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The downstream targets of ATR involved
2024-09-28
The downstream targets of ATR involved in mediating human telomerase recruitment have not yet been identified. Under stalled fork conditions, activated ATR is able to phosphorylate and activate ATM (Stiff et al., 2006, and Figures 4C and 4D); whether this nitric oxide inhibitor of ATM participates
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Of the many different types of DNA lesions DNA double
2024-09-28
Of the many different types of DNA lesions, DNA double strand breaks (DSBs) are amongst the most deleterious. It has been suggested that a single unrepaired DSB may be sufficient to induce cell death (Bennett et al., 1993), whereas misrepaired DSBs can result in loss of genetic information, potentia
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Activated MAP kinases transform the
2024-09-28
Activated MAP kinases transform the stimulus into the pathophysiological responses by phosphorylating downstream substrates, including transcription factors, cytoskeletal proteins involved in mRNA translation (Li et al., 2015). Among the numerous effectors that intervene in the TNF-α action is an ac
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It is well known that neurosteroids such
2024-09-28
It is well-known that neurosteroids such as testosterone and their metabolites endogenously modulate neural excitability in animals and humans. Testosterone has protective effects against seizures induced by KA and PTZ (Frye et al., 2001b; Reddy, 2004b). Estrogens, on the other hand, have proconvuls
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The activity of MMPs is regulated at the
2024-09-28
The activity of MMPs is regulated at the level of gene transcription or by the enzymatic activation of latent enzymes. Inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 are elevated in synovial fluid, synovium and cartilage in patients with OA, and these cyto
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Plant defensins Vriens et al and linear AMPs Domingues et
2024-09-28
Plant defensins (Vriens et al., 2014) and linear AMPs (Domingues et al., 2015, Liu et al., 2008) have been shown to present several modes of action. Among these different mechanisms, permeabilization of the fungal membrane has been described as a secondary effect of plant defensin action (Vriens et
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br Acknowledgements We thank the National Natural Science Fo
2024-09-28
Acknowledgements We thank the National Natural Science Foundation of China (41576156), Shandong Province Science and Technology Development Plan (2015GSF121045), Yantai Science and Technology Development Plan (2015ZH078), and the Public Science and Technology Research Funds Projects of Ocean (No.
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However from our meta analysis
2024-09-28
However, from our meta-analysis emerge some strategic considerations for the continued use of antiangiogenic drugs for glioblastoma patients: Conflict of interest Funding Introduction Angiogenesis is a physiological process involving the formation of new blood vessels from pre-existing blo
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It has been reported that NLRP product caspase is increased
2024-09-28
It has been reported that NLRP3 product, caspase-1, is increased in the brains of AD patients and experimental AD animals. NLRP3- and caspase-1-deficient animals are resistant to experimental development of AD, and have decreased IL-1β production and significantly increased Aβ clearance (Heneka et a
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The lactam emerged as lead candidate due
2024-09-28
The lactam (6) emerged as lead candidate due to its high selectivity, outstanding potency (against ALK or in clinically known ALK mutants), low in vitro clearance, and low efflux potential. The lactam (6) was selected for further profiling against the resistant ALK mutants. Preclinical rat pharmacok
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Pioneering studies on the immunomodulatory role of adenosine
2024-09-27
Pioneering studies on the immunomodulatory role of adenosine date back to the early ‘70 s of last century (Fig. 1), when the critical role of this nucleoside in shaping the development and the activity of several immune cell populations was first established [[18], [19], [20], [21], [22]]. This then
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A selected set of these
2024-09-27
A selected set of these new derivatives was then used for functional assays at the human A1AR showing, as expected, an antagonist profile with IC50 values at nanomolar level. The same molecules showed also to be efficacious as nanomolar antagonists in a functional assay aimed at analyzing their abil
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Multiple ASD susceptibility genes converge on cellular pathw
2024-09-27
Multiple ASD susceptibility genes converge on cellular pathways that intersect at the postsynaptic site of glutamatergic synapses (Bourgeron, 2015; Peca & Feng, 2012), the development and maturation of synaptic contacts (Gilman et al., 2011) or synaptic transmission (Li et al., 2014). The majority o
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ribosomal s6 kinase The geometry of two three four and
2024-09-27
The geometry of two, three, four and five ribosomal s6 kinase neutral radical ACh molecule complexes with various electronic configurations, i.e. with various multiplicities equal to 1, 2 and 4 (for ACh trimer) were determined using DFT with the unrestricted B97d/SVP potential/basis set in Gaussian
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HT modulates cortical and hippocampal pyramidal
2024-09-27
5-HT modulates cortical and hippocampal pyramidal cell function in a very complex manner, since most 5-HT receptor subtypes (excitatory as well as inhibitory) are expressed on pyramidal Gardiquimod as well as GABAergic interneurons that exert inhibitory control over pyramidal cells (Leiser et al.,
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