Terrestrial space weather involves the transfer of energy and momentum from the solar wind into geospace. Despite recently discovered seasonal asymmetries between auroral forms and the intensity of ...emissions between northern and southern hemispheres, seasonally averaged energy input into the ionosphere is still generally considered to be symmetric. Here we show, using Swarm satellite data, a preference for electromagnetic energy input at 450 km altitude into the northern hemisphere, on both the dayside and the nightside, when averaged over season. We propose that this is explained by the offset of the magnetic dipole away from Earth's center. This introduces a larger separation between the magnetic pole and rotation axis in the south, creating different relative solar illumination of northern and southern auroral zones, resulting in changes to the strength of reflection of incident Alfvén waves from the ionosphere. Our study reveals an important asymmetry in seasonally averaged electromagnetic energy input to the atmosphere. Based on observed lower Poynting flux on the nightside this asymmetry may also exist for auroral emissions. Similar offsets may drive asymmetric energy input, and potentially aurora, on other planets.
This study reports the discovery that trithiocarbonate RAFT agents can significantly reduce the amount of dissolved oxygen when irradiated with visible light ( λ max ≈ 460 nm) in the presence of a ...sacrificial tertiary amine. By taking advantage of this effect, we conducted a series of photo-CRPs of acrylates without the requirement of pre-degassing the reaction mixtures. In these systems, the trithiocarbonate plays a triple role of photocatalyst for oxygen removal, initiator, and RAFT agent for polymerization control. We believe this robust and facile synthetic method will be beneficial for cost-effective industrial applications as well as the laboratory-scale synthesis of functional polymeric materials.
Hyperactivation of transforming growth factor-β (TGF-β) signaling pathway is a common feature of hepatocellular carcinoma (HCC) progression. However, the driver factors leading to enhanced TGF-β ...activity are not well characterized. Here, we explore the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic TGF-β signaling in human HCC. The expression of KLF4 and TGF-β signaling components in primary HCC and their clinicopathologic relevance and significance was evaluated by using tissue microarray and immunohistochemistry. Cellular and molecular impacts of altered KLF4 expression and TGF-β signaling were determined using immunofluorescence, western blot, reverse-transcriptase PCR, chromatin immunoprecipitation and promoter reporter assays. Loss of KLF4 expression in primary HCC closely correlated with decreased Smad7 expression, increased p-Smad2/3 expression and independently predicts reduced overall and relapse-free survival after surgery. TGF-β signaling components were expressed in most HCC cells, and activation of TGF-β signaling promoted cell migration and invasion. Enforced KLF4 expression blocked TGF-β signal transduction and inhibited cell migration and invasion via activation of Smad7 transcription, whereas deletion of its C-terminal zinc-finger domain diminished this effect. KLF4 protein physically interacts with the Smad7 promoter. Promoter deletion and point mutation analyses revealed that a region between nucleotides -15 bp and -9 bp of the Smad7 promoter was required for the induction of Smad7 promoter activity by KLF4. Our data indicate that KLF4 suppresses oncogenic TGF-β signaling by activation of Smad7 transcription, and that loss of KLF4 expression in primary HCC may contribute to activation of oncogenic TGF-β signaling and subsequent tumor progression.
Novel polymer grafted metal-organic framework (MOF) nanoparticles were synthesized. The formed core/shell nanoparticles exhibit outstanding water dispersity and pH sensitivity, and show their ...catalytic effect for the reduction reaction of 4-nitrophenol (NP) to 4-aminophenol (AP) when loaded with Pd(0) catalyst.
Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the ...optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. Behavioral and gene expression changes did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.
Hepatocyte growth factor (HGF)/Met signaling has critical roles in pancreatic ductal adenocarcinoma (PDA) development and progression and is considered a potential therapeutic target for this ...disease. However, the mechanism of aberrant activation of HGF/Met signaling and resistance to Met inhibition in PDA remains unclear. The mechanistic role of cross talk between Forkhead box M1 (FOXM1) and HGF/Met signaling in promotion of PDA growth and resistance to Met inhibition was examined using cell culture, molecular biology and mouse models; and the relevance of our experimental and mechanistic findings were validated using human PDA tissues. Met was markedly overexpressed in both PDA cell lines and pancreatic tumor specimens, and the expression of Met correlated directly with that of FOXM1 in human tumor specimens. Mechanistically, FOXM1 bound to the promoter region of the Met gene and transcriptionally increased the expression of Met. Increased expression of FOXM1 enhanced the activation of HGF/Met signaling and its downstream pathways, including retrovirus-associated DNA sequences/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/AKT and signal transducer and activator of transcription 3. Furthermore, activation of HGF/Met signaling increased the expression and transcriptional activity of FOXM1, and the cross talk between FOXM1 and HGF/Met signaling promoted PDA growth and resistance to Met inhibition. Collectively, our findings identified a positive feedback loop formed by FOXM1 and HGF/Met and revealed that this loop is a potentially effective therapeutic target for PDA.
A reduced copper metal-organic framework (rCu-MOF) containing Cu
ions was prepared by reducing raw MOFs (Cu-BTC). A series of polymer functionalizations and coupling reactions could subsequently be ...achieved via CuAAC click chemistry, thus demonstrating the high activity, facile recyclability and good structural stability of rCu-MOFs for catalytic applications.
Abstract Osthole, a bioactive simple coumarin derivative extracted from many medicinal plants such as Cnidium monnieri (L.) Cusson, exerts a broad spectrum of pharmacological activities and is ...considered to have potential therapeutic applications. The aim of this study was to investigate the potential neuroprotective role of osthole against ischemic injury in vitro , as well as the potential mechanism. Cultured cortical neurons were exposed to oxygen and glucose deprivation (OGD) for 4 h followed by a 24 h reperfusion. Osthole exhibited remarkable neuroprotection in a dose-dependent manner and the effect required presence of osthole during both OGD and reperfusion phases. Western blot was used to examine the activation of three members of mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 kinase (p38). We found that osthole prolonged activation of ERK1/2 and prevented activation of JNK. Furthermore, we investigated the effects of MAPKs inhibitors on osthole-induced protection. The results demonstrated that the protection of osthole was partly reversed by PD98059, a selective inhibitor of ERK1/2, but further enhanced by the JNK inhibitor SP600125. In addition, osthole-induced reduction of neuronal apoptosis was abrogated by the ERK1/2 inhibitor PD98059, whereas the total neuronal death was further decreased by the JNK inhibitor SP600125. In summary, these data suggested that osthole had neuroprotective effect against ischemic injury in vitro , and the protection possibly was associated with prolonged activation of ERK1/2 and suppression of JNK activity.
Abstract Some types of peripheral neuropathic pain are associated with damage to myelin rather than to axons of primary sensory neurons. It is extremely important to develop selective demyelination ...animal models for understanding neuropathic pain caused by demyelination. We induced a rapid-onset and reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by a single injection of cobra venom into the sciatic nerve. The relation between A-fiber demyelination and the abnormal pain behaviors was investigated using this model. Microfilament recordings revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. The axons of the demyelinated A-fibers appeared to be otherwise normal. Neuropathic pain behaviors appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from both peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evan's Blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-fiber polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field.
A laboratory-scale submerged anaerobic membrane bioreactor (SAnMBR) was operated for over 160 days to assess the potential to treat kraft pulp mill evaporator condensate. Cake formation was ...identified as a dominant feature contributing to the deterioration of membrane performance. The influence of various operational parameters and sludge properties on sludge cake formation rate (CFR) was investigated. These included biogas sparging and permeate flow rates, as well as mixed liquor suspended solids (MLSS), soluble chemical oxygen demand (COD
s) in the mixed liquor, and particle size distribution (PSD) and fractal dimension (
D
f) of particles. CFR was highly dependent on biogas sparging rate and permeate flow rate, and less dependent on MLSS. COD
s, PSD and
D
f were found to significantly influence the CFR. Confocal laser scanning microscopic (CLSM) imaging and chemical analyses of extracellular polymeric substances (EPS) indicated that EPS was involved in sludge cake formation. Characterization of the sludge cake layers, when compared to the bulk sludge, indicated that smaller flocs and EPS preferentially accumulated in the sludge cake. The identification of factors including biogas sparging rate, permeate flow rate, COD
s, EPS, PSD, and
D
f that impact the cake formation process provides a basis for selecting operating conditions to manage fouling in an SAnMBR.
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