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Recently AFF was used to convert
2025-01-27
Recently, AFF was used to convert an FN3-based binder specific to the Src homology 2 (SH2) domain of cAbl kinase into an allosterically regulated, intermolecular fluorescent switch (Figure 2D). Binding to cAbl kinase co-operatively stabilized the assembly of the FN3-based binder from two partial fra
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Our conclusion was confirmed by
2025-01-27
Our conclusion was confirmed by two experiments. The addition of aminopeptidase-specific inhibitors at high concentrations allowed us to exclude the possibility of substrate hydrolysis by other proteases present in the samples, for example, endoproteases. After the application of inhibitors, we were
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The same applies also to
2025-01-26
The same applies also to intermediate , formally obtained by elimination of the R substituent from compound . If compared to the thienopyrimidine derivatives (series , C), the thieno[3,2-]pyridazin-5(4H)-ones – explored herein seem to maintain similar size and shape and also analogue structural char
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Since the localization of LO depends on phosphorylation we
2025-01-26
Since the localization of 5-LO depends on phosphorylation, we also analyzed the phosphorylation profile of 5-LO-WT and all isoforms by Western blot using specific Natural anthraquinone against the phosphorylation sites S271 and S523. Whereas phosphorylation at S271 activates the 5-LO, inhibits nucl
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Although we have achieved a great deal
2025-01-26
Although we have achieved a great deal of success in the development of tools to understand autophagy in health and disease, highly specific reagents for autophagy manipulation and deep knowledge of autophagy is required to advance the research in therapeutic treatment. Better disease (ischemia) ani
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br Discussion Herein we demonstrate that mice
2025-01-26
Discussion Herein, we demonstrate that mice deficient in L-12/15 LO are more sensitive to 3-NP-induced toxicity although a substantial individual variability in striatal lesion size in response to 3-NP in both genotypes was observed. This variability is not atypical; several studies demonstrate s
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In pancreatic islets we found an increase in protein express
2025-01-26
In pancreatic islets we found an increase in protein expression of leukocyte 12/15-LO that paralleled the metabolic decline characterized by severe hyperglycemia and reduced islet numbers. Similar increase in 12/15-LO expression by Western blot was found in the control mice, which have a normal meta
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Earlier studies showed that exposure of cells
2025-01-26
Earlier studies showed that exposure of cells to IR caused ATM-dependent phosphorylation of 53BP1, as judged by electrophoretic mobility shift [24], [25], [26]. To date, the only known in vivo 53BP1 phosphorylation site(s) are Ser25 and possibly Ser29 [27]. In the course of our studies, we noticed t
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Since at least prospective cohort studies
2025-01-24
Since 2005, at least 14 prospective cohort studies have been conducted to clarify inconsistencies in the field, ten of which suggested a direct correlation between antibiotic use and atopy or wheezing later in life [51–60], three found no association [61–63], and one found positive association only
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Recent retrospective cohort studies have supported these pre
2025-01-24
Recent retrospective cohort studies have supported these preclinical findings in animals indicating the correlation of AR activation with the induction of BQ-788 endothelin receptor antagonist carcinogenesis. First, men with prostate cancer who underwent androgen deprivation therapy were shown to h
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br Conflict of interest statement br Introduction
2025-01-24
Conflict of interest statement Introduction The global prevalence of Alzheimer's disease (AD) is expected to increase to 106 million in 2050 from 30 million in 2010 (Brookmeyer et al., 2007), which will further impose a significant economic burden on health systems and society as a whole (Broo
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In this study we designed and
2025-01-24
In this study, we designed and synthesized two ALK PROTACs (degraders), 5 (MS4077) and 6 (MS4078), by linking ceritinib and pomalidomide [45] through two different linkers. Using human ALCL and NSCLC cells, we characterized both compounds in a battery of assays to demonstrate their effects on reduci
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A straightforward synthetic pathway was adopted to
2025-01-24
A straightforward synthetic pathway was adopted to synthesize the target compounds as outlined in . The starting chloromethylquinazolinones (–) were synthesized from anthranilic mst1 kinase in two steps following reported procedures., , , The first step involves chloroacetylation of anthranilic ac
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br Introduction The traditional Chinese
2025-01-24
Introduction The traditional Chinese medicine (TCM), Ganoderma (G.) lucidum Karst is a well-known mushroom which has been used clinically in some Asian countries. It is termed “Lingzhi” in China, “Reishi” in Japan and “Yeongji” in Korea. It has long been used in TCM for the promotion of longevity
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Based on the observation that
2025-01-24
Based on the observation that antipsychotic drugs increase 5-HT1A–D2 heteromerization level (Łukasiewicz et al., 2016), we set out to compare the effect of paroxetine to that of risperidone. Paroxetine, a potent SSRI, is very effective in the treatment of depression and anxiety disorders, e.g., gen
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