2,068 research outputs found

    Hippocampal BDNF regulates a shift from flexible, goal-directed to habit memory system function following cocaine abstinence.

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    The transition from recreational drug use to addiction involves pathological learning processes that support a persistent shift from flexible, goal-directed to habit behavioral control. Here, we examined the molecular mechanisms supporting altered function in hippocampal (HPC) and dorsolateral striatum (DLS) memory systems following abstinence from repeated cocaine. After 3 weeks of cocaine abstinence (experimenter- or self-administered), we tested new behavioral learning in male rats using a dual-solution maze task, which provides an unbiased approach to assess HPC- versus DLS-dependent learning strategies. Dorsal hippocampus (dHPC) and DLS brain tissues were collected after memory testing to identify transcriptional adaptations associated with cocaine-induced shifts in behavioral learning. Our results demonstrate that following prolonged cocaine abstinence rats show a bias toward the use of an inflexible, habit memory system (DLS) in lieu of a more flexible, easily updated memory system involving the HPC. This memory system bias was associated with upregulation and downregulation of brain-derived neurotrophic factor (BDNF) gene expression and transcriptionally permissive histone acetylation (acetylated histone H3, AcH3) in the DLS and dHPC, respectively. Using viral-mediated gene transfer, we overexpressed BDNF in the dHPC during cocaine abstinence and new maze learning. This manipulation restored HPC-dependent behavioral control. These findings provide a system-level understanding of altered plasticity and behavioral learning following cocaine abstinence and inform mechanisms mediating the organization of learning and memory more broadly

    Blood signs| [Stories]

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    Hydrophobic Ligand Binding by Zn-α_2-glycoprotein, a Soluble Fat-depleting Factor Related to Major Histocompatibility Complex Proteins

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    Zn-alpha2-glycoprotein (ZAG) is a member of the major histocompatibility complex (MHC) class I family of proteins and is identical in amino acid sequence to a tumor-derived lipid-mobilizing factor associated with cachexia in cancer patients. ZAG is present in plasma and other body fluids, and its natural function, like leptin's, probably lies in lipid store homeostasis. X-ray crystallography has revealed an open groove between the helices of ZAG's alpha1 and alpha2 domains, containing an unidentified small ligand in a position similar to that of peptides in MHC proteins (Sanchez, L. M., Chirino, A. J., and Bjorkman, P. J. (1999) Science 283, 1914-1919). Here we show, using serum-derived and bacterial recombinant protein, that ZAG binds the fluorophore-tagged fatty acid 11-(dansylamino)undecanoic acid (DAUDA) and, by competition, natural fatty acids such as arachidonic, linolenic, eicosapentaenoic, and docosahexaenoic acids. Other MHC class I-related proteins (FcRn, HFE, HLA-Cw*0702) showed no such evidence of binding. Fluorescence and isothermal calorimetry analysis showed that ZAG binds DAUDA with Kd in the micromolar range, and differential scanning calorimetry showed that ligand binding increases the thermal stability of the protein. Addition of fatty acids to ZAG alters its intrinsic (tryptophan) fluorescence emission spectrum, providing a strong indication that ligand binds in the expected position close to a cluster of exposed tryptophan side chains in the groove. This study therefore shows that ZAG binds small hydrophobic ligands, that the natural ligand may be a polyunsaturated fatty acid, and provides a fluorescence-based method for investigating ZAG-ligand interactions

    Wound dressing techniques and costs at a county hospital

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    Background: Wound management is one of the commonest procedures conducted in surgical departments across health facilities in Kenya.Objective: This study aimed at exploring wound dressing techniques used at Migori County Referral Hospital (MCRH) and the cost of treatment to patients.Methods: Convenience sampling was used to select inpatients presenting with wounds undergoing treatment at the time of recruitment. Five patients (2 male and 3 female) were enrolled after obtaining informed consents. Wounds were examined during cleaning and dressing and healing process follow-ups made. Selection of wound dressing technique was done by the primary clinicians with no bias from the research team.Results: One patient’s wound was an open fracture resulting from a road traffic accident; three patients had pyomyositis following thorn pricks; and the last patient’s was sustained following a blast injury. Wound management methods employed at MCRH included cleaning with vinegar, irrigation with normal saline, dressing with honey, and improvised negative pressure wound therapy. Total cost incurred was affordable to patients, and ranged between Kenya shillings 100–360 (USD 1–3.60) weekly.Conclusion: Wound management techniques at MCRH were effective and affordable. Additional studies with a larger sample size are recommended.Keywords: Wound dressing, costs, NPWT, vinegar cleaning, honey dressin

    A Cross-cultural Comparative Study of Uses and Perceptions of Technology in Education among Turkish and US Undergraduates

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    The purpose of this study was to investigate differences and similarities among United States (US) and Turkish university students in technology ownership, uses of technology for academic purposes, perceived importance of technology, and preferences for technology in education. The EDUCAUSE Center for Analytics and Research (ECAR) undergraduate student technology survey was used to collect data from Turkish students (N=384) at Abant Izzet Baysal University and US students (N=399) at Louisiana State University (LSU). The findings revealed significant differences in uses and ownership of most technological devices in favor of the US students in comparison to the Turkish students. The results of the study pointed to differences in information technology (IT) ownership and access, largely as a function of local infrastructure and economic settings rather than cultural diversities between Turkey and the US

    Intergenerational and Peer Communication in the Workplace: An Analysis of Satisfaction and Dissatisfaction

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    This research used an on-line survey to examine intergenerational communication in the workplace. Respondents were 165 young, middle-aged, and older working adults randomly assigned to report on workplace communication with either peer or intergenerational co-workers. All completed a questionnaire assessing satisfaction with communication with coworkers in the target group, and 134 respondents also provided descriptions of a satisfactory and a dissatisfactory work conversation with a member of the target group, following Williams and Giles (1996). Young and older respondents reported greater satisfaction with peer than intergenerational coworker communication on the questionnaire as predicted, but middle-aged respondents indicated equivalent satisfaction with peer and older coworker communication. Emergent theme analysis of the conversational descriptions revealed that, consistent with communication accommodation theory (Giles, Coupland, & Coupland, 1991), satisfactory conversations were characterized by accommodative communication behaviors, positive feelings, and goal accomplishment, whereas dissatisfactory conversations were associated with underaccommodative communication behaviors, negative feelings, and goal non-accomplishment. Although the forms of accommodation and underaccommodation varied in emphasis across age groups and descriptions of peer and intergenerational conversations, more similarities than differences were noted. The ways in which the work context shapes conceptions of age were also identified. Together, these results provide evidence that the work context may foster a shared identity that serves to reduce the salience of age in workplace interactions, consistent with the common ingroup identity model (Dovidio & Gaertner, 2000), but that shared identity at the interpersonal level does not necessarily lead to general communication satisfaction with intergenerational coworkers

    Mixed Ca/Sr salt forms of salicylic acid, tuning structure and aqueous solubility

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    Ten isostructural single-crystal diffraction studies of mixed cation Ca/Sr salt forms of the salicylate anion are presented, [Ca(1 − x)Srx(C7H5O3)2(OH2)2], where x = 0, 0.041, 0.083, 0.165, 0.306, 0.529, 0.632, 0.789, 0.835 and 1. The structure of an isostructural Sr/Ba species [Sr0.729Ba0.271(C7H5O3)2(OH2)2], is also described. The Ca/Sr structures form a series where, with increasing Sr content, the unit cell expands in both the crystallographic a and c directions (by 1.80 and 3.18% respectively), but contracts slightly in the b direction (−0.31%). The largest percentage structural expansion lies parallel to the direction of propagation of the one-dimensional coordination polymer that is the primary structural feature. This structural expansion is thus associated with increased M—O distances. Aqueous solubility measurements show that solubility generally increases with increasing Sr content·Thus tuning the composition of these mixed counterion salt forms leads to sytematic structural changes and allows solubility to be tuned to values between those for the pure Ca and Sr species

    The Fall and Rise of US Inequities in Premature Mortality: 1960–2002

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    Nancy Krieger and colleagues found evidence of decreasing, and then increasing or stagnating, socioeconomic and racial inequities in US premature mortality and infant death from 1960 to 2002

    Cell-Extrinsic Defective Lymphocyte Development in Lmna-/- Mice

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    Background: Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna-/- mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna-/- mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development. Principal Findings: Lmna-/- mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna-/- bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4 + and CD8 + T cells. Transplantation of Lmna-/- neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development. Conclusions: Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna-/- mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna-/- mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striate

    A structural comparison of salt forms of dopamine with the structures of other phenylethylamines

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    The structures of four salt forms of dopamine are reported. These are dopamine [2‐(3,4‐dihydroxyphenyl)ethan‐1‐aminium] benzoate, C8H12NO2+·C7H5O2−, I, dopamine 4‐nitrobenzoate, C8H12NO2+·C7H4NO4−, II, dopamine ethanedisulfonate, 2C8H12NO2+·C2H4O6S22−, III, and dopamine 4‐hydroxybenzenesulfonate monohydrate, C8H12NO2+·C6H5O4S−·H2O, IV. In all four structures, the dopamine cation adopts an extended conformation. Intermolecular interaction motifs that are common in the salt forms of tyramine can be found in related dopamine structures, but hydrogen bonding in the dopamine structures appear to be more variable and less predictable than for tyramine. Packing analysis discovered three dopamine‐containing groups of structures that can be described as isostructural with regards to the cation positions. Two of these groups contain both dopamine and tyramine species, and one of these is also highly variable in other ways too, containing anhydrous and hydrated forms, different anion types and ionized and neutral phenylethylamine species. As such, the group illustrates that packing behaviour can be robust and similar even where intermolecular interactions such as hydrogen bonds are very different
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