Highlights • The VSOR anion channel is expressed in all types of cells in the CNS. • The channel produces a major anion flux during cell volume regulation. • The channel is permeable not only to Cl− ...ions but also to amino acids. • Here we review and discuss the characteristics and roles of the channel in the CNS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Blue light irradiation of aryldiazoacetates leads to the formation of free carbenes, which can react with carbazoles, pyrazoles and 1,2,3‐triazoles to afford the corresponding N−H inserted products. ...These reactions are performed under air and at room temperature, allowing the mild preparation of a variety of motifs found in biologically relevant targets.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although we have obtained comprehensive catalogs of genetic risk loci that are linked to human diseases, little is known regarding how to devise a systematic strategy to integrate genetic study ...results with diverse biological resources. Such strategies will be crucial for providing novel insights into disease biology and for aiding drug discovery as an ultimate goal. Here we describe the current progress in this field using a pioneering example of large‐scale genetic association studies on rheumatoid arthritis (RA), an autoimmune disease characterized by inflammation and destruction of joints. Through functional and bioinformatic annotations of risk single nucleotide polymorphisms (SNPs) and genes from >100 RA risk loci identified by genome‐wide association study (GWAS) meta‐analysis, we found novel biological insights into RA pathogenicity. Further, by integrating RA genetic findings with the complete catalog of approved drugs for RA and other diseases, we provide empirical data to indicate that human genetic‐based approaches may be useful for supporting ‘genetics‐driven genomic drug discovery’ efforts in complex human traits and suggest that further development of integrative approaches should be undertaken.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Two new visible-light-mediated strategies are described starting from aryldiazoacetates. The first approach describes their reaction with azides to afford the corresponding imines, and then reaction ...with aryldiazoketones produces alkyl 2-carboxylate-2,3,3-trisubstituted β-lactams. The second approach describes the reaction with sulfoxides to afford the corresponding sulfoxonium ylides, followed by reaction with aryldiazoketones to produce 5-alkoxy-2,2,4-trisubstituted furan-3(2H)-ones. These protocols take advantage of the photolysis of aryldiazoacetates and the photochemically promoted Wolff rearrangement of aryldiazoketones.
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IJS, KILJ, NUK, PNG, UL, UM
Aims. We observationally investigate the relation between the photoelectric heating efficiency in photodissociation regions (PDRs) and the charge of polycyclic aromatic hydrocarbons (PAHs), which are ...considered to play a key role in photoelectric heating. Methods. Using PACS onboard Herschel, we observed six PDRs spanning a wide range of far-ultraviolet radiation fields (G0 = 100−105). To measure the photoelectric heating efficiency, we obtained the intensities of the main cooling lines in these PDRs, i.e., the O i 63 μm, 145 μm, and C ii 158 μm, as well as the far-infrared (FIR) continuum intensity. We used Spitzer/IRS spectroscopic mapping observations to investigate the mid-infrared (MIR; 5.5−14 μm) PAH features in the same regions. We decomposed the MIR PAH emission into that of neutral (PAH0) and positively ionized (PAH+) species to derive the fraction of the positively charged PAHs in each region, and compare it to the photoelectric heating efficiency. Results. The heating efficiency traced by (O i 63 μm + O i 145 μm + C ii 158 μm)/TIR, where TIR is the total infrared flux, ranges between 0.1% and 0.9% in different sources, and the fraction of PAH+ relative to (PAH0+ PAH+) spans from 0 (+11)% to 87 (±10)%. All positions with a high PAH+ fraction show a low heating efficiency, and all positions with a high heating efficiency have a low PAH+ fraction, supporting the scenario in which a positive grain charge results in a decreased heating efficiency. Theoretical estimates of the photoelectric heating efficiency show a stronger dependence on the charging parameter γ = G0T1/2/ne than the observed efficiency reported in this study, and the discrepancy is significant at low γ. The photoelectric heating efficiency on PAHs, traced by (O i 63 μm + O i 145 μm + C ii 158 μm)/(PAH-band emission + O i 63 μm + O i 145 μm + C ii 158 μm), shows a much better match between the observations and the theoretical estimates. Conclusions. The good agreement of the photoelectric heating efficiency on PAHs with a theoretical model indicates the dominant contribution of PAHs to the photoelectric heating. This study demonstrates the fundamental role that PAHs have in photoelectric heating. More studies of their charging behavior are crucial to understand the thermal balance of the interstellar medium.
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FMFMET, NUK, UL, UM, UPUK
Intra-articular injection of hyaluronan (HA) has been suggested to have a disease-modifying effect in osteoarthritis, but little is known about the possible mechanisms.
To investigate the effects of ...HA species of different molecular mass, including 800 kDa (HA800) and 2700 kDa (HA2700), on the expression of aggrecanases (ie, ADAMTS species), which play a key role in aggrecan degradation.
The effects of HA species on the expression of ADAMTS1, 4, 5, 8, 9 and 15 in interleukin 1alpha (IL1alpha)-stimulated osteoarthritic chondrocytes were studied by reverse transcription PCR and real-time PCR. Expression of ADAMTS4 protein and aggrecanase activity and signal transduction pathways of IL1, CD44 and intracellular adhesion molecule 1 (ICAM1) were examined by immunoblotting.
IL1alpha treatment of chondrocytes induced ADAMTS4, and HA800 and HA2700 significantly decreased IL1alpha-induced expression of ADAMTS4 mRNA and protein. IL1alpha-stimulated aggrecanase activity in osteoarthritic chondrocytes was reduced by treatment with HA2700 or transfection of small interfering RNA for ADAMTS4. A similar result was obtained when HA2700 was added to explant cultures of osteoarthritic cartilage. HA2700 neither directly inhibited nor bound to ADAMTS4. Downregulation of ADAMTS4 expression by HA2700 was attenuated by treatment of IL1alpha-treated chondrocytes with antibodies to CD44 and/or ICAM1. The increased phosphorylation of IL1 receptor-associated kinase-1 and extracellular signal-regulated protein kinase1/2 induced by the IL1alpha treatment was downregulated by enhanced IRAK-M expression after HA2700 treatment.
These data suggest that HA2700 suppresses aggrecan degradation by downregulating IL1alpha-induced ADAMTS4 expression through the CD44 and ICAM1 signalling pathways in osteoarthritic chondrocytes.
A 50-layer stacked InGaAs/GaAs quantum dot solar cell (QDSC) grown on GaAs (100) with a self-organized texture formed on its backside has been fabricated in aim for enhancing the photoabsorption by ...the QD layers. Since doped GaAs substrate has a large free-carrier absorption, a semi-insulating substrate was used for fabricating the QDSC with backside texture. A micrometer-scale texture was formed by a simple wet-etching in a NH4OH solution. The light scattering at the textured backside surface caused a light trapping effect and resulted in an increased effective optical path length by multiple reflection inside QDSC, and this effect was confirmed by the external quantum efficiency (EQE) measurement. The photoabsorption attributed to InGaAs QD layers increased by about 2.4 times compared to QDSC without a textured backside. As a result, the short-circuit current density (Jsc) measured at an air-mass 1.5 global (AM1.5G) spectrum illumination increased from Jsc = 20.9 to 21.5 mA/cm2.
•50-layer InGaAs/GaAs QD solar cell with a self-organized texture on its backside.•Total QD density of 2 × 1012/cm2 was achieved after 50 layer stacks.•Photoabsorption in InGaAs QD layers increased by 2.4 times with light trapping.•Jsc increased from 20.9 to 21.5 mA/cm2 under AM1.5G.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
We present new
13
CO (1−0), C
18
O (1−0), HCO
+
(1−0), and H
13
CO
+
(1−0) maps from the IRAM 30 m telescope and a spectrally resolved C
ii
158
μ
m map observed with the SOFIA telescope ...toward the massive DR21 cloud. This traces the kinematics from low- to high-density gas in the cloud, which allows us to constrain the formation scenario of the high-mass star-forming DR21 ridge. The molecular line data reveal that the subfilaments are systematically redshifted relative to the dense ridge. We demonstrate that C
ii
unveils the surrounding CO-poor gas of the dense filaments in the DR21 cloud. We also show that this surrounding gas is organized in a flattened cloud with curved redshifted dynamics perpendicular to the ridge. The subfilaments thus form in this curved and flattened mass reservoir. A virial analysis of the different lines indicates that self-gravity should drive the evolution of the ridge and surrounding cloud. Combining all results, we propose that bending of the magnetic field, due to the interaction with a mostly atomic colliding cloud, explains the velocity field and resulting mass accretion on the ridge. This is remarkably similar to what was found for at least two nearby low-mass filaments. We tentatively propose that this scenario might be a widespread mechanism to initiate star formation in the Milky Way. However, in contrast to low-mass clouds, gravitational collapse plays a role on the parsec scale of the DR21 ridge because of the higher density. This allows more effective mass collection at the centers of collapse and should facilitate massive cluster formation.
MYC activation at modest levels has been frequently found in hepatocellular carcinoma. However, its significance in hepatocarcinogenesis has remained obscure. Here we examined the role of Myc ...activation in mouse liver tumours induced by hepatocytic expression of myristoylated AKT (AKT) and/or mutant HRAS
(HRAS) via transposon-mediated gene integration. AKT or HRAS alone required 5 months to induce liver tumours, whereas their combination generated hepatocellular carcinoma within 8 weeks. Co-introduction of AKT and HRAS induced lipid-laden preneoplastic cells that grew into nodules composed of tumour cells with or without intracytoplasmic lipid, with the latter being more proliferative and associated with spontaneous Myc expression. AKT/HRAS-induced tumorigenesis was almost completely abolished when MadMyc, a competitive Myc inhibitor, was expressed simultaneously. The Tet-On induction of MadMyc in preneoplastic cells significantly inhibited the progression of AKT/HRAS-induced tumours; its induction in transformed cells suppressed their proliferative activity with alterations in lipid metabolism and protein translation. Transposon-mediated Myc overexpression facilitated tumorigenesis by AKT or HRAS, and when it was co-introduced with AKT and HRAS, diffusely infiltrating tumours without lipid accumulation developed as early as 2 weeks. Examination of the dose-responses of Myc in the enhancement of AKT/HRAS-induced tumorigenesis revealed that a reduction to one-third retained enhancing effect but three-times greater introduction damped the process with increased apoptosis. Myc overexpression suppressed the mRNA expression of proteins involved in the synthesis of fatty acids, and when combined with HRAS introduction, it also suppressed the mRNA expression of proteins involved in their degradation. Finally, the MYC-positive human hepatocellular carcinoma was characterized by the cytoplasm devoid of lipid accumulation, prominent nucleoli and a higher proliferative activity. Our results demonstrate that in hepatocarcinogenesis induced by both activated AKT and HRAS, activation of endogenous Myc is an enhancing factor and adequate levels of Myc deregulation further facilitate the process with alterations in cellular metabolism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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