Centered Early Childhood Program
ERIC Educational Resources Information Center
Keyser, Janis
2006-01-01
Partnering with parents is essential if an early childhood program is to succeed. "From Parents to Partners" explores the reasons and methods for developing ongoing partnerships with parents and other family members. It also provides the tools and strategies needed to build the communication and support networks within which these partnerships…
Biological Sensitivity to Context in Couples: Why Partner Aggression Hurts Some More than Others
ERIC Educational Resources Information Center
Lorber, Michael F.; Erlanger, Ann C. Eckardt; Slep, Amy M. Smith
2013-01-01
Objective: Cardiovascular reactivity to laboratory stressors was investigated as (a) a moderator of associations of partner aggression with affective functioning, alcohol problems, and parenting; and (b) a consequence of partner aggression. Method: Cohabiting adult couples (N = 453) with 3- to 7-year-old children were recruited by random digit…
Stockman, Jamila K; Syvertsen, Jennifer L; Robertson, Angela M; Ludwig-Barron, Natasha T; Bergmann, Julie N; Palinkas, Lawrence A
2014-01-01
Female-initiated barrier methods for the prevention of HIV may be an effective alternative for drug-using women who are unable to negotiate safe sex, often as a result of physical and/or sexual partner violence. Utilizing a SAVA (substance abuse, violence, and AIDS) syndemic framework, we qualitatively examined perspectives on female condoms and vaginal microbicides among 18 women with histories of methamphetamine abuse and partner violence in San Diego, California. Most women were not interested in female condoms owing to perceived discomfort, difficulty of insertion, time-intensive effort, and unappealing appearance. Alternatively, most women viewed vaginal microbicides as a useful method. Positive aspects included convenience, ability to disguise as a lubricant, and a sense of control and empowerment. Concerns included possible side effects, timing of application, and unfavorable characteristics of the gel. Acceptability of female-initiated barrier methods was context dependent (i.e., partner type, level of drug use and violence that characterized the sexual relationship). Findings indicate that efforts are needed to address barriers identified for vaginal microbicides to increase its uptake in future HIV prevention trials and marketing of future Food and Drug Administration-approved products. Strategies should address gender-based inequalities (e.g., partner violence) experienced by drug-using women and promote female empowerment. Education on female-initiated barrier methods is also needed for women who use drugs, as well as health care providers and other professionals providing sexual health care and contraception to women with histories of drug use and partner violence. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.
Pearlstein, Robert A; McKay, Daniel J J; Hornak, Viktor; Dickson, Callum; Golosov, Andrei; Harrison, Tyler; Velez-Vega, Camilo; Duca, José
2017-01-01
Cellular drug targets exist within networked function-generating systems whose constituent molecular species undergo dynamic interdependent non-equilibrium state transitions in response to specific perturbations (i.e.. inputs). Cellular phenotypic behaviors are manifested through the integrated behaviors of such networks. However, in vitro data are frequently measured and/or interpreted with empirical equilibrium or steady state models (e.g. Hill, Michaelis-Menten, Briggs-Haldane) relevant to isolated target populations. We propose that cells act as analog computers, "solving" sets of coupled "molecular differential equations" (i.e. represented by populations of interacting species)via "integration" of the dynamic state probability distributions among those populations. Disconnects between biochemical and functional/phenotypic assays (cellular/in vivo) may arise with targetcontaining systems that operate far from equilibrium, and/or when coupled contributions (including target-cognate partner binding and drug pharmacokinetics) are neglected in the analysis of biochemical results. The transformation of drug discovery from a trial-and-error endeavor to one based on reliable design criteria depends on improved understanding of the dynamic mechanisms powering cellular function/dysfunction at the systems level. Here, we address the general mechanisms of molecular and cellular function and pharmacological modulation thereof. We outline a first principles theory on the mechanisms by which free energy is stored and transduced into biological function, and by which biological function is modulated by drug-target binding. We propose that cellular function depends on dynamic counter-balanced molecular systems necessitated by the exponential behavior of molecular state transitions under non-equilibrium conditions, including positive versus negative mass action kinetics and solute-induced perturbations to the hydrogen bonds of solvating water versus kT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Cellular phosphoinositides and the maturation of bluetongue virus, a non-enveloped capsid virus
2013-01-01
Background Bluetongue virus (BTV), a member of Orbivirus genus in the Reoviridae family is a double capsid virus enclosing a genome of 10 double-stranded RNA segments. A non-structural protein of BTV, NS3, which is associated with cellular membranes and interacts with outer capsid proteins, has been shown to be involved in virus morphogenesis in infected cells. In addition, studies have also shown that during the later stages of virus infection NS3 behaves similarly to HIV protein Gag, an enveloped viral protein. Since Gag protein is known to interact with membrane lipid phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2] and one of the known binding partners of NS3, cellular protein p11 also interacts with annexin a PI(4,5)P2 interacting protein, this study was designed to understand the role of this negatively charged membrane lipid in BTV assembly and maturation. Methods Over expression of cellular enzymes that either depleted cells of PI(4,5)P2 or altered the distribution of PI(4,5)P2, were used to analyze the effect of the lipid on BTV maturation at different times post-infection. The production of mature virus particles was monitored by plaque assay. Microscopic techniques such as confocal microscopy and electron microscopy (EM) were also undertaken to study localization of virus proteins and virus particles in cells, respectively. Results Initially, confocal microscopic analysis demonstrated that PI(4,5)P2 not only co-localized with NS3, but it also co-localized with VP5, one of the outer capsid proteins of BTV. Subsequently, experiments involving depletion of cellular PI(4,5)P2 or its relocation demonstrated an inhibitory effect on normal BTV maturation and it also led to a redistribution of BTV proteins within the cell. The data was supported further by EM visualization showing that modulation of PI(4,5)P2 in cells indeed resulted in less particle production. Conclusion This study to our knowledge, is the first report demonstrating involvement of PI(4,5)P2 in a non-enveloped virus assembly and release. As BTV does not have lipid envelope, this finding is unique for this group of viruses and it suggests that the maturation of capsid and enveloped viruses may be more closely related than previously thought. PMID:23497128
Choice of birth control methods among European women and the role of partners and providers.
de Irala, Jokin; Osorio, Alfonso; Carlos, Silvia; Lopez-del Burgo, Cristina
2011-12-01
The choice of a birth control method is influenced by sociocultural and personal factors. We explored the perceived influences in women's choice of a birth control method in five European countries (Germany, France, the UK, Romania and Sweden), where contraception is widely used. This is a cross-sectional study of 1137 randomly selected women aged 18-49 years. An anonymous, 31-item questionnaire related to birth control methods was used. Logistic regression was used to identify variables associated with partner participation in choice of a contraceptive. Oral contraceptives were mainly used in Germany (54.3%), France (50.5%) and Sweden (34.6%) and condoms in the UK (29.6%) and Romania (22.9%). Sweden showed the highest use of intrauterine devices (IUD, 19%). Romania had the lowest use of contraception. Oral contraceptives and IUDs use were frequently suggested by providers instead of by women. Choosing the method with the partner was associated with age [odds ratio (OR)=0.97, 95% confidence interval (CI) 0.94-0.99], being a university graduate (OR=1.59, 95% CI 1.01-2.29), married (OR=1.52, 95% CI 1.01-2.29) and with using a method that requires partner's cooperation (OR=8.18, 95% CI 5.46-12.27). Hormonal contraceptives and IUDs are commonly recommended by providers rather than requested by women. Partner preferences are taken into account when his cooperation in the use of the method is needed. As fertility care is a male and female issue, there is still more room for actively involving both women and men in their choice of a birth control method. Copyright © 2011 Elsevier Inc. All rights reserved.
How membranes shape plant symbioses: signaling and transport in nodulation and arbuscular mycorrhiza
Bapaume, Laure; Reinhardt, Didier
2012-01-01
As sessile organisms that cannot evade adverse environmental conditions, plants have evolved various adaptive strategies to cope with environmental stresses. One of the most successful adaptations is the formation of symbiotic associations with beneficial microbes. In these mutualistic interactions the partners exchange essential nutrients and improve their resistance to biotic and abiotic stresses. In arbuscular mycorrhiza (AM) and in root nodule symbiosis (RNS), AM fungi and rhizobia, respectively, penetrate roots and accommodate within the cells of the plant host. In these endosymbiotic associations, both partners keep their plasma membranes intact and use them to control the bidirectional exchange of signaling molecules and nutrients. Intracellular accommodation requires the exchange of symbiotic signals and the reprogramming of both interacting partners. This involves fundamental changes at the level of gene expression and of the cytoskeleton, as well as of organelles such as plastids, endoplasmic reticulum (ER), and the central vacuole. Symbiotic cells are highly compartmentalized and have a complex membrane system specialized for the diverse functions in molecular communication and nutrient exchange. Here, we discuss the roles of the different cellular membrane systems and their symbiosis-related proteins in AM and RNS, and we review recent progress in the analysis of membrane proteins involved in endosymbiosis. PMID:23060892
Biochemistry of the tale transcription factors PREP, MEIS, and PBX in vertebrates.
Longobardi, E; Penkov, D; Mateos, D; De Florian, G; Torres, M; Blasi, Francesco
2014-01-01
TALE (three amino acids loop extension) homeodomain transcription factors are required in various steps of embryo development, in many adult physiological functions, and are involved in important pathologies. This review focuses on the PREP, MEIS, and PBX sub-families of TALE factors and aims at giving information on their biochemical properties, i.e., structure, interactors, and interaction surfaces. Members of the three sets of protein form dimers in which the common partner is PBX but they can also directly interact with other proteins forming higher-order complexes, in particular HOX. Finally, recent advances in determining the genome-wide DNA-binding sites of PREP1, MEIS1, and PBX1, and their partial correspondence with the binding sites of some HOX proteins, are reviewed. These studies have generated a few general rules that can be applied to all members of the three gene families. PREP and MEIS recognize slightly different consensus sequences: PREP prefers to bind to promoters and to have PBX as a DNA-binding partner; MEIS prefers HOX as partner, and both PREP and MEIS drive PBX to their own binding sites. This outlines the clear individuality of the PREP and MEIS proteins, the former mostly devoted to basic cellular functions, the latter more to developmental functions. Copyright © 2013 Wiley Periodicals, Inc.
Coral Reef Genomics: Developing tools for functional genomics ofcoral symbiosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schwarz, Jodi; Brokstein, Peter; Manohar, Chitra
Symbioses between cnidarians and dinoflagellates in the genus Symbiodinium are widespread in the marine environment. The importance of this symbiosis to reef-building corals and reef nutrient and carbon cycles is well documented, but little is known about the mechanisms by which the partners establish and regulate the symbiosis. Because the dinoflagellate symbionts live inside the cells of their host coral, the interactions between the partners occur on cellular and molecular levels, as each partner alters the expression of genes and proteins to facilitate the partnership. These interactions can examined using high-throughput techniques that allow thousands of genes to be examinedmore » simultaneously. We are developing the groundwork so that we can use DNA microarray profiling to identify genes involved in the Montastraea faveolata and Acropora palmata symbioses. Here we report results from the initial steps in this microarray initiative, that is, the construction of cDNA libraries from 4 of 16 target stages, sequencing of 3450 cDNA clones to generate Expressed Sequenced Tags (ESTs), and annotation of the ESTs to identify candidate genes to include in the microarrays. An understanding of how the coral-dinoflagellate symbiosis is regulated will have implications for atmospheric and ocean sciences, conservation biology, the study and diagnosis of coral bleaching and disease, and comparative studies of animal-protest interactions.« less
ERIC Educational Resources Information Center
Kapur, Nitin A.; Windish, Donna M.
2011-01-01
Contradictory data exist regarding optimal methods and instruments for intimate partner violence (IPV) screening in primary care settings. The purpose of this study was to determine the optimal method and screening instrument for IPV among men and women in a primary-care resident clinic. We conducted a cross-sectional study at an urban, academic,…
Prevalence of and Risk Factors for Intimate Partner Violence in China
Xu, Xiao; Zhu, Fengchuan; O’Campo, Patricia; Koenig, Michael A.; Mock, Victoria; Campbell, Jacquelyn
2005-01-01
Objectives. We estimated the prevalence of and risk factors for intimate partner violence in China. Methods. Our cross-sectional, comparative prevalence study used a face-to-face survey of randomly selected women attending an urban outpatient gynecological clinic at a major teaching hospital in Fuzhou, China. Multiple logistic regression models were used to assess risk factors for intimate partner violence. Results. Of the 600 women interviewed, the prevalence of lifetime intimate partner violence and violence taking place within the year before the interview was 43% and 26%, respectively. For lifetime intimate partner violence, partners who had extramarital affairs and who refused to give respondents money were the strongest independent predictors. For intimate partner violence taking place within the year before the interview, frequent quarreling was the strongest predictor. Conclusions. Intimate partner violence is prevalent in China, with strong associations with male patriarchal values and conflict resolutions. Efforts to reduce intimate partner violence should be given high priority in health care settings where women can be reached. PMID:15623864
Partner alcohol use, violence and women’s mental health: population-based survey in India
Nayak, Madhabika B.; Patel, Vikram; Bond, Jason C.; Greenfield, Thomas K.
2010-01-01
Background The relationship between partner alcohol use and violence as risk factors for poor mental health in women is unclear. Aims To describe partner-related and other psychosocial risk factors for common mental disorders in women and examine interrelationships between these factors. Method Data are reported on 821 women aged 18–49 years from a larger population study in north Goa, India. Logistic regression models evaluated the risks for women’s common mental disorders and tested for mediation effects in the relationship between partner alcohol use and these disorders. Results Excessive partner alcohol use increased the risk for common mental disorders two- to threefold. Partner violence and alcohol-related problems each partially mediated the association between partner excessive alcohol use and these mental disorders. Women’s own violence-related attitudes were also independently associated with them. Conclusions Partner alcohol use, partner violence and women’s violence-related attitudes must be addressed to prevent and treat common mental disorders in women. PMID:20194540
Effectiveness of a Pilot Partner Notification Program for New HIV Cases in Barcelona, Spain
Garcia de Olalla, Patricia; Molas, Ema; Barberà, María Jesús; Martín, Silvia; Arellano, Encarnació; Gosch, Mercè; Saladie, Pilar; Carbonell, Teresa; Knobel, Hernando; Diez, Elia; Caylà, Joan A
2015-01-01
Background An estimated 30% of HIV cases in the European Union are not aware of their serological status. This study aimed to assess the effectiveness of a pilot HIV partner notification program. Methods HIV cases diagnosed between January 2012 and June 2013 at two healthcare settings in Barcelona were invited to participate in a prospective survey. We identified process and outcome measures to evaluate this partner notification program, including the number of partners identified per interviewed index case, the proportion of partners tested for HIV as a result of the partner notification, and the proportion of new HIV diagnoses among their sex or needle-sharing partners. Results Of the 125 index cases contacted, 108 (86.4%) agreed to provide information about partners. A total of 199 sexual partners were identified (1.8 partners per interviewed index case). HIV outcome was already known for 58 partners (70.7% were known to be HIV-positive), 141 partners were tested as result of partner notification, and 26 were newly diagnosed with HIV. The case-finding effectiveness of the program was 18.4%. Conclusion This pilot program provides evidence of the effectiveness of a partner notification program implemented in healthcare settings. This active partner notification program was feasible, acceptable to the user, and identified a high proportion of HIV-infected patients previously unaware of their status. PMID:25849451
RanBPM: a potential therapeutic target for modulating diverse physiological disorders.
Das, Soumyadip; Suresh, Bharathi; Kim, Hyongbum Henry; Ramakrishna, Suresh
2017-12-01
The Ran-binding protein microtubule-organizing center (RanBPM) is a highly conserved nucleocytoplasmic protein involved in a variety of intracellular signaling pathways that control diverse cellular functions. RanBPM interacts with proteins that are linked to various diseases, including Alzheimer's disease (AD), schizophrenia (SCZ), and cancer. In this article, we define the characteristics of the scaffolding protein RanBPM and focus on its interaction partners in diverse physiological disorders, such as neurological diseases, fertility disorders, and cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.
PML nuclear bodies: regulation, function and therapeutic perspectives.
Sahin, Umut; Lallemand-Breitenbach, Valérie; de Thé, Hugues
2014-11-01
PML nuclear bodies (NBs) were first described by electron microscopy and rediscovered through their treatment-reversible disruption in a rare leukaemia. They recruit multiple partner proteins and now emerge as interferon- and oxidative stress-responsive sumoylation factories. NBs mediate interferon-induced viral restriction, enhance proteolysis, finely tune metabolism and enforce stress-induced senescence. Apart from being markers of cellular stress, PML NBs could be harnessed pharmacologically in a number of conditions, including cancer, viral infection or neurodegenerative diseases. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Bergsdorf, Christian; Fiez-Vandal, Cédric; Sykes, David A; Bernet, Pascal; Aussenac, Sonia; Charlton, Steven J; Schopfer, Ulrich; Ottl, Johannes; Duckely, Myriam
2016-03-01
Integral membrane proteins (IMPs) play an important role in many cellular events and are involved in numerous pathological processes. Therefore, understanding the structure and function of IMPs is a crucial prerequisite to enable successful targeting of these proteins with low molecular weight (LMW) ligands early on in the discovery process. To optimize IMP purification/crystallization and to identify/characterize LMW ligand-target interactions, robust, reliable, high-throughput, and sensitive biophysical methods are needed. Here, we describe a differential scanning fluorimetry (DSF) screening method using the thiol-reactive BODIPY FL-cystine dye to monitor thermal unfolding of the G-protein-coupled receptor (GPCR), CXCR2. To validate this method, the seven-transmembrane protein CXCR2 was analyzed with a set of well-characterized antagonists. This study showed that the new DSF assay assessed reliably the stability of CXCR2 in a 384-well format. The analysis of 14 ligands with a potency range over 4 log units demonstrated the detection/characterization of LMW ligands binding to the membrane protein target. Furthermore, DSF results cross-validated with the label-free differential static light scattering (DSLS) thermal denaturation method. These results underline the potential of the BODIPY assay format as a general tool to investigate membrane proteins and their interaction partners. © 2015 Society for Laboratory Automation and Screening.
Matson, Pamela A.; Chung, Shang-en; Ellen, Jonathan M.
2014-01-01
Purpose This research examined the association between a novel measure of perceived partner availability and discordance between ideal and actual partner characteristics as well as trajectories of ideal partner preferences and perceptions of partner availability over time. Methods A clinic recruited cohort of adolescent females (N = 92), aged 16 -19, were interviewed quarterly for 12 months using audio computer-assisted self-interview. Participants ranked the importance of characteristics for their ideal main sex partner and then reported on these characteristics for their current main partner. Participants reported on perceptions of availability of ideal sex partners in their neighborhood. Paired t-tests examined discordance between ideal and actual partner characteristics. Random-intercept regression models examined repeated measures. Results Actual partner ratings were lower than ideal partner preferences for fidelity, equaled ideal preferences for emotional support and exceed ideal preferences for social/economic status and physical attractiveness. Discordance on emotional support and social/economic status was associated with sex partner concurrency. Participants perceived low availability of ideal sex partners. Those who perceived more availability were less likely to be ideal/actual discordant on fidelity [OR = 0.88, 95%CI: 0.78,1.0]. Neither ideal partner preferences nor perceptions of partner availability changed over 12 months. Conclusions Current main sex partners met or exceeded ideal partner preferences in all domains except fidelity. If emotional needs are met, adolescents may tolerate partner concurrency in areas of limited partner pools. Urban adolescent females who perceive low availability may be at increased risk for STI as they may be more likely to have non-monogamous partners. PMID:24393545
Acceptance of routine or case-based inquiry for intimate partner violence: a mixed method study.
Stöckl, Heidi; Hertlein, Linda; Himsl, Isabelle; Ditsch, Nina; Blume, Carolin; Hasbargen, Uwe; Friese, Klaus; Stöckl, Doris
2013-03-26
The prevalence and detrimental health effects of intimate partner violence have resulted in international discussions and recommendations that health care professionals should screen women for intimate partner violence during general and antenatal health care visits. Due to the lack of discussion on routine or case-based inquiry for intimate partner violence during antenatal care in Germany, this study seeks to explore its acceptability among pregnant German women. A mixed methods approach was used, utilizing a self-administered survey on the acceptability of routine or case-based inquiry for intimate partner violence in a university hospital's maternity ward in Munich and in-depth interviews with seven women who experienced violence during pregnancy. Of the 401 women who participated in the survey, 92 percent were in favor of routine or case-based inquiry for intimate partner violence during antenatal care. Acceptance of routine or case-based inquiry for intimate partner violence during antenatal care was significantly associated with women's experiences of child sexual abuse, being young, less educated, single or divorced and smoking during pregnancy. Open-ended survey questions and in-depth interviews stressed adequate training for screening, sufficient time and provision of referral information as important conditions for routine or case-based inquiry for intimate partner violence. Women in this study showed an overwhelming support for routine or case-based screening for intimate partner violence in antenatal care in Germany. Until adequate training is in place to allow providers to inquire for intimate partner violence in a professional manner, this study recommends that health care providers are made aware of the prevalence and health consequences of violence during pregnancy.
van den Hurk, Desiree G M; Schellekens, Melanie P J; Molema, Johan; Speckens, Anne E M; van der Drift, Miep A
2015-07-01
Lung cancer patients and partners show high rates of impaired quality of life and heightened distress levels. Mindfulness-Based Stress Reduction has proven to be effective in reducing psychological distress in cancer patients. However, studies barely included lung cancer patients. We examined whether Mindfulness-Based Stress Reduction might be a feasible and effective intervention for patients with lung cancer and partners. Mindfulness-Based Stress Reduction is a training in which mindfulness practices are combined with psycho-education to help participants cope with distress. In this mixed methods pilot study, questionnaires on psychological distress and quality of life were administered before, directly after and 3 months after the Mindfulness-Based Stress Reduction training, in combination with semi-structured interviews. Patients with lung cancer and partners were recruited at one tertiary care academic medical centre. A total of 19 lung cancer patients and 16 partners participated in the Mindfulness-Based Stress Reduction training. Most patients were diagnosed with advanced stage lung cancer. Vast majority completed the training. Those receiving anti-cancer treatment did not miss more sessions than patients who were not currently treated. Patients and partners felt positive about participating in a peer group and with their partner. Among participants no significant changes were found in psychological distress. Caregiver burden in partners decreased significantly after following Mindfulness-Based Stress Reduction. The qualitative analysis showed that the training seemed to instigate a process of change in participants. The Mindfulness-Based Stress Reduction training seemed to be feasible for patients with lung cancer and their partners. A randomized controlled trial is needed to examine the effectiveness of Mindfulness-Based Stress Reduction in reducing psychological distress in lung cancer patients and partners. © The Author(s) 2015.
Risky Business: An Ecological Analysis of Intimate Partner Violence Disclosure
ERIC Educational Resources Information Center
Alaggia, Ramona; Regehr, Cheryl; Jenney, Angelique
2012-01-01
Objective: A multistage, mixed-methods study using grounded theory with descriptive data was conducted to examine factors in disclosure of intimate partner violence (IPV). Method: In-depth interviews with individuals and focus groups were undertaken to collect data from 98 IPV survivors and service providers to identify influential factors.…
Smith, Sharon G; Fowler, Katherine A; Niolon, Phyllis H
2014-03-01
We estimated the frequency and examined the characteristics of intimate partner homicide and related deaths in 16 US states participating in the National Violent Death Reporting System (NVDRS), a state-based surveillance system. We used a combination of quantitative and qualitative methods to analyze NVDRS data from 2003 to 2009. We selected deaths linked to intimate partner violence for analysis. Our sample comprised 4470 persons who died in the course of 3350 intimate partner violence-related homicide incidents. Intimate partners and corollary victims represented 80% and 20% of homicide victims, respectively. Corollary homicide victims included family members, new intimate partners, friends, acquaintances, police officers, and strangers. Our findings, from the first multiple-state study of intimate partner homicide and corollary homicides, demonstrate that the burden of intimate partner violence extends beyond the couple involved. Systems (e.g., criminal justice, medical care, and shelters) whose representatives routinely interact with victims of intimate partner violence can help assess the potential for lethal danger, which may prevent intimate partner and corollary victims from harm.
Velagapudi, Sai Pradeep; Luo, Yiling; Tran, Tuan; Haniff, Hafeez S; Nakai, Yoshio; Fallahi, Mohammad; Martinez, Gustavo J; Childs-Disney, Jessica L; Disney, Matthew D
2017-03-22
RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs.
2017-01-01
RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif–small molecule interactions identified via selection. Named High Throughput Structure–Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif–small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule–RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs. PMID:28386598
Close partner as sculptor of the ideal self: behavioral affirmation and the Michelangelo phenomenon.
Drigotas, S M; Rusbult, C E; Wieselquist, J; Whitton, S W
1999-08-01
This work incorporates concepts from the behavioral confirmation tradition, self tradition, and interdependence tradition to identify an interpersonal process termed the Michelangelo phenomenon. The Michelangelo phenomenon describes the means by which the self is shaped by a close partner's perceptions and behavior. Specifically, self movement toward the ideal self is described as a product of partner affirmation, or the degree to which a partner's perceptions of the self and behavior toward the self are congruent with the self's ideal. The results of 4 studies revealed strong associations between perceived partner affirmation and self movement toward the ideal self, using a variety of participant populations and measurement methods. In addition, perceived partner affirmation--particularly perceived partner behavioral affirmation--was strongly associated with quality of couple functioning and stability in ongoing relationships.
The External Globus Pallidus: Progress and Perspectives
Hegeman, Daniel J.; Hong, Ellie S.; Hernández, Vivian M.; Chan, C. Savio
2016-01-01
The external globus pallidus (GPe) of the basal ganglia is in a unique and powerful position to influence processing of motor information by virtue of its widespread projections to all basal ganglia nuclei. Despite the clinical importance of the GPe in common motor disorders such as Parkinson’s disease, we have only limited information about its cellular composition and organizational principles. In this review, we describe recent advances in our understanding of the diversity in the molecular profile, anatomy, physiology, and corresponding behavior during movement of GPe neurons. Importantly, we attempt to build consensus and highlight commonalities of the cellular classification based on existing but contentious literature. Additionally, we provide an analysis of the literature concerning the intricate reciprocal loops formed between the GPe and major synaptic partners, including both the striatum and the subthalamic nucleus. In conclusion, the GPe has emerged as a crucial node in the basal ganglia macrocircuit. While subtleties in the cellular makeup and synaptic connection of the GPe create new challenges, modern research tools have shown promise in untangling such complexity and will provide better understanding of the roles of the GPe in encoding movements and their associated pathologies. PMID:26841063
The external globus pallidus: progress and perspectives.
Hegeman, Daniel J; Hong, Ellie S; Hernández, Vivian M; Chan, C Savio
2016-05-01
The external globus pallidus (GPe) of the basal ganglia is in a unique and powerful position to influence processing of motor information by virtue of its widespread projections to all basal ganglia nuclei. Despite the clinical importance of the GPe in common motor disorders such as Parkinson's disease, there is only limited information about its cellular composition and organizational principles. In this review, recent advances in the understanding of the diversity in the molecular profile, anatomy, physiology and corresponding behaviour during movement of GPe neurons are described. Importantly, this study attempts to build consensus and highlight commonalities of the cellular classification based on existing but contentious literature. Additionally, an analysis of the literature concerning the intricate reciprocal loops formed between the GPe and major synaptic partners, including both the striatum and the subthalamic nucleus, is provided. In conclusion, the GPe has emerged as a crucial node in the basal ganglia macrocircuit. While subtleties in the cellular makeup and synaptic connection of the GPe create new challenges, modern research tools have shown promise in untangling such complexity, and will provide better understanding of the roles of the GPe in encoding movements and their associated pathologies. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Klaić, Lada; Morimoto, Richard I.; Silverman, Richard B.
2012-01-01
The natural product celastrol (1) possesses numerous beneficial therapeutic properties and affects numerous cellular pathways. The mechanism of action and cellular target(s) of celastrol, however, remain unresolved. While a number of studies have proposed that the activity of celastrol is mediated through reaction with cysteine residues, these observations have been based on studies with specific proteins or by in vitro analysis of a small fraction of the proteome. In this study, we have investigated the spatial and structural requirements of celastrol for the design of suitable affinity probes to identify cellular binding partners of celastrol. Although celastrol has several potential sites for modification, some of these were not synthetically amenable or yielded unstable analogs. Conversion of the carboxylic acid functionality to amides and long-chain analogs, however, yielded bioactive compounds that induced the heat shock response (HSR) and antioxidant response and inhibited Hsp90 activity. This led to the synthesis of biotinylated celastrols (23 and 24) that were used as affinity reagents in extracts of human Panc-1 cells to identify Annexin II, eEF1A, and β-tubulin as potential targets of celastrol. PMID:22380712
Proteomic analysis identifies a novel function for galectin-3 in the cell entry of parvovirus.
Garcin, Pierre; Cohen, Sarah; Terpstra, Sanne; Kelly, Isabelle; Foster, Leonard J; Panté, Nelly
2013-02-21
Cellular factors associated with the parvovirus minute virus of mice (MVM) during infection are thought to play important roles in the MVM life cycle but only a few of these have been identified. Here we used a proteomic-based approach in order to identify host-binding partners of MVM. Using purified MVM as bait for immunoprecipitation assays, a total of 150 proteins were identified in MVM immunoprecipitates by quantitative liquid chromatography-tandem mass spectrometry. Galectin-3 was one of six proteins showing a statistically significant enrichment across replicates. Small interfering RNA depletion studies revealed an important role for galectin-3 in MVM endocytosis and infectivity in LA9 mouse fibroblast cells. Galectin-3-depleted cells were less susceptible to MVM infection than control cells and showed a significant reduction of MVM cellular uptake, but not of MVM binding to the cell surface. Our results indicate an important role for galectin-3 in the cellular uptake of MVM. We propose that galectin-3 facilitates the access of MVM to its receptor(s) at the plasma membrane and in this way promotes MVM endocytosis. Copyright © 2012 Elsevier B.V. All rights reserved.
Assari, Shervin; Jeremiah, Rohan D
2018-01-01
Background: Although male partners' socioeconomic status (SES) and substance use is associated with worse health of female partners, the mechanism behind this link is still unknown. Objectives: To investigate whether intimate partner violence (IPV) is a mechanism by which male partners' SES and substance use influence female partners' self-rated health (SRH) as victims and survivors of IPV. Materials and Methods: Fragile Families and Child Wellbeing Study (FFCWS) is an ongoing population-based cohort. Male and female partners' SES, anxiety, depression, and substance use, and their relationship status were measured at baseline. IPV victimization was also asked among female partners' at baseline. Female partners' subjective health was measured 3 times (baseline-1998, 3 years later-2001, and 5 years later-2003). Using AMOS, we fitted two structural equation models (SEM) for data analysis. In Model 1 we tested direct paths from male partners' SES and mental health to female partners' SRH, in the absence of IPV. In the Model 2 we conceptualized female partners' IPV victimization between male partners' SES and mental health and female partners' SRH. In both models we controlled for the effect of female partners' SES and mental health. Results: In Model 1 , male partners' poor SES and substance use were associated with worse trajectory of SRH of female partner. In Model 2 , male to female IPV was the mechanism by which male partners' SES and substance use were associated with female partners' SRH. Conclusions: IPV is one of the mechanisms by which male partners' SES and substance use can influence female partners' health. That is, IPV may operate as a vehicle by which male partners' social and psychological risk factors impact female partners' health. Thus, this study demonstrates how male partners' socio-ecological risk factors such as low SES and substance use impact female partners' health. Therefore, there is a need for broader socio-ecological approach to IPV prevention and intervention that recognizes the relationship between male partners' risk factors and their female partners' health outcomes. Such approach can inform prevention and treatment of IPV and enhance partner wellbeing.
Partner smoking and maternal cotinine during pregnancy: Implications for negative control methods☆
Taylor, Amy E.; Davey Smith, George; Bares, Cristina B.; Edwards, Alexis C.; Munafò, Marcus R.
2014-01-01
Background Comparison of the associations of maternal and mother's partner smoking with offspring outcomes is, in theory, a useful method for assessing whether there may be an intrauterine effect of tobacco exposure on these outcomes. However, this approach assumes that the effects of passive smoking from exposure to partner smoking during pregnancy are minimal. We evaluated this assumption using a biochemical measure of tobacco exposure in pregnant women. Methods Cotinine levels taken during the first trimester of pregnancy were measured in a sample of 3928 women from the Avon Longitudinal Study of Parents and Children. Median cotinine values were compared across categories of smoking heaviness (cigarettes per day) of the women during the first trimester and in non-smoking women by the smoking heaviness of their partner. Results Cotinine levels were substantially higher in women who smoked compared to non-smokers (range of medians across smoking heaviness categories: 900–5362 ng/ml versus 20 ng/ml, interquartile range (IQR) (0–63) for non-smokers). In contrast, cotinine levels in non-smoking women were only very weakly related to partner smoking status (range of medians in women with smoking partners: 34–69 ng/ml versus 12 ng/ml, IQR (0–48) in women with non-smoking partners). Conclusions Levels of tobacco exposure from partner smoking, as assessed by cotinine, were low in non-smoking pregnant women. This suggests that using mother's partner's smoking as a negative control for investigating intrauterine effects is valid. PMID:24726428
Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks
NASA Astrophysics Data System (ADS)
White, Forest M.; Wolf-Yadlin, Alejandro
2016-06-01
Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.
Sukumaran, Salil K.; Blau-Wasser, Rosemarie; Rohlfs, Meino; Gallinger, Christoph; Schleicher, Michael; Noegel, Angelika A
2015-01-01
CEP161 is a novel component of the Dictyostelium discoideum centrosome which was identified as binding partner of the pericentriolar component CP250. Here we show that the amino acids 1-763 of the 1381 amino acids CEP161 are sufficient for CP250 binding, centrosomal targeting and centrosome association. Analysis of AX2 cells over-expressing truncated and full length CEP161 proteins revealed defects in growth and development. By immunoprecipitation experiments we identified the Hippo related kinase SvkA (Hrk-svk) as binding partner for CEP161. Both proteins colocalize at the centrosome. In in vitro kinase assays the N-terminal domain of CEP161 (residues 1-763) inhibited the kinase activity of Hrk-svk. A comparison of D. discoideum Hippo kinase mutants with mutants overexpressing CEP161 polypeptides revealed similar defects. We propose that the centrosomal component CEP161 is a novel player in the Hippo signaling pathway and affects various cellular properties through this interaction. PMID:25607232
Neural Precursor-Derived Pleiotrophin Mediates Subventricular Zone Invasion by Glioma.
Qin, Elizabeth Y; Cooper, Dominique D; Abbott, Keene L; Lennon, James; Nagaraja, Surya; Mackay, Alan; Jones, Chris; Vogel, Hannes; Jackson, Peter K; Monje, Michelle
2017-08-24
The lateral ventricle subventricular zone (SVZ) is a frequent and consequential site of pediatric and adult glioma spread, but the cellular and molecular mechanisms mediating this are poorly understood. We demonstrate that neural precursor cell (NPC):glioma cell communication underpins this propensity of glioma to colonize the SVZ through secretion of chemoattractant signals toward which glioma cells home. Biochemical, proteomic, and functional analyses of SVZ NPC-secreted factors revealed the neurite outgrowth-promoting factor pleiotrophin, along with required binding partners SPARC/SPARCL1 and HSP90B, as key mediators of this chemoattractant effect. Pleiotrophin expression is strongly enriched in the SVZ, and pleiotrophin knock down starkly reduced glioma invasion of the SVZ in the murine brain. Pleiotrophin, in complex with the binding partners, activated glioma Rho/ROCK signaling, and ROCK inhibition decreased invasion toward SVZ NPC-secreted factors. These findings demonstrate a pathogenic role for NPC:glioma interactions and potential therapeutic targets to limit glioma invasion. PAPERCLIP. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Compere, A L; Marcoccia, B S; Elliott, J
2012-08-31
Work with industrial partners to perform the studies needed to commercialize U.S. patent 7,699,958 for separation of carbohydrates from wood pulping liquors and wood or biomass hydrolysis liquors. These include: 1) selection of the best pulp mill liquor withdrawal sites, 2) additional purification or enzyme hydrolysis required to obtain acceptable sugar feedstocks, 3) and work with partners to optimize the stream and purification methods to provide acceptable feedstocks for algal fuels and industrial chemicals production, and 4) preparation of samples large enough for testing by downstream partners.
Xu, Feng; Beyazoglu, Turker; Hefner, Evan; Gurkan, Umut Atakan
2011-01-01
Cellular alignment plays a critical role in functional, physical, and biological characteristics of many tissue types, such as muscle, tendon, nerve, and cornea. Current efforts toward regeneration of these tissues include replicating the cellular microenvironment by developing biomaterials that facilitate cellular alignment. To assess the functional effectiveness of the engineered microenvironments, one essential criterion is quantification of cellular alignment. Therefore, there is a need for rapid, accurate, and adaptable methodologies to quantify cellular alignment for tissue engineering applications. To address this need, we developed an automated method, binarization-based extraction of alignment score (BEAS), to determine cell orientation distribution in a wide variety of microscopic images. This method combines a sequenced application of median and band-pass filters, locally adaptive thresholding approaches and image processing techniques. Cellular alignment score is obtained by applying a robust scoring algorithm to the orientation distribution. We validated the BEAS method by comparing the results with the existing approaches reported in literature (i.e., manual, radial fast Fourier transform-radial sum, and gradient based approaches). Validation results indicated that the BEAS method resulted in statistically comparable alignment scores with the manual method (coefficient of determination R2=0.92). Therefore, the BEAS method introduced in this study could enable accurate, convenient, and adaptable evaluation of engineered tissue constructs and biomaterials in terms of cellular alignment and organization. PMID:21370940
Partner Services in STD Prevention Programs: A Review
Hogben, Matthew; Collins, Dayne; Hoots, Brooke; O’Connor, Kevin
2015-01-01
Background Partner services have been a mainstay of public health sexually transmitted disease (STD) prevention programs for decades. The principal goals are to interrupt transmission and reduce STD morbidity and sequelae. In this paper, we review current literature with the goal of informing STD prevention programs. Methods We searched the literature for systematic reviews. We found nine reviews published between 2005 and 2014 (covering 108 studies). The reviews varied by study inclusion criteria (e.g., study methods, geographic location, infections). We abstracted major conclusions and recommendations from the reviews. Results Conclusions and recommendations were divided into patient referral interventions and provider referral interventions. For patient referral, there was evidence supporting the use of expedited partner therapy and interactive counseling, but not purely didactic instruction. Provider referral through Disease Intervention Specialists was efficacious and particularly well-supported for HIV. For other studies, modeling data and testing outcomes showed that partner notification in general reached high-prevalence populations. Reviews also suggested more focus on using technology and population-level implementation strategies. However, partner services may not be the most efficient means to reach infected persons. Conclusions Partner services programs constitute a large proportion of program STD prevention activities. Value is maximized by balancing a portfolio of patient and provider referral interventions and by blending partner notification interventions with other STD prevention interventions in overall partner services program structure. STD prevention needs program-level research and development to generate this portfolio. PMID:26779688
Derrick, Jaye L; Testa, Maria; Leonard, Kenneth E
2014-10-01
Agreement within couples regarding the occurrence of aggression is surprisingly low. Survey research often collapses across partners' reports to create a pooled estimate of aggression in the relationship. This method ignores possible differences in partners' perceptions of the event, potentially weakening researchers' ability to detect consequences of aggression. The current study examines both partners' reports of verbal aggression to determine whether aggression reported by only one partner influences both partners' short-term outcomes. We used a 56-day daily diary to examine the effect of verbal aggression on short-term negative outcomes. We examined whether aggression reported by either partner is sufficient to predict consequences for both partners, or if an individual must report aggression to experience consequences. Victims' reports of receiving verbal aggression were a better predictor of next day victim consequences than perpetrators' reports. Perpetrators' reports of perpetrating verbal aggression were a better predictor of next day perpetrator consequences than victims' reports. Days when partners agreed that aggression had occurred generally predicted the worst outcomes. People's own reports of verbal aggression are the best predictor of short-term consequences. Pooling partner reports of aggression may make it more difficult to understand the consequences of intimate partner aggression.
Interdependence in Women with Breast Cancer and Their Partners: An Interindividual Model of Distress
ERIC Educational Resources Information Center
Dorros, Sam M.; Card, Noel A.; Segrin, Chris; Badger, Terry A.
2010-01-01
Objective: The aim of this investigation was to test whether interdependence in dyads living with breast cancer could account for person-partner crossover effects in distress outcomes. Method: The sample consisted of 95 dyads with early-stage breast cancer. By using reciprocal dyadic data from women with breast cancer and their partners, we fit a…
Strategies Pregnant Rural Women Employ to Deal with Intimate Partner Violence
ERIC Educational Resources Information Center
Bhandari, Shreya; Bullock, Linda F. C.; Sharps, Phyllis W.
2013-01-01
This study explored strategies from the Intimate Partner Violence Strategy Index (IPVSI) that a sub-set of 20 rural, low-income, abused women of a larger, multi-site, mixed-method study employed to deal with Intimate Partner Violence (IPV) during the perinatal period. We conducted 32 in-depth interviews with women who were pregnant (N = 12) and/or…
ERIC Educational Resources Information Center
Taft, Casey T.; O'Farrell, Timothy J.; Doron-Lamarca, Susan; Panuzio, Jillian; Suvak, Michael K.; Gagnon, David R.; Murphy, Christopher M.
2010-01-01
Objective: This study examined static and time-varying risk factors for perpetration of intimate partner violence (IPV) among men in treatment for alcohol use disorders. Method: Participants were 178 men diagnosed with alcohol abuse or dependence and their partners. Most (85%) of the men were European American; their average age was 41.0 years.…
Jones, Ashlin; Pope, James; Coberley, Carter; Wells, Aaron
2017-01-01
Objective: To evaluate the relationship between partner well-being and outcomes of chronically diseased individuals participating in an employer sponsored well-being improvement program. Methods: Using the Actor Partner Interdependence Model, we evaluated whether prior partner well-being was associated with well-being change among 2025 couples. Logistic regression models were then used to explore how spousal well-being risks relate to development and elimination of risks among program participants. Results: High well-being partners were associated with positive well-being change. Specifically, the partner effect for spouses’ high well-being on disease management participants was a 1.5 point higher well-being in the following time period (P = 0.001) while the partner effect of participants’ high well-being on spouses was nearly 1.1 points (P = 0.010). Conclusions: Well-being within couples is interdependent, and partner well-being is an important predictor of individual well-being change. PMID:28045795
Tomnay, J E; Pitts, M K; Kuo, T C; Fairley, C K
2006-06-01
The primary outcome was to determine the acceptability of the Internet, specifically a website for use in standard partner notification. A secondary objective was to determine if a website would enhance the outcomes of currently used partner notification methods. In a randomized control trial, 105 participants diagnosed with chlamydia and non-gonoccocal urethritis (NGU) were randomized and 97 completed the study. About 30% of participants were provided a standard partner letter and 70% were provided the standard partner letter and website. All participants reported that their partners had no objections to the website (0%, 95% confidence interval [CI] 0-5%). There were no complaints received from any partner. The odds ratio for contacting partners was not significantly different between the two groups of participants. The results of this study indicate that providing a website with specific information about the infection to which a partner has been exposed is not harmful.
Phosphorylated c-Mpl tyrosine 591 regulates thrombopoietin-induced signaling.
Sangkhae, Veena; Saur, Sebastian Jonas; Kaushansky, Alexis; Kaushansky, Kenneth; Hitchcock, Ian Stuart
2014-06-01
Thrombopoietin (TPO) is the primary regulator of platelet production, affecting cell survival, proliferation, and differentiation through binding to and stimulation of the cell surface receptor the cellular myeloproliferative leukemia virus oncogene (c-Mpl). Activating mutations in c-Mpl constitutively stimulate downstream signaling pathways, leading to aberrant hematopoiesis, and contribute to development of myeloproliferative neoplasms. Several studies have mapped the tyrosine residues within the cytoplasmic domain of c-Mpl that mediate these cellular signals; however, secondary signaling pathways are incompletely understood. In this study, we focused on c-Mpl tyrosine 591 (Y591). We found Y591 of wild-type c-Mpl to be phosphorylated in the presence of TPO. Additionally, eliminating Y591 phosphorylation by mutation to Phe resulted in decreased total receptor phosphorylation. Using a Src homology 2/phosphotyrosine-binding (SH2/PTB) domain binding microarray, we identified novel c-Mpl binding partners for phosphorylated Y591, including Src homology region 2 domain-containing phosphatase-1 (SHP-1), spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK). The functional significance of binding partners was determined through small interfering RNA treatment of Ba/F3-Mpl cells, confirming that the increase in pERK1/2 resulting from removal of Y591 may be mediated by spleen tyrosine kinase. These findings identify a novel negative regulatory pathway that controls TPO-mediated signaling, advancing our understanding of the mechanisms required for successful maintenance of hematopoietic stem cells and megakaryocyte development. Copyright © 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng
2013-01-01
Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909
Direct structural evidence of protein redox regulation obtained by in-cell NMR.
Mercatelli, Eleonora; Barbieri, Letizia; Luchinat, Enrico; Banci, Lucia
2016-02-01
The redox properties of cellular environments are critical to many functional processes, and are strictly controlled in all living organisms. The glutathione-glutathione disulfide (GSH-GSSG) couple is the most abundant intracellular redox couple. A GSH redox potential can be calculated for each cellular compartment, which reflects the redox properties of that environment. This redox potential is often used to predict the redox state of a disulfide-containing protein, based on thermodynamic considerations. However, thiol-disulfide exchange reactions are often catalyzed by specific partners, and the distribution of the redox states of a protein may not correspond to the thermodynamic equilibrium with the GSH pool. Ideally, the protein redox state should be measured directly, bypassing the need to extrapolate from the GSH. Here, by in-cell NMR, we directly observe the redox state of three human proteins, Cox17, Mia40 and SOD1, in the cytoplasm of human and bacterial cells. We compare the observed distributions of redox states with those predicted by the GSH redox potential, and our results partially agree with the predictions. Discrepancies likely arise from the fact that the redox state of SOD1 is controlled by a specific partner, its copper chaperone (CCS), in a pathway which is not linked to the GSH redox potential. In principle, in-cell NMR allows determining whether redox proteins are at the equilibrium with GSH, or they are kinetically regulated. Such approach does not need assumptions on the redox potential of the environment, and provides a way to characterize each redox-regulating pathway separately. Copyright © 2015 Elsevier B.V. All rights reserved.
Extensive Differences in Gene Expression Between Symbiotic and Aposymbiotic Cnidarians
Lehnert, Erik M.; Mouchka, Morgan E.; Burriesci, Matthew S.; Gallo, Natalya D.; Schwarz, Jodi A.; Pringle, John R.
2013-01-01
Coral reefs provide habitats for a disproportionate number of marine species relative to the small area of the oceans that they occupy. The mutualism between the cnidarian animal hosts and their intracellular dinoflagellate symbionts provides the nutritional foundation for coral growth and formation of reef structures, because algal photosynthesis can provide >90% of the total energy of the host. Disruption of this symbiosis (“coral bleaching”) is occurring on a large scale due primarily to anthropogenic factors and poses a major threat to the future of coral reefs. Despite the importance of this symbiosis, the cellular mechanisms involved in its establishment, maintenance, and breakdown remain largely unknown. We report our continued development of genomic tools to study these mechanisms in Aiptasia, a small sea anemone with great promise as a model system for studies of cnidarian–dinoflagellate symbiosis. Specifically, we have generated de novo assemblies of the transcriptomes of both a clonal line of symbiotic anemones and their endogenous dinoflagellate symbionts. We then compared transcript abundances in animals with and without dinoflagellates. This analysis identified >900 differentially expressed genes and allowed us to generate testable hypotheses about the cellular functions affected by symbiosis establishment. The differentially regulated transcripts include >60 encoding proteins that may play roles in transporting various nutrients between the symbiotic partners; many more encoding proteins functioning in several metabolic pathways, providing clues regarding how the transported nutrients may be used by the partners; and several encoding proteins that may be involved in host recognition and tolerance of the dinoflagellate. PMID:24368779
Sexual Risk Taking Among Transgender Male-to-Female Youths With Different Partner Types
Garofalo, Robert; Harris, D. Robert; Belzer, Marvin
2010-01-01
Objectives. We examined associations between partner types (categorized as main, casual, or commercial) and sexual risk behaviors of sexually active male-to-female (transgender female) youths. Methods. We interviewed 120 transgender female youths aged 15 to 24 years recruited from clinics, community-based agencies, club and bar venues, referrals, and the streets of Los Angeles, California, and Chicago, Illinois. Results. Sexual risk behaviors varied by partner type. Transgender female youths were less likely to use condoms during receptive anal intercourse with their main partner and were less likely to use condoms with a main partner while under the influence of substances. Youth participants were also more likely to talk to a main partner about their HIV status. Our data identified no demographic or social factors that predicted condom use during receptive anal intercourse by partner type. Conclusions. Research and interventions that focus on understanding and mitigating risk behaviors by partner type, especially those that tackle the unique risks incurred with main partners, may make important contributions to risk reduction among transgender female youths. PMID:20622176
McBride, Kimberly R; Goldsworthy, Richard C; Fortenberry, J Dennis
2010-10-01
The study examined willingness to engage in patient-delivered partner screening (PDPS) and preferences for expedited partner services (EPS). Forty urban U.S. sexually transmitted infection (STI) clinic patients participated in individual mixed-methods interviews exploring EPS preferences and PDPS willingness. Most participants selected PDPS and PDPT together and uptake varied by patient–partner relationship closeness. For PDPS, several potentially important barriers and benefits were identified. Perceived benefits included improved sexual health for patients and their sexual partner(s) as well as convenience, privacy, and the potential to enhance trust between sexual partners. Perceived barriers included concerns about PDPS processes (e.g., time it would take to receive the result, risk of sample contamination), the accuracy of results, STI stigma and associated blame, lack of trust for a sexual partner, and the packaging/appearance of the screening kit. PDPS affords benefits and may overcome treatment barriers in some situations; however, it shares common PDPT barriers and has its own unique challenges. There are also concerns regarding how the offer of PDPS may interact with PDPT utilization.
2014-01-01
Background Family violence is a significant and complex public health problem that demands collaboration between researchers, practitioners, and policymakers for systemic, sustainable solutions. An integrated knowledge translation network was developed to support joint research production and application in the area. The purpose of this study was to determine the extent to which the international Preventing Violence Across the Lifespan (PreVAiL) Research Network built effective partnerships among its members, with a focus on the knowledge user partner perspective. Methods This mixed-methods study employed a combination of questionnaire and semi-structured interviews to understand partnerships two years after PreVAiL’s inception. The questionnaire examined communication, collaborative research, dissemination of research, research findings, negotiation, partnership enhancement, information needs, rapport, and commitment. The interviews elicited feedback about partners’ experiences with being part of the network. Results Five main findings were highlighted: i) knowledge user partner involvement varied across activities, ranging from 11% to 79% participation rates; ii) partners and researchers generally converged on their assessment of communication indicators; iii) partners valued the network at both an individual level and to fulfill their organizations’ mandates; iv) being part of PreVAiL allowed partners to readily contact researchers, and partners felt comfortable acting as an intermediary between PreVAiL and the rest of their own organization; v) application of research was just emerging; partners needed more actionable insights to determine ways to move forward given the research at that point in time. Conclusions Our results demonstrate the importance of developing and nurturing strong partnerships for integrated knowledge translation. Our findings are applicable to other network-oriented partnerships where a diversity of stakeholders work to address complex, multi-faceted public health problems. PMID:24886489
Partner symmetries and non-invariant solutions of four-dimensional heavenly equations
NASA Astrophysics Data System (ADS)
Malykh, A. A.; Nutku, Y.; Sheftel, M. B.
2004-07-01
We extend our method of partner symmetries to the hyperbolic complex Monge-Ampère equation and the second heavenly equation of Plebañski. We show the existence of partner symmetries and derive the relations between them. For certain simple choices of partner symmetries the resulting differential constraints together with the original heavenly equations are transformed to systems of linear equations by an appropriate Legendre transformation. The solutions of these linear equations are generically non-invariant. As a consequence we obtain explicitly new classes of heavenly metrics without Killing vectors.
Cellular water distribution, transport, and its investigation methods for plant-based food material.
Khan, Md Imran H; Karim, M A
2017-09-01
Heterogeneous and hygroscopic characteristics of plant-based food material make it complex in structure, and therefore water distribution in its different cellular environments is very complex. There are three different cellular environments, namely the intercellular environment, the intracellular environment, and the cell wall environment inside the food structure. According to the bonding strength, intracellular water is defined as loosely bound water, cell wall water is categorized as strongly bound water, and intercellular water is known as free water (FW). During food drying, optimization of the heat and mass transfer process is crucial for the energy efficiency of the process and the quality of the product. For optimizing heat and mass transfer during food processing, understanding these three types of waters (strongly bound, loosely bound, and free water) in plant-based food material is essential. However, there are few studies that investigate cellular level water distribution and transport. As there is no direct method for determining the cellular level water distributions, various indirect methods have been applied to investigate the cellular level water distribution, and there is, as yet, no consensus on the appropriate method for measuring cellular level water in plant-based food material. Therefore, the main aim of this paper is to present a comprehensive review on the available methods to investigate the cellular level water, the characteristics of water at different cellular levels and its transport mechanism during drying. The effect of bound water transport on quality of food product is also discussed. This review article presents a comparative study of different methods that can be applied to investigate cellular water such as nuclear magnetic resonance (NMR), bioelectric impedance analysis (BIA), differential scanning calorimetry (DSC), and dilatometry. The article closes with a discussion of current challenges to investigating cellular water. Copyright © 2017 Elsevier Ltd. All rights reserved.
Determinants of Recent HIV Infection Among Seattle-Area Men Who Have Sex with Men
Jenkins, Richard A.; Carey, James W.; Hutcheson, Rebecca; Thomas, Katherine K.; Stall, Ronald D.; White, Edward; Allen, Iris; Mejia, Roberto; Golden, Matthew R.
2009-01-01
Objectives. We sought to identify HIV-infection risk factors related to partner selection and sexual behaviors with those partners among men who have sex with men (MSM) in King County, Washington. Methods. Participants were recruited from HIV testing sites in the Seattle area. Recent HIV infection status was determined by the Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) or a self-reported previous HIV-negative test. Data on behaviors with 3 male partners were collected via computer-based self-interviews. Generalized estimating equation models identified partnership factors associated with recent infection. Results. We analyzed data from 32 HIV-positive MSM (58 partners) and 110 HIV-negative MSM (213 partners). In multivariate analysis, recent HIV infection was associated with meeting partners at bathhouses or sex clubs, bars or dance clubs, or online; methamphetamine use during unprotected anal intercourse; and unprotected anal intercourse, except with HIV-negative primary partners. Conclusions. There is a need to improve efforts to promote condom use with casual partners, regardless of their partner's HIV status. New strategies to control methamphetamine use in MSM and to reduce risk behaviors related to meeting partners at high-risk venues are needed. PMID:18445808
Bryant, Amy G; Hamela, Gloria; Gotter, Ann; Stuart, Gretchen S; Kamanga, Gift
2015-12-01
The copper intrauterine device (IUD) is a safe, long-acting, and effective method of contraception that is under-utilized in many countries, including Malawi. A unique cohort of women who had enrolled in a trial of postpartum IUD use one year earlier gave insights into reasons for using, discontinuing, or not using the IUD. We conducted in-depth interviews with 18 women one year after they participated in a pilot study of a randomized controlled trial of postpartum IUD insertion, and 10 of their male partners. Women and their partners expressed a strong desire for family planning, and perceived numerous benefits of the IUD. However, fear of the IUD was common among successful users and non-users alike. This fear arose from rumours from friends and neighbors who were non-users. How women and their partners responded to this fear affected IUD adoption and continuation. Key themes included (1) Trust in information received from health care providers versus rumours from community members; (2) Partner involvement in IUD decision-making; and (3) Experience with side effects from short-term hormonal contraceptive methods. Broad community education about the IUD's benefits and safety, and proactive counseling to address couples' specific fears, may be needed to increase uptake of the method.
Rabano, Miriam; Vivanco, Maria d M; Perrin, Florence Evelyne
2012-01-01
Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective motoneurons degeneration. There is today no clear-cut pathogenesis sequence nor any treatment. However growing evidences are in favor of the involvement, besides neurons, of several partners such as glia and muscles. To better characterize the time course of pathological events in an animal model that recapitulates human ALS symptoms, we investigated functional and cellular characteristics of hSOD1G93A mice. Methods and Findings We have evaluated locomotor function of hSOD1G93A mice through dynamic walking patterns and spontaneous motor activity analysis. We detected early functional deficits that redefine symptoms onset at 60 days of age, i.e. 20 days earlier than previously described. Moreover, sequential combination of these approaches allows monitoring of motor activity up to disease end stage. To tentatively correlate early functional deficit with cellular alterations we have used flow cytometry and immunohistochemistry approaches to characterize neuromuscular junctions, astrocytes and microglia. We show that (1) decrease in neuromuscular junction's number correlates with motor impairment, (2) astrocytes number is not altered at pre- and early-symptomatic ages but intraspinal repartition is modified at symptoms onset, and (3) microglia modifications precede disease onset. At pre-symptomatic age, we show a decrease in microglia number whereas at onset of the disease two distinct microglia sub-populations emerge. Conclusions In conclusion, precise motor analysis updates the onset of the disease in hSOD1G93A mice and allows locomotor monitoring until the end stage of the disease. Early functional deficits coincide with alterations of neuromuscular junctions. Importantly, we identify different sets of changes in microglia before disease onset as well as at early-symptomatic stage. This finding not only brings a new sequence of cellular events in the natural history of the disease, but it may also provide clues in the search for biomarkers of the disease, and potential therapeutic targets. PMID:22558300
Mirzarezaee, Mitra; Araabi, Babak N; Sadeghi, Mehdi
2010-12-19
It has been understood that biological networks have modular organizations which are the sources of their observed complexity. Analysis of networks and motifs has shown that two types of hubs, party hubs and date hubs, are responsible for this complexity. Party hubs are local coordinators because of their high co-expressions with their partners, whereas date hubs display low co-expressions and are assumed as global connectors. However there is no mutual agreement on these concepts in related literature with different studies reporting their results on different data sets. We investigated whether there is a relation between the biological features of Saccharomyces Cerevisiae's proteins and their roles as non-hubs, intermediately connected, party hubs, and date hubs. We propose a classifier that separates these four classes. We extracted different biological characteristics including amino acid sequences, domain contents, repeated domains, functional categories, biological processes, cellular compartments, disordered regions, and position specific scoring matrix from various sources. Several classifiers are examined and the best feature-sets based on average correct classification rate and correlation coefficients of the results are selected. We show that fusion of five feature-sets including domains, Position Specific Scoring Matrix-400, cellular compartments level one, and composition pairs with two and one gaps provide the best discrimination with an average correct classification rate of 77%. We study a variety of known biological feature-sets of the proteins and show that there is a relation between domains, Position Specific Scoring Matrix-400, cellular compartments level one, composition pairs with two and one gaps of Saccharomyces Cerevisiae's proteins, and their roles in the protein interaction network as non-hubs, intermediately connected, party hubs and date hubs. This study also confirms the possibility of predicting non-hubs, party hubs and date hubs based on their biological features with acceptable accuracy. If such a hypothesis is correct for other species as well, similar methods can be applied to predict the roles of proteins in those species.
Contributions of Work Stressors, Alcohol, and Normative Beliefs to Partner Violence
Ames, Genevieve M.; Cunradi, Carol B.; Duke, Michael; Todd, Michael; Chen, Meng-Jinn
2013-01-01
Objective: A body of research has established that lower socioeconomic populations, including blue-collar workers, are at higher risk for problem drinking and intimate partner violence. This study of married/cohabiting construction workers and their spouses/partners describes how work stressors, hazardous drinking, and couple characteristics interact to influence normative beliefs around partner violence and, thereafter, its occurrence. Method: Our survey respondents from a sample of 502 dual-earner couples were asked about drinking patterns, past-year partner violence, normative beliefs about partner violence, work-related stressors, impulsivity, and childhood exposure to violence and other adverse events. We conducted semi-structured qualitative interviews with 81 workers on context of work stress, partner violence, and drinking. Results: Analyses of data revealed that men’s and women’s normative beliefs about partner violence were positively related to male-to-female partner violence; female partner violence normative beliefs were associated with female-to-male partner violence. Both partners’ levels of impulsivity were directly associated with male-to-female and female-to-male partner violence, and male partner’s frequency of intoxication mediated the association between level of impulsivity and male-to-female partner violence. Female partner’s adverse childhood experience was directly associated with male-to-female partner violence. Both survey and qualitative interviews identified individual and work-related factors that influence the occurrence of violence between men and women. Discussion: These findings provide guidelines for prevention of partner violence that can be implemented in the workplace with attention to hazardous drinking, job stress, treatment, education, and work culture. PMID:23384367
Personal and Relationship Challenges of Adults With Type 1 Diabetes
Trief, Paula M.; Sandberg, Jonathan G.; Dimmock, Jacqueline A.; Forken, Patricia J.; Weinstock, Ruth S.
2013-01-01
OBJECTIVE Little is known about the psychosocial challenges of adults living with type 1 diabetes or its impact on partner relationships. This qualitative study was undertaken to gain better understanding of these issues. RESEARCH DESIGN AND METHODS Four focus groups were held, two with adult type 1 diabetic patients (n = 16) and two with partners (n = 14). Two broad questions were posed: “What are the emotional and interpersonal challenges you have experienced because you have (your partner has) type 1 diabetes?” and “How does the fact that you have (your partner has) type 1 diabetes affect your relationship with your partner, positively and/or negatively?” Sessions were recorded and transcribed, and analyzed by a team of four researchers, using constant comparative methods to identify core domains and concepts. RESULTS Four main domains were identified: 1) impact of diabetes on the relationship, including level of partner involvement, emotional impact of diabetes on the relationship, and concerns about child-rearing; 2) understanding the impact of hypoglycemia; 3) stress of potential complications; and 4) benefits of technology. Themes suggest that, although partner involvement varies (very little to significant), there exists significant anxiety about hypoglycemia and future complications and sources of conflict that may increase relationship stress. Partner support is highly valued, and technology has a positive influence. CONCLUSIONS Adults with type 1 diabetes face unique emotional and interpersonal challenges. Future research should focus on gaining a better understanding of how they cope and the effect of psychosocial stressors and coping on adherence, quality of life, and glycemic control. PMID:23474590
van Wyk, Neltjie; van Rensburg, Elsie Janse
2016-01-01
Background Millennium Developmental Goal 3 (MDG 3) aims at enhancing gender equity and empowerment of women. Emergency nurses who often encounter women injured by their intimate partners are at risk of developing vicarious traumatisation, which may influence their ability to empower women to move beyond the oppression of intimate partner violence. Aim This article aims to, (1) describe emergency nurses’ ways of coping with the exposure to survivors of intimate partner violence, and (2) recommend a way towards effective coping that will enhance emergency nurses’ abilities to empower women to move beyond the oppression of intimate partner violence to contribute to the achievement of MDG 3. Setting The study was conducted in emergency units of two public hospitals in an urban setting in South Africa. Method A qualitative design and descriptive phenomenological method was used. Emergency nurses working in the setting were purposively sampled and interviewed. The data were analysed by searching for the essence and meaning attached to the exposure of emergency nurses to survivors of intimate partner violence. Results Emergency nurses’ coping responses were either aimed at avoiding or dealing with their exposure to survivors of intimate partner violence. Coping aimed at dealing with the exposure included seeking support, emotion regulation and accommodative coping. Conclusion Emergency nurses employ either effective or ineffective ways of coping. Less effective ways of coping may increase their risk of vicarious and secondary traumatisation, which in turn may influence their ability to empower women to move beyond the oppression of intimate partner violence. PMID:27380838
Aguado Loi, Claudia X; Alfonso, Moya L; Chan, Isabella; Anderson, Kelsey; Tyson, Dinorah Dina Martinez; Gonzales, Junius; Corvin, Jaime
2017-08-01
The purpose of this paper is to share lessons learned from a collaborative, community-informed mixed-methods approach to adapting an evidence-based intervention to meet the needs of Latinos with chronic disease and minor depression and their family members. Mixed-methods informed by community-based participatory research (CBPR) were employed to triangulate multiple stakeholders' perceptions of facilitators and barriers of implementing the adapted intervention in community settings. Community partners provided an insider perspective to overcome methodological challenges. The study's community informed mixed-methods: research approach offered advantages to a single research methodology by expanding or confirming research findings and engaging multiple stakeholders in data collection. This approach also allowed community partners to collaborate with academic partners in key research decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.
Yee, L M; Goldberger, A R; Garcia, P M; Miller, E S
2017-01-01
To characterize pregnant patients' knowledge, attitudes and preferences regarding antenatal HIV testing for themselves and their sexual partners. Observational, mixed methods study of HIV-negative pregnant women from a university-based urban clinic. Participants completed an anonymous survey about HIV testing for themselves and their partners. Descriptive statistics, bivariable analyses, multivariable logistic regression and qualitative thematic analysis were utilized. One hundred and forty-two patients (mean age 28.6±5.5 years) participated. A majority (57.7%) were married or partnered, and 92.9% reported having at least one current sexual partner. Although a majority (62.8%) reported their partner had a prior HIV test, and 93.0% of these women were aware of test results, only 20.7% reported partner testing had occurred in the past 6 months. Women who had a prior HIV test, who were older or who were non-white were more likely to be aware of their partner's HIV status. A majority (66.9%) of women desired knowledge of their partner's current status and 76.0% believed their partners would like to know his HIV status; in addition, 74% were interested in receiving partner testing at the site of prenatal care. Qualitative analysis demonstrated that health concerns and believing HIV knowledge is important to the relationship were motivators for desiring partner testing. In this urban community, a majority of pregnant women do not know HIV test results of their sexual partner during the current pregnancy. Women desired to know their partner's HIV status and were receptive to partner testing at the site of prenatal care or other locations. Partner testing may be a critical step toward elimination of seroconversion during pregnancy and maternal-to-child HIV transmission.
Clark, Jesse L.; Perez-Brumer, Amaya G.; Segura, Eddy R.; Salvatierra, Hector J.; Sanchez, Jorge; Lama, Javier R.
2016-01-01
Background New strategies to support partner notification (PN) are critical for STD control and require detailed understanding of how specific individual and partnership characteristics guide notification decisions. Methods From 2011 to 2012, 397 MSM and TW recently diagnosed with HIV, syphilis, or another STD completed a survey on anticipated notification of recent sexual partners and associated factors. Qualitative interviews were conducted with a subset of participants to provide further depth to quantitative findings. Prevalence ratios and generalized estimating equation (GEE) models were used to analyze participant- and partner-level factors associated with anticipated PN. Results Among all partners reported, 52.5% were described as “Very Likely” or “Somewhat Likely” to be notified. Anticipated notification was more likely for main partners than casual (adjusted Prevalence Ratio [aPR], 95% CI: 0.63, 0.54–0.75) or commercial (aPR, 95% CI: 0.44, 0.31–0.62) partners. Other factors associated with likely notification included perception of the partner as an STD source (aPR, 95% CI: 1.27, 1.10–1.48) and anticipated future sexual contact with the partner (aPR, 95% CI: 1.30, 1.11–1.52). An HIV diagnosis was associated with a lower likelihood of notification than non-HIV STDs (aPR: 0.68, 0.55–0.86). Qualitative discussion of the barriers and incentives to PN reflected a similar differentiation of anticipated notification according to partnership type and type of HIV/STD diagnosis. Discussion Detailed attention to how partnership characteristics guide notification outcomes is essential to the development of new PN strategies. By accurately and thoroughly assessing the diversity of partnership interactions among individuals with HIV/STD, new notification techniques can be tailored to partner-specific circumstances. PMID:27685158
An improved cellular automaton method to model multispecies biofilms.
Tang, Youneng; Valocchi, Albert J
2013-10-01
Biomass-spreading rules used in previous cellular automaton methods to simulate multispecies biofilm introduced extensive mixing between different biomass species or resulted in spatially discontinuous biomass concentration and distribution; this caused results based on the cellular automaton methods to deviate from experimental results and those from the more computationally intensive continuous method. To overcome the problems, we propose new biomass-spreading rules in this work: Excess biomass spreads by pushing a line of grid cells that are on the shortest path from the source grid cell to the destination grid cell, and the fractions of different biomass species in the grid cells on the path change due to the spreading. To evaluate the new rules, three two-dimensional simulation examples are used to compare the biomass distribution computed using the continuous method and three cellular automaton methods, one based on the new rules and the other two based on rules presented in two previous studies. The relationship between the biomass species is syntrophic in one example and competitive in the other two examples. Simulation results generated using the cellular automaton method based on the new rules agree much better with the continuous method than do results using the other two cellular automaton methods. The new biomass-spreading rules are no more complex to implement than the existing rules. Copyright © 2013 Elsevier Ltd. All rights reserved.
Recruiting patients as partners in health research: a qualitative descriptive study.
Vat, Lidewij Eva; Ryan, Devonne; Etchegary, Holly
2017-01-01
Increasingly, funders and researchers want to partner with patients in health research, but it can be challenging for researchers to find patient partners. More than taking part in research as participants, patient partners help design, carry out and manage research projects. The goal of this study was to describe ways that patient partners have been recruited by researchers and patient engagement leads (individuals within organizations responsible for promoting and supporting patients as research partners). We talked with researchers and patient engagement leads in Canada and the United Kingdom, as well as a patient representative. We found three ways that could help researchers and patients find each other. One way is a case-by-case basis, where patients are often sought with experience of a health condition that is the focus of the research. The other ways involved directories where projects were posted and could be found by patients and researchers, or a third party matched patients with research projects. We found four recruitment strategies:Social marketingCommunity outreachHealth systemPartnering with other organizations (e.g., advocacy groups) There are many influences on finding, selecting and retaining patient partners: patient characteristics, the local setting, the opportunity, work climate, education and support. We hope study results will provide a useful starting point for research teams in recruiting their patient partners. Background Patient engagement in clinical trials and other health research continues to gain momentum. While the benefits of patient engagement in research are emerging, relatively little is known about recruiting patients as research partners. The purpose of this study was to describe recruitment strategies and models of recruiting patients as partners in health research. Methods Qualitative descriptive study. Thirteen patient engagement leads and health researchers from Canada and the United Kingdom, as well as one patient representative from a national patient organization (7 female) completed semi-structured interviews. Results Recruitment infrastructures available to respondents varied, but could be categorized into three models including the traditional, third-party and directory models. Four categories of recruitment strategies were identified, representing multiple ways of recruiting patient partners: social marketing recruitment, community outreach recruitment, health system recruitment, and partnering recruitment. Conclusions Multiple recruitment strategies were identified for engaging patient partners in research, and some common factors influenced recruitment. Study findings contribute to the evidence base in patient engagement and provide guidance for research teams to help identify potential recruitment methods for their patient partners.
Negroni-Belén, Mirka; Vargas-Guadarrama, Galileo; Rueda-Neria, Celina Magally; Bassett-Hileman, Sarah; Weir, Sharon; Bronfman, Mario
2003-01-01
To identify the meeting sites of new sexual partners in two Southern border cities in Mexico. A descriptive epidemiologic study was carried out in May 2001, by surveying key informants in two border cities. Each reported site was visited to interview a resident subject. Subjects socializing in a subsample of sites were also interviewed. The key informants of the community reported 134 meeting sites in Chetumal and 111 in Ciudad Hidalgo. Both sites had scarce HIV/AIDS prevention activities. Characteristics were obtained for 89 sites in Chetumal and 42 in Ciudad Hidalgo. Almost 21% of interviewees reportedly met a new sexual partner in these sites in the past four weeks. Preventive actions are needed in meeting sites of new sexual partners. This method may provide information to plan for future interventions. The English version of this paper is available too at:http://www.insp.mx/salud/index.html.
Reactivity to a Spouse's Interpersonal Suffering in Late Life Marriage: A Mixed-Methods Approach
Mitchell, Hannah-Rose; Levy, Becca R.; Keene, Danya E.; Monin, Joan K.
2015-01-01
Objective To determine how older adult spouses react to their partners' interpersonal suffering. Method Spouses of individuals with musculoskeletal pain were recorded describing their partners' suffering while their blood pressure (BP) was monitored. After the account, spouses described their distress. Speeches were transcribed and analyzed with Linguistic Inquiry and Word Count software and coded for interpersonal content. Multivariate regression analyses were conducted with interpersonal content variables predicting BP and distress. Exploratory qualitative analysis was conducted using ATLAS.ti to explore mechanisms behind quantitative results. Results Describing partners' suffering as interpersonal and using social (family) words were associated with higher systolic BP reactivity. Husbands were more likely to describe partners' suffering as interpersonal. Qualitative results suggested shared stressors and bereavement-related distress as potential mechanisms for heightened reactivity to interpersonal suffering. Discussion Spouses' interpersonal suffering may negatively affect both men and women's cardiovascular health, and older husbands may be particularly affected. PMID:25659746
Novel approach using DNA-RNA hybrids in RNA nanotechnology | Center for Cancer Research
Developing simple approaches to detect interactions, modifications, and cellular locations of macromolecules is essential for understanding biochemical processes. The use of protein fragment complementation assays, also called split-protein systems, is a highly sensitive approach for studying protein interactions in biological systems. In this approach, functional proteins are split into non-functional fragments, and when attached to possible interacting partners, can reassemble and become functional again. Use of split-protein assays can establish differences between a healthy and a diseased state in the cell as well as determine the outcome of a therapeutic intervention.
Lallemand-Breitenbach, Valérie; de Thé, Hugues
2010-01-01
PML nuclear bodies are matrix-associated domains that recruit an astonishing variety of seemingly unrelated proteins. Since their discovery in the early 1960s, PML bodies have fascinated cell biologists because of their beauty and their tight association with cellular disorders. The identification of PML, a gene involved in an oncogenic chromosomal translocation, as the key organizer of these domains drew instant interest onto them. The multiple levels of PML body regulation by a specific posttranslational modification, sumoylation, have raised several unsolved issues. Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma. PMID:20452955
Lallemand-Breitenbach, Valérie; de Thé, Hugues
2010-05-01
PML nuclear bodies are matrix-associated domains that recruit an astonishing variety of seemingly unrelated proteins. Since their discovery in the early 1960s, PML bodies have fascinated cell biologists because of their beauty and their tight association with cellular disorders. The identification of PML, a gene involved in an oncogenic chromosomal translocation, as the key organizer of these domains drew instant interest onto them. The multiple levels of PML body regulation by a specific posttranslational modification, sumoylation, have raised several unsolved issues. Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma.
Mutations in the NHEJ Component XRCC4 Cause Primordial Dwarfism
Murray, Jennie E.; van der Burg, Mirjam; IJspeert, Hanna; Carroll, Paula; Wu, Qian; Ochi, Takashi; Leitch, Andrea; Miller, Edward S.; Kysela, Boris; Jawad, Alireza; Bottani, Armand; Brancati, Francesco; Cappa, Marco; Cormier-Daire, Valerie; Deshpande, Charu; Faqeih, Eissa A.; Graham, Gail E.; Ranza, Emmanuelle; Blundell, Tom L.; Jackson, Andrew P.; Stewart, Grant S.; Bicknell, Louise S.
2015-01-01
Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation. PMID:25728776
Novel interactive partners of neuroligin 3: new aspects for pathogenesis of autism.
Shen, Chen; Huo, Li-rong; Zhao, Xin-liang; Wang, Pei-rong; Zhong, Nanbert
2015-05-01
Autism is a neurodevelopmental disorder with a strong genetic predisposition. Neurolign 3 (NLGN3) as a postsynaptic transmembrane protein, functions in both neuron synaptogenesis and glia-neuron communications. Previously, a gain of function mutation (R451C) in NLGN3 was identified in autistic patients, which illustrates the involvement of NLGN3 in autism pathogenesis. As proper synaptic targeting and functioning are controlled by intracellular protein interactions, in the current study, we tried to discover the intracellular regulation network in which NLGN3 might be involved by a yeast two-hybrid-based interactor identification. Fifty-one protein candidate partners were identified after screening a human fetal complementary DNA (cDNA) library with an intracellular fragment of NLGN3. The interactions of NLGN3 with a subset of candidates, including EEF1A1, FLNA, ITPRIP, CYP11A1, MT-CO2, GPR175, ACOT2, and QPRT, were further validated in human neuroblastoma cells or brain tissues. Furthermore, our study suggested that NLGN3 was functioning in cytosolic calcium balance and participating in calcium-regulated cellular processes. Our findings of novel NLGN3 binding partners provide evidences of involvement of NLGN3 in multiple biological pathways, especially calcium regulating and mitochondrial function, thus suggesting further significance. This new data not only leads to a better understanding of the physiological functions of NLGN3, but also provide new aspects for pathogenesis of autism.
Violence against Educated Women by Intimate Partners in Urban Karnataka, India
Kundapur, Rashmi; Shetty, Shruthi M.; Kempaller, Vinayak J.; Kumar, Ashwini; Anurupa, M.
2017-01-01
Background: Initially viewed as a human rights issue, partner violence is increasingly seen as an important public health problem of international concern. Objectives: To assess the extent of physical, sexual, psychological, and controlling behavior of intimate partners against women in an educated society and find the association with age, age of marriage, married years, educational status of the women and that of partner. Materials and Methods: A prevalence of 15% was taken and final sample was 200, after considering loss of follow-up. Statistical Methods: Proportion, Z-test, Chi-square test. Results: The prevalence of violence against intimate partner in educated society was found to be 40.5% in a South Indian city. Physical assault was high in 30–50 years and increased with duration of marriage from 5.5% at 5 years to 33.3% in 10–20 years of married life. Sexual and psychological assault also increased in <5 years of married life to 35% and 47.6% in 10–20 years duration of marriage, which was statistically significant. Sexual and psychological assault showed a bimodal presentation. Less educated women and their partners were found to report more violence, which was statistically significant. Conclusion: Violence against women is not uncommon in the educated society. PMID:28852277
Predicting receptor-ligand pairs through kernel learning
2011-01-01
Background Regulation of cellular events is, often, initiated via extracellular signaling. Extracellular signaling occurs when a circulating ligand interacts with one or more membrane-bound receptors. Identification of receptor-ligand pairs is thus an important and specific form of PPI prediction. Results Given a set of disparate data sources (expression data, domain content, and phylogenetic profile) we seek to predict new receptor-ligand pairs. We create a combined kernel classifier and assess its performance with respect to the Database of Ligand-Receptor Partners (DLRP) 'golden standard' as well as the method proposed by Gertz et al. Among our findings, we discover that our predictions for the tgfβ family accurately reconstruct over 76% of the supported edges (0.76 recall and 0.67 precision) of the receptor-ligand bipartite graph defined by the DLRP "golden standard". In addition, for the tgfβ family, the combined kernel classifier is able to relatively improve upon the Gertz et al. work by a factor of approximately 1.5 when considering that our method has an F-measure of 0.71 while that of Gertz et al. has a value of 0.48. Conclusions The prediction of receptor-ligand pairings is a difficult and complex task. We have demonstrated that using kernel learning on multiple data sources provides a stronger alternative to the existing method in solving this task. PMID:21834994
Dynamics of ARF regulation that control senescence and cancer.
Ko, Aram; Han, Su Yeon; Song, Jaewhan
2016-11-01
ARF is an alternative reading frame product of the INK4a/ARF locus, inactivated in numerous human cancers. ARF is a key regulator of cellular senescence, an irreversible cell growth arrest that suppresses tumor cell growth. It functions by sequestering MDM2 (a p53 E3 ligase) in the nucleolus, thus activating p53. Besides MDM2, ARF has numerous other interacting partners that induce either cellular senescence or apoptosis in a p53-independent manner. This further complicates the dynamics of the ARF network. Expression of ARF is frequently disrupted in human cancers, mainly due to epigenetic and transcriptional regulation. Vigorous studies on various transcription factors that either positively or negatively regulate ARF transcription have been carried out. However, recent focus on posttranslational modifications, particularly ubiquitination, indicates wider dynamic controls of ARF than previously known. In this review, we discuss the role and dynamic regulation of ARF in senescence and cancer. [BMB Reports 2016; 49(11): 598-606].
The BioPlex Network: A Systematic Exploration of the Human Interactome.
Huttlin, Edward L; Ting, Lily; Bruckner, Raphael J; Gebreab, Fana; Gygi, Melanie P; Szpyt, John; Tam, Stanley; Zarraga, Gabriela; Colby, Greg; Baltier, Kurt; Dong, Rui; Guarani, Virginia; Vaites, Laura Pontano; Ordureau, Alban; Rad, Ramin; Erickson, Brian K; Wühr, Martin; Chick, Joel; Zhai, Bo; Kolippakkam, Deepak; Mintseris, Julian; Obar, Robert A; Harris, Tim; Artavanis-Tsakonas, Spyros; Sowa, Mathew E; De Camilli, Pietro; Paulo, Joao A; Harper, J Wade; Gygi, Steven P
2015-07-16
Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors. Copyright © 2015 Elsevier Inc. All rights reserved.
The BioPlex Network: A Systematic Exploration of the Human Interactome
Huttlin, Edward L.; Ting, Lily; Bruckner, Raphael J.; Gebreab, Fana; Gygi, Melanie P.; Szpyt, John; Tam, Stanley; Zarraga, Gabriela; Colby, Greg; Baltier, Kurt; Dong, Rui; Guarani, Virginia; Vaites, Laura Pontano; Ordureau, Alban; Rad, Ramin; Erickson, Brian K.; Wühr, Martin; Chick, Joel; Zhai, Bo; Kolippakkam, Deepak; Mintseris, Julian; Obar, Robert A.; Harris, Tim; Artavanis-Tsakonas, Spyros; Sowa, Mathew E.; DeCamilli, Pietro; Paulo, Joao A.; Harper, J. Wade; Gygi, Steven P.
2015-01-01
SUMMARY Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally-related proteins. Finally, BioPlex, in combination with other approaches can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial Amyotrophic Lateral Sclerosis perturb a defined community of interactors. PMID:26186194
Female contact modulates male aggression via a sexually dimorphic GABAergic circuit in Drosophila
Yuan, Quan; Song, Yuanquan; Yang, Chung-Hui; Jan, Lily Yeh; Jan, Yuh Nung
2014-01-01
Intraspecific male-male aggression, important for sexual selection, is regulated by environment, experience and internal states through largely undefined molecular and cellular mechanisms. To understand the basic neural pathway underlying the modulation of this innate behavior, we established a behavioral paradigm in Drosophila melanogaster and investigated the relationship between sexual experience and aggression. In the presence of mating partners, adult male flies exhibited elevated levels of aggression, which was largely suppressed by prior exposure to females via a sexually dimorphic neural mechanism. The suppression involved the ability of male flies to detect females by contact chemosensation through the pheromone-sensing ion channel, ppk29, and was mediated by male specific GABAergic neurons acting upon GABA-a receptor RDL in target cells. Silencing or activation of this circuit led to dis-inhibition or elimination of sex-related aggression, respectively. We propose that the GABAergic inhibition represents a critical cellular mechanism that enables prior experience to modulate aggression. PMID:24241395
The retrovirus RNA trafficking granule: from birth to maturity
Cochrane, Alan W; McNally, Mark T; Mouland, Andrew J
2006-01-01
Post-transcriptional events in the life of an RNA including RNA processing, transport, translation and metabolism are characterized by the regulated assembly of multiple ribonucleoprotein (RNP) complexes. At each of these steps, there is the engagement and disengagement of RNA-binding proteins until the RNA reaches its final destination. For retroviral genomic RNA, the final destination is the capsid. Numerous studies have provided crucial information about these processes and serve as the basis for studies on the intracellular fate of retroviral RNA. Retroviral RNAs are like cellular mRNAs but their processing is more tightly regulated by multiple cis-acting sequences and the activities of many trans-acting proteins. This review describes the viral and cellular partners that retroviral RNA encounters during its maturation that begins in the nucleus, focusing on important events including splicing, 3' end-processing, RNA trafficking from the nucleus to the cytoplasm and finally, mechanisms that lead to its compartmentalization into progeny virions. PMID:16545126
Exploring the Yeast Acetylome Using Functional Genomics
Duffy, Supipi Kaluarachchi; Friesen, Helena; Baryshnikova, Anastasia; Lambert, Jean-Philippe; Chong, Yolanda T.; Figeys, Daniel; Andrews, Brenda
2014-01-01
SUMMARY Lysine acetylation is a dynamic posttranslational modification with a well-defined role in regulating histones. The impact of acetylation on other cellular functions remains relatively uncharacterized. We explored the budding yeast acetylome with a functional genomics approach, assessing the effects of gene overexpression in the absence of lysine deacetylases (KDACs). We generated a network of 463 synthetic dosage lethal (SDL) interactions involving class I and II KDACs, revealing many cellular pathways regulated by different KDACs. A biochemical survey of genes interacting with the KDAC RPD3 identified 72 proteins acetylated in vivo. In-depth analysis of one of these proteins, Swi4, revealed a role for acetylation in G1-specific gene expression. Acetylation of Swi4 regulates interaction with its partner Swi6, both components of the SBF transcription factor. This study expands our view of the yeast acetylome, demonstrates the utility of functional genomic screens for exploring enzymatic pathways, and provides functional information that can be mined for future studies. PMID:22579291
Structural Mechanism of Voltage-Dependent Gating in an Isolated Voltage-Sensing Domain
Li, Qufei; Wanderling, Sherry; Paduch, Marcin; Medovoy, David; Singharoy, Abhishek; McGreevy, Ryan; Villalba-Galea, Carlos; Hulse, Raymond E.; Roux, Benoit; Schulten, Klaus; Kossiakoff, Anthony; Perozo, Eduardo
2014-01-01
SUMMARY The transduction of transmembrane electric fields into protein motion plays an essential role in the generation and propagation of cellular signals. Voltage-sensing domains (VSD) carry out these functions through reorientations of S4 helix with discrete gating charges. Here, crystal structures of the VSD from Ci-VSP were determined in both, active (Up) and resting (Down) conformations. The S4 undergoes a ~5 Å displacement along its main axis accompanied by a ~60o rotation, consistent with the helix-screw gating mechanism. This movement is stabilized by a change in countercharge partners in helices S1 and S3, generating an estimated net charge transfer of ~1 eo. Gating charges move relative to a “hydrophobic gasket” that electrically divides intra and extracellular compartments. EPR spectroscopy confirms the limited nature of S4 movement in a membrane environment. These results provide an explicit mechanism for voltage sensing and set the basis for electromechanical coupling in voltage-dependent cellular activities. PMID:24487958
Uversky, Vladimir N.
2014-01-01
Biologically active proteins without stable tertiary structure are common in all known proteomes. Functions of these intrinsically disordered proteins (IDPs) are typically related to regulation, signaling, and control. Cellular levels of these important regulators are tightly regulated by a variety mechanisms ranging from firmly controlled expression to precisely targeted degradation. Functions of IDPs are controlled by binding to specific partners, alternative splicing, and posttranslational modifications among other means. In the norm, right amounts of precisely activated IDPs have to be present in right time at right places. Wrecked regulation brings havoc to the ordered world of disordered proteins, leading to protein misfolding, misidentification, and missignaling that give rise to numerous human diseases, such as cancer, cardiovascular disease, neurodegenerative diseases, and diabetes. Among factors inducing pathogenic transformations of IDPs are various cellular mechanisms, such as chromosomal translocations, damaged splicing, altered expression, frustrated posttranslational modifications, aberrant proteolytic degradation, and defective trafficking. This review presents some of the aspects of deregulated regulation of IDPs leading to human diseases. PMID:25988147
Allosteric conformational barcodes direct signaling in the cell.
Nussinov, Ruth; Ma, Buyong; Tsai, Chung-Jung; Csermely, Peter
2013-09-03
The cellular network is highly interconnected. Pathways merge and diverge. They proceed through shared proteins and may change directions. How are cellular pathways controlled and their directions decided, coded, and read? These questions become particularly acute when we consider that a small number of pathways, such as signaling pathways that regulate cell fates, cell proliferation, and cell death in development, are extensively exploited. This review focuses on these signaling questions from the structural standpoint and discusses the literature in this light. All co-occurring allosteric events (including posttranslational modifications, pathogen binding, and gain-of-function mutations) collectively tag the protein functional site with a unique barcode. The barcode shape is read by an interacting molecule, which transmits the signal. A conformational barcode provides an intracellular address label, which selectively favors binding to one partner and quenches binding to others, and, in this way, determines the pathway direction, and, eventually, the cell's response and fate. Copyright © 2013 Elsevier Ltd. All rights reserved.
NF90 isoforms, a new family of cellular proteins involved in viral replication?
Patiño, Claudia; Haenni, Anne-Lise; Urcuqui-Inchima, Silvio
2015-01-01
The Nuclear Factor 90 (NF90) and its isoforms constitute a family of proteins that can interact with double-stranded (ds) RNA, through its dsRNA binding motifs. Due to various potential translational events such as alternative splicing, the human Interleukin enhancer binding factor 3 (ilf3) gene codes for multifunctional proteins that are NF90 and its isoforms, involved in transcription, translation, mRNA export and microRNA biogenesis. These proteins can act as cellular partners affecting viral replication and they are also implicated in host defense. As a result of these numerous functions, these protein isoforms have been given various names over the years, leading to confusion in determining their specific functions. In this review we focus on the role of the human NF90 protein isoforms in DNA and RNA virus replication. Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.
Increased Risks of Needing Long-Term Care Among Older Adults Living With Same-Sex Partners
Brodoff, Lisa
2013-01-01
Objectives. We examined whether older individuals living with same-sex partners face greater risks of needing long-term care than their counterparts living with different-sex partners or spouses. Methods. With data on older couples (at least 1 individual aged 60 years or older) from the 2009 American Community Survey, we estimated logistic regression models of 2 activity limitations that signal a long-term care need: difficulty dressing or bathing and difficulty doing errands alone. Results. When we controlled for age, race/ethnicity, and education, older women who lived with female partners were statistically significantly more likely than those who lived with male partners or spouses to have difficulty dressing or bathing. Older men who lived with male partners were statistically significantly more likely than those who lived with female spouses or partners to need assistance with errands. Conclusions. Older individuals living with same-sex partners face greater risks of needing long-term care than those living with different-sex partners or spouses, but the role of relationship status differs by gender. These findings suggest more broadly that older gay men and lesbians may face greater risks of needing long-term care than their heterosexual counterparts. PMID:23763396
Lewis, Robin J.; Mason, Tyler B.; Winstead, Barbara A.; Kelley, Michelle L.
2015-01-01
Objective This study proposed and tested the first conceptual model of sexual minority specific (discrimination, internalized homophobia) and more general risk factors (perpetrator and partner alcohol use, anger, relationship satisfaction) for intimate partner violence among partnered lesbian women. Method Self-identified lesbian women (N=1048) were recruited from online market research panels. Participants completed an online survey that included measures of minority stress, anger, alcohol use and alcohol-related problems, relationship satisfaction, psychological aggression, and physical violence. Results The model demonstrated good fit and significant links from sexual minority discrimination to internalized homophobia and anger, from internalized homophobia to anger and alcohol problems, and from alcohol problems to intimate partner violence. Partner alcohol use predicted partner physical violence. Relationship dissatisfaction was associated with physical violence via psychological aggression. Physical violence was bidirectional. Conclusions Minority stress, anger, alcohol use and alcohol-related problems play an important role in perpetration of psychological aggression and physical violence in lesbian women's intimate partner relationships. The results of this study provide evidence of potentially modifiable sexual minority specific and more general risk factors for lesbian women's partner violence. PMID:28239508
[Status on sexual partners among men who have sex with men among college students in Qingdao, 2016].
Zhang, X F; Lyu, C X; Zheng, J T; Dong, L; Jiang, Z X; Fu, J H
2017-12-10
Objective: To investigate the situation of sexual partners and related factors among men who have sex with men (MSM) in college students. Methods: Snowball sampling and Convenience sampling were both used to recruit MSM from colleges in Tsingtao in 2016. Questionnaire-based interviews were conducted to collect data of socio-demographic and situation of sexual partners. Sample Size was estimated based on cross-sectional study, and theoretical 267. SPSS 17.0 software was used for statistical analysis. Results: A total of 300 MSM, average aged 20.7, were analyzed. Both first sex partner and the last same-sex sexual partner were met instantly, with proportions as 58.7% (176/300) and 62.3% (187/300) respectively. Among all the MSM, 88.3% (265/300) preferred selecting men as sex partners and 42.7% (128/300) enjoyed finding sex partners in college, while 86.0% (258/300) preferred finding their sex partners through internet. Conclusions: Internet had been the major way of looking for sex partner among MSM in college students, the male sexual partner were met instantly. We should focus on men who have sex with men and their sexual health among college students to prevent and control HIV/AIDS.
Olive, Philippa
2017-08-01
To explore the naming, or classification, of physical assaults by a partner as 'intimate partner violence' during emergency department consultations. Research continues to evidence instances when intimate partner physical violence is 'missed' or unacknowledged during emergency department consultations. Theoretically, this research was approached through complexity theory and the sociology of diagnosis. Research design was an applied, descriptive and explanatory, multiple-method approach that combined qualitative semistructured interviews with service-users (n = 8) and emergency department practitioners (n = 9), and qualitative and quantitative document analysis of emergency department health records (n = 28). This study found that multiple classifications of intimate partner violence were mobilised during emergency department consultations and that these different versions of intimate partner violence held different diagnostic categories, processes and consequences. The construction of different versions of intimate partner violence in emergency department consultations could explain variance in people's experiences and outcomes of consultations. The research found that the classificatory threshold for 'intimate partner violence' was too high. Strengthening systems of diagnosis (identification and intervention) so that all incidents of partner violence are named as 'intimate partner violence' would reduce the incidence of missed cases and afford earlier specialist intervention to reduce violence and limit its harms. This research found that identification of and response to intimate partner violence, even in contexts of severe physical violence, was contingent. By lowering the classificatory threshold so that all incidents of partner violence are named as 'intimate partner violence', practitioners could make a significant contribution to reducing missed intimate partner violence during consultations and improving health outcomes for this population. This research has relevance for practitioners in any setting where service-user report of intimate partner violence is possible. © 2016 John Wiley & Sons Ltd.
Maarschalk, Silvia; Grobler, Anneke C.; Mansoor, Leila E.; Frohlich, Janet A.; Madlala, Bernadette; Ngcobo, Nelisiwe; Abdool Karim, Salim S.; Karim, Quarraisha Abdool
2014-01-01
Young women in sub-Saharan Africa are disproportionately affected by HIV, making the development of women initiated and controlled methods of prevention, including microbicides, a priority. Adherence is pivotal to microbicide efficacy and partner related factors are known to impact adherence. An analysis of disclosure of gel use to sexual partners and adherence in CAPRISA 004 women was conducted to better understand this relationship. Partner disclosure was significantly associated with a modest 4.2 % increased adherence (71.0 vs. 66.8 %, p = 0.03). Most women rated the experience of disclosure as positive, despite 6.7 % of partners expressing a negative reaction. Participants who disclosed were more likely to reside with their regular partner (14.4 vs. 8.4 %; p = 0.01) and reported consistent condom use at baseline (32.9 vs. 20.9 %; p< 0.01). Partner disclosure needs to be better understood as a potential facilitator or barrier to microbicide adherence. PMID:24633715
Pyle, Tara M; Bridges, Ana J
2012-12-01
Background and aims Research indicates that excessive pornography use can negatively impact romantic relationships. However, it is unclear whether these negative outcomes are different than negative outcomes produced by other compulsive or addictive behaviors, such as drug use. This study compared perceptions of relationship outcomes from either a romantic partner's excessive marijuana or pornography use. Furthermore, this study experimentally manipulated four factors potentially related to perceptions of relationship satisfaction and addictive behavior. Methods A total of 186 college-aged women read 16 scenarios describing heterosexual romantic relationships in which one partner used either pornography or marijuana. Each scenario varied on four variables: relationship commitment, secrecy of partner's behavior, frequency of partner's behavior, and context of partner's behavior. Results Results suggest that partner pornography and marijuana use are perceived to impact romantic relationships similarly and are influenced by similar factors, such as greater frequency, higher secrecy, and partner's availability for interaction. Conclusions Such findings are consistent with recommendations by professionals that compulsive pornography use be considered worthy of treatment intervention.
Casás-Selves, Matias; Zhang, Andrew X; Dowling, James E; Hallén, Stefan; Kawatkar, Aarti; Pace, Nicholas J; Denz, Christopher R; Pontz, Timothy; Garahdaghi, Farzin; Cao, Qing; Sabirsh, Alan; Thakur, Kumar; O'Connell, Nichole; Hu, Jun; Cornella-Taracido, Iván; Weerapana, Eranthie; Zinda, Michael; Goodnow, Robert A; Castaldi, M Paola
2017-06-21
Wnt signaling is critical for development, cell proliferation and differentiation, and mutations in this pathway resulting in constitutive signaling have been implicated in various cancers. A pathway screen using a Wnt-dependent reporter identified a chemical series based on a 1,2,3-thiadiazole-5-carboxamide (TDZ) core with sub-micromolar potency. Herein we report a comprehensive mechanism-of-action deconvolution study toward identifying the efficacy target(s) and biological implication of this chemical series involving bottom-up quantitative chemoproteomics, cell biology, and biochemical methods. Through observing the effects of our probes on metabolism and performing confirmatory cellular and biochemical assays, we found that this chemical series inhibits ATP synthesis by uncoupling the mitochondrial potential. Affinity chemoproteomics experiments identified sarco(endo)plasmic reticulum Ca 2+ -dependent ATPase (SERCA2) as a binding partner of the TDZ series, and subsequent validation studies suggest that the TDZ series can act as ionophores through SERCA2 toward Wnt pathway inhibition. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Design Optimization of Irregular Cellular Structure for Additive Manufacturing
NASA Astrophysics Data System (ADS)
Song, Guo-Hua; Jing, Shi-Kai; Zhao, Fang-Lei; Wang, Ye-Dong; Xing, Hao; Zhou, Jing-Tao
2017-09-01
Irregularcellular structurehas great potential to be considered in light-weight design field. However, the research on optimizing irregular cellular structures has not yet been reporteddue to the difficulties in their modeling technology. Based on the variable density topology optimization theory, an efficient method for optimizing the topology of irregular cellular structures fabricated through additive manufacturing processes is proposed. The proposed method utilizes tangent circles to automatically generate the main outline of irregular cellular structure. The topological layoutof each cellstructure is optimized using the relative density informationobtained from the proposed modified SIMP method. A mapping relationship between cell structure and relative densityelement is builtto determine the diameter of each cell structure. The results show that the irregular cellular structure can be optimized with the proposed method. The results of simulation and experimental test are similar for irregular cellular structure, which indicate that the maximum deformation value obtained using the modified Solid Isotropic Microstructures with Penalization (SIMP) approach is lower 5.4×10-5 mm than that using the SIMP approach under the same under the same external load. The proposed research provides the instruction to design the other irregular cellular structure.
Mayanja, Yunia; Mukose, Aggrey David; Nakubulwa, Susan; Omosa-Manyonyi, Gloria
2016-01-01
Background The prevalence of sexually transmitted infections (STIs) among female sex workers (FSWs) in sub-Saharan Africa remains high. Providing treatment to the affected FSWs is a challenge, and more so to their stable sexual partners. There is scanty research information on acceptance of STI treatment for stable sexual partners by FSWs. We conducted a study to assess acceptance of STI treatment for stable sexual partners by FSWs, and to identify factors associated with acceptance. Methods We enrolled 241 FSWs in a cross sectional study; they were aged ≥ 18 years, had a stable sexual partner and a diagnosis of STI. Factors associated with acceptance of STI treatment for stable sexual partners were analysed in STATA (12) using Poisson regression. Mantel-Haenszel tests for interaction were performed. Results Acceptance of partner treatment was 50.6%. Majority (83.8%) of partners at the last sexual act were stable partners, and 32.4% of participants had asymptomatic STIs. Factors independently associated with acceptance were: earning ≤ $4 USD per sexual act (aPR 0.68; 95% CI: 0.49–0.94) and a clinical STI diagnosis (aPR 1.95; 95% CI: 1.30–2.92). The effect of low income on acceptance of partner treatment was seen in those with less education. Conclusion Acceptance of STI treatment for stable sexual partners was lower than that seen in other studies. Interventions to improve economic empowerment among FSWs may increase acceptance of partner treatment. PMID:27171270
Environmental bacteriophages: viruses of microbes in aquatic ecosystems
Sime-Ngando, Télesphore
2014-01-01
Since the discovery 2–3 decades ago that viruses of microbes are abundant in marine ecosystems, viral ecology has grown increasingly to reach the status of a full scientific discipline in environmental sciences. A dedicated ISVM society, the International Society for Viruses of Microorganisms, (http://www.isvm.org/) was recently launched. Increasing studies in viral ecology are sources of novel knowledge related to the biodiversity of living things, the functioning of ecosystems, and the evolution of the cellular world. This is because viruses are perhaps the most diverse, abundant, and ubiquitous biological entities in the biosphere, although local environmental conditions enrich for certain viral types through selective pressure. They exhibit various lifestyles that intimately depend on the deep-cellular mechanisms, and are ultimately replicated by members of all three domains of cellular life (Bacteria, Eukarya, Archaea), as well as by giant viruses of some eukaryotic cells. This establishes viral parasites as microbial killers but also as cell partners or metabolic manipulators in microbial ecology. The present chapter sought to review the literature on the diversity and functional roles of viruses of microbes in environmental microbiology, focusing primarily on prokaryotic viruses (i.e., phages) in aquatic ecosystems, which form the bulk of our knowledge in modern environmental viral ecology. PMID:25104950
Gilsohn, Eli; Volk, Talila
2010-01-01
The formation of complex tissues during embryonic development is often accompanied by directed cellular migration towards a target tissue. Specific mutual recognition between the migrating cell and its target tissue leads to the arrest of the cell migratory behavior and subsequent contact formation between the two interacting cell types. Recent studies implicated a novel family of surface proteins containing a trans-membrane domain and single leucine-rich repeat (LRR) domain in inter-cellular recognition and the arrest of cell migration. Here, we describe the involvement of a novel LRR surface protein, LRT, in targeting migrating muscles towards their corresponding tendon cells in the Drosophila embryo. LRT is specifically expressed by the target tendon cells and is essential for arresting the migratory behavior of the muscle cells. Additional studies in Drosophila S2 cultured cells suggest that LRT forms a protein complex with the Roundabout (Robo) receptor, essential for guiding muscles towards their tendon partners. Genetic analysis supports a model in which LRT performs its activity non-autonomously through its interaction with the Robo receptors expressed on the muscle surfaces. These results suggest a novel mechanism of intercellular recognition through interactions between LRR family members and Robo receptors.
Rabies virus matrix protein interplay with eIF3, new insights into rabies virus pathogenesis
Komarova, Anastassia V.; Real, Eléonore; Borman, Andrew M.; Brocard, Michèle; England, Patrick; Tordo, Noël; Hershey, John W.B.; Jacob, Yves
2007-01-01
Viral proteins are frequently multifunctional to accommodate the high density of information encoded in viral genomes. Matrix (M) protein of negative-stranded RNA viruses such as Rhabdoviridae is one such example. Its primary function is virus assembly/budding but it is also involved in the switch from viral transcription to replication and the concomitant down regulation of host gene expression. In this study we undertook a search for potential rabies virus (RV) M protein's cellular partners. In a yeast two-hybrid screen the eIF3h subunit was identified as an M-interacting cellular factor, and the interaction was validated by co-immunoprecipitation and surface plasmon resonance assays. Upon expression in mammalian cell cultures, RV M protein was localized in early small ribosomal subunit fractions. Further, M protein added in trans inhibited in vitro translation on mRNA encompassing classical (Kozak-like) 5′-UTRs. Interestingly, translation of hepatitis C virus IRES-containing mRNA, which recruits eIF3 via a different noncanonical mechanism, was unaffected. Together, the data suggest that, as a complement to its functions in virus assembly/budding and regulation of viral transcription, RV M protein plays a role in inhibiting translation in virus-infected cells through a protein–protein interaction with the cellular translation machinery. PMID:17287294
Reconceptualizing and operationalizing context in survey research on intimate partner violence.
Lindhorst, Taryn; Tajima, Emiko
2008-03-01
Survey research in the field of intimate partner violence is notably lacking in its attention to contextual factors. Early measures of intimate partner violence focused on simple counts of behaviors, yet attention to broader contextual factors remains limited. Contextual factors not only shape what behaviors are defined as intimate partner violence but also influence the ways women respond to victimization, the resources available to them, and the environments in which they cope with abuse. This article advances methods for reconceptualizing and operationalizing contextual factors salient to the measurement of intimate partner violence. The analytic focus of the discussion is on five dimensions of the social context: the situational context, the social construction of meaning by the survivor, cultural and historical contexts, and the context of systemic oppression. The authors consider how each dimension matters in the measurement of intimate partner violence and offer recommendations for systematically assessing these contextual factors in future research.
Cook, Won Kim; Weir, Rosy Chang; Ro, Margeurite; Ko, Kathy Lim; Panapasa, Sela; Bautista, Roxanna; Asato, Lloyd; Chung, Corina; Cabllero, Jeffery; Islam, Nadia
2012-01-01
Background Functionally, many CBPR projects operate through a model of academic partners providing research expertise and community partners playing a supporting role. Objectives To demonstrate how national umbrella organizations deeply rooted in communities, cognizant of community needs, and drawing on the insights and assets of community partners, can lead efforts to address health disparities affecting their constituents through research. Methods Case studies of two Asian American, Native Hawaiian, and Pacific Islander national organizations Results Strategically engaging a diverse range of partners and securing flexible funding mechanisms that support research were important facilitators. Main challenges included limited interest of local community organizations whose primary missions as service or health care providers may deprioritize research. Conclusions Efforts to make research relevant to the work of community partners and to instill the value of research in community partners, as well as flexible funding mechanisms, may help to promote community-driven research. PMID:22643786
Imai, Hirohisa; Nakao, Hiroyuki; Shinohara, Hisae; Watarai, Mutsuko; Matsumoto, Noriko; Yamagishi, Takuya; Saito, Masuko; Kitamura, Tadaichi
2015-01-01
Background and Methods We conducted a community-based study to evaluate genotype-specific prevalence of high-risk HPV (HR-HPV) and potential predictors of its presence in young, asymptomatic, female college students. Self-administered surveys and vaginal swabs for self collection were distributed to students of participating schools. A sufficient cellular component in cervical samples was verified by examining for the presence of human β-globin DNA by PCR. A total of 1,118 valid cervical samples were subjected to screening for HR-HPV infection with the Digene Hybrid Capture 2 assay, followed by identification of HPV genotypes with GENOSEARCH HPV31 kit. Logistic regression was used to adjust for confounding factors associated with HR-HPV positivity and the adjusted odds ratio (AOR) was calculated. Results The median age of recruited students was 20 years. Of the 1,118 women who provided valid cervical samples for testing, 770 had sexual intercourse in the past, of which 125 (16.2%) were positive for HR-HPV. Logistic regression analysis revealed that HR-HPV infection was associated with smoking history (AOR 2.13; 95% confidence interval [CI] 1.98 to 5.05; p < 0.01), total number of partners (AOR 4.72; 95% CI 1.97 to 11.32 if > 5 partners; p < 0.001), number of partners in the past 6 months (AOR 3.12; 95% CI 1.42 to 6.87; p < 0.01), improper use of condoms (AOR 2.21; 95% CI 1.25 to 3.90; p < 0.01), and chlamydia infection (AOR 2.61; 95% CI 1.28 to 5.34; p < 0.01). The most common HR-HPV genotype was type 52 (6.4%), followed by 16 (3.1%), 56 (3.0%), and 58 (2.6%). Conclusion Compared with previous reports in East Asian coutries, the prevalence of HR-HPV infection among young, asymptomatic, female students before the nationwide use of vaccination in Japan was in the intermediate range. The most common HR-HPV genotypes were HPV 52, 16, 56, and 58. PMID:26176861
Kim, Tyson N.; Goodwill, Patrick W.; Chen, Yeni; Conolly, Steven M.; Schaffer, Chris B.; Liepmann, Dorian; Wang, Rong A.
2012-01-01
Background The ability to measure blood velocities is critical for studying vascular development, physiology, and pathology. A key challenge is to quantify a wide range of blood velocities in vessels deep within living specimens with concurrent diffraction-limited resolution imaging of vascular cells. Two-photon laser scanning microscopy (TPLSM) has shown tremendous promise in analyzing blood velocities hundreds of micrometers deep in animals with cellular resolution. However, current analysis of TPLSM-based data is limited to the lower range of blood velocities and is not adequate to study faster velocities in many normal or disease conditions. Methodology/Principal Findings We developed line-scanning particle image velocimetry (LS-PIV), which used TPLSM data to quantify peak blood velocities up to 84 mm/s in live mice harboring brain arteriovenous malformation, a disease characterized by high flow. With this method, we were able to accurately detect the elevated blood velocities and exaggerated pulsatility along the abnormal vascular network in these animals. LS-PIV robustly analyzed noisy data from vessels as deep as 850 µm below the brain surface. In addition to analyzing in vivo data, we validated the accuracy of LS-PIV up to 800 mm/s using simulations with known velocity and noise parameters. Conclusions/Significance To our knowledge, these blood velocity measurements are the fastest recorded with TPLSM. Partnered with transgenic mice carrying cell-specific fluorescent reporters, LS-PIV will also enable the direct in vivo correlation of cellular, biochemical, and hemodynamic parameters in high flow vascular development and diseases such as atherogenesis, arteriogenesis, and vascular anomalies. PMID:22761686
Bouraï, Mehdi; Lucas-Hourani, Marianne; Gad, Hans Henrik; Drosten, Christian; Jacob, Yves; Tafforeau, Lionel; Cassonnet, Patricia; Jones, Louis M.; Judith, Delphine; Couderc, Thérèse; Lecuit, Marc; André, Patrice; Kümmerer, Beate Mareike; Lotteau, Vincent; Desprès, Philippe; Vidalain, Pierre-Olivier
2012-01-01
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has been responsible for an epidemic outbreak of unprecedented magnitude in recent years. Since then, significant efforts have been made to better understand the biology of this virus, but we still have poor knowledge of CHIKV interactions with host cell components at the molecular level. Here we describe the extensive use of high-throughput yeast two-hybrid (HT-Y2H) assays to characterize interactions between CHIKV and human proteins. A total of 22 high-confidence interactions, which essentially involved the viral nonstructural protein nsP2, were identified and further validated in protein complementation assay (PCA). These results were integrated to a larger network obtained by extensive mining of the literature for reports on alphavirus-host interactions. To investigate the role of cellular proteins interacting with nsP2, gene silencing experiments were performed in cells infected by a recombinant CHIKV expressing Renilla luciferase as a reporter. Collected data showed that heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and ubiquilin 4 (UBQLN4) participate in CHIKV replication in vitro. In addition, we showed that CHIKV nsP2 induces a cellular shutoff, as previously reported for other Old World alphaviruses, and determined that among binding partners identified by yeast two-hybrid methods, the tetratricopeptide repeat protein 7B (TTC7B) plays a significant role in this activity. Altogether, this report provides the first interaction map between CHIKV and human proteins and describes new host cell proteins involved in the replication cycle of this virus. PMID:22258240
Evolution of crystallins for a role in the vertebrate eye lens.
Slingsby, Christine; Wistow, Graeme J; Clark, Alice R
2013-04-01
The camera eye lens of vertebrates is a classic example of the re-engineering of existing protein components to fashion a new device. The bulk of the lens is formed from proteins belonging to two superfamilies, the α-crystallins and the βγ-crystallins. Tracing their ancestry may throw light on the origin of the optics of the lens. The α-crystallins belong to the ubiquitous small heat shock proteins family that plays a protective role in cellular homeostasis. They form enormous polydisperse oligomers that challenge modern biophysical methods to uncover the molecular basis of their assembly structure and chaperone-like protein binding function. It is argued that a molecular phenotype of a dynamic assembly suits a chaperone function as well as a structural role in the eye lens where the constraint of preventing protein condensation is paramount. The main cellular partners of α-crystallins, the β- and γ-crystallins, have largely been lost from the animal kingdom but the superfamily is hugely expanded in the vertebrate eye lens. Their structures show how a simple Greek key motif can evolve rapidly to form a complex array of monomers and oligomers. Apart from remaining transparent, a major role of the partnership of α-crystallins with β- and γ-crystallins in the lens is to form a refractive index gradient. Here, we show some of the structural and genetic features of these two protein superfamilies that enable the rapid creation of different assembly states, to match the rapidly changing optical needs among the various vertebrates. Copyright © 2013 The Protein Society.
Evolution of crystallins for a role in the vertebrate eye lens
Slingsby, Christine; Wistow, Graeme J; Clark, Alice R
2013-01-01
The camera eye lens of vertebrates is a classic example of the re-engineering of existing protein components to fashion a new device. The bulk of the lens is formed from proteins belonging to two superfamilies, the α-crystallins and the βγ-crystallins. Tracing their ancestry may throw light on the origin of the optics of the lens. The α-crystallins belong to the ubiquitous small heat shock proteins family that plays a protective role in cellular homeostasis. They form enormous polydisperse oligomers that challenge modern biophysical methods to uncover the molecular basis of their assembly structure and chaperone-like protein binding function. It is argued that a molecular phenotype of a dynamic assembly suits a chaperone function as well as a structural role in the eye lens where the constraint of preventing protein condensation is paramount. The main cellular partners of α-crystallins, the β- and γ-crystallins, have largely been lost from the animal kingdom but the superfamily is hugely expanded in the vertebrate eye lens. Their structures show how a simple Greek key motif can evolve rapidly to form a complex array of monomers and oligomers. Apart from remaining transparent, a major role of the partnership of α-crystallins with β- and γ-crystallins in the lens is to form a refractive index gradient. Here, we show some of the structural and genetic features of these two protein superfamilies that enable the rapid creation of different assembly states, to match the rapidly changing optical needs among the various vertebrates. PMID:23389822
Fredman, Steffany J.; Pukay-Martin, Nicole D.; Macdonald, Alexandra; Wagner, Anne C.; Vorstenbosch, Valerie; Monson, Candice M.
2015-01-01
Objective Partner accommodation of posttraumatic stress disorder (PTSD) symptoms (i.e., altering one’s own behaviors to minimize patient distress and/or relationship conflict due to patients’ PTSD symptoms) has been shown to be positively associated with patient and partner psychopathology and negatively associated with patient and partner relationship satisfaction cross-sectionally. However, the prognostic value of partner accommodation in treatment outcomes is unknown. The goals of the present study were to determine if partner accommodation decreases as a function of couple therapy for PTSD and if pretreatment partner accommodation moderates the efficacy of couple therapy for PTSD. Method Thirty-nine patients with PTSD and their intimate partners (n = 39) were enrolled in a randomized controlled trial of cognitive-behavioral conjoint therapy (CBCT) for PTSD (Monson & Fredman, 2012) and received CBCT for PTSD immediately or after three months of waiting. Blinded assessors determined clinician-rated PTSD symptoms and patient-rated PTSD and depressive symptoms and relationship satisfaction at baseline, mid-treatment/4 weeks of waiting, and posttreatment/12 weeks of waiting. Results Contrary to expectation, partner accommodation levels did not change over time for either treatment condition. However, baseline partner accommodation significantly moderated treatment outcomes. Higher levels of partner accommodation were associated with greater improvements in PTSD, depressive symptoms, and relationship satisfaction among patients receiving CBCT for PTSD compared with waiting list. At lower levels of partner accommodation, patients in both groups improved or remained at low levels of these outcomes. Conclusions Individuals with PTSD who have more accommodating partners may be particularly well-suited for couple therapy for PTSD. PMID:26501498
Tassiopoulos, Katherine; Kapiga, Saidi; Sam, Noel; Ao, Trong T H; Hughes, Michael; Seage, George R
2009-01-01
Background Factors related to specific sexual encounters can influence condom use during these encounters. These situation-specific factors have not been adequately studied in resource-poor countries where HIV infection has in some areas reached epidemic levels. This study was undertaken to identify situation-specific factors associated with condom use among 465 female bar and hotel workers in Moshi, Tanzania. Methods We conducted a case-crossover study in which women provided information about their most recent unprotected and protected sexual encounters. Conditional logistic regression was used to estimate paired odds ratios and 95% confidence intervals for the association between situation-specific factors and condom use. Results A subject-based or mutual decision about condom use (compared with partner based), casual partner type, a first-time sexual encounter and receiving gifts in exchange for sex were independently associated with increased odds of condom use, while sex at home and sex with a partner more than 10 years older was associated with reduced odds of use. There was also effect modification between partner type and decision-making: subject-based or mutual decisions were more protective with casual than regular partners; also, when the partner made the decisions about condom use, the type of partner had no effect. Conclusions Decision-making about condom use is a potentially modifiable predictor of unprotected sex, but its effect varies by partner type. Behavioural interventions are needed that encourage discussion about condom use and increase women's self-efficacy, but other types of interventions as well as female-controlled HIV prevention methods are needed for women in regular partnerships. PMID:19147705
Ikebe, Jinzen; Umezawa, Koji; Higo, Junichi
2016-03-01
Molecular dynamics (MD) simulations using all-atom and explicit solvent models provide valuable information on the detailed behavior of protein-partner substrate binding at the atomic level. As the power of computational resources increase, MD simulations are being used more widely and easily. However, it is still difficult to investigate the thermodynamic properties of protein-partner substrate binding and protein folding with conventional MD simulations. Enhanced sampling methods have been developed to sample conformations that reflect equilibrium conditions in a more efficient manner than conventional MD simulations, thereby allowing the construction of accurate free-energy landscapes. In this review, we discuss these enhanced sampling methods using a series of case-by-case examples. In particular, we review enhanced sampling methods conforming to trivial trajectory parallelization, virtual-system coupled multicanonical MD, and adaptive lambda square dynamics. These methods have been recently developed based on the existing method of multicanonical MD simulation. Their applications are reviewed with an emphasis on describing their practical implementation. In our concluding remarks we explore extensions of the enhanced sampling methods that may allow for even more efficient sampling.
Tanton, Clare; Johnson, Anne M; Macdowall, Wendy; Datta, Jessica; Clifton, Soazig; Field, Nigel; Mitchell, Kirstin R; Wellings, Kaye; Sonnenberg, Pam; Mercer, Catherine H
2016-01-01
Objectives Travelling away from home presents opportunities for new sexual partnerships, which may be associated with sexually transmitted infection (STI) risk. We examined the prevalence of, and factors associated with, reporting new sexual partner(s) while overseas, and whether this differed by partners’ region of residence. Methods We analysed data from 12 530 men and women aged 16–74 years reporting ≥1 sexual partner(s) in the past 5 years in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability survey undertaken 2010–2012. Results 9.2% (95% CI 8.3% to 10.1%) of men and 5.3% (4.8% to 5.8%) of women reported new sexual partner(s) while overseas in the past 5 years. This was strongly associated with higher partner numbers and other sexual and health risk behaviours. Among those with new partners while overseas, 72% of men and 58% of women reported partner(s) who were not UK residents. Compared with those having only UK partners while abroad, these people were more likely to identify as ‘White Other’ or ‘Non-White’ (vs White British ethnicity), report higher partner numbers, new partners from outside the UK while in the UK and paying for sex (men only) all in the past 5 years. There was no difference in reporting STI diagnosis/es during this time period. Conclusions Reporting new partners while overseas was associated with a range of sexual risk behaviours. Advice on sexual health should be included as part of holistic health advice for all travellers, regardless of age, destination or reason for travel. PMID:27272533
Estcourt, Claudia; Sutcliffe, Lorna; Cassell, Jackie; Mercer, Catherine H; Copas, Andrew; James, Laura; Low, Nicola; Horner, Patrick; Clarke, Michael; Symonds, Merle; Roberts, Tracy; Tsourapas, Angelos; Johnson, Anne M
2012-02-01
To develop two new models of expedited partner therapy for the UK, and evaluate them for feasibility, acceptability and preliminary outcome estimates to inform the design of a randomised controlled trial (RCT). Two models of expedited partner therapy (APTHotline and APTPharmacy), known as 'Accelerated Partner Therapy' (APT) were developed. A non-randomised comparative study was conducted of the two APT models and routine partner notification (PN), in which the index patient chose the PN option for his/her partner(s) in two contrasting clinics. The proportion of contactable partners treated when routine PN was chosen was 42/117 (36%) and was significantly higher if either APT option was chosen: APTHotline 80/135 (59%), p=0.003; APTPharmacy 29/44 (66%) p=0.001. However, partner treatment was often achieved through other routes. Although 40-60% of partners in APT groups returned urine samples for sexually transmitted infection (STI) testing, almost none accessed HIV and syphilis testing. APT options appear to facilitate faster treatment of sex partners than routine PN. Preferences and recruitment rates varied between sites, related to staff satisfaction with existing routine PN; approach to consent; and possibly, characteristics of local populations. Both methods of APT were feasible and acceptable to many patients and led to higher rates of partner treatment than routine PN. Preferences and recruitment rates varied greatly between settings, suggesting that organisational and cultural factors may have an important impact on the feasibility of an RCT and on outcomes. Mindful of these factors, it is proposed that APT should now be evaluated in a cluster RCT.
Novel functions of CCM1 delimit the relationship of PTB/PH domains.
Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed
2017-10-01
Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and relationship of PTB, PH and FERM domains has been proposed, which extends the importance of the NPXY-PTB/PH interaction on the CSC signaling and/or other cell receptors with great potential pointing to new therapeutic strategies. The study provides new insight into the structural characteristics of PTB/PH domains, essential structural elements of PTB/PH domain required for NPXY motif-binding, and function and relationship among PTB, PH and FERM domains. Copyright © 2017 Elsevier B.V. All rights reserved.
Bloyet, Louis-Marie; Welsch, Jérémy; Enchery, François; Mathieu, Cyrille; de Breyne, Sylvain
2016-01-01
ABSTRACT Nonsegmented negative-stranded RNA viruses, or members of the order Mononegavirales, share a conserved gene order and the use of elaborate transcription and replication machinery made up of at least four molecular partners. These partners have coevolved with the acquisition of the permanent encapsidation of the entire genome by the nucleoprotein (N) and the use of this N-RNA complex as a template for the viral polymerase composed of the phosphoprotein (P) and the large enzymatic protein (L). Not only is P required for polymerase function, but it also stabilizes the L protein through an unknown underlying molecular mechanism. By using NVP-AUY922 and/or 17-dimethylaminoethylamino-17-demethoxygeldanamycin as specific inhibitors of cellular heat shock protein 90 (HSP90), we found that efficient chaperoning of L by HSP90 requires P in the measles, Nipah, and vesicular stomatitis viruses. While the production of P remains unchanged in the presence of HSP90 inhibitors, the production of soluble and functional L requires both P and HSP90 activity. Measles virus P can bind the N terminus of L in the absence of HSP90 activity. Both HSP90 and P are required for the folding of L, as evidenced by a luciferase reporter insert fused within measles virus L. HSP90 acts as a true chaperon; its activity is transient and dispensable for the activity of measles and Nipah virus polymerases of virion origin. That the cellular chaperoning of a viral polymerase into a soluble functional enzyme requires the assistance of another viral protein constitutes a new paradigm that seems to be conserved within the Mononegavirales order. IMPORTANCE Viruses are obligate intracellular parasites that require a cellular environment for their replication. Some viruses particularly depend on the cellular chaperoning apparatus. We report here that for measles virus, successful chaperoning of the viral L polymerase mediated by heat shock protein 90 (HSP90) requires the presence of the viral phosphoprotein (P). Indeed, while P protein binds to the N terminus of L independently of HSP90 activity, both HSP90 and P are required to produce stable, soluble, folded, and functional L proteins. Once formed, the mature P+L complex no longer requires HSP90 to exert its polymerase functions. Such a new paradigm for the maturation of a viral polymerase appears to be conserved in several members of the Mononegavirales order, including the Nipah and vesicular stomatitis viruses. PMID:27170753
Bloyet, Louis-Marie; Welsch, Jérémy; Enchery, François; Mathieu, Cyrille; de Breyne, Sylvain; Horvat, Branka; Grigorov, Boyan; Gerlier, Denis
2016-08-01
Nonsegmented negative-stranded RNA viruses, or members of the order Mononegavirales, share a conserved gene order and the use of elaborate transcription and replication machinery made up of at least four molecular partners. These partners have coevolved with the acquisition of the permanent encapsidation of the entire genome by the nucleoprotein (N) and the use of this N-RNA complex as a template for the viral polymerase composed of the phosphoprotein (P) and the large enzymatic protein (L). Not only is P required for polymerase function, but it also stabilizes the L protein through an unknown underlying molecular mechanism. By using NVP-AUY922 and/or 17-dimethylaminoethylamino-17-demethoxygeldanamycin as specific inhibitors of cellular heat shock protein 90 (HSP90), we found that efficient chaperoning of L by HSP90 requires P in the measles, Nipah, and vesicular stomatitis viruses. While the production of P remains unchanged in the presence of HSP90 inhibitors, the production of soluble and functional L requires both P and HSP90 activity. Measles virus P can bind the N terminus of L in the absence of HSP90 activity. Both HSP90 and P are required for the folding of L, as evidenced by a luciferase reporter insert fused within measles virus L. HSP90 acts as a true chaperon; its activity is transient and dispensable for the activity of measles and Nipah virus polymerases of virion origin. That the cellular chaperoning of a viral polymerase into a soluble functional enzyme requires the assistance of another viral protein constitutes a new paradigm that seems to be conserved within the Mononegavirales order. Viruses are obligate intracellular parasites that require a cellular environment for their replication. Some viruses particularly depend on the cellular chaperoning apparatus. We report here that for measles virus, successful chaperoning of the viral L polymerase mediated by heat shock protein 90 (HSP90) requires the presence of the viral phosphoprotein (P). Indeed, while P protein binds to the N terminus of L independently of HSP90 activity, both HSP90 and P are required to produce stable, soluble, folded, and functional L proteins. Once formed, the mature P+L complex no longer requires HSP90 to exert its polymerase functions. Such a new paradigm for the maturation of a viral polymerase appears to be conserved in several members of the Mononegavirales order, including the Nipah and vesicular stomatitis viruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Insulation of a synthetic hydrogen metabolism circuit in bacteria
2010-01-01
Background The engineering of metabolism holds tremendous promise for the production of desirable metabolites, particularly alternative fuels and other highly reduced molecules. Engineering approaches must redirect the transfer of chemical reducing equivalents, preventing these electrons from being lost to general cellular metabolism. This is especially the case for high energy electrons stored in iron-sulfur clusters within proteins, which are readily transferred when two such clusters are brought in close proximity. Iron sulfur proteins therefore require mechanisms to ensure interaction between proper partners, analogous to many signal transduction proteins. While there has been progress in the isolation of engineered metabolic pathways in recent years, the design of insulated electron metabolism circuits in vivo has not been pursued. Results Here we show that a synthetic hydrogen-producing electron transfer circuit in Escherichia coli can be insulated from existing cellular metabolism via multiple approaches, in many cases improving the function of the pathway. Our circuit is composed of heterologously expressed [Fe-Fe]-hydrogenase, ferredoxin, and pyruvate-ferredoxin oxidoreductase (PFOR), allowing the production of hydrogen gas to be coupled to the breakdown of glucose. We show that this synthetic pathway can be insulated through the deletion of competing reactions, rational engineering of protein interaction surfaces, direct protein fusion of interacting partners, and co-localization of pathway components on heterologous protein scaffolds. Conclusions Through the construction and characterization of a synthetic metabolic circuit in vivo, we demonstrate a novel system that allows for predictable engineering of an insulated electron transfer pathway. The development of this system demonstrates working principles for the optimization of engineered pathways for alternative energy production, as well as for understanding how electron transfer between proteins is controlled. PMID:20184755
Starcevic, Antonio; Dunlap, Walter C; Cullum, John; Shick, J Malcolm; Hranueli, Daslav; Long, Paul F
2010-11-12
The success of tropical reef-building corals depends on the metabolic co-operation between the animal host and the photosynthetic performance of endosymbiotic algae residing within its cells. To examine the molecular response of the coral Acropora microphthalma to high levels of solar irradiance, a cDNA library was constructed by PCR-based suppression subtractive hybridisation (PCR-SSH) from mRNA obtained by transplantation of a colony from a depth of 12.7 m to near-surface solar irradiance, during which the coral became noticeably paler from loss of endosymbionts in sun-exposed tissues. A novel approach to sequence annotation of the cDNA library gave genetic evidence for a hypothetical biosynthetic pathway branching from the shikimic acid pathway that leads to the formation of 4-deoxygadusol. This metabolite is a potent antioxidant and expected precursor of the UV-protective mycosporine-like amino acids (MAAs), which serve as sunscreens in coral phototrophic symbiosis. Empirical PCR based evidence further upholds the contention that the biosynthesis of these MAA sunscreens is a 'shared metabolic adaptation' between the symbiotic partners. Additionally, gene expression induced by enhanced solar irradiance reveals a cellular mechanism of light-induced coral bleaching that invokes a Ca(2+)-binding synaptotagmin-like regulator of SNARE protein assembly of phagosomal exocytosis, whereby algal partners are lost from the symbiosis. Bioinformatics analyses of DNA sequences obtained by differential gene expression of a coral exposed to high solar irradiance has revealed the identification of putative genes encoding key steps of the MAA biosynthetic pathway. Revealed also by this treatment are genes that implicate exocytosis as a cellular process contributing to a breakdown in the metabolically essential partnership between the coral host and endosymbiotic algae, which manifests as coral bleaching.
Liu, Suxuan; Xiong, Xinyu; Zhao, Xianxian; Yang, Xiaofeng; Wang, Hong
2015-05-09
Eukaryotic cell membrane dynamics change in curvature during physiological and pathological processes. In the past ten years, a novel protein family, Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain proteins, has been identified to be the most important coordinators in membrane curvature regulation. The F-BAR domain family is a member of the Bin/Amphiphysin/Rvs (BAR) domain superfamily that is associated with dynamic changes in cell membrane. However, the molecular basis in membrane structure regulation and the biological functions of F-BAR protein are unclear. The pathophysiological role of F-BAR protein is unknown. This review summarizes the current understanding of structure and function in the BAR domain superfamily, classifies F-BAR family proteins into nine subfamilies based on domain structure, and characterizes F-BAR protein structure, domain interaction, and functional relevance. In general, F-BAR protein binds to cell membrane via F-BAR domain association with membrane phospholipids and initiates membrane curvature and scission via Src homology-3 (SH3) domain interaction with its partner proteins. This process causes membrane dynamic changes and leads to seven important cellular biological functions, which include endocytosis, phagocytosis, filopodium, lamellipodium, cytokinesis, adhesion, and podosome formation, via distinct signaling pathways determined by specific domain-binding partners. These cellular functions play important roles in many physiological and pathophysiological processes. We further summarize F-BAR protein expression and mutation changes observed in various diseases and developmental disorders. Considering the structure feature and functional implication of F-BAR proteins, we anticipate that F-BAR proteins modulate physiological and pathophysiological processes via transferring extracellular materials, regulating cell trafficking and mobility, presenting antigens, mediating extracellular matrix degradation, and transmitting signaling for cell proliferation.
The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms.
Fulcher, Luke J; Bozatzi, Polyxeni; Tachie-Menson, Theresa; Wu, Kevin Z L; Cummins, Timothy D; Bufton, Joshua C; Pinkas, Daniel M; Dunbar, Karen; Shrestha, Sabin; Wood, Nicola T; Weidlich, Simone; Macartney, Thomas J; Varghese, Joby; Gourlay, Robert; Campbell, David G; Dingwell, Kevin S; Smith, James C; Bullock, Alex N; Sapkota, Gopal P
2018-05-22
Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Mercer, C H; Jones, K G; Johnson, A M; Lewis, R; Mitchell, K R; Clifton, S; Tanton, C; Sonnenberg, P; Wellings, K; Cassell, J A; Estcourt, C S
2017-01-01
Background Partnership type is a determinant of STI risk; yet, it is poorly and inconsistently recorded in clinical practice and research. We identify a novel, empirical-based categorisation of partnership type, and examine whether reporting STI diagnoses varies by the resulting typologies. Methods Analyses of probability survey data collected from 15 162 people aged 16–74 who participated in Britain's third National Survey of Sexual Attitudes and Lifestyles were undertaken during 2010–2012. Computer-assisted self-interviews asked about participants' ≤3 most recent partners (N=14 322 partners/past year). Analysis of variance and regression tested for differences in partnership duration and perceived likelihood of sex again across 21 ‘partnership progression types’ (PPTs) derived from relationship status at first and most recent sex. Multivariable regression examined the association between reporting STI diagnoses and partnership type(s) net of age and reported partner numbers (all past year). Results The 21 PPTs were grouped into four summary types: ‘cohabiting’, ‘now steady’, ‘casual’ and ‘ex-steady’ according to the average duration and likelihood of sex again. 11 combinations of these summary types accounted for 94.5% of all men; 13 combinations accounted for 96.9% of all women. Reporting STI diagnoses varied by partnership-type combination, including after adjusting for age and partner numbers, for example, adjusted OR: 6.03 (95% CI 2.01 to 18.1) for men with two ‘casual’ and one ‘now steady’ partners versus men with one ‘cohabiting’ partner. Conclusions This typology provides an objective method for measuring partnership type and demonstrates its importance in understanding STI risk, net of partner numbers. Epidemiological research and clinical practice should use these methods and results to maximise individual and public health benefit. PMID:27535765
Baresic, Mario; Salatino, Silvia; Kupr, Barbara
2014-01-01
Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here, we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1α and gene expression upon PGC-1α overexpression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto-underestimated number of transcription factor partners involved in mediating PGC-1α action. In particular, principal component analysis of TFBSs at PGC-1α binding regions predicts that, besides the well-known role of the estrogen-related receptor α (ERRα), the activator protein 1 complex (AP-1) plays a major role in regulating the PGC-1α-controlled gene program of the hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1α. PMID:24912679
Intramolecular interactions regulate SAP97 binding to GKAP
Wu, Hongju; Reissner, Carsten; Kuhlendahl, Sven; Coblentz, Blake; Reuver, Susanne; Kindler, Stefan; Gundelfinger, Eckart D.; Garner, Craig C.
2000-01-01
Membrane-associated guanylate kinase homologs (MAGUKs) are multidomain proteins found to be central organizers of cellular junctions. In this study, we examined the molecular mechanisms that regulate the interaction of the MAGUK SAP97 with its GUK domain binding partner GKAP (GUK-associated protein). The GKAP–GUK interaction is regulated by a series of intramolecular interactions. Specifically, the association of the Src homology 3 (SH3) domain and sequences situated between the SH3 and GUK domains with the GUK domain was found to interfere with GKAP binding. In contrast, N-terminal sequences that precede the first PDZ domain in SAP97, facilitated GKAP binding via its association with the SH3 domain. Utilizing crystal structure data available for PDZ, SH3 and GUK domains, molecular models of SAP97 were generated. These models revealed that SAP97 can exist in a compact U-shaped conformation in which the N-terminal domain folds back and interacts with the SH3 and GUK domains. These models support the biochemical data and provide new insights into how intramolecular interactions may regulate the association of SAP97 with its binding partners. PMID:11060025
J domain independent functions of J proteins.
Ajit Tamadaddi, Chetana; Sahi, Chandan
2016-07-01
Heat shock proteins of 40 kDa (Hsp40s), also called J proteins, are obligate partners of Hsp70s. Via their highly conserved and functionally critical J domain, J proteins interact and modulate the activity of their Hsp70 partners. Mutations in the critical residues in the J domain often result in the null phenotype for the J protein in question. However, as more J proteins have been characterized, it is becoming increasingly clear that a significant number of J proteins do not "completely" rely on their J domains to carry out their cellular functions, as previously thought. In some cases, regions outside the highly conserved J domain have become more important making the J domain dispensable for some, if not for all functions of a J protein. This has profound effects on the evolution of such J proteins. Here we present selected examples of J proteins that perform J domain independent functions and discuss this in the context of evolution of J proteins with dispensable J domains and J-like proteins in eukaryotes.
mpMoRFsDB: a database of molecular recognition features in membrane proteins.
Gypas, Foivos; Tsaousis, Georgios N; Hamodrakas, Stavros J
2013-10-01
Molecular recognition features (MoRFs) are small, intrinsically disordered regions in proteins that undergo a disorder-to-order transition on binding to their partners. MoRFs are involved in protein-protein interactions and may function as the initial step in molecular recognition. The aim of this work was to collect, organize and store all membrane proteins that contain MoRFs. Membrane proteins constitute ∼30% of fully sequenced proteomes and are responsible for a wide variety of cellular functions. MoRFs were classified according to their secondary structure, after interacting with their partners. We identified MoRFs in transmembrane and peripheral membrane proteins. The position of transmembrane protein MoRFs was determined in relation to a protein's topology. All information was stored in a publicly available mySQL database with a user-friendly web interface. A Jmol applet is integrated for visualization of the structures. mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins. http://bioinformatics.biol.uoa.gr/mpMoRFsDB
B′-protein phosphatase 2A is a functional binding partner of delta-retroviral integrase
Maertens, Goedele N.
2016-01-01
To establish infection, a retrovirus must insert a DNA copy of its RNA genome into host chromatin. This reaction is catalysed by the virally encoded enzyme integrase (IN) and is facilitated by viral genus-specific host factors. Herein, cellular serine/threonine protein phosphatase 2A (PP2A) is identified as a functional IN binding partner exclusive to δ-retroviruses, including human T cell lymphotropic virus type 1 and 2 (HTLV-1 and HTLV-2) and bovine leukaemia virus (BLV). PP2A is a heterotrimer composed of a scaffold, catalytic and one of any of four families of regulatory subunits, and the interaction is specific to the B′ family of the regulatory subunits. B′-PP2A and HTLV-1 IN display nuclear co-localization, and the B′ subunit stimulates concerted strand transfer activity of δ-retroviral INs in vitro. The protein–protein interaction interface maps to a patch of highly conserved residues on B′, which when mutated render B′ incapable of binding to and stimulating HTLV-1 and -2 IN strand transfer activity. PMID:26657642
GENDER DIFFERENCES IN INTIMATE PARTNER HOMICIDES AMONG ETHNIC SUBGROUPS OF ASIANS
SABRI, BUSHRA; CAMPBELL, JACQUELYN C.; DABBY, FIROZA CHIC
2013-01-01
This study explored differences in intimate partner homicides (IPHs) among Asian Americans. Data from newspapers and femicide reports by different state coalitions on 125 intimate partner killings occurring between 2000 and 2005 was analyzed. Men were the perpetrators in nearly nine out of ten cases of Asian IPHs. Gender differences were found in ages of victims and perpetrators, types of relationship between partners, and methods of killing. Most homicides occurred among South-east Asians, and East Asians had the highest within group proportion of suicides. The findings call for culturally competent risk assessment and intervention strategies to prevent IPHs among at-risk Asian Americans. PMID:26391620
Involving the male partner for interpreting the basal body temperature graph.
Dunlop, A L; Allen, A S; Frank, E
2001-07-01
To determine if the male cohabiting partner of a woman may serve as a control for exogenous influences on basal body temperature (BBT). Twelve couples from the Atlanta area were enrolled for a total of 41 couple-cycles. Couples recorded their oral temperatures daily and used urinary test kits for luteinizing hormone to estimate the day of ovulation. The covariability between the pre-ovulatory temperature of the women and their partners was assessed. The gaps in the couples' temperatures (female temperature minus male temperature) were compared in the pre- and postovulatory phases. Considerable covariability was found between temperatures of partners in the pre-ovulatory phase (covariance parameter = 0.49; P <.001). The pre- and postovulatory temperature gaps for all couples were significantly different in size (P <.001). For all couple-cycles, the size of the mean postovulatory temperature gap was at least 0.3-degree Fahrenheit greater than the mean pre-ovulatory temperature gap. Recording the BBT of women's partners may improve interpretation and accuracy of the BBT method. An increase in the size of a couple's temperature gap accompanies the transition from the pre- to the postovulatory phase. By this method, a given couple could determine their unique temperature gap indicating this transition.
ACOG Committee opinion no. 554: reproductive and sexual coercion.
2013-02-01
Reproductive and sexual coercion involves behavior intended to maintain power and control in a relationship related to reproductive health by someone who is, was, or wishes to be involved in an intimate or dating relationship with an adult or adolescent. This behavior includes explicit attempts to impregnate a partner against her will, control outcomes of a pregnancy, coerce a partner to have unprotected sex, and interfere with contraceptive methods. Obstetrician-gynecologists are in a unique position to address reproductive and sexual coercion and provide screening and clinical interventions to improve health outcomes. Because of the known link between reproductive health and violence, health care providers should screen women and adolescent girls for intimate partner violence and reproductive and sexual coercion at periodic intervals such as annual examinations, new patient visits, and during obstetric care (at the first prenatal visit, at least once per trimester, and at the postpartum checkup). Interventions include education on the effect of reproductive and sexual coercion and intimate partner violence on patients' health and choices, counseling on harm-reduction strategies, and prevention of unintended pregnancies by offering long-acting methods of contraception that are less detectable to partners.
Chabalier, Julie; Capponi, Cécile; Quentin, Yves; Fichant, Gwennaele
2005-04-01
Complex biological functions emerge from interactions between proteins in stable supra-molecular assemblies and/or through transitory contacts. Most of the time protein partners of the assemblies are composed of one or several domains which exhibit different biochemical functions. Thus the study of cellular process requires the identification of different functional units and their integration in an interaction network; such complexes are referred to as integrated systems. In order to exploit with optimum efficiency the increased release of data, automated bioinformatics strategies are needed to identify, reconstruct and model such systems. For that purpose, we have developed a knowledge warehouse dedicated to the representation and acquisition of bacterial integrated systems involved in the exchange of the bacterial cell with its environment. ISYMOD is a knowledge warehouse that consistently integrates in the same environment the data and the methods used for their acquisition. This is achieved through the construction of (1) a domain knowledge base (DKB) devoted to the storage of the knowledge about the systems, their functional specificities, their partners and how they are related and (2) a methodological knowledge base (MKB) which depicts the task layout used to identify and reconstruct functional integrated systems. Instantiation of the DKB is obtained by solving the tasks of the MKB, whereas some tasks need instances of the DKB to be solved. AROM, an object-based knowledge representation system, has been used to design the DKB, and its task manager, AROMTasks, for developing the MKB. In this study two integrated systems, ABC transporters and two component systems, both involved in adaptation processes of a bacterial cell to its biotope, have been used to evaluate the feasibility of the approach.
Fernando, Ruani N; Chaudhari, Umesh; Escher, Sylvia E; Hengstler, Jan G; Hescheler, Jürgen; Jennings, Paul; Keun, Hector C; Kleinjans, Jos C S; Kolde, Raivo; Kollipara, Laxmikanth; Kopp-Schneider, Annette; Limonciel, Alice; Nemade, Harshal; Nguemo, Filomain; Peterson, Hedi; Prieto, Pilar; Rodrigues, Robim M; Sachinidis, Agapios; Schäfer, Christoph; Sickmann, Albert; Spitkovsky, Dimitry; Stöber, Regina; van Breda, Simone G J; van de Water, Bob; Vivier, Manon; Zahedi, René P; Vinken, Mathieu; Rogiers, Vera
2016-06-01
SEURAT-1 is a joint research initiative between the European Commission and Cosmetics Europe aiming to develop in vitro- and in silico-based methods to replace the in vivo repeated dose systemic toxicity test used for the assessment of human safety. As one of the building blocks of SEURAT-1, the DETECTIVE project focused on a key element on which in vitro toxicity testing relies: the development of robust and reliable, sensitive and specific in vitro biomarkers and surrogate endpoints that can be used for safety assessments of chronically acting toxicants, relevant for humans. The work conducted by the DETECTIVE consortium partners has established a screening pipeline of functional and "-omics" technologies, including high-content and high-throughput screening platforms, to develop and investigate human biomarkers for repeated dose toxicity in cellular in vitro models. Identification and statistical selection of highly predictive biomarkers in a pathway- and evidence-based approach constitute a major step in an integrated approach towards the replacement of animal testing in human safety assessment. To discuss the final outcomes and achievements of the consortium, a meeting was organized in Brussels. This meeting brought together data-producing and supporting consortium partners. The presentations focused on the current state of ongoing and concluding projects and the strategies employed to identify new relevant biomarkers of toxicity. The outcomes and deliverables, including the dissemination of results in data-rich "-omics" databases, were discussed as were the future perspectives of the work completed under the DETECTIVE project. Although some projects were still in progress and required continued data analysis, this report summarizes the presentations, discussions and the outcomes of the project.
Fernando, Ruani N.; Chaudhari, Umesh; Escher, Sylvia E.; Hengstler, Jan G.; Hescheler, Jürgen; Jennings, Paul; Keun, Hector C.; Kleinjans, Jos C. S.; Kolde, Raivo; Kollipara, Laxmikanth; Kopp-Schneider, Annette; Limonciel, Alice; Nemade, Harshal; Nguemo, Filomain; Peterson, Hedi; Prieto, Pilar; Rodrigues, Robim M.; Sachinidis, Agapios; Schäfer, Christoph; Sickmann, Albert; Spitkovsky, Dimitry; Stöber, Regina; van Breda, Simone G.J.; van de Water, Bob; Vivier, Manon; Zahedi, René P.
2017-01-01
SEURAT-1 is a joint research initiative between the European Commission and Cosmetics Europe aiming to develop in vitro and in silico based methods to replace the in vivo repeated dose systemic toxicity test used for the assessment of human safety. As one of the building blocks of SEURAT-1, the DETECTIVE project focused on a key element on which in vitro toxicity testing relies: the development of robust and reliable, sensitive and specific in vitro biomarkers and surrogate endpoints that can be used for safety assessments of chronically acting toxicants, relevant for humans. The work conducted by the DETECTIVE consortium partners has established a screening pipeline of functional and “-omics” technologies, including high-content and high-throughput screening platforms, to develop and investigate human biomarkers for repeated dose toxicity in cellular in vitro models. Identification and statistical selection of highly predictive biomarkers in a pathway- and evidence-based approach constitutes a major step in an integrated approach towards the replacement of animal testing in human safety assessment. To discuss the final outcomes and achievements of the consortium, a meeting was organized in Brussels. This meeting brought together data-producing and supporting consortium partners. The presentations focused on the current state of ongoing and concluding projects and the strategies employed to identify new relevant biomarkers of toxicity. The outcomes and deliverables, including the dissemination of results in data-rich “-omics” databases, were discussed as were the future perspectives of the work completed under the DETECTIVE project. Although some projects were still in progress and required continued data analysis, this report summarizes the presentations, discussions and the outcomes of the project. PMID:27129694
Predictors of intimate partner problem-related suicides among suicide decedents in Kentucky
Comiford, Ashley L.; Sanderson, Wayne T.; Chesnut, Lorie; Brown, Sabrina
2016-01-01
Abstract: Background: Suicide is the 10th leading cause of death in the United States. Furthermore, intimate partner problems are amid the top precipitating circumstances among suicide decedents. The aim of this study was to determine circumstantial associations of intimate partner problem-related suicides in suicide decedents in Kentucky. Methods: All suicides that were reported to the Kentucky Violent Death Reporting System between 2005 and 2012 were eligible for this study. Multiple logistic regression was used to explore predictors (precipitating health-related problems, life stressors, and criminal/legal issues) of intimate partner problem-related suicides. Results: Of the 4,754 suicides, included in this study, approximately 17% had intimate partner problems prior to suicide. In the adjusted analysis, mental health issues, alcohol problems, history of suicides attempts, suicides precipitated by another crime, and other legal problems increased the odds of having an intimate partner-related suicide. However, having physical health problems, prior to the suicide, decreased the odds of intimate partner-related suicide. Conclusions: These results provide insight for the development of suicide interventions for individuals with intimate partner problems by targeting risk factors that are prevalent among this population. Moreover, these results may help marriage/relationship and/or family/divorce court representatives identify individuals with intimate partner problems more at risk for suicide and alleviate the influence these suicide risk factors have on individuals experiencing Intimate partner problems. PMID:27092956
An Examination of the Partner Cyber Abuse Questionnaire in a College Student Sample
Wolford-Clevenger, Caitlin; Zapor, Heather; Brasfield, Hope; Febres, Jeniimarie; Elmquist, JoAnna; Brem, Meagan; Shorey, Ryan C.; Stuart, Gregory L.
2015-01-01
Objective To examine the factor structure and convergent validity of a newly developed measure of an understudied form of partner abuse, cyber abuse, and to examine the prevalence of, and gender differences in, victimization by cyber abuse. Method College students in a dating relationship (N = 502) completed the Partner Cyber Abuse Questionnaire (Hamby, 2013), as well as measures of partner abuse victimization and depression. Results Using exploratory factor analysis, we determined a one-factor solution was the most statistically and conceptually best fitting model. The cyber abuse victimization factor was correlated with depressive symptoms and physical, psychological, and sexual partner abuse victimization, supporting the convergent validity of the measure. The overall prevalence of victimization by cyber abuse was 40%, with victimization by specific acts ranging from 2–31%. Men and women did not differ in their victimization by cyber abuse. Conclusions Cyber abuse is prevalent among college students and occurs concurrently with other partner abuse forms and depressive symptoms. Given the interrelated nature of partner abuse forms, prevention and intervention programs should address partner abuse occurring in-person and through technology. Cyber abuse should also be considered in the conceptualization and measurement of partner abuse to more fully understand this social problem. PMID:27014498
Reverse correlating love: highly passionate women idealize their partner's facial appearance.
Gunaydin, Gul; DeLong, Jordan E
2015-01-01
A defining feature of passionate love is idealization--evaluating romantic partners in an overly favorable light. Although passionate love can be expected to color how favorably individuals represent their partner in their mind, little is known about how passionate love is linked with visual representations of the partner. Using reverse correlation techniques for the first time to study partner representations, the present study investigated whether women who are passionately in love represent their partner's facial appearance more favorably than individuals who are less passionately in love. In a within-participants design, heterosexual women completed two forced-choice classification tasks, one for their romantic partner and one for a male acquaintance, and a measure of passionate love. In each classification task, participants saw two faces superimposed with noise and selected the face that most resembled their partner (or an acquaintance). Classification images for each of high passion and low passion groups were calculated by averaging across noise patterns selected as resembling the partner or the acquaintance and superimposing the averaged noise on an average male face. A separate group of women evaluated the classification images on attractiveness, trustworthiness, and competence. Results showed that women who feel high (vs. low) passionate love toward their partner tend to represent his face as more attractive and trustworthy, even when controlling for familiarity effects using the acquaintance representation. Using an innovative method to study partner representations, these findings extend our understanding of cognitive processes in romantic relationships.
Care Partners and Multiple Sclerosis
Quig, Mary Elizabeth; Tyry, Tuula; Marrie, Ruth Ann; Cutter, Gary; Shearin, Edward; Johnson, Kamau; Simsarian, James
2015-01-01
Background: Caring for someone with multiple sclerosis (MS) can be a stressful experience that requires clinical attention. We investigated the impact of caregiver stress on the emotional well-being and physical health of the MS care partner using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Methods: Care partners of NARCOMS participants were invited to complete an online questionnaire that captured demographic characteristics, health status, caregiver burden as measured by the Zarit Caregiver Burden Interview, and impact of caregiving on employment. Results: Of 1446 care partners who agreed to participate, 1333 had complete data. Most were men (n = 825, 61.9%), with a mean (SD) age of 51.1 (11.2) years. The mean (SD) Zarit total score was 24.6 (15.1), placing the overall group in the mild caregiver burden range. Compared with male care partners, female care partners reported higher levels of burden and stress and more medication use for stress/anxiety and mood disorders. Male care partners were more likely to report physical concerns. Care partners of people with primary progressive MS reported greater perceived burden than did partners of people with secondary progressive MS and relapsing-remitting MS. More than 40% of care partners (559 of 1288) had missed work during the past year owing to caregiving responsibilities. Conclusions: Care partners of people with MS have substantial physical and psychological health concerns and experience an adverse impact on employment. Future research should evaluate how to mitigate the adverse effects of caregiving and evaluate positive aspects of the role. PMID:26664330
Gürsoy, Ayla; Koçan, Sema; Aktuğ, Cemile
2017-08-01
The aim of this study was to acquire a deeper understanding of male experiences on the emotional and social impact of their partners' mastectomy and chemotherapy-induced alopecia. A purposive sample of 16 males whose partners had undergone mastectomy and alopecia due to chemotherapy was chosen. The data were collected through a semi-structured interview method. Interpretative Phenomenological Analysis of tape-recorded interviews was employed. Two main themes emerged from the data: facing the changes and my wife and I at present. Male partners were affected differently by the change in the physical appearance of their female partners. Our study participants said it was a difficult experience to see their partners for the first time after the surgery, but they emphasized that it was more important that their partners were healthy than the fact that they did not have a breast and hair. They also said they did not know how to behave towards their partners after surgery and/or chemotherapy. Nevertheless, they felt that the disease process of their partners had strengthened their bond and had not negatively influenced their relationship with others. The changes in the partners' physical appearance after mastectomy and chemotherapy affected males differently in psychological, emotional and social terms. Since nurses working in this field are in contact with patients during all phases of treatment and care, it would be positive and beneficial to plan nursing interventions that give emotional support for male partners of patients with breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.
Porter, Laura S; Keefe, Francis J; Baucom, Donald H; Hurwitz, Herbert; Moser, Barry; Patterson, Emily; Kim, Hong Jin
2009-09-15
For patients with cancer who are married or in an intimate relationship, their relationships with their partners play a critical role in their adaptation to illness. However, cancer patients and their partners often have difficulty in talking with each other about their cancer-related concerns. Difficulties in communication ultimately may compromise both the patient-partner relationship and the patient's psychological adjustment. The current study tested the efficacy of a novel partner-assisted emotional disclosure intervention in a sample of patients with gastrointestinal (GI) cancer. One hundred thirty patients with GI cancer and their partners were assigned randomly to receive 4 sessions of either partner-assisted emotional disclosure or a couples cancer education/support intervention. Patients and partners completed measures of relationship quality, intimacy with their partner, and psychological distress before randomization and at the end of the intervention sessions. Data were analyzed using multilevel modeling. Compared with an education/support condition, the partner-assisted emotional disclosure condition led to improvements in relationship quality and intimacy for couples in which the patient initially reported higher levels of holding back from discussing cancer-related concerns. Partner-assisted emotional disclosure is a novel intervention that builds on both the private emotional disclosure and the cognitive-behavioral marital literature. The results of this study suggested that this intervention may be beneficial for couples in which the patient tends to hold back from discussing concerns. The authors concluded that future research on methods of enhancing the effects of partner-assisted emotional disclosure is warranted. Copyright (c) 2009 American Cancer Society.
Use of new technologies to notify possible contagion of sexually-transmitted infections among men.
Carnicer-Pont, Dolors; Barbera-Gracia, María Jesús; Fernández-Dávila, Percy; García de Olalla, Patricia; Muñoz, Rafael; Jacques-Aviñó, Constanza; Saladié-Martí, María Pilar; Gosch-Elcoso, Mercè; Arellano Muñoz, Encarna; Casabona, Jordi
2015-01-01
Among men who have sex with men (MSM), the association between searching for sexual partners' on the Internet and increased risk of sexually transmitted infections (STIs)/HIV infection, together with current low levels of partner notification (PN), justifies a study to explore the intention to use new communication technologies for PN in Spain. Two cross-sectional surveys were performed: the first was administered online to visitors to web pages where the survey was advertised; the second was administered on paper to patients attending an STI Unit and centres similar to Community-Based Voluntary Counselling and Testing centres. The study population comprised 1578 Spanish residents (median age, 34 years [range: 18 to 74]); 84% lived in urban areas, and 69% reported searching for sexual partners on the Internet. Thirty-seven per cent would be willing to use a website for PN, 26% did not know if they would use one, and 37% would not want to use one. The main reasons for not intending to notify STI/HIV were "shame or fear" (stable partner) and "not knowing how to contact them" (casual partner). The preferred method of notification was face to face (73%) for both stable and casual partners, although using new technologies (Short Messaging System, e-mail, web page, phone applications) was widely accepted for notifying casual partners. Fighting stigma and promoting alternative methods of PN among MSM and health professionals through new technologies could increase the frequency of PN. This approach will improve early detection and reduce transmission in Spain. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.
Male partner reproductive coercion among women veterans.
Rosenfeld, Elian A; Miller, Elizabeth; Zhao, Xinhua; Sileanu, Florentina E; Mor, Maria K; Borrero, Sonya
2018-02-01
Male partner reproductive coercion is defined as male partners' attempts to promote pregnancy through interference with women's contraceptive behaviors and reproductive decision-making. Male partners may try to promote pregnancy through birth control sabotage such as taking away or destroying their partners' contraceptives, refusing to wear condoms, and/or verbally pressuring their partners to abstain from contraceptive use. Reproductive coercion is associated with an elevated risk for unintended pregnancy. Women who experience intimate partner violence, who are in racial/ethnic minorities, and who are of lower socioeconomic status are more likely to experience reproductive coercion. Women veterans who use Veterans Affairs for health care may be particularly vulnerable to reproductive coercion because they are disproportionally from racial/ethnic minority groups and experience high rates of intimate partner violence. We sought to examine the prevalence, correlates, and impact of reproductive coercion among women veterans who are served by the Veterans Affairs healthcare system. We analyzed data from a national telephone survey of women veterans aged 18-44 years, with no history of sterilization or hysterectomy, who had received care within the Veterans Affairs system in the previous 12 months. Participants who had sex with men in the last year were asked if they experienced male partner reproductive coercion. Adjusted logistic regression was used to examine the relationship between participant characteristics and male partner reproductive coercion and the relationship between reproductive coercion and the outcomes of contraceptive method used at last sex and pregnancy and unintended pregnancy in the last year. Among the 1241 women veterans in our study cohort, 11% reported experiencing male partner reproductive coercion in the past year. Black women, younger women, and single women were more likely to report reproductive coercion than their white, older, and married counterparts. Women who experienced military sexual trauma were also more likely to report reproductive coercion compared with women who did not report military sexual trauma. In adjusted analyses, compared with women who did not experience reproductive coercion, those who did were less likely at last sex to have used any method of contraception (76% vs 80%; adjusted odds ratio, 0.61; 95% confidence interval, 0.38-0.96), prescription contraception (43% vs 55%; adjusted odds ratio, 0.62; 95% confidence interval, 0.43-0.91), and their ideal method of contraception (35% vs 45%; adjusted odds ratio, 0.63; 95% confidence interval, 0.43-0.93). Those who reported coercion were more likely to have had a pregnancy in the last year (14% vs 10%; adjusted odds ratio, 2.07; 95% confidence interval, 1.17-3.64); there were no significant differences in unintended pregnancy by coercion status (6% vs 4%; adjusted odds ratio, 1.63; 95% confidence interval, 0.71-3.76). Eleven percent of women veterans in our sample experienced male partner reproductive coercion, which may impact their use of contraception and ability to prevent pregnancy. Published by Elsevier Inc.
Albaugh, Jeffrey A; Sufrin, Nat; Lapin, Brittany R; Petkewicz, Jacqueline; Tenfelde, Sandi
2017-06-15
Prostate cancer is the most common non-skin cancer in men and sexual dysfunction is the most frequently reported long-term side effect of prostate cancer surgery or radiation. The aim of this study was to examine the experiences of men with sexual dysfunction and their partners following prostate cancer treatment. Men with sexual dysfunction from either surgical removal or radiation therapy 1-5 years after treatment were interviewed, as well as their partners. A mixed method design was used to determine the lived experience of men with sexual dysfunction. Open-ended questions guided the interviews. Twenty seven men completed the study with a mean age of 61 years (SD = 8.0; range = 44-77 years). Nine partners also participated. The majority of men (92.6%) had surgery. The average time from treatment to the interview was 23.5 months (SD = 11.7). Themes were frustration with sexual dysfunction, importance of support and understanding from others, depression and anxiety related to sexual dysfunction, importance of intimacy with partner, factors that impact treatment satisfaction, and education and comprehensive information about sex. Prostate cancer survivors and partners need accurate information about sexual side effects before during and after treatment. Men and partners required individualized help and guidance to manage sexual dysfunction. Support and understanding from partners, family, and others was also identified as an important aspect of healing and adjustment after prostate cancer treatment. Prostate cancer education/support groups played a key role in helping men and partners gain advocacy, education, and support. Psychological problems such as depression and anxiety need to be identified and addressed in men after prostate cancer treatment. Men and partners need assistance in understanding and navigating their way through intimacy to move forward with connectedness in their relationship. Satisfaction with treatment and with providers is dependent on patient education and understanding of all aspects of prostate cancer treatment including sexual side effects and incontinence.
Wagner, Glenn J; Woldetsadik, Mahlet A; Beyeza-Kashesya, Jolly; Goggin, Kathy; Mindry, Deborah; Finocchario-Kessler, Sarah; Khanakwa, Sarah; Wanyenze, Rhoda K
2016-03-01
Many people living with HIV desire childbearing, but low cost safer conception methods (SCM) such as timed unprotected intercourse (TUI) and manual self-insemination (MSI) are rarely used. We examined awareness and attitudes towards SCM, and the correlates of these constructs among 400 HIV clients with fertility intentions in Uganda. Measures included awareness, self-efficacy, and motivation regarding SCM, as well as demographics, health management, partner and provider characteristics. Just over half knew that MSI (53%) and TUI (51%) reduced transmission risk during conception, and 15% knew of sperm washing and pre-exposure prophylaxis. In separate regression models for SCM awareness, motivation, and self-efficacy, nearly all independent correlates were related to the partner, including perceived willingness to use SCM, knowledge of respondent's HIV status, HIV-seropositivity, marriage and equality in decision making within the relationship. These findings suggest the importance of partners in promoting SCM use and partner inclusion in safer conception counselling.
Pleasants, Elizabeth; Reddy, Krishnaveni; Atujuna, Millicent; Nakyanzi, Teopista; Chitukuta, Miria; Naidoo, Sarita; Palanee-Phillips, Thesla; Baeten, Jared M.; Montgomery, Elizabeth T.
2018-01-01
Vaginally-inserted HIV prevention methods have been reported to impact the sexual experience for women and their partners, and hence impacts acceptability of and adherence to the method. We analyzed in-depth interviews and focus group discussions about participants’ sexual experiences while wearing the ring, collected during the MTN-020/ASPIRE phase 3 safety and effectiveness trial of a dapivirine vaginal ring for HIV prevention in Malawi, South Africa, Uganda, and Zimbabwe. Most women reported that partners did not feel the ring during sex, however, women felt they had to manage their partners’ interaction with or reaction to the ring. In maintaining positive relationships, women were concerned about partners’ discovering ring use and about ensuring that partners had a good sexual experience with them. Finally women were concerned about how they themselves experienced sex with the ring. Some found that the ring made the vaginal environment more desirable for their partners and themselves. PMID:29151197
The role of the Standard Days Method in modern family planning services in developing countries.
Lundgren, Rebecka I; Karra, Mihira V; Yam, Eileen A
2012-08-01
The mere availability of family planning (FP) services is not sufficient to improve reproductive health; services must also be of adequate quality. The introduction of new contraceptive methods is a means of improving quality of care. The Standard Days Method (SDM) is a new fertility-awareness-based contraceptive method that has been successfully added to reproductive health care services around the world. Framed by the Bruce-Jain quality-of-care paradigm, this paper describes how the introduction of SDM in developing country settings can improve the six elements of quality while contributing to the intrinsic variety of available methods. SDM meets the needs of women and couples who opt not to use other modern methods. SDM providers are sensitised to the potential of fertility-awareness-based contraception as an appropriate choice for these clients. SDM requires the involvement of both partners and thus offers a natural entry point for providers to further explore partner communication, intimate partner violence, condoms, and HIV/STIs. SDM introduction broadens the range of FP methods available to couples in developing countries. SDM counselling presents an opportunity for FP providers to discuss important interpersonal and reproductive health issues with potential users.
Miller, W B; Pasta, D J
2001-01-01
In this study we develop and then test a couple model of contraceptive method choice decision-making following a pregnancy scare. The central constructs in our model are satisfaction with one's current method and confidence in the use of it. Downstream in the decision sequence, satisfaction and confidence predict desires and intentions to change methods. Upstream they are predicted by childbearing motivations, contraceptive attitudes, and the residual effects of the couples' previous method decisions. We collected data from 175 mostly unmarried and racially/ethnically diverse couples who were seeking pregnancy tests. We used LISREL and its latent variable capacity to estimate a structural equation model of the couple decision-making sequence leading to a change (or not) in contraceptive method. Results confirm most elements in our model and demonstrate a number of important cross-partner effects. Almost one-half of the sample had positive pregnancy tests and the base model fitted to this subsample indicates less accuracy in partner perception and greater influence of the female partner on method change decision-making. The introduction of some hypothesis-generating exogenous variables to our base couple model, together with some unexpected findings for the contraceptive attitude variables, suggest interesting questions that require further exploration.
Predictive testing for Huntington's disease: relationship with partners after testing.
Decruyenaere, M; Evers-Kiebooms, G; Cloostermans, T; Boogaerts, A; Demyttenaere, K; Dom, R; Fryns, J P
2004-01-01
This study focuses on the partner relationship of tested persons, 5 years after their predictive test result for Huntington's disease (HD). We describe changes in marital status, quality of the relationship, and perceived changes in the relationship. Twenty-six carriers, 14 of their partners, 33 non-carriers, and 17 of their partners participated in the study. Qualitative and quantitative methods were used. For the majority of tested persons (about 70%), the marital status was unchanged 5 years post test. Overall, carriers rated the quality of the relationship higher than their partners did and they perceived more positive changes. Qualitative data show that a test result leading to changed roles may induce significant marital distress. Another consequence of the test may be the changes in dynamics in asymptomatic carrier couples. A pre-test discussion of the possible impact of the test result on the relationship should result in a better preparation for and more understanding of the reactions after testing. Counselling after testing should stimulate an open communication between partners with consideration of needs and anxieties of both partners.
Reed, Jennifer L.; Huppert, Jill S.; Gillespie, Gordon L.; Taylor, Regina G.; Holland, Carolyn K.; Alessandrini, Evaline A.; Kahn, Jessica A.
2015-01-01
Objectives Important barriers to addressing the sexually transmitted infection (STI) epidemic among adolescents are the inadequate partner notification of positive STI results and insufficient rates of partner testing and treatment. However, adolescent attitudes regarding partner notification and treatment are not well understood. The aim was to qualitatively explore the barriers to and preferences for partner notification and treatment among adolescent males and females tested for STIs in an emergency department (ED) setting and to explore the acceptability of ED personnel notifying their sexual partners. Methods This was a descriptive, qualitative study in which a convenience sample of 40 adolescents (18 females, 22 males) 14 to 21 years of age who presented to either adult or pediatric EDs with STI-related complaints participated. Individualized, semistructured, confidential interviews were administered to each participant. Interviews were audiotaped and transcribed verbatim by an independent transcriptionist. Data were analyzed using framework analysis. Results Barriers to partner notification included fear of retaliation or loss of the relationship, lack of understanding of or concern for the consequences associated with an STI, and social stigma and embarrassment. Participants reported two primary barriers to their partners obtaining STI testing and treatment: lack of transportation to the health care site and the partner's fear of STI positive test results. Most participants preferred to notify their main sexual partners of an STI exposure via a face-to-face interaction or a phone call. Most participants were agreeable with a health care provider (HCP) notifying their main sexual partners of STI exposure and preferred that the HCP notify the partner by phone call. Conclusions There are several adolescent preferences and barriers for partner notification and treatment. To be most effective, future interventions to prevent adolescent STIs should incorporate these preferences and address the barriers to partner notification. In an ED setting, using HCPs to provide partner notification of STI exposures is acceptable to adolescent patients; however, the feasibility of this type of program needs further exploration. PMID:25545855
NASA Astrophysics Data System (ADS)
Patkin, M. L.; Rogachev, G. N.
2018-02-01
A method for constructing a multi-agent control system for mobile robots based on training with reinforcement using deep neural networks is considered. Synthesis of the management system is proposed to be carried out with reinforcement training and the modified Actor-Critic method, in which the Actor module is divided into Action Actor and Communication Actor in order to simultaneously manage mobile robots and communicate with partners. Communication is carried out by sending partners at each step a vector of real numbers that are added to the observation vector and affect the behaviour. Functions of Actors and Critic are approximated by deep neural networks. The Critics value function is trained by using the TD-error method and the Actor’s function by using DDPG. The Communication Actor’s neural network is trained through gradients received from partner agents. An environment in which a cooperative multi-agent interaction is present was developed, computer simulation of the application of this method in the control problem of two robots pursuing two goals was carried out.
Mechanistic insights into phosphoprotein-binding FHA domains.
Liang, Xiangyang; Van Doren, Steven R
2008-08-01
[Structure: see text]. FHA domains are protein modules that switch signals in diverse biological pathways by monitoring the phosphorylation of threonine residues of target proteins. As part of the effort to gain insight into cellular avoidance of cancer, FHA domains involved in the cellular response to DNA damage have been especially well-characterized. The complete protein where the FHA domain resides and the interaction partners determine the nature of the signaling. Thus, a key biochemical question is how do FHA domains pick out their partners from among thousands of alternatives in the cell? This Account discusses the structure, affinity, and specificity of FHA domains and the formation of their functional structure. Although FHA domains share sequence identity at only five loop residues, they all fold into a beta-sandwich of two beta-sheets. The conserved arginine and serine of the recognition loops recognize the phosphorylation of the threonine targeted. Side chains emanating from loops that join beta-strand 4 with 5, 6 with 7, or 10 with 11 make specific contacts with amino acids of the ligand that tailor sequence preferences. Many FHA domains choose a partner in extended conformation, somewhat according to the residue three after the phosphothreonine in sequence (pT + 3 position). One group of FHA domains chooses a short carboxylate-containing side chain at pT + 3. Another group chooses a long, branched aliphatic side chain. A third group prefers other hydrophobic or uncharged polar side chains at pT + 3. However, another FHA domain instead chooses on the basis of pT - 2, pT - 3, and pT + 1 positions. An FHA domain from a marker of human cancer instead chooses a much longer protein fragment that adds a beta-strand to its beta-sheet and that presents hydrophobic residues from a novel helix to the usual recognition surface. This novel recognition site and more remote sites for the binding of other types of protein partners were predicted for the entire family of FHA domains by a bioinformatics approach. The phosphopeptide-dependent dynamics of an FHA domain, SH2 domain, and PTB domain suggest a common theme: rigid, preformed binding surfaces support van der Waals contacts that provide favorable binding enthalpy. Despite the lack of pronounced conformational changes in FHA domains linked to binding events, more subtle adjustments may be possible. In the one FHA domain tested, phosphothreonine peptide binding is accompanied by increased flexibility just outside the binding site and increased rigidity across the beta-sandwich. The folding of the same FHA domain progresses through near-native intermediates that stabilize the recognition loops in the center of the phosphoprotein-binding surface; this may promote rigidity in the interface and affinity for targets phosphorylated on threonine.
How to select the correct education strategy: when not to go online.
Klingbeil, Carol G; Johnson, Norah L; Totka, Joan P; Doyle, Lynn
2009-01-01
Screening for intimate partner violence is an important injury prevention strategy. Nurses who develop staff education, to promote screening, need to select a method that is sensitive to learners. Online learning, although convenient, is not well suited to sensitive topics such as screening for intimate partner violence. The purpose of this article is to describe a curriculum for intimate partner violence screening based on self-efficacy theory, which includes a hospital-produced video, a role play, and a discussion.
Mutations in the NHEJ component XRCC4 cause primordial dwarfism.
Murray, Jennie E; van der Burg, Mirjam; IJspeert, Hanna; Carroll, Paula; Wu, Qian; Ochi, Takashi; Leitch, Andrea; Miller, Edward S; Kysela, Boris; Jawad, Alireza; Bottani, Armand; Brancati, Francesco; Cappa, Marco; Cormier-Daire, Valerie; Deshpande, Charu; Faqeih, Eissa A; Graham, Gail E; Ranza, Emmanuelle; Blundell, Tom L; Jackson, Andrew P; Stewart, Grant S; Bicknell, Louise S
2015-03-05
Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
HDGF: a novel jack-of-all-trades in cancer.
Bao, Cihang; Wang, Jianbo; Ma, Wei; Wang, Xintong; Cheng, Yufeng
2014-12-01
HDGF is an important regulator of a broad range of cancer cell activities and plays important roles in cancer cell transformation, apoptosis, angiogenesis and metastasis. Such a divergent influence of HDGF on cancer cell activities derives from its multiple inter- and sub-cellular localizations where it interacts with a range of different binding partners. Interestingly, high levels of HDGF could be detected in patients' serum of some cancers. This review is focused on the role of HDGF in tumorigenesis and metastasis, and provides insight for application in clinical cancer therapy as well as its clinical implications as a prognostic marker in cancer progression.
Weiss, Daniel J; Turner, Leigh; Levine, Aaron D; Ikonomou, Laertis
2018-02-01
Businesses marketing unproven stem cell interventions proliferate within the U.S. and in the larger global marketplace. There have been global efforts by scientists, patient advocacy groups, bioethicists, and public policy experts to counteract the uncontrolled and premature commercialization of stem cell interventions. In this commentary, we posit that medical societies and associations of health care professionals have a particular responsibility to be an active partner in such efforts. We review the role medical societies can and should play in this area through patient advocacy and awareness initiatives. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Protein Arginine Methylation in Mammals: Who, What, and Why
Bedford, Mark T.; Clarke, Steven G.
2012-01-01
The covalent marking of proteins by methyl group addition to arginine residues can promote their recognition by binding partners or can modulate their biological activity. A small family of gene products that catalyze such methylation reactions in eukaryotes (PRMTs) work in conjunction with a changing cast of associated subunits to recognize distinct cellular substrates. These reactions display many of the attributes of reversible covalent modifications such as protein phosphorylation or protein lysine methylation; however, it is unclear to what extent protein arginine demethylation occurs. Physiological roles for protein arginine methylation have been established in signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. PMID:19150423
Female partners of opioid-injecting men in the Republic of Georgia: an initial characterization
2012-01-01
Background HIV and Hepatitis C virus (HCV) infections are strongly related to injection drug use in the Republic of Georgia. Little information is available about HIV and HCV status, sexual risk, support for their partner, and risk for physical violence among the female partners of opioid-injecting men in the Republic of Georgia, many of whom may not be using drugs, yet may be at high risk of being infected with HIV and HCV from their drug-using partners. Methods In order to better understand the risks for females whose partners are injecting drugs, the present study conducted an initial investigation of the non-substance-using female partners of 40 opioid-injecting men who were participating in a clinical trial examining the feasibility and efficacy of a 22-week comprehensive intervention that paired behavioral treatment with naltrexone. The 40 female partners were assessed at their male partners’ study intake. Results The female sample was 32.3 years old (SD=6.7), 37 (93%) were married, with 15.5 years of education. A majority reported at least partial employment the majority of the time during the past 3 years, with only one woman reported being unemployed most of the time during the past 3 years. They self-reported they were 3% HIV-positive and 8% HCV-positive. Their HIV sex risk scores indicated a relatively low risk. However, only 4 (10%) women reported using a condom most of the time while having sex and 15 (38%) report not having had sex during the last 30 days. Experiences of interpersonal violence were common, with 42% reporting physical abuse by their partner during the last year and 48% reporting feeling unsafe in their current relationship. Conclusions The alarmingly high rate of failure to use barrier protection methods, together with the high percentage who did not know their HIV and HCV status, suggest that it may be beneficial to include non-substance-using female partners in prevention programs along with their partners to reduce the risk of HIV and HCV spreading from the population of injection-drug–using males into the general population. [This secondary analysis study was funded by an international supplement to the parent randomized clinical trial “Treating the Partners of Drug Using Pregnant Women: Stage II (HOPE)”. ClinicalTrials.gov Identifier: NCT00496990.] PMID:23157895
2018-01-01
Introduction Discrimination related to gender identity may directly influence vulnerability to HIV through increased exposure to unprotected receptive anal intercourse (URAI). Little is known about the relationship between gender-based discrimination (GBD) and URAI with stable partners among transgender women. Methods This mixed-methods research began with a cross-sectional survey conducted between 2014 and 2016 with transgender women in Salvador, the capital city in one of the poorest regions in Brazil. Respondent-driven sampling was used to recruit the study population. GBD was defined through Latent Class Analysis. Additionally, 19 semi-structured interviews with participants were transcribed and analyzed through thematic content analysis. Results URAI with stable partners was commonly reported (37.3%). GDB was positively associated with URAI among stable partners (OR = 6.47; IC 95%: 1.67–25.02). The analysis of the interviews illustrated how GBD impacted transgender women in diverse ways. Experiences with GBD perpetrated by the family often initiated a trajectory of economic vulnerability that led many to engage in survival sex work. The constant experience with GBD contributed to participants feeling an immense sense of trust with their stable partners, ultimately diminished their desire to use condoms. Further, the high frequency of GBD contributed to poor mental health overall, though some participants said engagement in transgender advocacy efforts provided a vital source of resilience and support. Conclusion Our mixed-method study capitalizes upon the strengths of diverse data sets to produce a holistic understanding of GBD and URAI with stable partners. Furthermore, by confirming the association between greater GBD and URAI, we have demonstrated how GBD can impact condom negotiation in diverse relationships. PMID:29641528
The Development of an eHealth Tool Suite for Prostate Cancer Patients and Their Partners
Van Bogaert, Donna; Hawkins, Robert; Pingree, Suzanne; Jarrard, David
2013-01-01
Background eHealth resources for people facing health crises must balance the expert knowledge and perspective of developers and clinicians against the very different needs and perspectives of prospective users. This formative study explores the information and support needs of posttreatment prostate cancer patients and their partners as a way to improve an existing eHealth information and support system called CHESS (Comprehensive Health Enhancement Support System). Methods Focus groups with patient survivors and their partners were used to identify information gaps and information-seeking milestones. Results Both patients and partners expressed a need for assistance in decision making, connecting with experienced patients, and making sexual adjustments. Female partners of patients are more active in searching for cancer information. All partners have information and support needs distinct from those of the patient. Conclusions Findings were used to develop a series of interactive tools and navigational features for the CHESS prostate cancer computer-mediated system. PMID:22591675
Neural Responses to Partner Rejection Cues
Zayas, Vivian; Shoda, Yuichi; Mischel, Walter; Osterhout, Lee; Takahashi, Melissa
2009-01-01
Little is known about neural responses in the early automatic-stage processing of rejection cues from a partner. Event-related potentials (ERPs) offer a window to study processes that may be difficult to detect via behavioral methods. We focused on the N400 ERP component, which reflects the amount of semantic processing prompted by a target. When participants were primed by attachment-related contexts (“If I need help from my partner, my partner will be …”), rejection-related words (e.g., dismissing) elicited greater N400 amplitudes than acceptance-related words (e.g., supporting). Analyses of results for nonattachment primes suggest that these findings were not simply caused by target valence; the brain responds differentially to cues of partner rejection versus acceptance in under 300 ms. Moreover, these early-stage neurophysiological responses were heightened or dampened as a function of individuals’ adult attachment; women characterized by high anxiety and low avoidance showed the greatest N400 responses to cues of partner rejection (vs. acceptance). PMID:19493321
To have and to hold: gratitude promotes relationship maintenance in intimate bonds.
Gordon, Amie M; Impett, Emily A; Kogan, Aleksandr; Oveis, Christopher; Keltner, Dacher
2012-08-01
This multimethod series of studies merges the literatures on gratitude and risk regulation to test a new process model of gratitude and relationship maintenance. We develop a measure of appreciation in relationships and use cross-sectional, daily experience, observational, and longitudinal methods to test our model. Across studies, we show that people who feel more appreciated by their romantic partners report being more appreciative of their partners. In turn, people who are more appreciative of their partners report being more responsive to their partners' needs (Study 1), and are more committed and more likely to remain in their relationships over time (Study 2). Appreciative partners are also rated by outside observers as relatively more responsive and committed during dyadic interactions in the laboratory, and these behavioral displays are one way in which appreciation is transmitted from one partner to the other (Study 3). These findings provide evidence that gratitude is important for the successful maintenance of intimate bonds.
Ranneberg-Nilsen, Toril; Rollag, Halvor; Slettebakk, Ragnhild; Backe, Paul Hoff; Olsen, Øyvind; Luna, Luisa; Bjørås, Magnar
2012-01-01
Background Human cytomegalovirus (HCMV) uracil DNA glycosylase, UL114, is required for efficient viral DNA replication. Presumably, UL114 functions as a structural partner to other factors of the DNA-replication machinery and not as a DNA repair protein. UL114 binds UL44 (HCMV processivity factor) and UL54 (HCMV-DNA-polymerase). In the present study we have searched for cellular partners of UL114. Methodology/Principal Findings In a yeast two-hybrid screen SMARCB1, a factor of the SWI/SNF chromatin remodeling complex, was found to be an interacting partner of UL114. This interaction was confirmed in vitro by co-immunoprecipitation and pull-down. Immunofluorescence microscopy revealed that SMARCB1 along with BRG-1, BAF170 and BAF155, which are the core SWI/SNF components required for efficient chromatin remodeling, were present in virus replication foci 24–48 hours post infection (hpi). Furthermore a direct interaction was also demonstrated for SMARCB1 and UL44. Conclusions/Significance The core SWI/SNF factors required for efficient chromatin remodeling are present in the HCMV replication foci throughout infection. The proteins UL44 and UL114 interact with SMARCB1 and may participate in the recruitment of the SWI/SNF complex to the chromatinized virus DNA. Thus, the presence of the SWI/SNF chromatin remodeling complex in replication foci and its association with UL114 and with UL44 might imply its involvement in different DNA transactions. PMID:22479537
Tsai, Laura Cordisco
2016-04-27
This study explores the causal impact of independent management of household finances upon women's experiences of intimate partner violence (IPV) in the Philippines. Propensity score matching is used to generate a casual estimate of the impact of women's roles as household financial managers on their experiences of IPV. Findings demonstrate that managing household finances independently significantly increased the severity of IPV women experienced from their partners compared with women who managed finances jointly with partners. Findings reinforce the importance of explicit attention to intrahousehold power dynamics and gender norms in the implementation of microfinance interventions intended to empower women. © The Author(s) 2016.
Gender Differences in Intimate Partner Homicides Among Ethnic Sub-Groups of Asians.
Sabri, Bushra; Campbell, Jacquelyn C; Dabby, Firoza Chic
2016-03-01
This study explored differences in intimate partner homicides (IPHs) among Asian Americans. Data from newspapers and femicide reports by different state coalitions on 125 intimate partner killings occurring between 2000 and 2005 were analyzed. Men were the perpetrators in nearly 9 out of 10 cases of Asian IPHs. Gender differences were found in ages of victims and perpetrators, types of relationship between partners, and methods of killing. Most homicides occurred among South-east Asians, and East Asians had the highest within-group proportion of suicides. The findings call for culturally competent risk assessment and intervention strategies to prevent IPHs among at-risk Asian Americans. © The Author(s) 2015.
Integrated cellular network of transcription regulations and protein-protein interactions
2010-01-01
Background With the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway. Results In this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated. Conclusions We successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology. PMID:20211003
Integrated cellular network of transcription regulations and protein-protein interactions.
Wang, Yu-Chao; Chen, Bor-Sen
2010-03-08
With the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway. In this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated. We successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology.
Alemani, Davide; Pappalardo, Francesco; Pennisi, Marzio; Motta, Santo; Brusic, Vladimir
2012-02-28
In the last decades the Lattice Boltzmann method (LB) has been successfully used to simulate a variety of processes. The LB model describes the microscopic processes occurring at the cellular level and the macroscopic processes occurring at the continuum level with a unique function, the probability distribution function. Recently, it has been tried to couple deterministic approaches with probabilistic cellular automata (probabilistic CA) methods with the aim to model temporal evolution of tumor growths and three dimensional spatial evolution, obtaining hybrid methodologies. Despite the good results attained by CA-PDE methods, there is one important issue which has not been completely solved: the intrinsic stochastic nature of the interactions at the interface between cellular (microscopic) and continuum (macroscopic) level. CA methods are able to cope with the stochastic phenomena because of their probabilistic nature, while PDE methods are fully deterministic. Even if the coupling is mathematically correct, there could be important statistical effects that could be missed by the PDE approach. For such a reason, to be able to develop and manage a model that takes into account all these three level of complexity (cellular, molecular and continuum), we believe that PDE should be replaced with a statistic and stochastic model based on the numerical discretization of the Boltzmann equation: The Lattice Boltzmann (LB) method. In this work we introduce a new hybrid method to simulate tumor growth and immune system, by applying Cellular Automata Lattice Boltzmann (CA-LB) approach. Copyright © 2011 Elsevier B.V. All rights reserved.
Grey, Jeremy Alexander; Rothenberg, Richard B.; Sullivan, Patrick Sean; Rosenberg, Eli Samuel
2015-01-01
Objective Age disassortativity is one hypothesis for HIV disparities between Black and White MSM. We examined differences in age mixing by race and the effect of partner age difference on the association between race and HIV status. Design We used data from four studies of MSM. Participants reported information about recent sexual partners, including age, race, and sexual behavior. Two studies were online with a US sample and two focused on MSM in Atlanta. Methods We computed concordance correlation coefficients (CCCs) by race across strata of partner type, participant HIV status, condom use, and number of partners. We used Wilcoxon rank-sum tests to compare Black and White MSM on partner age differences across five age groups. Finally, we used logistic regression models using race, age, and partner age difference to determine the odds ratio of HIV-positive serostatus. Results Of 48 CCC comparisons, Black MSM were more age-disassortative than White MSM in only two. Furthermore, of 20 comparisons of median partner age, Black and White MSM differed in two age groups. One indicated larger age gaps among the Black MSM (18-19). Prevalent HIV infection was associated with race and age. Including partner age difference in the model resulted in a 2% change in the relative odds of infection among Black MSM. Conclusions Partner age disassortativity and partner age differences do not differ by race. Partner age difference offers little predictive value in understanding prevalent HIV infection among Black and White MSM, including diagnosis of HIV-positive status among self-reported HIV-negative individuals. PMID:26090814
Robinson, June K.; Stapleton, Jerod; Turrisi, Rob
2010-01-01
Objective We sought to identify relationship and partner-related moderating variables that influence the effectiveness of both a couples and a solo learning intervention designed to increase skin self-examination behavior in a sample of patients at risk for developing melanoma. Methods Patients received a brief intervention designed to teach skin self-examination skills and were randomly assigned into either a solo learning condition where the intervention was administered to the patient alone (n = 65) or a couple learning condition where the intervention was administered to the patient and patient’s spouse or cohabiting partner (n = 65). The main outcome measure was skin self-examination self-efficacy, which is the strongest mediator of skin self-examination. The relationship moderator variables measured were quality of relationship, partner motivation, and ability to assist in implementation of the intervention. Results When quality of the marital/partner relationship was high, the beneficial effects provided by the partner being included in the skin self-examination skills training were the highest and patients exhibited higher self-efficacy. Similar effects were observed for those with partners who were motivated to implement the intervention, and for those with partners high in ability to provide support. Limitations Study limitations include the need to evaluate whether the effects can be sustained long term and the exclusion of patients with melanoma without partners. Conclusions The amount of beneficial effects gained by the patient from the skin self-examination intervention was influenced by marital/partner relationships. Clinicians may need to consider these relationship and partner characteristics when communicating to patients about skin cancer screening. PMID:18258332
Roberts, Andrea L.; Gilman, Stephen E.; Fitzmaurice, Garrett; Decker, Michele R.; Koenen, Karestan C.
2011-01-01
Background At least half a million women are victims of intimate partner violence in the United States annually, resulting in substantial harm. However, the etiology of violence to intimate partners is not well understood. Witnessing such violence in childhood has been proposed as a principal cause of adulthood perpetration, yet it remains unknown whether the association between witnessing intimate partner violence and adulthood perpetration is causal. Method We conducted a propensity-score analysis of intimate partner violence perpetration to determine whether childhood witnessing is associated with perpetration in adulthood, independent of a wide range of potential confounding variables, and therefore might be a causal factor. We used data from 14,564 U.S. men ages 20 and older from the 2004–2005 wave of the National Epidemiologic Survey on Alcohol and Related Conditions. Results Nearly 4% of men reported violent behavior toward an intimate partner in the past year. In unadjusted models, we found a strong association between childhood witnessing of intimate partner violence and adulthood perpetration (for witnessing any intimate partner violence, risk ratio [RR] = 2.6 [95% confidence interval = 2.1–3.2]; for witnessing frequent or serious violence, 3.0 [2.3–3.9]). In propensity-score models, the association was substantially attenuated (for witnessing any intimate partner violence, adjusted RR = 1.6 [1.2–2.0]; for witnessing frequent or serious violence, 1.6 [1.2–2.3]). Conclusions Men who witness intimate partner violence in childhood are more likely to commit such acts in adulthood, compared with men who are otherwise similar with respect to a large range of potential confounders. Etiological models of intimate partner violence perpetration should consider a constellation of childhood factors. PMID:20811285
Effect of study partner on the conduct of Alzheimer disease clinical trials
Raman, Rema; Ernstrom, Karin; Aisen, Paul; Karlawish, Jason
2013-01-01
Objective: Alzheimer disease (AD) dementia clinical trials require 2 participants: a patient and a study partner. We assessed the prevalence of study partner types and how these types associate with patient-related outcome measures. Methods: Retrospective analyses of 6 Alzheimer’s Disease Cooperative Study (ADCS) randomized clinical trials were conducted. Study partners were categorized as spouse, adult child, or other. Prevalence of study partner type and associations between study partner type and trial outcomes including study completion and placebo decline on the Mini-Mental State Examination, the Alzheimer’s Disease Assessment Scale–cognitive subscale, the Clinical Dementia Rating scale Sum of the Boxes score, and the ADCS–Activities of Daily Living were examined. Results: More participants (67%) enrolled with spouses than adult children (26%) or other study partners (7%). Participants with spouse partners had a lower dropout rate (25%) than those with adult child (32%) or other study partners (34%); only the difference vs others was statistically significant. Participants with adult child and other partners randomized to placebo performed worse at baseline than those with spouse partners on the ADCS–Activities of Daily Living (p = 0.04), but were not different at 18 months. There were no differences at baseline for the Mini-Mental State Examination, Clinical Dementia Rating scale Sum of the Boxes score, or Alzheimer’s Disease Assessment Scale–cognitive subscale. In multivariate models of the rates of change over time among placebo participants, no differences among study partner groups reached statistical significance. Conclusions: Patients with nonspouse caregivers less frequently participate in AD dementia trials. Increased enrollment of AD patients with nonspouse caregivers may require additional recruitment and retention strategies. PMID:23255824
Bosire, Wilkister; Nelson, Gill; Kingola, Nzioki; Zhang, Xu-Dong; Temmerman, Marleen; Chersich, Matthew F.
2013-01-01
Objectives To assess sexual risk-taking of female sex workers (FSWs) with emotional partners (boyfriends and husbands), compared to regular and casual clients. Experiences of violence and the degree of relationship control that FSWs have with emotional partners are also described. Design Cohort study with quarterly follow-up visit over 12-months. Methods Four hundred HIV-uninfected FSWs older than 16 years were recruited from their homes and guesthouses in Mombasa, Kenya. A structured questionnaire assessed participant characteristics and study outcomes at each visit, and women received risk-reduction counselling, male and female condoms, and HIV testing. Results Four or more unprotected sex acts in the past week were reported by 21.3% of women during sex with emotional partners, compared to 5.8% with regular and 4.8% with casual clients (P<0.001). Total number of unprotected sex acts per week was 5–6-fold higher with emotional partners (603 acts with 259 partners) than with regular or casual clients (125 acts with 456, and 98 acts with 632 clients, respectively; P<0.001). Mostly, perceptions of “trust” underscored unprotected sex with emotional partners. Low control over these relationships, common to many women (36.9%), was linked with higher partner numbers, inconsistent condom use, and being physically forced to have sex by their emotional partners. Half experienced sexual or physical violence in the past year, similarly associated with partner numbers and inconsistent condom use. Conclusions High-risk sexual behaviour, low control and frequent violence in relationships with emotional partners heighten FSWs' vulnerability and high HIV risk, requiring targeted interventions that also encompass emotional partners. PMID:23950879
Heterosexual behaviours among men who sell sex to men in coastal Kenya.
Smith, Adrian D; Muhaari, Allan D; Agwanda, Carole; Kowuor, Dickens; van der Elst, Elise; Davies, Alun; Graham, Susan M; Jaffe, Harold W; Sanders, Eduard J
2015-12-01
African men who have sex with men often sell sex to men, and MSM who sell sex (MSM-SW) often also have female partners. We compared sexual risk behaviour of MSM-SW who were sexually active with female partners (bisexual MSW) to MSM-SW with only male partners (exclusive MSW). Descriptive behavioural study : A novel, validated daily event and partner diary self-completed by 82 MSM who sold sex over a follow-up period of 42 days with weekly review. Cumulative individual counts of sex and condomless sex were compiled by partner characteristics. The incidence of specific partnerships and sex acts were compared within and between bisexual and exclusive MSW. Most (59%) MSM-SW reported female partners during follow-up. The majority of both male and female partners were cash-paying clients originating locally. Bisexual MSW reported a similar rate of condomless sex with male and female partners, but significantly fewer male partners than exclusive MSW. Bisexual MSW had lower HIV prevalence, were more likely to only report insertive anal sex roles, and reported lower frequencies of condomless receptive anal sex than exclusive MSW. Bisexually active male sex workers in coastal Kenya create HIV and other sexually transmitted infection transmission pathways to partners and clients in both MSM and heterosexual networks, but differed from exclusive MSW in having lower HIV acquisition and transmission risks. Epidemiological projection methods are liable to overestimate bridging potential of MSM-SW and MSM populations without account for systematic differences in risk within these populations.
Esber, Allahna; Foraker, Randi E; Hemed, Maryam; Norris, Alison
2014-07-01
We examined the effect of partner approval of contraception on intention to use contraception among women obtaining post-abortion care in Zanzibar. Our data source was a 2010 survey of 193 women obtaining post-abortion care at a large public hospital in Zanzibar. We used multivariable logistic regression analysis to assess associations between partner approval and intention to use contraception. Overall, 23% of participants had used a contraceptive method in the past, and 66% reported intending to use contraception in the future. We found that partner approval of contraception and ever having used contraception in the past were each associated with intending to use contraception in the future. In the multivariable model, adjusting for past contraception use, partner approval of contraception was associated with 20 times the odds of intending to use contraception (odds ratio, 20.25; 95% confidence interval, 8.45-48.56). We found a strong association between partner approval and intention to use contraception. Efforts to support contraceptive use must include both male and female partners. Public health and educational efforts to increase contraceptive use must include men and be targeted to both male and female partners. Given that male partners are often not present when women obtain health care, creative efforts will be required to meet men in community settings. Copyright © 2014 Elsevier Inc. All rights reserved.
Violence Among Men and Women in Substance Use Disorder Treatment: A Multi-level Event-based Analysis
Chermack, Stephen T.; Grogan-Kaylor, Andy; Perron, Brian E.; Murray, Regan L.; De Chavez, Peter; Walton, Maureen A.
2010-01-01
Background This study examined associations between acute alcohol and drug use and violence towards others in conflict incidents (overall, partner, and non-partner conflict incidents) by men and women recruited from substance use disorder (SUD) treatment. Methods Semi-structured interviews were used to obtain details about interpersonal conflict incidents (substance use, whether specific conflicts were with intimate partners or non-partners) in the 180 days pre-treatment. Participants for this study were selected for screening positive for past-year violence (N = 160; 77% men, 23% women). Results Multilevel multinomial regression models showed that after adjusting for clustering within individual participants, the most consistent predictors of violence across models were acute cocaine use (significant for overall, intimate partner and non-partner models), acute heavy alcohol use (significant for overall and non-partner models), and male gender (significant in all models). Conclusions This study was the first to explicitly examine the role of acute alcohol and drug use across overall, partner and non-partner conflict incidents. Consistent with prior studies using a variety of methodologies, alcohol, cocaine use and male gender were most consistently and positively related to violence severity (e.g., resulting in injury). The results provide important and novel event-level information regarding the relationship between acute alcohol and specific drug use and the severity of violence in interpersonal conflict incidents. PMID:20667666
Living Anatomy. Second Edition.
ERIC Educational Resources Information Center
Donnelly, Joseph E.
This book is a text intended for undergraduates who are preparing to be physical education teachers, coaches, or athletic directors. It presents a method of instruction that uses a partner system by which students locate anatomical structures in the illustrations and on their partners, and then learn the structures' functions by manipulating their…
A Telephone Intervention for Substance-Using Adult Male Perpetrators of Intimate Partner Violence
ERIC Educational Resources Information Center
Mbilinyi, Lyungai F.; Neighbors, Clayton; Walker, Denise D.; Roffman, Roger A.; Zegree, Joan; Edleson, Jeffrey; O'Rourke, Allison
2011-01-01
Objective: To preliminarily evaluate telephone-delivered motivational enhancement therapy (MET) in motivating unadjudicated and nontreatment seeking intimate partner violence (IPV) perpetrators, who also use substances, to self-refer into treatment. Method: 124 adult men were recruited via a multimedia marketing campaign and were randomly assigned…
LRE Project Exchange: Building a Community through Partners in Human Rights Education.
ERIC Educational Resources Information Center
Anderson, Marna; Rudelius-Palmer, Kristi
1998-01-01
Describes Partners in Human Rights Education in which the Universal Declaration of Human Rights provides the framework for using interactive teaching methods to relate human-rights concepts to students' lives. Highlights Amnesty International's "Urgent Action Network" that encourages children to become lobbyists in a letter-writing…
ERIC Educational Resources Information Center
Eckhardt, Christopher I.; Samper, Rita; Suhr, Laura; Holtzworth-Munroe, Amy
2012-01-01
Whereas cognitive variables are hypothesized to play an important role in intimate partner violence (IPV) etiology and intervention, cognitive assessment methods have largely targeted offenders' explicit, controlled cognitive processing using paper-and-pencil questionnaires prone to social desirability biases. Using an implicit measure of…
26 CFR 1.704-3 - Contributed property.
Code of Federal Regulations, 2011 CFR
2011-04-01
... partners with respect to precontribution gain or loss. Under section 704(c), a partnership must allocate income, gain, loss, and deduction with respect to property contributed by a partner to the partnership so...) to reflect built-in gain (or loss), or a method under which the partnership creates tax allocations...
26 CFR 1.704-3 - Contributed property.
Code of Federal Regulations, 2013 CFR
2013-04-01
... partners with respect to precontribution gain or loss. Under section 704(c), a partnership must allocate income, gain, loss, and deduction with respect to property contributed by a partner to the partnership so...) to reflect built-in gain (or loss), or a method under which the partnership creates tax allocations...
26 CFR 1.704-3 - Contributed property.
Code of Federal Regulations, 2012 CFR
2012-04-01
... partners with respect to precontribution gain or loss. Under section 704(c), a partnership must allocate income, gain, loss, and deduction with respect to property contributed by a partner to the partnership so...) to reflect built-in gain (or loss), or a method under which the partnership creates tax allocations...
26 CFR 1.704-3 - Contributed property.
Code of Federal Regulations, 2014 CFR
2014-04-01
... partners with respect to precontribution gain or loss. Under section 704(c), a partnership must allocate income, gain, loss, and deduction with respect to property contributed by a partner to the partnership so...) to reflect built-in gain (or loss), or a method under which the partnership creates tax allocations...
SI – SRH Sexual-risk factors of partner age-discordance in adolescent girls and their male partners
Morrison-Beedy, Dianne; Xia, Yinglin; Passmore, Denise
2013-01-01
Aim and objectives To investigate differences in sexual-risk factors between adolescent girls reporting similar-aged or older sex partners. Background Adolescent girls are at significant risk for heterosexual-acquired HIV infection and other long term reproductive health issues. Sexual partner age-discordance in teen girls has been correlated with STIs, lack of protection, multiple partners, and earlier age of sexual transition. Design A descriptive study comparing girls currently involved with age-discordant partners to those with similar-aged partners. Two-sample t-test for continuous variables and for categorical variables, Chi-square or Fisher exact test were used to compare groups. Methods Baseline data from 738 sexually-active, urban, adolescent girls ages 15 to 19, were analyzed to determine which behaviors were more likely to occur in girls with older partners. Data were collected as part of a gender specific HIV-prevention intervention in a randomized controlled trial tailored to adolescent girls. Results Multiple reported sexual risk behaviors were found to significantly differ between the two groups at baseline. Overall, girls with older partners had more episodes of sexual instances (vaginal, anal, and oral). Specific sexual risk behaviors were found to be statistically significant between the two groups. Girls with older partners started having sex at earlier ages, had more lifetime sexual partners, higher incidents of STIs and were reluctant to discuss using condoms with their partners. Girls with similar-aged partners were less willing to engage in risky sexual behaviors. Conclusions Findings from this investigation support data from other studies. Relationships with older male partners place adolescent girls at increased risk for HIV/STIs and unintended pregnancy. Relevance to clinical practice Adolescent girls in age-discordant relationships are at risk for immediate and long term sexual health morbidities. Identifying girls who are at increased risk by asking tailored questions will enable nurses to recommend appropriate diagnostics for this population and provide age specific counseling. PMID:24580784
Gender and Role Differences in Couples Communication during Cancer Survivorship
Lim, Jung-won; Paek, Min-so; Shon, En-jung
2014-01-01
Background Individuals with cancer and their partners often experience communication difficulties. However, questions still remain regarding the influence of gender and role in cancer survivor-partner communication within couples. Objective The current study intended to examine the communication patterns in breast, colorectal, and prostate cancer survivor-partner couples during cancer survivorship and whether gender and role differences in couples communication exist. Methods The dominant-less dominant methods of sequential mixed design was utilized. Ten couples who were recruited from the University Hospital registry in Cleveland, Ohio participated in both mail surveys and individual interviews. Family and cancer-related communication was assessed in the quantitative phase. Results Both male survivors and partners demonstrated better family communication scores compared to their female counterparts, whereas there were no gender differences in the cancer-related communication scores. In the qualitative phase, 3 major themes were identified: 1) selective sharing of cancer-related issues, 2) initiation of cancer-related communication, and 3) emotional reaction in communication. The patterns associated with these themes differed between the male survivor-female partner and female survivor-male partner couples. Conclusions This study provides new knowledge about family and cancer-related communication. Our findings highlight the importance of understanding different perspectives in the quality of communication by gender and role. Implications for Practice Exploring couples' communication patterns by gender and role stimulates the research and the development of effective consumer-centered communication interventions. The findings provide assessment tools to inform dyadic communication patterns for clinical and scientific purposes. PMID:25122132
Research on couples: are feminist approaches useful?
Peters, Kathleen; Jackson, Debra; Rudge, Trudy
2008-05-01
This paper is an exploration of the utility and value of feminist approaches when undertaking narrative-based research with partner dyads (within both heterosexual and same sex partnerships) and when researching sensitive issues. Adverse life events or conditions experienced by individuals have been found also to have a negative impact on their partners. Most literature addressing partner issues uses quantitative methods, and existing qualitative research on couples has traditionally interviewed only one person in the partnership or coupled partners together. There is little discussion in the literature about the use of feminist research when researching male perspectives and experiences, and even less discussion of the possibilities that feminist research methods bring to the study of couple dyads. Qualitative methodologies informed by feminist perspectives, including issues of reciprocity and self disclosure, can be used to unpack structural, personal and political issues related to couples' experiences. A feminist approach allows us to show that the origin of oppression is not personal but very much about power and that men as well as women, regardless of their sexuality, may experience the effects of oppression. Narrative and story-telling complements feminist research because of the value it assigns to the storytellers. To care for women effectively, we must also consider the experiences of their partners as the health of one partner has the potential to impact on the other. The concept of oppression is not absent, but indeed is illuminated, in the lives of some men. Gathering stories using feminist perspectives enhances respect and mutuality in the research process.
Sanchez, Diana Maria; Schoenbach, Victor J.; Harvey, S. Marie; Warren, Jocelyn T.; Poole, Charles; Leone, Peter A.; Adimora, Adaora A.; Agnew, Christopher R.
2016-01-01
Background Sexual partnership dates are critical to STI/HIV research and control programs, though validity is limited by inaccurate recall and reporting. Methods We examined data from 302 heterosexual adults (151 index-partner dyads) to assess reliability of reporting. Dates of first and last sex were collected through individual interviews and joint dyad questionnaires which partners completed together. We compared index- and partner-reported dates to estimate inter-partner agreement (IPA). We used log-linear regression to model associations between inter-partner differences and partnership characteristics. To assess validity, we compared individually-reported dates to those from joint dyad questionnaires. Results Most partnerships (66.2%) were ≤2 years in duration and many (36.2%) were non-monogamous. IPA to within 1-, 30-, and 365-days was, respectively, 5.6%, 43.1% and 81.3% for first sex; and 32.9%, 94.5%, and 100.0% for last sex. In adjusted models: longer relationship duration was associated with disagreement on first sex dates; partnership non-monogamy was associated with disagreement on dates of first and last sex. Within dyads, several participant characteristics were associated with reporting dates closer to joint dyad responses [e.g., for first sex date, female gender (54.7%), having fewer sex partners (58.5%), and greater relationship commitment (57.3%)]. However, percent agreement to within 30, 60, and 90 days was similar for all groups for both first and last sex dates. Conclusions Agreement was high on date of last sex but only moderate on date of first sex. Methods to increase accuracy of reporting of dates of sex may improve STI research. PMID:27100770
The Structure of Policy Networks for Injury and Violence Prevention in 15 US Cities
Jonson-Reid, Melissa; Carothers, Bobbi J.; Fowler, Patrick
2017-01-01
Objectives: Changes in policy can reduce violence and injury; however, little is known about how partnerships among organizations influence policy development, adoption, and implementation. To understand partnerships among organizations working on injury and violence prevention (IVP) policy, we examined IVP policy networks in 15 large US cities. Methods: In summer 2014, we recruited 15 local health departments (LHDs) to participate in the study. They identified an average of 28.9 local partners (SD = 10.2) working on IVP policy. In late 2014, we sent survey questionnaires to 434 organizations, including the 15 LHDs and their local partners, about their partnerships and the importance of each organization to local IVP policy efforts; 319 participated. We used network methods to examine the composition and structure of the policy networks. Results: Each IVP policy network included the LHD and an average of 21.3 (SD = 6.9) local partners. On average, nonprofit organizations constituted 50.7% of networks, followed by government agencies (26.3%), schools and universities (11.8%), coalitions (11.2%), voluntary organizations (9.6%), hospitals (8.5%), foundations (2.2%), and for-profit organizations (0.7%). Government agencies were perceived as important by the highest proportion of partners. Perceived importance was significantly associated with forming partnerships in most networks; odds ratios ranged from 1.07 (95% CI, 1.02-1.13) to 2.35 (95% CI, 1.68-3.28). Organization type was significantly associated with partnership formation in most networks after controlling for an organization’s importance to the network. Conclusions: Several strategies could strengthen local IVP policy networks, including (1) developing connections with partners from sectors that are not well integrated into the networks and (2) encouraging indirect or less formal connections with important but missing partners and partner types. PMID:28426291
Altschuler, Andrea; Ramirez, Michelle; Grant, Marcia; Wendel, Christopher; Hornbrook, Mark C.; Herrinton, Lisa; Krouse, Robert S.
2009-01-01
Objective Some patients with colorectal cancer (CRC) require a permanent ostomy, which changes bodily function and can create psychosocial distress. However, little is known about the influence of men's support on women's psychosocial adjustment to having an ostomy as a result of CRC. Methods Participants initially completed the City of Hope-CRC Quality of Life questionnaire. We then conducted in-depth interviews with 30 female participants. Interview questions focused on body image, gender, and sexuality. Interviews were recorded and transcribed. We used qualitative methods to analyze the interview data and compared global HRQOL quartile scores to the overall ways that women discussed husbands' or partners' support regarding psychosocial adjustments to having ostomies. Results Of 30 participants, 22 were married or partnered at the time of surgery and 8 were single. The non-partnered respondents are not included in this analysis. Of the 22 married/partnered women, 17 described positive support from husbands being central to their psychosocial adjustment, 3 described a lack or withdrawal of support negatively affecting adjustment, and 2 described support as neither positive nor negative. In 17 cases, women's high or low quantitative HRQOL scores matched the positive or negative qualitative findings. There were 3 cases in which there were positive qualitative data and low HRQOL scores, but each of these cases, women reported serious current co-morbidities. Conclusions These findings suggest that the provision or withdrawal of husbands' or partners' support can have a considerable impact on the psychosocial adjustment of female CRC patients with ostomies. These findings appear to be both short- and long-term. Survivorship assessments should include appraisals of women's relationships to spouses/partners. PMID:19448512
Zhai, Jing-Xuan; Cao, Tian-Jie; An, Ji-Yong; Bian, Yong-Tao
2017-11-07
It is a challenging task for fundamental research whether proteins can interact with their partners. Protein self-interaction (SIP) is a special case of PPIs, which plays a key role in the regulation of cellular functions. Due to the limitations of experimental self-interaction identification, it is very important to develop an effective biological tool for predicting SIPs based on protein sequences. In the study, we developed a novel computational method called RVM-AB that combines the Relevance Vector Machine (RVM) model and Average Blocks (AB) for detecting SIPs from protein sequences. Firstly, Average Blocks (AB) feature extraction method is employed to represent protein sequences on a Position Specific Scoring Matrix (PSSM). Secondly, Principal Component Analysis (PCA) method is used to reduce the dimension of AB vector for reducing the influence of noise. Then, by employing the Relevance Vector Machine (RVM) algorithm, the performance of RVM-AB is assessed and compared with the state-of-the-art support vector machine (SVM) classifier and other exiting methods on yeast and human datasets respectively. Using the fivefold test experiment, RVM-AB model achieved very high accuracies of 93.01% and 97.72% on yeast and human datasets respectively, which are significantly better than the method based on SVM classifier and other previous methods. The experimental results proved that the RVM-AB prediction model is efficient and robust. It can be an automatic decision support tool for detecting SIPs. For facilitating extensive studies for future proteomics research, the RVMAB server is freely available for academic use at http://219.219.62.123:8888/SIP_AB. Copyright © 2017 Elsevier Ltd. All rights reserved.
Rosengard, C; Adler, N; Millstein, S; Gurvey, J; Ellen, J
2004-01-01
Objectives: To examine the amount of time adolescents waited to have intercourse with past partners (main and casual), and intentions to delay with future partners. To determine psychosocial factors which predict delay intentions among adolescent males and females with future partners (main and casual). Methods: Adolescent STD clinic attendees were approached before clinical appointments to participate in an interview. Data from 205 participants who had previous experience with both main and casual partners were used in the current study. Results: Adolescents waited less time to have intercourse with most recent casual than with most recent main partners (χ2 = 31.97, p<0.0001). The amount of time waited with past partners was shorter than intended time to wait in future relationships (medians of 1 month v 2 months (main) (t = 3.47, p<0.0010; medians of 2 weeks v 1 month (casual) (t = 6.14, p<0.0001)). Factors influencing intentions to delay intercourse with future main partners differed by sex; males were negatively influenced by importance of sex in relationships, while females were positively influenced by importance of intimacy in relationships, perceived risk of STDs, and health values. Conclusions: Implications for designing interventions for adolescent males and females are discussed. PMID:15054176
Robertson, Angela M; Syvertsen, Jennifer L; Martinez, Gustavo; Rangel, M Gudelia; Palinkas, Lawrence A; Stockman, Jamila K; Ulibarri, Monica D; Strathdee, Steffanie A
2013-01-01
Female sex workers (FSWs) may benefit from pre-exposure prophylaxis (PrEP) including microbicides for HIV prevention. Since adherence is a key factor in PrEP efficacy, we explored microbicide acceptability and potential barriers to use within FSWs' intimate relationships in Tijuana and Ciudad Juárez, Mexico, where HIV prevalence is increasing. FSWs and their verified intimate (non-commercial) male partners completed quantitative and qualitative interviews from 2010 to 2012. Our complementary mixed methods design followed an iterative process to assess microbicide acceptability, explore related relationship dynamics and identify factors associated with concern about male partners' anger regarding microbicide use. Among 185 couples (n=370 individuals), interest in microbicides was high. In qualitative interviews with 28 couples, most participants were enthusiastic about microbicides for sex work contexts but some explained that microbicides could imply mistrust/infidelity within their intimate relationships. In the overall sample, nearly one in six participants (16%) worried that male partners would become angry about microbicides, which was associated with higher self-esteem among FSWs and lower self-esteem and past year conflicts causing injury within relationships among men. HIV prevention interventions should consider intimate relationship dynamics posing potential barriers to PrEP acceptability and adherence, involve male partners and promote risk communication skills.
Protein-Protein Interface Predictions by Data-Driven Methods: A Review
Xue, Li C; Dobbs, Drena; Bonvin, Alexandre M.J.J.; Honavar, Vasant
2015-01-01
Reliably pinpointing which specific amino acid residues form the interface(s) between a protein and its binding partner(s) is critical for understanding the structural and physicochemical determinants of protein recognition and binding affinity, and has wide applications in modeling and validating protein interactions predicted by high-throughput methods, in engineering proteins, and in prioritizing drug targets. Here, we review the basic concepts, principles and recent advances in computational approaches to the analysis and prediction of protein-protein interfaces. We point out caveats for objectively evaluating interface predictors, and discuss various applications of data-driven interface predictors for improving energy model-driven protein-protein docking. Finally, we stress the importance of exploiting binding partner information in reliably predicting interfaces and highlight recent advances in this emerging direction. PMID:26460190
Syvertsen, Jennifer L.; Robertson, Angela M.; Strathdee, Steffanie A; Martinez, Gustavo; Rangel, M. Gudelia; Wagner, Karla D
2014-01-01
Background Studies of injection drug-using couples suggest a gendered performance of risk in which men exert greater control over drug use and render their female partners vulnerable to HIV infection and other negative health outcomes. This study assesses gender roles in injection drug use as practiced among female sex workers and their intimate male partners within a risk environment marked by rapid socioeconomic changes. Methods We draw on quantitative surveys, semi-structured interviews, and ethnographic fieldwork conducted as part of cohort study of HIV/STI risk among female sex workers and their intimate, non-commercial partners along the Mexico-U.S. border. This study employed descriptive statistics and inductive analyses of transcripts and field notes to examine practices related to drug procurement, syringe sharing, and injection assistance among couples in which both partners reported injecting drugs in the past six months. Results Among 156 couples in which both partners injected drugs (n=312), our analyses revealed that women’s roles in drug use were active and multidimensional, and both partners’ injection risk practices represented embodied forms of cooperation and compassion. Women often earned money to purchase drugs and procured drugs to protect their partners from the police. Sharing drugs and syringes and seeking injection assistance were common among couples due to drug market characteristics (e.g., the use of “black tar” heroin that clogs syringes and damages veins). Both women and men provided and received injection assistance, which was typically framed as caring for the partner in need of help. Conclusion Our mixed methods study suggests that in certain risk environments, women are more active participants in injection-related practices than has often been revealed. This participation is shaped by dynamic relationship and structural factors. Our suggestion to consider gendered injection risk as a nuanced and relational process has direct implications for future research and interventions. PMID:24641906
Koblin, Beryl A.; Chesney, Margaret A.; Husnik, Marla J.; Bozeman, Sam; Celum, Connie L.; Buchbinder, Susan; Mayer, Kenneth; McKirnan, David; Judson, Franklyn N.; Huang, Yijian; Coates, Thomas J.
2003-01-01
Objectives. We describe the prevalence of risk behaviors at baseline among men who have sex with men (MSM) who were enrolled in a randomized behavioral intervention trial conducted in 6 US cities. Methods. Data analyses involved MSM who were negative for HIV antibodies and who reported having engaged in anal sex with 1 or more partners in the previous year. Results. Among 4295 men, 48.0% and 54.9%, respectively, reported unprotected receptive and insertive anal sex in the previous 6 months. Unprotected sex was significantly more likely with 1 primary partner or multiple partners than with 1 nonprimary partner. Drug and alcohol use were significantly associated with unprotected anal sex. Conclusions. Our findings support the continued need for effective intervention strategies for MSM that address relationship status, serostatus of partners, and drug and alcohol use. PMID:12773357
Partner Caregiving in Older Cohabiting Couples
2011-01-01
Objectives. Despite the rapidly increasing prevalence of cohabitation among older adults, the caregiving literature has exclusively focused on formally married individuals. Extending prior work on intra-couple care, this study contrasts frail cohabitors’ patterns of care receipt from a partner to that of frail spouses. Methods. Using nationally representative panel data from the Health and Retirement Study (2000, 2002, 2004, and 2006), we estimate random effects cross-sectional times series models predicting frail cohabitors’ likelihood of receiving partner care compared with their married counterparts’. Conditional on the receipt of intra-couple care, we also examine differences in marital and nonmarital partners’ caregiving hours and caregiving involvement relative to other helpers. Results. Net of sociodemographic, disability, and comorbidity factors, we find that cohabitors are less likely to receive partner care than married individuals. However, caregiving nonmarital partners provide as many hours of care as spouses while providing a substantially larger share of disabled respondents’ care than marital partners. Discussion. Cohabitation and marriage have distinct implications for older adults’ patterns of partner care receipt. This study adds weight to a growing body of research emphasizing the importance of accounting for older adults’ nontraditional union forms and of examining the ramifications of cohabitation for older adults’ well-being. PMID:21482588
National Needs of Family Planning Among US Men Aged 15 to 44 Years
Gibbs, Susannah E.; Choiriyyah, Ifta; Sonenstein, Freya L.; Astone, Nan M.; Pleck, Joseph H.; Dariotis, Jacinda K.
2016-01-01
Objectives. To estimate national need for family planning services among men in the United States according to background characteristics, access to care, receipt of services, and contraception use. Methods. We used weighted data from the 2006–2010 National Survey of Family Growth to estimate the percentage of men aged 15 to 44 years (n = 10 395) in need of family planning, based on sexual behavior, fecundity, and not trying to get pregnant with his partner. Results. Overall, 60% of men were in need of family planning, defined as those who ever had vaginal sex, were fecund, and had fecund partner(s) who were not trying to get pregnant with partner or partner(s) were not currently pregnant. The greatest need was among young and unmarried men. Most men in need of family planning had access to care, but few reported receiving family planning services (< 19%), consistently using condoms (26%), or having partners consistently using contraception (41%). Conclusions. The need for engaging men aged 15 to 44 years in family planning education and care is substantial and largely unmet despite national public health priorities to include men in reducing unintended pregnancies. PMID:26890180
LINEs, SINEs and other retroelements: do birds of a feather flock together?
Roy-Engel, Astrid M
2012-01-01
Mobile elements account for almost half of the mass of the human genome. Only the retroelements from the non-LTR (long terminal repeat) retrotransposon family, which include the LINE-1 (L1) and its non-autonomous partners, are currently active and contributing to new insertions. Although these elements seem to share the same basic amplification mechanism, the activity and success of the different types of retroelements varies. For example, Alu-induced mutagenesis is responsible for the majority of the documented instances of human disease induced by insertion of retroelements. Using copy number in mammals as an indicator, some SINEs have been vastly more successful than other retroelements, such as the retropseudogenes and even L1, likely due to differences in post-insertion selection and ability to overcome cellular controls. SINE and LINE integration can be differentially influenced by cellular factors, indicating some differences between in their amplification mechanisms. We focus on the known aspects of this group of retroelements and highlight their similarities and differences that may significantly influence their biological impact.
LINEs, SINEs and other retroelements: do birds of a feather flock together?
Roy-Engel, Astrid M.
2012-01-01
Mobile elements account for almost half of the mass of the human genome. Only the retroelements from the non-LTR (long terminal repeat) retrotransposon family, which include the LINE-1 (L1) and its non-autonomous partners, are currently active and contributing to new insertions. Although these elements seem to share the same basic amplification mechanism, the activity and success of the different types of retroelements varies. For example, Alu-induced mutagenesis is responsible for the majority of the documented instances of human disease induced by insertion of retroelements. Using copy number in mammals as an indicator, some SINEs have been vastly more successful than other retroelements, such as the retropseudogenes and even L1, likely due to differences in post-insertion selection and ability to overcome cellular controls. SINE and LINE integration can be differentially influenced by cellular factors, indicating some differences between in their amplification mechanisms. We focus on the known aspects of this group of retroelements and highlight their similarities and differences that may significantly influence their biological impact. PMID:22201808
P21-activated kinase 4--not just one of the PAK.
Dart, Anna E; Wells, Claire M
2013-01-01
P21-activated kinase 4 (PAK4) is a member of the p21-activated kinase (PAK) family. Historically much of the attention has been directed towards founding family member PAK1 but the focus is now shifting towards PAK4. It is a pluripotent serine/threonine kinase traditionally recognised as a downstream effector of the Rho-family GTPases. However, emerging research over the last few years has revealed that this kinase is much more than that. New findings have shed light on the molecular mechanism of PAK4 activation and how this kinase is critical for early development. Moreover, the number of PAK4 substrates and binding partners is rapidly expanding highlighting the increasing amount of cellular functions controlled by PAK4. We propose that PAK4 should be considered a signalling integrator regulating numerous fundamental cellular processes, including actin cytoskeletal dynamics, cell morphology and motility, cell survival, embryonic development, immune defence and oncogenic transformation. This review will outline our current understanding of PAK4 biology. Copyright © 2013 Elsevier GmbH. All rights reserved.
Roles and regulations of the ETS transcription factor ELF4/MEF
Suico, Mary Ann; Shuto, Tsuyoshi; Kai, Hirofumi
2017-01-01
Abstract Most E26 transformation-specific (ETS) transcription factors are involved in the pathogenesis and progression of cancer. This is in part due to the roles of ETS transcription factors in basic biological processes such as growth, proliferation, and differentiation, and also because of their regulatory functions that have physiological relevance in tumorigenesis, immunity, and basal cellular homoeostasis. A member of the E74-like factor (ELF) subfamily of the ETS transcription factor family—myeloid elf-1-like factor (MEF), designated as ELF4—has been shown to be critically involved in immune response and signalling, osteogenesis, adipogenesis, cancer, and stem cell quiescence. ELF4 carries out these functions as a transcriptional activator or through interactions with its partner proteins. Mutations in ELF4 cause aberrant interactions and induce downstream processes that may lead to diseased cells. Knowing how ELF4 impinges on certain cellular processes and how it is regulated in the cells can lead to a better understanding of the physiological and pathological consequences of modulated ELF4 activity. PMID:27932483
Chen, Haiqi; Li, Michelle W.M.
2018-01-01
Drebrin is a family of actin-binding proteins with two known members called drebrin A and E. Apart from the ability to stabilize F-actin microfilaments via their actin-binding domains near the N-terminus, drebrin also regulates multiple cellular functions due to its unique ability to recruit multiple binding partners to a specific cellular domain, such as the seminiferous epithelium during the epithelial cycle of spermatogenesis. Recent studies have illustrated the role of drebrin E in the testis during spermatogenesis in particular via its ability to recruit branched actin polymerization protein known as actin-related protein 3 (Arp3), illustrating its involvement in modifying the organization of actin microfilaments at the ectoplasmic specialization (ES) which includes the testis-specific anchoring junction at the Sertoli-spermatid (apical ES) interface and at the Sertoli cell-cell (basal ES) interface. These data are carefully evaluated in light of other recent findings herein regarding the role of drebrin in actin filament organization at the ES. We also provide the hypothetical model regarding its involvement in germ cell transport during the epithelial cycle in the seminiferous epithelium to support spermatogenesis. PMID:28865027
Cellular projections from sensory hair cells form polarity-specific scaffolds during synaptogenesis
Dow, Eliot; Siletti, Kimberly
2015-01-01
The assembly of a nervous system requires the extension of axons and dendrites to specific regions where they are matched with appropriate synaptic targets. Although the cues that guide long-range outgrowth have been characterized extensively, additional mechanisms are required to explain short-range guidance in neural development. Using a complementary combination of time-lapse imaging by fluorescence confocal microscopy and serial block-face electron microscopy, we identified a novel type of presynaptic projection that participates in the assembly of the vertebrate nervous system. Synapse formation by each hair cell of the zebrafish's lateral line occurs during a particular interval after the cell's birth. During the same period, projections emerge from the cellular soma, extending toward a specific subpopulation of mature hair cells and interacting with polarity-specific afferent nerve terminals. The terminals then extend along the projections to reach appropriately matched presynaptic sites, after which the projections recede. Our results suggest that presynaptic projections act as transient scaffolds for short-range partner matching, a mechanism that may occur elsewhere in the nervous system. PMID:25995190
Lamina-independent lamins in the nuclear interior serve important functions.
Dechat, T; Gesson, K; Foisner, R
2010-01-01
Nuclear lamins were originally described as the main constituents of the nuclear lamina, a filamentous meshwork closely associated with the inner nuclear membrane. However, within recent years, it has become increasingly evident that a fraction of lamins also resides throughout the nuclear interior. As intermediate-filament-type proteins, lamins have been suggested to fulfill mainly structural functions such as providing shape and mechanical stability to the nucleus. But recent findings show that both peripheral and nucleoplasmic lamins also have important roles in essential cellular processes such as transcription, DNA replication, cell cycle progression, and chromatin organization. Furthermore, more than 300 mutations in the gene encoding A-type lamins have been associated with several human diseases now generally termed laminopathies and comprising muscular dystrophies, lipodystrophies, cardiomyopathies, and premature aging diseases. This review focuses on the lamina-independent pool of lamins in the nuclear interior, which surprisingly has not been studied in much detail so far. We discuss the properties and regulation of nucleoplasmic lamins during the cell cycle, their interaction partners, and their potential involvement in cellular processes and the development of laminopathies.
Goodwin, Edward C.; Lipovsky, Alex; Inoue, Takamasa; Magaldi, Thomas G.; Edwards, Anne P. B.; Van Goor, Kristin E. Y.; Paton, Adrienne W.; Paton, James C.; Atwood, Walter J.; Tsai, Billy; DiMaio, Daniel
2011-01-01
ABSTRACT Simian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required for SV40 infection. SV40 infection was specifically inhibited by up to 50-fold by knockdown of four different DNAJ molecular cochaperones or by inhibition of BiP, the Hsp70 partner of DNAJB11. These proteins were not required for the initiation of capsid disassembly, but knockdown markedly inhibited SV40 exit from the ER. In addition, BiP formed a complex with SV40 capsids in the ER in a DNAJB11-dependent fashion. These experiments identify five new cellular proteins required for SV40 infection and suggest that the binding of BiP to the capsid is required for ER exit. Further studies of these proteins will provide insight into the molecular mechanisms of polyomavirus infection and ER function. PMID:21673190
Tremblay, Joël; Dufour, Magali; Bertrand, Karine; Blanchette-Martin, Nadine; Ferland, Francine; Savard, Annie-Claude; Saint-Jacques, Marianne; Côté, Mélissa
2017-01-01
Context: Couple treatment for pathological gambling is an innovative strategy. There are some results supporting its potential effectiveness, but little is known about the subjective experiences of the participants. Objective: The aim of this article is to document the experiences of gamblers and their partners participating in one of two treatments, namely individual or couple. Method: In a study aiming to evaluate the efficacy of the Integrative Couple Treatment for Pathological Gambling (ICT-PG), couples who were entering specialized treatment for the addiction of one member who was a pathological gambler were randomly assigned to individual or ICT-PG. Nine months after their admission to treatment, gamblers and partners ( n = 21 couples; n = 13 ICT-PG; n = 8 individual treatment) were interviewed in semi-structured interviews. A sequenced thematization method was used to extract the major themes. Results: This study highlighted five major themes in the therapeutic process noted by the gamblers and their partners mainly after the couple treatment but also partly through the individual therapy. These were: (1) the gamblers' anxiety about having to reveal their gambling problems in couple therapy; (2) the wish to develop a mutually beneficial understanding of gambling and its effects on the partners in the two types of treatments; (3) the transformation of negative attributions through a more effective intra-couple communication fostered by the couple therapy; (4) the partners' contribution to changes in gambling behavior and prevention of relapses, which were both better supported in couple therapy; and (5) the interpersonal nature of gambling and its connections with the couples' relationship. However, gamblers who were in individual treatment were more likely to mention that their partners' involvement was not necessary. Participants likewise made a few recommendations about the conditions underlying the choice of one treatment method or the other. Discussion: Participants reported satisfaction with both treatment models, but their experience was more positive in couple treatment. Complementary benefits emerged from each form of treatment, which points to future treatments involving both types. Future research should explore both the couple processes associated with attempts to stop pathological gambling and the various ways of involving partners in the gamblers' treatment.
Tremblay, Joël; Dufour, Magali; Bertrand, Karine; Blanchette-Martin, Nadine; Ferland, Francine; Savard, Annie-Claude; Saint-Jacques, Marianne; Côté, Mélissa
2018-01-01
Context: Couple treatment for pathological gambling is an innovative strategy. There are some results supporting its potential effectiveness, but little is known about the subjective experiences of the participants. Objective: The aim of this article is to document the experiences of gamblers and their partners participating in one of two treatments, namely individual or couple. Method: In a study aiming to evaluate the efficacy of the Integrative Couple Treatment for Pathological Gambling (ICT-PG), couples who were entering specialized treatment for the addiction of one member who was a pathological gambler were randomly assigned to individual or ICT-PG. Nine months after their admission to treatment, gamblers and partners (n = 21 couples; n = 13 ICT-PG; n = 8 individual treatment) were interviewed in semi-structured interviews. A sequenced thematization method was used to extract the major themes. Results: This study highlighted five major themes in the therapeutic process noted by the gamblers and their partners mainly after the couple treatment but also partly through the individual therapy. These were: (1) the gamblers' anxiety about having to reveal their gambling problems in couple therapy; (2) the wish to develop a mutually beneficial understanding of gambling and its effects on the partners in the two types of treatments; (3) the transformation of negative attributions through a more effective intra-couple communication fostered by the couple therapy; (4) the partners' contribution to changes in gambling behavior and prevention of relapses, which were both better supported in couple therapy; and (5) the interpersonal nature of gambling and its connections with the couples' relationship. However, gamblers who were in individual treatment were more likely to mention that their partners' involvement was not necessary. Participants likewise made a few recommendations about the conditions underlying the choice of one treatment method or the other. Discussion: Participants reported satisfaction with both treatment models, but their experience was more positive in couple treatment. Complementary benefits emerged from each form of treatment, which points to future treatments involving both types. Future research should explore both the couple processes associated with attempts to stop pathological gambling and the various ways of involving partners in the gamblers' treatment. PMID:29416520
Molecular origin of the binding of WWOX tumor suppressor to ErbB4 receptor tyrosine kinase.
Schuchardt, Brett J; Bhat, Vikas; Mikles, David C; McDonald, Caleb B; Sudol, Marius; Farooq, Amjad
2013-12-23
The ability of WWOX tumor suppressor to physically associate with the intracellular domain (ICD) of ErbB4 receptor tyrosine kinase is believed to play a central role in downregulating the transcriptional function of the latter. Herein, using various biophysical methods, we show that while the WW1 domain of WWOX binds to PPXY motifs located within the ICD of ErbB4 in a physiologically relevant manner, the WW2 domain does not. Importantly, while the WW1 domain absolutely requires the integrity of the PPXY consensus sequence, nonconsensus residues within and flanking this motif do not appear to be critical for binding. This strongly suggests that the WW1 domain of WWOX is rather promiscuous toward its cellular partners. We also provide evidence that the lack of binding of the WW2 domain of WWOX to PPXY motifs is due to the replacement of a signature tryptophan, lining the hydrophobic ligand binding groove, with tyrosine (Y85). Consistent with this notion, the Y85W substitution within the WW2 domain exquisitely restores its binding to PPXY motifs in a manner akin to the binding of the WW1 domain of WWOX. Of particular significance is the observation that the WW2 domain augments the binding of the WW1 domain to ErbB4, implying that the former serves as a chaperone within the context of the WW1-WW2 tandem module of WWOX in agreement with our findings reported previously. Altogether, our study sheds new light on the molecular basis of an important WW-ligand interaction involved in mediating a plethora of cellular processes.
Molecular Origin of the Binding of WWOX Tumor Suppressor to ErbB4 Receptor Tyrosine Kinase
Schuchardt, Brett J.; Bhat, Vikas; Mikles, David C.; McDonald, Caleb B.; Sudol, Marius; Farooq, Amjad
2014-01-01
The ability of WWOX tumor suppressor to physically associate with the intracellular domain (ICD) of ErbB4 receptor tyrosine kinase is believed to play a central role in down-regulating the transcriptional function of the latter. Herein, using various biophysical methods, we show that while the WW1 domain of WWOX binds to PPXY motifs located within the ICD of ErbB4 in a physiologically-relevant manner, the WW2 domain does not. Importantly, while the WW1 domain absolutely requires the integrity of the PPXY consensus sequence, non-consensus residues within and flanking this motif do not appear to be critical for binding. This strongly suggests that the WW1 domain of WWOX is rather promiscuous toward its cellular partners. We also provide evidence that the lack of binding of WW2 domain of WWOX to PPXY motifs is due to the replacement of a signature tryptophan, lining the hydrophobic ligand binding groove, with tyrosine (Y85). Consistent with this notion, the Y85W substitution within the WW2 domain exquisitely restores its binding to PPXY motifs in a manner akin to the binding of WW1 domain of WWOX. Of particular significance is the observation that WW2 domain augments the binding of WW1 domain to ErbB4, implying that the former serves as a chaperone within the context of the WW1–WW2 tandem module of WWOX in agreement with our findings reported previously. Taken together, our study sheds new light on the molecular basis of an important WW-ligand interaction involved in mediating a plethora of cellular processes. PMID:24308844
MacPhail, Catherine; Pettifor, Audrey E; Pascoe, Sophie; Rees, Helen V
2007-10-28
Adolescent reproductive health has not continued to receive the attention it deserves since the start of the HIV epidemic. In South Africa, high numbers of adolescent women report pregnancies that are unwanted and yet few have accessed available termination of pregnancy services. Enabling contraception use is vital for meeting the goals of HIV prevention. A nationally representative survey of South African 15-24 year olds was undertaken. Participants completed a questionnaire on sexual behaviour and provided an oral fluid sample for HIV testing. Analysis of the data was restricted to women (n = 6217), particularly those who reported being sexual active in the last 12 months (n = 3618) and was conducted using svy methods in the program STATA 8.0 to take account of sampling methods. Univariate and multivariate analyses were conducted to explore factors associated with contraceptive use. Two thirds of all women reported having ever been sexually active and among these 87% were sexually active in the past 12 months. Among women who reported currently being sexually active, 52.2% reported using contraceptives. There was evidence of association between contraceptive use and being employed or a student (vs unemployed); fewer sex partners; type of last sex partner; having talked to last partner about condom use and having ever been pregnant. Specific emphasis must be placed on encouraging young women to use contraceptive methods that offer protection against pregnancy and STIs/HIV. Our consistent finding of a relationship between discussing condom use with partners and condom use indicates the importance of involvement of male partners in women's contraceptive decisions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dilling, Thomas J., E-mail: Thomas.Dilling@moffitt.org; Bae, Kyounghwa; Paulus, Rebecca
Purpose: We investigated the impact of race, in conjunction with gender and partner status, on locoregional control (LRC) and overall survival (OS) in three head and neck trials conducted by the Radiation Therapy Oncology Group (RTOG). Methods and Materials: Patients from RTOG studies 9003, 9111, and 9703 were included. Patients were stratified by treatment arms. Covariates of interest were partner status (partnered vs. non-partnered), race (white vs. non-white), and sex (female vs. male). Chi-square testing demonstrated homogeneity across treatment arms. Hazards ratio (HR) was used to estimate time to event outcome. Unadjusted and adjusted HRs were calculated for all covariatesmore » with associated 95% confidence intervals (CIs) and p values. Results: A total of 1,736 patients were analyzed. Unpartnered males had inferior OS rates compared to partnered females (adjusted HR = 1.22, 95% CI, 1.09-1.36), partnered males (adjusted HR = 1.20, 95% CI, 1.09-1.28), and unpartnered females (adjusted HR = 1.20, 95% CI, 1.09-1.32). White females had superior OS compared with white males, non-white females, and non-white males. Non-white males had inferior OS compared to white males. Partnered whites had improved OS relative to partnered non-white, unpartnered white, and unpartnered non-white patients. Unpartnered males had inferior LRC compared to partnered males (adjusted HR = 1.26, 95% CI, 1.09-1.46) and unpartnered females (adjusted HR = 1.30, 95% CI, 1.05-1.62). White females had LRC superior to non-white males and females. White males had improved LRC compared to non-white males. Partnered whites had improved LRC compared to partnered and unpartnered non-white patients. Unpartnered whites had improved LRC compared to unpartnered non-whites. Conclusions: Race, gender, and partner status had impacts on both OS and locoregional failure, both singly and in combination.« less
Induced abortion, pregnancy loss and intimate partner violence in Tanzania: a population based study
2012-01-01
Background Violence by an intimate partner is increasingly recognized as an important public and reproductive health issue. The aim of this study is to investigate the extent to which physical and/or sexual intimate partner violence is associated with induced abortion and pregnancy loss from other causes and to compare this with other, more commonly recognized explanatory factors. Methods This study analyzes the data of the Tanzania section of the WHO Multi-Country Study on Women's Health and Domestic Violence, a large population-based cross-sectional survey of women of reproductive age in Dar es Salaam and Mbeya, Tanzania, conducted from 2001 to 2002. All women who answered positively to at least one of the questions about specific acts of physical or sexual violence committed by a partner towards her at any point in her life were considered to have experienced intimate partner violence. Associations between self reported induced abortion and pregnancy loss with intimate partner violence were analysed using multiple regression models. Results Lifetime physical and/or sexual intimate partner violence was reported by 41% and 56% of ever partnered, ever pregnant women in Dar es Salaam and Mbeya respectively. Among the ever pregnant, ever partnered women, 23% experienced involuntary pregnancy loss, while 7% reported induced abortion. Even after adjusting for other explanatory factors, women who experienced intimate partner violence were 1.6 (95%CI: 1.06,1.60) times more likely to report an pregnancy loss and 1.9 (95%CI: 1.30,2.89) times more likely to report an induced abortion. Intimate partner violence had a stronger influence on induced abortion and pregnancy loss than women's age, socio-economic status, and number of live born children. Conclusions Intimate partner violence is likely to be an important influence on levels of induced abortion and pregnancy loss in Tanzania. Preventing intimate partner violence may therefore be beneficial for maternal health and pregnancy outcomes. PMID:22390254
Wang, Sijia; Song, Dandan; Huang, Wen; He, Huan; Wang, Min; Manning, David; Zaller, Nickolas; Zhang, Hongbo; Operario, Don
2015-04-01
Previous studies have reported that approximately 30% of men who have sex with men (MSM) in China have concurrent female partners. Men who have sex with men and women (MSMW) might "bridge" HIV transmission to their female sex partners. This study aimed to explore (a) motivations for why MSMW in China engage in relationships and sexual behaviors with female partners; (b) patterns of sexual behaviors and condom use between MSMW and their female partners; and (c) barriers to and strategies for encouraging MSMW and their female partners to undergo HIV testing. The authors conducted in-depth interviews with 30 MSMW in two urban cities in China, Guangzhou and Chengdu, and used thematic analysis methods to code and interpret the data. MSMW described family, social, and workplace pressures to have a female partner, and expressed futility about their ability to form stable same-sex relationships. Although participants reported concern about the risk of personally acquiring and transmitting HIV or other sexually transmitted infections (STIs) to their female partners, they described the challenges to using condoms with female partners. HIV-positive participants described how stigma restricted their ability to disclose their HIV status to female partners, and HIV-negative participants displayed less immediate concern about the need for female partners to undergo HIV testing. Participants described a range of possible strategies to encourage HIV testing among female partners. These findings highlight the urgent need for HIV risk reduction and testing interventions for Chinese MSMW in the context of heterosexual partnerships, and they also underscore the additional need for privacy and cultural sensitivity when designing future studies.
It's the Motive That Counts: Perceived Sacrifice Motives and Gratitude in Romantic Relationships.
Visserman, Mariko L; Righetti, Francesca; Impett, Emily A; Keltner, Dacher; Van Lange, Paul A M
2017-06-12
Gratitude is robustly linked to many positive outcomes for individuals and relationships (e.g., greater life and relationship satisfaction). However, little is known about how romantic partners come to feel grateful for each other's pro-relational acts, such as when a partner makes a sacrifice. The present research examines how perceptions of partner sacrifice motives evoke gratitude. We distinguish between partner, relationship, and self-focused motives, and how they are guided by approach or avoidance orientations. We expected that perceiving a partner to sacrifice for partner-focused approach motives (i.e., to promote the partner's well-being) should evoke gratitude, as this type of motive may signal a genuine departure from self-interest. Moreover, we expected these motives to provoke greater perceptions of partner responsiveness, which should partially explain why they elicit gratitude. In contrast, perceiving a partner to sacrifice for relationship-focused motives (e.g., to promote the well-being of the relationship), or self-focused motives (e.g., to feel good about oneself), should not evoke gratitude-irrespective of an approach or avoidance orientation-as these motives may, to some extent, be perceived as tainted by self-interest. Two studies of romantic couples (N = 413), using diary methods (Studies 1 and 2) and having couples converse about a major sacrifice in the laboratory (Study 2), consistently showed that perceived partner-focused approach motives promote gratitude and that this association is partly mediated by perceived partner responsiveness. In contrast, relationship and self-focused motives (approach and avoidance oriented) were not associated with gratitude. Implications regarding perceiving and displaying sacrifice motives are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Gatski, Megan; Mena, Leandro; Levison, Judy; Clark, Rebecca A.; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan L.; Martin, David H.; Kissinger, Patricia
2013-01-01
Background Repeat infections with Trichomonas vaginalis (TV) among human immunodeficiency virus (HIV)-infected women are common and may increase the risk of HIV transmission. Patient delivered partner treatment (PDPT) has been shown to reduce repeat infections of other sexually transmitted diseases. The purpose of this study was to evaluate adherence to PDPT and possible causes of repeat TV infection among HIV-infected women. Methods A multicentered cohort study was conducted in 3 US cities. Women coinfected with HIV and TV were treated with metro-nidazole and given treatment to deliver to all reported sex partners. A test-of-cure visit was conducted 6 to 12 days post index treatment completion and behavioral data were collected. Results Of 252 women (mean age = 40 years, s.d. 9.1) enrolled, 92.5% were black, 26.2% had CD4 cell counts <200/mm3, 34.1% had plasma viral loads >10,000 copies, 58.3% were taking antiretrovial therapy, and 15.1% had multiple partners. Of the 183 women with partners at baseline, 75.4% provided PDPT to all partners and 61.7% reported they were sure all of their partners took the medication. Factors associated with not giving medications to all partner(s) were multiple sex partners, being single, and having at least one partner unaware of the index woman’s HIV status. At test-of-cure, 10.3% were TV-positive and 16.7% reported having sex since baseline. Of the 24 repeat infections, 21 (87.5%) reported adherence to medication and no sexual exposure. Conclusion HIV-infected women with TV reported high adherence to PDPT, and treatment failure was the most common probable cause of repeat infection. PMID:20502393
Estcourt, Claudia S; Sutcliffe, Lorna J; Copas, Andrew; Mercer, Catherine H; Roberts, Tracy E; Jackson, Louise J; Symonds, Merle; Tickle, Laura; Muniina, Pamela; Rait, Greta; Johnson, Anne M; Aderogba, Kazeem; Creighton, Sarah; Cassell, Jackie A
2015-01-01
Background Accelerated partner therapy (APT) is a promising partner notification (PN) intervention in specialist sexual health clinic attenders. To address its applicability in primary care, we undertook a pilot randomised controlled trial (RCT) of two APT models in community settings. Methods Three-arm pilot RCT of two adjunct APT interventions: APTHotline (telephone assessment of partner(s) plus standard PN) and APTPharmacy (community pharmacist assessment of partner(s) plus routine PN), versus standard PN alone (patient referral). Index patients were women diagnosed with genital chlamydia in 12 general practices and three community contraception and sexual health (CASH) services in London and south coast of England, randomised between 1 September 2011 and 31 July 2013. Results 199 women described 339 male partners, of whom 313 were reported by the index as contactable. The proportions of contactable partners considered treated within 6 weeks of index diagnosis were APTHotline 39/111 (35%), APTPharmacy 46/100 (46%), standard patient referral 46/102 (45%). Among treated partners, 8/39 (21%) in APTHotline arm were treated via hotline and 14/46 (30%) in APTPharmacy arm were treated via pharmacy. Conclusions The two novel primary care APT models were acceptable, feasible, compliant with regulations and capable of achieving acceptable outcomes within a pilot RCT but intervention uptake was low. Although addition of these interventions to standard PN did not result in a difference between arms, overall PN uptake was higher than previously reported in similar settings, probably as a result of introducing a formal evaluation. Recruitment to an individually randomised trial proved challenging and full evaluation will likely require service-level randomisation. Trial registration number Registered UK Clinical Research Network Study Portfolio id number 10123. PMID:26019232
Reisner, Sari L.; Gamarel, Kristi E.; Nemoto, Tooru; Operario, Don
2014-01-01
Background Despite evidence that interpersonal processes shape health behaviors, research concerning the dyadic effects of gender minority stressors on substance use behaviors of transgender people is scarce. The objective of this study was to use dyadic analysis to examine whether transgender discrimination was associated with substance use among transgender women and their male partners. Methods Transgender women and their male partners (N=191 couples; N=382 individuals) completed questionnaires. Participants’ mean age was 37.1; 79.1% were racial/ethnic minority; 61.3% earned <$500 per-month. The mean relationship duration was 37.9 months. Actor-Partner Interdependence Models were used to examine the associations between transgender-related discrimination and past 30-day non-marijuana illicit drug use adjusting for age, relationship length, financial hardship, and depressive distress among partners in these dyads. Results Illicit drug use was reported by 31.4% of transgender women and 25.1% of their male partners. Perceived transgender discrimination was independently associated with increased odds of illicit drug use for transgender women (actor effect) but not for their male partners. Financial hardship statistically predicted drug use for both partners (actor effects). There were no partner effects for financial hardship on drug use. Overall, 34.5% of dyads had discrepant substance use. Discrimination scores of male partners differentiated dyads who reported discrepant substance use. Discussion Gender minority stressors are critical to understanding substance use among transgender women and their male partners. Integrating socioeconomic status into gender minority stress frameworks is essential. Results have implications for substance use prevention and treatment, including the need to incorporate gender minority stressors into interventions. PMID:25642440
Perez-Brumer, Amaya G.; Oldenburg, Catherine E.; Segura, Eddy R.; Sanchez, Jorge; Lama, Javier R.; Clark, Jesse L.
2016-01-01
Objectives Partner notification (PN) following STI diagnosis is a key strategy for controlling HIV/STI transmission. Anonymous partnerships are an important barrier to PN and often associated with high-risk sexual behaviour. Limited research has examined the profile of MSM and TW who engage in anonymous sex. To better understand anonymous partnership practices in Lima, Peru, we assessed participant- and partnership-level characteristics associated with anonymous sex among a sample of MSM and TW recently diagnosed with HIV/STI. Methods MSM and TW diagnosed with HIV/STI within the past month completed a cross-sectional survey regarding anticipated PN practices. Participants reported sexual partnership types and characteristics of up to 3 of their most recent partners. Using a Poisson generalised estimating equation (GEE) model we assessed participant- and partnership-level characteristics associated with anonymous partnerships. Results Among 395 MSM and TW with HIV/STI, 36.0% reported at least one anonymous sexual partner in the past three months (mean of 8.6 anonymous partners per participant; SD 17.0). Of the 971 partnerships reported, 118 (12.2%) were anonymous and the majority (84.8%) were with male partners, followed by 11.0% with female partners, and 4.2% with transgender/travesti partners. Partner-level characteristics associated with increased likelihood of having an anonymous partner included female (aPR 2.28, 95% CI 1.05 to 4.95, P=0.04) or transgender/travesti (aPR 4.03, 95% CI 1.51 to 10.78, P=0.006) partner gender. Conclusions By assessing both individual- and dyadic-level factors, these results represent an important step in understanding the complexity of partnership interactions and developing alternative partner notification strategies for Latin America. PMID:26912910
Wang, Sijia; Song, Dandan; Huang, Wen; He, Huan; Wang, Min; Manning, David; Zaller, Nickolas; Zhang, Hongbo; Operario, Don
2016-01-01
Previous studies have reported that approximately 30% of men who have sex with men (MSM) in China have concurrent female partners. Men who have sex with men and women (MSMW) might “bridge” HIV transmission to their female sex partners. This study aimed to explore (a) motivations for why MSMW in China engage in relationships and sexual behaviors with female partners; (b) patterns of sexual behaviors and condom use between MSMW and their female partners; and (c) barriers to and strategies for encouraging MSMW and their female partners to undergo HIV testing. The authors conducted in-depth interviews with 30 MSMW in two urban cities in China, Guangzhou and Chengdu, and used thematic analysis methods to code and interpret the data. MSMW described family, social, and workplace pressures to have a female partner, and expressed futility about their ability to form stable same-sex relationships. Although participants reported concern about the risk of personally acquiring and transmitting HIV or other sexually transmitted infections (STIs) to their female partners, they described the challenges to using condoms with female partners. HIV-positive participants described how stigma restricted their ability to disclose their HIV status to female partners, and HIV-negative participants displayed less immediate concern about the need for female partners to undergo HIV testing. Participants described a range of possible strategies to encourage HIV testing among female partners. These findings highlight the urgent need for HIV risk reduction and testing interventions for Chinese MSMW in the context of heterosexual partnerships, and they also under-score the additional need for privacy and cultural sensitivity when designing future studies. PMID:25915698
Treatment of sexual dysfunctions in male-only groups: predicting outcome.
Dekker, J; Dronkers, J; Staffeleu, J
1985-01-01
Forty men complaining of sexual dysfunctions were treated in male-only groups, using RET, masturbation exercises and social skills training. Sexual functioning improved and social anxiety decreased. Combining these data with previously reported data on 21 men, we tried to predict treatment outcome. Sexual functioning of men with a steady partner and men with varying partners improved; in men without partner(s) no effect could be demonstrated, probably due to a methodological artifact. Inhibited sexual desire was associated with a poor outcome. Several other variables (among them type of dysfunction, social anxiety, age, educational level) did not predict improvement of sexual functioning. This method seems to provide adequate treatment for various complaints of men with quite different backgrounds.
The Use of Technology for STD Partner Services in the United States: A Structured Review.
Kachur, Rachel; Hall, Wendasha; Coor, Alexandra; Kinsey, Jennine; Collins, Dayne; Strona, F V
2018-05-01
Since the late 1990s, health departments and STD programs throughout the U.S. have used technologies, such as the internet and mobile phones, to provide services to persons with a sexually transmitted infection, including HIV, and their sex partners, also known as partner services. This study reviewed the published literature to assess and compare partner services outcomes as a result of using technology and to calculate cost savings through cases averted. We conducted a structured literature review of all U.S. studies that examined the use of technology to notify persons exposed to an STD (syphilis, chlamydia, gonorrhea), including HIV, by health care professionals in the U.S. from 2000 to 2017. Outcome measures, including the number of the number of partners notified, screened or tested; and new positives identified, were captured and cost savings were calculated, when data were available. Seven studies were identified. Methods used for partner services differed across studies, although email was the primary mode in 6 (83%) of the 7 studies. Only 2 of the 7 studies compared use of technology for partner services to traditional partner services. Between 10% and 97% of partners were successfully notified of their exposure through the use of technology and between 34% and 81% were screened or tested. Five studies reported on new infections identified, which ranged from 3-19. Use of technology for partner serves saved programs between $22,795 and $45,362 in direct and indirect medical costs. Use of technology for partner services increased the number of partners notified, screened or tested, and new infections found. Importantly, the use of technology allowed programs to reach partners who otherwise would not have been notified of their exposure to an STD or HIV. Improved response times and time to treatment were also seen as was re-engagement into care for previous HIV positive patients. Data and outcome measures across the studies were not standardized, making it difficult to generalize conclusions. Although not a replacement for traditional partner services, the use of technology enhances partner service outcomes.
ERIC Educational Resources Information Center
McDonald, Renee; Jouriles, Ernest N.; Tart, Candyce D.; Minze, Laura C.
2009-01-01
Objective: This research examined whether additional forms of family violence (partner-child aggression, mother-child aggression, and women's intimate partner violence [IPV]) contribute to children's adjustment problems in families characterized by men's severe violence toward women. Methods: Participants were 258 children and their mothers…
The Effective Methods for Providing Preconception Health Education
ERIC Educational Resources Information Center
Thompson, Terri Lynn
2017-01-01
Background: Infant mortality and maternal deaths are steadily increasing in the United States. Infant mortality and maternal deaths may be preventable if education is offered to the woman and her partner prior to conception. Preconception health education is not routinely addressed with a woman and her partner in routine visits to a health care…
Adolescent Contraceptive Use and Communication: Changes over a Decade.
ERIC Educational Resources Information Center
Poppen, Paul J.
1994-01-01
Compared sexual experiences of 186 college students in 1979 to those of 215 college students in 1989. Found that self-reported condom use increased over decade. Percentage of respondents using any method of contraception and percentage who discussed contraception with partner increased from first to current partner but did not increase between…
Risk of Intimate Partner Violence among Young Adult Males with Childhood ADHD
ERIC Educational Resources Information Center
Wymbs, Brian; Molina, Brooke; Pelham, William; Cheong, JeeWon; Gnagy, Elizabeth; Belendiuk, Kat; Walther, Christine; Babinski, Dara; Waschbusch, Dan
2012-01-01
Objective: Research has clearly documented the social dysfunction of youth with ADHD. However, little is known about the interpersonal relationships of adults diagnosed with ADHD in childhood, including rates of intimate partner violence (IPV). Method: Using data from the Pittsburgh ADHD Longitudinal Study, analyses compared the level of IPV…
Working Women Making It Work: Intimate Partner Violence, Employment, and Workplace Support
ERIC Educational Resources Information Center
Swanberg, Jennifer; Macke, Caroline; Logan, TK
2007-01-01
Partner violence may have significant consequences on women's employment, yet limited information is available about how women cope on the job with perpetrators' tactics and the consequences of her coping methods on employment status. This article investigates whether there is an association between workplace disclosure of victimization and…
34 CFR 692.100 - What requirements must a State meet to receive an allotment under this program?
Code of Federal Regulations, 2010 CFR
2010-07-01
... Federal funds allotted under this subpart and the non-Federal matching funds; and (ii) The methods by..., other contributing partners. (b) Serve as the primary administrative unit for the partnership; (c) Provide or coordinate non-Federal share funds, and coordinate activities among partners; (d) Encourage...
ERIC Educational Resources Information Center
Lipsky, Sherry; Cristofalo, Meg; Reed, Sarah; Caetano, Raul; Roy-Byrne, Peter
2012-01-01
The objectives of this study were to examine racial and ethnic disparities in perpetrator and incident characteristics and discrepancies between police charges and reported perpetrator behaviors in police-reported intimate partner violence (IPV). This cross-sectional study used standardized police data and victim narratives of IPV incidents…
Detection of Intimate Partner Violence in a General Medicine Practice
ERIC Educational Resources Information Center
Soglin, Lenore F.; Bauchat, Jeanette; Soglin, David F.; Martin, Gary J.
2009-01-01
In this study, an assessment phase is undertaken to determine intimate partner violence (IPV) prevalence. An anonymous survey is followed by a chart review documenting identification of IPV. Two methods are attempted to increase assessment/documentation of IPV: a physician educational intervention and a nursing routine inquiry intervention in one…
Cai, Y M; Song, Y J; Liu, H; Hong, F C
2017-11-06
Objective: To investigate the factors associated with syphilis/HIV infection among men who have sex with men (MSM) maintaining a single sexual partner in Shenzhen. Methods: Respondent driven sampling and snowball sampling method were used to recruit MSM receiving voluntary counseling and testing in Shenzhen Rainbow clinic from 2011 to 2016. aged 18 years and above; reported having one or more anal sexual partners in the recent 6 months. A total of 3 109 men who have sex with men (MSM) were involved in the study. Questionnaire-based interviews were conducted on a one-on-one basis. Data were collected including socio-demographic information, human immunodeficiency virus (HIV) testing history, history of blood donation and drug abuse in the recent two years, self-identified sexual orientation, role in homosexual behavior, ever being money boys (MB) and clients of MB, female sexual partners in the recent 6 months. 5 ml blood samples were taken after questionnaires. Syphilis was screened using toluidine red unheated serum test for the antibody of treponema pallidum and then confirmed by treponema pallidum particle assay. The enzyme-linked immunosorbent assay (ELISA) was used for screening HIV and western blot was used to confirm the HIV screening results. The difference of condom use among MSM between female sexual partners and male sexual partners were compared. Multivariate unconditional stepwise logistic regression model was used to analyze factors associated with syphilis infection and HIV positive among MSM. Results: A total of 3 109 eligible participants with mean (SD) age of 31.49 (8.64) years were enrolled in this study. Among them, 565 cases were infected with syphilis (18.17%), 330 cases were infected with HIV (10.61%), and 165 cases (5.31%) were syphilis co-infected with HIV. 791 (25.44%) reported maintaining a single sexual partners in the recent 6 months. Compared to MSM with multiple sexual partners, the prevalence of syphilis and HIV infection among MSM with a single sexual partner were lower, and the OR (95% CI ) were 0.64 (0.51-0.81) and 0.66 (0.49-0.90), respectively. Conclusion: The proportion of fixed single sexual partner was much lower among MSM in Shenzhen. Maintaining a single sexual partners can reduce the risk of syphilis/HIV infection among MSM.
Robertson, Angela M.; Syvertsen, Jennifer L.; Rangel, M. Gudelia; Staines, Hugo S.; Morris, Martina; Patterson, Thomas L.; Ulibarri, Monica D.; Strathdee, Steffanie A.
2013-01-01
Objectives To investigate the prevalence and correlates of concurrent (overlapping) sexual partnerships among female sex workers (FSWs) and their non-commercial male partners in two Mexico-U.S. border cities. Methods A cross-sectional survey of FSWs and their non-commercial male partners was conducted in Tijuana and Ciudad Juárez, Mexico (2010–2011). Eligible FSWs and verified non-commercial partners were aged ≥18 years; FSWs had ever used hard drugs (lifetime) and recently exchanged sex for money, drugs, or other goods (past month). Participants underwent baseline questionnaires obtaining dates of sex and condom use with ≤5 other recurring partners, including FSWs’ regular clients. These dates were compared to dates of sex with enrolled study partners to determine overlap (i.e., “recurring” concurrency). Bivariate probit regression identified recurring concurrency correlates. Results Among 428 individuals (214 couples), past-year recurring concurrency prevalence was 16% and was higher among women than their non-commercial male partners (26% vs. 6%). In 10 couples (5%), both partners reported recurring concurrency. The majority of couples (64%) always had unprotected sex, and most of the individuals (70%) with recurring concurrency “sometimes” or “never” used condoms with their concurrent partners. Recurring concurrency was positively associated with FSWs’ income, men’s caballerismo (a form of traditional masculinity), and men’s belief that their FSW-partners had STIs. Conclusions Recurring concurrency, representing sustained periods of overlapping partnerships in which unprotected sex was common, should be addressed by couple-based STI prevention interventions. PMID:23172036
Sexual violence against intimate partners in Cape Town: prevalence and risk factors reported by men.
Abrahams, Naeemah; Jewkes, Rachel; Hoffman, Margaret; Laubsher, Ria
2004-01-01
OBJECTIVE: To describe the prevalence of and risk factors for the perpetration of sexual violence by men against female intimate partners. METHODS: A cross-sectional study was conducted on 1368 randomly selected men working in three Cape Town municipalities. The men were interviewed with the aid of a questionnaire on current sexual partners in the preceding 10 years, personal and relationship characteristics and the use of violence against their partners. RESULTS: The perpetration of sexual violence against intimate partners in the past 10 years was reported by 15.3% of the men. After adjustment for sociodemographic circumstances, the factors associated with such violence were involvement in physical conflict outside the home, problematic alcohol use, having more than one current partner and abusing partners verbally. While having frequent conflict with partners was important for the risk of sexual violence, only two types of conflict sources were significantly associated with this risk, namely conflict over sexual refusal and conflict when men perceived their authority to be undermined. CONCLUSION: Sexual violence in intimate relations was common. The risk of being sexually violent was associated with the use of violence to solve problems in other settings, having more than one current partner, alcohol abuse and verbally abusing a partner. It was also associated with particular types of conflict stemming from ideas of male sexual entitlement and dominance. Prevention programmes that focus on gender relations and non-violent conflict resolution for men and youths may be useful in combating such sexual violence. PMID:15298223
CHARACTERISTICS OF MULTIPLE AND CONCURRENT PARTNERSHIPS AMONG WOMEN AT HIGH RISK FOR HIV INFECTION
Adimora, Adaora A.; Hughes, James P.; Wang, Jing; Haley, Danielle F.; Golin, Carol E.; Magnus, Manya; Rompalo, Anne; Justman, Jessica; del Rio, Carlos; El-Sadr, Wafaa; Mannheimer, Sharon; Soto-Torres, Lydia; Hodder, Sally L.
2014-01-01
Objectives We examined parameters of sexual partnerships, including respondents’ participation in concurrency, belief that their partner had concurrent partnerships (partners’ concurrency), and partnership intervals, among the 2,099 women in HIV Prevention Trials Network 064, a study of women at high risk for HIV infection, in ten US communities. Methods We analyzed baseline survey responses about partnership dates to determine prevalence of participants’ and partners’ concurrency, intervals between partnerships, knowledge of whether recent partner(s) had undergone HIV testing, and intercourse frequency during the preceding 6 months. Results Prevalence of participants’ and partners’ concurrency was 40% and 36% respectively; 24% of respondents had both concurrent partnerships and non-monogamous partners. Among women with >1 partner and no concurrent partnerships themselves, the median gap between partners was one month. Multiple episodes of unprotected vaginal intercourse with >2 of their most recent partners was reported by 60% of women who had both concurrent partnerships and non-monogamous partners, 50% with only concurrent partners and no partners’ concurrency, and 33% with only partners’ concurrency versus 14% of women with neither type of concurrency (p<.0001). Women who had any involvement with concurrency were also more likely than women with no concurrency involvement to report lack of awareness of whether recent partners had undergone HIV testing (participants’ concurrency 41%, partners’ concurrency 40%, both participants’ and partners’ concurrency 48%, neither 17%; p<.0001). Conclusions These network patterns and short gaps between partnerships may create substantial opportunities for HIV transmission in this sample of women at high risk for HIV infection. PMID:24056163
Appel, David I.; Brinda, Bryan; Markowitz, John S.; Newcorn, Jeffrey H.; Zhu, Hao-Jie
2012-01-01
A simple, rapid and sensitive method for quantification of atomoxetine by liquid chromatography- tandem mass spectrometry (LC-MS/MS) was developed. This assay represents the first LC-MS/MS quantification method for atomoxetine utilizing electrospray ionization. Deuterated atomoxetine (d3-atomoxetine) was adopted as the internal standard. Direct protein precipitation was utilized for sample preparation. This method was validated for both human plasma and in vitro cellular samples. The lower limit of quantification was 3 ng/ml and 10 nM for human plasma and cellular samples, respectively. The calibration curves were linear within the ranges of 3 ng/ml to 900 ng/ml and 10 nM to 10 μM for human plasma and cellular samples, respectively (r2 > 0.999). The intra- and inter-day assay accuracy and precision were evaluated using quality control samples at 3 different concentrations in both human plasma and cellular lysate. Sample run stability, assay selectivity, matrix effect, and recovery were also successfully demonstrated. The present assay is superior to previously published LC-MS and LC-MS/MS methods in terms of sensitivity or the simplicity of sample preparation. This assay is applicable to the analysis of atomoxetine in both human plasma and in vitro cellular samples. PMID:22275222
Sontag, Timothy J.; Chellan, Bijoy; Bhanvadia, Clarissa V.; Getz, Godfrey S.; Reardon, Catherine A.
2015-01-01
Macrophage conversion to atherosclerotic foam cells is partly due to the balance of uptake and efflux of cholesterol. Cholesterol efflux from cells by HDL and its apoproteins for subsequent hepatic elimination is known as reverse cholesterol transport. Numerous methods have been developed to measure in vivo macrophage cholesterol efflux. Most methods do not allow for macrophage recovery for analysis of changes in cellular cholesterol status. We describe a novel method for measuring cellular cholesterol balance using the in vivo entrapment of macrophages in alginate, which retains incorporated cells while being permeable to lipoproteins. Recipient mice were injected subcutaneously with CaCl2 forming a bubble into which a macrophage/alginate suspension was injected, entrapping the macrophages. Cells were recovered after 24 h. Cellular free and esterified cholesterol mass were determined enzymatically and normalized to cellular protein. Both normal and cholesterol loaded macrophages undergo measureable changes in cell cholesterol when injected into WT and apoA-I-, LDL-receptor-, or apoE-deficient mice. Cellular cholesterol balance is dependent on initial cellular cholesterol status, macrophage cholesterol transporter expression, and apolipoprotein deficiency. Alginate entrapment allows for the in vivo measurement of macrophage cholesterol homeostasis and is a novel platform for investigating the role of genetics and therapeutic interventions in atherogenesis. PMID:25465389
Visness, C M; Ulin, P; Pfannenschmidt, S; Zekeng, L
1998-11-01
Five hundred and twenty female Cameroonian sex workers participating in a clinical trial of the effectiveness of nonoxynol-9 (N-9) contraceptive film to prevent HIV infection were interviewed to determine their experience with this woman-controlled method. The sex workers liked the film, with over 80% stating they would continue to use it if it were shown to be effective against HIV and were to become widely available. However, they were much more likely to use condoms and films simultaneously with their clients (40%) than with their regular partners (16%). The advantages ascribed to the film were that its use was under the woman's control; it could be used without the partner's knowledge; it allowed direct contact between partners; and it provided back-up protection in case of condom breakage. Data from this small study suggest that development of an effective, woman-controlled method of pregnancy and disease protection would be welcomed by these women.
NASA Astrophysics Data System (ADS)
Garbacz, Tomasz; Dulebova, Ludmila
2012-12-01
Partnering Patterns and Sexual Behavior Among Korean Men Who Have Sex With Men.
Jung, Minsoo
2016-01-01
This qualitative study investigates the different methods for selecting sex partners by Korean homosexuals considering factors related to homosexual identity and sexual behavior. We take the approach of the grounded theory to examine the issue of sexual partnering of men who have sex with men (MSM). In-depth interviews of urban MSM and bisexual men were conducted. The snowball sampled through a MSM portal web site. Three key informants from the several areas were collected through a MSM portal website, and then, participants were gradually recruited with the snowball samplings in South Korea, 2011 (n=32). The results of coding the interviews based on the grounded theory approach identified three types of partnering: 1) MSM who do not prefer anal intercourse, but pursue safe sex in long-term relationships with fixed partners; 2) those who have fixed partners and perform anal sex, a category into which both MSM and bisexuals fall; and 3) those engaged in anal sex, but enjoy a concurrent sexual relationship without having fixed partners, which was common among bisexuals. The findings from this study elucidate several MSM and bisexual partnering types practice safe sex. This diversity in MSM partnering may increase the vulnerability of some MSM to HIV infection as safe-sex practices remain a matter of individual choice. Changes in Korean societal policies are necessary to enhance capacity building and encourage the practice of safe sex at the community level.
Reverse Correlating Love: Highly Passionate Women Idealize Their Partner’s Facial Appearance
Gunaydin, Gul; DeLong, Jordan E.
2015-01-01
A defining feature of passionate love is idealization—evaluating romantic partners in an overly favorable light. Although passionate love can be expected to color how favorably individuals represent their partner in their mind, little is known about how passionate love is linked with visual representations of the partner. Using reverse correlation techniques for the first time to study partner representations, the present study investigated whether women who are passionately in love represent their partner’s facial appearance more favorably than individuals who are less passionately in love. In a within-participants design, heterosexual women completed two forced-choice classification tasks, one for their romantic partner and one for a male acquaintance, and a measure of passionate love. In each classification task, participants saw two faces superimposed with noise and selected the face that most resembled their partner (or an acquaintance). Classification images for each of high passion and low passion groups were calculated by averaging across noise patterns selected as resembling the partner or the acquaintance and superimposing the averaged noise on an average male face. A separate group of women evaluated the classification images on attractiveness, trustworthiness, and competence. Results showed that women who feel high (vs. low) passionate love toward their partner tend to represent his face as more attractive and trustworthy, even when controlling for familiarity effects using the acquaintance representation. Using an innovative method to study partner representations, these findings extend our understanding of cognitive processes in romantic relationships. PMID:25806540
Karlson, Elizabeth W.; Boutin, Natalie T.; Hoffnagle, Alison G.; Allen, Nicole L.
2016-01-01
The Partners HealthCare Biobank is a Partners HealthCare enterprise-wide initiative whose goal is to provide a foundation for the next generation of translational research studies of genotype, environment, gene-environment interaction, biomarker and family history associations with disease phenotypes. The Biobank has leveraged in-person and electronic recruitment methods to enroll >30,000 subjects as of October 2015 at two academic medical centers in Partners HealthCare since launching in 2010. Through a close collaboration with the Partners Human Research Committee, the Biobank has developed a comprehensive informed consent process that addresses key patient concerns, including privacy and the return of research results. Lessons learned include the need for careful consideration of ethical issues, attention to the educational content of electronic media, the importance of patient authentication in electronic informed consent, the need for highly secure IT infrastructure and management of communications and the importance of flexible recruitment modalities and processes dependent on the clinical setting for recruitment. PMID:26784234
What constitutes meaningful engagement for patients and families as partners on research teams?
Black, Agnes; Strain, Kimberly; Wallsworth, Christine; Charlton, Sara-Grey; Chang, Wilma; McNamee, Kate; Hamilton, Clayon
2018-01-01
Objective There is growing emphasis on health care organizations to ensure that lay people are meaningfully engaged as partners on research teams. Our aim was to explore the perspectives of patients, family members and informal caregivers who have been involved on health care research teams in Canada and elicit their recommendations for meaningful engagement. Methods We conducted a qualitative study guided by thematic analysis of transcripts of focus groups and interviews of 19 experienced patient research partners in Canada. Results We identified four main themes: research environment, expectations, support and value, which highlight participants' combined perspectives on important factors to ensure their engagement in research is meaningful. Conclusions Our findings add to the evolving evidence base on the perspectives of lay people involved in health care research and their recommendations for research leaders on meaningful engagement. Our study suggests that research leaders should provide a welcoming research environment, outline appropriate expectations for patient research partners on research teams, support patient research partners' engagement in projects and recognize the value patient research partners bring to health research.
Design and implementation of a novel mechanical testing system for cellular solids.
Nazarian, Ara; Stauber, Martin; Müller, Ralph
2005-05-01
Cellular solids constitute an important class of engineering materials encompassing both man-made and natural constructs. Materials such as wood, cork, coral, and cancellous bone are examples of cellular solids. The structural analysis of cellular solid failure has been limited to 2D sections to illustrate global fracture patterns. Due to the inherent destructiveness of 2D methods, dynamic assessment of fracture progression has not been possible. Image-guided failure assessment (IGFA), a noninvasive technique to analyze 3D progressive bone failure, has been developed utilizing stepwise microcompression in combination with time-lapsed microcomputed tomographic imaging (microCT). This method allows for the assessment of fracture progression in the plastic region, where much of the structural deformation/energy absorption is encountered in a cellular solid. Therefore, the goal of this project was to design and fabricate a novel micromechanical testing system to validate the effectiveness of the stepwise IGFA technique compared to classical continuous mechanical testing, using a variety of engineered and natural cellular solids. In our analysis, we found stepwise compression to be a valid approach for IGFA with high precision and accuracy comparable to classical continuous testing. Therefore, this approach complements the conventional mechanical testing methods by providing visual insight into the failure propagation mechanisms of cellular solids. (c) 2005 Wiley Periodicals, Inc.
Transcriptional Networks in Epithelial-Mesenchymal Transition
Venkov, Christo; Plieth, David; Ni, Terri; Karmaker, Amitava; Bian, Aihua; George, Alfred L.; Neilson, Eric G.
2011-01-01
Backround Epithelial-mesenchymal transition (EMT) changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis. Methods and Findings Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs) in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding these CREs, establish their importance in the initiation and propagation of EMT. Oligonucleotides that block the most frequent CREs restrain EMT at early and intermediate stages through apoptosis of the cells. Conclusions Our results identify new transcriptional interactions with high frequency CREs that modulate the stability of cellular plasticity, and may serve as targets for modulating these transitional states in fibroblasts. PMID:21980432
Das, Raibatak; Cairo, Christopher W.; Coombs, Daniel
2009-01-01
The extraction of hidden information from complex trajectories is a continuing problem in single-particle and single-molecule experiments. Particle trajectories are the result of multiple phenomena, and new methods for revealing changes in molecular processes are needed. We have developed a practical technique that is capable of identifying multiple states of diffusion within experimental trajectories. We model single particle tracks for a membrane-associated protein interacting with a homogeneously distributed binding partner and show that, with certain simplifying assumptions, particle trajectories can be regarded as the outcome of a two-state hidden Markov model. Using simulated trajectories, we demonstrate that this model can be used to identify the key biophysical parameters for such a system, namely the diffusion coefficients of the underlying states, and the rates of transition between them. We use a stochastic optimization scheme to compute maximum likelihood estimates of these parameters. We have applied this analysis to single-particle trajectories of the integrin receptor lymphocyte function-associated antigen-1 (LFA-1) on live T cells. Our analysis reveals that the diffusion of LFA-1 is indeed approximately two-state, and is characterized by large changes in cytoskeletal interactions upon cellular activation. PMID:19893741
Next-Generation Methods for HIV Partner Services: A Systematic Review.
Hochberg, Chad H; Berringer, Kathryn; Schneider, John A
2015-09-01
Partner notification is a widely accepted method whose intent is to limit onward HIV transmission. With increasing use of new technologies such as text messaging, e-mail, and social network sites, there is growing interest in using these techniques for "next-generation" HIV partner services (PS). We conducted a systematic review to assess the use and effectiveness of these technologies in HIV PS. Our literature search resulted in 1343 citations, with 7 meeting inclusion criteria. We found programs in 2 domains: (1) Public Health Department usage of new technologies to augment traditional partner notification (n = 3) and (2) patient or provider-led usage of partner notification Web sites (n = 4) The health department-based efforts showed an ability to find new cases in a previously unreachable population but in the limited comparisons to traditional PS had a lower rate of successful contact. Usage data from the partner notification Web sites revealed a high total number of e-notifications sent, with less than 10% of cards sent for HIV. Clear evidence on outcomes and directly traceable utilization for these Web services was lacking. When given a choice, most clients chose to send e-notifications via text versus e-mail. Although successful notification may be lower overall, use of next-generation services provides an avenue to contact those who would previously have been untraceable. Additional research is needed to determine to what extent technology-enhanced PS improves the identification of newly infected persons as well as the initiation of new prevention interventions for HIV-negative clients within high-risk networks.
Self-Control and Emotional and Verbal Aggression in Dating Relationships: A Dyadic Understanding.
Baker, Elizabeth A; Klipfel, Katherine M; van Dulmen, Manfred H M
2016-08-01
Guided by the dynamic developmental systems perspective, this study extends past research by examining the association between self-control and emotional and verbal aggression (EVA) using a dyadic multi-method design. Guided by empirical research and the dynamic developmental systems perspective, we hypothesized that (a) there would be a negative association between one's own self-control and one's own perpetration of EVA and (b) there would also be a negative association between one's partner's self-control and one's own perpetration of EVA. One hundred twenty heterosexual dating couples (ages 18-25 years) provided data on self-control (Grasmick et al.'s Low Self-Control Scale; reverse scored for ease of interpretation), self-reported perpetration of EVA (Emotional and Verbal Abuse subscale of the Conflict in Adolescent Dating Relationships Inventory), and observationally assessed perpetration of EVA. Data were analyzed using path analyses within the Actor-Partner Interdependence Model (APIM) framework. Consistent with previous findings, we found that self-control was negatively associated with the perpetration of EVA. Furthermore, we found partner effects, such that female-but not male-self-control predicted partner-observed perpetration of EVA. These findings highlight the importance of examining risk factors for EVA of both partners. Our findings also suggest that the association between self-control and EVA is partially a function of whether EVA is assessed through self-report or observational methodology. This highlights the need to conduct multi-method assessments in future research. As discussed in the article, our findings have implications for theories on intimate partner violence, study designs, and couple interventions.
Nguyen, Marie L.; Nguyen, Minh M.; Lee, Denis; Griep, Anne E.; Lambert, Paul F.
2003-01-01
Human papillomaviruses (HPVs) are the causative agent of warts. Infections with high-risk HPVs are associated with anogenital and head and neck cancers. One of the viral genes responsible for HPV's oncogenic activity is E6. Mice expressing the HPV-16 E6 protein in their epidermis (K14E6WT) develop epithelial hyperplasia and squamous carcinomas. Numerous cellular proteins interact with E6, some of which can be grouped based on common amino acid motifs in their E6-binding domains. One such group, the PDZ partners, including hDLG, hSCRIBBLE, MUPP1, and MAGI, bind to the carboxy-terminal four amino acids of E6 through their PDZ domains. E6's interaction with the PDZ partners leads to their degradation. Additionally, E6's binding to PDZ proteins has been correlated with its ability to transform baby rat kidney cells in tissue culture and to confer tumorigenicity onto cells in xenograft experiments. To address whether the ability of E6 to bind PDZ domain partners is necessary for E6 to confer epithelial hyperproliferation in vivo, we generated transgenic mice that express in stratified squamous epithelia a mutant of E6 lacking the last six amino acids at its carboxyl terminus, E6Δ146-151, from the human keratin 14 (K14) promoter. The K14E6Δ146-151 mice exhibit a radiation response similar to that of the K14E6WT mice, demonstrating that this protein, as predicted, retains an ability to inactivate p53. However, the K14E6Δ146-151 mice fail to display epithelial hyperplasia. These results indicate that an interaction of E6 with PDZ partners is necessary for its induction of epithelial hyperplasia. PMID:12768014
Ectromelia virus encodes a novel family of F-box proteins that interact with the SCF complex.
van Buuren, Nick; Couturier, Brianne; Xiong, Yue; Barry, Michele
2008-10-01
Poxviruses are notorious for encoding multiple proteins that regulate cellular signaling pathways, including the ubiquitin-proteasome system. Bioinformatics indicated that ectromelia virus, the causative agent of lethal mousepox, encoded four proteins, EVM002, EVM005, EVM154, and EVM165, containing putative F-box domains. In contrast to cellular F-box proteins, the ectromelia virus proteins contain C-terminal F-box domains in conjunction with N-terminal ankyrin repeats, a combination that has not been previously reported for cellular proteins. These observations suggested that the ectromelia virus F-box proteins interact with SCF (Skp1, cullin-1, and F-box) ubiquitin ligases. We focused our studies on EVM005, since this protein had only one ortholog in cowpox virus. Using mass spectrometry, we identified cullin-1 as a binding partner for EVM005, and this interaction was confirmed by overexpression of hemagglutinin (HA)-cullin-1. During infection, Flag-EVM005 and HA-cullin-1 colocalized to distinct cellular bodies. Significantly, EVM005 coprecipitated with endogenous Skp1, cullin-1, and Roc1 and associated with conjugated ubiquitin, suggesting that EVM005 interacted with the components of a functional ubiquitin ligase. Interaction of EVM005 with cullin-1 and Skp1 was abolished upon deletion of the F-box, indicating that the F-box played a crucial role in interaction with the SCF complex. Additionally, EVM002 and EVM154 interacted with Skp1 and conjugated ubiquitin, suggesting that ectromelia virus encodes multiple F-box-containing proteins that regulate the SCF complex. Our results indicate that ectromelia virus has evolved multiple proteins that interact with the SCF complex.
Gimenez, Ana Paula Lappas; Richter, Larissa Morato Luciani; Atherino, Mariana Campos; Beirão, Breno Castello Branco; Fávaro, Celso; Costa, Michele Dietrich Moura; Zanata, Silvio Marques; Malnic, Bettina; Mercadante, Adriana Frohlich
2015-01-01
ABSTRACT Prion diseases involve the conversion of the endogenous cellular prion protein, PrPC, into a misfolded infectious isoform, PrPSc. Several functions have been attributed to PrPC, and its role has also been investigated in the olfactory system. PrPC is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp−/− mice showed impaired behavior in olfactory tests. Given the high PrPC expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrPC-binding partners. Ten different putative PrPC ligands were identified, which were involved in functions such as cellular proliferation and apoptosis, cytoskeleton and vesicle transport, ubiquitination of proteins, stress response, and other physiological processes. In vitro binding assays confirmed the interaction of PrPC with STIP1 homology and U-Box containing protein 1 (Stub1) and are reported here for the first time. Stub1 is a co-chaperone with ubiquitin E3-ligase activity, which is associated with neurodegenerative diseases characterized by protein misfolding and aggregation. Physiological and pathological implications of PrPC-Stub1 interaction are under investigation. The PrPC-binding proteins identified here are not exclusive to the OE, suggesting that these interactions may occur in other tissues and play general biological roles. These data corroborate the proposal that PrPC is part of a multiprotein complex that modulates several cellular functions and provide a platform for further studies on the physiological and pathological roles of prion protein. PMID:26237451
Surtees, Rebecca; Dowall, Stuart D; Shaw, Amelia; Armstrong, Stuart; Hewson, Roger; Carroll, Miles W; Mankouri, Jamel; Edwards, Thomas A; Hiscox, Julian A; Barr, John N
2016-10-15
The Nairovirus genus of the Bunyaviridae family contains serious human and animal pathogens classified within multiple serogroups and species. Of these serogroups, the Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole members CCHFV and Hazara virus (HAZV). CCHFV is an emerging zoonotic virus that causes often-fatal hemorrhagic fever in infected humans for which preventative or therapeutic strategies are not available. In contrast, HAZV is nonpathogenic to humans and thus represents an excellent model to study aspects of CCHFV biology under conditions of more-accessible biological containment. The three RNA segments that form the nairovirus genome are encapsidated by the viral nucleocapsid protein (N) to form ribonucleoprotein (RNP) complexes that are substrates for RNA synthesis and packaging into virus particles. We used quantitative proteomics to identify cellular interaction partners of CCHFV N and identified robust interactions with cellular chaperones. These interactions were validated using immunological methods, and the specific interaction between native CCHFV N and cellular chaperones of the HSP70 family was confirmed during live CCHFV infection. Using infectious HAZV, we showed for the first time that the nairovirus N-HSP70 association was maintained within both infected cells and virus particles, where N is assembled as RNPs. Reduction of active HSP70 levels in cells by the use of small-molecule inhibitors significantly reduced HAZV titers, and a model for chaperone function in the context of high genetic variability is proposed. These results suggest that chaperones of the HSP70 family are required for nairovirus replication and thus represent a genetically stable cellular therapeutic target for preventing nairovirus-mediated disease. Nairoviruses compose a group of human and animal viruses that are transmitted by ticks and associated with serious or fatal disease. One member is Crimean-Congo hemorrhagic fever virus (CCHFV), which is responsible for fatal human disease and is recognized as an emerging threat within Europe in response to climate change. No preventative or therapeutic strategies against nairovirus-mediated disease are currently available. Here we show that the N protein of CCHFV and the related Hazara virus interact with a cellular protein, HSP70, during both the intracellular and extracellular stages of the virus life cycle. The use of inhibitors that block HSP70 function reduces virus titers by up to 1,000-fold, suggesting that this interaction is important within the context of the nairovirus life cycle and may represent a potent target for antinairovirus therapies against which the virus cannot easily develop resistance. Copyright © 2016 Surtees et al.
Verzi, Michael P.; Shin, Hyunjin; San Roman, Adrianna K.
2013-01-01
Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulate cell-specific chromatin and if such abilities might underlie lineage determination and maintenance. One prevailing view is that several transcription factors enable chromatin access in combination. The homeodomain protein CDX2 specifies the embryonic intestinal epithelium, through unknown mechanisms, and partners with transcription factors such as HNF4A in the adult intestine. We examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas CDX2 depletion modified chromatin significantly at CDX2-bound enhancers, disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus, CDX2 maintains transcription-permissive chromatin, illustrating a powerful and dominant effect on enhancer configuration in an adult tissue. Similar, hierarchical control of cell-specific chromatin states is probably a general property of master transcription factors. PMID:23129810
Jaendling, Alessa; Ramayah, Soshila; Pryce, David W; McFarlane, Ramsay J
2008-02-01
Translin is a conserved protein which associates with the breakpoint junctions of chromosomal translocations linked with the development of some human cancers. It binds to both DNA and RNA and has been implicated in mRNA metabolism and regulation of genome stability. It has a binding partner, translin-associated protein X (TRAX), levels of which are regulated by the translin protein in higher eukaryotes. In this study we find that this regulatory function is conserved in the lower eukaryotes, suggesting that translin and TRAX have important functions which provide a selective advantage to both unicellular and multi-cellular eukaryotes, indicating that this function may not be tissue-specific in nature. However, to date, the biological importance of translin and TRAX remains unclear. Here we systematically investigate proposals that suggest translin and TRAX play roles in controlling mitotic cell proliferation, DNA damage responses, genome stability, meiotic/mitotic recombination and stability of GT-rich repeat sequences. We find no evidence for translin and/or TRAX primary function in these pathways, indicating that the conserved biochemical function of translin is not implicated in primary pathways for regulating genome stability and/or segregation.
Zhu, Hao; Sun, Yan; Rajagopal, Gunaretnam; Mondry, Adrian; Dhar, Pawan
2004-01-01
Background Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level. Methods We have developed a method to build large-scale electrophysiological models by using extended cellular automata, and to run such models on a cluster of shared memory machines. We describe here the method, including the extension of a language-based cellular automaton to implement quantitative computing, the building of a whole-heart model with Visible Human Project data, the parallelization of the model on a cluster of shared memory computers with OpenMP and MPI hybrid programming, and a simulation algorithm that links cellular activity with the ECG. Results We demonstrate that electrical activities at channel, cell, and organ levels can be traced and captured conveniently in our extended cellular automaton system. Examples of some ECG waveforms simulated with a 2-D slice are given to support the ECG simulation algorithm. A performance evaluation of the 3-D model on a four-node cluster is also given. Conclusions Quantitative multicellular modeling with extended cellular automata is a highly efficient and widely applicable method to weave experimental data at different levels into computational models. This process can be used to investigate complex and collective biological activities that can be described neither by their governing differentiation equations nor by discrete parallel computation. Transparent cluster computing is a convenient and effective method to make time-consuming simulation feasible. Arrhythmias, as a typical case, can be effectively simulated with the methods described. PMID:15339335
DOE Office of Scientific and Technical Information (OSTI.GOV)
Saripalli, Prasad; Brown, Christopher F.; Lindberg, Michael J.
We report on a new Cellular Absorptive Tracers (CATs) method, for a simple, non-destructive characterization of bacterial mass in flow systems. Results show that adsorption of a CAT molecule into the cellular mass results in its retardation during flow, which is a good, quantitative measure of the biomass quantity and distribution. No such methods are currently available for a quantitative characterization of cell mass.
Cabecinha, Melissa; Mercer, Catherine H; Jones, Kyle G; Wellings, Kaye; Sonnenberg, Pam; Field, Nigel
2017-01-01
Objectives Online venues might facilitate sexual encounters, but the extent to which finding partners online is associated with sexual risk behaviour and sexual health outcomes is unclear. We describe use of the internet to find sexual partners in a representative sample in Britain. Methods The third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) was a cross-sectional probability survey of 15 162 adults (aged 16–74 years) undertaken 2010–2012. We estimated prevalence of, and identified factors associated with, finding sexual partners online among those reporting ≥1 new sexual partners in the past year. Results Finding sexual partners online in the past year was reported by 17.6% (95% CI 15.6 to 19.9) of men and 10.1% (8.5–11.9) of women, and most common among those aged 35–44 years. After age-adjustment, those reporting a non-heterosexual identity were more likely to report this. Finding partners online was also associated with reporting sexual risk behaviours: condomless sex with ≥2 partners (adjusted OR (aOR) men: 1.52 (1.03 to 2.23); women: 1.62 (1.06 to 2.49)), concurrent partnerships (aOR men: 2.33 (1.62 to 3.35); women: 2.41 (1.49 to 3.87)) and higher partner numbers (reporting ≥5 partners aOR men: 5.95 (3.78 to 9.36); women: 7.00 (3.77 to 13.00)) (all past year). STI diagnoses and HIV testing were more common among men reporting finding partners online (adjusted for age, partner numbers, same-sex partnerships), but not women. Conclusions Finding partners online was associated with markers of sexual risk, which might be important for clinical risk assessment, but this was not matched by uptake of sexual health services. Online opportunities to find partners have increased, so these data might underestimate the importance of this social phenomenon for public health and STI control. PMID:28396557
2014-01-01
Background Chlamydia trachomatis infections in pregnancy can cause maternal disease, adverse pregnancy outcomes and neonatal disease, which is why chlamydia screening during pregnancy has been advocated. The effectiveness of a screening program depends on the knowledge of health care professionals, women and partners and the acceptability for screening of the target population. We assessed the knowledge of chlamydia infection among pregnant women and their partners in the Netherlands, their attitudes towards testing, and their experiences of being offered a chlamydia test. In addition, we evaluated the association between participants’ background characteristics and knowledge of chlamydia. Methods Pregnant women aged ≤ 30 years and their partners (regardless of their age) attending one of the participating primary midwifery care practices in the Netherlands were invited to participate. All participants completed a questionnaire, pregnant women provided a vaginal swab and partners provided a urine sample to test for C. trachomatis. Results In total, 383 pregnant women and 282 partners participated in the study of whom 1.9% women and 2.6% partners tested chlamydia positive. Participants had high levels of awareness (92.8%) of chlamydial infection. They were knowledgeable about the risk of chlamydia infection; median knowledge score was 9.0 out of 12.0. Lower knowledge scores were found among partners (p-value <0.001), younger aged (p-value 0.02), non-western origin (p-value <0.001), low educational level (p-value <0.001), and no history of sexually transmitted infections (p-value <0.001). In total, 78% of respondents indicated that when pregnant women are tested for chlamydia, their partners should also be tested; 54% believed that all women should routinely be tested. Pregnant women more often indicated than partners that testing partners for chlamydial infection was not necessary (p-value <0.001). The majority of pregnant women (56.2%) and partners (59.2%) felt satisfied by being offered the test during antenatal care. Conclusion Pregnant women and their partners were knowledgeable about chlamydial infection, found testing, both pregnant women and their partners, for chlamydia acceptable and not stigmatizing. PMID:25011479
Reimann, Ronny; Kost, Benedikt; Dettmer, Jan
2017-01-01
Tetraspanins are small transmembrane proteins that laterally associate with each other and cluster with numerous partner proteins as well as lipids. These interactions result in the formation of a distinct class of membrane domains, the tetraspanin-enriched microdomains (TEMs), which influence numerous cellular processes such as cell adhesion and fusion, intracellular membrane trafficking, signaling, morphogenesis, motility as well as interaction with pathogens and cancer development. The majority of information available about tetraspanins is based on studies using animal models or cell lines, but tetraspanins are also present in fungi and plants. Recent studies indicate that tetraspanins have important functions in plant development, reproduction and stress responses. Here we provide a brief summary of the current state of tetraspanin research in plants. PMID:28458676
Barteneva, Natasha S; Vorobjev, Ivan A
2018-01-01
In this paper, we review some of the recent advances in cellular heterogeneity and single-cell analysis methods. In modern research of cellular heterogeneity, there are four major approaches: analysis of pooled samples, single-cell analysis, high-throughput single-cell analysis, and lately integrated analysis of cellular population at a single-cell level. Recently developed high-throughput single-cell genetic analysis methods such as RNA-Seq require purification step and destruction of an analyzed cell often are providing a snapshot of the investigated cell without spatiotemporal context. Correlative analysis of multiparameter morphological, functional, and molecular information is important for differentiation of more uniform groups in the spectrum of different cell types. Simplified distributions (histograms and 2D plots) can underrepresent biologically significant subpopulations. Future directions may include the development of nondestructive methods for dissecting molecular events in intact cells, simultaneous correlative cellular analysis of phenotypic and molecular features by hybrid technologies such as imaging flow cytometry, and further progress in supervised and non-supervised statistical analysis algorithms.
Kerani, Roxanne Pieper; Fleming, Mark; Golden, Matthew Robert
2013-02-01
Little is known about how men who have sex with men (MSM) exposed to a sexually transmitted infection respond to receiving patient-delivered partner therapy (PDPT) or electronic partner notification postcards (e-cards). We anonymously surveyed MSM in a sexually transmitted disease (STD) clinic and a private medical practice. Three scenarios were presented in which participants had oral or anal sex with a new partner and were subsequently notified of a chlamydia or gonorrhea exposure and offered PDPT by the partner. A fourth scenario described partner notification via an anonymous inSPOT e-card. We asked participants if they would see a doctor, test for HIV/STD, and/or notify other partners in each situation. Among 198 MSM, the percentage indicating that they would seek a medical evaluation was higher when scenarios described proctitis (97%-98%) versus pharyngitis (84%) or no symptoms (84%-89%). In the absence of symptoms, men indicated that they would be less likely to seek care (62% vs. 84%-88%, P < 0.0001) and notify partners (85% vs. 69%, P < 0.0001) if notified via an anonymous e-card than if notified directly by a partner. Approximately half reported that they would use PDPT provided by a partner. In the absence of symptoms, men who indicated that they would use PDPT reported that they would seek medical care less frequently than men who indicated that they would not take PDPT (74% vs. 92% [P = 0.0007 for oral sex exposure] 82% vs. 94%-94% [P = 0.01 or unprotected anal sex exposure]). Although many MSM express interest in using PDPT and anonymous e-cards, these methods may result in missed opportunities to test for HIV and other STDs.
2014-01-01
Background Intimate partner violence (IPV) and coercion have been associated with negative health outcomes, including increased HIV risk behaviors, among men who have sex with men (MSM). This is the first study to describe the prevalence and factors associated with experiencing IPV or coercion among US MSM dyads using the actor-partner interdependence model (APIM), an analytic framework to describe interdependent outcomes within dyads. Methods Among MSM couples enrolled as dyads in an HIV prevention randomized controlled trial (RCT), two outcomes are examined in this cross-sectional analysis: 1) the actor experiencing physical or sexual IPV from the study partner in the past 3-months and 2) the actor feeling coerced to participate in the RCT by the study partner. Two multilevel APIM logistic regression models evaluated the association between each outcome and actor, partner, and dyad-level factors. Results Of 190 individuals (95 MSM couples), 14 reported experiencing physical or sexual IPV from their study partner in the past 3 months (7.3%) and 12 reported feeling coerced to participate in the RCT by their study partner (6.3%). Results of multivariate APIM analyses indicated that reporting experienced IPV was associated (p < 0.1) with non-Black/African American actor race, lower actor education, and lower partner education. Reporting experienced coercion was associated (p < 0.1) with younger actor age and lower partner education. Conclusions These findings from an HIV prevention RCT for MSM show considerable levels of IPV experienced in the past 3-months and coercion to participate in the research study, indicating the need for screening tools and support services for these behaviors. The identification of factors associated with IPV and coercion demonstrate the importance of considering actor and partner effects, as well as dyadic-level effects, to improve development of screening tools and support services for these outcomes. PMID:24580732
2017-01-01
Background Many factors contribute to an enhanced risk of infant HIV acquisition, two of which may include failure of a mother to disclose her HIV-positive status to her partner and exclusion of male partners in preventing mother-to-child transmission of HIV (PMTCT) interventions. To justify why HIV programmes need to integrate male partner involvement and partner disclosure, we need to establish an association between the two factors and infant HIV acquisition. Objective To determine whether failure to disclose an HIV-positive status to a male partner is associated with increased risk of infant HIV acquisition, and whether part of the association is explained by exclusion of male partner in PMTCT programmes. Methods Using a case–control study design, we identified a total of 180 mother–baby pairs with HIV-exposed infants. Thirty-six pairs with HIV-positive babies (cases) were compared to 144 pairs with HIV-negative babies (controls) on whether the mothers had disclosed their HIV status to their partner in order to determine whether a disclosure or lack of it contributed to increased risk of mother-to-child transmission of HIV (MTCT). Each case pair was matched to four control pairs from the same facility. Results Overall, 16.7% of mothers had not disclosed their HIV status to their partners, the proportion being significantly more among cases (52.8% vs. 7.6%, p < 0.001). Non-disclosure was significantly associated with infant HIV acquisition (aOR 9.8 (3.0–26.3); p < 0.001) and male partner involvement partially mediated the effect of non-disclosure on infant HIV acquisition (indirect coefficient = 0.17, p < 0.005). Conclusions Failure of an HIV-positive woman to disclose her status to her male partner and exclusion of male partners in PMTCT programmes are two social factors that may curtail success of interventions towards the goal of eliminating MTCT. PMID:29568627
Williams, Jessica R; Halstead, Valerie; Salani, Deborah; Koermer, Natasha
2017-08-01
Explore different methods by which intimate partner violence screening practices are implemented in clinic and emergency settings and better understand barriers and facilitators. Healthcare visits provide an opportunity for providers to identify and provide assistance to victims of intimate partner violence. However, wide variation exists in the implementation of screening and response protocols. In addition, providers experience barriers and facilitators to intimate partner violence screening and response. A comprehensive understanding of these factors is necessary to improve the role that providers play in detection and intervention of intimate partner violence. Qualitative descriptive research design. Sixteen healthcare facilities were recruited from a large metropolitan area in the USA. Data were collected through semi-structured, in-depth interviews with individuals knowledgeable about intimate partner violence screening and response within their facility. Data were analysed using directive content analysis. Major themes and patterns concerning intimate partner violence screening and response were identified within the following areas: procedural characteristics, barriers, facilitators and additional needs. Patient-provider communication and operational/facility characteristics emerged as critical aspects that impact the successful implementation of intimate partner violence screening and response programmes. Differences were found between clinic and emergency settings stemming from variations in health delivery models. Results provide important information on how healthcare facilities implement intimate partner violence screening and response, suggestions for practice improvement and directions for future interventions. Additional guidance is needed to ensure intimate partner violence identification, and response procedures are effective and tailored to needs of patients, providers and the facility. Nurses are in a strategic position to play a pivotal role in identification of and response to intimate partner violence. It is essential that nurses are cognizant of this, and understand the actions they can take to assist patients who have been victims of intimate partner violence. Recommendations on how to do this are provided. © 2016 John Wiley & Sons Ltd.
ERIC Educational Resources Information Center
Robison, Julie; Curry, Leslie; Gruman, Cynthia; Porter, Martha; Henderson, Charles R., Jr.; Pillemer, Karl
2007-01-01
Purpose: This article reports the results of a randomized, controlled evaluation of Partners in Caregiving in a Special Care Environment, an intervention designed to improve communication and cooperation between staff and families of residents in nursing home dementia programs. Design and Methods: Participants included 388 family members and 384…
Behavioral Problems among Children Whose Mothers Are Abused by an Intimate Partner
ERIC Educational Resources Information Center
Kernic, Mary A.; Wolf, Marsha E.; Holt, Victoria L.; McKnight, Barbara; Huebner, Colleen E.; Rivara, Frederick P.
2003-01-01
Objectives: To determine the association between children's exposure to maternal intimate partner violence (IPV) and behavior problems as measured by the parent report version of the Child Behavior Checklist (CBCL). Methods: The study population was comprised of 167 2- to 17-year-old children of Seattle women with police-reported or court-reported…
Child and Adolescent Predictors of Male Intimate Partner Violence
ERIC Educational Resources Information Center
Theobald, Delphine; Farrington, David P.
2012-01-01
Background: This study addresses to what extent child and adolescent explanatory factors predict male perpetrated intimate partner violence (IPV) in adulthood. Methods: We use prospective longitudinal data from the Cambridge Study in Delinquent Development (CSDD). The CSDD is a survey of 411 male born in the 1950s in an inner London area. The men…
ERIC Educational Resources Information Center
Choi, Y. Joon; An, Soonok
2016-01-01
Objective: The purpose of the study is to systematically review the available evidence on the effectiveness of interventions to improve the response of various helping professionals who come into contact with female victims of intimate partner violence (IPV). Methods: Several databases were searched, and N = 38 studies met the inclusion criteria…
ERIC Educational Resources Information Center
Kaslow, Nadine J.; Thompson, Martie P.
2008-01-01
Objective: This study assessed the unique and interactive effects of child maltreatment and mothers' physical intimate partner violence (IPV) status on low-SES African American children's psychological functioning. Methods: Mothers were recruited from a large, inner-city hospital, and those who met eligibility criteria were asked to complete a…
ERIC Educational Resources Information Center
Lamers-Winkelman, Francien; Willemen, Agnes M.; Visser, Margreet
2012-01-01
Objective: This study investigated the relationships among Adverse Childhood Experiences (ACEs) in a high risk clinical sample of Dutch children whose mothers were abused by an intimate partner, and the severity of behavioral and emotional problems and trauma symptoms. Methods: The study population comprised 208 children (M = 7.81 years, SD =…
ERIC Educational Resources Information Center
Wainwright, Megan; Bingham, Shantell; Sicwebu, Namhla
2017-01-01
Background: Field school research, which begins by considering community partners as pedagogues and thus exploring their perspectives on student learning, is uncommon. Photovoice is a method for self-expression of such marginalized voices. Purpose: Describe the photovoice to photodocumentary process and present results of its evaluation.…
Strategies for partner notification for sexually transmitted infections, including HIV.
Ferreira, Adel; Young, Taryn; Mathews, Catherine; Zunza, Moleen; Low, Nicola
2013-10-03
Partner notification (PN) is the process whereby sexual partners of an index patient are informed of their exposure to a sexually transmitted infection (STI) and the need to obtain treatment. For the person (index patient) with a curable STI, PN aims to eradicate infection and prevent re-infection. For sexual partners, PN aims to identify and treat undiagnosed STIs. At the level of sexual networks and populations, the aim of PN is to interrupt chains of STI transmission. For people with viral STI, PN aims to identify undiagnosed infections, which can facilitate access for their sexual partners to treatment and help prevent transmission. To assess the effects of different PN strategies in people with STI, including human immunodeficiency virus (HIV) infection. We searched electronic databases (the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE) without language restrictions. We scanned reference lists of potential studies and previous reviews and contacted experts in the field. We searched three trial registries. We conducted the most recent search on 31 August 2012. Published or unpublished randomised controlled trials (RCTs) or quasi-RCTs comparing two or more PN strategies. Four main PN strategies were included: patient referral, expedited partner therapy, provider referral and contract referral. Patient referral means that the patient notifies their sexual partners, either with (enhanced patient referral) or without (simple patient referral) additional verbal or written support. In expedited partner therapy, the patient delivers medication or a prescription for medication to their partner(s) without the need for a medical examination of the partner. In provider referral, health service personnel notify the partners. In contract referral, the index patient is encouraged to notify partner, with the understanding that the partners will be contacted if they do not visit the health service by a certain date. We analysed data according to paired partner referral strategies. We organised the comparisons first according to four main PN strategies (1. enhanced patient referral, 2. expedited partner therapy, 3. contract referral, 4. provider referral). We compared each main strategy with simple patient referral and then with each other, if trials were available. For continuous outcome measures, we calculated the mean difference (MD) with 95% confidence intervals (CI). For dichotomous variables, we calculated the risk ratio (RR) with 95% CI. We performed meta-analyses where appropriate. We performed a sensitivity analysis for the primary outcome re-infection rate of the index patient by excluding studies with attrition of greater than 20%. Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. We included 26 trials (17,578 participants, 9015 women and 8563 men). Five trials were conducted in developing countries. Only two trials were conducted among HIV-positive patients. There was potential for selection bias, owing to the methods of allocation used and of performance bias, owing to the lack of blinding in most included studies. Seven trials had attrition of greater than 20%, increasing the risk of bias.The review found moderate-quality evidence that expedited partner therapy is better than simple patient referral for preventing re-infection of index patients when combining trials of STIs that caused urethritis or cervicitis (6 trials; RR 0.71, 95% CI 0.56 to 0.89, I(2) = 39%). When studies with attrition greater than 20% were excluded, the effect of expedited partner therapy was attenuated (2 trials; RR 0.8, 95% CI 0.62 to 1.04, I(2) = 0%). In trials restricted to index patients with chlamydia, the effect was attenuated (2 trials; RR 0.90, 95% CI 0.60 to 1.35, I(2) = 22%). Expedited partner therapy also increased the number of partners treated per index patient (three trials) when compared with simple patient referral in people with chlamydia or gonorrhoea (MD 0.43, 95% CI 0.28 to 0.58) or trichomonas (MD 0.51, 95% CI 0.35 to 0.67), and people with any STI syndrome (MD 0.5, 95% CI 0.34 to 0.67). Expedited partner therapy was not superior to enhanced patient referral in preventing re-infection (3 trials; RR 0.96, 95% CI 0.60 to 1.53, I(2) = 33%, low-quality evidence). Home sampling kits for partners (four trials) did not result in lower rates of re-infection in the index case (measured in one trial), or higher numbers of partners elicited (three trials), notified (two trials) or treated (one trial) when compared with simple patient referral. There was no consistent evidence for the relative effects of provider, contract or other patient referral methods. In one trial among men with non-gonococcal urethritis, more partners were treated with provider referral than with simple patient referral (MD 0.5, 95% CI 0.37 to 0.63). In one study among people with syphilis, contract referral elicited treatment of more partners than provider referral (MD 2.2, 95% CI 1.95 to 2.45), but the number of partners receiving treatment was the same in both groups. Where measured, there was no statistical evidence of differences in the incidence of adverse effects between PN strategies. The evidence assessed in this review does not identify a single optimal strategy for PN for any particular STI. When combining trials of STI causing urethritis or cervicitis, expedited partner therapy was more successful than simple patient referral for preventing re-infection of the index patient but was not superior to enhanced patient referral. Expedited partner therapy interventions should include all components that were part of the trial intervention package. There was insufficient evidence to determine the most effective components of an enhanced patient referral strategy. There are too few trials to allow consistent conclusions about the relative effects of provider, contract or other patient referral methods for different STIs. More high-quality RCTs of PN strategies for HIV and syphilis, using biological outcomes, are needed.
PIAS1 interacts with FLASH and enhances its co-activation of c-Myb
2011-01-01
Background FLASH is a huge nuclear protein involved in various cellular functions such as apoptosis signalling, NF-κB activation, S-phase regulation, processing of histone pre-mRNAs, and co-regulation of transcription. Recently, we identified FLASH as a co-activator of the transcription factor c-Myb and found FLASH to be tightly associated with active transcription foci. As a huge multifunctional protein, FLASH is expected to have many interaction partners, some which may shed light on its function as a transcriptional regulator. Results To find additional FLASH-associated proteins, we performed a yeast two-hybrid (Y2H) screening with FLASH as bait and identified the SUMO E3 ligase PIAS1 as an interaction partner. The association appears to involve two distinct interaction surfaces in FLASH. We verified the interaction by Y2H-mating, GST pulldowns, co-IP and ChIP. FLASH and PIAS1 were found to co-localize in nuclear speckles. Functional assays revealed that PIAS1 enhances the intrinsic transcriptional activity of FLASH in a RING finger-dependent manner. Furthermore, PIAS1 also augments the specific activity of c-Myb, and cooperates with FLASH to further co-activate c-Myb. The three proteins, FLASH, PIAS1, and c-Myb, are all co-localized with active RNA polymerase II foci, resembling transcription factories. Conclusions We conclude that PIAS1 is a common partner for two cancer-related nuclear factors, c-Myb and FLASH. Our results point to a functional cooperation between FLASH and PIAS1 in the enhancement of c-Myb activity in active nuclear foci. PMID:21338522
Tarnowski, Krzysztof; Fituch, Kinga; Szczepanowski, Roman H; Dadlez, Michal; Kaus-Drobek, Magdalena
2014-01-01
RACK1 is a member of the WD repeat family of proteins and is involved in multiple fundamental cellular processes. An intriguing feature of RACK1 is its ability to interact with at least 80 different protein partners. Thus, the structural features enabling such interactomic flexibility are of great interest. Several previous studies of the crystal structures of RACK1 orthologs described its detailed architecture and confirmed predictions that RACK1 adopts a seven-bladed β-propeller fold. However, this did not explain its ability to bind to multiple partners. We performed hydrogen-deuterium (H-D) exchange mass spectrometry on three orthologs of RACK1 (human, yeast, and plant) to obtain insights into the dynamic properties of RACK1 in solution. All three variants retained similar patterns of deuterium uptake, with some pronounced differences that can be attributed to RACK1's divergent biological functions. In all cases, the most rigid structural elements were confined to B-C turns and, to some extent, strands B and C, while the remaining regions retained much flexibility. We also compared the average rate constants for H-D exchange in different regions of RACK1 and found that amide protons in some regions exchanged at least 1000-fold faster than in others. We conclude that its evolutionarily retained structural architecture might have allowed RACK1 to accommodate multiple molecular partners. This was exemplified by our additional analysis of yeast RACK1 dimer, which showed stabilization, as well as destabilization, of several interface regions upon dimer formation. PMID:24591271
CCHCR1 interacts with EDC4, suggesting its localization in P-bodies
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ling, Y.H.; Wong, C.C.; Li, K.W.
2014-09-10
Coiled‐coil alpha‐helical rod protein 1 (CCHCR1) is suggested as a candidate biomarker for psoriasis for more than a decade but its function remains poorly understood because of the inconsistent findings in the literature. CCHCR1 protein is suggested to be localized in the cytoplasm, nucleus, mitochondria, or centrosome and to regulate various cellular functions, including steroidogenesis, proliferation, differentiation, and cytoskeleton organization. In this study, we attempted to find a consensus between these findings by identifying the interaction partners of CCHCR1 using co-immunoprecipiation with a stable cell line expressing EGFP-tagged CCHCR1. Out of more than 100 co-immunoprecipitants identified by liquid chromatography-tandem massmore » spectrometry (LC-MS/MS), the enhancer of mRNA-decapping protein 4 (EDC4), which is a processing body (P-body) component, was particularly found to be the major interacting partner of CCHCR1. Confocal imaging confirmed the localization of CCHCR1 in P-bodies and its N-terminus is required for this subcellular localization, suggesting that CCHCR1 is a novel P-body component. As P-bodies are the site for mRNA metabolism, our findings provide a molecular basis for the function of CCHCR1, any disruption of which may affect the transcriptome of the cell, and causing abnormal cell functions. - Highlights: • We identified CCHCR1 as a novel P-body component. • We identified EDC4 as the major interacting partner of CCHCR1. • N-terminus of CCHCR1 protein is required for its P-bodies localization.« less
2010-01-01
Background Few studies have explored the women's experiences as a result of a partners' diagnosis of prostate cancer. This study begins to explore women's interactions with physicians (primary care and urologist) and the support needs associated with the diagnosis and treatment of their partners' prostate cancer. Methods Two focus groups (n = 14) of women whose partners were diagnosed with prostate cancer (diagnoses' 1 - 18 months). A trained facilitator used open-ended questions to explore ideas. The framework approach was used to analyze the transcripts. Results Three main themes emerged: 1. More support. Validation and information is needed for women including emotional support and opportunities to share experiences. 2. Role of the physician. The transfer of care once specialized treatment is no longer needed remained poorly defined, which increased confusion and feelings of abandonment related to the role of the primary physician. 3. Partners' relationship changes. Men became more dependent on their partners for support and to act as the primary communicator and caregiver. Conclusions Additional research is needed in this field to confirm the importance of training primary care physicians to consider holistic treatment approaches that recognize the partner and family needs as important in the complete physical and emotional healing of their patients. PMID:20211019
Young Adults With Type 1 Diabetes: Romantic Relationships and Implications for Well-Being
2017-01-01
Objective. The study goal was to examine whether young adults with type 1 diabetes involve romantic partners in their illness, and, if so, how their involvement is related to relationship quality and psychological well-being. Methods. A total of 68 people (mean age 25.5 years, [SD 3.7 years]) with type 1 diabetes (mean diabetes duration 6 years, [SD 6.7]) involved in a romantic relationship (mean relationship duration 25 months, [SD 27 months]) completed phone interviews. Communal coping (shared illness appraisal and collaborative problem-solving), partner supportive and unsupportive behavior, relationship quality, and psychological well-being were assessed with standardized measures. The study was partly descriptive in identifying the extent of communal coping and specific supportive and unsupportive behaviors and partly correlational in connecting communal coping and supportive or unsupportive behaviors to relationship quality and psychological well-being. Results. Descriptive findings showed that partners were somewhat involved in diabetes, but communal coping was less common compared to other chronically ill populations. The most common partner supportive behaviors were emotional and instrumental support. The most common partner unsupportive behavior was worry about diabetes. Correlational results showed that communal coping was related to greater partner emotional and instrumental support, but also to greater partner overprotective and controlling behaviors (P <0.01 for all). Communal coping was unrelated to relationship quality or psychological distress. Partner overinvolvement in diabetes management had a mixed relation to outcomes, whereas partner underinvolvement was uniformly related to poor outcomes. Conclusion. People with type 1 diabetes may benefit from increased partner involvement in illness. This could be facilitated by health care professionals. PMID:28588377
Clark, Jesse L; Perez-Brumer, Amaya G; Segura, Eddy R; Salvatierra, Hector J; Sanchez, Jorge; Lama, Javier R
New strategies to support partner notification (PN) are critical for STD control and require detailed understanding of how specific individual and partnership characteristics guide notification decisions. From 2011 to 2012, 397 MSM and TW recently diagnosed with HIV, syphilis, or another STD completed a survey on anticipated notification of recent sexual partners and associated factors. Qualitative interviews were conducted with a subset of participants to provide further depth to quantitative findings. Prevalence ratios and generalized estimating equation (GEE) models were used to analyze participant- and partner-level factors associated with anticipated PN. Among all partners reported, 52.5% were described as "Very Likely" or "Somewhat Likely" to be notified. Anticipated notification was more likely for main partners than casual (adjusted Prevalence Ratio [aPR], 95% CI: 0.63, 0.54-0.75) or commercial (aPR, 95% CI: 0.44, 0.31-0.62) partners. Other factors associated with likely notification included perception of the partner as an STD source (aPR, 95% CI: 1.27, 1.10-1.48) and anticipated future sexual contact with the partner (aPR, 95% CI: 1.30, 1.11-1.52). An HIV diagnosis was associated with a lower likelihood of notification than non-HIV STDs (aPR: 0.68, 0.55-0.86). Qualitative discussion of the barriers and incentives to PN reflected a similar differentiation of anticipated notification according to partnership type and type of HIV/STD diagnosis. Detailed attention to how partnership characteristics guide notification outcomes is essential to the development of new PN strategies. By accurately and thoroughly assessing the diversity of partnership interactions among individuals with HIV/STD, new notification techniques can be tailored to partner-specific circumstances.
Older partner selection in young African-American men who have sex with men.
Arrington-Sanders, Renata; Leonard, Lori; Brooks, Durryle; Celentano, David; Ellen, Jonathan
2013-06-01
Young African-American (AA) men who have sex with men (YAAMSM) have experienced the greatest proportional increase in new HIV cases compared with other groups. Bridging sexual partnerships between YAAMSM and older aged cohorts with higher rates of primary HIV infection has emerged as an important independent risk factor for the development of HIV. We explored reasons young AAMSM cite for being attracted to and seeking an older partner and the interpersonal needs met within older sexual partnerships. Seventeen in-depth semistructured qualitative interviews were conducted in YAAMSM residing in a midsized urban city with high HIV prevalence. Two coders independently evaluated transcribed data to identify/collapse codes that emerged. We analyzed data using categorical and contextualizing analytic methods. Two themes emerged from the text for seeking an older sexual partner: the emotional maturity the older partner represented and the ability of the older partner to expose the younger partner to more life experiences. In addition, two themes emerged around attraction: support and physical attractiveness of the older partner. Few men described seeking age-discordant relationships for the sole purpose of exchange sex. Older partners during first same-sex experience helped younger partners sort through sexual position and how to perform in relationships. These interviews suggest that YAAMSM may be seeking older partners to fulfill desires to be in a stable, emotionally mature relationship and for exposure in the larger community. Prevention strategies aimed at targeting adolescent MSM age-discordant relationships will need to address the interpersonal needs met within older sexual partnerships. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Roberts, Tracy E; Tsourapas, Angelos; Sutcliffe, Lorna; Cassell, Jackie; Estcourt, Claudia
2012-02-01
To undertake a cost-consequence analysis to assess two new models of partner notification (PN), known as Accelerated Partner Therapy (APT Hotline and APT Pharmacy), as compared with routine patient referral PN, for sex partners of people with chlamydia, gonorrhoea and non-gonococcal urethritis. Comparison of costs and outcomes alongside an exploratory trial involving two genitourinary medicine clinics and six community pharmacies. Index patients selected the PN method (APT Hotline, APT Pharmacy or routine PN) for their partners. Clinics and pharmacies recorded cost and resource use data including duration of consultation and uptake of treatment pack. Cost data were collected prospectively for two out of three interventions, and data were synthesised and compared in terms of effectiveness and costs. Routine PN had the lowest average cost per partner treated (approximately £46) compared with either APT Hotline (approximately £54) or APT Pharmacy (approximately £53) strategies. The cost-consequence analysis revealed that APT strategies were more costly but also more effective at treating partners compared to routine PN. The hotline strategy costs more than both the alternative PN strategies. If we accept that strategies which identify and treat partners the fastest are likely to be the most effective in reducing reinfection and onward transmission, then APT Hotline appears an effective PN strategy by treating the highest number of partners in the shortest duration. Whether the additional benefit is worth the additional cost cannot be determined in this preliminary analysis. These data will be useful for informing development of future randomised controlled trials of APT.
German, Danielle; Sherman, Susan A.; Latkin, Carl A.; Sirirojn, Bangorn; Thomson, Nick; Sutcliffe, Catherine G.; Aramrattana, Apinun; Celentano, David D.
2009-01-01
Background Given high rates of methamphetamine (MA) use among young people in Thailand and evidence of an association between MA and increased sexual risk behavior, we examined the association between women’s recent sexual partnerships, social network characteristics and drug and alcohol use. Methods Female participants (n=320) in an HIV behavioral trial among young (18–25 years) MA users in Chiang Mai completed a drug and sexual behavior survey and social network inventory. Multinomial regression analyses accounting for clustered data examined individual and network characteristics associated with recent sexual partnership category. We compared women with only one male partner in the past year (39%) to those with multiple male partners (37%) and those with only female partners (24%). Results Differences in levels of drug and alcohol use and social and sexual network characteristics were dependent on recent sexual partnership profiles. The multiple partner group reported an average of five male partners in the past year; 12% reported consistent condom use in the past 30 days. Compared to both groups, women with multiple male partners used MA more frequently, had larger non-sex networks with more MA users, were more likely to have an MA-using sex partner, and received less emotional support from their partners. Women with multiple male partners and only female partners reported more frequent alcohol use. Conclusions Policy and intervention efforts targeting drug use and sexual behavior among young Thai women are drastically needed and may benefit from consideration of the diversity within the population. These data point to the need for targeted prevention approaches that take into account the varying characteristics and social influences of these different groups of women. PMID:18191393
Nurses' roles in screening for intimate partner violence: a phenomenological study.
Al-Natour, A; Qandil, A; Gillespie, G L
2016-09-01
To describe Jordanian nurses' roles and practices in screening for intimate partner violence. Intimate partner violence is a recognized global health problem with a prevalence of 37% for the Eastern Mediterranean region. Jordanian nurses screening for intimate partner violence is as low as 10.8%. Nurses have encountered institutional and personal barriers hindering their screening practice. A descriptive phenomenological design was used for this study. A purposive sample of 12 male and female Jordanian nurses working at a university hospital in Jordan participated. Participants were interviewed in 2014 using a semi-structured, face-to-face interview. Steps of Colaizzi's phenomenological method were used to analyse the qualitative data. Four themes were derived from the data: (1) screening practices and roles for suspected IPV cases, (2) advantages for screening and disadvantages for not screening for intimate partner violence, (3) factors hindering screening practice and (4) feelings towards screening and not screening for intimate partner violence. Increasing Jordanian nurses' awareness of the need for intimate partner violence screening in this sample was needed. Professional education and training may facilitate the adoption of intimate partner violence screening practices. A key barrier to intimate partner violence screening is Jordanian nurses' personal beliefs. Overcoming these personal beliefs will necessitate a multi-faceted approach starting with schools of nursing and bridging into healthcare settings. Healthcare professionals including nursing and policy makers at health institutions should enforce screening policies and protocols for all receipt of care at first contact. In addition, an emphasis on modelling culturally congruent approaches to develop the trusting nurse-patient relationships and process for screening patients for intimate partner violence. © 2016 International Council of Nurses.
Lewis, Laura Foran
2017-03-01
Several qualitative studies explore the experience of being a partner to an individual with schizophrenia spectrum disorder, but these studies remain isolated "islands of knowledge." This meta-ethnography aimed to synthesize current qualitative studies using Noblit and Hare's method. Thirteen studies were identified for inclusion. Three overarching themes were revealed: unmet expectations of relationship, renegotiating relationship roles, and separation versus togetherness. Themes interacted as a cycle with separation versus togetherness as temporal endpoints. Partners also renegotiated relationships with mental health professionals to accommodate unmet expectations. Leverage points for intervention were identified.
Ron Levey, Ilana; Wang, Wenjuan
2014-01-01
Background Despite the substantial investment for providing HIV counselling and testing (VCT) services in Zambia, there has been little effort to systematically evaluate the quality of VCT services provided by various types of health providers. This study, conducted in 2009, examines VCT in the public and private sectors including private for-profit and NGO/faith-based sectors in Copperbelt and Luapula. Methods The study used five primary data collection methods to gauge quality of VCT services: closed-ended client interviews with clients exiting VCT sites; open-ended client interviews; interviews with facility managers; review of service statistics; and an observation of the physical environment for VCT by site. Over 400 clients and 87 facility managers were interviewed from almost 90 facilities. Sites were randomly selected and results are generalizable at the provincial level. Results The study shows concerning levels of underperformance in VCT services across the sectors. It reveals serious underperformance in counselling about key risk-reduction methods. Less than one-third of clients received counselling on reducing number of sexual partners and only approximately 5% of clients received counselling about disclosing test results to partners. In terms of client profiles, the NGO sector attracts the most educated clients and less educated Zambians seek VCT services at very low rates (7%). The private for-profit performs equally or sometimes better than other sectors even though this sector is not adequately integrated into the Zambian national response to HIV. Conclusion The private for-profit sector provides VCT services on par in quality with the other sectors. Most clients did not receive counselling on partner reduction or disclosure of HIV test results to partners. In a generalized HIV epidemic where multiple concurrent sexual partners are a significant problem for transmitting the disease, risk-reduction methods and discussion should be a main focus of pre-test and post-test counselling. PMID:25012796
Magno, Laio; Dourado, Inês; Silva, Luís Augusto V da; Brignol, Sandra; Amorim, Leila; MacCarthy, Sarah
2018-01-01
Discrimination related to gender identity may directly influence vulnerability to HIV through increased exposure to unprotected receptive anal intercourse (URAI). Little is known about the relationship between gender-based discrimination (GBD) and URAI with stable partners among transgender women. This mixed-methods research began with a cross-sectional survey conducted between 2014 and 2016 with transgender women in Salvador, the capital city in one of the poorest regions in Brazil. Respondent-driven sampling was used to recruit the study population. GBD was defined through Latent Class Analysis. Additionally, 19 semi-structured interviews with participants were transcribed and analyzed through thematic content analysis. URAI with stable partners was commonly reported (37.3%). GDB was positively associated with URAI among stable partners (OR = 6.47; IC 95%: 1.67-25.02). The analysis of the interviews illustrated how GBD impacted transgender women in diverse ways. Experiences with GBD perpetrated by the family often initiated a trajectory of economic vulnerability that led many to engage in survival sex work. The constant experience with GBD contributed to participants feeling an immense sense of trust with their stable partners, ultimately diminished their desire to use condoms. Further, the high frequency of GBD contributed to poor mental health overall, though some participants said engagement in transgender advocacy efforts provided a vital source of resilience and support. Our mixed-method study capitalizes upon the strengths of diverse data sets to produce a holistic understanding of GBD and URAI with stable partners. Furthermore, by confirming the association between greater GBD and URAI, we have demonstrated how GBD can impact condom negotiation in diverse relationships.
Protein arginine methylation: Cellular functions and methods of analysis.
Pahlich, Steffen; Zakaryan, Rouzanna P; Gehring, Heinz
2006-12-01
During the last few years, new members of the growing family of protein arginine methyltransferases (PRMTs) have been identified and the role of arginine methylation in manifold cellular processes like signaling, RNA processing, transcription, and subcellular transport has been extensively investigated. In this review, we describe recent methods and findings that have yielded new insights into the cellular functions of arginine-methylated proteins, and we evaluate the currently used procedures for the detection and analysis of arginine methylation.
Methods work better when couples talk.
Keller, S
1996-01-01
Sexual partners who communicate about reproductive health issues reduce their risk of acquiring a sexually transmitted disease (STD) or of unintended pregnancy, but few couples feel comfortable talking openly about sex. AIDS prevention programs have focused on improving couple communication, but family planning programs have emphasized women-controlled contraception as more reliable than barrier methods. The effectiveness of barrier methods would likely improve, however, if clients are counseled in couple communication. Effective communication about sexual issues requires self-confidence, and strengthening a woman's self-confidence may also improve her ability to negotiate condom use. Small discussion groups held among female factory workers in Thailand in 1993-94 led to an increase from 60% to 90% in the number of women who felt confident in discussing STD risk with a partner and to an increase from 36% to 82% in those who said they would not be embarrassed to give a partner a condom. A Nigerian study also suggested that more education may also improve prospects for couple communication and contraceptive usage. A US study showed that adolescent women who communicated openly with their partners reduced their risks of unintended pregnancy and STDs, and a Kenyan study indicated that communication increases contraceptive usage among married couples. Various projects around the world are attempting to counsel women on communication and condom negotiation, and counselors are beginning the difficult task of teaching women how to convince men to use condoms.
Robertson, Angela M.; Syvertsen, Jennifer L.; Martinez, Gustavo; Rangel, M. Gudelia; Palinkas, Lawrence A.; Stockman, Jamila K.; Ulibarri, Monica D.; Strathdee, Steffanie A.
2013-01-01
Background Female sex workers (FSWs) may benefit from pre-exposure prophylaxis (PrEP) including microbicides for HIV prevention. Since adherence is a key factor in PrEP efficacy, we explored microbicide acceptability and potential barriers to use within FSWs’ intimate relationships in Tijuana and Ciudad Juárez, Mexico, where HIV prevalence is increasing. Methods FSWs and their verified intimate (non-commercial) male partners completed quantitative and qualitative interviews from 2010–2012. Our complementary mixed methods design followed an iterative process to assess microbicide acceptability, explore related relationship dynamics, and identify factors associated with concern about male partners’ anger regarding microbicide use. Results Among 185 couples (n=370 individuals), interest in microbicides was high. In qualitative interviews with 28 couples, most participants were enthusiastic about microbicides for sex work contexts but some explained that microbicides could imply mistrust/infidelity within their intimate relationships. In the overall sample, nearly 1 in 6 participants (16%) worried that male partners would become angry about microbicides, which was associated with higher self-esteem among FSWs and lower self-esteem and past year conflict causing injury within relationships among men. Conclusions HIV prevention interventions should consider intimate relationship dynamics posing potential barriers to PrEP acceptability and adherence, involve male partners, and promote risk communication skills. PMID:23398385
Marembo, Joan; Zvinavashe, Mathilda; Nyamakura, Rudo; Shaibu, Sheila; Mogobe, Keitshokile Dintle
2014-10-01
To assess factors influencing infant-feeding methods selected by HIV-infected mothers. A descriptive quantitative study was conducted among 80 mothers with babies aged 0-6 months who were randomly selected and interviewed. Descriptive statistics were used to summarize the findings. Factors considered by women in choosing the infant-feeding methods included sociocultural acceptability (58.8%), feasibility and support from significant others (35%), knowledge of the selected method (55%), affordability (61.2%), implementation of the infant-feeding method without interference (62.5%), and safety (47.5%). Exclusive breast-feeding was the most preferred method of infant feeding. Disclosure of HIV status by a woman to her partner is a major condition for successful replacement feeding method, especially within the African cultural context. However, disclosure of HIV status to the partner was feared by most women as only 16.2% of the women disclosed their HIV status to partners. The factors considered by women in choosing the infant-feeding option were ability to implement the options without interference from significant others, affordability, and sociocultural acceptability. Knowledge of the selected option, its advantages and disadvantages, safety, and feasibility were also important factors. Nurses and midwives have to educate clients and support them in their choice of infant-feeding methods. © 2013 The Authors. Japan Journal of Nursing Science © 2013 Japan Academy of Nursing Science.
Makela, Ashley V; Murrell, Donna H; Parkins, Katie M; Kara, Jenna; Gaudet, Jeffrey M; Foster, Paula J
2016-10-01
Cellular magnetic resonance imaging (MRI) is an evolving field of imaging with strong translational and research potential. The ability to detect, track, and quantify cells in vivo and over time allows for studying cellular events related to disease processes and may be used as a biomarker for decisions about treatments and for monitoring responses to treatments. In this review, we discuss methods for labeling cells, various applications for cellular MRI, the existing limitations, strategies to address these shortcomings, and clinical cellular MRI.
Ogura-Tsujita, Yuki; Yukawa, Tomohisa
2008-01-01
Because mycoheterotrophic plants fully depend on their mycorrhizal partner for their carbon supply, the major limiting factor for the geographic distribution of these plants may be the presence of their mycorrhizal partner. Although this factor may seem to be a disadvantage for increasing geographic distribution, widespread mycoheterotrophic species nonetheless exist. The mechanism causing the wide distribution of some mycoheterotrophic species is, however, seldom discussed. We identified the mycorrhizal partner of a widespread mycoheterotrophic orchid, Eulophia zollingeri, using 12 individuals from seven populations in Japan, Myanmar, and Taiwan by DNA-based methods. All fungal ITS sequences from the roots closely related to those of Psathyrella candolleana (Coprinaceae) from GenBank accessions and herbarium specimens. These results indicate that E. zollingeri is exclusively associated with the P. candolleana species group. Further, the molecular data support the wide distribution and wide-ranging habitat of this fungal partner. Our data provide evidence that a mycoheterotrophic plant can achieve a wide distribution, even though it has a high mycorrhizal specificity, if its fungal partner is widely distributed.
Love, Trust, and HIV Risk Among Female Sex Workers and Their Intimate Male Partners
Bazzi, Angela Robertson; Martinez, Gustavo; Rangel, M. Gudelia; Ulibarri, Monica D.; Fergus, Kirkpatrick B.; Amaro, Hortensia; Strathdee, Steffanie A.
2015-01-01
Objectives. We examined correlates of love and trust among female sex workers and their noncommercial male partners along the Mexico–US border. Methods. From 2011 to 2012, 322 partners in Tijuana and Ciudad Juárez, Mexico, completed assessments of love and trust. Cross-sectional dyadic regression analyses identified associations of relationship characteristics and HIV risk behaviors with love and trust. Results. Within 161 couples, love and trust scores were moderately high (median 70/95 and 29/40 points, respectively) and correlated with relationship satisfaction. In regression analyses of HIV risk factors, men and women who used methamphetamine reported lower love scores, whereas women who used heroin reported slightly higher love. In an alternate model, men with concurrent sexual partners had lower love scores. For both partners, relationship conflict was associated with lower trust. Conclusions. Love and trust are associated with relationship quality, sexual risk, and drug use patterns that shape intimate partners’ HIV risk. HIV interventions should consider the emotional quality of sex workers’ intimate relationships. PMID:26066947
Condom Use by Partner Type Among Military and Police Personnel in Peru
Villaran, Manuel V.; Bayer, Angela; Konda, Kelika A.; Mendoza, Carlos; Quijandria, Hilda; Ampuero, Julia S.; Apolaya, Moises; Palacios, Oswaldo; Lescano, Andres G.; Vega, Antonio M.; Blazes, David L.; Kochel, Tadeusz; Montano, Silvia M.
2014-01-01
The aim of this study was to analyze the rates of condom use among military and police populations in Peru, focusing on differences in use by type of partner. A Knowledge Attitudes and Practices survey was conducted among 6,808 military and police personnel in 18 Peruvian cities between August–September 2006 and September–October 2007. A total of 90.2% of the survey respondents were male; mean age was 37.8 years and 77.9% were married/cohabiting. In all, 99.5% reported having had sex; 89% of the participants had their last sexual contact with their stable partner, 9.7% with a nonstable partner, and 0.8% with a sex worker. Overall, 20.4% used a condom during their most recent sexual contact. Reasons for nonuse of condoms included the following: perception that a condom was not necessary (31.3%) and using another birth control method (26.7%). Prevention efforts against sexually transmitted diseases should focus on strengthening condom use, especially among individuals with nonstable partners. PMID:22398988
CHIAO, CHI; MORISKY, DONALD E.
2011-01-01
Objective The main objective of this study is to understand the association between living with a regular sex partner, risk-taking behaviors, and one’s history of sexually transmitted infections (STIs). Methods Data on sexual behavior and STI histories were obtained from 876 Filipina entertainment establishment workers (FEEWs) through a large-scale participatory research survey. Results About one-third of FEEWs live with a regular sex partner. Single FEEWs are significantly more likely than partnered FEEWs to engage in commercial sex. Being single, engaging in commercial sex, and using condoms inconsistently, in turn, are significantly associated with a positive STI history. Conclusion These results suggest that living with a regular sex partner is an independent and protective factor against having an initial STI and subsequent reinfection. Programmatic strategies aimed at reducing STIs among entertainment establishment workers through promoting safer sex behaviors could potentially benefit by including a component that addresses sexual networks. PMID:17710751
Hoffman, Susie; Morrow, Kate M; Mantell, Joanne E; Rosen, Rochelle K; Carballo-Diéguez, Alex; Gai, Fang
2010-06-01
Using data from a U.S. clinical safety trial of tenofovir gel, a candidate microbicide, we explored the intersection of sexual pleasure and vaginal lubrication to understand whether and under what circumstances women would use a microbicide gel covertly with primary partners. This study question emerged from acceptability research in diverse settings showing that even though future microbicides are extolled as a disease prevention method that women could use without disclosing to their partners, many women assert they would inform their primary partner. Participants (N = 84), stratified by HIV-status and sexual activity (active vs. abstinent), applied the gel intra-vaginally for 14 days. At completion, quantitative acceptability data were obtained via questionnaire (N = 79) and qualitative data via small group discussions (N = 15 groups, 40 women). Quantitatively, 71% preferred a microbicide that could not be noticed by a sex partner and 86% experienced greater vaginal lubrication with daily use. Based on our analysis of the qualitative data, we suggest that women's perception that their primary partners would notice a microbicide gel is a more important reason for their caution regarding covert use than may previously have been recognized. Our findings also showed that women's assessment of the possibility of discreet, if not covert, use was strongly related to their perception of how a microbicide's added vaginal lubrication would influence their own and their partner's pleasure, as well as their partner's experience of his sexual performance. A microbicide that increases pleasure for both partners could potentially be used without engendering opposition from primary partners.
Harden, Janet K.; Sanda, Martin G.; Wei, John T.; Yarandi, Hossein; Hembroff, Larry; Hardy, Jill; Northouse, Laurel L.
2013-01-01
Background Partners of men treated for prostate cancer report more emotional distress associated with a diagnosis of prostate cancer than the men report; the duration of distress for partners is seldom examined. Objectives The purpose of this study was to determine the long-term effects of prostate cancer treatment on partners’ appraisal of their caregiving experience, marital satisfaction, sexual satisfaction, and quality of life (QOL) and factors related to these variables. Methods This exploratory study evaluated QOL among spouses of prostate cancer survivors at 24 months after treatment. Partners completed a battery of self-report questionnaires in a computer-assisted telephone interview. Results The sample consisted of 121 partners with average age of 60 years. There was a significant relationship between partners’ perceptions of bother about the man’s treatment outcomes and negative appraisal of their caregiving experience and poorer QOL. Younger partners who had a more negative appraisal of caregiving also had significantly worse QOL. Conclusions Men’s treatment outcomes continued to bother the partner and resulted in more negative appraisal and lower QOL 2 years after initial prostate cancer treatment. Younger partners may be at greater risk of poorer QOL outcomes especially if they have a more negative view of their caregiving experience. Implications for Practice Findings support prior research indicating that prostate cancer affects not only the person diagnosed with the disease but also his partner. Partners may benefit from tailored interventions designed to decrease negative appraisal and improve symptom management and QOL during the survivorship period. PMID:22728952
How reliable are self-reports of HIV status disclosure? Evidence from couples in Malawi
Conroy, Amy A.; Wong, Lauren H.
2015-01-01
Introduction The majority of research on human immunodeficiency virus (HIV) disclosure utilizes the perspective from a single individual, which cannot be substantiated in the absence of supporting data such as from a primary partner. Objectives The objectives of this study were to evaluate: (1) the extent to which self-reported HIV disclosure was confirmed by a primary partner; (2) individual and relationship-level predictors of self-reported versus confirmed disclosure; and (3) whether confirmed disclosure was a stronger predictor of correctly assessing a partner's HIV status compared to self-reported disclosure. Methods As part of an 8-wave longitudinal study from 2009-2011 in southern Malawi, 366 individuals (183 couples) were interviewed about their primary relationship (wave 3), individually tested for HIV (wave 4), and then asked whether they disclosed to their primary partner (wave 5). Results While 93% of respondents reported that they disclosed, only 64% of respondents had confirmed reports from their partner. Having communicated with partner about HIV was positively associated with self-reported disclosure; this association remained significant but became more precise in the models for confirmed disclosure. Confirmed disclosure, but not self-report, was a significant predictor of correctly assessing a partner's HIV status. Being male, having lower perceived partner infidelity, having higher relationship unity, and testing HIV-negative were positively and significantly associated with correct assessment. Dyadic data from two partners provide an improved measure of disclosure as compared to a single individual's self-report and could be used to identify behavioral and biomedical opportunities to prevent HIV transmission within couples. PMID:26379084
Partners' ambivalence towards cardiac arrest and hypothermia treatment: a qualitative study.
Holm, Marianne S; Norekvål, Tone M; Fålun, Nina; Gjengedal, Eva
2012-01-01
The purpose of this study was to examine the experiences of partners of patients who had cardiac arrest and subsequent hypothermia treatment in an intensive care unit (ICU). Nine in-depth interviews were conducted 5 months to 1 year after hospitalization. The participants were partners of patients who had survived cardiac arrest and had undergone hypothermia treatment without serious brain damage. All the interviews were analysed using Giorgi's phenomenological method. Six main themes emerged from the analysis: (1) terrified by witnessing the cardiac arrest; (2) ambivalence towards the ICU room and the cold body; (3) need for honest and realistic information; (4) anticipating the awakening; (5) social network as support and burden; and (6) the frightening homecoming. The essential structure of the partners' experiences of loved ones' cardiac arrest and hypothermia treatment was characterized by ambivalence; they experienced both fear and relief. There may be a relationship between experiences before entering the ICU and reactions during hypothermia treatment and afterwards. Some partners experienced a feeling of guilt after the resuscitation event, and especially during the awakening phase. After discharge, the partners described feeling anxiety. Nurses play a pivotal role in providing partners with information and in nurturing hope and feelings of security. Partners need to fully understand the reason for hypothermia treatment to enable them to accept the cold body as part of a life-saving process. We recommend follow-up after discharge. This may increase the partners' sense of security and control. © 2012 The Authors. Nursing in Critical Care © 2012 British Association of Critical Care Nurses.
Borus, Jonathan F; Alexander, Erik K; Bierer, Barbara E; Bringhurst, F Richard; Clark, Christopher; Klanica, Kaley E; Stewart, Erin C; Friedman, Lawrence S
2015-12-01
Concerns about the influence of industry support on medical education, research, and patient care have increased in both medical and political circles. Some academic medical centers, questioning whether industry support of medical education could be appropriate and not a conflict of interest, banned such support. In 2009, a Partners HealthCare System commission concluded that interactions with industry remained important to Partners' charitable academic mission and made recommendations to transparently manage such relationships. An Education Review Board (ERB) was created to oversee and manage all industry support of Partners educational activities.Using a case review method, the ERB developed guidelines to implement the commission's recommendations. A multi-funder rule was established that prohibits industry support from only one company for any Partners educational activity. Within that framework, the ERB established guidelines on industry support of educational conferences, clinical fellowships, and trainees' expenses for attending external educational programs; gifts of textbooks and other educational materials; promotional opportunities associated with Partners educational activities; Partners educational activities under contract with an industry entity; and industry-run programs using Partners resources.Although many changes have resulted from the implementation of the ERB guidelines, the number of industry grants for Partners educational activities has remained relatively stable, and funding for these activities declined only moderately during the first three full calendar years (2011-2013) of ERB oversight. The ERB continually educates both the Partners community and industry about the rationale for its guidelines and its openness to their refinement in response to changes in the external environment.
Intimate-partner homicide among pregnant and postpartum women.
Cheng, Diana; Horon, Isabelle L
2010-06-01
To identify pregnancy-associated homicide cases and to estimate the proportion that were perpetrated by a current or former intimate partner. This was an analysis of pregnancy-associated homicides occurring from 1993 to 2008 among Maryland residents using linked birth and death certificates, medical examiner charts, police records, and news publications. Homicides (n=110) were the leading cause of death during pregnancy and the first postpartum year. Women who were African American, younger than 25 years, and unmarried were at the highest risk for homicide. Firearms were the most common (61.8%) method of death. A current or former intimate partner was the perpetrator in 54.5% (n=60) of homicide deaths and a nonpartner in 31.8% (n=35). If the cases (n=15) in which the victim-offender relationship could not be identified are excluded, 63.2% of homicides were committed by an intimate partner. Compared with homicides in which the perpetrator was not an intimate partner, a significantly higher percentage (P<.05) of intimate-partner homicides occurred at home (66.7% compared with 28.6%), among women who had completed more than 12 years of education (23.3% compared with 5.7%), and who were married (28.3% compared with 8.6%). Intimate-partner homicides were most prevalent (25.0%) during the first 3 months of pregnancy and least prevalent during the first 3 months postpartum (5.0%). The majority of pregnancy-associated homicides were committed by current or former intimate partners, most commonly during the first 3 months of pregnancy. Efforts to protect women from partners optimally should begin before conception or very early in pregnancy. III.
2012-01-01
Background Prior longitudinal studies have shown high cumulative dating violence exposure rates among U.S adolescents, with 36 percent of males and 44 percent to 88 percent of females experiencing victimization across adolescence/young adulthood. Despite promising information characterizing adolescents’ dating violence experiences longitudinally, prior studies tended to concentrate on physical and sexual types of violence only, and did not report information on the number of times dating violence was experienced across multiple abusive partners. We used a method similar to the timeline follow-back interview to query adolescents about dating violence victimization from age 13 to 19—including dating violence types (physical, sexual, and psychological), frequency, age at first occurrence, and number of abusive partners. Methods A total of 730 subjects were randomly sampled from university registrar records and invited to complete an online survey, which utilized methods similar to the timeline follow-back interview, to retrospectively assess relationship histories and dating violence victimization from age 13 to 19 (eight questions adapted from widely-used surveys covering physical, sexual, and psychological abuse). Then, for each dating violence type, we asked about the number of occurrences, number of abusive partners, and age at first occurrence. Of 341 subjects who completed the survey, we included 297 (64 percent females; 36 percent males) who had a dating partner from age 13 to 19. Results Fully 64.7 percent of females and 61.7 percent of males reported dating violence victimization between age 13 and 19, with most experiencing multiple occurrences. More than one-third of abused females had two or more abusive partners: controlling behavior (35.6 percent); put downs/name calling (37.0); pressured sex (42.9); insults (44.3); slapped/hit (50.0); and threats (62.5). Males also had two or more abusive partners, as follows: controlling behavior (42.1 percent); insults (51.2); put downs (53.3); threats (55.6); and unwanted calls/texts/visits (60.7). Among abused females, 44.7 percent first experienced controlling behavior between age 13 and 15, whereas the majority (62.5 percent) first experienced pressured sex between age 16 and 17. Among males, for most abuse types, 16 percent to 30 percent of victimization began before age 15. Conclusions Our study adds information to a substantial, but still growing, body of literature about dating violence frequency, age of occurrence, and number of abusive partners among adolescents. PMID:22882898
2013-01-01
Background Knowledge of a sex partner’s HIV serostatus can influence sexual behavior and inform harm-reduction strategies. We sought to determine how often Peruvian men who have sex with men (MSM) and transgender women (TW) knew the HIV serostatus of their sex partners, if this knowledge was associated with any predictive factors or unprotected anal intercourse (UAI), and if UAI was associated with partner serostatus. Methods We analyzed data from the 2008 Peruvian MSM Sentinel Surveillance Survey. Data were collected by CASI about each participant’s three most recent male sex partners. Primary outcome was knowledge of a partner's HIV test result. Multivariate analysis assessed the effect of age, education, sexual identity, number of male partners, alcohol use during intercourse, type of partnership and length of partnership using logistic regression. Results 735 participants provided data on 1,643 of their most recent sex partners from the last 3 months. 179/735 (24.4%) of all participants knew HIV test results for at least one of their 3 most recent partners, corresponding to 230/1643 (14.0%) of all sexual partnerships in the last 3 months. In multivariate analysis, casual (OR: 0.27, 95% CI: 0.17-0.42) and exchange sex (OR: 0.31, 95% CI: 0.11-0.88) partners, compared to stable partners, were negatively associated with knowledge of partner serostatus, whereas relationships lasting longer than one night (<3 months OR: 2.20, 95% CI: 1.39-3.51; 3 months to 1 year OR: 3.00, 95% CI: 1.80-5.01; ≥ 1 year OR: 4.13, 95% CI: 2.40-7.10) were positively associated with knowledge of partner serostatus. Knowledge of partner serostatus was not associated with unprotected anal intercourse with that partner. Conclusions Few MSM and TW in Peru know their partners’ HIV serostatus. Our findings suggest that the type and length of partnership influence the likelihood of knowing a partner’s serostatus. Further research should explore the contexts and practices of partner communication, their effect on sexual behavior, and interventions to promote discussion of HIV testing and serostatus as an HIV prevention strategy in this population. PMID:23448153
Cellular automatons applied to gas dynamic problems
NASA Technical Reports Server (NTRS)
Long, Lyle N.; Coopersmith, Robert M.; Mclachlan, B. G.
1987-01-01
This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.
2011-01-01
Background There is a global consensus towards universal access to human immunodeficiency virus (HIV) services consequent to the increasing availability of antiretroviral therapy. However, to benefit from these services, knowledge of one's HIV status is critical. Partner notification for HIV is an important component of HIV counselling because it is an effective strategy to prevent secondary transmission, and promote early diagnosis and prompt treatment of HIV patients' sexual partners. However, counsellors are often frustrated by the reluctance of HIV-positive patients to voluntarily notify their sexual partners. This study aimed to explore tuberculosis (TB)/HIV counsellors' perspectives regarding confidentiality and partner notification. Methods Qualitative research interviews were conducted in the Northwest Region of Cameroon with 30 TB/HIV counsellors in 4 treatment centres, and 2 legal professionals between September and December 2009. Situational Analysis (positional map) was used for data analysis. Results Confidentiality issues were perceived to be handled properly despite concerns about patients' reluctance to report cases of violation due to apprehension of reprisals from health care staffs. All the respondents encouraged voluntary partner notification, and held four varying positions when confronted with patients who refused to voluntarily notify their partners. Position one focused on absolute respect of patients' autonomy; position two balanced between the respect of patients' autonomy and their partners' safety; position three wished for protection of sexual partners at risk of HIV infection and legal protection for counsellors; and position four requested making HIV testing and partner notification routine processes. Conclusion Counsellors regularly encounter ethical, legal and moral dilemmas between respecting patients' confidentiality and autonomy, and protecting patients' sexual partners at risk of HIV infection. This reflects the complexity of partner notification and demonstrates that no single approach is optimal, but instead certain contextual factors and a combination of different approaches should be considered. Meanwhile, adopting a human rights perspective in HIV programmes will balance the interests of both patients and their partners, and ultimately enhance universal access to HIV services. PMID:21639894
Jewett-Tennant, Jeri; Collins, Cyleste; Matloub, Jacqueline; Patrick, Alison; Chupp, Mark; Werner, James J.; Borawski, Elaine A.
2017-01-01
Background Community engagement and rigorous science are necessary to address health issues. Increasingly, community health organizations are asked to partner in research. To strengthen such community organization–academic partnerships, increase research capacity in community organizations, and facilitate equitable partnered research, the Partners in Education Evaluation and Research (PEER) program was developed. The program implements an 18-month structured research curriculum for one mid-level employee of a health-focused community-based organization with an organizational mentor and a Case Western Reserve University faculty member as partners. Methods The PEER program was developed and guided by a community–academic advisory committee and was designed to impact the research capacity of organizations through didactic modules and partnered research in the experiential phase. Active participation of community organizations and faculty during all phases of the program provided for bidirectional learning and understanding of the challenges of community-engaged health research. The pilot program evaluation used qualitative and quantitative data collection techniques, including experiences of the participants assessed through surveys, formal group and individual interviews, phone calls, and discussions. Statistical analysis of the change in fellows’ pre-test and post-test survey scores were conducted using paired sample t tests. The small sample size is recognized by the authors as a limitation of the evaluation methods and would potentially be resolved by including more cohort data as the program progresses. Qualitative data were reviewed by two program staff using content and narrative analysis to identify themes, describe and assess group phenomena and determine program improvements. Objectives The objective of PEER is to create equitable partnerships between community organizations and academic partners to further research capacity in said organizations and develop mutually beneficial research partnerships between academia and community organizations. Conclusion PEER demonstrates a commitment to successfully developing sustainable research capacity growth in community organizations, and improved partnered research with academic institutions. PMID:28230553
2013-01-01
Background Women’s ability to safely disclose their HIV-positive status to male partners is essential for uptake and continued use of prevention of mother-to-child transmission (PMTCT) services. However, little is known about the acceptability of potential approaches for facilitating partner disclosure. To lay the groundwork for developing an intervention, we conducted formative qualitative research to elicit feedback on three approaches for safe HIV disclosure for pregnant women and male partners in rural Kenya. Methods This qualitative acceptability research included in-depth interviews with HIV-infected pregnant women (n = 20) and male partners of HIV-infected women (n = 20) as well as two focus groups with service providers (n = 16). The participants were recruited at health care facilities in two communities in rural Nyanza Province, Kenya, during the period June to November 2011. Data were managed in NVivo 9 and analyzed using a framework approach, drawing on grounded theory. Results We found that facilitating HIV disclosure is acceptable in this context, but that individual participants have varying expectations depending on their personal situation. Many participants displayed a strong preference for couples HIV counseling and testing (CHCT) with mutual disclosure facilitated by a trained health worker. Home-based approaches and programs in which pregnant women are asked to bring their partners to the healthcare facility were equally favored. Participants felt that home-based CHCT would be acceptable for this rural setting, but special attention must be paid to how this service is introduced in the community, training of the health workers who will conduct the home visits, and confidentiality. Conclusion Pregnant couples should be given different options for assistance with HIV disclosure. Home-based CHCT could serve as an acceptable method to assist women and men with safe disclosure of HIV status. These findings can inform the design and implementation of programs geared at promoting HIV disclosure among pregnant women and partners, especially in the home-setting. PMID:24294994
Viral Linkage in HIV-1 Seroconverters and Their Partners in an HIV-1 Prevention Clinical Trial
Campbell, Mary S.; Mullins, James I.; Hughes, James P.; Celum, Connie; Wong, Kim G.; Raugi, Dana N.; Sorensen, Stefanie; Stoddard, Julia N.; Zhao, Hong; Deng, Wenjie; Kahle, Erin; Panteleeff, Dana; Baeten, Jared M.; McCutchan, Francine E.; Albert, Jan; Leitner, Thomas; Wald, Anna; Corey, Lawrence; Lingappa, Jairam R.
2011-01-01
Background Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519) was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners. Methodology/Principal Findings We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥50%. Adjudicators classified each seroconversion, finding 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%). Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters. Conclusions/Significance In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage determination process. PMID:21399681
Sexual behaviour of adolescents before and after the advent of AIDS.
Ostergaard, L
1997-12-01
To asses changes in sexual behaviour and use of contraceptive methods in Danish adolescents from the period before the advent of AIDS up to the present. Comparative study comparing data obtained from two identical cross sectional surveys Grenaa Gymnasium, Denmark. 626 high school students in 1982 and 499 high school students in 1996. An anonymous standardised self administered questionnaire handed out to high school students at Grenaa Gymnasium in spring 1982. In spring 1996 an identical questionnaire was handed out to every high school student at the same gymnasium. Age at first sexual intercourse, contraceptive use, and reasons for choice of contraceptive strategy. Today more males had experienced the first sexual intercourse before their 16th birthday (p = 0.047) compared with 1982, the reverse held for females (p = 0.003). From 1982 to 1996 condom use increased in males with no regular partner (p = 0.009). In females with no regular partner, there was during the same period an increase in considering the condom a personal contraceptive method (p = 0.017). In 1982 and 1996 protection from sexually transmitted diseases was given as reason for the choice of contraceptive strategy by 21% and 72% of males with no regular partner (p < 0.001), and by 7% and 32% of males with a regular partner (p < 0.001). The corresponding figures for females in 1982 and 1996 were 10% and 71% (p < 0.001) for those with no regular partner and 4% and 21% (p < 0.001) for those with a regular partner. Condom use has increased among adolescents with no regular partner brought up under the widespread awareness of AIDS, and the reason for this is to be protected from sexually transmitted diseases. A future decline in the incidence of various sexually transmitted diseases may be expected, and information on safe sexual practices should be continued.
ERIC Educational Resources Information Center
Atkinson, Amanda Marie; Sumnall, Harry; Measham, Fiona
2011-01-01
Aims: This study analysed the depiction of alcohol in an online government partnered social marketing campaign: Hollyoaks "The Morning After the Night Before". This was a new initiative, providing Internet-delivered episodes of a popular terrestrial drama targeted at young people. Methods: All the 12 episodes were coded for "visual…
ERIC Educational Resources Information Center
DePrince, Anne P.; Labus, Jennifer; Belknap, Joanne; Buckingham, Susan; Gover, Angela
2012-01-01
Objective: Using a longitudinal, randomized controlled trial, this study assessed the impact of a community-based outreach versus a more traditional criminal justice system-based referral program on women's distress and safety following police-reported intimate partner abuse (IPA). Method: Women (N = 236 women) with police-reported IPA were…
ERIC Educational Resources Information Center
Hamby, Sherry; Finkelhor, David; Turner, Heather; Ormrod, Richard
2010-01-01
Objective: To examine the co-occurrence of witnessing partner violence with child maltreatment and other forms of victimization. Method: Data are from the National Survey of Children's Exposure to Violence (NatSCEV), a nationally representative telephone survey of the victimization experiences of 4,549 youth aged 0-17. Results: Witnessing partner…
Child and Partner Abuse: Self-Reported Prevalence and Attitudes in the North of Portugal
ERIC Educational Resources Information Center
Machado, Carla; Goncalves, Miguel; Matos, Marlene; Dias, Ana Rita
2007-01-01
Objectives: To determine the self-reported prevalence of child and partner physical and emotional abuse in the north of Portugal and to investigate attitudes about these forms of family violence. Methods: Data were collected by questionnaire from a representative sample of parents in two-parent families with children under the age of 18 years. A…
ERIC Educational Resources Information Center
Suvak, Michael K.; Taft, Casey T.; Goodman, Lisa A.; Dutton, Mary Ann
2013-01-01
Objective: We examined 4 separate dimensions of functional social support (tangible, appraisal, self-esteem, and belonging) as predictors of change in depression over 4.5 years in a sample of women reporting intimate partner violence. Method: Participants were recruited as they sought help for violence perpetrated by a current or former male…
ERIC Educational Resources Information Center
Coco, Charles M.; Crumbly, Jack; Jackson, Faye Hall
2014-01-01
In this study, students of an undergraduate business course were introduced to industry partners via teleconferencing methods. The students were assigned to groups during the semester and each group had an industry partner that assisted in the learning process. The six dimensions of Fink's integrated course design were examined in order to…
Gesselman, Amanda N.; Bigatti, Silvia M.; Garcia, Justin R.; Coe, Kathryn; Cella, David; Champion, Victoria L.
2016-01-01
Background The association between spirituality and emotional health has been well documented in healthy individuals. A small literature has shown that spirituality plays a role in well-being for some breast cancer (BC) survivors; however, this link is virtually unexplored in partners/spouses of survivors. The current study aimed to assess the relationship between spirituality, emotional distress, and post-traumatic growth for BC survivors and their partners using a dyadic analyses approach. Methods A total of 498 couples who were 3–8 years post-BC diagnosis were recruited from the Eastern Oncology Group database. Results For BC survivors and their partners, greater levels of spirituality were associated with increases in their own post-traumatic growth. There was no relation between BC and partner spirituality and their own emotional distress, but partner’s spirituality was associated with reduced occurrence of intrusive thoughts in the BC survivor. In contrast, BC survivors’ spirituality was found to be wholly unrelated to partner’s mental health and adjustment. Conclusions Following diagnosis and treatment, spirituality appears to associate with positive growth in BC survivors and their partners. However, BC survivor and partner spirituality seem to be ineffective at impacting the other’s post-traumatic growth or emotional distress, with the exception of intrusive thoughts. Dyadic analysis takes into account the reciprocal influence of close relationships on health and is an important and under-utilized methodology in behavioral oncology research and clinical practice. PMID:27280320
Wolka, Anne M; Fairchild, Angelyn O; Reed, Shelby D; Anglin, Greg; Johnson, F Reed; Siegel, Michael; Noel, Rebecca
2017-01-01
Formal incorporation of patients' perspectives is becoming increasingly important in medical product development and decision making. This article shares practical advice regarding how patient advocacy organizations, the pharmaceutical industry, and academic experts in stated-preference research can effectively partner on benefit-risk patient preference studies. The authors partnered on a benefit-risk patient preference study related to the treatment of psoriasis. The authors from Duke Clinical Research Institute also share their experiences in collaborating with numerous other organizations in conducting benefit-risk patient preference studies. Upon initiation of the study partnership with appropriate experts, training is important to ensure all collaborators have a common understanding of the methodology, what objectives stated-preference methods can support, and expectations for the project. To the extent possible, partners should align on and document relevant clinical and logistical details prior to study implementation. During study implementation, partners should use good communication practices and document and maintain a record of any changes to the original plan. Presentation of the study results should be tailored to the particular audience, with the appropriate partner leading the presentation based on its format and audience. Partners from patient advocacy organizations, the pharmaceutical industry, and academia can effectively collaborate on benefit-risk patient preference studies with sufficient planning and ongoing communication. This article is a call for action for other organizations to engage in sharing of experiences regarding effective partnering in quantifying patient preferences in medical product development.
Attribution of Mild Cognitive Impairment Etiology in Patients and Their Care-Partners
Rodakowski, Juleen; Schulz, Richard; Gentry, Amanda; Garand, Linda; Lingler, Jennifer Hagerty
2013-01-01
Objective This study examined the attribution of MCI etiology assigned by individuals with MCI and their care-partners, and the extent to which the dyads agreed on the attribution of MCI etiology. Methods We conducted secondary analyses of cross-sectional data from a cohort of individuals with MCI (n=60) and their care-partners (n=60). The mean age of the individuals with MCI was 71.0±9.4 and of care-partners 64.2±11.0 years. The primary outcome was attribution assigned to memory deficits on the Illness Perception Questionnaire. We categorized the attribution of MCI etiology as either potentially controllable or uncontrollable factors. We described the distribution of MCI etiology with descriptive and contingency tables. We determined the odds of a patient or care-partner choosing one type of MCI etiology over another. Results Although individuals with MCI and their care-partners most frequently attributed MCI to uncontrollable factors (81.7% and 61.0%, respectively), care-partners were 28.41 [95% CI, 1.26 to 645.48] times more likely to attribute MCI etiology to potentially controllable factors than individuals with MCI. No significant associations between demographic factors and attribution of MCI etiology were found for the individuals with MCI or the care-partners. Conclusion Findings demonstrated that members of the dyad attributed MCI etiology to different causes. Attributions of MCI etiology should be explored by professionals to clarify misconceptions and potentially improve subsequent voluntary actions intended to assist oneself or others. PMID:24123240
Calzo, Jerel P.; Bogart, Laura M.; Francis, Evelyn; Kornetsky, Susan Z.; Winkler, Sabune J.; Kaberry, Julie M.
2017-01-01
BACKGROUND Engaging community partners as co-investigators in community-based participatory research (CBPR) requires certification in the rules, ethics, and principles governing research. Despite developments in making human research protection trainings more convenient and standardized (e.g., self-paced Internet modules), time constraints and the structure of the content (which may favor academic audiences) may hinder the training of community partners. OBJECTIVES This paper is motivated by a case example in which academic and community partners, and stakeholders of a community-based organization actively engaged the leadership of a pediatric hospital-based Institutional Review Board (IRB) in implementing a brief, community-responsive human subjects training session. METHODS A two hour, discussion-based human subjects training was developed via collaborations between the IRB and the community and academic partners. Interviews with trainees and facilitators after the training were used to evaluate its acceptability and possible future applications. CONCLUSIONS Local Institutional Review Boards have the potential to assist community partners in building sufficient knowledge of human subjects research protections to engage in specific projects, thereby expediting the progress of vital research to address community needs. We propose the need for developing truncated human subjects education materials to train and certify community partners, and creating formally organized entities within academic and medical institutions that specialize in community-based research to guide the development and implementation of alternative human subjects training certification opportunities for community partners. PMID:28230554
Demelash, Habtamu; Nigatu, Dabere; Gashaw, Ketema
2015-01-01
Introduction. Violence against women has serious consequences for their reproductive and sexual health including birth outcomes. In Ethiopia, though the average parity of pregnant women is much higher than in other African countries, the link between intimate partner violence with low birth weight is unknown. Objective. The aim of this study was to examine the association between intimate partner violence and low birth weight among pregnant women. Method. Hospital based case-control study was conducted among 387 mothers (129 cases and 258 controls). Anthropometric measurements were taken both from mothers and their live births. The association between intimate partner violence and birth weight was computed through bivariable and multivariable logistic regression analyses and statistical significance was declared at P < 0.05. Result. Out of 387 interviewed mothers, 100 (25.8%) had experienced intimate partner violence during their index pregnancy period. Relatively more mothers of low birth weight infants were abused (48%) compared with controls (16.4%). Those mothers who suffered acts of any type of intimate partner violence during pregnancy were three times more likely to have a newborn with low birth weight (95% CI; (1.57 to 7.18)). The association between overall intimate partner violence and LBW was adjusted for potential confounder variables. Conclusion. This research result gives insight for health professional about the importance of screening for intimate partner violence during pregnancy. Health care providers should consider violence in their practice and try to identify women at risk. PMID:26798345
Postpartum depression among visible and invisible sexual minority women: a pilot study.
Flanders, Corey E; Gibson, Margaret F; Goldberg, Abbie E; Ross, Lori E
2016-04-01
Significant numbers of sexual minority women are choosing to parent. Despite this, there is limited research on postpartum depression (PPD) with sexual minority mothers and less research considering differences within sexual minority women in the experience of PPD. This research examines two questions to address this gap in research: (1) Do experiences of PPD symptoms vary between different subgroups of sexual minority women, and (2) Which recruitment strategies effectively address the challenge of recruiting sexual minority women who are pregnant? Two Canadian studies recruited participants via consecutive or convenience sampling from midwifery clinics and hospital sites. Participants completed prenatal and postnatal measures of PPD symptoms, social support, and perceived discrimination. Considering our first question, we found an interaction effect between past sexual behavior and current partner gender. Women currently partnered with men reported higher scores on the Edinburgh Postpartum Depression Scale when their sexual history included partners of more than one gender, whereas this effect was not found among women who were currently partnered with women or not partnered. Regarding our second question, most sexual minority participants recruited through convenience sampling were partnered with women and identified as lesbian or queer, while most participants recruited through consecutive sampling were partnered with men and identified as bisexual. Women whose sexual histories include more than one gender and are currently partnered with men may be at a higher risk for PPD symptoms. Recruitment method may influence the type of sample recruited for perinatal mental health research among sexual minority women.
Sawyer, Pamela J.; Casad, Bettina J.; Townsend, Sarah S. M.; Mendes, Wendy Berry
2012-01-01
Objectives. We sought to demonstrate that individuals who anticipate interacting with a prejudiced cross-race/ethnicity partner show an exacerbated stress response, as measured through both self-report and hemodynamic and vascular responses, compared with individuals anticipating interacting with a nonprejudiced cross-race/ethnicity partner. Methods. Through a questionnaire exchange with a White interaction partner (a confederate) Latina participants learned that their partner had racial/ethnic biased or egalitarian attitudes. Latina participants reported their cognitive and emotional states, and cardiovascular responses were measured while participants prepared and delivered a speech to the White confederate. Results. Participants who believed that their interaction partner held prejudiced attitudes reported greater concern and more threat emotions before the interaction, and more stress after the interaction, and showed greater cardiovascular response than did participants who believed that their partner had egalitarian attitudes. Conclusions. This study shows that merely anticipating prejudice leads to both psychological and cardiovascular stress responses. These results are consistent with the conceptualization of anticipated discrimination as a stressor and suggest that vigilance for prejudice may be a contributing factor to racial/ethnic health disparities in the United States. PMID:22420818
Better Off Alone Than With a Smoker: The Influence of Partner’s Smoking Behavior in Later Life
Wright, Laura
2016-01-01
Objectives: We examine how the likelihood of smoking cessation among smokers and patterns of adherence to smoking cessation differ by partnership status, partnership changes, and partners’ smoking behavior. The data are a nationally representative sample of smokers in middle and older age from the Health and Retirement Study (1992–2010). Method: We use multivariate logistic regression models to analyze the likelihood of smoking cessation among smokers and then estimate adherence to smoking cessation using discrete-time event history models. Results: Those partnered with smokers and those whose partners relapse into smoking are much less likely than the unpartnered to quit smoking and adhere to smoking cessation. Respondents partnered with non-smokers and those whose partners quit smoking are more likely to quit smoking than the unpartnered. Those recently widowed, divorced, and repartnered have similar smoking changes to the consistently unpartnered. Discussion: Being partnered does not always mean healthier behavior changes. Rather, the association between partnership status and smoking changes depends greatly on the health behavior changes of the partner. The partnership context at the time of smoking cessation sets the stage for longer term patterns of adherence, shaping health in older age. PMID:25693998
Roman, Joan Garcia; Flood, Sarah M.; Genadek, Katie R.
2017-01-01
BACKGROUND Time shared with a partner is an indicator of marital well-being and couples want to spend time together. However, time with a partner depends on work and family arrangements as well as the policies, norms, and values that prevail in society. Contrary to time spent with children, couples’ shared time in cross-national context is relatively unstudied. Previous studies from specific countries show that dual-earner couples spend less time together and that parents spend less time alone together. OBJECTIVE The aim of our study is to investigate partnered parents’ shared time across countries to understand how social conditions, cultural norms, and policy contexts are related to the amount and nature of couples’ shared time. Specifically, we compare time with a partner in the US, France, and Spain. METHODS We use data from national time use surveys conducted in the US, France, and Spain. We leverage information about with whom activities are done to examine three types of time shared with a partner for parents with children under age 10: total time with a partner indicates the minutes per day spent in the presence of a partner; exclusive time corresponds to the minutes per day spent alone with a partner when no one else is present; and family time indicates the minutes per day spent with a partner and a child at the same time. RESULTS Our results show that American couples spend the least time together, and Spanish couples spend the most time together. Parents in France spend the most time alone together. The most striking difference across countries is in time with a partner and children, which is much higher among Spanish families. CONCLUSION Paid work constraints explain a small part of the differences in couples’ shared time that we observe between countries. Differences in couples’ shared time across countries seem to be related to social norms surrounding family and general time use. PMID:29416440
Argento, Elena; Shannon, Kate; Nguyen, Paul; Dobrer, Sabina; Chettiar, Jill; Deering, Kathleen N.
2015-01-01
Background Despite high HIV burden among sex workers (SWs) globally, and relatively high prevalence of client condom use, research on potential HIV/STI risk pathways of intimate partnerships is limited. This study investigated partner/dyad-level factors associated with inconsistent condom use among SWs with intimate partners in Vancouver, Canada. Methods Baseline data (2010–2013) were drawn from a community-based prospective cohort of women SWs. Multivariable generalized estimating equations logistic regression examined dyad-level factors associated with inconsistent condom use (<100% in last six months) with up to three male intimate partners per SW. Adjusted odds ratios and 95% confidence intervals were reported (AOR[95%CI]). Results Overall, 369 SWs reported having at least one intimate partner, with 70.1% reporting inconsistent condom use. Median length of partnerships was 1.8 years, with longer duration linked to inconsistent condom use. In multivariable analysis, dyad factors significantly associated with increased odds of inconsistent condom use included: having a cohabiting (5.43[2.53–11.66]) or non-cohabiting intimate partner (2.15[1.11–4.19]) (versus casual partner), providing drugs (3.04[1.47–6.30]) or financial support to an intimate partner (2.46[1.05–5.74]), physical intimate partner violence (2.20[1.17–4.12]), and an intimate partner providing physical safety (2.08[1.11–3.91]); non-injection drug use was associated with a 68% reduced odds (0.32[0.17–0.60]). Conclusions Our study highlights the complex role of dyad-level factors in shaping sexual and drug-related HIV/STI risk pathways for SWs from intimate partners. Couple and gender-focused interventions efforts are needed to reduce HIV/STI risks to SWs through intimate partnerships. This research supports further calls for integrated violence and HIV prevention within broader sexual/reproductive health efforts for SWs. PMID:26585612
Starcevic, Antonio; Dunlap, Walter C.; Cullum, John; Shick, J. Malcolm; Hranueli, Daslav; Long, Paul F.
2010-01-01
Background The success of tropical reef-building corals depends on the metabolic co-operation between the animal host and the photosynthetic performance of endosymbiotic algae residing within its cells. To examine the molecular response of the coral Acropora microphthalma to high levels of solar irradiance, a cDNA library was constructed by PCR-based suppression subtractive hybridisation (PCR-SSH) from mRNA obtained by transplantation of a colony from a depth of 12.7 m to near-surface solar irradiance, during which the coral became noticeably paler from loss of endosymbionts in sun-exposed tissues. Methodology/Principal Findings A novel approach to sequence annotation of the cDNA library gave genetic evidence for a hypothetical biosynthetic pathway branching from the shikimic acid pathway that leads to the formation of 4-deoxygadusol. This metabolite is a potent antioxidant and expected precursor of the UV-protective mycosporine-like amino acids (MAAs), which serve as sunscreens in coral phototrophic symbiosis. Empirical PCR based evidence further upholds the contention that the biosynthesis of these MAA sunscreens is a ‘shared metabolic adaptation’ between the symbiotic partners. Additionally, gene expression induced by enhanced solar irradiance reveals a cellular mechanism of light-induced coral bleaching that invokes a Ca2+-binding synaptotagmin-like regulator of SNARE protein assembly of phagosomal exocytosis, whereby algal partners are lost from the symbiosis. Conclusions/Significance Bioinformatics analyses of DNA sequences obtained by differential gene expression of a coral exposed to high solar irradiance has revealed the identification of putative genes encoding key steps of the MAA biosynthetic pathway. Revealed also by this treatment are genes that implicate exocytosis as a cellular process contributing to a breakdown in the metabolically essential partnership between the coral host and endosymbiotic algae, which manifests as coral bleaching. PMID:21103042
Cellular RNA binding proteins NS1-BP and hnRNP K regulate influenza A virus RNA splicing.
Tsai, Pei-Ling; Chiou, Ni-Ting; Kuss, Sharon; García-Sastre, Adolfo; Lynch, Kristen W; Fontoura, Beatriz M A
2013-01-01
Influenza A virus is a major human pathogen with a genome comprised of eight single-strand, negative-sense, RNA segments. Two viral RNA segments, NS1 and M, undergo alternative splicing and yield several proteins including NS1, NS2, M1 and M2 proteins. However, the mechanisms or players involved in splicing of these viral RNA segments have not been fully studied. Here, by investigating the interacting partners and function of the cellular protein NS1-binding protein (NS1-BP), we revealed novel players in the splicing of the M1 segment. Using a proteomics approach, we identified a complex of RNA binding proteins containing NS1-BP and heterogeneous nuclear ribonucleoproteins (hnRNPs), among which are hnRNPs involved in host pre-mRNA splicing. We found that low levels of NS1-BP specifically impaired proper alternative splicing of the viral M1 mRNA segment to yield the M2 mRNA without affecting splicing of mRNA3, M4, or the NS mRNA segments. Further biochemical analysis by formaldehyde and UV cross-linking demonstrated that NS1-BP did not interact directly with viral M1 mRNA but its interacting partners, hnRNPs A1, K, L, and M, directly bound M1 mRNA. Among these hnRNPs, we identified hnRNP K as a major mediator of M1 mRNA splicing. The M1 mRNA segment generates the matrix protein M1 and the M2 ion channel, which are essential proteins involved in viral trafficking, release into the cytoplasm, and budding. Thus, reduction of NS1-BP and/or hnRNP K levels altered M2/M1 mRNA and protein ratios, decreasing M2 levels and inhibiting virus replication. Thus, NS1-BP-hnRNPK complex is a key mediator of influenza A virus gene expression.
Proteomic Analysis of Virus-Host Interactions in an Infectious Context Using Recombinant Viruses*
Komarova, Anastassia V.; Combredet, Chantal; Meyniel-Schicklin, Laurène; Chapelle, Manuel; Caignard, Grégory; Camadro, Jean-Michel; Lotteau, Vincent; Vidalain, Pierre-Olivier; Tangy, Frédéric
2011-01-01
RNA viruses exhibit small-sized genomes encoding few proteins, but still establish complex networks of interactions with host cell components to achieve replication and spreading. Ideally, these virus-host protein interactions should be mapped directly in infected cell culture, but such a high standard is often difficult to reach when using conventional approaches. We thus developed a new strategy based on recombinant viruses expressing tagged viral proteins to capture both direct and indirect physical binding partners during infection. As a proof of concept, we engineered a recombinant measles virus (MV) expressing one of its virulence factors, the MV-V protein, with a One-STrEP amino-terminal tag. This allowed virus-host protein complex analysis directly from infected cells by combining modified tandem affinity chromatography and mass spectrometry analysis. Using this approach, we established a prosperous list of 245 cellular proteins interacting either directly or indirectly with MV-V, and including four of the nine already known partners of this viral factor. These interactions were highly specific of MV-V because they were not recovered when the nucleoprotein MV-N, instead of MV-V, was tagged. Besides key components of the antiviral response, cellular proteins from mitochondria, ribosomes, endoplasmic reticulum, protein phosphatase 2A, and histone deacetylase complex were identified for the first time as prominent targets of MV-V and the critical role of the later protein family in MV replication was addressed. Most interestingly, MV-V showed some preferential attachment to essential proteins in the human interactome network, as assessed by centrality and interconnectivity measures. Furthermore, the list of MV-V interactors also showed a massive enrichment for well-known targets of other viruses. Altogether, this clearly supports our approach based on reverse genetics of viruses combined with high-throughput proteomics to probe the interaction network that viruses establish in infected cells. PMID:21911578
A Direct Cell Quenching Method for Cell-Culture Based Metabolomics
A crucial step in metabolomic analysis of cellular extracts is the cell quenching process. The conventional method first uses trypsin to detach cells from their growth surface. This inevitably changes the profile of cellular metabolites since the detachment of cells from the extr...
Transcription Regulation of HYPK by Heat Shock Factor 1
Das, Srijit; Bhattacharyya, Nitai Pada
2014-01-01
HYPK (Huntingtin Yeast Partner K) was originally identified by yeast two-hybrid assay as an interactor of Huntingtin, the protein mutated in Huntington's disease. HYPK was characterized earlier as an intrinsically unstructured protein having chaperone-like activity in vitro and in vivo. HYPK has the ability of reducing rate of aggregate formation and subsequent toxicity caused by mutant Huntingtin. Further investigation revealed that HYPK is involved in diverse cellular processes and required for normal functioning of cells. In this study we observed that hyperthermia increases HYPK expression in human and mouse cells in culture. Expression of exogenous Heat Shock Factor 1 (HSF1), upon heat treatment could induce HYPK expression, whereas HSF1 knockdown reduced endogenous as well as heat-induced HYPK expression. Putative HSF1-binding site present in the promoter of human HYPK gene was identified and validated by reporter assay. Chromatin immunoprecipitation revealed in vivo interaction of HSF1 and RNA polymerase II with HYPK promoter sequence. Additionally, acetylation of histone H4, a known epigenetic marker of inducible HSF1 binding, was observed in response to heat shock in HYPK gene promoter. Overexpression of HYPK inhibited cells from lethal heat-induced death whereas knockdown of HYPK made the cells susceptible to lethal heat shock-induced death. Apart from elevated temperature, HYPK was also upregulated by hypoxia and proteasome inhibition, two other forms of cellular stress. We concluded that chaperone-like protein HYPK is induced by cellular stress and under transcriptional regulation of HSF1. PMID:24465598
Majerciak, Vladimir; Lu, Mathew; Li, Xiaofan
2014-01-01
Kaposi sarcoma–associated herpesvirus (KSHV) ORF57 is a multifunctional post-transcriptional regulator essential for viral gene expression during KSHV lytic infection. ORF57 requires interactions with various cellular proteins for its function. Here, we identified serine/arginine-rich splicing factor 3 (SRSF3, formerly known as SRp20) as a cellular cofactor involved in ORF57-mediated splicing of KSHV K8β RNA. In the absence of ORF57, SRSF3 binds to a suboptimal K8β intron and inhibits K8β splicing. Knockdown of SRSF3 promotes K8β splicing, mimicking the effect of ORF57. The N-terminal half of ORF57 binds to the RNA recognition motif of SRSF3, which prevents SRSF3 from associating with the K8β intron RNA and therefore attenuates the suppressive effect of SRSF3 on K8β splicing. ORF57 also promotes splicing of heterologous non-KSHV transcripts that are negatively regulated by SRSF3, indicating that the effect of ORF57 on SRSF3 activity is independent of RNA target. SPEN proteins, previously identified as ORF57-interacting partners, suppress ORF57 splicing activity by displacing ORF57 from SRSF3–RNA complexes. In summary, we have identified modulation of SRSF3 activity as the molecular mechanism by which ORF57 promotes RNA splicing. PMID:25234929
Majerciak, Vladimir; Lu, Mathew; Li, Xiaofan; Zheng, Zhi-Ming
2014-11-01
Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 is a multifunctional post-transcriptional regulator essential for viral gene expression during KSHV lytic infection. ORF57 requires interactions with various cellular proteins for its function. Here, we identified serine/arginine-rich splicing factor 3 (SRSF3, formerly known as SRp20) as a cellular cofactor involved in ORF57-mediated splicing of KSHV K8β RNA. In the absence of ORF57, SRSF3 binds to a suboptimal K8β intron and inhibits K8β splicing. Knockdown of SRSF3 promotes K8β splicing, mimicking the effect of ORF57. The N-terminal half of ORF57 binds to the RNA recognition motif of SRSF3, which prevents SRSF3 from associating with the K8β intron RNA and therefore attenuates the suppressive effect of SRSF3 on K8β splicing. ORF57 also promotes splicing of heterologous non-KSHV transcripts that are negatively regulated by SRSF3, indicating that the effect of ORF57 on SRSF3 activity is independent of RNA target. SPEN proteins, previously identified as ORF57-interacting partners, suppress ORF57 splicing activity by displacing ORF57 from SRSF3-RNA complexes. In summary, we have identified modulation of SRSF3 activity as the molecular mechanism by which ORF57 promotes RNA splicing. Published by Cold Spring Harbor Laboratory Press for the RNA Society.
Xie, Li; Yamamoto, Brenda; Haoudi, Abdelali; Semmes, O John; Green, Patrick L
2006-03-01
HTLV-1 cellular transformation and disease induction is dependent on expression of the viral Tax oncoprotein. PDZ is a modular protein interaction domain used in organizing signaling complexes in eukaryotic cells through recognition of a specific binding motif in partner proteins. Tax-1, but not Tax-2, contains a PDZ-binding domain motif (PBM) that promotes the interaction with several cellular PDZ proteins. Herein, we investigate the contribution of the Tax-1 PBM in HTLV-induced proliferation and immortalization of primary T cells in vitro and viral survival in an infectious rabbit animal model. We generated several HTLV-1 and HTLV-2 Tax viral mutants, including HTLV-1deltaPBM, HTLV-2+C22(+PBM), and HTLV-2+ C18(deltaPBM). All Tax mutants maintained the ability to significantly activate the CREB/ATF or NFkappaB signaling pathways. Microtiter proliferation assays revealed that the Tax-1 PBM significantly increases both HTLV-1- and HTLV-2-induced primary T-cell proliferation. In addition, Tax-1 PBM was responsible for the micronuclei induction activity of Tax-1 relative to that of Tax-2. Viral infection and persistence were severely attenuated in rabbits inoculated with HTLV-1deltaPBM. Our results provide the first direct evidence suggesting that PBM-mediated associations between Tax-1 and cellular proteins play a key role in HTLV-induced cell proliferation and genetic instability in vitro and facilitate viral persistence in vivo.
Excoffon, Katherine J D Ashbourne; Hruska-Hageman, Alesia; Klotz, Michael; Traver, Geri L; Zabner, Joseph
2004-09-01
The coxsackie and adenovirus receptor (CAR) plays a role in viral infection, maintenance of the junction adhesion complex in polarized epithelia, and modulation of cellular growth properties. As a viral receptor, the C-terminus appears to play no role indicating that the major function of CAR is to tether the virus to the cell. By contrast, the C-terminus is known to play a role in cellular localization and probably has a significant function in CAR-mediated adhesion and cell growth properties. We hypothesized that the CAR PDZ (PSD-95/Disc-large/ZO-1) binding motif interacts with PDZ-domain-containing proteins to modulate the cellular phenotype. CAR was modified by deleting the last four amino acids (CARDeltaGSIV) and evaluated for cell-cell adhesion in polarized primary human airway epithelia and growth characteristics in stably transfected L-cells. Although ablation of the CAR PDZ-binding motif did not affect adenoviral infection, it did have a significant effect both on cell-cell adhesion and on cell growth. Expression of CARDeltaGSIV failed to increase the transepithelial resistance in polarized epithelia to the same degree as wild-type CAR and failed to act as a growth modulator in L-cells. Furthermore, we provide evidence for three new CAR interacting partners, including MAGI-1b, PICK1 and PSD-95. CAR appears to interact with several distinct PDZ-domain-containing proteins and may exert its biological function through these interactions.
Improved Endpoints for Cancer Immunotherapy Trials
Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd
2010-01-01
Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737
McPhillips, M. G.; Oliveira, J. G.; Spindler, J. E.; Mitra, R.; McBride, A. A.
2006-01-01
Bromodomain protein 4 (Brd4) has been identified as the cellular binding target through which the E2 protein of bovine papillomavirus type 1 links the viral genome to mitotic chromosomes. This tethering ensures retention and efficient partitioning of genomes to daughter cells following cell division. E2 is also a regulator of viral gene expression and a replication factor, in association with the viral E1 protein. In this study, we show that E2 proteins from a wide range of papillomaviruses interact with Brd4, albeit with variations in efficiency. Moreover, disruption of the E2-Brd4 interaction abrogates the transactivation function of E2, indicating that Brd4 is required for E2-mediated transactivation of all papillomaviruses. However, the interaction of E2 and Brd4 is not required for genome partitioning of all papillomaviruses since a number of papillomavirus E2 proteins associate with mitotic chromosomes independently of Brd4 binding. Furthermore, mutations in E2 that disrupt the interaction with Brd4 do not affect the ability of these E2s to associate with chromosomes. Thus, while all papillomaviruses attach their genomes to cellular chromosomes to facilitate genome segregation, they target different cellular binding partners. In summary, the E2 proteins from many papillomaviruses, including the clinically important alpha genus human papillomaviruses, interact with Brd4 to mediate transcriptional activation function but not all depend on this interaction to efficiently associate with mitotic chromosomes. PMID:16973557
Choudhry, Priya
2016-01-01
Counting cells and colonies is an integral part of high-throughput screens and quantitative cellular assays. Due to its subjective and time-intensive nature, manual counting has hindered the adoption of cellular assays such as tumor spheroid formation in high-throughput screens. The objective of this study was to develop an automated method for quick and reliable counting of cells and colonies from digital images. For this purpose, I developed an ImageJ macro Cell Colony Edge and a CellProfiler Pipeline Cell Colony Counting, and compared them to other open-source digital methods and manual counts. The ImageJ macro Cell Colony Edge is valuable in counting cells and colonies, and measuring their area, volume, morphology, and intensity. In this study, I demonstrate that Cell Colony Edge is superior to other open-source methods, in speed, accuracy and applicability to diverse cellular assays. It can fulfill the need to automate colony/cell counting in high-throughput screens, colony forming assays, and cellular assays. PMID:26848849
ChainMail based neural dynamics modeling of soft tissue deformation for surgical simulation.
Zhang, Jinao; Zhong, Yongmin; Smith, Julian; Gu, Chengfan
2017-07-20
Realistic and real-time modeling and simulation of soft tissue deformation is a fundamental research issue in the field of surgical simulation. In this paper, a novel cellular neural network approach is presented for modeling and simulation of soft tissue deformation by combining neural dynamics of cellular neural network with ChainMail mechanism. The proposed method formulates the problem of elastic deformation into cellular neural network activities to avoid the complex computation of elasticity. The local position adjustments of ChainMail are incorporated into the cellular neural network as the local connectivity of cells, through which the dynamic behaviors of soft tissue deformation are transformed into the neural dynamics of cellular neural network. Experiments demonstrate that the proposed neural network approach is capable of modeling the soft tissues' nonlinear deformation and typical mechanical behaviors. The proposed method not only improves ChainMail's linear deformation with the nonlinear characteristics of neural dynamics but also enables the cellular neural network to follow the principle of continuum mechanics to simulate soft tissue deformation.
Das, Debanjan; Shiladitya, Kumar; Biswas, Karabi; Dutta, Pranab Kumar; Parekh, Aditya; Mandal, Mahitosh; Das, Soumen
2015-12-01
The paper presents a study to differentiate normal and cancerous cells using label-free bioimpedance signal measured by electric cell-substrate impedance sensing. The real-time-measured bioimpedance data of human breast cancer cells and human epithelial normal cells employs fluctuations of impedance value due to cellular micromotions resulting from dynamic structural rearrangement of membrane protrusions under nonagitated condition. Here, a wavelet-based multiscale quantitative analysis technique has been applied to analyze the fluctuations in bioimpedance. The study demonstrates a method to classify cancerous and normal cells from the signature of their impedance fluctuations. The fluctuations associated with cellular micromotion are quantified in terms of cellular energy, cellular power dissipation, and cellular moments. The cellular energy and power dissipation are found higher for cancerous cells associated with higher micromotions in cancer cells. The initial study suggests that proposed wavelet-based quantitative technique promises to be an effective method to analyze real-time bioimpedance signal for distinguishing cancer and normal cells.
MASON, ASHLEY E.; LAW, RITA W.; BRYAN, AMANDA E. B.; PORTLEY, ROBERT M.; SBARRA, DAVID A.
2015-01-01
Romantic breakups arouse fundamental questions about the self: Who am I without my partner? This study examined self-concept reorganization and psychological well-being over an 8-week period in the months following a breakup. Multilevel analyses revealed that poorer self-concept recovery preceded poorer well-being and was associated with love for an ex-partner, suggesting that failure to redefine the self contributes to post-breakup distress. Psychophysiological data revealed that greater activity in the corrugator supercilia facial muscle while thinking about an ex-partner predicted poorer self-concept recovery and strengthened the negative association between love for an ex-partner and self-concept recovery. Thus, the interaction between self-report and psychophysiological data provided information about the importance of self-concept recovery to post-breakup adjustment not tapped by either method alone. PMID:26167126
Harrington, Elizabeth K; Gordon, Diana; Bahulekar, Pramod; Garg, B S; Osgood-Roach, Isabel; Jensen, Jeffrey T; Aengst, Jennifer
2015-08-01
We examined the men's attitudes and perceptions toward the concept of female nonsurgical permanent contraception (NSPC) or novel approaches to permanent contraception (PC) that do not require incisions or surgical equipment/hysteroscope. Cross-sectional survey of married/partnered men in Portland, OR, and rural eastern Maharashtra, India. Descriptive analysis was performed. In India (N=150), most men (80%) anticipated that their partners would undergo PC in the future, compared to 30% in Portland (N=170). About a third (39.6% in India, 82% in Portland) reported being uncomfortable with PC for partners due to the need for surgery. Most men (85% in India, 82% in Portland) expressed a preference for a hypothetical new method of female NSPC over surgery, if safe and effective. Most men sampled in two diverse settings expressed interest in NSPC for women. Men's perceptions of new female contraceptive methods are important to the contraceptive development process. Men may find a safe and effective nonsurgical method of permanent female contraception more acceptable than surgical PC. Copyright © 2015 Elsevier Inc. All rights reserved.
Nurius, Paula S; Macy, Rebecca J
2010-06-01
Violence researchers have called for the use of person-oriented methods to understand differences that have been found in biopsychosocial consequences among those who experience intimate partner violence (IPV). To address this issue, we apply a person-oriented statistical method, latent profile analysis (LPA), to test for meaningful subgroups of a sample of 448 battered women based on participants' appraisals of their vulnerability relative to their violent partner, depressive symptoms, physical injuries, overall physical health functioning, and their positive and negative social relationships with friends and family. The LPA established five significantly distinct subgroups. Using MANOVA, we examined these subgroups and their respective IPV exposure, both concomitant and separate incidents within the past year. Those with the most intensive violence exposure show the greatest level of challenge and impairment. However, the groups with comparable levels of IPV exposure manifest distinctly different configurations of biopsychosocial profiles, indicating a need for adaptive interventions commensurate with these profiles. We discuss the implications these findings have for developing adaptive interventions for battered women, as well as the potential utility of person-oriented tools for violence researchers.
Nurius, Paula S.; Macy, Rebecca J.
2014-01-01
Violence researchers have called for the use of person-oriented methods to understand differences that have been found in biopsychosocial consequences among those who experience intimate partner violence (IPV). To address this issue, we apply a person-oriented statistical method, latent profile analysis (LPA), to test for meaningful subgroups of a sample of 448 battered women based on participants’ appraisals of their vulnerability relative to their violent partner, depressive symptoms, physical injuries, overall physical health functioning, and their positive and negative social relationships with friends and family. The LPA established five significantly distinct subgroups. Using MANOVA, we examined these subgroups and their respective IPV exposure, both concomitant and separate incidents within the past year. Those with the most intensive violence exposure show the greatest level of challenge and impairment. However, the groups with comparable levels of IPV exposure manifest distinctly different configurations of biopsychosocial profiles, indicating a need for adaptive interventions commensurate with these profiles. We discuss the implications these findings have for developing adaptive interventions for battered women, as well as the potential utility of person-oriented tools for violence researchers. PMID:19897777
Yoshihama, Mieko; Bybee, Deborah
2011-03-01
Intimate partner violence (IPV) is prevalent and often recurrent in women's lives. To better understand the changing risk of IPV over the life course, which could guide more effective policies and program responses, methodological innovations are needed. Life History Calendar methods enhance respondents' recall of the timing of specific types of IPV experienced over the life course. Multilevel modeling provides a way to analyze individual and collective trajectories and examine covariates of IPV risk. We apply these complementary methods to examine IPV trajectories for a sample of women of Filipina descent living in the United States, examining life course timing and cohort effects. © The Author(s) 2011.
Live CLEM imaging to analyze nuclear structures at high resolution.
Haraguchi, Tokuko; Osakada, Hiroko; Koujin, Takako
2015-01-01
Fluorescence microscopy (FM) and electron microscopy (EM) are powerful tools for observing molecular components in cells. FM can provide temporal information about cellular proteins and structures in living cells. EM provides nanometer resolution images of cellular structures in fixed cells. We have combined FM and EM to develop a new method of correlative light and electron microscopy (CLEM), called "Live CLEM." In this method, the dynamic behavior of specific molecules of interest is first observed in living cells using fluorescence microscopy (FM) and then cellular structures in the same cell are observed using electron microscopy (EM). Following image acquisition, FM and EM images are compared to enable the fluorescent images to be correlated with the high-resolution images of cellular structures obtained using EM. As this method enables analysis of dynamic events involving specific molecules of interest in the context of specific cellular structures at high resolution, it is useful for the study of nuclear structures including nuclear bodies. Here we describe Live CLEM that can be applied to the study of nuclear structures in mammalian cells.
Gebrezgi, Berhane Hailu; Badi, Marta Berta; Cherkose, Endashaw Admassu; Weldehaweria, Negassie Berhe
2017-06-24
Intimate partner physical violence is a common global phenomenon. About 30.00% and 38.83% of women in the world and in sub-Saharan Africa experienced physical violence by their partner respectively in 2013. Though intimate partner violence has serious adverse health consequences, there is limited information about partner violence during pregnancy in Ethiopia. Therefore, the aim of this study was to assess the prevalnce of physical intimate partner violence during pregnancy and associated factors among women attending antenatal care in Shire Endaselassie town, Tigray, northen Ethiopia METHODS: A facility based cross-sectional study was conducted from May 3 to July 6, 2015. Four hundred and twenty-two pregnant women attending three public health facilities were included using systematic sampling technique. In addition, twenty-two purposely selected key informants were interviewed. The data collectors and supervisors were trained on all data collection processes. Data were entered to Epi-Info version 7.1.2.00 and exported to SPSS version 20.00. Logistic regression was used to identify factors associated with intimate partner physical violence. Statistical significance was declared at p < 0.05. Qualitative data were categorized into themes and triangulated with the quantitative results. The prevalence of intimate partner physical violence in pregnancy was 20.6% (CI = 16.70, 24.90). Age at first marriage greater than or equal to 17 years (AOR = 4.42, CI = 2.07, 9.42), women with no formal education (AOR = 2.78 CI = 1.10, 7.08), rural dwellers (AOR = 2.63 CI = 1.24, 5.58), intimate partners with no formal education (AOR = 2.78 CI = 1.10, 7.08) and intimate partner alcohol consumption (AOR = 3.8 CI = 1.85, 7.82) were factors associated with intimate partner physical violence towards pregnant women. Nearly one fifth of women surveyed experienced intimate partner physical violence during pregnancy. Early marriage, rural dwelling, intimate partner alcohol consumption, and educational status were associated with intimate partner physical violence during pregnancy. Urgent attention to women's rights and health is essential at all levels to alleviate the problem and its risk factors in Tigray regional state of Ethiopia.
USAFSAM Review and Analysis of Radiofrequency Radiation Bioeffects Literature: Second Report.
1982-05-01
10 Cellular 11 Mechanisms of interaction 12 Environmental 13 Medical applications 14 Review 15 Ecological 16 Physical methods/dosimetry 17 Other 18...APPLICATIONS List of Analyses ......... .................... 137 (14) REVIEW List of Analyses ......... .................... 138 (16) PHYSICAL METHODS/DOSIMETRY...physiological 10 Cellular 11 Mechanisms of interaction 12 Environmental 13 Medical applications 14 Review 15 Ecological 16 Physical methods/dosimetry 17
Microfluidic systems and methods of transport and lysis of cells and analysis of cell lysate
Culbertson, Christopher T.; Jacobson, Stephen C.; McClain, Maxine A.; Ramsey, J. Michael
2004-08-31
Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.
Microfluidic systems and methods for transport and lysis of cells and analysis of cell lysate
Culbertson, Christopher T [Oak Ridge, TN; Jacobson, Stephen C [Knoxville, TN; McClain, Maxine A [Knoxville, TN; Ramsey, J Michael [Knoxville, TN
2008-09-02
Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.
Dual Method Use Among a Sample of First-Year College Women
Walsh, Jennifer L.; Fielder, Robyn L.; Carey, Kate B.; Carey, Michael P.
2014-01-01
CONTEXT Dual method use—using one type of contraceptive to reduce the risk of STDs and another to prevent pregnancy—is effective but understudied. No prior studies have employed an event-level approach to examining characteristics associated with dual method use among college women. METHODS In 12 consecutive monthly surveys conducted in 2009–2010, data on 1,843 vaginal intercourse events were collected from 296 first-year college women. Women reported on their use of condoms and hormonal contraceptives during all events. Multilevel regression analysis was used to assess associations between event-, month- and person-level characteristics and hormonal use and dual method use. RESULTS Women used hormonal contraceptives during 53% of events and condoms during 63%. Dual method use was reported 28% of the time, and only 14% of participants were consistent users of both methods. The likelihood of dual method use was elevated when sex partners were friends as opposed to romantic partners or ex-boyfriends, and among women who had received an STD diagnosis prior to college (odds ratios, 2.5–2.9); it also increased with level of religiosity (coefficient, 0.8). Dual use was less likely when less reliable methods were used (odds ratio, 0.2) and when women reported more months of hormonal use (0.8), were older (coefficient, −4.7) and had had a greater number of partners before college (−0.3). CONCLUSIONS A better understanding of the characteristics associated with dual method use may help in the design of potential intervention efforts. PMID:24684480
A conserved juxtacrine signal regulates synaptic partner recognition in Caenorhabditis elegans
2011-01-01
Background An essential stage of neural development involves the assembly of neural circuits via formation of inter-neuronal connections. Early steps in neural circuit formation, including cell migration, axon guidance, and the localization of synaptic components, are well described. However, upon reaching their target region, most neurites still contact many potential partners. In order to assemble functional circuits, it is critical that within this group of cells, neurons identify and form connections only with their appropriate partners, a process we call synaptic partner recognition (SPR). To understand how SPR is mediated, we previously developed a genetically encoded fluorescent trans-synaptic marker called NLG-1 GRASP, which labels synaptic contacts between individual neurons of interest in dense cellular environments in the genetic model organism Caenorhabditis elegans. Results Here, we describe the first use of NLG-1 GRASP technology, to identify SPR genes that function in this critical process. The NLG-1 GRASP system allows us to assess synaptogenesis between PHB sensory neurons and AVA interneurons instantly in live animals, making genetic analysis feasible. Additionally, we employ a behavioral assay to specifically test PHB sensory circuit function. Utilizing this approach, we reveal a new role for the secreted UNC-6/Netrin ligand and its transmembrane receptor UNC-40/Deleted in colorectal cancer (DCC) in SPR. Synapses between PHB and AVA are severely reduced in unc-6 and unc-40 animals despite normal axon guidance and subcellular localization of synaptic components. Additionally, behavioral defects indicate a complete disruption of PHB circuit function in unc-40 mutants. Our data indicate that UNC-40 and UNC-6 function in PHB and AVA, respectively, to specify SPR. Strikingly, overexpression of UNC-6 in postsynaptic neurons is sufficient to promote increased PHB-AVA synaptogenesis and to potentiate the behavioral response beyond wild-type levels. Furthermore, an artificially membrane-tethered UNC-6 expressed in the postsynaptic neurons promotes SPR, consistent with a short-range signal between adjacent synaptic partners. Conclusions These results indicate that the conserved UNC-6/Netrin-UNC-40/DCC ligand-receptor pair has a previously unknown function, acting in a juxtacrine manner to specify recognition of individual postsynaptic neurons. Furthermore, they illustrate the potential of this new approach, combining NLG-1 GRASP and behavioral analysis, in gene discovery and characterization. PMID:21663630
Cahn, Marjorie A.; Auston, Ione; Selden, Catherine R.; Cogdill, Keith; Baker, Stacy; Cavanaugh, Debra; Elliott, Sterling; Foster, Allison J.; Leep, Carolyn J.; Perez, Debra Joy; Pomietto, Blakely R.
2007-01-01
Objective: The paper provides a complete accounting of the Partners in Information Access for the Public Health Workforce (Partners) initiative since its inception in 1997, including antecedent activities since 1995. Methods: A descriptive overview is provided that is based on a review of meeting summaries, published reports, Websites, project reports, databases, usage statistics, and personal experiences from offices in the National Library of Medicine (NLM), six organizations that collaborate formally with NLM on the Partners initiative, and one outside funding partner. Results: With ten years of experience, the initiative is an effective and unique public-private collaboration that builds on the strengths and needs of the organizations that are involved and the constituencies that they serve. Partners-supported and sponsored projects include satellite broadcasts or Webcasts, training initiatives, Web resource development, a collection of historical literature, and strategies for workforce enumeration and expansion of public health systems research, which provide excellent examples of the benefits realized from collaboration between the public health community and health sciences libraries. Conclusions: With continued funding, existing and new Partners-sponsored projects will be able to fulfill many public health information needs. This collaboration provides excellent opportunities to strengthen the partnership between library science and public health in the use of health information and tools for purposes of improving and protecting the public's health. PMID:17641765
Tilley, Donna Scott; Brackley, Margaret
2005-04-01
Intimate partner violence is a serious and pervasive problem in U.S. society, with 25% of women and 7.6% of men reporting physical abuse by an intimate partner each year. Understanding the risk factors for development of violence is essential toward the development of interventions to reduce partner violence. Much of the understanding about the development of partner violence is based on research with victims rather than perpetrators. The study was conducted with men convicted of assault on an intimate female partner. Grounded theory was the method used to analyze data from interviews with 16 men participating in a batterers' intervention and prevention program. From the data, the Violent Couples Model was developed. The primary elements of the Violent Couples Model are justifying violence, minimizing violence, childhood exposure to violence, ineffective anger management, childhood experience of violence, and ineffective conflict resolution. Social and familial factors serve as moderating elements. Contextual elements of the model include power and control, social isolation, desensitization, insecure maternal relationships, the view of violence as a private problem, ambivalent intimate relationships, objectification of women, immaturity, lack of awareness about what constitutes violence, mistrust, traditional views of the roles of women, financial issues, and jealousy. Interventions indicated in the model are primary, or preventive, in nature. The model focuses on prevention efforts with the family as a whole, rather than on batterers alone.
Do Drinking Episodes Contribute to Sexual Aggression Perpetration in College Men?
Testa, Maria; Parks, Kathleen A.; Hoffman, Joseph H.; Crane, Cory A.; Leonard, Kenneth E.; Shyhalla, Kathleen
2015-01-01
Objective: Survey and experimental analog studies suggest that alcohol consumption contributes to perpetration of sexual aggression. However, few studies have considered the temporal association between naturally occurring episodes of drinking and subsequent sexual aggression. This daily report study was designed to examine whether alcohol consumption increases the odds of aggressive sexual activity within the next 4 hours. Method: First-year male college students (N = 427) completed daily online reports of drinking and sexual activity for up to 56 days. Multilevel modeling was used to determine whether drinking episodes increased the odds of the following outcomes occurring within 4 hours: (a) aggressive sex with a new partner, (b) non-aggressive sex with a new partner, (c) aggressive sex with a previous partner, and (d) non-aggressive sex with a previous partner. Results: Drinking episodes increased the odds of both aggressive and non-aggressive sex with a new partner. In contrast, drinking episodes did not predict aggression involving previous partners and decreased the odds of non-aggressive sex with a previous partner. Contrary to hypotheses, individual difference variables associated with propensity toward sexual aggression (sexual misperception, antisocial behavior, hostility toward women) did not interact with daily alcohol. Conclusions: The complex pattern of results is more consistent with situational as opposed to pharmacological effects of alcohol on sexual aggression and suggests that prevention efforts focus on drinking contexts known to facilitate sexual activity. PMID:26098025
Manne, Sharon; Badr, Hoda
2009-01-01
Objective Couples coping with head and neck and lung cancers are at increased risk for psychological and relationship distress given patients’ poor prognosis and aggressive and sometimes disfiguring treatments. The relationship intimacy model of couples’ psychosocial adaptation proposes that relationship intimacy mediates associations between couples’ cancer-related support communication and psychological distress. Because the components of this model have not yet been evaluated in the same study, we examined associations between three types of cancer-related support communication (self-disclosure, perceived partner disclosure, and protective buffering), intimacy (global and cancer-specific), and global distress among patients coping with either head and neck or lung cancer and their partners. Method One hundred and nine patients undergoing active treatment and their partners whose average time since diagnosis was 15 months completed cross-sectional surveys. Results For both patients and their partners, multilevel analyses using the Actor-Partner Interdependence Model showed that global and cancer-specific intimacy fully mediated associations between self- and perceived partner disclosure and distress; global intimacy partially mediated the association between protective buffering and distress. Evidence for moderated mediation was found; specifically, lower levels of distress were reported as a function of global and cancer-specific intimacy, but these associations were stronger for partners than for patients. Conclusions Enhancing relationship intimacy by disclosing cancer-related concerns may facilitate both partners’ adjustment to these illnesses. PMID:19885852
Strategies and help-seeking behavior among Mexican women experiencing partner violence.
Frías, Sonia M
2013-01-01
According to a recent Mexican survey, 10.72% of women have at some point experienced sexual partner violence, and 23.71% physical violence at the hands of their current or last partner. Using this survey and a series of semi-structured interviews with experts, this study used a mixed-methods approach to examine, first, whether women who experienced violence turned to law enforcement agencies for help, and the characteristics of these women. Second, the research examined what type of service and treatment they reported receiving from these agencies. Finally, the research examined reasons women did not request help from police and law enforcement agencies.
Lohman, Brenda J; Neppl, Tricia K; Senia, Jennifer M; Schofield, Thomas J
2013-04-01
The intergenerational transmission of violence directed toward intimate partners has been documented for the past three decades. Overall, the literature shows that violence in the family of origin leads to violence in the family of destination. However, this predominately cross-sectional or retrospective literature is limited by self-selection, endogeneity, and reporter biases as it has not been able to assess how individual and family behaviors simultaneously experienced during adolescence influence intimate partner violence throughout adulthood. The present study used data from the Iowa Youth and Families Project (IYFP; N = 392; 52 % Female), a multi-method, multi-trait prospective approach, to overcome this limitation. We focused on psychological intimate partner violence in both emerging adulthood (19-23 years) and adulthood (27-31 years), and include self and partner ratings of violence as well as observational data in a sample of rural non-Hispanic white families. Controlling for a host of individual risk factors as well as interparental psychological violence from adolescence (14-15 years), the results show that exposure to parent-to-child psychological violence during adolescence is a key predictor of intimate partner violence throughout adulthood. In addition, negative emotionality and the number of sexual partners in adolescence predicted intimate partner violence in both emerging adulthood and adulthood. Exposure to family stress was associated positively with intimate partner violence in adulthood but not in emerging adulthood, whereas academic difficulties were found to increase violence in emerging adulthood only. Unlike previous research, results did not support a direct effect of interparental psychological violence on psychological violence in the next generation. Gender differences were found only in emerging adulthood. Implications of these findings are discussed in light of the current literature and future directions.
Using smartphone apps in STD interviews to find sexual partners.
Pennise, Melissa; Inscho, Roxana; Herpin, Kate; Owens, John; Bedard, Brenden A; Weimer, Anita C; Kennedy, Byron S; Younge, Mary
2015-01-01
Smartphone applications (apps) are increasingly used to facilitate casual sexual relationships, increasing the risk of sexually transmitted diseases (STDs). In STD investigations, traditional contact elicitation methods can be enhanced with smartphone technology during field interviews. In 2013, the Monroe County Department of Public Health conducted a large, multi-infection STD investigation among men who have sex with men (MSM) using both index case and cluster interviews. When patients indicated meeting sexual partners online, disease intervention specialists (DISs) had access to smartphone apps and were able to elicit partners through access to inboxes and profiles where traditional contact information was lacking. Social network mapping was used to display the extent of the investigation and the impact of access to smartphones on the investigation. A total of 14 index patient interviews and two cluster interviews were conducted; 97 individuals were identified among 117 sexual dyads. On average, eight partners were elicited per interview (range: 1-31). The seven individuals who used apps to find partners had an average of three Internet partners (range: 1-5). Thirty-six individuals either had a new STD (n=7) or were previously known to be HIV-positive (n=29). Of the 117 sexual dyads, 21 (18%) originated either online (n=8) or with a smartphone app (n=13). Of those originating online or with a smartphone app, six (29%) partners were located using the smartphone and two (10%) were notified of their exposure via a website. Three of the new STD/HIV cases were among partners who met online. Smartphone technology used by DISs in the field improved contact elicitation and resulted in successful partner notification and case finding.
Meier, Caroline; Bodenmann, Guy; Mörgeli, Hanspeter; Jenewein, Josef
2011-01-01
Background Successfully coping with a chronic disease depends significantly on social support, particularly that of a significant other. Thus, it depends on the ways of dealing with stress within a couple (dyadic coping). In this study, the relationship between dyadic coping and well-being was investigated among couples in which one partner suffers from chronic obstructive pulmonary disease (COPD). Methods A total of 43 couples participated. They were mailed questionnaires on anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (World Health Organization Quality of Life Questionnaire-BREF), and dyadic coping (Dyadic Coping Inventory). Results Low scores of positive and high scores of negative dyadic coping were associated with poorer quality of life and higher psychological distress among couples. Delegated coping (assistance with daily tasks) was higher among partners. When estimated by patients, high delegated partner coping (frequent provision of support by partners) and low delegated personal coping (low provision of support by patients) were associated with poorer quality of life for both patient and partner. COPD patients suffering from depression were supported more often and attributed deficits in dyadic coping primarily to themselves, whereas partners with higher scores of depression provided higher estimates of both their own negative coping and the negative coping of their partner. Conclusion The higher the patient perceived the imbalance in delegated dyadic coping, the lower the couple’s quality of life. More negative and less positive dyadic coping were associated with lower quality of life and higher psychological distress. Psychotherapeutic interventions to improve dyadic coping may lead to better quality of life and less psychological distress among COPD patients and their partners. PMID:22135491