Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of the NMDA receptor subunit NR3B regulates dendrite morphogenesis in spinal motor neurons

During postnatal development, the dendrites of spinal motor neurons are refined in an activity-dependent manner that can be influenced by blocking activation of N-Methyl- D -Aspartate (NMDA) receptors. In late postnatal life, dendritic refinement ceases, and dendrite architecture is unaffected by NMDA antagonists; however the molecular substrate for limiting dendritic plasticity is not understood. During late postnatal development, expression of the NR3B NMDA receptor subunit, a putative dominant-negative subunit that reduces glutamate-induced ionic currents, is upregulated within motor neurons. To investigate whether increasing NR3B expression may contribute to the loss in late development of activity-dependent dendritic reorganization in the spinal cord, we overexpressed NR3B in cultured spinal motor neurons, and compared its effects on dendrite morphology with the effects of pharmacological blockade of NMDA receptors. We found that over-expression of the NR3B receptor subunit increased the length and complexity of dendritic arbor, and increased numbers of dendritic filopodia, suggesting that NR3B promotes the addition of branch segments in developing motor neurons. In contrast, blockade of NMDA receptor activity by the NMDA antagonist AP5 had little effect on the overall length or complexity of dendritic arbor. Instead, treatment with AP5 resulted in significant reorganization of dendritic arbor in a manner that favored addition of dendritic segments of high branch orders, at the expense of those closer to the cell body. These results suggest that expression of the NR3B subunit may participate in activity-dependent reorganization of dendritic architecture, but via a mechanism that may be inconsistent with loss of NMDA receptor activity.
Molecular Multitasking in the Airspace

well delineated, but, may in part involve cleavage of macrophage recognition molecules by NE, impairing apoptotic cell uptake (15). Bridging molecules, SP-A and -D are also decreased in the lungs of smokers (16), also potentially contributing to the defect. Of note, statins (17) and macrolides (18) were recently reported to enhance phagocytosis. This might help explain their anti-inflammatory properties and provide a mechanism of action to be pursued as therapy for COPD. The neutrophilic response to cigarette smoke is clearly a false alarm with detrimental consequences. However, neutrophils are required to remove pathogens, particularly during acute airway infections that occur in patients with COPD. It has been very difficult to determine whether exacerbations themselves contribute to decline in lung function, although most evidence does point to an additional loss of FEV1 with each exacerbation (19). It is also believed that the host response to a greater degree than the inciting infection is responsible for the lung damage. However, strategies to prevent neutrophils from gaining access to the infected airway seem riskier than removing the neutrophil quickly after pathogen clearance. The findings in this manuscript suggest that this might be difficult since H. influenza leads to neutrophil necrosis. A better understanding of the apoptotic versus necrotic response could lead to strategies to prevent necrosis and clear bacteria. In the meantime, limiting excess inflammation might be the simplest therapeutic strategy for COPD.
Housing Transformation in Government Constructed ResidentialEstates in Lagos Nigeria

The desire to remodel houses in line with changing needs of occupants is on the increase, but there is a lack of understanding of the processes involved in housing transformation by residents in public housing estates in a developing country like Nigeria. This study investigated housing transformation in two low-cost public residential estates in Lagos, Nigeria, with a view to understanding the socio-economic characteristics of those engaged in housing transformation and how their undertake this. The data were derived through a cross sectional survey of 614 household heads in the estates using questionnaire and interview guide, and analysed using descriptive statistics and correlation analysis The result shows that most of those involved in housing transformation were male low-income household heads with large families living in owner-occupied houses for over 15 years. It was also found that a significant correlation exist between housing transformation and the socio-economic characteristics of the residents except age. Although housing transformation involved substantial amount of money, yet it was undertaken using direct labour and self-help approach without building plans and authorisations. The paper concludes by highlighting the need for appropriate actions to check the current spate of transformation activities by residents in public housing estates in the study area. Keywords: Housing transformation, low-cost housing; government residential estate, survey, Lagos -----------------------------------------------------------------------------------------------------------------------------------
DSM-IV Twelve Month and Lifetime Major Depressive Disorder and Romantic Relationships among African Americans

Robert Joseph Taylor, MSW, PhD.1,2, David H. Chae, PhD.3, Linda M. Chatters, PhD.1,2, Karen D. Lincoln, MSW, PhD.4, and Edna Brown, MSW, PhD.5 1School of Social Work, University of Michigan, Ann Arbor 2Program for Research on Black Americans, Institute for Social Research, University of Michigan, Ann Arbor 3School of Public Health, Emory University 4School of Social Work, University of Southern California 5Department of Human Development & Family Studies, University of Connecticut
Plasmid-Mediated Mechanism of Quinolone Resistance on E. coli Isolates from Different Clinical Samples.

Quinolone antimicrobials are widely used in clinical medicine due to their wide spectrum with high tissue penetration and ease of use; but increasing resistance with clinical use appears to be common in some bacterial pathogens, including Escherichia coli (E.coli). The aim of this study was to investigate plasmid-mediated quinolone resistance determinants (PMQR) including, qnrA, qnrB, and qnrS as the emerging mechanisms of quinolone resistance of E.coli isolates from different clinical sites in Karbala province, Iraq. A total of 200 clinical samples were collected from patients suffering from infections such as UTI, gastro enteritis (diarrhea), vaginitis, and wound infections; 30 samples were diagnosed as E.coli clinical strain from both sexes and different ages after identification by biochemical test, VITEK-2 compact system, and by molecular method using 16Sr DNA marker. Antimicrobial susceptibility and minimal inhibition concentration (MIC) testing for nalidixic acid, norfloxacin, ciprofloxacin, levofloxacin, and gatifloxacin was performed using the broth microdilution method. All strains were screened for PMQR genes qnrA, qnrB, and qnrS by the PCR method after DNA extraction from tested clinical isolates of E.coli. The results showed that E. coli is largely isolated from vaginal (40%) and urine (32%) samples, followed by wound infections (24%) and stools (21%). The high occurrence rate of E. coli(33.33%) isolates was observed in participants aged 31-45 years, while a lower occurrence (10%)was recorded in a group of ˃ 60-year-old female participants. Females have a notably increased frequency of E.coli compared to males, with the female to male ratio being 87%: 13%. Molecular investigation showed the total percentage of E.coli isolates harboring qnr genes to be 21/30 (70%); this figure is composed of 14/30 isolates harboring qnr in combined or mixed form (46.66%) and 7/30 (23.33%) isolates harboring qnr in single form (3 isolates harboring qnrA alone, 1 isolate harboring qnrB alone, 3 isolates harboring qnrS alone). The prevalence rates of qnrA, qnrB, and qnrS were 40%, 43.33%, and 53.33%, respectively. The results also showed that among E.coli isolates encoding qnr genes A, B, and S, 24%, 12%, and 36% were resistant to nalidixic acid, respectively. Among those isolates carrying qnrA, qnrB, and qnrS genes, 15.8%, 5.3%, and 26.3%, respectively, were resistant to ciprofloxacin. Moreover, Norfloxacin resistance was seen in 20.0%, 5.0%, and 30.0% of E.coli isolates harboring qnr A, B, and S genes, respectively. Levofloxacin resistance was seen in 37.5%, 75.0%, and 37.5% of the isolates carrying the qnrA, qnrB, and qnrS genes, respectively. The lowest resistance rates of qnrA, B, and S-positive E.coli strains were against gatifloxacin (0,0, and 25%, respectively). A high prevalence of qnr genes enhances the increasing resistance rate of E.coli against the quinolone antibiotic under study.
ICU capacity strain and adherence to prophylaxis guidelines

Purpose—To examine the relationship between different measures of capacity strain and adherence to prophylaxis guidelines in the intensive care unit (ICU). Materials and Methods—We conducted a retrospective cohort study within the Project IMPACT database. We used multivariable logistic regression to examine relationships between ICU capacity strain and appropriate usage of venous thromboembolism prophylaxis (VTEP) and stress ulcer prophylaxis (SUP). Results—Of 776,905 patient-days eligible for VTEP, appropriate therapy was provided on 68%. Strain as measured by proportion of new admissions (OR 0.91, 95% CI 0.90 – 0.91) and census (OR 0.97, 95% CI 0.97 – 0.98) was associated with decreased odds of receiving VTEP. With increasing strain as measured by new admissions, the degradation of VTEP utilization was more severe in ICUs with closed (OR 0.85, 95% CI 0.83 – 0.88) than open (OR 0.91, 95% CI 0.91 – 0.92) staffing models (interaction p-value < 0.001). Of 185,425 patient-days eligible for SUP, 48% received appropriate therapy. Administration of SUP was not significantly influenced by any measure of strain. Correspondence and requests for reprints should be addressed to Scott D. Halpern, Perelman School of Medicine, University of Pennsylvania, 719 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021. shalpern@exchange.upenn. edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript J Crit Care. Author manuscript; available in PMC 2016 December 01. Published in final edited form as: J Crit Care. 2015 December ; 30(6): 1303–1309. doi:10.1016/j.jcrc. 2015.08. 015. A uhor M anscript
BJRD16115 1..7

Objective: The middle interhemispheric (MIH) variant of holoprosencephaly (HPE) is the incomplete separation of midline cerebral hemispheres with the absence of callosal body. We aimed to describe the additional knowledge of diffusion tensor imaging (DTI) over conventional MRI in the evaluation of patients with MIH variant of HPE. Methods: Conventional MRI and DTI data of five patients were retrospectively evaluated. The parenchymal anomalies as well as changes at white matter tracts were systematically reviewed. Results: Except the callosal body and central cingulum fibres, which were missing in all patients, all other major white matter tracts (superior and inferior longitudinal, superior and inferior fronto-occipital, subcallosal and uncinate fasciculi and anterior commissure) had a normal course, thickness and integrity on diffusion tensor images. The genial and splenial callosal fibres were altered and rarefied on tractography. All patients had a central ventricular notch extending into the noncleaved heterotopic grey matter involving the body of the corpus callosum, which is very typical for the MIH variant of HPE. The remnant traversing white matter fibres above the non-cleaved heterotopic grey matter and incomplete partition of the interhemispheric fissure were also identified. No Probst bundles were detected. A single common ventricle without the septum pellucidum was noted in all patients. One patient had incomplete partition of the thalami, and two patients had abnormally oriented thalami without any prominent interthalamic connection. Vertically oriented hippocampi were detected in four out of five patients. Three patients had relatively flat and vertically oriented Sylvian fissures and in two patients, fissures were abnormally connected over the vertex. Conclusion: Additional DTI findings can not only clearly reveal the white matter alterations better than conventional MRI but also provide a better understanding of the aetiological changes that cause the MIH variant of HPE. Advances in knowledge: DTI can provide a better analysis of cerebral white matter connectivity and promotes understanding of the underlying microstructural changes that occur in patients with the MIH variant of HPE.
Brain Region Specific Actions of RGS4 Oppose Morphine Reward and Dependence but Promote Analgesia

Background— Regulator of G protein signaling 4 (RGS4) is one of the smaller members of the RGS family of proteins, which are known to control signaling amplitude and duration via interactions with G protein α subunits or other signaling molecules. Earlier evidence suggests dynamic regulation of RGS4 levels in neuronal networks mediating actions of opiates and other drugs of abuse, but the consequences of RGS4 actions in vivo are largely unknown. Methods— In this study, we use constitutive and nucleus accumbens-inducible RGS4 knockout mice, as well as mice overexpressing RGS4 in the nucleus accumbens via viral mediated gene transfer, to examine the influence of RGS4 on behavioral responses to opiates. We also use electrophysiology and immunoprecipitation assays to further understand the mechanisms underlying the tissue-specific actions of RGS4. Results— Inducible knockout or selective overexpression of RGS4 in the nucleus accumbens reveals that, in this brain region, RGS4 acts as a negative regulator of morphine reward, while in the locus coeruleus RGS4 opposes morphine physical dependence. In contrast, we show that RGS4 does not affect morphine analgesia or tolerance, but is a positive modulator of certain opiate analgesics, such as methadone and fentanyl. Conclusions— These findings provide fundamentally novel information concerning the role of RGS4 in the cellular mechanisms underlying the diverse actions of opiate drugs in the nervous system.
Early Cardiac Dysfunction in the Type 1 Diabetic Heart Using Speckle-Tracking Based Strain Imaging

Enhanced sensitivity in echocardiographic analyses may allow for early detection of changes in cardiac function beyond the detection limits of conventional echocardiographic analyses, particularly in a small animal model. The goal of this study was to compare conventional echocardiographic measurements and speckle-tracking based strain imaging analyses in a small animal model of type 1 diabetes mellitus. Conventional analyses revealed differences in ejection fraction, fractional shortening, cardiac output, and stroke volume in diabetic animals relative to controls at 6-weeks post-diabetic onset. In contrast, when assessing shortand long-axis speckletracking based strain analyses, diabetic mice showed changes in average systolic radial strain, radial strain rate, radial displacement, and radial velocity, as well as decreased circumferential and longitudinal strain rate, as early as 1-week post-diabetic onset and persisting throughout the diabetic study. Further, we performed regional analyses for the LV and found that the free wall region was affected in both the shortand long-axis when assessing radial dimension parameters. These changes began 1-week post-diabetic onset and remained throughout the progression of the Corresponding Author: John M. Hollander, Department of Exercise Physiology, West Virginia University School of Medicine, PO Box 9227, 1 Medical Center Drive, Morgantown, WV 26506, Tel: 1-(304) 293-3683, Fax: 1-(304) 293-7105, jhollander@hsc.wvu. edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Author Contributions D.L. S. , T.L. C. , C.E. N. , S.E. L. , S.L. M. researched data. D.L. S. , T.L. C. , A.B. P., G.M.D., J.M. H. performed statistical analyses. D.L. S. wrote the manuscript. D.L. S. , C.E. N. , D.T. , G.M.D., T.L. C. , S.L. M. , A.B. P., S.E. L. , J.M. H. reviewed/edited manuscript. D.L. S. , C.E. N. , D.T. , J.M. H. contributed to discussion. Disclosures None HHS Public Access Author manuscript J Mol Cell Cardiol. Author manuscript; available in PMC 2017 January 01. Published in final edited form as: J Mol Cell Cardiol. 2016 January ; 90: 74–83. doi:10.1016/j.yjmcc. 2015.12. 001. A uhor M anscript
Hypoxia Inducible Factor-2 a Is Translationally Repressed in Response to Dietary Iron Deﬁciency in Sprague-Dawley Rats 1–3

Iron regulatory proteins (IRP) regulate cellular iron metabolism by binding to iron-responsive elements (IRE) located in untranslated regions of mRNA-encoding proteins of iron metabolism. Recently, IRE have been identiﬁed in mRNA-encoding proteins with previously uncharacterized roles in iron metabolism, thus expanding the role of IRP beyond the regulation of cellular iron homeostasis. The mRNA for HIF 2- a contains an IRE and undergoes iron-dependent regulation in vitro, though the translational regulation of HIF-2 a in vivo remains unknown. To examine HIF-2 a translational regulation in vivo, we evaluated the effects of iron deﬁciency on the regulation of hepatic IRP activity and HIF-2 a translation. Rats were fed either a control (C; 50 mg Fe/kg diet) or iron-deﬁcient (ID; , 5 mg Fe/kg diet) diet or were pair-fed (PF) the C diet for 21 d. In ID rats, there was a 2-fold increase in IRP activity compared to the PF group ( P , 0.05), which was reﬂected by a 30– 40% increase in HIF-2 a repression ( P , 0.05). In agreement with a decrease in translation, the levels of HIF-2 a proteins were also decreased. The relative abundance of HIF-2 a mRNA did not differ between treatment groups. Taken together, these results suggest that the translation of HIF-2 a in the liver is regulated in part by the action of IRP in response to dietary iron deﬁciency and provide evidence that IRP may assist in coordinating the cellular response to alterations in iron and oxygen status associated with iron deﬁciency anemia. J. Nutr. 141: 1590–1596, 2011. secondary antibodies at 1:10,000 dilutions in Blotto-Tween were used to detect primary antibody binding using chemiluminescence (SuperSignal West Pico) and analyzed using Optiquant software. Statistical analysis. Statistical analyses using 1-way ANOVA and Student’s t test techniques were performed to determine treatment effects using SPSS v17.0 software (IBM-SPSS). All tests were done at the 95% conﬁdence level ( a = 0.05). Descriptive statistics were calculated for all variables and include mean 6 SEM. Data for percentage distribution of mRNA in hepatic gradient fractions were log-transformed prior to statistical analysis.
Bactericidal Antibody Responses Elicited by A Meningococcal Outer Membrane Vesicle Vaccine with Over-Expressed fHbp and Genetically-Attenuated Endotoxin

Background— Outer membrane vesicle (OMV) vaccines from mutant N. meningitidis strains engineered to over-express factor H-binding protein (fHbp) elicited broadly protective serum antibody responses in mice. The vaccines investigated were not treated with detergents to avoid extracting fHbp, which is a lipoprotein. Because of their high endotoxin content, the vaccines would not be safe to administer to humans. Methods— We prepared a native OMV vaccine from a strain engineered to over-express fHbp and in which the gene encoding LpxL1 was inactivated, which reportedly decreased endotoxin activity. Results— The OMV vaccine from the mutant had similar or lower ability to induce proinflammatory cytokines by human peripheral blood mononuclear cells as a detergent-extracted wildtype OMV, and 1000- to 10,000-fold lower activity than a native wildtype OMV. In mice, the OMV vaccine from the mutant elicited higher serum bactericidal antibody responses against a panel of heterologous N. meningitidis strains than a control multicomponent recombinant protein vaccine, or a detergent-extracted OMV vaccine that previously had been demonstrated to confer protection against meningococcal disease in humans. Conclusions— The data illustrate the potential to develop a broadly immunogenic native OMV vaccine with decreased endotoxin activity that is potentially suitable for testing in humans. G-CSF, IFN- , IP-10, MCP-1, , , The 4.1
Targeted Disruption of Orchestration between Stroma and Tumor Cells in Pancreatic Cancer: Molecular Basis and Therapeutic Implications

Pancreatic cancer is one of the most lethal malignancies, with a prominent desmoplastic reaction as the defining hallmark of the disease. The past several decades have seen dramatic progress in understanding of pancreatic cancer pathogenesis, including the identification of precursor lesions, sequential transformation from normal pancreas to invasive pancreatic cancer and corresponding signature genetic events, and the biological impact of those alterations on malignant behaviors. However, the current therapeutic strategies for epithelial tumor cells, which have exhibited potent antitumor activity in cell culture and animal models, have failed to have significant effects in the clinic. The desmoplastic stroma surrounding pancreatic cancer cells, which accounts for about 90% of a tumor’s mass, clearly is not a passive scaffold for cancer cells but an active contributor to carcinogenesis. Improved understanding of the dynamic interaction between cancer cells and their stroma will be important to designing new, effective therapeutic strategies for pancreatic cancer. This review focuses on the origination of stromal molecular and cellular components in pancreatic tumors, their biological effects on pancreatic cancer cells, and the orchestration between these two components. in the and interplay of multiple Dr. Li is currently the Director of the Gastroenterology Department Military Medical University, as well as Chairman of the Chinese Society of Digestive Endoscope in China. His major interest has been exploring the genetic and epigenetic mechanisms governing chronic pancreatitis and pancreatic cancer, especially those key molecules involved in the process of pancreatic carcinogenesis, e.g., K-ras, NF- κ B, Hedgehog, and etc. As a gastroenterologist, Dr. Li has long been devoting to the studies, which are aimed to identify aberrantly expressed molecules and translate into clinically useful biomarkers for early detection and diagnosis of pancreatic cancer. molecular mechanisms governing cancer and