Miracle-dz/UniFAR-FTUs huggingface dataset:
The antiarrhythmic agent cibenzoline inhibits KATP channels by binding to Kir6.2.

We reported previously that cibenzoline, an antiarrhythmic agent, inhibits the ATP-sensitive K+ (KATP) channels of pancreatic beta-cells through a binding site distinct from that for glibenclamide. In the present study, we have determined the locus of the action of cibenzoline on KATP channels reconstituted with mutant Kir6.2 and SUR1. We expressed a C-terminal truncated Kir6.2 (Kir6. 2DeltaC26) with and without SUR1 in COS7 cells. Both Kir6.2DeltaC26 and Kir6.2DeltaC26 + SUR1 formed functional KATP channels. Glibenclamide inhibited Kir6.2DeltaC26 + SUR1 channels but failed to inhibit Kir6.2DeltaC26. In contrast, cibenzoline inhibited equally Kir6.2DeltaC26 and Kir6.2DeltaC26 + SUR1 channels, in a dose-dependent manner, the half-maximal concentrations of channel inhibition being 22.2 +/- 6.1 and 30.9 +/- 9.4 microM, respectively. Furthermore, we determined also that [3H]cibenzoline bound to Kir6. 2DeltaC26. These findings confirm that cibenzoline inhibits KATP channels by a novel inhibitory mechanism in which cibenzoline directly affects the pore-forming Kir6.2 subunit rather than the SUR1 subunit.
Parkinson’s disease with camptocormia

Background: Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position. The origin of the disorder is unknown, but it is usually attributed either to a primary or a secondary paravertebral muscle myopathy or a motor neurone disorder. Camptocormia is also observed in a minority of patients with parkinsonism. Objective: To characterise the clinical and electrophysiological features of camptocormia and parkinsonian symptoms in patients with Parkinson’s disease and camptocormia compared with patients with Parkinson’s disease without camptocormia. Methods: Patients with parkinsonism and camptocormia (excluding patients with multiple system atrophy) prospectively underwent a multidisciplinary clinical (neurological, neuropsychological, psychological, rheumatological) and neurophysiological (electromyogram, ocular movement recording) examination and were compared with age-matched patients with Parkinson’s disease without camptocormia. Results: The camptocormia developed after 8.5 (SD 5.3) years of parkinsonism, responded poorly to levodopa treatment (20%) and displayed features consistent with axial dystonia. Patients with camptocormia were characterised by prominent levodopa-unresponsive axial symptoms (ie, axial rigidity, gait disorder and postural instability), along with a tendency for greater error in the antisaccade paradigm. Conclusion: We suggest that (1) the salient features of parkinsonism observed in patients with camptocormia are likely to represent a specific form of Parkinson’s disease and camptocormia is an axial dystonia and (2) both camptocormia and parkinsonism in these patients might result from additional, non-dopaminergic neuronal dysfunction in the basal ganglia.
Autotransporter and Two-Partner Secretion: Delivery of Large-Size Virulence Factors by Gram-Negative Bacterial Pathogens

A number of protein secretion mechanisms have been identified in gram-negative pathogens. Many of these secretion systems are dependent upon the Sec translocase for protein export from the cytoplasm into the periplasm and then utilize other mechanisms for transport from the periplasm through the outer membrane. In this article, we review secretion similarities between autotransporter and two-partner secretion systems, and we report similarities between the autotransporter secretion mechanism with that of intimin/invasins. Considering that many secreted proteins are virulence factors, a better understanding of their secretion mechanisms will aid in the development of disease treatments and new bacterial vaccines.
Ownership Structure, Financial Constraints and Investment Decisions: Evidence from a Panel of Italian Firms

Over the part two decades, a wide empirical literature has addressed the theme of firmtevel financial constraints, supporting the hypothesis that the availability of internal funds is indeed a major driver of investment decisions (Himmeiberg and Petersen, 1994). The largest part of such empirical analyses is based on refinements of the original model by Fazzari, Hubbard and Petersen (1988) which derives the presente of liquidity constraints from the observation of differentials in Investment-cash flow elasticities among sub groups of companies. However, the theoretical ride of the issue is stili debated. Following Iladlock (1998) and Degryse and de jong (2006), investment - cash flow sensitivities can be attributed to the presente of two different factors: asymmetric information on capital markets or internal agency problems leading to overinvestment by the management. In this paper, we try to disentangle the different potential determinante underlving the observed positive elasticity between investments and internal resources using a new sample of 1035 Italian manufacturing firms observed in the period 1998-2003. In order to analyse to what extent investment elasticity might be related to agency problems, we account for both the ownership strutture of the companies and the role played by financial intermediaries as both investors and debt-holders. The most interesting result emerging from our analysis is related to the presente of an inverted - U relationship between concentration of ownership and the elasticity of investment to cashflow. The overall evidente, which includer analysis accounting for innovation effort and for the effect of industrial group membership, is supportive of the hypothesis that the elevated dependance of investment in both tangible and intangible capital on internal resources cannot be fully attributed to frictions on the credit market.
The Wealth Effects of Takeover Announcement on Acquiring Firms: The Case of the Athens Stock Exchange

An event study methodology was employed to investigate the wealth effects on Greek acquiring companies of merger and acquisition announcements. 38 cases were found of acquiring companies listed on the Athens Stock Exchange in which acquisitions subsequently occurred. For the population as a whole, results were in line with findings from studies in other countries, which show negative abnormal returns for acquiring companies. However, noticeable differences were found between sub-groups. While horizontal acquisitions revealed clear wealth-destructive effects for the acquiring company in the immediate post-announcement period, no such effects were observed in the case of vertical acquisitions. Conglomerate acquisitions produced ambivalent results.
Recombinant Production of Human Microsomal Cytochrome P450 2D6 in the Methylotrophic Yeast Pichia pastoris

Microsomal cytochrome P450 monooxygenases of groups 1–3 are mainly expressed in the liver and play a crucial role in phase 1 reactions of xenobiotic metabolism. The cDNAs encoding human CYP2D6 and human NADPH‐P450 oxidoreductase (CPR) were transformed into the methylotrophic yeast Pichia pastoris and expressed with control of the methanol‐inducible AOX1 promoter. The determined molecular weights of the recombinant CYP2D6 and CPR closely matched the calculated values of 55.8 and 76.6 kDa. CPR activity was detected by conversion of cytochrome c by using isolated microsomes. Nearly all of the recombinant CYP was composed of the active holoenzyme, as confirmed by reduced CO difference spectra, which showed a single peak at 450 nm. Only by coexpression of human CPR and CYP was CYP2D6 activity obtained. Microsomes containing human CPR and CYP2D6 converted different substrates, such as 3‐cyano‐7‐ethoxycoumarin, parathion and dextrometorphan. The kinetic parameters of dextrometorphan conversion closely matched those of CYP2D6 from other recombinant expression systems and human microsomes. The endogenous NADPH‐P450 oxidoreductase of Pichia pastoris seems to be incompatible with human CYP2D6, as expression of CYP2D6 without human CPR did not result in any CYP activity. These recombinant strains provide a novel, easy‐to‐handle and cheap source for the biochemical characterisation of single microsomal cytochromes, as well as their allelic variants.
Adaptation of Escherichia coli to the Bovine Mammary Gland

ABSTRACT Clinical mastitis in six Somerset dairy herds was monitored over a 12-month period. Escherichia coli was implicated in 34.7% of all clinical cases. Forty-one percent of all clinicalE. coli mastitis cases occurred in just 2.2% of the population. A total of 23.9% of clinical E. coli cases occurred in quarters suffering recurrent cases of E. coli mastitis. The genotypes of strains involved in recurrent cases of clinical E. coli mastitis were compared by DNA fingerprinting with enterobacterial repetitive intergenic consensus primers. In 85.7% of cases of recurrent quarter E. coli mastitis, the same genotype was implicated as the cause of disease, suggesting persistence of the organism within the mammary environment. The same genotype as that in the original case was also implicated in 8.5% of recurrent cases occurring in different quarters of the same cow, suggesting spread between quarters. These findings challenge our current understanding of the epidemiology of E. coli mastitis and suggest that pathogen adaptation and host susceptibility may be playing a part in the changing pattern of clinical mastitis experienced in the modern dairy herd.
Suppressors of DnaAATP imposed overinitiation in Escherichia coli

Chromosome replication in Escherichia coli is limited by the supply of DnaA associated with ATP. Cells deficient in RIDA (Regulatory Inactivation of DnaA) due to a deletion of the hda gene accumulate suppressor mutations (hsm) to counteract the overinitiation caused by an elevated DnaAATP level. Eight spontaneous hda suppressor mutations were identified by whole‐genome sequencing, and three of these were analysed further. Two mutations (hsm‐2 and hsm‐4) mapped in the dnaA gene and led to a reduced ability to initiate replication from oriC. One mutation (hsm‐1) mapped to the seqA promoter and increased the SeqA protein level in the cell. hsm‐1 cells had prolonged origin sequestration, reduced DnaA protein level and reduced DnaA‐Reactivating Sequence (DARS)‐mediated rejuvenation of DnaAADP to DnaAATP, all of which could contribute to the suppression of RIDA deficiency. Despite of these defects hsm‐1 cells were quite similar to wild type with respect to cell cycle parameters. We speculate that since SeqA binding sites might overlap with DnaA binding sites spread throughout the chromosome, excess SeqA could interfere with DnaA titration and thereby increase free DnaA level. Thus, in spite of reduction in total DnaA, the amount of DnaA molecules available for initiation may not be reduced.
Ganirelix acetate causes a rapid reduction in estradiol levels without adversely affecting oocyte maturation in women pretreated with leuprolide acetate who are at risk of ovarian hyperstimulation syndrome.

BACKGROUND Elevated estradiol (E(2)) levels predispose to development of ovarian hyperstimulation syndrome (OHSS). Since GnRH antagonist is associated with a reduction in E(2) levels, we hypothesized that GnRH-antagonist treatment of women down-regulated with GnRH agonist who are at risk of OHSS might reduce E(2) levels and avoid cycle cancellation. METHODS Retrospective study in a university-based assisted reproduction technology (ART) programme in 87 patients treated with long luteal (LL) or microdose flare (MDF) with ovarian hyperresponse and 87 control patients without ovarian hyperresponse. GnRH-antagonist (ganirelix acetate) treatment was started and leuprolide acetate discontinued in women who failed to respond to a reduction in gonadotrophin dosage. RESULTS In the treatment group, there was a significant, reproducible reduction in serum E(2) levels. Mean E(2) at the start of ganirelix treatment was 4219.8 pg/ml and decreased in 24 h to 2613.7 pg/ml (36.7%; P < 0.001). An average of 24.9 +/- 8.8 oocytes were obtained at retrieval and an average of 19.1 +/- 8.0 were metaphase II (79.2%). Fertilization occurred in 13.9 +/- 8.1 embryos (72.8%). In this high risk group, two cases of severe OHSS (2.3%) occurred. The ongoing pregnancy rate was 51.8%. Compared with the control group, there were no statistically significant differences in the rate of oocyte recovery, oocyte maturity, 2PN rate, fertilization, cancellation, OHSS or pregnancy. CONCLUSIONS GnRH-antagonist treatment of women pretreated with GnRH agonist rapidly reduced circulating serum E(2) without adversely affecting oocyte maturation, fertilization rates or embryo quality and resulted in a high pregnancy rate in this subgroup of patients at risk of OHSS.
Assessment of the sensitivity and specificity of a phallometric test: An update of phallometric diagnosis of pedophilia.

The specificity and sensitivity of the phallometric test of an erotic preference for minors was assessed. The specificity was determined to be 96.9% if using a group of sex offenders against female adults and 80.6% if using a group of paid volunteers. Test results of 27 sex offenders against at least 2 female children each and of 22 offenders against at least 2 male minors each (either against children or against pubescents, but not against both), demonstratedsensitivitiesof 78.2% for heterosexual pedophiles and 88.6% for homosexual pedophiles or hebephiles. From these test sensitivities, the percentage of subjects preferring minors in a group of offenders against only 1 female child each, a group of offenders against at least 1 female child and at least 1 female pubescent each, and a group of offenders against only 1 male minor each (child or pubescent) were determined as being 44.5%, 74.6%, and 86.7%, respectively. The differential diagnosis between the various erotic preferences can be established by means of the phallometric test, which uses continuous recording of penile volume changes while a subject views potentially arousing pictures on screens or listens to such taped narratives (Abel, Becker, Murphy, & Flanagan, 1981). The current study was limited to the phallometric test of pedophilia and homosexual hebephilia as it is used in the differential diagnosis between pedophilia or homosexual hebephilia and gynephilia (Freund, Diamant, & Pinkava, 1958; Quinsey, Steinman, Bergersen, & Holmes, 1975).
High Frequency Trading in the Equity Markets During US Treasury POMO

We analyze high frequency trading (HFT) activity in equities during U.S. Treasury permanent open market (POMO) purchases by the Federal Reserve. We construct a model to study HFT quote and trade behavior when private information is released and confirm it empirically. We estimate that HFT firms reduce their inside quote participation by up to 8% during POMO auctions. HFT firms trade more aggressively, and they supply less passive liquidity to non-HFT firms. Market impact also rises during Treasury POMO. Aggressive HFT trading becomes more consistently profitable, and HFT firms earn a higher return per share. We also estimate that HFT firms earn profits of over $105 million during U.S. Treasury POMO events.
Nuclear Ca2+ concentration measured with specifically targeted recombinant aequorin.

Activation of nuclear transcription factors, breakdown of nuclear envelope and apoptosis represent a group of nuclear events thought to be modulated by changes in nucleoplasmic Ca2+ concentration, [Ca2+]n. Direct evidence for, or against, this possibility has been, however, difficult to obtain because measurements of [Ca2+]n are hampered by major technical problems. Here we describe a new approach for selectively monitoring Ca2+ concentrations inside the nucleus of living cells, which is based on the construction of a chimeric cDNA encoding a fusion protein composed of the photoprotein aequorin and a nuclear translocation signal derived from the rat glucocorticoid receptor. This modified aequorin (nuAEQ), stably expressed in HeLa cells, was largely confined to the nucleoplasm and thus utilized for monitoring [Ca2+]n in intact cells. No significant differences were observed between [Ca2+]n and cytosolic Ca2+ concentration ([Ca2+]i) under resting conditions. Upon stimulation of surface receptors linked to inositol‐1,4,5‐trisphosphate (InsP3) generation, and thus to intracellular Ca2+ signalling, the kinetics of [Ca2+]i and [Ca2+]n increases were indistinguishable. However, for the same rise in [Ca2+]i, the amplitude of [Ca2+]n increase was larger when evoked by Ca2+ mobilization from internal stores than when induced by Ca2+ influx across the plasma membrane. The functional significance of these transient nucleus‐cytosol Ca2+ gradients is discussed.
Partial restoration of the keratocyte phenotype to bovine keratocytes made fibroblastic by serum.

PURPOSE To determine whether keratocytes made fibroblastic in vitro by addition of fetal bovine serum to the medium regain the keratocyte phenotype after culture in serum-free medium. METHODS Collagenase-isolated keratocytes from bovine corneas were plated in DMEM/F-12 containing 1% horse plasma, to allow cell attachment, and then cultured until day 4 in either DMEM/F-12 alone, to retain the keratocyte phenotype, or in DMEM containing 10% fetal bovine serum, to cause the keratocytes to become fibroblastic. Medium for the fibroblastic cells was replaced on day 4 with serum-free medium, and cells were cultured until day 12. Cell phenotypes were determined on days 4 to 5 and 11 to 12 of culture as follows: (1) by the morphologic appearance on phase-contrast microscopy; (2) by the levels of aldehyde dehydrogenase in the cells, determined by SDS-PAGE and Coomassie blue staining; (3) by the relative synthesis of collagen types I and V, determined by (14)C-proline radiolabeling; (4) by pepsin digestion and analysis of collagen types by SDS-PAGE autoradiography; (5) by relative synthesis of cornea-specific proteoglycan core proteins determined by analysis of chondroitinase- or endo-beta-galactosidase-generated radiolabeled core proteins by SDS-PAGE autoradiography; and (6) by the relative synthesis of keratan sulfate and chondroitin sulfate determined by (35)SO(4) radiolabeling and measuring the sensitivity to endo-beta-galactosidase and chondroitinase ABC. RESULTS Keratocytes cultured in serum-free medium appeared dendritic and became fibroblastic in appearance when exposed to medium containing serum. Keratocytes and fibroblasts synthesized a similar proportion of collagen types I and V. However, compared with the keratocytes, the fibroblasts possessed no aldehyde dehydrogenase and synthesized significantly higher levels of decorin and significantly lower levels of prostaglandin D synthase (PGDS) and keratan sulfate. Subsequent culture of the fibroblasts in serum-free medium did not restore aldehyde dehydrogenase to keratocyte levels but did restore the cell morphology to a more dendritic appearance and returned the synthesis of decorin, PGDS, and keratan sulfate to keratocyte levels. CONCLUSIONS The results of these studies indicate that primary cultures of keratocytes made fibroblastic by exposure to serum can return to their keratocyte phenotype in synthesizing extracellular matrix. These results also indicate that the differences in the organization of the collagenous matrix produced by keratocytes and fibroblasts may be related more to the different proteoglycan types than to the collagen types produced.
Relational bonding strategies in the franchise industry: the moderating role of duration of the relationship

Purpose – This paper aims to examine the effect of different relational bonding strategies on franchisees’ perceptions of benefits. The duration of the relationship is framed as a moderator between three types of relational bonds and the perceived benefits. Design/methodology/approach – The data are collected via a survey from foodservice franchisees in South Korea. To test the study’s hypotheses, the research model was estimated with two-stage least squares. Findings – The result shows that social and structural bonds have a significant impact on franchisees’ perceptions of benefits. There are some significant interactions between different types of relational bonds and the duration of the relationship. Perceptions of benefits are found to influence satisfaction, intentions to recommend, intentions to renew the contract and long-term orientation. Practical implications – The study suggests that franchisors may want to focus on developing and strengthening social bonds, and also customize their relational.
What is the Correlation between Ratings and Measures of Olfactory Function in Patients with Olfactory Loss?

Background Major complaints of many patients with olfactory dysfunction relate to the impairment of quality of life. Nevertheless, it is unclear to what extent there is a correlation between ratings of olfactory abilities/impairment and olfactory function. Methods Patients with olfactory dysfunction (n = 152) were examined psychometrically using the “Sniffin’ Sticks” test battery. Ratings of olfactory function and ratings of impairment were recorded using visual analog scales. Results Following standardized olfactory testing, 78 of the 152 patients were categorized as functionally anosmic, 64 as hyposmic, and 10 as normosmic. Groups differed significantly with regard to ratings of olfactory function. Functionally anosmic patients rated impairment to be significantly higher compared with hyposmic and normosmic patients. Ratings of olfactory function correlated significantly with measured olfactory function (r = +0.57) and ratings of impairment (r = —0.30). Conclusion There was a moderate correlation between ratings and measures of olfactory function. On average, functionally anosmic patients recognized their olfactory loss, although, on an individual basis, there were striking differences between measures and ratings of olfactory function.
Association between Dermatoglyphic Configuration and the ACTN3 Genotype in Juvenile Male Athletes

This study examined whether dermatoglyphic characteristics are associated with the α-actinin isoform 3 (ACTN3) R577X sequence variant, employing descriptive and comparative approaches. Boys (N=82) were classified according to the dermatoglyphic configuration of their digital impressions into the following groups: Anaerobic Power (AP=8); Speed Resistance (SR=44); Pure Force (PF=5), and Aerobic Resistance (AR=25). All of the AP group subjects (9.76% of the subjects) had a genetic predisposition for anaerobic power performance, with 37.5% being RR homozygotes and 62.5% being RX heterozygotes. The dermatoglyphic profiles, correlated with the ALW fingerprint formulas, classified the SR group (53.66% of the subjects) as having speed resistance. The PF group (6.09% of the subjects) notably all had AL fingerprints and an absence of W. Finally, the AR group (30.49% of the subjects) had a predisposition for aerobic capacity. In conclusion, dermatoglyphic features can be associated with the R577X allelic variant of the ACTN3 gene, as much through anaerobic muscle power profiling as through the ACTN3 genotype.