Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the ENPP1 and PLIN Single Nucleotide Polymorphisms With Type 2 Diabetes in a Taiwanese Population

Background Addressing gene-gene interactions is essential in defining a trait implicating complex disease-related mechanisms. In this study, we aimed to explore both main effects of single-locus and multi-locus interactions to test the hypothesis that the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and perilipin (PLIN) genes may contribute to the etiology of type 2 diabetes (T2D) independently and/or through complex interactions in a Taiwanese population. Methods There were 416 patients with a diagnosis of T2D and 188 age- and sex-similar control subjects. To investigate gene-gene interactions, we used both the generalized multifactor dimensionality reduction method and logistic regression models. Results Allelic and genotypic analyses showed significant main effects of ENPP1 rs1044498 (P = 0.000005 and 0.00007, respectively) on the risk of T2D after Bonferroni correction (P < 0.05/2 = 0.025). Compared to the carrier of the AA genotype of the ENPP1 rs1044498 polymorphism, the likelihood of T2D was 2.442 (95% confidence interval, 1.592–3.747) for the carrier of combined AC+CC genotypes after adjustment of sex and body mass index. In addition, the carriers of AA variant in the PLIN rs894160 polymorphism had a higher risk to T2D than those with the combined AG+GG variants (adjusted odds ratio, 1.856; 95% confidence interval, 1.106–3.115) after adjustment of sex and body mass index. Furthermore, the significant 2-locus (P = 0.001) generalized multifactor dimensionality reduction model was identified between ENPP1 and PLIN. Analyses using logistic regression models confirmed the gene-gene interaction. Conclusions The results suggest that the ENPP1 and PLIN genes may contribute to the risk of T2D independently and/or in an interactive manner in a Taiwanese population.
VoIP services with embedded CAC over cable modem systems

VoIP (voice over Internet protocol) technology has rapidly been growing up recently, which transmits voice packets by using the user datagram protocol (UDP). VoIP quality is difficult to expect because it is hard to predict the influence of packet delay, packet lose, packet error, etc. This paper proposes an embedded call admission control (CAC) mechanism by applying real-time transfer protocol (RTP) and the real-time control protocol (RTCP) for VoIP services over hybrid fiber/coaxial (HFC) networks. The proposed CAC mechanism is evaluated by the impact of the various traffic load in cable modem termination system (CMTS), which estimates how VoIP quality satisfies the user's requirements under different constrains on cable networks. We discuss VoIP CAC mechanism for the upstream channel according to the data over cable service interface specifications (DOCSIS) version 1.1 and particularly consider G.723. 1 voice packets at the transmission rate of 6.3 kbps. The performance measurement of the proposed embedded CAC mechanism is obtained by simulation experiments under various network constrains, which includes throughput, packet dropping ratio and call blocking ratio. Obviously this paper provides an efficiency and fast method for CMTS to decide how many calls can be accepted.
Multiple Mechanistically Distinct Functions of SAGA at the PHO5 Promoter

ABSTRACT Our previous studies have shown that the rate of chromatin remodeling and consequently the rate of PHO5 activation are strongly decreased in the absence of Gcn5 histone acetyltransferase activity. Using chromatin immunoprecipitation, we demonstrate that SAGA is physically recruited to the PHO5 promoter. Recruitment is dependent on the specific activator Pho4 and occurs only under inducing conditions. Spt3, another subunit of SAGA, also plays a role in PHO5 activation but has a function that is completely different from that of Gcn5. An SPT3 deletion severely compromises the PHO5 promoter and reduces the extent of transcriptional activation by diminishing the binding of the TATA binding protein to the promoter without, however, affecting the rate or the extent of chromatin remodeling. A gcn5 spt3 double mutant shows a synthetic phenotype almost as severe as that observed for an spt7 or spt20 mutant. The latter two mutations are known to prevent the assembly of the complex and consequently lead to the loss of all SAGA functions. The absence of the Ada2 subunit causes a strong delay in chromatin remodeling and promoter activation that closely resembles the delay observed in the absence of Gcn5. A deletion of only the Ada2 SANT domain has exactly the same effect, strongly suggesting that Ada2 controls Gcn5 activity by virtue of its SANT domain. Finally, the Gcn5 bromodomain also contributes to but is not essential for Gcn5 function at the PHO5 promoter. Taken together, the results provide a detailed and differentiated description of the role of SAGA as a coactivator at the PHO5 promoter.
Immunization with native surface protein NcSRS 2 induces a Th 2 immune response and reduces congenital Neospora caninum transmission in mice *

NcSRS2, a tachyzoite surface protein of Neospora caninum, is an immunodominant protein with respect to induction of antibody production and has a role in attachment and invasion of host cells. Native NcSRS2 was isolated from whole tachyzoite lysate antigen by affinity chromatography using NcSRS2 specific monoclonal antibody and used to immunize BALB/c mice in a congenital transmission study. NcSRS2 was a highly conserved protein as indicated by comparison of deduced amino acid sequence obtained from NcSRS2 gene sequences of 10 geographically distinct N. caninum isolates. Mice immunized with purified native NcSRS2 produced antigen-specific antibody, primarily of IgG 1 subtype. Following challenge during gestation with 10 tachyzoites, immunized mice had a statistically significant decreased frequency of congenital transmission compared to non-immunized mice (P%0.05) or mice inoculated with adjuvant alone (P%0.01). Decreased congenital transmission among immunized mice correlated with a predominately Th2 immune response compared to non-immunized mice as indicated by an increased ratio of interleukin 4 (IL-4) to interferon gamma (IFN-g) secretion from antigen-stimulated splenocytes. The results provide a rationale for NcSRS2 as a candidate subunit vaccine antigen for reduction of N. caninum congenital transmission. Furthermore, the studies suggest that a Th2 immune response, if directed against an appropriate antigen, may induce protection against N. caninum congenital infection in mice. q 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
Polyurethane/Poly(2-(Diethyl Amino)Ethyl Methacrylate) blend for drug delivery applications

A pH-sensitive blend of polyurethane (PU) and poly(2-(diethyl amino)ethyl methacrylate (PDEA) with good film-forming capacity was prepared from the corresponding aqueous dispersions. The polymer matrix was first characterized by using FTIR, DSC, water vapor transmission and water swelling capacity at different pHs. The drug release profile of films was evaluated using a vertical Franz Cell and theophylline as model drug. The water swelling degree increases from 54 to 180% when the pH of the medium is changed from 6 to 2, demonstrating the pH-responsive behavior of the film. The in-vitro release studies indicate that an anomalous transport mechanism governs the theophylline release.
Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C.

AIM TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations. PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection. This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS Fifteen patients infected with HCV were treated with PEG-IFN(0.5 microg/body weight/week) and ribavirin (1 000 mg-1 200 mg/daily) for 48 weeks. Blood samples were drawn at the beginning and the end of the therapy. Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS At the beginning of treatment, TTV infection was detected in 10/15 (66.6%) of HCV-infected patients. Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients. Out of these 6 patients, 4 (67%) became positive for TTV DNA after 6 months of therapy. Regarding HCV viremia, 11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy, 7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment. In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy, TTV DNA was detected as well. Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.
Glutathione transferase zeta-catalyzed biotransformation of deuterated dihaloacetic acids.

Glutathione transferase zeta (GSTZ) catalyzes the biotransformation of alpha-haloalkanoic acids. Treatment of rats or humans with dichloroacetic acid prolongs its elimination half-life, and preliminary studies in this laboratory show that fluorine-lacking, but not fluorine-containing dihaloacetic acids inactivate GSTZ. In the present study, the GSTZ-catalyzed biotransformation of unlabeled and deuterated dihaloacetic acids was investigated. With [(2)H]dichloroacetic acid and [(2)H]chlorofluoroacetic acid as substrates, the deuterium present in the [(2)H]dihaloacetic acid was retained in the [(2)H]glyoxylic acid formed. This finding indicates that the enol of the dihaloacetic acid does not serve as the substrate for the enzyme. The data afford an explanation of the failure of fluorine-containing dihaloacetic acids to inactivate GSTZ: dichloroacetic acid is converted to glyoxylic acid and inactivates GSTZ, whereas chlorofluoroacetic acid is biotransformed to glyoxylic acid, but produces negligible inactivation. Mechanisms are presented indicating that this difference may be attributed to the nucleofugicity of the leaving group.
A Genetic Locus Controlling Aging‐sensitive Regression of B Lymphopoiesis in an Autoimmune‐prone MRL/lpr Strain of Mice

Aging readily affects immune system under the influence of environmental and/or intrinsic factors while accelerating the development of various immune disorders including autoimmune diseases. Little is known about molecular and cellular mechanisms connecting between immune senescence and development of autoimmune diseases. Here, we first show strain‐specific and aging‐sensitive onset of B‐cell abnormality in a lupus‐prone MRL/Mp.Faslpr (MRL/lpr) strain of mice. This abnormality was characterized by the regression of B lymphopoiesis in the bone marrow of this strain. We next examined the association between the B‐cell regression and onset of autoimmune diseases in aged (MRL/lpr × C3H/He.Faslpr) F2 mice, in which pathologic phenotypes, such as glomerulonephritis, vasculitis, sialoadenitis and arthritis, variously developed. We also searched whole genome to identify genetic loci linked to the B‐cell regression by using the same F2 mice. The B‐cell regression manifested in the spleen of F2 mice was retrospectively evaluated by reverse transcriptase‐based PCR quantification. The results demonstrated that the onset of autoimmune diseases in the F2 mice was not associated with the aging‐sensitive B‐cell regression. The genetic study identified a significant locus responsible for the B‐cell regression in the vicinity of D5Mit233 (29 cM). This is first evidence for the presence of a genetic locus that affects B lymphopoiesis in an aging‐sensitive manner.
Assortative Pairing in Ixodes ricinus (Acari: Ixodidae), the European Vector of Lyme Borreliosis

ABSTRACT In sexual organisms, the way in which gametes associate can greatly influence the maintenance of genetic variation, the structure of this variation in space, and ultimately organismal evolution. Based on patterns of genetic structure previously found, we explicitly tested whether adults of the sheep tick Ixodes ricinus pair according to their genetic relatedness. We sampled tick pairs from the vegetation in four natural populations and genotyped individual ticks at seven microsatellite loci. Based on this data, we observed highly significant assortative mating in two of the four locations, a pattern that could not be accounted for by a spatial autocorrelation in the distribution of related ticks. One explanation for these observations may be the existence of local host associations that develop independently in different populations. Assortative mating in I ricinus will have clear consequences for its population dynamics and, through processes of adaptation and transmission, may significantly alter the epidemiological patterns of the pathogens it carries, including the Lyme disease agent Borrelia burgdorferi s.l. Future tests will now be required to examine the mechanisms leading to this pattern and its epidemiological consequences.
Functional role of phosphatidylcholine‐specific phospholipase C in regulating CD16 membrane expression in natural killer cells

CD16, the low‐affinity FcIgG receptor (FcγRIIIA), is predominantly expressed in human NK cells. Our recent findings indicate that CD16 expression on the outer membrane surface of NK cells is correlated with the membrane expression of phosphatidylcholine‐specific phospholipase C (PC‐PLC). In the present study we analyzed the trafficking of CD16 from the plasma membrane to cytoplasmic regions, after stimulation with specific mAb. The CD16 receptor is internalized, likely degraded and newly synthesized; its endocytosis is independent of ATP, but requires an integral and functional actin cytoskeleton. Antibody‐mediated CD16 cross‐linking results in an approximately twofold increase in PC‐PLC enzymatic activity within 10 min. Analysis of PC‐PLC and CD16 distribution in NK cell plasma membrane demonstrates that the proteins are physically associated and partially accumulated in lipid rafts. Pre‐incubation of NK cells with a PC‐PLC inhibitor, D609, causes a dramatic decrease both in CD16 receptor and PC‐PLC enzyme expression on the plasma membrane. Interestingly, among phenotype PBL markers, only CD16 is strongly down‐modulated by D609 treatment. CD16‐mediated cytotoxicity is also reduced after D609 incubation. Taken together, these data suggest that the PC‐PLC enzyme could play an important role in regulating CD16 membrane expression, the CD16‐mediated cytolytic mechanism and CD16‐triggered signal transduction.
Integrating Levels of Analysis in World Politics

`Levels of analysis' problems can involve issues regarding (1) the relative potency of different categories of explanatory factors, (2) the relationship between analyses focusing on different units of analysis or (3) the relationship between assumptions about individual social entities and hypotheses regarding interactions among those entities. An analysis of the manner in which economists have dealt with levels of analysis issues and recent developments in the field of international politics focusing on the relationship between regime types and international conflict can facilitate the integration of research efforts involving different levels of analysis. Advocates of `democratic peace' rely increasingly on an assumption that leaders of states place the highest priority on staying in power. This assumption offers a useful basis for the integration of domestic as well as international or environmental explanatory factors. Since this assumption and theoretical notions based on it imply that different types of states behave differently, however, it can also complicate the analysis of interactions among states. Directed dyadic level analyses, and analyses of more complex aggregates using directed dyads as building blocks, can produce data that are more germane to the evaluation of hypotheses regarding the impact of differences between states than aggregate level analyses that typically tend to obscure `who does what to whom'.
Main Pulmonary Arterial Wall Shear Stress Correlates with Invasive Hemodynamics and Stiffness in Pulmonary Hypertension

Pulmonary hypertension (PH) is associated with proximal pulmonary arterial remodeling characterized by increased vessel diameter, wall thickening, and stiffness. In vivo assessment of wall shear stress (WSS) may provide insights into the relationships between pulmonary hemodynamics and vascular remodeling. We investigated the relationship between main pulmonary artery (MPA) WSS and pulmonary hemodynamics as well as markers of stiffness. As part of a prospective study, 17 PH patients and 5 controls underwent same-day four-dimensional flow cardiac magnetic resonance imaging (4-D CMR) and right heart catheterization. Streamwise velocity profiles were generated in the cross-sectional MPA in 45° increments from velocity vector fields determined by 4-D CMR. WSS was calculated as the product of hematocrit-dependent viscosity and shear rate generated from the spatial gradient of the velocity profiles. In-plane average MPA WSS was significantly decreased in the PH cohort compared with that in controls (0.18 ± 0.07 vs. 0.32 ± 0.08 N/m2; P = 0.01). In-plane MPA WSS showed strong inverse correlations with multiple hemodynamic indices, including pulmonary resistance (ρ = –0.74, P < 0.001), mean pulmonary pressure (ρ = –0.64, P = 0.006), and elastance (ρ = –0.70, P < 0.001). In addition, MPA WSS had significant associations with markers of stiffness, including capacitance (ρ = 0.67, P < 0.001), distensibility (ρ = 0.52, P = 0.013), and elastic modulus (ρ = –0.54, P = 0.01). In conclusion, MPA WSS is decreased in PH and is significantly associated with invasive hemodynamic indices and markers of stiffness. 4-D CMR-based assessment of WSS may represent a novel methodology to study blood-vessel wall interactions in PH.
Age and growth of early life stages of European pilchard ( Sardina pilchardus ) from the western Adriatic Sea

European pilchard or sardine (Sardina pilchardus, Walbaum, 1792) is a member of the family Clupeidae. It is a coastal pelagic and euryhaline species distributed across the northeastern Atlantic, from Iceland to Senegal, and in the Mediterranean, including the Adriatic Sea (WHITEHEAD, 1985). It represents one of the most important pelagic fish resources in the Mediterranean Sea, being one of the target species of purse seine and mid-water pair trawl fishing fleet operating across the basin. Overall, this species account for about 41% of the total catches (MORELLO & ARNERI, 2009). From ecological perspective, the key role of small pelagic fishes has been recently reported from the northern and central Adriatic Sea, where anchovy and sardine overwhelmingly dominate the pelagic component, which has a large impact on the food chain through the transfer of energy from the lowest to the highest trophic levels. As the small pelagic species represent the intermediate trophic level, and the Age and growth of early life stages of sardine, Sardina pilchardus, were investigated by microincrement counts on sagittal otoliths. Postlarval and juvenile specimens were collected in the coastal waters off Ortona (central Adriatic Sea) from December 1996 to May 1997. Otolith microstructure analysis was conducted on 286 specimens ranging from 30 to 68 mm TL. Age estimates ranged from 65 to 151 days. The precision of age estimates was tested by applying both the average percent error (APE) and the coefficient of variation (CV). The hatch date distribution, back-calculated from the date of capture, was spread over a long period lasting from September to March, with two main cohorts hatched in autumn (October) and winter (February), consistently with a long spawning season reported for this species. Applying the Gompertz growth model to the age-length data set, a growth curve was obtained for each cohort. The mean absolute daily growth rate was 0.33 mm day-1 and 0.22 mm day-1 for the autumn and winter cohorts, respectively. Otolith growth increment patterns was rather similar in the two cohorts, but they differed for the amplitude and timing of increment width deposition, being otoliths accurate proxies of larval fish growth rate. Strong seasonality of environmental features, such as water temperature and food resources, and endogenous factors linked to the larval ontogeny, largely contributed to affect the early life history stages of sardine.
The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis

Background Interferon (IFN) signature has been reported in definite systemic sclerosis (SSc) but it has not been characterised in early SSc (EaSSc). We aim at characterising IFN type I signature in SSc before overt skin fibrosis develops. Methods The expression of 11 IFN type I inducible genes was tested in whole-blood samples from 30 healthy controls (HCs), 12 subjects with primary Raynaud's phenomenon (RP), 19 patients with EaSSc, 7 patients with definite SSc without cutaneous fibrosis, 21 limited cutaneous SSc and 10 diffuse cutaneous SSc subjects. The correlation between IFN activity in monocytes, B cell activating factor (BAFF) mRNA expression and type III procollagen N-terminal propeptide (PIIINP) serum levels was tested. Results In all the SSc groups, higher IFN scores were observed compared with HC. An IFN score ≥7.09 discriminated HCs from patients with SSc (sensitivity=0.7, specificity=0.88, area under receiving operating characteristic (AUROC)=0.82); the prevalence of an elevated IFN score was: HC=3.3%; RP=33.3%, EaSSc=78.9%, definite SSc=100%, limited cutaneous SSc=42.9%, diffuse cutaneous SSc=70.0%. In monocytes an IFN score ≥4.12 distinguished HCs from patients with fibrotic SSc (sensitivity=0.62, specificity=0.85, AUROC=0.76). Compared with IFN-negative subjects, IFN-positive subjects had higher monocyte BAFF mRNA levels (19.7±5.2 vs 15.20±4.0, p=2.1×10−5) and serum PIIINP levels (median=6.0 (IQR 5.4–8.9) vs median=3.9 (IQR 3.3–4.7), p=0.0004). Conclusions An IFN type I signature is observed in patients with SSc from the earliest phases of the disease, even before overt skin fibrosis. The presence of IFN type I signature in monocytes is correlated with BAFF mRNA expression and serum PIIINP levels, supporting a contribution in the pathogenesis and progression of SSc.
Interstitial deletion del(10)(q25.2q25.3 approximately 26.11)--case report and review of the literature.

OBJECTIVES To present the clinical, cytogenetic, and molecular cytogenetic findings of prenatally diagnosed interstitial deletion 10q25.2-q26.1. The majority of distal 10q deletions are pure terminal deletions with breakpoints in 10q25 and 10q26. Only four patients have been described so far with interstitial deletions involving bands 10q25.2-q26.1. METHODS Postmortem physical examination and autopsy of the foetus after medically terminated pregnancy. GTG-banding, reverse painting, and FISH analysis with BAC clones on amniocyte metaphases were performed to determine the extent of the deletion. RESULTS At 20 weeks the eutrophic female foetus showed pronounced microretrogeny and hypertelorism, clubfeet as well as minor internal anomalies like pancreas anulare, atypically lobed liver, and missing choleocystis. Cardiac anomalies were not observed and the genitalia were of a normal female. The deletion encompasses 6-Mb and is associated with hemizygosity for 30 genes, including the genes for beta-tectorin, the beta-1 adrenergic receptor, and the alpha-2A adrenergic receptor. CONCLUSION An interstitial deletion del(10)(q25.2q25.3 approximately 26.11) was confirmed by FISH with mapped BAC clones. Clinical and molecular cytogenetic analyses of further interstitial 10q deletions are necessary to assess whether the phenotypic manifestations differ between deletions that are interstitial compared to those that include also the terminal region of chromosome 10.