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ITK-SYK and TEL-SYK (also known as ETV6-SYK) are human tumor-causing chimeric proteins containing the kinase region of SYK, and the membrane-targeting, N-terminal, PH-TH domain-doublet of ITK or the dimerizing SAM-PNT domain of TEL, respectively. ITK-SYK causes peripheral T cell lymphoma, while TEL-SYK was reported in myelodysplastic syndrome. BTK is a kinase highly related to ITK and to further delineate the role of the N-terminus, we generated the corresponding fusion-kinase BTK-SYK. By generating and analyzing these fusion kinases, we aim to understand the contribution of N-terminal domains to their distinct cellular behavior and oncogenic properties. The fusion kinases were found to behave differently. TEL-SYK showed stronger oncogenic capacity when compared with ITK-SYK and BTK-SYK. Furthermore, ITK-SYK and BTK-SYK triggered IL-3-independent growth of BAF3 pro-B cells. In contrast to BTK-SYK and TEL-SYK, which predominantly localized in perinuclear region and cytoplasm respectively, ITK-SYK exhibits a more diverse cellular distribution, being present in the nucleus, cytoplasm and membrane-bound compartments. Notably, we observed that ITK-SYK undergoes activation-mediated nuclear translocation, a phenomenon that is uncommon among kinases. This unique feature of ITK-SYK is therefore of particular interest due to its potential connection to its transforming capability. [ABSTRACT FROM AUTHOR]

In this investigation, the influence of a combination of poly(ethylene-oxide) (PEO) and salt (NaCl) as water-soluble porogens on the synthesis of sustainable porous poly(ε-caprolactone) (PCL) membranes is explored. Nine mixture compositions are examined. PCL sheets are fabricated through the cryomilling, hot pressing, and porogen leaching approach. The resulting sheets are investigated for their morphologies, porosities, water uptake, and mechanical properties. Thick sheets display a porous lamellar structure with porosities ranging from 47.4% to 70.8%. Lamellae exhibit various surface features ranging from smooth surfaces, rough with pinholes, globular, fibrillar, and finally skeletal structures. Higher salt contents result in more compact lamellae with higher interconnected porosities on the lamellae surfaces. Samples demonstrate significant water uptake, increasing with higher porosities, while mechanical properties decrease. Regression analysis is used to fit the mechanical properties of the thin sheets, revealing second order polynomial functions of porosity. Additionally, the sandwich method is successfully employed to create porous membrane surfaces, yielding various distinct morphologies, including a notable feather-like layered structure and a hierarchal particulate structure with large particles coated with aggregates of tiny particles. These findings contribute to understanding the synthesis and properties of sustainable porous polymer membranes, with implications for various applications. [ABSTRACT FROM AUTHOR]