Miracle-dz/UniFAR-FTUs huggingface dataset:
Human recombinant monocyte chemotactic protein and other c‐c chemokines bind and induce directional migration of dendritic cells in vitro

Because dendritic cells (DC) are the most potent antigen‐presenting cells involved in many pathophysiological responses, we investigated the effect of chemokines on the migration of these cells in an effort to determine whether chemokines may contribute to the initiation of immune responses. CD34+ progenitor cells isolated from umbilical cord blood were grown in suspension cultures with cytokines and expanded 50‐ to 100‐fold. A variable proportion of the cells expressed markers consistent with DC. The proportion of CD1a+ DC was increased when the cells were cultured with interleukin‐4 (IL‐4). These cells expressed specific binding sites for C‐C and C‐X‐C chemokines. Cells cultured with or without IL‐4 had similar binding profiles. All C‐C chemokines tested, including monocyte chemotactic protein (MCP)‐1, MCP‐2, MCP‐3, macrophage inflammatory protein‐1α (MIP1α), MIP‐1β, and RAN‐TES, induced migration of DC‐enriched cells cultured with or without IL‐4 with MCP‐3 being the most potent chemoattractant. Phenotypic analysis of cell migrating in response to C‐C chemokines showed that CD1a+ cells were indeed attracted across the polycarbonate filters, and there was no preferential attraction of contaminating CD14+ monocytes by C‐C chemokines. DC‐enriched cells also expressed specific binding sites for IL‐8 and NAP2, which failed to induce cell migration. Our results suggest that C‐C chemokines may participate in the recruitment of DC to amplify host defense. J. Leukoc. Biol. 60: 365–371; 1996.
The Insulin-like Growth Factor (IGF)Binding Protein 1 Binding Epitope on IGF-I Probed by Heteronuclear NMR Spectroscopy and Mutational Analysis*

NMR spectroscopy studies and biosensor interaction analysis of native and site-directed mutants of insulin-like growth factor I (IGF-I) was applied to identify the involvement of individual residues in IGF-I binding to IGF-binding protein 1 (IGFBP-1). Backbone NMR chemical shifts were found to be affected by IGFBP-1 binding in the following residues: Pro2, Glu3, Cys6, Gly7, Gly19, Pro28–Gly30, Gly32, Arg36, Arg37, Gln40–Gly42, Pro63, Lys65, Pro66, and Lys68–Ala70. Three IGF-I arginine side chains were identified by NMR to participate in IGFBP-1 binding. All IGF-I arginine residues were replaced by alanines, using site-directed mutagenesis, in four single substituted variants, IGF-I(R21A), IGF-I(R50A), IGF-I(R55A), and IGF-I(R56A), and one double replacement mutant, IGF-I(R36A/R37A). Biosensor interaction analysis binding studies demonstrate the involvement of Arg36-Arg37 and Arg50 in IGFBP-1 binding, while experiments with the IGF-I receptor implicate Arg21, Arg36-Arg37, and Arg56 as part of the receptor binding epitope. These overlapping binding surfaces explain why IGF-I receptor and IGFBP-1 binding to IGF-I is competitive. The C terminus of free, but not IGFBP-1-bound, IGF-I is found to exist in two distinct, NMR-detectable conformations at 30 °C. One possible explanation for this structural heterogeneity could be cis-trans isomerization of the Cys6–Cys48 disulfide bond.
Transepithelial transport of the fluoroquinolone ciprofloxacin by human airway epithelial Calu-3 cells

Although fluoroquinolone antibiotics such as ciprofloxacin are able to gain access to lung tissue and both pleural and bronchial secretions, the characteristics of transport and cellular uptake of ciprofloxacin in human epithelial lung tissue remain obscure. We have chosen human airway epithelial (Calu-3) cells, reconstituted as functional epithelial layers grown on permeable filter supports, as a model with which to assess both transepithelial transport and cellular uptake of ciprofloxacin. Transepithelial ciprofloxacin fluxes in absorptive (apical-to-basal) and secretory (basal-to-apical) directions were similar throughout the concentration range studied (1.0 microM to 3.0 mM). Transepithelial mannitol fluxes measured concurrently were substantially smaller than ciprofloxacin fluxes in Calu-3 epithelia, suggesting the existence of a mediated transcellular route in addition to a paracellular route for transepithelial permeation. Apical-to-basal ciprofloxacin flux (at 10 microM) was inhibited by a 100-fold excess of unlabelled norfloxacin, enoxacin, and ofloxacin, while secretory flux was unaffected. Cellular uptake of ciprofloxacin, determined as a cell/medium ratio, was greater from the basal compartment (2.7-fold) than apical uptake (1.39-fold) measured at 100 microM ciprofloxacin and showed no saturation up to 3 mM ciprofloxacin. Comparison of the permeation of ciprofloxacin was made with that of lipophilic substrates such as vinblastine and digoxin. There was a linear correlation between transepithelial permeability (Pa-b) and their oil/water partition coefficients with mannitol < ciprofloxacin < digoxin < vinblastine. Comparison of transport of ciprofloxacin across human airway Calu-3 epithelia with that across intestinal Caco-2 epithelia emphasizes the absence of a specific secretory pathway; ciprofloxacin permeation in Calu-3 epithelia appears to be mediated primarily by a transcellular route, with mediated transfer at apical and basal membranes occurring via transporters with low affinity to ciprofloxacin.
Intravenous Chlorhexidine Gluconate Causing Acute Respiratory Distress Syndrome

Case Report: A 67-year-old man undergoing a colectomy for colon cancer was unintentionally administered 0.8 mg of chlorhexidine gluconate intravenously and subsequently developed acute respiratory distress syndrome. The operation was discontinued immediately. Respiratory failure progressed despite three cycles of plasma exchange beginning on day 1. Extracorporeal membrane oxygenation for 72 h beginning on day 3 was associated with dramatic improvement. The patient showed complete recovery of intellectual function and subsequently underwent a colectomy with lymph node dissection for colon cancer. Conclusion: For acute respiratory distress syndrome secondary to chlorhexidine gluconate intoxication, consideration should be given to the treatment of initial respiratory distress and subsequent pneumonia. The benefit of extracorporeal membrane oxygenation and plasma exchange may merit further investigation.
Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: From tuberous sclerosis to common acquired epilepsies

Most current treatments for epilepsy are symptomatic therapies that suppress seizures but do not affect the underlying course or prognosis of epilepsy. The need for disease‐modifying or “antiepileptogenic” treatments for epilepsy is widely recognized, but no such preventive therapies have yet been established for clinical use. A rational strategy for preventing epilepsy is to target primary signaling pathways that initially trigger the numerous downstream mechanisms mediating epileptogenesis. The mammalian target of rapamycin (mTOR) pathway represents a logical candidate, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. The importance of the mTOR pathway in epileptogenesis is best illustrated by tuberous sclerosis complex (TSC), one of the most common genetic causes of epilepsy. In mouse models of TSC, mTOR inhibitors prevent the development of epilepsy and underlying brain abnormalities associated with epileptogenesis. Accumulating evidence suggests that mTOR also participates in epileptogenesis due to a variety of other causes, including focal cortical dysplasia and acquired brain injuries, such as in animal models following status epilepticus or traumatic brain injury. Therefore, mTOR inhibition may represent a potential antiepileptogenic therapy for diverse types of epilepsy, including both genetic and acquired epilepsies.
A longitudinal assessment on the economic effects of hosting major sporting events

ABSTRACT Hosting major sporting events (MSEs) has become a globalized strategy for many countries. This paper is to incorporate event study and dynamic panel data analysis with annual secondary data to examine and clarify the long-term economic effects of host countries that had hosted the Asian Games and the Olympic Games from 1950 to 2014. The results indicate that hosting MSEs to create positive economic effects like the real economic growth rate, investment, employment and international trade may be a myth even for developing countries. The evidences can provide the sport management or authority with longitudinal and comprehensive elaboration for biding or hosting MSEs in the future.
The influence of methylenetetrahydrofolate reductase and thymidylate synthetase gene polymorphisms on lung adenocarcinoma occurrence.

PURPOSE Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthetase (TYMS) are suggested as risk factors for lung cancer. The purpose of this study was to analyze the association of MTHFR C677T polymorphism and variable number tandem repeat 2R/3R and single nucleotide polymorphism G>C in the 3R allele of the TYMS gene with lung adenocarcinoma. METHODS A case-control study including lung adenocarcinoma patients and healthy subjects was performed. Restriction fragment length polymorphism analysis was used for genotyping. Descriptive analyses included genotype and allelic frequencies; the odds ratio and 95% confidence interval were calculated as an estimate of relative risk. Significance was set at p<0.05. RESULTS A significant difference in CC vs TT+CT MTHFR genotype distribution was observed between patients and controls. There was no significant association between the TYMS polymorphisms and the risk of lung adenocarcinoma. CONCLUSIONS The MTHFR 677T allele is likely to have a protective effect against lung adenocarcinoma development.
The Properties of Steric Gate Mutants Reveal Different Constraints within the Active Sites of Y-family and A-family DNA Polymerases*

Y-family (lesion-bypass) DNA polymerases show the same overall structural features seen in other members of the polymerase superfamily, yet their active sites are more open, with fewer contacts to the DNA and nucleotide substrates. This raises the question of whether analogous active-site side chains play equivalent roles in the bypass polymerases and their classical DNA polymerase counterparts. In Klenow fragment, an A-family DNA polymerase, the steric gate side chain (Glu710) not only prevents ribonucleotide incorporation but also plays an important role in discrimination against purine-pyrimidine mispairs. In this work we show that the steric gate (Phe12) of the Y-family polymerase Dbh plays a very minor role in fidelity, despite its analogous role in sugar selection. Using ribonucleotide discrimination to report on the positioning of a mispaired dNTP, we found that the pyrimidine of a Pu-dPyTP nascent mispair occupies a similar position to that of a correctly paired dNTP in the Dbh active site, whereas in Klenow fragment the mispaired dNTP sits higher in the active site pocket. If purine-pyrimidine mispairs adopt the expected wobble geometry, the difference between the two polymerases can be attributed to the binding of the templating base, with the looser binding site of Dbh permitting a variety of template conformations with only minimal adjustment at the incoming dNTP. In Klenow fragment the templating base is more rigidly held, so that changes in base pair geometry would affect the dNTP position, allowing the Glu710 side chain to serve as a sensor of nascent mispairs.
Primary Hyperparathyroidism in Patients with Gastric Carcinoid Tumors Type 1: An Unusual Coexistence

Objective: Although a number of familiar syndromes are associated with primary hyperparathyroidism (PHP), there is no information regarding the prevalence of PHP in other sporadic neuroendocrine diseases. The aim of this study is to investigate the prevalence of PHP in our group of patients with gastric carcinoid (GC) type 1 tumors. Methods: Twenty-six patients with biopsy-proven GC type 1 tumors were retrospectively studied. The diagnosis of PHP was suspected following elevated or high-normal serum calcium levels and elevated or inappropriate normal parathyroid hormone levels. Further tests for the localization of the hyperfunctioning parathyroid glands included neck ultrasound, 99mTc-SESTAMIBI scanning, and cervical or upper mediastinal MR imaging studies. Four control groups were also studied: two age- and sex-matched groups of individuals with (n = 49) and without (n = 34) thyroid autoimmunity and normal endoscopy of the stomach, a third group with nongastric neuroendocrine tumors (n = 68), and a fourth group with atrophic gastritis and hypergastrinemia, without gastric endocrine tumors (n = 30). Results: PHP was diagnosed in 4 (15.38%) patients with GC type 1 tumors compared to none of the 4 control groups. Three of the 4 patients with PHP were operated and proved to have a parathyroid adenoma. No statistically significant differences were observed between patients with or without PHP in mean gastrin and chromogranin A levels, number of lesions, ki-67 labeling index expression, and maximum GC type 1 tumor diameter. Conclusion: PHP seems to be relatively common, approximately 15% in the present cohort, in patients with GC type 1 tumors. PHP should be actively looked for in such patients and treated accordingly.
Regime-Shifts, Multicointegration and Fiscal Sustainability: Further Evidence on Poland (1999-2015)

This paper reassesses the sustainability of fiscal policy in Poland, extending the analysis of Tronzano (forthcoming) to a multicointegration test allowing for regime shifts. The empirical evidence strongly rejects the existence of multicointegration, thus suggesting that Poland’s fiscal process is unsustainable in a stochastic environment. In line with my previous research and other recent applied literature on Poland, the main policy implications are twofold. First, a prosecution of the ongoing fiscal consolidation process is needed. Second, the above process should be implemented introducing a systematic response of fiscal policy to contingent disequilibria in public debt. Cambiamenti di regime, multicointegrazione e sostenibilita della politica fiscale: ulteriore evidenza empirica sulla Polonia (1999-2015) L’articolo riesamina la sostenibilita della politica fiscale in Polonia, estendendo l’analisi condotta in Tronzano (forthcoming) ad una analisi di multicointegrazione che incorpori la possibilita di cambiamenti di regime. I risultati ottenuti respingono fortemente l’esistenza di multicointegrazione, indicando quindi che la politica fiscale della Polonia non e sostenibile in un contesto stocastico. In linea con mie precedenti analisi empiriche e con altra recente letteratura applicata sulla Polonia, si ottengono due principali implicazioni di politica economica. In primo luogo, e necessaria una prosecuzione dell’attuale processo di consolidamento fiscale. In secondo luogo, questo processo dovrebbe essere condotto introducendo una reazione sistematica della politica fiscale a squilibri imprevisti nella dinamica del debito pubblico.
Adolescent and Caregiver Experiences With Epilepsy

Epilepsy during adolescence can impede the development of psychosocial independence and typical biological maturational processes. We examined in parallel the experiences and perceptions of adolescent patients with epilepsy and their caregivers. Specifically, we focused on frequency and type of seizures, comorbid conditions, adherence to therapies, productivity, clinical and quality of life consequences of seizures, estimated use and content of seizure emergency plans, and the patient—physician relationship. Two cross-sectional online surveys were conducted among 153 adolescent patients with epilepsy and their respective caregivers. A total of 35% of adolescents indicated that they had been nonadherent to antiepileptic medications in the prior month. Adolescents scored significantly lower compared with their peers on quality-of-life measures. Adolescents and caregivers reported similarly on nearly all domains. An adolescent-centered epilepsy management program may help alleviate concerns and also help the adolescent independently manage their epilepsy as they transition into adulthood.
Alexithymia impairs the cognitive control of negative material while facilitating the recall of neutral material in both younger and older adults

We investigated the moderating impact of the personality construct alexithymia on the ability of younger and older adults to control the recall of negative and neutral material. We conducted two experiments using the directed forgetting paradigm with younger and older adults. Participants studied negative (Experiment 1) or neutral (Experiment 2) words. Participants were instructed to forget the first half and remember the second half of an entire list of words. Overall, we found that alexithymia impairs the ability of both younger and older adults to cognitively control negative material (through both recall and inhibition). The “externally oriented thinking” factor of alexithymia appears to play a particularly pertinent role in terms of inhibiting negative material. Furthermore, older adults recalled fewer sought after negative items, but this was not evident in terms of inhibition. In contrast, only age (older adults) negatively impacted the recall of sought after neutral items. Interestingly, alexithymia had the opposite effect: the “difficulty in identifying emotions” factor of alexithymia was associated with an increased recall of neutral items. We discuss these results in terms of alexithymia and its impact on cognitive control.
Prolyl hydroxylase‐2 (PHD2) exerts tumor‐suppressive activity in pancreatic cancer

Pancreatic cancer is 1 of the most common and poorly treated tumors. In search of new therapeutic approaches, the oxygen sensors prolyl hydroxylases (PHD) are potential targets. PHD2 is considered the key oxygen sensor‐regulating hypoxia‐inducible factor (HIF). Currently, there is conflicting evidence regarding the exact role of PHD2 in tumorigenesis. The objective of this study was to investigate the role of PHD2 in pancreatic cancer growth and progression.
The Maize Mitochondrial cox2 Gene Has Five Promoters in Two Genomic Regions, Including a Complex Promoter Consisting of Seven Overlapping Units*

Plant mitochondrial genes are often transcribed into complex sets of RNAs, resulting from multiple initiation sites and processing steps. To elucidate the role of initiation in generating the more than 10 cox2 transcripts found in maize mitochondria, we surveyed sequences upstream of cox2 for active promoters. Because the cox2 coding region is immediately downstream of a 0.7-kb recombination repeat, cox2 is under the control of two different sets of potential expression signals. Using an in vitro transcription assay, we localized four promoters upstream of the coding region in the so-called master chromosome, and two promoters upstream of the coding region in the recombinant subgenome. Ribonuclease protection analysis of labeled primary transcripts confirmed that all but one of these promoters is active in vivo. Primer extension was used to identify the promoter sequences and initiation sites, which agree with the consensus established earlier for maize mitochondria. This study identified two unusual promoters, the core sequences of which were composed entirely of adenines and thymines, and one of which was a complex promoter consisting of seven overlapping units. Deletion mutagenesis of the complex promoter suggested that each of its units was recognized independently by RNA polymerase. While each active promoter fit the maize core consensus sequence YRTAT, not all such sequences surveyed supported initiation. We conclude that in vitrotranscription is a powerful tool for locating mitochondrial promoters and that, in the case of cox2, promoter multiplicity contributes strongly to transcript complexity.
Evidence for the evolutionary relatedness of the proteins of the bacterial phosphoenolpyruvate:Sugar phosphotransferase system

The phosphoenolpyruvate:sugar phosphotransferase system (PTS) found in enteric bacteria is a complex enzyme system consisting of a non‐sugar‐specific phospho‐transfer protein called Enzyme I, two small non‐sugar‐specific phosphocarrier substrates of Enzyme I, designated HPr and FPr, and at least 11 sugar‐specific Enzymes II or Enzyme II‐III pairs which are phosphorylated at the expense of phospho‐HPr or phospho‐FPr. In this communication, evidence is presented which suggests that these proteins share a common evolutionary origin and that a fructose‐specific phosphotransferase may have been the primordial ancestor of them all. The evidence results from an evaluation of (1) PTS protein sequence data; (2) structural analysis of operons encoding proteins of the PTS; (3) genetic regulatory mechanisms controlling expression of these operons; (4) enzymatic characteristics of the PTS systems; (5) immunological cross reactivities of these proteins; (6) comparative studies of phosphotransferase systems from evolutionarily divergent bacteria; (7) the nature of the phosphorylated protein intermediates; (8) molecular weight comparisons among the different Enzymes II and Enzyme II‐III pairs; and (9) interaction studies involving different PTS protein constituents. The evidence leads to a unifying theory concerning the evolutionary origin of the system, explains many structural, functional, and regulatory properties of the phosphotransferase system, and leads to specific predictions which should guide future research concerned with genetic, biochemical, and physiological aspects of the system.