Miracle-dz/UniFAR-FTUs huggingface dataset:
High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus

The release of neurotransmitters is modulated by presynaptic metabotropic glutamate receptors (mGluRs), which show a highly selective expression and subcellular location in glutamatergic terminals in the hippocampus. Using immunocytochemistry, we investigated whether one of the receptors, mGluR7, whose level of expression is governed by the postsynaptic target, was present in GABAergic terminals and whether such terminals targeted particular cells. A total of 165 interneuron dendritic profiles receiving 466 synapses (82% mGluR7a‐positive) were analysed. The presynaptic active zones of most GAD‐(77%) or GABA‐positive (94%) synaptic boutons on interneurons innervated by mGluR7a‐enriched glutamatergic terminals (mGluR7a‐decorated) were immunopositive for mGluR7a. GABAergic terminals on pyramidal cells and most other interneurons in str. oriens were mGluR7a‐immunonegative. The mGluR7a‐decorated cells were mostly somatostatin‐ and mGluR1α‐immunopositive neurons in str. oriens and the alveus. Their GABAergic input mainly originated from VIP‐positive terminals, 90% of which expressed high levels of mGluR7a in the presynaptic active zone. Parvalbumin‐positive synaptic terminals were rare on mGluR7a‐decorated cells, but on these neurons 73% of them were mGluR7a‐immunopositive. Some type II synapses innervating interneurons were immunopositive for mGluR7b, as were some type I synapses. Because not all target cells of VIP‐positive neurons are known it has not been possible to determine whether mGluR7 is expressed in a target‐cell‐specific manner in the terminals of single GABAergic cells. The activation of mGluR7 may decrease GABA release to mGluR7‐decorated cells at times of high pyramidal cell activity, which elevates extracellular glutamate levels. Alternatively, the presynaptic receptor may be activated by as yet unidentified endogenous ligands released by the GABAergic terminals or the postsynaptic dendrites.
Phylogeny of the Drosophila immigrans Species Group (Diptera: Drosophilidae) Based on Adh and Gpdh Sequences

Abstract The immigrans species group in the Drosophilinae is one of the representative species groups of Drosophila in East Asia. Although this group constitutes a significant part of the drosophilid fauna in the Old World, only a few species have been analyzed in previous molecular phylogenetic studies. To study the phylogeny of the immigrans group, we analyzed the nucleotide sequences of two nuclear genes, alcohol dehydrogenase (Adh) and glycerol-3-phosphate dehydrogenase (Gpdh), for 36 drosophilid species, including 12 species of the immigrans group. In the resultant phylogenetic trees, 10 species of the immigrans group (D. immigrans, D. formosana, D. ruberrima, D. albomicans, D. nasuta, D. neonasuta, D. pallidifrons, D. hypocausta, D. neohypocausta, D. siamana) consistently formed a clade (the immigrans group proper), although the phylogeny within this clade did not exactly correspond to the classification of species subgroups. However, D. annulipes and D. quadrilineata, both of which belong to the quadrilineata subgroup of the immigrans group, were not included in the immigrans group proper. Furthermore, we obtained the unexpected result that D. annulipes was included in a clade comprising Scaptomyza and Hawaiian Drosophila, together with D. maculinotata of the funebris group, although the phylogenetic relationships within this clade remain uncertain and need to be substantiated with further studies. Thus, according to the present study, the immigrans group is polyphyletic.
Activation of Excitatory Amino Acid Receptors in Bovine Dental Pulp Evokes the Release of iCGRP

The activation of excitatory amino acid (EAA) receptors within the central nervous system is associated with numerous centrally mediated phenomena, including hyperalgesia. However, relatively little is known about the peripheral mechanisms which these receptors may regulate when activated. This research evaluated the hypothesis that EAA receptors in bovine dental pulp activate a population of peptidergic sensory neurons as measured by the release of immunoreactive calcitonin gene-related peptide (iCGRP), a neuropeptide associated with neurogenic inflammation. In vitro superfusion of bovine dental pulp was used to evaluate the regulation of iCGRP secretion by the EAA receptor agonists AMPA, kainate, NMDA, and L-glutamate. Both AMPA and kainate stimulated the release of iCGRP in a concentration-dependent manner (AMPA EC50 = 0.27 ± 3.3 nM; kainate EC50 = 3.2 ± 1.1 μM). Pre-treatment and coadministration of the AMPA/kainate receptor antagonist CNQX significantly reduced the iCGRP release evoked by either of these agonists. In contrast, neither NMDA nor L-glutamate induced any consistent changes in iCGRP release. These results suggest that the activation of AMPA and kainate receptors in dental pulp may contribute to peripheral release of vasoactive neuropeptides which mediate a neurogenic component of inflammation.
MiR‐34a chemosensitizes bladder cancer cells to cisplatin treatment regardless of p53‐Rb pathway status

MiR‐34a is a downstream effector of p53 that has been shown to target several molecules associated with cell cycle and cell survival pathways. As alterations in these pathways are frequent in muscle invasive transitional cell carcinoma of the bladder (MI‐TCC), for example mutation or loss of p53 and Rb, the goal of this study was to determine whether manipulation of miR‐34a expression levels could abrogate the effect of these alterations and sensitize bladder cancer cells to chemotherapy. We demonstrate that transfection of T24, TCCSUP and 5637 with pre‐miR‐34a followed by cisplatin treatment results in a dramatic reduction in clonogenic potential and induction of senescence compared to treatment with cisplatin alone. Molecular analyses identified Cdk6 and sirtuin (SIRT)‐1 as being targeted by miR‐34a in MI‐TCC cells, however, inhibition of Cdk6 and SIRT‐1 was not as effective as pre‐miR‐34a in mediating chemosensitization. Analysis of 27 preneoadjuvant chemotherapy patient samples revealed many of the patients who subsequently did not respond to treatment (based on surgical resection postchemotherapy and 5‐year survival data) express lower levels of miR‐34a, however, a statistically significant difference between the responder and nonresponder groups was not observed (p = 0.1174). Analysis of eight sets of pre‐ and postneoadjuvant chemotherapy patient samples determined miR‐34a expression increased postchemotherapy in only two of the eight patients. The combined data indicate that elevation of miR‐34a expression levels before chemotherapy would be of benefit to MI‐TCC patients, particularly in a setting of low miR‐34a expression.
Assessing Open Government Performance through Three Public Administration Perspectives: Efficiency, Democratic Responsiveness, and Legal-rational Process

Open government is a growing feature of public administration in governments across the globe. Open government has long been considered vital to democratic society but, with the arrival of digital government, openness has become touted by governments that use information and communication technologies (ICT) without making the necessary legal and institutional reforms to support accountability and transparency. The intersection of openness and ICT challenges our approach to digital government in public administration practice and theory, and it calls for better theoretical frameworks to make sense of open government performance. In this paper, I propose a threefold framework of efficiency, democratic responsiveness, and legal-rational process. The framework is conceptually analyzed through four types of open government: budget transparency, citizen engagement, open data, and freedom of information. The analysis results in the creation of a set of measurement items that help to clarify important aspects of open government performance, and which can be used to generate indicators for evaluating open government initiatives.
Glucose pathways adaptation supports acquisition of activated microglia phenotype

With its capacity to survey the environment and phagocyte debris, microglia assume a diversity of phenotypes to respond specifically through neurotrophic and toxic effects. Although these roles are well accepted, the underlying energetic mechanisms associated with microglial activation remain largely unclear. This study investigates microglia metabolic adaptation to ATP, NADPH, H+, and reactive oxygen species production. To this end, in vitro studies were performed with BV‐2 cells before and after activation with lipopolysaccharide + interferon‐γ. Nitric oxide (NO) was measured as a marker of cell activation. Our results show that microglial activation triggers a metabolic reprogramming based on an increased glucose uptake and a strengthening of anaerobic glycolysis, as well as of the pentose pathway oxidative branch, while retaining the mitochondrial activity. Based on this energy commitment, microglial defense capacity increases rapidly as well as ribose‐5‐phosphate and nucleic acid formation for gene transcription, essential to ensure the newly acquired functions demanded by central nervous system signaling. We also review the role of NO in this microglial energy commitment that positions cytotoxic microglia within the energetics of the astrocyte–neuron lactate shuttle. © 2014 Wiley Periodicals, Inc.
Short‐term effects of a low carbohydrate diet on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes: A randomized open‐label crossover trial

The aim of the present study was to assess the effects of a high carbohydrate diet (HCD) vs a low carbohydrate diet (LCD) on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes. Ten patients (4 women, insulin pump‐treated, median ± standard deviation [s.d.] age 48 ± 10 years, glycated haemoglobin [HbA1c] 53 ± 6 mmol/mol [7.0% ± 0.6%]) followed an isocaloric HCD (≥250 g/d) for 1 week and an isocaloric LCD (≤50 g/d) for 1 week in random order. After each week, we downloaded pump and sensor data and collected fasting blood and urine samples. Diet adherence was high (225 ± 30 vs 47 ± 10 g carbohydrates/d; P < .0001). Mean sensor glucose levels were similar in the two diets (7.3 ± 1.1 vs 7.4 ± 0.6 mmol/L; P = .99). The LCD resulted in more time with glucose values in the range of 3.9 to 10.0 mmol/L (83% ± 9% vs 72% ± 11%; P = .02), less time with values ≤3.9 mmol/L (3.3% ± 2.8% vs 8.0% ± 6.3%; P = .03), and less glucose variability (s.d. 1.9 ± 0.4 vs 2.6 ± 0.4 mmol/L; P = .02) than the HCD. Cardiovascular markers were unaffected, while fasting glucagon, ketone and free fatty acid levels were higher at end of the LCD week than the HCD week. In conclusion, the LCD resulted in more time in euglycaemia, less time in hypoglycaemia and less glucose variability than the HCD, without altering mean glucose levels.
Morphological and Functional Aspects of the Senile Larynx

Objective: To analyze the senile larynx, considering morphological aspects during respiration and functional aspects during phonation, comparing it to the young adult larynx. Patients and Methods: A retrospective study was conducted of 100 laryngeal images of adults without vocal complaints, 50 laryngeal images of young adults aged 20–45 years and 50 laryngeal images of elderly individuals aged 65–85 years, of both genders. Images were produced by means of a rigid endoscope and stroboscopy. The morphological aspects analyzed were: laryngeal symmetry, vocal fold bowing, prominence of the vocal process and glottic proportion. The functional aspects analyzed were glottic closure, laryngeal vestibule behavior, phase (timing of closure) and amplitude symmetry of mucosal wave and tremor of laryngeal structures. Results: Significant differences between the young adult larynx and the geriatric larynx were found for the following parameters: vocal fold bowing, prominence of the vocal process, glottic proportion, phase and amplitude symmetry of mucosal wave and tremor of laryngeal structures. Conclusion: The data suggests that the geriatric larynx differs from the young adult larynx in many characteristic aspects.
Visualization of Rab3A dissociation during exocytosis: A study by total internal reflection microscopy

Rab3A is a small G protein in the Rab3 subfamily, and is thought to act at late stage of exocytosis. However, the detailed mechanism of its action is not completely understood. To study the role of Rab3A in exocytosis, we used a total internal reflection fluorescence microscope to examine the fluorescence changes of EGFP‐Rab3A‐labeled and NPY‐EGFP‐labeled vesicles in PC12 cells upon stimulation. The fluorescence of EGFP‐Rab3A‐labeled and NPY‐EGFP‐labeled vesicles decreased while showing different patterns. The NPY‐EGFP‐labeled vesicles that exocytosed showed a transient fluorescence increase before NPY‐EGFP fluorescence disappearance, which represents fusion and NPY release. This transient increase was diminished in cells that co‐expressed the GDP‐bound Rab3A mutant. The fluorescence of EGFP‐Rab3A‐labeled vesicles dispersed before disappearance, which represents the dissociation of Rab3A from the vesicles. The dispersion was not found in GTP‐bound Rab3A mutant‐labeled vesicles. Interestingly, EGFP‐Rab3A F59S, a mutant unable to bind rabphilin, dissociates slower from the vesicles than wild type Rab3A and caused a slower release of NPY‐EGFP. The results provide direct evidence to support the hypothesis that GTP hydrolysis and rabphilin are involved in Rab3A dissociation from the vesicles and the occurrence of exocytosis. J. Cell. Physiol. 211: 316–326, 2007. © 2006 Wiley‐Liss, Inc.
Technological Progress, Labour Productivity and Economic Growth: Disentangling the Negative and Positive Effects

This study simply claims that technological progress has positive and negative effects on the labour productivity, so, on the economic growth. Technological progress may have a negative effect on economic growth because of skills obsolescence of labour. For this reason, if the nature of technological progress is assumed as Harrod-neutral for the steady-state analysis, then, the net effect of the technological progress on the economic growth can be examined. Using Hicks-neutrality, it cannot be possible to investigate positive and negative effects. The present study offers a simple calculation procedure in order to disentangle the positive and negative effects. Finally, the study tries to introduce capital-deepening-induced technological progress, if the growth rate and contribution of technological progress is found negative while there is positive economic growth and the steady state conditions are hold at the final state.
Psychopathology and substance abuse in parents of young children with attention-deficit/hyperactivity disorder.

OBJECTIVE To compare the prevalence of psychological disorders in parents of young children with and without attention-deficit/hyperactivity disorder (ADHD) and comorbid disruptive behavior disorders (DBD). METHOD Subjects included 98 three- to seven-year-old children with DSM-IV ADHD (68 with ADHD and comorbid oppositional defiant or conduct disorder [ADHD+ODD/CD]) and 116 non-ADHD comparison children recruited in 1995-96 during the first wave of a longitudinal study. Biological mothers were administered interviews to assess ADHD and DBD in their children and mood, anxiety, and substance use disorders in themselves. In addition, they were queried about symptoms of childhood ADHD and DBD, and antisocial personality disorder in themselves and their children's biological fathers. RESULTS Child ADHD was associated with increased rates of maternal and paternal childhood ADHD relative to comparison children. Child ADHD+ODD/CD was associated with maternal mood disorders, anxiety disorders, and stimulant/cocaine dependence, and paternal childhood DBD. Mothers of children with ADHD+ODD/CD also reported increased drinking problems in their children's fathers. CONCLUSIONS These findings indicate that many young children with ADHD, particularly those with comorbid ODD/CD, require comprehensive services to address both their ADHD and the mental health needs of their parents.
Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials

Objective:Conjugated estrogens/bazedoxifene reduces vasomotor symptoms and prevents postmenopausal bone loss without stimulating the breast and endometrium. We analyzed changes in bone mineral density (BMD) and bone markers using pooled data from two phase-3 trials. Methods:Selective Estrogens, Menopause, and Response to Therapy (SMART)-1 and SMART-5 were randomized, double-blind, placebo- and active-controlled studies conducted in postmenopausal nonhysterectomized women. BMD and turnover marker data were pooled for women given conjugated estrogens (0.45 or 0.625 mg) plus bazedoxifene 20 mg or placebo over 12 months. Sensitivity analyses were conducted using baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, race, and geographic region. Results:There were 1,172 women, mean age 54.9 years, mean 6.21 years since menopause, mean lumbar spine, and total hip T scores −1.05 and −0.58; 58.8% had a Fracture Risk Assessment Tool score less than 5% indicating low fracture risk. At 12 months, adjusted differences (vs placebo) in BMD change in the groups taking conjugated estrogens 0.45 or 0.625 mg plus bazedoxifene 20 mg were 2.3% and 2.4% for lumbar spine, 1.4% and 1.5% for total hip, and 1.1% and 1.5% for femoral neck (all P < 0.001 vs placebo). These increases were unrelated to baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, or geographic region. Both doses reduced bone turnover markers (P < 0.001). Conclusions:Conjugated estrogens/bazedoxifene significantly improved BMD and turnover in a large population of younger postmenopausal women at low fracture risk and is a promising therapy for preventing postmenopausal bone loss.
Effect of Sema4D on microglial function in middle cerebral artery occlusion mice

Cerebral ischemia evokes neuroinflammatory response. Inflammatory stimulation induces microglial activation, such as changes of their morphology from ramified to ameboid, expression of iNOS and cytokines, and the elevation of proliferative activity. Activated microglia play important roles in pathogenesis of cerebral ischemia. A previous study indicated that Sema4D promoted iNOS expression in cultured microglia; however, roles of Sema4D on microglial activation in ischemic injury remains unclear. We investigated the effect of Sema4D‐deficiency on microglial activation by using permanent middle cerebral artery occlusion (MCAO) in mice. In this study, ischemia‐induced activated microglia were classified into activated‐ramified microglia and ameboid microglia based on their morphology. We demonstrated that the rate of iNOS expression in activated‐ramified microglia was lower than that in ameboid microglia, while the most proliferating microglia were activated‐ramified microglia but not ameboid microglia after cerebral ischemia. Sema4D‐deficiency decreased the number of ameboid microglia and iNOS‐expressing activated‐ramified microglia in the peri‐ischemic cortex. These changes by Sema4D‐deficiency contributed to the reduction of NO production that was estimated by nitrite concentration in ischemic cortex. On the other hand, Sema4D‐deficiency promoted proliferation of microglia in the peri‐ischemic cortex. Importantly, ischemia‐induced apoptosis and postischemic behavioral abnormality were moderated in Sema4D−/− mice. These findings suggest that Sema4D promotes cytotoxic activation of microglia and inhibits functional recovery after cerebral ischemia. GLIA 2015;63:2249–2259
A Stably Protonated Adenine Nucleotide with a Highly Shifted pKa Value Stabilizes the Tertiary Structure of a GTP-Binding RNA Aptamer.

RNA tertiary structure motifs are stabilized by a wide variety of hydrogen-bonding interactions. Protonated A and C nucleotides are normally not considered to be suitable building blocks for such motifs since their pKa values are far from physiological pH. Here, we report the NMR solution structure of an in vitro selected GTP-binding RNA aptamer bound to GTP with an intricate tertiary structure. It contains a novel kind of base quartet stabilized by a protonated A residue. Owing to its unique structural environment in the base quartet, the pKa value for the protonation of this A residue in the complex is shifted by more than 5 pH units compared to the pKa for A nucleotides in single-stranded RNA. This is the largest pKa shift for an A residue in structured nucleic acids reported so far, and similar in size to the largest pKa shifts observed for amino acid side chains in proteins. Both RNA pre-folding and ligand binding contribute to the pKa shift.
Study of Scientific Collaborations in the Intelligence and Security Informatics Research Community by Social Network Analysis

The field of Intelligence and Security Informatics (ISI) is a relatively new research area and co-authorship is the predominant trend in the field of ISI. This study aims to investigate the collaborative characteristics in the ISI research community through social network analysis. The collaboration network of ISI researchers at the domain/disciplinary level based on publications in the field of ISI is built, and three centrality measures, closeness, betweenness, and degree centralities, are used to identify the most prominent researchers in the community. The visualization tool of pajek is also used to identify the main actors, clusters and components in the network.
Intracellular Ca2+ and not the extracellular matrix determines surface dynamics of AMPA-type glutamate receptors on aspiny neurons

The perisynaptic extracellular matrix (ECM) contributes to the control of the lateral mobility of AMPA-type glutamate receptors (AMPARs) at spine synapses of principal hippocampal neurons. Here, we have studied the effect of the ECM on the lateral mobility of AMPARs at shaft synapses of aspiny interneurons. Single particle tracking experiments revealed that the removal of the hyaluronan-based ECM with hyaluronidase does not affect lateral receptor mobility on the timescale of seconds. Similarly, cross-linking with specific antibodies against the extracellular domain of the GluA1 receptor subunit, which affects lateral receptor mobility on spiny neurons, does not influence receptor mobility on aspiny neurons. AMPARs on aspiny interneurons are characterized by strong inward rectification indicating a significant fraction of Ca2+-permeable receptors. Therefore, we tested whether Ca2+ controls AMPAR mobility in these neurons. Application of the membrane-permeable Ca2+ chelator BAPTA-AM significantly increased the lateral mobility of GluA1-containing synaptic and extrasynaptic receptors. These data indicate that the perisynaptic ECM affects the lateral mobility differently on spiny and aspiny neurons. Although ECM structures on interneurons appear much more prominent, their influence on AMPAR mobility seems to be negligible at short timescales.