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Pancreatic cancer has a dismal prognosis and to date there are no targeted therapies for this malignancy. Using shotgun proteomics, the mRNA binding protein cold shock domain containing E1 (CSDE1), also called upstream‐of‐N‐Ras, is detected in pancreatic cancer cell lines but not in normal pancreatic epithelial cells. The expression of CSDE1 in pancreatic cancer cells is confirmed by Western blotting and immunohistochemistry of human pancreatic tumors. In vitro functional assays show that siRNA downregulation of CSDE1 or gene knockout using CRISPR‐Cas9 significantly reduce the invasiveness of pancreatic cancer cells. Together, this study reveals that CSDE1 is overexpressed in pancreatic cancer and is a potential therapeutic target to inhibit pancreatic cancer cell invasion.  相似文献   
173.
Neurodevelopmental disorders are characterized by deficits in communication, cognition, attention, social behavior and/or motor control. Previous studies have pointed to the involvement of genes that regulate synaptic structure and function in the pathogenesis of these disorders. One such gene, GRM7, encodes the metabotropic glutamate receptor 7 (mGlu7), a G protein‐coupled receptor that regulates presynaptic neurotransmitter release. Mutations and polymorphisms in GRM7 have been associated with neurodevelopmental disorders in clinical populations; however, limited preclinical studies have evaluated mGlu7 in the context of this specific disease class. Here, we show that the absence of mGlu7 in mice is sufficient to alter phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep. Moreover, Grm7 knockout mice exhibit an attenuated response to amphetamine. These findings provide rationale for further investigation of mGlu7 as a potential therapeutic target for neurodevelopmental disorders such as idiopathic autism, attention deficit hyperactivity disorder and Rett syndrome.  相似文献   
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Compared to conjugated polymers, small‐molecule organic semiconductors present negligible batch‐to‐batch variations, but presently provide comparatively low power conversion efficiencies (PCEs) in small‐molecular organic solar cells (SM‐OSCs), mainly due to suboptimal nanomorphology. Achieving precise control of the nanomorphology remains challenging. Here, two new small‐molecular donors H13 and H14 , created by fluorine and chlorine substitution of the original donor molecule H11 , are presented that exhibit a similar or higher degree of crystallinity/aggregation and improved open‐circuit voltage with IDIC‐4F as acceptor. Due to kinetic and thermodynamic reasons, H13 ‐based blend films possess relatively unfavorable molecular packing and morphology. In contrast, annealed H14 ‐based blends exhibit favorable characteristics, i.e., the highest degree of aggregation with the smallest paracrystalline π–π distortions and a nanomorphology with relatively pure domains, all of which enable generating and collecting charges more efficiently. As a result, blends with H13 give a similar PCE (10.3%) as those made with H11 (10.4%), while annealed H14 ‐based SM‐OSCs have a significantly higher PCE (12.1%). Presently this represents the highest efficiency for SM‐OSCs using IDIC‐4F as acceptor. The results demonstrate that precise control of phase separation can be achieved by fine‐tuning the molecular structure and film formation conditions, improving PCE and providing guidance for morphology design.  相似文献   
176.
In agriculture, antibiotics are used for the treatment and prevention of livestock disease. Antibiotics perturb the bacterial gut composition but the extent of these changes and potential consequences for animal and human health is still debated. Six calves were housed in a controlled environment. Three animals received an injection of the antibiotic florfenicol (Nuflor), and three received no treatment. Faecal samples were collected at 0, 3 and 7 days, and bacterial communities were profiled to assess the impact of a therapy on the gut microbiota. Phylogenetic analysis (16S-rDNA) established that at day 7, antibiotic-treated microbiota showed a 10-fold increase in facultative anaerobic Escherichia spp, a signature of imbalanced microbiota, dysbiosis. The antibiotic resistome showed a high background of antibiotic resistance genes, which did not significantly change in response to florfenicol. However, the maintenance of Escherichia coli plasmid-encoded quinolone, oqxB and propagation of mcr-2, and colistin resistance genes were observed and confirmed by Sanger sequencing. The microbiota of treated animals was enriched with energy harvesting bacteria, common to obese microbial communities. We propose that antibiotic treatment of healthy animals leads to unbalanced, disease- and obese-related microbiota that promotes growth of E. coli carrying resistance genes on mobile elements, potentially increasing the risk of transmission of antibiotic resistant bacteria to humans.  相似文献   
177.
Globally, carbon‐rich mangrove forests are deforested and degraded due to land‐use and land‐cover change (LULCC). The impact of mangrove deforestation on carbon emissions has been reported on a global scale; however, uncertainty remains at subnational scales due to geographical variability and field data limitations. We present an assessment of blue carbon storage at five mangrove sites across West Papua Province, Indonesia, a region that supports 10% of the world's mangrove area. The sites are representative of contrasting hydrogeomorphic settings and also capture change over a 25‐years LULCC chronosequence. Field‐based assessments were conducted across 255 plots covering undisturbed and LULCC‐affected mangroves (0‐, 5‐, 10‐, 15‐ and 25‐year‐old post‐harvest or regenerating forests as well as 15‐year‐old aquaculture ponds). Undisturbed mangroves stored total ecosystem carbon stocks of 182–2,730 (mean ± SD: 1,087 ± 584) Mg C/ha, with the large variation driven by hydrogeomorphic settings. The highest carbon stocks were found in estuarine interior (EI) mangroves, followed by open coast interior, open coast fringe and EI forests. Forest harvesting did not significantly affect soil carbon stocks, despite an elevated dead wood density relative to undisturbed forests, but it did remove nearly all live biomass. Aquaculture conversion removed 60% of soil carbon stock and 85% of live biomass carbon stock, relative to reference sites. By contrast, mangroves left to regenerate for more than 25 years reached the same level of biomass carbon compared to undisturbed forests, with annual biomass accumulation rates of 3.6 ± 1.1 Mg C ha?1 year?1. This study shows that hydrogeomorphic setting controls natural dynamics of mangrove blue carbon stocks, while long‐term land‐use changes affect carbon loss and gain to a substantial degree. Therefore, current land‐based climate policies must incorporate landscape and land‐use characteristics, and their related carbon management consequences, for more effective emissions reduction targets and restoration outcomes.  相似文献   
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Anthropological models of personhood suggest that the individual is produced through relational ties to others, including humans and nonhumans. American ideas about the individual are deeply ideological, obscuring the human relations that make ‘personhood’ a possible, desirable concept that motivates subjection. Attending to neurological disorders and the technologies that attempt to remedy communication impairments shows that not only is the labour of other humans obscured in producing the individual, but so are the facilitating capacities of technologies and institutions. This article focuses on memoirs of disability and ethnographic and historiographic research on neuroscience to show how personhood is facilitated and produced through engagements with people, technologies, and institutions that attempt to render particular forms of subjection through communicative practices.  相似文献   
180.
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