Either FOXO1 or HBP1 transcription factor is a downstream effector of the PI3K/Akt pathway and associated with tumorigenesis. However, the relationship between FOXO1 and HBP1 in oral cancer remains ...unclear. Analysis of 30 oral tumor specimens revealed that mean mRNA levels of both FOXO1 and HBP1 in non-invasive and invasive oral tumors were found to be significantly lower than that of the control tissues, and the status of low FOXO1 and HBP1 (< 0.3 fold of the control) was associated with invasiveness of oral tumors. To investigate if HBP1 is a direct transcription target of FOXO1, we searched potential FOXO1 binding sites in the HBP1 promoter using the MAPPER Search Engine, and two putative FOXO1 binding sites located in the HBP1 promoter -132 to -125 bp and -343 to -336 bp were predicted. These binding sites were then confirmed by both reporter gene assays and the in cellulo ChIP assay. In addition, Akt activity manipulated by PI3K inhibitor LY294002 or Akt mutants was shown to negatively affect FOXO1-mediated HBP1 promoter activation and gene expression. Last, the biological significance of the FOXO1-HBP1 axis in oral cancer malignancy was evaluated in cell growth, colony formation, and invasiveness. The results indicated that HBP1 knockdown potently promoted malignant phenotypes of oral cancer and the suppressive effect of FOXO1 on cell growth, colony formation, and invasion was alleviated upon HBP1 knockdown in invasive oral cancer cells. Taken together, our data provide evidence for HBP1 as a direct downstream target of FOXO1 in oral cancer malignancy.
Human sulfotransferase 2A1 (SULT2A1) is a member of the hydroxysteroid sulfotransferase (SULT2) family that mediates sulfo-conjugation of a variety of endogenous molecules including ...dehydroepiandrosterone (DHEA) and bile acids. In this study, we have constructed a stable cell line expressing SULT2A1 by transfection into HEK293 cells. The expression system was used to characterize and compare the sulfation kinetics of DHEA and 15 human bile acids by SULT2A1.
Formation of DHEA sulfate demonstrated Michaelis-Menten kinetics with apparent Km and Vmax values of 3.8 μM and 130.8 pmol min−1 mg−1 protein, respectively. Sulfation kinetics of bile acids also demonstrated Michaelis-Menten kinetics with a marked variation in apparent Km and Vmax values between individual bile acids.
Sulfation affinity was inversely proportional to the number of hydroxyl groups of bile acids. The monohydroxy- and most toxic bile acid (lithocholic acid) had the highest affinity, whereas the trihydroxy- and least toxic bile acid (cholic acid) had the lowest affinity to sulfation by SULT2A1. Intrinsic clearance (CLint) of ursodeoxycholic acid (UDCA) was approximately 1.5- and 9.0-fold higher than that of deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA), respectively, despite the fact that all three are dihydroxy bile acids.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Step-by-step, time-consuming scanning of the sample is still the state-of-the-art in imaging Raman spectroscopy. Even for a few 100 image points the measurement time may add up to minutes or hours. A ...radical decrease in measurement time can be achieved by applying multiplex spectrographs coupled to imaging fiber bundles that are successfully used in astronomy. For optimal use of the scarce and expensive observation time at astronomical observatories, special high-performance spectrograph systems were developed. They are designed for recording thousands of spatially resolved spectra of a two-dimensional image field within one single exposure. Transferring this technology to imaging Raman spectroscopy allows a considerably faster acquisition of chemical maps. Currently, an imaging field of up to 1 cm2 can be investigated. For porcine skin the required measurement time is less than 1 min. For this reason, this technique is of particular interest for medical diagnostics, e.g., the identification of potentially cancerous abnormalities of skin tissue.
We review recent advances and results in enhancing and developing helioseismic analysis methods and in solar data assimilation. In the first part of this paper we will focus on selected developments ...in time-distance and global helioseismology. In the second part, we review the application of data assimilation methods on solar data. Relating solar surface observations as well as helioseismic proxies with solar dynamo models by means of the techniques from data assimilation is a promising new approach to explore and to predict the magnetic activity cycle of the Sun.
How are visual scenes encoded in local neural networks of visual cortex? In rodents, visual cortex lacks a columnar organization so that processing of diverse features from a spot in visual space ...could be performed locally by populations of neighboring neurons. To examine how complex visual scenes are represented by local microcircuits in mouse visual cortex we measured visually evoked responses of layer 2/3 neuronal populations using 3D two-photon calcium imaging. Both natural and artificial movie scenes (10 seconds duration) evoked distributed and sparsely organized responses in local populations of 70-150 neurons within the sampled volumes. About 50% of neurons showed calcium transients during visual scene presentation, of which about half displayed reliable temporal activation patterns. The majority of the reliably responding neurons were activated primarily by one of the four visual scenes applied. Consequently, single-neurons performed poorly in decoding, which visual scene had been presented. In contrast, high levels of decoding performance (>80%) were reached when considering population responses, requiring about 80 randomly picked cells or 20 reliable responders. Furthermore, reliable responding neurons tended to have neighbors sharing the same stimulus preference. Because of this local redundancy, it was beneficial for efficient scene decoding to read out activity from spatially distributed rather than locally clustered neurons. Our results suggest a population code in layer 2/3 of visual cortex, where the visual environment is dynamically represented in the activation of distinct functional sub-networks.
Summary
The traditional view of the pathophysiology of asthma is that its characteristic features are secondary to a major allergic or immunological dysfunction. However, this does not explain ...intrinsic asthma, which can occur in the absence of atopy. An alternative view is that an abnormality in the airway smooth muscle cell, which is capable of producing inflammatory, immunological and growth factors as well as molecules, which facilitate interaction with inflammatory cells, is the primary or instigating event. Evidence is rapidly accumulating that the smooth muscle is abnormal, in that it proliferates faster, produces more chemokines and cytokines as well as a different profile of extracellular matrix proteins than its non‐asthmatic counterpart. These abnormalities may arise from altered calcium homoeostasis leading to increased mitochondrial biogenesis and/or decreases in the levels of key transcription factors such as CCAAT enhancer binding protein−α. Conditions under which smooth muscle is ablated, such as bronchial thermoplasty, may help us to understand more about the contribution of an airway smooth muscle dysfunction to asthma aetiology.
Adenylyl cyclases (ACs) are a family of effector molecules for G-protein-coupled receptors. The 2 ACs most abundantly expressed in cardiac myocytes are types 5 (AC5) and 6 (AC6), which have 65% amino ...acid homology. It has been speculated that coexpression of 2 AC types in cardiac myocytes represents redundancy, but the specific role of AC6 in cardiac physiology and its differences from AC5 remain to be defined.
We generated transgenic mice with targeted deletion of AC6. Deletion of AC6 was associated with reduced left ventricular contractile function (P=0.026) and relaxation (P=0.041). The absence of AC6 was associated with a 48% decay in beta-adrenergic receptor-stimulated cAMP production in cardiac myocytes (P=0.003) and reduced protein kinase A activity (P=0.015). In addition, phospholamban phosphorylation was reduced (P=0.015), sarcoplasmic reticulum Ca2+-ATPase activity was impaired (P<0.0001), and cardiac myocytes showed marked abnormalities in calcium transient formation (P=0.001).
The combination of impaired cardiac cAMP generation and calcium handling that result from AC6 deletion underlies abnormalities in left ventricular function. The biochemical and physiological consequences of AC6 deletion reveal it to be an important effector molecule in the adult heart, serving unique biological functions not replicated by AC5.
A new variable-rate coding technique is presented for two-dimensional (2-D) constraints. For certain constraints, such as the (0, 2) -runlength-limited (RLL) and (3,¿) -RLL constraints, the technique ...is shown to improve on previously published lower bounds on the capacity of the constraint.
The Ge–Sb binary system has been thermodynamically assessed using the CALPHAD method based on the available experimental information from the published literature. The solution phases, including ...liquid, fcc_A1(Au), diamond_A4(Ge) and rhombohedral_A7(Sb), were modeled as substitutional solutions, of which the excess Gibbs energies were expressed by a Redlich–Kister polynomial. The intermetallic compound AuSb
2 was assumed to have no ternary solubility because of the lack of experimental information. Combined with previous assessments of the Au–Ge and Au–Sb binary systems, the thermodynamic description of the Au–Ge–Sb ternary system has been performed. The liquidus projection and several vertical sections of this ternary system have been calculated, which are in reasonable agreement with the reported experimental data.
The two-temperature, 2D hydrodynamic code Hydro–ELectro–IOnization–2–Dimensional (HELIO2D), which takes into account self-consistently the laser energy absorption in a target, ionization, heating, ...and expansion of the created plasma is elaborated. The wide-range two-temperature equation of state is developed and used to model the metal target dynamics from room temperature to the conditions of weakly coupled plasma. The simulation results are compared and demonstrated a good agreement with experimental data on the Mg target being heated by laser pulses of the nanosecond high-energy laser for heavy ion experiments (NHELIX) at Gesellschaft fur Schwerionenforschung. The importance of using realistic models of matter properties is demonstrated.
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