Miracle-dz/UniFAR-FTUs huggingface dataset:
The Coactivator PGC-1 Is Involved in the Regulation of the Liver Carnitine Palmitoyltransferase I Gene Expression by cAMP in Combination with HNF4α and cAMP-response Element-binding Protein (CREB)*

Liver carnitine palmitoyltransferase I catalyzes the transfer of long-chain fatty acids into mitochondria. L-CPT I is considered the rate-controlling enzyme in fatty acid oxidation. Expression of the L-CPT I gene is induced by starvation in response to glucagon secretion from the pancreas, an effect mediated by cAMP. Here, the molecular mechanisms underlying the induction of L-CPT I gene expression by cAMP were characterized. We demonstrate that the cAMP response unit of the L-CPT I gene is composed of a cAMP-response element motif and a DR1 sequence located 3 kb upstream of the transcription start site. Our data strongly suggest that the coactivator PGC-1 is involved in the regulation of this gene expression by cAMP in combination with HNF4α and cAMP-response element-binding protein (CREB). Indeed, (i) cotransfection of CREB or HNF4α dominant negative mutants completely abolishes the effect of cAMP on the L-CPT I promoter, and (ii) the cAMP-responsive unit binds HNF4α and CREB through the DR1 and the cAMP-response element sequences, respectively. Moreover, cotransfection of PGC-1 strongly activates the L-CPT I promoter through HNF4α bound at the DR1 element. Finally, we show that the transcriptional induction of the PGC-1 gene by glucagon through cAMP in hepatocytes precedes that of L-CPT-1. In addition to the key role that PGC-1 plays in glucose homeostasis, it may also be critical for lipid homeostasis. Taken together these observations suggest that PGC-1 acts to coordinate the process of metabolic adaptation in the liver.
Effects of High-Pressure Annealing on Random Telegraph Signal Noise Characteristic of Source Follower Block in CMOS Image Sensor

The effect of high-pressure deuterium (D) and hydrogen (H) annealing on random telegraph signal (RTS) noise characteristics of source follower (SF) block, SF, and row selector (SEL) transistors in CMOS image sensor (CIS) active pixel sensor (APS) was comparatively analyzed in depth. RTS noise characteristics of SF transistor (M1) and SEL transistor (M2) with forming gas (FG) annealing showed the smallest Δ<i>I</i><sub>D</sub>/<i>I</i><sub>D</sub>, whereas FG annealing was not efficient to reduce the RTS noise of SF block (M1 + M2). Although Δ<i>I</i><sub>D</sub>/<i>I</i><sub>D</sub> of SF block was reduced by high-pressure H<sub>2</sub> annealing, high-pressure D<sub>2</sub> annealing showed the greatest reduction in Δ<i>I</i><sub>D</sub>/<i>I</i><sub>D</sub> of SF block (M1 + M2), which was believed to attribute to the effective passivation of interface traps by the isotope effect of D. Therefore, high-pressure D<sub>2</sub> annealing is potentially significant for reducing RTS noise characteristics and thermal budget as well as improving device performance in CIS APS.
Mutual Coupling Reduction for High-Performance Densely Packed Patch Antenna Arrays on Finite Substrate

This paper reports on an effective mutual coupling suppression technique in which a metamaterial superstrate is placed in between the elements of densely packed microstrip phased array. Modified complementary split ring resonators are printed on the decoupling superstrate slab which caters for both surface and space wave effects. A detailed analysis of this proposed scheme is carried out on a low as well as on a high-permittivity substrate. Coupling suppression of 27 and 11 dB is achieved experimentally on the low- and high-permittivity substrates, respectively, with an element separation of λo/8. The design is compact and easy to realize and it removes drawback of poor front-to-back ratio previously reported in other decoupling techniques. In addition to high-coupling suppression, the decoupling slab can be added or removed in real time which makes this technique versatile for various applications having stringent performance requirements.
When do the aminotransferases rise after acute acetaminophen overdose?

Context. Rising aminotransferases (ATs) [either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are one of the first signs of hepatotoxicity following acetaminophen (APAP)] overdose (OD). However, the timing and speed of such rises are not well characterized, hampering early risk prediction. Objective. To describe the kinetics of AT release in acute APAP OD patients who develop hepatotoxicity despite treatment. Methods. A descriptive study of acute APAP OD patients with peak AT > 1,000 IU/L taken from the derivation subset of the Canadian Acetaminophen Overdose Study (CAOS), a large, multicenter retrospective cohort of patients hospitalized for APAP poisoning. Results. Of 2,488 hospital admissions for acute APAP OD, 94 met inclusion criteria. Treatment with acetylcysteine, mostly intravenously, was begun in all cases within 24 h of ingestion. The initial AT concentration was already elevated in most patients at presentation [median 211 (IQR 77–511) IU/L obtained at 15.3 (12.1–19.2) h postingestion], and exceeded 100 IU/L in almost all patients within 24 h of ingestion. Serum AT concentrations rose rapidly [doubling time 9.5 h (95% CI: 8.7–10.4 h)], especially in patients who developed AT > 1,000 IU/L within 48 h of ingestion. Coagulopathy was worse in these patients and in those with an AT > 250 IU/L during the first 12 h of treatment with acetylcysteine. Discussion and conclusions. An abnormal and rapidly doubling AT at presentation is more typical in severely poisoned patients, as judged by the effects on clotting. These data suggest that risk prediction instruments may be improved by incorporating both the serum AT concentration at initiation of antidotal therapy and its rate of change. Further studies using such an approach are warranted.
Transposable Elements in Fish Chromosomes: A Study in the Marine Cobia Species

Rachycentron canadum, a unique representative of the Rachycentridae family, has been the subject of considerable biotechnological interest due to its potential use in marine fish farming. This species has undergone extensive research concerning the location of genes and multigene families on its chromosomes. Although most of the genome of some organisms is composed of repeated DNA sequences, aspects of the origin and dispersion of these elements are still largely unknown. The physical mapping of repetitive sequences on the chromosomes of R. canadum proved to be relevant for evolutionary and applied purposes. Therefore, here, we present the mapping by fluorescence in situ hybridization of the transposable element (TE) Tol2, the non-LTR retrotransposons Rex1 and Rex3, together with the 18S and 5S rRNA genes in the chromosome of this species. The Tol2 TE, belonging to the family of hAT transposons, is homogeneously distributed in the euchromatic regions of the chromosomes but with huge colocalization with the 18S rDNA sites. The hybridization signals for Rex1 and Rex3 revealed a semi-arbitrary distribution pattern, presenting differentiated dispersion in euchromatic and heterochromatic regions. Rex1 elements are associated preferentially in heterochromatic regions, while Rex3 shows a scarce distribution in the euchromatic regions of the chromosomes. The colocalization of TEs with 18S and 5S rDNA revealed complex chromosomal regions of repetitive sequences. In addition, the nonpreferential distribution of Rex1 and Rex3 in all heterochromatic regions, as well as the preferential distribution of the Tol2 transposon associated with 18S rDNA sequences, reveals a distinct pattern of organization of TEs in the genome of this species. A heterogeneous chromosomal colonization of TEs may confer different evolutionary rates to the heterochromatic regions of this species.
Immunoproteasome Subunit LMP7 Deficiency and Inhibition Suppresses Th1 and Th17 but Enhances Regulatory T Cell Differentiation

The immunoproteasome generates peptides presented on MHC class I molecules to cytotoxic T cells. ONX 0914 (formerly called PR-957) is a selective inhibitor of the immunoproteasome subunit low molecular mass polypeptide (LMP) 7 (β5i) that attenuates disease progression in mouse models of diabetes, colitis, and arthritis. The aim of this study was to investigate the effect of LMP7-specific inhibition on major Th cell differentiation pathways involved in the progression of autoimmune diseases in vitro and in vivo. We used ONX 0914-treated wild-type CD4+ T cells and also LMP7−/− CD4+ T cells under different Th cell-polarizing conditions, focusing on the effector cytokines and transcription factors involved, and compared them with wild-type CD4+ T cells. Mouse models of dextran sodium sulfate-induced colitis and a T cell transfer model of colitis were used for in vivo assessment. Deletion or inhibition of LMP7 suppressed generation of Th17 but promoted regulatory T cell (Treg) development. In developing Th17 cells, immunoproteasome inhibition blocked phosphorylation of STAT3, whereas in Tregs, SMAD phosphorylation was enhanced. Additionally, LMP7 inhibition led to reduced STAT1 phosphorylation and Th1 differentiation. These findings were confirmed in vivo as LMP7 inhibition or deficiency resulted in reduced Th1 and Th17 expansion while promoting Treg development in dextran sodium sulfate-induced colitis. Also, in a T cell-dependent transfer model of colitis, LMP7-specific inhibition led to reduced Th1 and Th17 differentiation in vivo. LMP7 governs Th cell lineage determination by affecting the balance of receptor proximal signals during differentiation. These data render LMP7 a promising drug target for the treatment of autoimmune diseases.
Influence of ozone-limonene reactions on perceived air quality.

UNLABELLED This study conducted short-term assessments of perceived air quality (PAQ) for six different realistic concentrations of ozone and limonene, separately or together, in room air. The impact of filtration and the influence of the ozone generation method were also examined. The evaluations were made in four identical 40 m3 low-polluting test offices ventilated at 1.4 h(-1) or in two identical 30 m3 stainless-steel chambers ventilated at 1.9 h(-1). Concentrations of ozone, total volatile organic compounds and size-fractionated particles were continuously monitored in each experiment. The results indicate that, for each of the six conditions, the PAQ was poorer when ozone and limonene were present together compared with when only ozone or only limonene was present. In the test offices a correlation was observed between the number of secondary organic aerosols produced by a given ozone/limonene condition and the sensory pollution load for that condition. The particles themselves do not appear to be the primary causative agents, but instead are co-varying surrogates for sensory offending gas-phase species. PRACTICAL IMPLICATIONS Although the health consequences of long-term exposures to the products of ozone-initiated indoor chemistry remain to be determined, we judge that the sensory offending nature of selected products provides an additional reason to limit indoor ozone levels. Devices that emit ozone at significant rates should not be used indoors. Ozone-filtration of make-up air should also be beneficial in mechanically ventilated buildings located in regions that repeatedly violate outdoor ozone standards. Additionally, the use of limonene containing products should be curtailed during periods when indoor ozone levels are elevated.
Nonlinear Effects of the Transport Costs on the Wage Inequality

This paper examines how transport costs affect wage inequality. Goods produced by the unskilled must pay higher transport costs because they have low market values. Reduction in transportation cost changes the relative wage. At first, only the skilled gains from the transportation improvement. Then the unskilled also gains from international trade. Therefore, transportation development causes Kuznets curve.
Biochemical Characterization of Human GMP Synthetase (*)

GMP synthetase (EC 6.3.5.2) plays a key role in the de novo synthesis of guanine nucleotides. It is a potential target for immunosuppressive therapy. Recently, the human enzyme was purified to homogeneity (Hirst, M., Haliday, E., Nakamura, J., and Lou, L.(1994) J. Biol. Chem. 269, 23830-23837). We now report the characterization of this enzyme in terms of its biochemical and kinetic properties. We found that there are distinct features of the human enzyme that has not been reported for GMP synthetase from other sources. There are two variant forms of human GMP synthetase. Their catalytic properties are very similar, although their isoelectric points are different. They most likely represent posttranslational modification variants. Magnesium ion is required for enzyme activity, and the requirement is beyond levels needed for ATP chelation. Magnesium appears to be an essential activator and there may be more than one binding site. Interaction of GMP synthetase with xanthosine 5′-monophosphate (XMP), a substrate, exhibits sigmoidal kinetics with a Hill coefficient of 1.48 ± 0.07. This positive cooperativity is not due to ligand-induced oligomerization, since GMP synthetase remains a monomer in the presence of XMP and other substrates. Decoyinine, a selective inhibitor of GMP synthetase, inhibits the human enzyme reversibly with uncompetitive inhibition kinetics toward glutamine and XMP and noncompetitive kinetics toward ATP.
SPOC-based University Course Instruction Reform Path

MOOC is a hot topic in online education research. However, MOOC has less application in school education. Only when MOOC is applied into school education can MOOC be filled with strong and vigorous vitality, and promote the reform and development of teaching situations, teaching models and assessment methods in school education Because of the poor teaching control in MOOC, SPOC is utilized to achieve better teaching controllability by the combination with the classroom and credits. In order to play the advantages of SPOC fully, this paper presents a SPOC-based teaching reform path for university course , which is described in every step, and then describes the practical application case and application result. The results shows that this reform path can integrate the SPOC and university course deeply, and can guide the construction of university course based on SPOC.
Acute and Chronic Efficacy of Bumetanide in an in vitro Model of Posttraumatic Epileptogenesis

Seizures triggered by acute injuries to the developing brain respond poorly to first‐line medications that target the inhibitory chloride‐permeable GABAA receptor. Neuronal injury is associated with profound increases in cytoplasmic chloride ([Cl−]i) resulting in depolarizing GABA signaling, higher seizure propensity and limited efficacy of GABAergic anticonvulsants. The Na+‐K+‐2Cl− (NKCC1) cotransporter blocker bumetanide reduces [Cl−]i and causes more negative GABA equilibrium potential in injured neurons. We therefore tested both the acute and chronic efficacy of bumetanide on early posttraumatic ictal‐like epileptiform discharges and epileptogenesis.
Sustainable Reserve Power From Demand Response and Fluctuating Production—Two Danish Demonstrations

The Danish grid is moving from a system based on centralized fossil-fueled power plants to a system based on renewable energy where wind is a major energy source. This raises a number of challenges. A main challenge is that the centralized power plants currently are the main providers of reserve power. Alternative sources of flexibility are consequently needed as the conventional power plants are being replaced with fluctuating renewable energy sources. In this paper, we present results from two key demonstrations which illustrate that alternative sources of flexibility exist and that this flexibility can be utilized for reserve power. In the first demonstration, a portfolio of inhabited households heated with heat pumps are remotely monitored and controlled such that the aggregate consumption follows a power reference. This experiment is conducted over a full week where an hourly power reference is tracked while the comfort of the inhabitants is ensured. In the second demonstration, an operational wind power plant is regulated to provide a system-stabilizing response. This experiment is conduced over a 2-h period where the wind power plant follows a 5-min power reference. Together, the two demonstrations illustrate that both consumption and fluctuating production can contribute as sources of reserve power and a sustainable alternative to conventional fossil-fueled power plants in the future grid.
Identification of PLOD2 as Telopeptide Lysyl Hydroxylase, an Important Enzyme in Fibrosis*

The hallmark of fibrotic processes is an excessive accumulation of collagen. The deposited collagen shows an increase in pyridinoline cross-links, which are derived from hydroxylated lysine residues within the telopeptides. This change in cross-linking is related to irreversible accumulation of collagen in fibrotic tissues. The increase in pyridinoline cross-links is likely to be the result of increased activity of the enzyme responsible for the hydroxylation of the telopeptides (telopeptide lysyl hydroxylase, or TLH). Although the existence of TLH has been postulated, the gene encoding TLH has not been identified. By analyzing the genetic defect of Bruck syndrome, which is characterized by a pyridinoline deficiency in bone collagen, we found two missense mutations in exon 17 of PLOD2, thereby identifying PLOD2 as a putative TLH gene. Subsequently, we investigated fibroblasts derived from fibrotic skin of systemic sclerosis (SSc) patients and found that PLOD2 mRNA is highly increased indeed. Furthermore, increased pyridinoline cross-link levels were found in the matrix deposited by SSc fibroblasts, demonstrating a clear link between mRNA levels of the putative TLH gene (PLOD2) and the hydroxylation of lysine residues within the telopeptides. These data underscore the significance of PLOD2 in fibrotic processes.
Stimulation of Ca2+ release-activated Ca2+ channels as a potential mechanism involved in non-genomic 1,25(OH)2-vitamin D3-induced Ca2+ entry in skeletal muscle cells.

As in other vitamin D target cells, activation of voltage-dependent Ca2+ channels (VDCC) mediates the fast, non-genomic, 1,25(OH)2D3 stimulation of Ca2+ influx in skeletal muscle cells (SMC). 1,25(OH)2D3 has also been shown to rapidly induce the release of Ins(1,4,5)P3 in SMC. Experiments were performed to investigate whether Ca2+ release-activated Ca2+ channels (CRAC) also participate in the mechanism by which 1,25(OH)2D3 regulates Ca2+ entry into these cells. In cultured chick SMC loaded with Fura-2/AM the hormone (10(-12) - 10(-8) M) induced a rapid (30 sec) followed by a sustained (up to 5 min) increase in intracellular Ca2+ concentration ([Ca2+]i) associated to Ca2+ mobilization from internal stores and influx of extracellular Ca2+, respectively. Thus, the initial, transient, 1,25(OH)2D3-dependent increment in [Ca2+]i could be observed in Ca2+-free medium and was abolished by the PLC inhibitor U73122. Readdition of Ca2+ to cells that had undergone the initial 1,25(OH)2D3-induced [Ca2+]i rise in Ca2+ free medium resulted in a fast increment in [Ca2+]i indicating the existence of a hormone-activated CRAC entry pathway. The sustained phase of the Ca2+ response to 1,25(OH)2D3 was only partially (60%) suppressed by nifedipine, whereas lanthanum (10 microM) completely abolished the hormone effects. Accordingly, depletion of intracellular Ca2+ stores by thapsigargin reproduced 1,25(OH)2D3-induced Ca2+ influx, inhibiting any further response to the sterol. 1,25(OH)2D3 increased the rate of quenching of Fura-2 fluorescence by Mn2+, indicating activation of Mn2+ permeable channels. Altogether, these results provide the first evidence involving CRAC channels in the rapid modulation of Ca2+ entry in animal cells by 1,25(OH)2D3.
Rift valley Fever in Kruger national park: do buffalo play a role in the inter-epidemic circulation of virus?

Rift Valley fever (RVF) is a zoonotic mosquito-borne virus disease of livestock and wild ruminants that has been identified as a risk for international spread. Typically, the disease occurs in geographically limited outbreaks associated with high rainfall events and can cause massive losses of livestock. It is unclear how RVF virus persists during inter-epidemic periods but cryptic cycling of the virus in wildlife populations may play a role. We investigated the role that free-living African buffalo (Syncerus caffer caffer) might play in inter-epidemic circulation of the virus and looked for geographic, age and sex patterns of Rift Valley fever virus (RVFV) infection in African buffalo. Buffalo serum samples were collected (n = 1615) in Kruger National Park (KNP), South Africa, during a period of 1996-2007 and tested for antibodies to RVF. We found that older animals were more likely to be seropositive for anti-RVFV antibody than younger animals, but sex was not correlated with the likelihood of being anti-RVFV antibody positive. We also found geographic variation within KNP; herds in the south were more likely to have acquired anti-RVFV antibody than herds farther north - which could be driven by host or vector ecology. In all years of the study between 1996 and 2007, we found young buffalo (under 2 years of age) that were seropositive for anti-RVFV antibody, with prevalence ranging between 0 and 27% each year, indicating probable circulation. In addition, we also conducted a 4-year longitudinal study on 227 initially RVFV seronegative buffalo to look for evidence of seroconversion outside known RVF outbreaks within our study period (2008-2012). In the longitudinal study, we found five individuals that seroconverted from anti-RVFV antibody negative to anti-RVFV antibody positive, outside of any detected outbreak. Overall, our results provide evidence of long-term undetected circulation of RVFV in the buffalo population.
Characterization of the R572T Point Mutant of a Putative Cleavage Site in Human Foamy Virus Env

ABSTRACT A putative cleavage site of the human foamy virus (HFV) envelope glycoprotein (Env) was altered. Transient env expression revealed that the R572T mutant Env was normally expressed and modified by asparagine-linked oligosaccharide chains. However, this single-amino-acid substitution was sufficient to abolish all detectable cleavage of the gp130 precursor polyprotein. Cell surface biotinylation demonstrated that the uncleaved mutant gp130 was transported to the plasma membrane. The uncleaved mutant protein was incapable of syncytium formation. Glycoprotein-driven virion budding, a unique aspect of HFV assembly, occurred despite the absence of Env cleavage. We then substituted the R572T mutant env into a replication-competent HFV molecular clone. Transfection of the mutant viral DNA into BHK-21 cells followed by viral titration with the FAB (foamy virus-activated β-galactosidase expression) assay revealed that proteolysis of the HFV Env was essential for viral infectivity. Wild-type HFV Env partially complemented the defective virus phenotype. Taken together, these experimental results established the location of the HFV Env proteolytic site; the effects of cleavage on Env transport, processing, and function; and the importance of Env proteolysis for virus maturation and infectivity.