1,244 research outputs found

    Plasmoid ejection and secondary current sheet generation from magnetic reconnection in laser-plasma interaction

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    Reconnection of the self-generated magnetic fields in laser-plasma interaction was first investigated experimentally by Nilson {\it et al.} [Phys. Rev. Lett. 97, 255001 (2006)] by shining two laser pulses a distance apart on a solid target layer. An elongated current sheet (CS) was observed in the plasma between the two laser spots. In order to more closely model magnetotail reconnection, here two side-by-side thin target layers, instead of a single one, are used. It is found that at one end of the elongated CS a fan-like electron outflow region including three well-collimated electron jets appears. The (>1>1 MeV) tail of the jet energy distribution exhibits a power-law scaling. The enhanced electron acceleration is attributed to the intense inductive electric field in the narrow electron dominated reconnection region, as well as additional acceleration as they are trapped inside the rapidly moving plasmoid formed in and ejected from the CS. The ejection also induces a secondary CS

    Identification of an important site for function of the type 2C protein phosphatase ABI2 in abscisic acid signalling in Arabidopsis

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    It is known that the clade A protein phosphatase 2Cs (PP2Cs), including ABI1 and ABI2 and other PP2C members, are key players that function directly downstream of the PYR/PYL/RCAR abscisic acid (ABA) receptors. Here, identification of a crucial site for function of ABI2 protein phosphatase in ABA signalling is reported. It was observed that a calcium-dependent protein kinase (CDPK) phosphorylation site-like motif (CPL) in the ABI2 molecule is required for the interactions of ABI2 with the two members of the ABA receptors PYL5 and PYL9 and with a downstream protein kinase SnRK2.6, and for the catalytic activity of ABI2 in vitro, as well as for the response of ABI2 to the ABA receptors PYL5/PYL9 in relation to the ABA receptor-induced inhibition of the ABI2 phosphatase activity. Further, genetic evidence was provided to demonstrate that this CPL is required for the function of ABI2 to mediate ABA signalling. These data reveal that this CPL is an important site necessary for both the phosphatase activity of ABI2 and the functional interaction between ABI2 and PYL5/9 ABA receptors, providing new information to understand primary events of ABA signal transduction

    Liraglutide Ameliorates β-Amyloid Deposits and Secondary Damage in the Ipsilateral Thalamus and Sensory Deficits After Focal Cerebral Infarction in Rats

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    Focal cerebral infarction causes β-amyloid (Aβ) deposition and secondary neuronal degeneration in the ipsilateral thalamus. Thalamus is the subcortical center of sensory, the damage of thalamus could cause sensory deficits. The present study aimed to investigate the protective effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP)-1 receptor agonist, on Aβ deposits and secondary damage in the ipsilateral thalamus after focal cerebral infarction. In addition, this study was conducted to investigate whether liraglutide could improve sensory function after focal cerebral infarction. Forty-two male Sprague–Dawley rats were subjected to distal middle cerebral artery occlusion (MCAO) and then randomly divided into liraglutide and vehicle groups, and 14 sham-operated rats as control. At 1 h after MCAO, rats in the liraglutide and vehicle groups were subcutaneously injected with liraglutide (100 μg/kg/d) and isopyknic vehicle, respectively, once a day for 7 days. Sensory function and secondary thalamic damage were assessed using adhesive-removal test and Nissl staining and immunostaining, respectively, at 7 days after MCAO. Terminal deoxynucleotidyl transferase 2’-deoxyuridine 5’-triphosphate nick end labeling and Western blot were used to detect neuronal apoptosis. The results showed that liraglutide improved sensory deficit compared to the controls. Liraglutide treatment significantly reduced Aβ deposition compared with the vehicle treatment. Liraglutide treatment decreased the neuronal loss, astroglial and microglial activation, and apoptosis compared with the vehicle treatment. Liraglutide significantly down-regulated the expression of Bcl-2 and up-regulated that of Bax in the ipsilateral thalamus compared with the vehicle group. These results suggest that liraglutide ameliorates the deposition of Aβ and secondary damage in the ipsilateral thalamus, potentially contributing to improve sensory deficit after focal cerebral infarction

    Genomic insights into adaptation to Karst limestone and incipient speciation in East Asian Platycarya spp. (Juglandaceae)

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    DATA AVAILABILITY : All sequencing data used in this study have been deposited at GenBank under the accession PRJNA356989. The reference genome and gene annotations have also been deposited on the website (http://cmb.bnu.edu.cn/juglans). All codes used for the main analyses in this paper are available for download from https://github.com/Caoyu819/protocols-for-karst-adaptation-of-Platycarya.git.When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes and its only congeneric species, Platycarya strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole-genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics and the driving forces underneath the incipient speciation of the two Platycarya lineages.The National Natural Science Foundation of China, the “111” Program of Introducing Talents of Discipline to Universities, Beijing Advanced Innovation Program for Land Surface Processes, the National Key R&D Program of China, the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program, Ghent University (Methusalem funding) and China Scholarship Council.https://academic.oup.com/mbehj2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-15:Life on lan

    Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

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    Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

    The Combination of RAD001 and NVP-BEZ235 Exerts Synergistic Anticancer Activity against Non-Small Cell Lung Cancer In Vitro and In Vivo

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    The phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit PI3K, mTOR or both are currently under development. The mTOR allosteric inhibitor, RAD001, and the PI3K/mTOR dual kinase inhibitor, BEZ235, are examples of these agents. We were interested in developing strategies to enhance mTOR-targeted caner therapy. In this study, we found that BEZ235 alone effectively inhibited the growth of rapamycin-resistant cancer cells. Interestingly, the combination of sub-optimal concentrations of RAD001 and BEZ235 exerted synergistic inhibition of the growth of human lung cancer cells along with induction of apoptosis and G1 arrest. Furthermore, the combination was also more effective than either agent alone in inhibiting the growth of lung cancer xenografts in mice. The combination showed enhanced effects on inhibiting mTOR signaling and reducing the expression of c-Myc and cyclin D1. Taken together, our results suggest that the combination of RAD001 and BEZ235 is a novel strategy for cancer therapy

    Scoliotic posture as the initial symptom in adolescents with lumbar disc herniation: its curve pattern and natural history after lumbar discectomy

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    <p>Abstract</p> <p>Background</p> <p>There have been few studies focusing on the curve pattern of scoliosis caused by lumbar disc herniation (LDH) in adolescents and the natural history of scoliosis after discectomy. The current study was carried out to identify the curve pattern of scoliosis and investigate the effect of posterior discectomy on the curve improvement in adolescents with LDH.</p> <p>Methods</p> <p>This review focused on a group of 26 adolescents with LDH who initially presented to our clinic for evaluation of scoliosis, followed by posterior discectomy between 2000 and 2009. Radiographic measurements included curve pattern, specific curve features, trunk shift, and sagittal profile. The correlation between the side of disc herniation and the direction of lumbosacral curve and the trunk shift was evaluated.</p> <p>Results</p> <p>A typical curve pattern was initially identified in all of the patients as a short lumbosacral curve accompanied with a long thoracic or thoracolumbar curve toward the opposite side. 23 of 26 patients (88.5%) had a trunk shift more than 2.0 cm away from the midline, showing a poor coronal balance. A relatively straight sagittal profile was noted in all the patients. 84.6% (22/26) patients had a disc herniation at the convex side of lumbosacral curve. Similarly, 73.1% (19/26) patients showed a trunk shift toward the opposite side of disc herniation. All of the patients had an marked curve improvement immediately after discectomy. In the 17 patients with a more than 2-year follow-up, only two had a residual lumbosacral curve greater than or equal to 20 degrees. The mean ODI improved from 21.4% before surgery to 7.3% at the final follow-up.</p> <p>Conclusions</p> <p>A short lumbosacral curve accompanied with a long thoracic or thoracolumbar curve toward the opposite side, and a relatively straight sagittal profile have been noted in all the patients. The direction of lumbosacral curve and trunk shift was related to the side of disc herniation. A majority of patients have a small curve size while assosiated with a significant coronal imbalance. Earlier decompression can provide a greater opportunity for spontaneous correction of scoliosis.</p
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