Miracle-dz/UniFAR-FTUs huggingface dataset:
Stromal cell‐derived factor‐1α directly modulates voltage‐dependent currents of the action potential in mammalian neuronal cells

Stromal cell‐derived factor‐1α (SDF‐1α) is a chemokine whose receptor, CXCR4, is distributed in specific brain areas including hypothalamus. SDF‐1α has recently been found to play important roles in neurons, although direct modulation of voltage‐gated ionic channels has never been shown. In order to clarify this issue, we performed patch‐clamp experiments in fetal mouse hypothalamic neurons in culture. SDF‐1α (10 nm) decreased the peak and rising slope of the action potentials and spike discharge frequency in 22% of hypothalamic neurons tested. This effect was blocked by the CXCR4 antagonist AMD 3100 (1 µm) but not by the metabotropic glutamate receptor antagonist MCPG (500 µm), indicating a direct action of SDF‐1α on its cognate receptor. This effect involved a depression of both inward and outward voltage‐dependent currents of the action potential. We confirmed these effects in the human neuroblastoma cell line SH‐SY5Y, which endogenously expresses CXCR4. Voltage‐clamp experiments revealed that SDF‐1α induced a 20% decrease in the peak of the tetrodotoxin‐sensitive sodium current and tetraethylammonium‐sensitive delayed rectifier potassium current, respectively. Both effects were concentration dependent, and blocked by AMD 3100 (200 nm). This dual effect was reduced or blocked by 0.4 mm GTPγS G‐protein pre‐activation or by pre‐treatment with the G‐protein inhibitor pertussis toxin (200 ng/mL), suggesting that it is mediated via activation of a Gi/o protein. This study extends the functions of SDF‐1α to a direct modulation of voltage‐dependent membrane currents of neuronal cells.
Gabapentin Versus Levodopa for the Treatment of Restless Legs Syndrome in Hemodialysis Patients: An Open‐Label Study

Background. Restless Legs Syndrome (RLS), a common problem increasing morbidity and mortality in hemodialysis (HD) patients, affects 20–30% of uremic patients. Our aim was to find the efficacy of gabapentin in the treatment of RLS in HD patients by comparing a largely used drug, levodopa. Methods. Patients with RLS answered three questionnaires (RLS rating scale proposed by IRLSSG, the Short Form (SF)‐36 and the Pittsburgh Sleep Quality Index) for the evaluation of severity of RLS, effects on quality of life and quality of sleep. Results. Fifteen patients (4.7%) (5 F, 10 M) with a mean age of 45.8 ± 15.3 years got RLS diagnosis. When we compare the two drugs for severity of RLS symptoms relief, the effect of gabapentin was more significant (p < 0.001). Gabapentin significantly improved general health, body pain and social functions (p < 0.001). Moreover, regarding sleep parameters, gabapentin was significantly superior to levodopa for sleep quality, sleep latency (p < 0.001) and sleep disturbance (p < 0.000). Conclusion. To our knowledge this was the first study comparing gabapentin and levodopa efficacy for the treatment of RLS in HD patients. Our results suggested that gabapentin is an effective drug for the management of RLS in hemodialysis patients.
Twelve years of chiari-like malformation and syringomyelia scanning in Cavalier King Charles Spaniels in the Netherlands: Towards a more precise phenotype

Chiari-like malformation (CM), syringomyelia (SM) and middle ear effusion (also called PSOM) are three conditions that frequently occur in Cavalier King Charles Spaniels (CKCS). Both CM and SM are currently screened in the Netherlands prior to breeding and are graded according to the British Veterinary Association’s Kennel Club (BVA/KC) scheme. This study evaluated the prevalence and estimated genetic parameter of CM, SM and middle ear effusion from 12 years of screening results. For SM, the classical method using the BVA/KC scheme, was compared with exact measuring of the central canal dilation. For CM, the BVA/KC scheme was compared with a more detailed scheme. Next to this the presence of microchip artifacts was assessed. 1249 screening of 1020 dogs were re-evaluated. Results indicated the presence of CM in all dogs, suggesting it has become a breed-specific characteristic. And although different grades of CM were observed, the condition did not deteriorate over time. SM was present in 39% of the dogs and a clear age effect was demonstrated, with SM increasing with age. This emphasizes the importance of screening at appropriate age, since SM can worsen with increasing age. One alternative is to promote repeated measures. The presence of middle ear effusion in this study was 19%–21% for dogs younger than 3 years, and 32%–38% for dogs older than 3 years. In as much as 60%, microchip artifacts were noticed, leading to the recommendation to place microchips in another location in breeds that are susceptible to developing SM. Finally, this study estimated the heritability of CM in this population, due to the lack of phenotypic variance, to be very low at 0.02–0.03. The heritability for SM central canal dilatation to be 0.30, compared to 0.13 for the classical BVA/KC method, using a model including the age effect and the combined effect of veterinary clinic and year of the evaluation. Genetic correlations were rather small, ranging from 0.16–0.33. As a conclusion, screening for SM and CM in the entire population should be maintained, and a selection scheme against SM should be based on estimated breeding values for the exact measurement of the central canal dilatation.
The impact of certain psychological factors of investors and managers on the capital structure

Psychology represents the basic requirement for the emergence of disciplines such as behavioral finance and behavioral economics. It has contributed to a better understanding of the behavior of economic actors under conditions of risk arising from the imperfections of cognitive abilities of human beings. Consequently, it is necessary to change the economic models based on mathematical laws in favor of descriptive models that consider the cognitive abilities of the human mind. The most common decisions that are being studied in the field of behavioral finance are the decisions regarding capital structure in companies. The methodology in this paper is based on the net operating income approach. This approach is analyzing the financial section of income statement that refers to the financial expenses of the companies. Financial expenses are assumed to be fixed, determining financial break even, as a consequence of use of financial leverage. The main task of this paper is to determine the impact of some psychological factors in the terms of capital structure and financial leverage, through two case studies of comparative analysis of income statements of the companies Puma and Adidas that will consequently affect the achievement of financial breakevens well as the profitability of the companies. Therefore it is possible to conclude that some analyzed psychological aspects in the process of financial decision making of investors and managers can influence the capital structure decisions, which can be a subject of further researches.
CPT1c Is Localized in Endoplasmic Reticulum of Neurons and Has Carnitine Palmitoyltransferase Activity*

CPT1c is a carnitine palmitoyltransferase 1 (CPT1) isoform that is expressed only in the brain. The enzyme has recently been localized in neuron mitochondria. Although it has high sequence identity with the other two CPT1 isoenzymes (a and b), no CPT activity has been detected to date. Our results indicate that CPT1c is expressed in neurons but not in astrocytes of mouse brain sections. Overexpression of CPT1c fused to the green fluorescent protein in cultured cells demonstrates that CPT1c is localized in the endoplasmic reticulum rather than mitochondria and that the N-terminal region of CPT1c is responsible for endoplasmic reticulum protein localization. Western blot experiments with cell fractions from adult mouse brain corroborate these results. In addition, overexpression studies demonstrate that CPT1c does not participate in mitochondrial fatty acid oxidation, as would be expected from its subcellular localization. To identify the substrate of CPT1c enzyme, rat cDNA was overexpressed in neuronal PC-12 cells, and the levels of acylcarnitines were measured by high-performance liquid chromatography-mass spectrometry. Palmitoylcarnitine was the only acylcarnitine to increase in transfected cells, which indicates that palmitoyl-CoA is the enzyme substrate and that CPT1c has CPT1 activity. Microsomal fractions of PC-12 and HEK293T cells overexpressing CPT1c protein showed a significant increase in CPT1 activity of 0.57 and 0.13 nmol·mg-1·min-1, respectively, which is ∼50% higher than endogenous CPT1 activity. Kinetic studies demonstrate that CPT1c has similar affinity to CPT1a for both substrates but 20–300 times lower catalytic efficiency.
Crisis bargaining in the European Union: Formal rules or market pressure?

To what extent did the European Monetary Union crisis alter the logic of European Union decision making? We analyze the relevance of asymmetric market pressures as compared to that of formal voting and agenda setting rules by applying three established bargaining models to the ‘EMU Positions’ data. Accounting for the interdependence between issues and agreements, we locate actors’ positions on three reform dimensions, namely the level of fiscal discipline, transfer payments and institutionalization. We find that market pressure during the height of the Eurozone crisis was particularly relevant, and that debtor countries were weakened by their difficulty in refinancing their public debt. Our finding shows that formal rules determining agenda setting and veto rights remain relevant even in times of crisis.
Biological variation of free β chorionic gonadotropin and pregnancy-associated plasma protein A in first trimester pregnancies

Abstract Background: Trisomy 21 risk estimation in first trimester pregnancies can be performed by a combined test based on ultrasound measurement of fetal nuchal translucency thickness and maternal plasma concentrations of free β human chorionic gonadotropin (hCGβ) and pregnancy-associated plasma protein A (PAPP-A). However, little knowledge exists regarding the biological variation of hCGβ and PAPP-A when the time interval between sampling increases. Methods: We estimated these variations from double mea-surements of hCGβ and PAPP-A in first trimester pregnancies in 167 women. Data were divided into three groups based on the number of days between sampling. The correlation coefficients and biological variation were estimated for each group. Results: The correlation coefficient between the first and second samples was 0.841 for hCGβ, and 0.706 for PAPP-A. The ranges for biological variation were 11.9%–48.5% for hCGβ and 31.6%–63.3% for PAPP-A, increasing with time between sampling. The average overall biological variation for hCGβ was 29%, and 49.7% for PAPP-A. Conclusions: We found high biological variation for plasma concentrations of hCGβ and PAPP-A, increasing with longer time intervals between sampling. From our data that showed high correlation of hCGβ and PAPP-A in the first and second sample, we found no reason to recommend retesting. However, new studies should clarify whether PAPP-A should be collected early, and hCGβ late, in the first trimester of pregnancy.
Cyclooxygenase‐1 and ‐2 enzymes differentially regulate the brain upstream NF‐κB pathway and downstream enzymes involved in prostaglandin biosynthesis

We have recently reported that cyclooxygenase (COX)‐2‐deficiency affects brain upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to prostaglandin E2 (PGE2), as well as enzyme activity, protein and mRNA levels of the reciprocal isozyme, COX‐1. To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade, we examined the expression and activity of COX‐2 and phospholipase A2 enzymes (cPLA2 and sPLA2), as well as the expression of terminal prostaglandin E synthases (cPGES, mPGES‐1, and − 2) in wild type and COX‐1–/– mice. We found that brain PGE2 concentration was significantly increased, whereas thromboxane B2 (TXB2) concentration was decreased in COX‐1–/– mice. There was a compensatory up‐regulation of COX‐2, accompanied by the activation of the NF‐κB pathway, and also an increase in the upstream cPLA2 and sPLA2 enzymes. The mechanism of NF‐κB activation in the COX‐1–/– mice involved the up‐regulation of protein expression of the p50 and p65 subunits of NF‐κB, as well as the increased protein levels of phosphorylated IκBα and of phosphorylated IKKα/β. Overall, our data suggest that COX‐1 and COX‐2 play a distinct role in brain PG biosynthesis, with basal PGE2 production being metabolically coupled with COX‐2 and TXB2 production being preferentially linked to COX‐1. Additionally, COX‐1 deficiency can affect the expression of reciprocal and coupled enzymes, COX‐2, Ca2+‐dependent PLA2, and terminal mPGES‐2, to overcome defects in brain AA cascade.
Patients with familial adenomatous polyposis experience better bowel function and quality of life after ileorectal anastomosis than after ileoanal pouch

Objective To evaluate the quality of life with emphasis on bowel function in patients undergoing either total colectomy with ileorectal anastomosis (IRA) or restorative proctocolectomy with ileal pouch‐anal anastomosis (IPAA) for familial adenomatous polyposis (FAP).
NEURONAL NETWORK OF PANIC DISORDER: THE ROLE OF THE NEUROPEPTIDE CHOLECYSTOKININ

Panic disorder (PD) is characterized by panic attacks, anticipatory anxiety and avoidance behavior. Its pathogenesis is complex and includes both neurobiological and psychological factors. With regard to neurobiological underpinnings, anxiety in humans seems to be mediated through a neuronal network, which involves several distinct brain regions, neuronal circuits and projections as well as neurotransmitters.
Actions by angiotensin II on esophageal contractility in humans.

BACKGROUND & AIMS Angiotensin II is a potent activator of smooth muscles but has not been much investigated with regard to gastrointestinal motor activity. This study explores expression of the renin-angiotensin system (RAS) in human esophageal musculature and actions by Angiotensin II both in vitro and in vivo. METHODS Muscular specimens of esophageal body and lower esophageal sphincter were obtained from patients undergoing resection as a result of mucosal neoplasm. Healthy volunteers participated in functional examinations of esophageal motility assessed by high-resolution manometry and multiple transmucosal potential-difference measurements. RESULTS Gene transcripts of key components of RAS were found in the esophageal musculature. Immunohistochemistry revealed a distinct staining for Angiotensin II type 1 (AT(1)) receptors in the muscular bundles and blood-vessel walls, whereas Angiotensin II type 2 receptors were confined to blood vessels only. Angiotensin II caused concentration-dependent contractions in vitro, which were inhibited by the AT(1) receptor antagonist losartan but not by the Angiotensin II type 2 receptor antagonist PD123319. Administration of the AT(1) receptor antagonist candesartan reduced the amplitude of swallow-induced peristaltic contractions and both the length and pressure amplitude of baseline high-pressure zone at the esophagogastric junction. Neither swallow-induced axial movements, nor the contraction after transient lower esophageal sphincter relaxations, were influenced by candesartan pretreatment. CONCLUSIONS The study demonstrates a local RAS in the musculature of the distal esophagus and that Angiotensin II is a potent stimulator of esophageal contractions via the AT(1) receptor. The results suggest that Angiotensin II participates in the physiological control of the human esophageal motor activity.
Neuropeptide Y, Tyrosine Hydroxylase and Vasoactive Intestinal Polypeptide‐Immunoreactive Nerve Fibers in the Vertebral Bodies, Discs, Dura Mater, and Spinal Ligaments of the Rat Lumbar Spine

The occurrence of autonomic nerves in the lumbar spine of rats was investigated by immunohistochemical technique, Both peptidergic nerves, represented by immunoreactivity to neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and noradrenergic nerves as reflected by tyrosine hydroxylase (TH) immunoreactivity, were identified. NPY- and TH-positive nerves were predominantly found in the blood vessels walls. They occurred in the bone and periosteum of the vertabral body, disc, dura matar, and in the spinal ligaments. They were particularly numerous along the growth plate and in the outer layers of the intervertebral discs. VIP-positive fibers were predominantly nonvascular, They occurred in all tissues analyzed, but were most abundant in the vertebral bone marrow and periosteum. The VIP-immunoreactive fibers in the outer fibrous layers of the disc and the spinal ligaments were occasionally observed in blood vessel walls. No immunoreactivity could be detected in the nucleus pulposus. In the dura mater, NPY-, TH- and VIP-positive fibers were found both in the ventral and dorsal portion. In view of the vasoconstrictive properties of both NPY and noradrenaline, it may be assumed that the abundance of NPY-and TH-immunoreactive nerves fibers in blood vessel walls reflects a vasoregulatory activity. The predominance of nonvascular VIP-positive fibers in the vertebral bone marrow and perlosteum may represent an involvement in local bone physiology.
Ultrastructural evidence for intra‐ and extranuclear projections of GABAergic neurons of the suprachiasmatic nucleus

GABAergic projections of the suprachiasmatic nucleus (SCN) were demonstrated in a double‐labelling ultrastructural study which visualised the efferents of the SCN by PHA‐L tracing, diaminobenzidine (DAB) immunocytochemistry, and GABA with immunogold postembedding staining. The results show a strong contralateral projections of the SCN that is partly GABA‐containing. In addition, ipsilateral SCN projections to the dorsomedial hypothalamus and periventricular part of the paraventricular nucleus and subparaventricular nucleus were shown to contain GABA. The present results indicate that the SCN may utilize this inhibitory neurotransmitter to regulate and organize its own circadian rhythm as well as using GABA to transmit its diurnal information to other regions of the brain. © Wiley‐Liss, Inc.
Investment Experience, Financial Literacy, and Investment‐Related Judgments

This research examines how individual investors’ financial literacy impacts their assessments of incentive-based conflicts of interest. Fundamental to many aspects of financial accounting, prior research suggests that less-sophisticated investors may be at a disadvantage in understanding the influence of incentives. I begin by documenting investors’ financial literacy skills using a relatively large sample of participants (n>1,000), benchmarked against national samples of financial capability skills in the United States. With replications of two financial accounting experiments, I then document that investors with higher financial literacy are more sensitive to others’ incentives and more likely to incorporate that understanding into their judgments than are investors with lower financial literacy or non-investors. This research extends the financial literacy literature by considering more detailed, accounting-based financial disclosures, and the accounting literature on the effect of individual cognitive characteristics by assessing conditions under which results from prior research using graduate business students would replicate to a broader range of individual investors.
Monocytes direct T lymphocyte stimulation of human peripheral blood granulocyte‐macrophage colony formation

The committed granulocyte‐macrophage progenitor cell (or colony‐forming unit, CFU‐GM) differentiates in vitro under the influence of the soluble glycoprotein factor(s) termed colony stimulating activity (GM‐CSA), which can be derived from several cellular sources, including normal human peripheral blood mononuclear cells (PBMNC). We have investigated the respective roles of the monocyte and T lymphocyte components of PBMNC in generating GM‐CSA using as an assay CFU‐GM colony formation by purified peripheral blood null cells. Highly purified unstimulated T‐lymphocytes did not themselves stimulate null cell CFU‐GM colony formation, but when monocytes were also included, large numbers of colonies were observed, far greater than those stimulated by monocytes alone. This synergism was independent of HLA phenotype, occurring with T‐lymphocyte and monocyte fractions from unrelated donors. Media conditioned by unstimulated purified monocytes promoted CFU‐GM colonies from null cells only in the presence of T‐Iymphocytes, suggesting that monocytes produce a factor directing the synthesis and/or release of GM‐CSA by T cells.
Identification of differentially expressed genes in keratoconus epithelium analyzed on microarrays.

PURPOSE The present study was conducted to investigate differential gene expression in individual samples derived from fresh-frozen human keratoconus and normal corneal epithelium, using gene microarrays. METHODS Total RNA was extracted (11 keratoconus and 8 normal samples), labeled, and hybridized to microarrays (GeneChip; Affymetrix, Inc., Santa Clara, CA). GeneChip data were validated by verifying the expression profiles of 10 genes by real-time PCR and by recalculation using dChip software (Wong Laboratory, Department of Biostatistics, Harvard School of Public Health, Boston, MA). Furthermore, 3 of the 10 encoded proteins were stained by immunohistochemistry. RESULTS In comparison with normal cornea, the expression of 471 of the 5600 genes on the microarrays was changed in the keratoconus samples. This number was reduced to 47 with increased expression and 9 with decreased expression when more stringent selection parameters were applied. These genes are believed to be involved in keratoconus. Two of the candidate genes, lysyl oxidase and tissue inhibitor of metalloproteinase 3, are known to be involved in other eye diseases. Expression profiles were reproduced with the software dChip (Wong Laboratory) and real-time PCR. Increases in keratin 6 and 13 were also detected at the protein level. CONCLUSIONS Keratoconus epithelium appears to be characterized by massive changes of the cytoskeleton, reduced extracellular matrix remodeling, altered transmembrane signaling, and modified cell-to-cell and cell-to-matrix interactions. Validation of gene expression with dChip analysis and real-time PCR indicates GeneChip to be a valid technique for investigation of epithelium from single dissected corneal samples. Association between alterations at RNA and protein levels was observed for some of the tested candidates.