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Toxicity is the main reason for the
2024-03-30

Toxicity is the main reason for the failure at all stages of the new drug development process. The major part of safety-related attrition occurs at preclinical phases while predicting preclinical safety liabilities earlier in the drug development process. This strategy enables the design and/or sele
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The first suggestions that the cleaved
2024-03-30

The first suggestions that the cleaved intracellular domain of APP, AICD, might transit to the nucleus and hence selectively regulate gene transcription arose from analogies with the Notch receptor signalling system where similar intra-membrane proteolysis occurs [84], [85] and it was later confirme
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br Author contributions br Competing interests br Transparen
2024-03-29

Author contributions Competing interests Transparency document Acknowledgments This research was funded by a TOP ZonMW grant (40-00812-98-10054) to R.O.E., a DFG grant (KR4391/1-1) and IZKF Erlangen grant (J36) to A.K. and supported in part by Centro de Investigación Biomédica en Red de
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br Results br Discussion Context specific and
2024-03-29

Results Discussion Context-specific and dynamic post-translational protein modifications are well-established regulators of the signaling pathways that protect eukaryotic DNA integrity during the tremendous task of replication. Advancements in speed, resolution, and sensitivity of MS-based tec
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Dopaminergic neurons are vulnerable to oxidative products an
2024-03-29

Dopaminergic neurons are vulnerable to oxidative products and inflammatory responses; these processes may play important roles in the etiology of PD. Because glial MK-3207 HCl synthesis are the main generators of inflammatory responses in the CNS, the possibility that PD results from glial cell dys
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About three weeks later the patient visited our outpatient c
2024-03-29

About three weeks later, the patient visited our outpatient clinic complaining of gingival bleeding and pus discharge. In clinical examination bone exposure was observed in both mandibular posterior regions and bone necrosis had developed surrounding the #35=37 and 46, 47 implants installed 6 years
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A previous review article suggested
2024-03-29

A previous review article suggested different washout intervals based on specific clinical contexts [4]. While no consensus was reached for the optimal interval between last dose of BV and surgery for CRLM, the authors of the review suggested waiting 6 to 8 weeks after BV before surgery, particularl
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Since HETEs and lipoxins the downstream products
2024-03-29

Since HETEs and lipoxins, the downstream products of 12/15-LOX from AA, may alter cellular proliferation and apoptosis,31, 32 and possibly explain the increase of tumour progression and metastasis. However, we here found that HETEs did not affect the proliferation of melanoma in vitro. This may part
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Nx rats feces collected in nd
2024-03-29

5/6Nx rats’ feces collected in 2 nd week, 4 th week, 6 th week, 8 th week and 10 th week were tested by 16S rDNA sequencing. The 16S rDNA sequencing data was analyzed in the level of PHYLUM, CLASS, ORDER, FAMILY and GENUS. There are more than 1000 types of gut microbiota in the level of Genus [50],
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To our knowledge BAY has not progressed to
2024-03-28

To our knowledge, BAY 60-6583 has not progressed to clinical development and remains to be the only ADORA2B agonist that has been developed.33, 34 Further development of similar compounds would be beneficial in future fibrosis research. One of the limitations of our study is being limited to in vit
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br Introduction Adenosine deaminase ADA which can catalyze t
2024-03-28

Introduction Adenosine deaminase (ADA), which can catalyze the conversion of AD to inosine by removing an amino group, is a key hydrolytic enzyme of purine metabolism (Conway and Cooke, 1939), and plays an important role in an amount of diseases. For example, an increase of ADA activity in serum
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A similar circuit between pyramidal neurons and SST interneu
2024-03-28

A similar circuit between pyramidal neurons and SST interneurons is also prevalent in layers 2/3 of the cortex. The synapses onto SST interneurons, however, are functionally weak, raising questions about their computational power. In the first set of experiments, Urban-Ciecko et al. (2018) show tha
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The gene SRD A encodes the reductase enzyme which
2024-03-28

The gene SRD5A2 encodes the 5-α-reductase enzyme, which converts testosterone into dihydrotestosterone. Although dihydrotestosterone levels are considerably lower than testosterone, dihydrotestosterone has a five-fold stronger binding capacity to the androgen receptor and, thereby, a considerably mo
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Skeletal pain associated with bone
2024-03-28

Skeletal pain associated with bone fracture is another area of critical need for a novel pain medication. NSAIDs and opiates are the two major therapies currently used to manage bone fracture pain. However, both of these therapies lead to significant unwanted side effects. Using the osteotomy model
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Interestingly this situation might be
2024-03-28

Interestingly, this situation might be changed by the immunological context, in particular by the cytokines encountered during differentiation or activation. LPS-activation of bone marrow-derived DCs differentiated in GM-CSF decreases autophagy, CP2, and subsequent activation of CD4+ T cells (Fig. 2
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