Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-based mutational analysis of ICAT residues mediating negative regulation of β-catenin co-transcriptional activity

ICAT (Inhibitor of β-CAtenin and TCF) is a small acidic protein that negatively regulates β-catenin co-transcriptional activity by competing with TCF/LEF factors in their binding to β-catenin superhelical core. In melanoma cells, ICAT competes with LEF1 to negatively regulate the M-MITF and NEDD9 target genes. The structure of ICAT consists of two domains: the 3-helix bundle N-terminal domain binds to β-catenin Armadillo (Arm) repeats 10–12 and the C-terminal tail binds to Arm repeats 5–9. To elucidate the structural mechanisms governing ICAT/β-catenin interactions in melanoma cells, three ICAT residues Y15, K19 and V22 in the N-terminal domain, contacting hydrophobic β-catenin residue F660, were mutated and interaction was assessed by immunoprecipitation. Despite the moderate hydrophobicity of the contact, its removal completely abolished the interaction. In the ICAT C-terminal tail consensus sequence, neutralization of the electrostatic interactions between residues D66, E75 and β-catenin residues K435, K312, coupled to deletion of the hydrophobic contact between F71 and β-catenin R386, markedly reduced, but failed to abolish the ICAT-mediated negative regulation of M-MITF and NEDD9 promoters. We conclude that in melanoma cells, anchoring of ICAT N-terminal domain to β-catenin through the hook made by residue F660, trapped in the pincers formed by ICAT residues Y15 and V22, is crucial for stabilizing the ICAT/β-catenin complex. This is a prerequisite for binding of the consensus peptide to Arm repeats 5–9 and competition with LEF1. Differences between ICAT and LEF1 in their affinity for β-catenin may rely on the absence in ICAT of hydrophilic residues between D66 and F71.
Association between breast cancer risk and the wild-type allele of human ABC transporter ABCC11.

BACKGROUND International mortality and frequency rates for breast cancer have been associated with the wet type of human earwax. It was recently found that earwax type is determined by a single nucleotide polymorphism (SNP), 538G>A (Gly180Arg), in ABCC11. The G allele determines the wet type of earwax as a Mendelian trait with a dominant phenotype. The present study examined the association between the frequency rate of breast cancer and the frequency of the G allele of ABCC11. PATIENTS AND METHODS Using blood samples from patients with invasive breast cancer (n = 270) and control volunteers (n = 273), the 538G>A SNP in ABCC11 was genotyped using the SmartAmp method. RESULTS The frequency of the G allele in breast cancer patients was higher than that in healthy controls. The odds ratio for the genotypes (G/G+G/A) to develop breast cancer was estimated to be 1.63 (p-value = 0.026), suggesting that the G allele in ABCC11 is associated with breast cancer risk. CONCLUSION This study showed that Japanese women with wet earwax have a higher relative risk of developing breast cancer than those with dry earwax. The ABCC11 SNPs that determine these phenotypes should be further investigated in order to obtain insights into the mechanisms by which breast cancer develops and progresses.
Lipid modification in type 2 diabetes: the role of LDL and HDL

Patients with type 2 diabetes feature important modification of both low density lipoprotein (LDL) and high density lipoprotein particles which are likely to play an important role in the development of atherosclerosis. Although plasma LDL cholesterol level is usually normal in type 2 diabetic patients, LDLs show a significant increase in their plasma residence time which may promote cholesterol deposition in the arterial wall. Moreover, important qualitative abnormalities of LDLs, potentially atherogenic, are observed in type 2 diabetic patients: small dense, triglyceride‐rich, LDL particles (known as subclass B), oxidized LDL and glycated LDL. All these qualitative modification of LDLs amplify the atherosclerotic process.
Physico-Chemistry, Morphology and Abundance of Finfish of Nkoro River, Niger Delta, Nigeria

There have been no reliable data on physico-chemical characteristics, morphology and abundance of fish species from Nkoro River in the Niger Delta Area of Nigeria. This is needed to formulate sound fisheries management and development programmes in the Nkoro River. This paper therefore provides information to fill that gap in Nkoro River fisheries by studying some physico-chemical parameters and morphology and abundance of five fish species. Temperature, pH, dissolved oxygen and salinity were monitored using standard methods. Fish samplings were carried out for twelve months biweekly from January to December 2006 from the artisanal fishers using cast nets, beach seine and canoes. The monthly physico-chemical characteristics showed that, salinity values ranged from 5‰ (September) to 17‰ (February and March). Dissolved oxygen values ranged from 6mg/l(January, April, July and October) to 10mg/l (September). pH values ranged from 6.1(August) to 8.5(November) and Temperature values ranged from 24 o C (July) to 32 o C (March). There was no significant difference in salinity and pH between stations, but dissolved oxygen, and temperature showed significant differences between stations (P<0.05). The monthly catch per unit effort values ranges were: E. fimbriata [(0.20 (November) to 8.16 (January)]; I. africana [0.1 (May) to 1.6 (February); S. maderensis [0.04 (October) to 6.8 (December]; C. senegalensis [0.12 (August) to 2.45 (December)] and C. senegalensis [0.11 (May) to 1.62 (December)] . There was an increase catch during the dry season. There was significant difference in monthly catch (P>0.05). There was no correlation between any of physio-chemical parameters and catch. The test for correlation between the condition factor and the physico-chemical parameters was negative except for temperature (only temperature showed slight correlation). The variation was significant between various stations. Salinity in Nkoro River played a major role in distribution and abundance of the five fish species; higher abundance of fish species during low salinity.
Phenomenology of Ground Scattering in a Tropical Forest Through Polarimetric Synthetic Aperture Radar Tomography

This paper aims at characterizing the scattering mechanisms occurring at the ground level in a tropical forest illuminated by a P-band synthetic aperture radar (SAR). The analysis is carried out based on the multibaseline, fully polarimetric, data set collected by ONERA over Paracou, French Guyana, in the frame of the European space agency campaign TropiSAR. The favorable baseline distribution of this data set results in the possibility of removing most contributions from the vegetation layer by tomographic techniques, thus allowing the generation of a new fully polarimetric single look complex SAR image relative to scattering contributions from the ground level only. Such a ground layer image is then analyzed by considering the variation of its polarimetric signature with respect to terrain local slope and Radar look angle. Two major conclusions are drawn: 1) double bounce scattering from trunk-ground interactions is observed to be the dominant scattering mechanism at the ground level on flat terrains, whereas it rapidly tends to vanish as the topographic slope increases, and 2) the characteristic parameter that rules trunk-ground scattering is not the tree height, but rather the available free path facing the tree, as a result of the presence of nearby trees, undulating topography, or understory preventing double bounce scattering from taking place whenever the ground bounce occurs too far away from the considered tree. The mean free path length resulting from the analysis of this data-set is found to be L ≅ 7 m. Finally, we discuss how the concept of free path length can be accounted for in simple terms by assuming an equivalent extinction model characterized by a variation along the horizontal dimension.
Length of operative procedures: reamed femoral intramedullary nailing performed with and without a fracture table.

OBJECTIVES To determine whether performing reamed intramedullary nailing of the femur without the use of a fracture table decreases the length of operation. DESIGN Retrospective. SETTING Level 1 trauma center, Nashville. Tennessee. PATIENTS/PARTICIPANTS Consecutively treated patients with fractures of the femoral shaft were treated with intramedullary nails from June 1986 to March 1996. INTERVENTION Reamed intramedullary nailing of the femoral shaft was performed with the use of a fracture table or with the leg draped free on a radiolucent table. MAIN OUTCOME MEASUREMENTS Length of anesthesia time, prep and drape time (from the point the anesthetized patient is turned over to the surgeons until incision), and intramedullary nailing time (from incision until end of surgery) for reamed intramedullary nailing of the femoral shaft performed with and without the use of a fracture table were compared. RESULTS Univariate analysis showed statistically significant decreases in the length of prep and drape time, operative time, and anesthetic time when fractures were treated without the use of a fracture table. Multivariate analysis showed that use of a fracture table prolongs prep and drape time (plus twenty minutes), operative time (plus seventeen minutes), and anesthesia time (plus seventy-three minutes) when the covariates of age, sex, fracture location, learning curve, position of the patient, nail brand, and number of distal bolts are controlled. CONCLUSIONS Reamed intramedullary nailing of the femoral shaft performed without the use of a fracture table is significantly faster than when the procedure is performed with a fracture table.
Contingency knowledge is necessary for learned motivated behaviour in humans: relevance for addictive behaviour.

AIMS Many forms of human conditioned behaviour depend upon explicit knowledge of the predictive contingency between stimuli, responses and the reinforcer. However, it remains uncertain whether the conditioning of three key behaviours in drug addiction-selective attention, instrumental drug-seeking behaviour and emotional state--are dependent upon contingency knowledge. To test this possibility, we employed an avoidance procedure to generate rapidly these three forms of conditioned behaviour without incurring the methodological problems of drug conditioning. DESIGN In two experiments, participants (16 students) were trained on a schedule in which one stimulus (S +) predicted the occurrence of a startling noise, which could be cancelled by performing an instrumental avoidance response. MEASUREMENTS The allocation of attention to the S + and the rate and probability of the avoidance response in the presence of S + were measured. Following training, participants were tested for their knowledge of the stimulus-noise contingencies arranged in the study and rated the emotional qualities of the stimuli. FINDINGS Both experiments showed that S + gained control of selective attention, instrumental avoidance behaviour and subjective anxiety, but only in participants who reported explicit knowledge of the Pavlovian contingency between the S + and the startling noise. CONCLUSIONS The implication of the present findings is that the control of selective attention, instrumental drug-seeking behaviour and emotional state by drug-paired stimuli is mediated by cognitive knowledge of the predictive contingency between the stimulus and the drug.
In vitro susceptibilities of four species of coagulase-negative staphylococci

The in vitro susceptibilities of 260 strains of coagulase-negative staphylococci to penicillin G, oxacillin, nafcillin, methicillin, cephalothin, and seven non-beta-lactam antimicrobial agents were determined and compared with the susceptibilities of 54 strains of Staphylococcus aureus with known patterns of susceptibility. Penicillin G susceptibility for S. aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis was readily determined by using beta-lactamase tests with induced cells and with a standardized microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to the coagulase-negative species. Percentages of organisms susceptible were as follows: S. epidermidis, 7%; S. haemolyticus, 5%; and S. hominis, 47%. Oxacillin susceptibility for these four species was readily determined by using a modification of the microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to S. haemolyticus and S. hominis, but alternate criteria were necessary for S. epidermidis. Percentages of organisms susceptible were as follows: S. epidermidis, 29%; S. haemolyticus, 36%; and S. hominis, 97%. Staphylococcus saprophyticus differed from the other staphylococcal species; all strains were beta-lactamase negative and were penicillin susceptible but had higher penicillin G MICs than did susceptible strains of the other species. There was total cross resistance among the penicillinase-resistant penicillins and cephalothin for the coagulase-negative staphylococci as well as for S. aureus; oxacillin MICs were more reliable than MICs of the other drugs or a standardized disk diffusion test for distinguishing resistant from susceptible strains. Vancomycin, rifampin, and ciprofloxacin were consistently active against all staphylococci. Erythromycin, clindamycin, gentamicin, and trimethoprim-sulfamethoxazole were more active against oxacillin-susceptible staphylococci than against oxacillin-resistant staphylococci.
Effect of topical corticosteroids on allergic airway inflammation and disease severity in obstructive sleep apnoea

The incidence of sleep‐related breathing disorders is correlated with lower and upper airway inflammatory diseases, such as asthma and allergic rhinitis. We hypothesized that corticosteroids treatment would lead to a greater reduction in disease severity in obstructive sleep apnoea syndrome (OSAS) patients with concomitant allergic rhinitis vs. non‐allergic OSAS patients by reducing the level of inflammation in upper airway tissues.
Arsenic Inhibits Autophagic Flux, Activating the Nrf2-Keap1 Pathway in a p62-Dependent Manner

ABSTRACT The Nrf2-Keap1 signaling pathway is a protective mechanism promoting cell survival. Activation of the Nrf2 pathway by natural compounds has been proven to be an effective strategy for chemoprevention. Interestingly, a cancer-promoting function of Nrf2 has recently been observed in many types of tumors due to deregulation of the Nrf2-Keap1 axis, which leads to constitutive activation of Nrf2. Here, we report a novel mechanism of Nrf2 activation by arsenic that is distinct from that of chemopreventive compounds. Arsenic deregulates the autophagic pathway through blockage of autophagic flux, resulting in accumulation of autophagosomes and sequestration of p62, Keap1, and LC3. Thus, arsenic activates Nrf2 through a noncanonical mechanism (p62 dependent), leading to a chronic, sustained activation of Nrf2. In contrast, activation of Nrf2 by sulforaphane (SF) and tert-butylhydroquinone (tBHQ) depends upon Keap1-C151 and not p62 (the canonical mechanism). More importantly, SF and tBHQ do not have any effect on autophagy. In fact, SF and tBHQ alleviate arsenic-mediated deregulation of autophagy. Collectively, these findings provide evidence that arsenic causes prolonged activation of Nrf2 through autophagy dysfunction, possibly providing a scenario similar to that of constitutive activation of Nrf2 found in certain human cancers. This may represent a previously unrecognized mechanism underlying arsenic toxicity and carcinogenicity in humans.
Understanding Your Needs: An Adaptive VoD System

Video-on-demand (VoD) is becoming a popular service for commercial content distribution by offering end users the freedom to access recorded programmes. The management of on-demand assets is essential to maximise the efficiency of storage and network utilisation as well as advertisement. This paper introduces our recent efforts in design and implementation of an adaptive VoD archive system in an IPTV infrastructure. The system exploits live statistics on the user behaviours as well as the dynamic popularity of VoD programmes. Using the modelled programme popularity function, the VoD archive is capable of managing the VoD repository by adapting to the most recent user requests. The design has greatly improved the activity of VoD repository and user experience in on-demand services.
Characterization of two unusual RS1 gene deletions segregating in Danish retinoschisis families

Over 100 distinct retinoschisis gene (RS1) mutations, of which approximately 10% are single exon deletions, have been described to date. In this paper we have characterized in detail two dissimilar RS1 gene deletions which are accountable for RS in one‐third of Danish patients. First, a 136 kb deletion, spanning from the 5′ region of the RS1 gene to intron 3, was identified. Unexpectedly this large deletion abolishes exons of three adjacent genes: serine‐threonine phosphatase gene (PPEF‐1)/serine‐threonine protein phosphatase gene (PP7), retinoschisis gene (RS1), and serine‐threonine kinase gene (STK9). We demonstrate that the RS1 and STK9 genes are partly overlapping and the sequences of the PP7 and PPEF‐1 genes are identical. This is the first study which reports of retinoschisis patients who also suffer from deletions in genes adjacent to RS1. The 136 kb deletion is also the first gross deletion of the retinoschisis gene deleting three exons. It results from a recombination between two repetitive sequences of the Alu family, one in 5′ region of the RS1 gene and the other in RS1 intron 3. The second alteration, the actual Danish RS founder mutation, is a 4.4 kb noncontiguous two‐part deletion composed of two deleted 1.5 and 2.9 kb segments, separated by an intact 1.2 kb segment. It extends from the 5′ flanking region of the retinoschisis gene to RS intron 1. RS1 gene deletions of this type have not been identified previously. Despite these two unique deletions, which either lead to severely defective transcription or total absence of the retinoschisin and PPEF‐1 protein, all the patients have a typical retinoschisis phenotype. Hum Mutat 16:307–314, 2000. © 2000 Wiley‐Liss, Inc.
Permeability of Human Placenta and Fetal Membranes to Thyrotropin-Stimulating Hormone in Vitro

We determined the placental transfer of TSH in an in vitro model of dually perfused isolated lobule in 28 human term placentas by adding varying concentrations (5-60 μIU mL-1) of TSH as a single bolus dose to the closed maternal circulation. Transmembrane transfer of TSH was also studied by adding 45 μIU mL-1 to the maternal or fetal compartment of a dual chamber of fetal membranes in culture. Passage of freely diffusible markers creatinine and antipyrine were also studied in this model. TSH concentration was measured by third generation chemiluminescence assay with a sensitivity of 10 mIU mL-1. In the perfusion experiments, at physiologic concentrations the slow decline of TSH in the maternal circulation was associated with a small linear increase in fetal levels to 0.11 ± 0.04% of initial dose at 2 h. The placental transfer rate was 0.08 μIU min-1. Increasing maternal concentrations of TSH were associated with proportional increases in transfer rate (y = 0.002x; R2= 0.99) and placental uptake (y = 0.01x; R2 = 0.97). The placental permeability of TSH was 2.4·10-4 mL min-1 g-1 and was proportional to its coefficients of diffusion in water and molecular size. The transmembrane transfer and permeability of TSH was comparable to those of the placenta. We conclude that TSH crosses the human term placenta and fetal membranes sparingly.
Does belief matter in climate change action?

We studied environmental action and its predictors in a multi-scalar context of climate change politics. We asked how belief in climate change, post-materialist values, trust and knowledge predict people’s engagement in environmental action by testing two alternative structural equation models (SEM). In one of these models all these factors directly predicted climate-friendly action, and in the other the effect of political trust, post-materialist values and climate change knowledge on climate-friendly action was mediated by belief in climate change. The models were tested with Eurobarometer 69.2 survey data of adult people living in Finland (N = 1,004). The SEM revealed that belief in climate change mediates the effect of post-material values, trust and knowledge on climate-friendly action. It is therefore important to recognize the role of belief in the public understanding of large-scale environmental problems. These results help political authorities to develop policies to encourage people’s engagement in climate-friendly action.
[The impact of HLA high resolution typing mismatching of donor-recipient pairs on outcome of unrelated donor hematopoietic stem cell transplantation].

OBJECTIVE To study the impact of various human leukocyte antigen (HLA) high resolution typing mismatching of donor-recipient pairs on prognosis of unrelated donor hematopoietic stem cell transplantation. METHODS 835 donor-recipient pairs of CMDP data from 2005 to 2010 were analyzed retrospectively. HLA-A, B, C, DRB1 and DQB1 typing were performed using SBT, SSOP and SSP methods. The diseases involved in acute myeloid leukemia (AML) (n = 288), acute lymphoid leukemia (ALL) (n = 227), chronic myeloid leukemia (CML) (n = 187), myelodysplastic syndrome (MDS) (n = 52), non-hodgkin's lymphoma(NHL) (n = 25), aplastic anemia(AA) (n = 42) and thalassemia (n = 14). Of 835 donor-recipient pairs, 362 were completely matched, 159 had a mismatch for a single allele, 125 had a mismatch for a single antigen, 95 had mismatched for both single allele and single antigen, 29 were mismatched at double allele, 20 at double antigen, 45 at multiple allele and antigen. The follow-up assessment was completed before March 2011. RESULTS HLA-matched pairs had higher overall survival (OS) than HLA-mismatched pairs (79.83% vs 73.15%), but there was no statistically significant differences (P > 0.05). HLA mismatch for a single allele plus a single antigen was a significantly risk factor for OS, disease free survival (DFS) and transplant-related mortality (TRM). The OS from high to low in different diseases were thalassemia, AA, CML, MDS, AML, NHL, and ALL. OS of HLA locus mismatch were DRB1 (94.4%), DQB1 (83.3%), B (75%), A (74.4%) and C (71.4%), respectively. OS of single allele mismatch at HLA locus from high to low were DRB1, C, A, B and DQB1.HLA-A, B, C locus mismatch were statistically significantly associated with lower OS and grade II-IV acute GVHD compared with HLA-matched pairs (P < 0.05). The donor-recipient pairs with HLA-B*15:01/B*15:05, DRB1*12:01/DRB1*12:02, C*04:01/C*03:04, DQB1*03:02/DQB1*03:03 alleles mismatch were given priority. But the donor-recipient pairs with HLA-B*39:01/B*39:05, C*15:02/C*14:02, C*08:01/C*03:04, C*07:02/C*15:02 alleles mismatch were risk factors for influence of OS and aGVHD. CONCLUSION The high resolution typing for HLA-A, B, C, DRB1, DQB1 can be identified nonpermissive mismatch, which is beneficial for the selection of a suitable donor improves survival on unrelated donor HSCT.
Immunoglobulin G Avidities in Infants in Mexico after Primary Immunization with Three Doses of Polyribosylribitol Phosphate-Tetanus Toxoid Haemophilus influenzae Type b Vaccine

ABSTRACT Serum immunoglobulin G concentrations and avidities specific to Haemophilus influenzae type b (Hib) were measured in 208 children living in Guadalajara and Mexico City. Protective concentrations were found in 98.9% and 100.0% of participants, respectively. Geometric mean concentrations differed between both populations and/or among age groups. Mean avidities differed only among the 7- to 12-month-old children. Diphtheria-tetanus-whole-cell pertussis-hepatitis B-Hib primary vaccination seems to induce protection in Mexican children.