Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Muscarinic Acetylcholine Receptor Concentration in Cloned Neuroblastoma Cells

Abstract: The concentration of muscarinic acetylcholine receptors in the neuroblastoma cell line NIE‐115 is regulated by receptor activation. Muscarinic agonists cause a time and dose‐dependent loss of [3H]quinuclidinyl benzilate binding sites from cultured cells. Muscarinic antagonists have no effect on receptor concentration and block agonist‐induced regulation. The maximum decrease in steady state receptor levels is 80% and occurs within 9 h. The altered steady state concentration persists as long as agonist remains present. Upon withdrawal of agonist, the concentration of receptors returns to control levels. This increase requires protein synthesis. Kinetically, the increase in receptors following withdrawal of agonist is slower than the decrease caused by addition of agonist, suggesting that bursts of receptor activation could lower receptor levels. In harmony with this prediction, cycles in which receptors are active for 15 min and then inactive for 15 min cause a 50% decrease in receptor concentration in a 6‐h period.
Climate Change and Culture Change on the Southern Coast of British Columbia 2400-1200 Cal. B.P.: An Hypothesis

The Marpole phase of the Gulf of Georgia, SW British Columbia (2400–1200 cal B.P.) is recognized by many archaeologists as a significant period of culture change. Concurrent with this cultural phase is a climatic regime characterized by a substantial increase in forest fires associated with persistent summer drought: the Fraser Valley Fire Period (FVFP). Culturally, the Marpole phase is characterized by the widespread appearance of large houses, standardized art forms, and elaborate burials. Interactions among people of this region intensified and were, as today, economically, socially, and ideologically linked to the lower Fraser River system. Ecologically, the FVFP likely resulted in a regional decline in salmon abundance and/or predictability, especially in small streams and offshore areas, but also more berries and wildlife, and easier overland access via trail networks. The ecological diversity of the lower Fraser region, both terrestrial and riverine, resulted in both more abundant and more predictable resources than surrounding areas during this period of changing climate. We hypothesize that social and economic networks throughout the Gulf of Georgia were solidified during the Marpole phase to ensure access to Fraser resources and allow social buffering of resource uncertainty. We suggest that the differential availability of resources also allowed and encouraged individuals who had access to Fraser Valley resources to gain relatively greater prestige.
Drinking patterns among older people in the community: hidden from medical attention?

AIMS To determine patterns of alcohol use and misuse among community-dwelling people aged 65 years and over in Christchurch and to assess how often this comes to medical attention. METHODS A cross-sectional survey of alcohol use and misuse was conducted followed by a self-administered postal survey among non- respondents. General practitioners (GPs) of the respondents completed a self-administered questionnaire on patients' alcohol use and misuse. RESULTS The response rate was 58% (141/243). The prevalence of hazardous alcohol consumption in the past twelve months (AUDIT cut-off score 8 or more) was 9.9% (95% CI = 4.9-14.9) and the prevalence of lifetime alcohol dependence using DSM-IV diagnostic criteria was 24.8% (95% CI = 17.6-32.0). Men were more likely than women to report lifetime dependency and current hazardous patterns. The response rate among GPs was 77.7% (108/139). None of the GPs identified or diagnosed alcohol problems in the past twelve months among this group and reported a history of alcohol problems in only four (4.0%) patients. Those with current hazardous patterns of alcohol use were twice as likely to be admitted to hospital (RR=2.4; 95% CI 1.2-5.1) but significantly less likely to visit their GPs in the previous twelve months (RR=0.55; 95% CI 0.7-1.1). CONCLUSION A significant proportion of community-dwelling elderly people reported patterns of alcohol consumption that put them at risk of future damage to physical or mental health. Hazardous drinkers were less likely to visit their GPs and only in a few cases, were GPs aware of such potential problems.
Bis(2,6-dimethylpyridinium) dibromoiodate bromide

In the title salt, 2C7H10N+·IBr2 −·Br−, each of the anions, viz. [IBr2]− and Br−, lie on a twofold axis. The IBr2 − anion is almost linear, with a Br—I—Br angle of 178.25 (3)°. The cation is essentially planar (r.m.s. deviation = 0.0067 Å). In the crystal, each Br− anion links two cations via N—H⋯Br⋯H—N hydrogen-bonding interactions.
Gender and Aging in the Developing World: Where Are the Men?

In recent years, both population aging and gender issues have gained prominence in international forums concerned with population. It is frequently asserted or implied that older women are universally more vulnerable to social, economic, and health disadvantages than older men. The most significant manifestation of this exclusive concern with women when considering gender and aging is the Plan of Action adopted by the Second World Assembly on Aging in 2002. The assumed relative disadvantage of elderly women is commonly attributed to gender differences in earlier life experiences. But are older women truly disadvantaged globally with respect to all or most essential aspects of well‐being? The authors provide empirical evidence that clearly shows that older women are not invariably disadvantaged vis‐a‐vis men. In particular, they call into question the wisdom and equity of a virtually exclusive emphasis on the needs of women when incorporating gender concerns into policies and programs related to aging. A more balanced perspective that recognizes gender as a potential, but not necessarily central, marker of vulnerability for various aspects of well‐being in specific settings and times, and that allows for male as well as female disadvantage, would serve the current and future elderly generations far better.
Correlation between the Size, CT Density of Otosclerotic Foci, and Audiological Tests in Cases of Otosclerosis

OBJECTIVE: To evaluate the relation between the Computed tomography (CT) densities, sizes of otosclerotic foci, and the bone conduction threshold (BC) and air bone gap (ABG) in cases of otosclerosis as well as between the lesions sizes and their CT densities. MATERIALS and METHODS: We included CT examinations of the temporal bones of 25 patients (34 ears, 9 cases were bilateral) with clinical and audiological diagnosis of otosclerosis. We measured the otosclerotic foci in their maximum dimensions as well as their CT densities and correlated them to the BC thresholds and ABG. We also studied the correlation between the sizes of the otosclerotic foci and their CT densities. RESULTS: There were no significant statistical correlations between the lesion size or CT density to either the BC or ABG in any of the CT grades of otosclerosis or any statistical correlation between the CT density and lesion size in any of the grades of otosclerosis.
Astragaloside IV Attenuates Injury Caused by Myocardial Ischemia/Reperfusion in Rats via Regulation of Toll‐Like Receptor 4/Nuclear Factor‐κB Signaling Pathway

Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and cell apoptosis play a vital role, is frequently encountered in clinical practice. Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus, has been shown to confer protective effects against many cardiovascular diseases. The present study was aimed to investigate the antiinflammatory and antiapoptotic effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were randomly divided into sham operation group, MI/R group and groups with combinations of MI/R and different doses of AsIV. The results showed that the expressions of myocardial toll‐like receptor 4 (TLR4) and nuclear factor‐κB (NF‐κB) were significantly increased, and apoptosis of cardiomyocytes was induced in MI/R group compared with that in sham operation group. Administration of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF‐κB and inhibited cell apoptosis as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, B‐cell lymphoma‐2 associated X protein and caspase‐3 expressions and increased B‐cell lymphoma‐2 expression compared with that in MI/R group. In addition, AsIV treatment reduced levels of inflammatory cytokines induced by MI/R injury. In conclusion, our results demonstrated that AsIV downregulates TLR4/NF‐κB signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R injury in rats. Copyright © 2015 John Wiley & Sons, Ltd.
Patterns of Resistance Mutations to Antiretroviral Drugs in Extensively Treated HIV‐1‐Infected Patients With Failure of Highly Active Antiretroviral Therapy

Summary: Resistance‐mutation patterns in the reverse transcriptase (RT) and protease genes of HIV‐1 were analyzed in 22 patients who had been extensively pretreated and who failed to respond to highly active antiretroviral therapy (HAART). The number of mutations ranged from 8 to 19 (median, 13): 4 to 12 (median, 6) mutations in the RT gene, and 4 to 8 (median, 7) mutations in the protease gene. In the RT gene, the most frequent resistance mutations were found at codons 215 (100%), 41 (95%), 67 (91%), and 210 (77%). Multidrug‐resistant mutation patterns including Q151M and insertion mutations at codon 69, which confer cross‐resistance to the different nucleoside analogue RT inhibitors were detected in 1 and 3 patients, respectively; 1 patient with insertion mutation displayed a NGQCV sequence at codons 67 to 70. In the protease gene, the most frequent mutations were found at codons 63 (95%), 10 (86%), 90(86%), 71(77%), 46 (50%), 36 (45%), and 84 (45%). Genotypic resistance to zidovudine, saquinavir, and indinavir was found in 100% of the patients. All patients showed also resistance or possible resistance to stavudine, abacavir, ritonavir, and nelfinavir. Mutations conferring genotypic resistance to nonnucleoside analogue RT inhibitors (NNRTIs) were found in 12 (80%) of the NNRTI‐experienced patients and 1 of 7 NNRTI‐naive patients. Our results indicate that failure of HAART in the patients extensively pretreated results from the multiplicity of RT and protease mutations that confer genotypic resistance to almost all available antiretroviral drugs. In these patients, genotypic resistance tests confirm the lack of alternative salvage therapy strategies based on the currently available antiretroviral drugs.
Interactions between the perception of age and ethnicity in faces: an event-related potential study

Face perception models propose that different facial attributes are processed by anatomically distinct neural pathways that partially overlap. Whether these attributes interact functionally is an open question. Our goal was to determine if there are interactions between age and ethnicity processing and, if so, at what temporal epoch these interactions are evident. We monitored event-related potentials on electroencephalography while subjects categorized faces by age or ethnicity in two conditions: a baseline in which the other of these two properties not being categorized was held constant and an interference condition in which it also varied, as modelled after the Garner interference paradigm. We found that, when participants were categorizing faces by age, variations in ethnicity increased the amplitude of the right face-selective N170 component. When subjects were categorizing faces by ethnicity, variations in age did not alter the N170. We concluded that there is an asymmetric pattern of influence between age and ethnicity on early face-specific stages of visual processing, which has parallels with behavioural evidence of asymmetric interactions between identity and expression processing of faces.
Pustular psoriasis and arthritis in congenital psoriasiform erythroderma.

The case of a patient with the rare combination of psoriasiform erythroderma, pustular psoriasis and arthritis is presented. The patient, now a 10½ -year-old boy, has had his skin disease since birth and a progressing arthritissince the age of five. Several skin biopsies have confirmed thediagnosis of pustular psoriasis. Methotrexate has had a beneficial effect on the skin; whether methotrexate also will influence his arthritis remains to be seen.
Induction of Memory in Rat Pancreatic Islets by Tolbutamide: Dependence on Ambient Glucose Level, Calcium, and Phosphoinositide Hydrolysis

The ability of the sulfonylurea tolbutamide to induce insulin output, increase phosphoinositide (PI) hydrolysis, and modulate the insulin response to other agonists was assessed. At 200 μM, tolbutamide increased both insulin release and the efflux of 3H from [3H]inositol-prelabeled islets only in the presence of 5.5 or 7 mM glucose. When the glucose level was maintained at 2.75 mM, tolbutamide (200 μM) had no positive impact on either parameter. The calcium-influx inhibitor nitrendipine (200 nM) blocked the effects of 200 μM tolbutamide (with 7 mM glucose) on 3H efflux and insulin output. Prior exposure of islets to tolbutamide (200 μM) in the presence of 7 mM glucose amplified their subsequent insulin response to 10 mM glucose and 5 mM glyceraldehyde. The effect of 200 μM tolbutamide (with 7 mM glucose) was blocked by nitrendipine. Furthermore, the effect of 200 μM tolbutamide was not observed with 2.75 mM glucose; however, if the level of tolbutamide was increased to 1 mM, both PI hydrolysis and potentiated release to subsequent stimulation with 10 mM glucose were observed. Tolbutamide (200 μM with 7 mM glucose) stimulation for 20 min resulted in an increase in 3H efflux from [3H]inositol-prelabeled islets. Despite the rapid fall in insulin secretion, elevated rates of 3H efflux persisted long after the removal of the sulfonylurea from the medium. The duration of the 3H-efflux response paralleled the duration of potentiation. Furthermore, nitrendipine (200 nM) blocked the sustained increase in 3H efflux usually noted after tolbutamide, indicating that this efflux represented the continued hydrolysis of PI and was not simply the result of the slow efflux and/or degradation of preformed labeled inositol phosphates. Direct measurements of labeled inositol phosphate accumulation substantiate all the 3H-efflux data. These results support the following conclusions: 1) tolbutamide increases PI hydrolysis in islets, an effect dependent on the level of tolbutamide, the ambient glucose concentration, and calcium influx; 2) once initiated, the increase in PI hydrolysis is sustained even after the removal of tolbutamide; and 3) biochemical events in the inositol cycle appear at least partly responsible for time-dependent potentiation (memory) to subsequent stimulation induced by prior exposure to tolbutamide.
Persuasion , Social Graces , and Computer Security

Although computer users want to behave securely, they often lack the motivation and confidence to protect themselves and their computers. In this paper, we propose a framework that harnesses aspects of social interaction and the Media Equation for designing a novel approach to persuasive technology for computer security. We then apply this framework to anti-virus software, and show how this social support addresses the current weaknesses, and thus might help users in better managing their computer security.
Chronic treatment with novel nanoformulated micelles of rapamycin, Rapatar, protects diabetic heart against ischaemia/reperfusion injury

Enhanced mammalian target of rapamycin (mTOR) signalling contributes to the pathogenesis of diabetes and plays a critical role in myocardial ischaemia/reperfusion (I/R) injury. Rapatar is a novel nanoformulated micellar of rapamycin, a putative inhibitor of mTOR that has been rationally designed to increase water solubility of rapamycin to facilitate p.o. administration and enhance bioavailability. We examined the effect of Rapatar on the metabolic status and protection against myocardial I/R injury in type 2 diabetic mice.
Cypher, a Striated Muscle-restricted PDZ and LIM Domain-containing Protein, Binds to α-Actinin-2 and Protein Kinase C*

We have cloned and characterized a novel striated muscle-restricted protein (Cypher) that has two mRNA splice variants, designated Cypher1 and Cypher2. Both proteins contain an amino-terminal PDZ domain. Cypher1, but not Cypher2, contains three carboxyl-terminal LIM domains and an amino acid repeat sequence that exhibits homology to a repeat sequence found in the largest subunit of RNA polymerase II. cypher1 and cypher2mRNAs exhibited identical expression patterns. Both are exclusively expressed in cardiac and striated muscle in embryonic and adult stages. By biochemical assays, we have demonstrated that Cypher1 and Cypher2 bind to α-actinin-2 via their PDZ domains. This interaction has been further confirmed by immunohistochemical studies that demonstrated co-localization of Cypher and α-actinin at the Z-lines of cardiac muscle. We have also found that Cypher1 binds to protein kinase C through its LIM domains. Phosphorylation of Cypher by protein kinase C has demonstrated the functional significance of this interaction. Together, our data suggest that Cypher1 may function as an adaptor in striated muscle to couple protein kinase C-mediated signaling, via its LIM domains, to the cytoskeleton (α-actinin-2) through its PDZ domain.
Regulation of Mycobacterial Heat‐Shock Protein‐Reactive T Cells by HLA Class II Molecules: Lessons from Leprosy

Major hislocompatibility (MHC) class II molecules are heterodimeric cell surface glycoproteins that are expressed by immunocompetenl cells. MHC class II molecules present processed peptide fragments to T-lymphocyte receptors, and thus can restrict and regulate T-cell responses against specific antigens. Class II molecules are highly polymorphic. This polymorphism is responsible for the genetically controlled differences in T cell-dependent responses and presumably also for genetic differences in disease susceptibility. A human disease where (HLA) class II genes play an important role is leprosy, the chronic infectious disease caused by Mycobacterium leprae. Protective immunity against M. leprae and other mycobacterial species is dependent on antigen-specific helper T lymphocytes. This is elegantly illustrated by the leprosy spectrum where strong Tlympbocyte reactivity to M. leprae is seen in the tuberculoid or high responder form of the disease as well as in healthy exposed individuals, but low or no Tcell responsiveness in the disseminated lepromatous form (Bloom & Godal 1983). HLA class Il-linked genes control the type of leprosy that develops upon infection as well as the type of cell-mediated immunity against M. leprae and related mycobacteria in skin testing (reviewed by Ottenhoff & de Vries 1987). Since leprosy type and skin test responsiveness both strongly correlate with M. lepraespecific T-cell reactivity, HLA class II gene products might regulate these responses by restricting and regulating T-helper cell activity against M. leprae
Mechanisms of Proton Conductance in Polymer Electrolyte Membranes

We provide a phenomenological description of proton conductance in polymer electrolyte membranes, based on contemporary views of proton transfer processes in condensed media and a model for heterogeneous polymer electrolyte membrane structure. The description combines the proton transfer events in a single pore with the total pore-network performance and, thereby, relates structural and kinetic characteristics of the membrane. The theory addresses specific experimentally studied issues such as the effect of the density of proton localization sites (equivalent weight) of the membrane material and the water content of the pores. The effect of the average distance between the sulfonate groups, which changes during membrane swelling, is analyzed in particular, and the factors which determine the temperature dependence of the macroscopic membrane conductance are disclosed. Numerical estimates of the specific membrane conductivity obtained from the theory agree very well with typical experimental data, thereby confirming the appropriateness of the theoretical concepts. Moreover, the versatility of the models offers a useful and transparent frame for combining the analysis of both experimental data and the results of molecular dynamics simulations.
Dynamic MR imaging of the breast: Analysis of kinetic and morphologic diagnostic criteria

Purpose: To assess the value of kinetic and architectural diagnostic criteria on dynamic MR breast imaging, and to construct a scoring system for lesion characterization. Material and Methods: A total of 92 women with 109 histopathologically verified breast lesions were included in this retrospective study. The patients were examined by a 1.5 T system using a dedicated double breast coil. A dynamic examination with one precontrast and seven postcontrast series was performed, using a T1-weighted 3D FLASH sequence. Thirty lesions (15 malignant and 15 benign) were randomly chosen for the validation set, and the remaining 79 lesions (62 malignant and 17 benign) formed the estimation set, in which multivariate analysis was performed in order to select the most important features. These parameters were then used for constructing the scoring system, which was tested on the validation set. The scoring system was compared with the routine standard evaluation that used all established diagnostic criteria. ROC curves were generated to assess the diagnostic accuracy of different approaches. Results: In the multivariate analysis of the 79 lesions, time-to-peak enhancement and the descriptor of margins were found to be the most important independent factors for distinguishing benign from malignant lesions, and formed the basis of the scoring system. The areas under the ROC curves for the standard evaluation, and the scoring system were 0.813 and 0.880 in the 30 lesions. Conclusion: Time-to-peak enhancement and the descriptor of margins appear to be the most important diagnostic criteria for mass lesions in dynamic breast MR imaging.