Miracle-dz/UniFAR-FTUs huggingface dataset:
Human FasL Gene Is a Target of β-Catenin/T-Cell Factor Pathway and Complex FasL Haplotypes Alter Promoter Functions

FasL expression on human immune cells and cancer cells plays important roles in immune homeostasis and in cancer development. Our previous study suggests that polymorphisms in the FasL promoter can significantly affect the gene expression in human cells. In addition to the functional FasL SNP -844C>T (rs763110), three other SNPs (SNP -756A>G or rs2021837, SNP -478A>T or rs41309790, and SNP -205 C>G or rs74124371) exist in the proximal FasL promoter. In the current study, we established three major FasL hyplotypes in humans. Interestingly, a transcription motif search revealed that the FasL promoter possessed two consensus T-cell factor (TCF/LEF1) binding elements (TBEs), which is either polymorphic (SNP -205C>G) or close to the functional SNP -844C>T. Subsequently, we demonstrate that both FasL TBEs formed complexes with the TCF-4 and β-catenin transcription factors in vitro and in vivo. Co-transfection of LEF-1 and β-catenin transcription factors significantly increased FasL promoter activities, suggesting that FasL is a target gene of the β-catenin/T-cell factor pathway. More importantly, we found that the rare allele (-205G) of the polymorphic FasL TBE (SNP -205C>G) failed to bind the TCF-4 transcription factor and that SNP -205 C>G significantly affected the promoter activity. Furthermore, promoter reporter assays revealed that FasL SNP haplotypes influenced promoter activities in human colon cancer cells and in human T cells. Finally, β-catenin knockdown significantly decreased the FasL expression in human SW480 colon cancer cells. Collectively, our data suggest that β-catenin may be involved in FasL gene regulation and that FasL expression is influenced by FasL SNP haplotypes, which may have significant implications in immune response and tumorigenesis.
Novel Interaction Mechanism of a Domain Antibody-based Inhibitor of Human Vascular Endothelial Growth Factor with Greater Potency than Ranibizumab and Bevacizumab and Improved Capacity over Aflibercept*

A potent VEGF inhibitor with novel antibody architecture and antigen binding mode has been developed. The molecule, hereafter referred to as VEGF dual dAb (domain antibody), was evaluated in vitro for binding to VEGF and for potency in VEGF-driven models and compared with other anti-VEGF biologics that have been used in ocular anti-angiogenic therapeutic regimes. VEGF dual dAb is more potent than bevacizumab and ranibizumab for VEGF binding, inhibition of VEGF receptor binding assays (RBAs), and VEGF-driven in vitro models of angiogenesis and displays comparable inhibition to aflibercept (Eylea). VEGF dual dAb is dimeric, and each monomer contains two distinct anti-VEGF domain antibodies attached via linkers to a human IgG1 Fc domain. Mechanistically, the enhanced in vitro potency of VEGF dual dAb, in comparison to other anti-VEGF biologics, can be explained by increased binding stoichiometry. A consistent model of the target engagement has been built based on the x-ray complexes of each of the two isolated domain antibodies with the VEGF antigen.
Optimal Inflation for the U.S. Economy

This paper characterizes the optimal inflation rate in a standard macro model, which accounts for an occasionally-binding zero lower bound on nominal interest rates and model uncertainty. Estimates of the optimal rate of inflation, as measured by the PCE price index, range 0.7 to 1.4 percent per year. Even under extreme model uncertainty, the optimal inflation rate is not as high as previous studies suggest.
Genetic prediction of the effectiveness of biologics for psoriasis treatment

Anti‐tumor necrosis factor (TNF)‐α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome‐wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti‐TNF‐α therapy using Human Omni Express‐8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms (SNP) and changes in the Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNPs were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNPs, such as those in JAG2 and ADRA2A, that were associated with treatment responses to anti‐TNF‐α agents (strongest effect, P < 7.11E‐06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti‐TNF‐α treatment response, which merit further study. Of these, rs11096957 on TLR10, which is associated with increased TNF‐α production, was previously reported to be associated with treatment responses to TNF‐α inhibitors.
PROBING STELLAR ACCRETION WITH MID-INFRARED HYDROGEN LINES

In this paper we investigate the origin of the mid-infrared (IR) hydrogen recombination lines for a sample of 114 disks in different evolutionary stages (full, transitional, and debris disks) collected from the Spitzer archive. We focus on the two brighter H i lines observed in the Spitzer spectra, the H i (7–6) at 12.37 μm and the H i (9–7) at 11.32 μm. We detect the H i (7–6) line in 46 objects, and the H i (9–7) in 11. We compare these lines with the other most common gas line detected in Spitzer spectra, the [Ne ii] at 12.81 μm. We argue that it is unlikely that the H i emission originates from the photoevaporating upper surface layers of the disk, as has been found for the [Ne ii] lines toward low-accreting stars. Using the H i (9–7)/H i (7–6) line ratios we find these gas lines are likely probing gas with hydrogen column densities of 1010–1011 cm−3. The subsample of objects surrounded by full and transitional disks show a positive correlation between the accretion luminosity and the H i line luminosity. These two results suggest that the observed mid-IR H i lines trace gas accreting onto the star in the same way as other hydrogen recombination lines at shorter wavelengths. A pure chromospheric origin of these lines can be excluded for the vast majority of full and transitional disks. We report for the first time the detection of the H i (7–6) line in eight young (<20 Myr) debris disks. A pure chromospheric origin cannot be ruled out in these objects. If the H i (7–6) line traces accretion in these older systems, as in the case of full and transitional disks, the strength of the emission implies accretion rates lower than 10−10 M☉ yr−1. We discuss some advantages of extending accretion indicators to longer wavelengths, and the next steps required pinning down the origin of mid-IR hydrogen lines.
Effect of experimental jaw muscle pain on EMG activity and bite force distribution at different level of clenching.

Bite force at different levels of clenching and the corresponding electromyographic (EMG) activity in jaw-closing muscles were recorded in 16 healthy women before, during and after painful stimulation of the left masseter muscle. Experimental pain was induced by infusion of 5·8% hypertonic saline (HS), and 0·9% isotonic saline (IS) was infused as a control. EMG activity was recorded bilaterally from the masseter and temporalis muscles, and static bite force was assessed by pressure-sensitive films (Dental Pre-scale) at 5, 50 and 100% of maximal voluntary contraction (MVC) during each session. Visual feedback was applied by showing EMG activity to help the subject perform clenching at 5, 50 and 100% MVC, respectively. EMG activity at 100% MVC in left and right masseter decreased significantly during painful HS infusion (1·7-44·6%; P < 0·05). EMG activity at 5% and 50% MVC was decreased during HS infusion in the painful masseter muscle (4·8-18·6%; P < 0·05); however, EMG activity in the other muscles increased significantly (18·5-128·3%; P < 0·05). There was a significant increase in bite force in the molar regions at 50% MVC during HS infusion and in the post-infusion condition (P < 0·05). However, there were no significant differences in the distribution of forces at 100% MVC. In conclusion, experimental pain in the masseter muscle has an inhibitory effect on jaw muscle activity at maximal voluntary contraction, and compensatory mechanisms may influence the recruitment pattern at submaximal efforts.
Anti-Tumor Effects of Mfn2 in Gastric Cancer

Mitofusin-2 (Mfn2) is a mitochondrial outer membrane protein involved in mitochondrial fusion. Its mutation can cause Charcot-Marie-Tooth disease. Recent studies of Mfn2 in cancer research have not included gastric cancer. We confirmed that Mfn2 expression was lower in tumor tissue than in normal gastric mucosal tissue and that it was negatively correlated with tumor size, indicating an anti-tumor role for Mfn2. In vitro experiments showed that Mfn2 overexpression suppressed gastric cancer cell proliferation and colony formation, weakened the invasion and migratory ability of cancer cells by downregulating MMP-2 and MMP-9, halted the cell cycle and induced apoptosis. Western blotting indicated the likely involvement of P21 and PI3K/Akt signaling. Therefore, Mfn2 is a potential anti-tumor gene and a potential therapeutic target for treating gastric cancer. The progress of gastric cancer may be delayed by controlling Mfn2 expression.
Messenger RNAs in metaphase II oocytes correlate with successful embryo development to the blastocyst stage

Summary The mRNAs accumulated in oocytes provide support for embryo development until embryo genomic activation. We hypothesized that the maternal mRNA stock present in bovine oocytes is associated with embryo development until the blastocyst stage. To test our hypothesis, we analyzed the transcriptome of the oocyte and correlated the results with the embryo development. Our goal was to identify genes expressed in the oocyte that correlate with its ability to develop to the blastocyst stage. A fraction of oocyte cytoplasm was biopsied using micro-aspiration and stored for further expression analysis. Oocytes were activated chemically, cultured individually and classified according to their capacity to develop in vitro to the blastocyst stage. Microarray analysis was performed on mRNA extracted from the oocyte cytoplasm fractions and correlated with its ability to develop to the blastocyst stage (good quality oocyte) or arrest at the 8–16-cell stage (bad quality oocyte). The expression of 4320 annotated genes was detected in the fractions of cytoplasm that had been collected from oocytes matured in vitro. Gene ontology classification revealed that enriched gene expression of genes was associated with certain biological processes: ‘RNA processing’, ‘translation’ and ‘mRNA metabolic process’. Genes that are important to the molecular functions of ‘RNA binding’ and ‘translation factor activity, RNA binding’ were also enriched in oocytes. We identified 29 genes with differential expression between the two groups of oocytes compared (good versus bad quality). The content of mRNAs expressed in metaphase II oocytes influences the activation of the embryonic genome and enables further develop to the blastocyst stage.
Motivational Interviewing to Improve Diabetes Outcomes in African Americans Adults With Diabetes

The purpose of this study was to determine the effect of a motivational interviewing intervention (MII) on regimen adherence and diabetes markers among African Americans with diabetes. Sixty-two participants were assigned to the usual care (UC; n = 36) or MII (n = 26) groups. UC participants received the usual clinic care. MII participants received a maximum of six motivational interviewing (MI) sessions over 3 months. Outcome variables were obtained at baseline and 3-month follow-up. Data were obtained using medical records, self-reports, and glucose monitor and accelerometer print-outs. MII significantly increased the odds of participants adhering to recommended physical activity level (66.7% vs. 38.8%, odds ratio = 2.92, 95% confidence interval = [1.6, 14.3], p = .018) and significantly decreased glucose levels (p = .043) and body mass index (p = .046) over time when compared with UC. Findings support using MI as an intervention for improving health outcomes and regimen adherence rates among the study population.
Environmental drivers of zooplankton variability in the coastal eastern Adriatic (Mediterranean Sea)

The objectives of this paper were to determine the main environmental drivers of zooplankton variability in coastal waters adjacent to urban areas and to evaluate the differences in zooplankton abundance and population structure in relation to chemical and biological parameters in the water column. Samples were collected seasonally from May 2006 to January 2009 at 8 sampling sites in the bays and channels along the eastern Adriatic coast. Zooplankton population structure showed high similarity within the investigated region, especially evident in the homogeneity of copepod community composition, where relative importance of the individual species showed characteristic high ranking of small and medium-sized taxa. Zooplankton numerical variability primarily responded to seasonal variation in water temperature and spatial variation in salinity, but spatial distribution of the collected data showed that abundances were also linked to chemical and biological parameters generally used as descriptors of water quality. This indicates that zooplankton community size reflects the trophic status of an area and supports the use of zooplankton studies as an auxiliary method in the evaluation of the trophic state of coastal waters.
A Review of the Role of Anthropogenic Effects on Microorganisms in Soil

Anthropogenic activities are progressively releasing pollutants to the soil, including heavy metals and other pollutants emanating from industries and overpopulated human settlements. Pollution by heavy metals and other physicochemical materials is gradually becoming an area of concern, especially in sub-Saharan Africa. The paper reviews the effects of anthropogenic activities on soil ecosystem integrity including physicochemical parameters as well as biological parameters in the soil. The review focuses on impact of the application of fertilisers in soil and seasonal influence in levels of physicochemical parameters in soil ecosystem as well as microorganism population shifts in soils affected by pollution as a need to alleviate soil contamination. The review established gaps to further understanding of the relationship between soil physicochemical parameters, soil biological parameters and influence of seasonality in the resilience of the soil ecosystem as a way to foster the integrity of soil. Review Article Wanjala et al.; JAERI, 16(4): 1-16, 2018; Article no.JAERI. 44994 2
Down‐modulation of programmed death 1 alters regulatory T cells and promotes experimental autoimmune encephalomyelitis

The regulatory role of programmed death 1 (PD‐1) was investigated in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Typical EAE could be induced by immunization without pertussis toxin (PTX) in PD‐1‐null but not in wild‐type (WT) mice. However, both strains developed a similar EAE phenotype when immunized with PTX or by adoptive transfer of pathogenic T cells. In WT mice that did not develop EAE after immunization without PTX, the frequency of CD4+FoxP3+ Treg cells was boosted in the periphery but not in the thymus. This increase in Treg frequency was abrogated by PD‐1 deficiency or inclusion of PTX. In addition, PD‐1 expression was critical to in vitro conversion of naïve myelin‐specific CD4 T cells into Treg cells and was directly related to Treg suppressive activity. Finally, PD‐1 was markedly down‐modulated in the periphery of WT mice after administration of PTX. Therefore, down‐modulation of PD‐1 in Treg cells may abrogate Treg‐mediated immune suppression, permitting the activation of myelin‐reactive T cells and induction of EAE. © 2009 Wiley‐Liss, Inc.
Geodesic Convexity and Covariance Estimation

Geodesic convexity is a generalization of classical convexity which guarantees that all local minima of g-convex functions are globally optimal. We consider g-convex functions with positive definite matrix variables, and prove that Kronecker products, and logarithms of determinants are g-convex. We apply these results to two modern covariance estimation problems: robust estimation in scaled Gaussian distributions, and Kronecker structured models. Maximum likelihood estimation in these settings involves non-convex minimizations. We show that these problems are in fact g-convex. This leads to straight forward analysis, allows the use of standard optimization methods and paves the road to various extensions via additional g-convex regularization.
method single-strand-DNA-compatible and strand-specific ChIP-seq Mapping genomic hotspots of DNA damage by a Material Supplemental

Material Supplemental http://genome.cshlp. org/content/suppl/2013/01/23/gr.146357. 112.DC1. html P<P Published online December 17, 2012 in advance of the print journal. License Commons Creative . http://creativecommons.org/licenses/by-nc/3.0/ described at as a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), ). After six months, it is available under http://genome.cshlp. org/site/misc/terms.xhtml for the first six months after the full-issue publication date (see This article is distributed exclusively by Cold Spring Harbor Laboratory Press
Predicting the lithospheric stress field and plate motions by joint modeling of lithosphere and mantle dynamics

The way in which basal tractions, associated with mantle convection, couples with the lithosphere is a fundamental problem in geodynamics. A successful lithosphere‐mantle coupling model for the Earth will satisfy observations of plate motions, intraplate stresses, and the plate boundary zone deformation. We solve the depth integrated three‐dimensional force balance equations in a global finite element model that takes into account effects of both topography and shallow lithosphere structure as well as tractions originating from deeper mantle convection. The contribution from topography and lithosphere structure is estimated by calculating gravitational potential energy differences. The basal tractions are derived from a fully dynamic flow model with both radial and lateral viscosity variations. We simultaneously fit stresses and plate motions in order to delineate a best‐fit lithosphere‐mantle coupling model. We use both the World Stress Map and the Global Strain Rate Model to constrain the models. We find that a strongly coupled model with a stiff lithosphere and 3–4 orders of lateral viscosity variations in the lithosphere are best able to match the observational constraints. Our predicted deviatoric stresses, which are dominated by contribution from mantle tractions, range between 20–70 MPa. The best‐fitting coupled models predict strain rates that are consistent with observations. That is, the intraplate areas are nearly rigid whereas plate boundaries and some other continental deformation zones display high strain rates. Comparison of mantle tractions and surface velocities indicate that in most areas tractions are driving, although in a few regions, including western North America, tractions are resistive.
New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication

Background Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed. Methodology/Principal Findings Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect. Conclusions/Significance We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.
Campylobacter fetus subsp. jejuni as a cause of gastroenteritis in Jakarta, Indonesia

Campylobacter fetus subsp. jejuni was isolated from the feces of 15 out of 144 (10%) children (0 to 9 years old) and 4 out of 251 (2%) adults with gastroenteritis and was found together with another enteric pathogen in 2 of the children and in all 4 adults. It was isolated from 2 out of 7 (28%) children and 3 out of 160 (2%) adults with suspected typhoid fever. The bacterium was recovered from 3 out of 4 orphanage children with diarrhea and from 1 without symptoms and was isolated from only 1 child in a control group of 221 persons.
Roles of fission yeast tea1p in the localization of polarity factors and in organizing the microtubular cytoskeleton

The cylindrical shape of the fission yeast cell is generated by linear polarized growth from its cell ends. Using immunofluorescence and live imaging microscopy, we have investigated the roles of the cell end marker tea1p in generating linear polarized growth. We found that tea1p is primarily transported on plus ends of microtubules from the vicinity of the nucleus to the cell ends, and that its movement near the nucleus is independent of the kinesin tea2p. Deletion analysis identified a coiled-coil domain in tea1p essential for its retention at cell ends, and demonstrated that tea1p exerts different functions dependent on its location. On the tips of microtubules, tea1p prevents the curling of microtubules around the cell ends, whereas it is required for maintaining linear cell growth and for retention of polarity factors such as the Dyrk kinase pom1p, the CLIP170-like tip1p, and tea2p at the cell ends. We propose that tea1p has roles in organizing the microtubule cytoskeleton on the tips of microtubules, and in the retention of factors at the cell ends necessary for the cell to grow in a straight line.
Comparison of ablation zone between 915- and 2,450-MHz cooled-shaft microwave antenna: results in in vivo porcine livers.

OBJECTIVE The objective of our study was to compare the ablation zones of two cooled-shaft microwave antennae-one operating at 915 MHz and one operating at 2,450 MHz-in in vivo porcine livers. CONCLUSION The 915-MHz cooled-shaft microwave antenna can lead to deeper penetration of liver tissue and can yield a significantly larger ablation zone than the 2,450-MHz cooled-shaft antenna in in vivo porcine livers. In light of the result, 915-MHz cooled-shaft microwaves may be more effective for tumor ablation, especially for large tumors.