Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the C Terminus in Histamine H2 Receptor Signaling, Desensitization, and Agonist-induced Internalization*

To evaluate the role of the histamine H2 receptor C terminus in signaling, desensitization, and agonist-induced internalization, canine H2 receptors with truncated C termini were generated. Wild-type (WT) and truncated receptors were tagged at their N termini with a hemagglutinin (HA) epitope and expressed in COS7 cells. Most of the C-terminal intracellular tail could be truncated (51 of 70 residues, termed T308mutant) without loss of functions: cAMP production, tiotidine binding, and plasma membrane targeting. In fact, the T308 mutant produced more cAMP than the WT when cell-surface expression per cell was equivalent. Pretreatment of cells with 10−5 m histamine desensitized cAMP productions via WT and T308 receptors to similar extents. Incubation of cells expressing WT receptors with 10−5 m histamine reduced cell-surface anti-HA antibody binding by approximately 30% (by 30 min, t 1/2 ∼ 15 min), but did not affect the B max of tiotidine in membrane fractions, which represents total receptor amounts, suggesting that WT receptors were internalized from the cell surface. In contrast, no internalization was observed with T308 receptors following histamine treatment. A mutant with a deletion of the 30 C-terminal amino acids, termed T329, was functional but was as potent as the WT in terms of cAMP production. Apart from being desensitized by histamine, the internalization of the receptor was indistinguishable from that of the WT. Internalization was observed in the T320 but not in T313 mutant, narrowing the region involved in internalization to that between Glu314 and Asn320 (ETSLRSN). Of these seven residues, either Thr315, Ser316, or both, were replaced with Ala. Thr315 and Ser316 are conserved among species. The mutation at Thr315 (but not that at Ser316) abolished internalization. Taken together, these results demonstrate that Thr315 is involved in agonist-induced internalization. Furthermore, the finding that T308 receptors were desensitized in the absence of internalization suggests that internalization and desensitization are meditated by independent mechanisms.
Effect of different stresses on trehalose levels in Rhizopus oryzae

Rhizopus oryzae accumulates and degrades trehalose in response to environmental stress conditions such as heat, osmotic stress, nitrogen starvation and pH. When heat stress was applied to R. oryzae, the trehalose content of the cells was increased from 0.9 to 4.8 mg/g dw and when the stress was relieved it decreased back to 1.1 mg/g dw. Under osmotic stress and nitrogen starvation, trehalose content was increased by 3.5 and 3 fold, respectively. The decrease in external pH increased trehalose level up to 2.6 mg/g dw from 1.1 mg/g dw. Increased trehalose level decreased back to normal after pH stress was relieved. These results indicate that trehalose accumulates and acts as a stress protectant in R. oryzae. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The effects of glibenclamide on tetanic force and intracellular calcium in normal and fatigued mouse skeletal muscle

In this study the effects of ATP‐sensitive K+ channel modulators were studied in intact single fibres dissected from mouse skeletal muscle. Indo‐1 was used to measure [Ca2+]i simultaneously with force during normal and fatiguing stimulation. In control fibres, opening of ATP‐sensitive K+ channels with BRL 38227 produced a small reduction in tetanic force and [Ca2+]i. In contrast, glibenclamide, a selective blocker of the ATP‐sensitive K+ channel, slightly increased tetanic force and [Ca2+]i in these fibres and also increased Ca2+ sensitivity. Glibenclamide produced a more marked increase in tetanic force and [Ca2+]i during the later stages of fatiguing stimulation, although this effect was observed in only 50% of fibres examined. We conclude from this study that glibenclamide produces a partial reversal of the later stages of fatigue in a subpopulation of muscle fibres. Opening of ATP‐sensitive K+ channels may therefore contribute to the decline in tetanic force and [Ca2+]i characteristic of skeletal muscle fatigue.
Levi's Challenge and Peirce's Theory/Practice Distinction

Isaac Levi (1980) targets an implicit tension in C.S. Peirce's epistemology, one that exists between the need to always be open-minded and aware of our propensity to make mistakes so that we do not "block the road of inquiry," and the need to treat certain beliefs as infallible and to doubt only in a genuine way so that inquiry can proceed in the first place. Attempts at alleviating this tension have typically involved interpreting Peirce as ascribing different normative standards to different areas of inquiry. I argue here that such "double-standard" interpretations face significant problems. I offer instead an interpretation of Peirce on which the differences between different areas of inquiry are descriptive rather than normative. Such a view resolves Levi's tension while interpreting Peirce as consistently subscribing to one normative standard for all inquiry.
Psychosocial aspects of chronic widespread pain and fibromyalgia

Purpose. To study the impact on health status as measured by SF-36 in groups of subjects having chronic musculoskeletal pain with different degree of generalization: No chronic pain (NCP), chronic regional pain (CRP), chronic widespread pain (CWP), CWP with a stricter ‘Manchester’ definition (CWP-M), and clinically defined fibromyalgia (FM). The study also examines the association between psychosocial and lifestyle background variables, and these pain-groups. Method. A cross-sectional study with a postal survey to 3928 subjects, constituting a representative sample of the adult general population, followed by clinical examination in a selected group of subjects with CWP. CWP and FM were diagnosed according to ACR 1990 fibromyalgia criteria. Health status was measured by SF-36 Health Survey. Results. Patients with CWP, CWP-M, and FM were found to present with more severe impairment of health status than the other two population groups. Several psychosocial factors, such as belonging to a lower socio-economic group, being an immigrant, living in a compromised housing area, having lower educational level, experiencing lower social support and having a family history of chronic pain, were associated with the populations with CWP and FM Conclusions. The spectrum of impact on health and association to background variables, with respect to a stricter definition of CWP, indicates that these factors are important to attend to in the understanding and management of CWP and FM.
Adaptive Hopping Transmission Strategy for Opportunistic Spectrum Access

This paper presents an adaptive hopping transmission strategy for secondary users (SUs) to access temporarily idle frequency-slots of a licensed frequency band in consideration of the random return of primary users (PUs), aiming to maximize the overall SU throughput. A SU dynamically hops over multiple idle frequency-slots, each with an adaptive activity factor so that possible PU return in a frequency-slot may destroy only a small fraction of the SU transmission that can be recovered by erasure-correction coding. SU activity factor optimization problems are formulated to develop adaptive SU access algorithms for both centralized and distributed structures. Numerical results confirm the effectiveness and demonstrate performance gains of the proposed approach as compared to existing schemes.
Differences between potential, new and experienced e-customers: Analysis of e-purchasing behaviour

Purpose – The purpose of the paper is to analyse the evolution of e-customer purchasing behaviour. Certain perceptions of electronic commerce (EC) may differ according to the purchasing experience of customers. Three groups of e-customers are differentiated: potential, new and experienced. Design/methodology/approach – First of all, the socio-demographic characteristics of each group were analysed using the Chi-squared test. Then, using ANOVA and post hoc analysis (Scheffe’s test), the differences that exist in their perceptions were analysed. Findings – Data analyses show that level of experience with Internet and the perceptions about EC differ according to the e-customer. Some variables, like perceived usefulness or attitude, increase significantly as the number of interchanges grows, while others, such as perceived ease of use, tend to stabilise. It can be affirmed that there is an evolving cycle of purchasing that will continue to develop as the individual acquires experience. Practical implications – This research enables the companies that want to compete in the e-market to know the type of customer they are addressing. Moreover, the results obtained show what perceptions must be concentrated on if these companies want to capture new customers (potential e-customers) or if they want to maintain existing customers (new and experienced). The evolution of this behaviour means that the strategies oriented to fomenting EC should stress one or another aspect depending on the target customer. Originality/value – While most research indistinctly analyses the behaviour of any e-customer, this study has considered it necessary to differentiate at least three types of e-customers in function of their purchasing experience. Thus, this is one of the few studies that allows us to know the evolution of the perceptions related to e-commerce.
Uptake of chloroquine-3-H3 by plasmodium knowlesi in vitro.

Certain aspects of chloroquine-3-H3 (CQ-3-H3) uptake by Plasmodium knowlesi were investigated in vitro. CQ-3-H3 uptake had a biphasic time course: an initial rapid uptake followed by a slow increase to a saturation value reached after three hours. CQ-3-H3 uptake was reduced in the presence of metabolic inhibitors, in the absence of glucose and at low temperature. Intra-and extracellular CQ-3-H3 appeared to be in a dynamic equilibrium in which dihydroquinine and quinacrine could participate. The characteristics of CQ-3-H3 uptake by plasmodia resembled uptake of albumin by mammalian cells. Pinocytosis, with subsequent accumulation in lysosomes, is proposed as the mechanism of CQ-3-H3 uptake by plasmodia.
A neurophylogenetic approach provides new insight to the evolution of Scaphopoda

The position of scaphopods in molluscan phylogeny remains singularly contentious, with several sister relationships supported by morphological and phylogenomic data: Scaphopoda + Bivalvia (Diasoma), Scaphopoda + Cephalopoda (Variopoda), and Scaphopoda + Gastropoda. Nervous system architecture has contributed significant insights to reconstructing phylogeny in the Mollusca and other invertebrate groups, but a modern neurophylogenetic approach has not been applied to molluscs, hampered by a lack of clearly defined homologous characters that can be unequivocally compared across the radical body plan disparity among the living clades. We present the first three‐dimensional reconstruction of the anterior nervous system of a scaphopod, Rhabdus rectius, using histological tomography. We also describe a new putative sensory organ, a paired and pigmented sensory mantle slit. This structure is restricted to our study species and not a general feature of scaphopods, but it forms an integral part of the description of the nervous system in R. rectius. It also highlights the potential utility of neuro‐anatomical characters for multiple levels of phylogenetic inference beyond this study. This potential has not previously been exploited for the thorny problem of molluscan phylogeny. The neuroanatomy of scaphopods demonstrates a highly derived architecture that shares a number of key characters with the cephalopod nervous system, and supports a Scaphopoda + Cephalopoda grouping.
Effect of feeding treated peat as a supplement on the parameters of cellular immunity , antioxidant status and performance of piglets in early post-weaning period

pigs. At the same time they indicate that peat supplement might influence the increase of pig’s body weight in the end of the post-weaning period (Trckova et al 2006b). At the same time, there was described the increasing of the piglets resistance level to the pathogen Actinobacillus pleuropneumiae and PRRSV infection after environmental peat enrichment in early life (Dixhoorn et al 2015). Although, as there is no data regarding the influence of supplements made of processed peat on the piglets’ immune system and because of the paucity of publications about the influence of the additive on piglets performance it will be discussed in our article.
Phenotypes of interferon-α-induced thyroid dysfunction among patients treated for hepatitis C are associated with pretreatment serum TSH and female sex.

CONTEXT Thyroid dysfunction is a common complication of interferon-α (IFNα) therapy, with many phenotypic patterns and the potential for significant morbidity. OBJECTIVE Our objective was to gain mechanistic insight and predict clinical presentations by determining the risk factors for distinct subtypes of IFNα-induced thyroid dysfunction. DESIGN ACHIEVE-1, a randomized trial conducted from 2005-2009, compared long-acting preparations of IFNα in 1323 patients with hepatitis C, genotype 1. SETTING A total of 149 outpatient clinics in North America, Europe, and Australia participated. PATIENTS We studied 1233 patients who were euthyroid at baseline. This population is 60% male and 82% Caucasian. INTERVENTIONS Patients were treated with pegylated IFNα2a weekly or albumin-IFNα2b every 2 wk for 48 wk. Serum TSH and free T(4) were measured before therapy and 12 or more times over 60 weeks. MAIN OUTCOME MEASURES Thyroid dysfunction was defined as a TSH outside the normal range during the course of therapy. Low serum TSH indicated thyrotoxicosis, elevated TSH indicated hypothyroidism, and both abnormalities occurred in biphasic thyroiditis. RESULTS Of previously euthyroid patients, 16.7% developed abnormal TSH values during therapy, including 24 with TSH below 0.1 mU/liter, 69 with TSH over 5.5 mU/liter, and 76 with biphasic thyroiditis. Biphasic thyroiditis was over 8-fold more common among women than men using multivariate logistic regression analysis [odds ratio (OR) = 8.4; 95% confidence interval (CI) = 4.5-15.8]. Thyrotoxicosis was most strongly associated with a lower pretreatment TSH (OR = 4.1 per -1 mU/liter decline; 95% CI = 1.9-9), whereas hypothyroidism was strongly associated with higher pretreatment TSH (OR = 3.9 per 1 mU/liter increase; 95% CI = 3-5.2). CONCLUSIONS Biphasic thyroiditis is common among women treated for hepatitis C with IFNα. Lower and higher pretreatment serum TSH are associated with greater likelihood of thyrotoxicosis and hypothyroidism, respectively. Antithyroid antibody levels were not available for the cohort, and thus we cannot clarify the role of pretreatment thyroid autoimmunity as a risk factor. Our results do show that readily identifiable patient characteristics are risk factors for specific patterns of IFN-induced thyroid dysfunction. These findings suggest that distinct mechanisms may underlie subtypes of thyroid dysfunction associated with immune-modulatory therapy for hepatitis C.
Fatiguing Upper Body Aerobic Exercise Impairs Balance

Douris, PC, Handrakis, JP, Gendy, J, Salama, M, Kwon, D, Brooks, R, Salama, N, and Southard, V. Fatiguing upper body aerobic exercise impairs balance. J Strength Cond Res 25(12): 3299–3305, 2011—There are many studies that have examined the effects of selectively fatiguing lower extremity muscle groups with various protocols, and they have all shown to impair balance. There is limited research regarding the effect of fatiguing upper extremity exercise on balance. Muscle fiber–type recruitment patterns may be responsible for the difference between balance impairments because of fatiguing aerobic and anaerobic exercise. The purpose of our study was to investigate the effect that aerobic vs. anaerobic fatigue, upper vs. lower body fatigue will have on balance, and if so, which combination will affect balance to a greater degree. Fourteen healthy subjects, 7 men and 7 women (mean age 23.5 ± 1.7 years) took part in this study. Their mean body mass index was 23.6 ± 3.2. The study used a repeated-measures design. The effect on balance was documented after the 4 fatiguing conditions: aerobic lower body (ALB), aerobic upper body (AUB), anaerobic lower body, anaerobic upper body (WUB). The aerobic conditions used an incremental protocol performed to fatigue, and the anaerobic used the Wingate protocol. Balance was measured as a single-leg stance stability score using the Biodex Balance System. A stability score for each subject was recorded immediately after each of the 4 conditions. A repeated-measures analysis of variance with the pretest score as a covariate was used to analyze the effects of the 4 fatiguing conditions on balance. There were significant differences between the 4 conditions (p = 0.001). Post hoc analysis revealed that there were significant differences between the AUB, mean score 4.98 ± 1.83, and the WUB, mean score 4.09 ± 1.42 (p = 0.014) and between AUB and ALB mean scores 4.33 ± 1.40 (p = 0.029). Normative data for single-leg stability testing for this age group are 3.9 ± 1.9. Higher scores reflect greater balance deficits. The AUB condition produced the greatest balance deficit. Our data provide evidence of the important role of the upper body in maintaining unilateral standing balance and supports its inclusion as part of rehabilitation and training protocols designed to improve balance.
Human brain aminopeptidase A: biochemical properties and distribution in brain nuclei

Aminopeptidase A (APA) generated brain angiotensin III, one of the main effector peptides of the brain renin angiotensin system, exerting a tonic stimulatory effect on the control of blood pressure in hypertensive rats. The distribution of APA in human brain has not been yet studied. We first biochemically characterized human brain APA (apparent molecular mass of 165 and 130 kDa) and we showed that the human enzyme exhibited similar enzymatic characteristics to recombinant mouse APA. Both enzymes had similar sensitivity to Ca2+. Kinetic studies showed that the Km (190 μmol/L) of the human enzyme for the synthetic substrate‐l‐glutamyl‐β‐naphthylamide was close from that of the mouse enzyme (256 μmol/L). Moreover, various classes of inhibitors including the specific and selective APA inhibitor, (S)‐3‐amino‐4‐mercapto‐butyl sulfonic acid, had similar inhibitory potencies toward both enzymes. Using (S)‐3‐amino‐4‐mercapto‐butyl sulfonic acid, we then specifically measured the activity of APA in 40 microdissected areas of the adult human brain. Significant heterogeneity was found in the activity of APA in the various analyzed regions. The highest activity was measured in the choroids plexus and the pineal gland. High activity was also detected in the dorsomedial medulla oblongata, in the septum, the prefrontal cortex, the olfactory bulb, the nucleus accumbens, and the hypothalamus, especially in the paraventricular and supraoptic nuclei. Immunostaining of human brain sections at the level of the medulla oblongata strengthened these data, showing for the first time a high density of immunoreactive neuronal cell bodies and fibers in the motor hypoglossal nucleus, the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, the Roller nucleus, the ambiguus nucleus, the inferior olivary complex, and in the external cuneate nucleus. APA immunoreactivity was also visualized in vessels and capillaries in the dorsal motor nucleus of the vagus and the inferior olivary complex. The presence of APA in several human brain nuclei sensitive to angiotensins and involved in blood pressure regulation suggests that APA in humans is an integral component of the brain renin angiotensin system and strengthens the idea that APA inhibitors could be clinically tested as an additional therapy for the treatment of certain forms of hypertension.
Dysplasia in Ulcerative Colitis as a Predictor of Unsuspected Synchronous Colorectal Cancer

BACKGROUND: Endoscopic surveillance of patients with ulcerative colitis aims to prevent cancer-related morbidity through the detection and treatment of dysplasia. The literature to date varies widely with regard to the importance of dysplasia as a marker for colorectal cancer at the time of colectomy. OBJECTIVE: The aim of this study was to accurately characterize the extent to which the preoperative detection of dysplasia is associated with undetected cancer in patients with ulcerative colitis. DESIGN/PATIENTS/SETTING: A retrospective chart review was conducted of patients undergoing surgery for colitis within the Mayo Clinic Health System between August 1993 and July 2012. MAIN OUTCOME MEASURES: Patient demographics and pre- and postoperative dysplasia were tabulated. The relationship between pre- and postoperative dysplasia/cancer in surgical pathology specimens was assessed. RESULTS: A total of 2130 patients underwent abdominal colectomy or proctocolectomy; 329 patients were identified (15%) as having at least 1 focus of dysplasia preoperatively. Of these 329 patients, the majority were male (69%) with a mean age of 49.7 years. Unsuspected cancer was found in 6 surgical specimens. Indeterminate dysplasia was not associated with cancer (0/50). Preoperative low-grade dysplasia was associated with a 2% (3/141) risk of undetected cancer when present in random surveillance biopsies and a 3% (2/79) risk if detected in endoscopically visible lesions. Similarly, 3% (1/33) of patients identified preoperatively with random surveillance biopsy high-grade dysplasia harbored undetected cancer. Unsuspected dysplasia was found in 62/1801 (3%) cases without preoperative dysplasia. LIMITATIONS: This study is limited by its retrospective nature and by its lack of evaluation of the natural history of dysplastic lesions that progress to cancer. CONCLUSIONS: The presence of dysplasia was associated with a low risk of unsuspected cancer at the time of colectomy. These findings will help inform the decision-making process for patients with ulcerative colitis who are considering intensive surveillance vs surgical intervention after a diagnosis of dysplasia.
Perindopril arginine: benefits of a new salt of the ACE inhibitor perindopril

ABSTRACT Background: The efficacy of the angiotensin-converting enzyme (ACE) inhibitor perindopril in the treatment of hypertension, stable coronary artery disease, and heart failure is well established. The reduced stability of the current salt, perindopril-tert-butylamine, in extreme climatic conditions has prompted research into more stable compounds. This article presents stability and bioequivalence results for a new l-arginine salt of perindopril. Methods: Drug stability studies were performed on nonsalified perindopril, perindopril-tert-butylamine, and perindopril arginine in closed and open containers. The bioequivalence of perindopril arginine was tested in 36 healthy male volunteers in an open-label, randomized, two-period, crossover pharmacokinetic study. A consumer study was carried out in 120 patients to assess preference for a simplified packaging using a high-density polyethylene canister designed for distribution to all climatic zones. Results and discussion: Perindopril arginine is 50% more stable than perindopril-tert-butylamine, which increases the shelf life from 2 to 3 years. At the revised dosage (perindopril arginine 5–10 mg/daycorresponds to perindopril-tert-butylamine 4–8 mg/day), the new salt is equivalent in terms of pharmacokinetics, efficacy, safety, and acceptability. The consumer studies indicate a preference for the new packaging, with 62% of patients nominating the canister as better than the blister packs. Conclusion: The new perindopril arginine salt is equivalent to perindopril-tert-butylamine and more stable, and can be distributed to climatic zones III and IV without the need for specific packaging. The patient preference for the new packaging could have positive implications for compliance.