WNKs are large serine/threonine protein kinases structurally distinct from all other members of the protein kinase superfamily. Of the four human WNK family members, WNK1 and WNK4 have been linked to a hereditary form of hypertension, pseudohypoaldosteronism type II. We characterized the biochemical properties and regulation of WNK1 that may contribute to its physiological activities and abnormal function in disease. We showed that WNK1 is activated by hypertonic stress in kidney epithelial cells and in breast and colon cancer cell lines. In addition, hypotonic stress also led to a modest increase in WNK1 activity. Gel filtration suggested that WNK1 exists as a tetramer, and yeast two-hybrid data showed that the N terminus of WNK1 (residues 1-222) interacts with residues 481-660, which includes the WNK1 autoinhibitory domain and a C-terminal coiled-coil domain. Although cell biological studies have suggested a functional interaction between WNK1 and WNK4, we found no evidence of stable interactions between these kinases. However, WNK1 phosphorylated both WNK4 and WNK2. In addition, the WNK1 autoinhibitory domain inhibited the catalytic activity of these WNKs. These findings suggest potential mechanisms for interconnected regulation of WNK family members.
Introduction: Preceptors are crucial in the education of physician assistant (PA) students, yet many lack formal preceptor training. The aim of this scoping review was to describe the curriculum and design of existing preceptor training programs for physician assistants, nurse practitioners, and physicians.
Methods: This scoping review was developed following the methodologic framework provided by the Joanna Briggs Institute.
A new member is incorporated into the SERS active materials family daily as a consequence of advances in materials science. Furthermore, it has been demonstrated that MXenes, which display remarkable physicochemical characteristics, are also encompassed within this family. This Review offers a comprehensive and systematic assessment of the potential of MXene structures in the context of SERS applications.
Accurate modeling of host-guest systems is challenging in modern computational chemistry. It requires intermolecular interaction patterns to be correctly described and, more importantly, the dynamic behaviors of macrocyclic hosts to be accurately modeled. Pillar[]arenes as a crucial family of macrocycles play a critical role in host-guest chemistry and biomedical applications.
Radiation therapy (RT) is one of the core therapies for current cancer management. However, the emergence of radioresistance has become a major cause of radiotherapy failure and disease progression. Therefore, overcoming radioresistance to achieve highly effective treatment for refractory tumors is significant yet challenging.
NAC [NO APICAL MERISTEM (NAM), ARABIDOPSIS TRANSCRIPTION ACTIVATOR FACTOR 1/2 (ATAF1/2), and CUP-SHAPED COTYLEDON (CUC2)] transcription factors are key regulators of plant growth, development, and stress responses but were also crucial players during land plant adaptation and crop domestication. Using representative members of green algae, bryophytes, lycophytes, gymnosperms, and angiosperms, we expanded the evolutionary history of NAC transcription factors to unveil the relationships among members of this gene family. We found a massive increase in the number of NAC transcription factors from green algae to lycophytes and an even larger increase in flowering plants.
