Proteolytic analysis of Trichoderma reesei in celluase-inducing condition reveals a role for trichodermapepsin (TrAsP) in cellulase production

Journal of Industrial Microbiology & Biotechnology - Filamentous fungi produce a variety of proteases with significant biotechnological potential and show diverse substrate specificities....     

A novel GSK3 inhibitor that promotes self-renewal in mouse embryonic stem cells

ABSTRACT

Small molecules that regulate cell stemness have the potential to make a major contribution to regenerative medicine. In the course of screening for small molecules that affect stemness in mouse embryonic stem cells (mESCs), we discovered that NPD13432, an aurone derivative, promoted self-renewal of mESCs. Normally, mESCs start to differentiate upon withdrawal of 2i/LIF. However, cells treated with the compound continued to express endogenous Nanog, a pluripotency marker protein essential for sustaining the undifferentiated state, even in the absence of 2i/LIF. Biochemical characterization revealed that NPD13432 inhibited GSK3α and GSK3β with IC₅₀ values of 92 nM and 310 nM, respectively, suggesting that the compound promotes self-renewal in mESCs by inhibiting GSK3. The chemical structure of the compound is unique among known molecules with this activity, providing an opportunity to develop new inhibitors of GSK3, as well as chemical tools for investigating cell stemness.     

IL-26 mediates epidermal growth factor receptor-tyrosine kinase inhibitor resistance through endoplasmic reticulum stress signaling pathway in triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. Although epidermal growth factor receptor (EGFR) is overexpressed in TNBC, clinical trials with EGFR inhibitors including tyrosine kinase inhibitors (EGFR-TKI) in TNBC have heretofore been unsuccessful. To develop effective EGFR-targeted therapy for TNBC, the precise mechanisms of EGFR-TKI resistance in TNBC need to be elucidated. In this study, to understand the molecular mechanisms involved in the differences in EGFR-TKI efficacy on TNBC between human and mouse, we focused on the effect of IL-26, which is absent in mice. In vitro analysis showed that IL-26 activated AKT and JNK signaling of bypass pathway of EGFR-TKI in both murine and human TNBC cells. We next investigated the mechanisms involved in IL-26-mediated EGFR-TKI resistance in TNBC. We identified EphA3 as a novel functional receptor for IL-26 in TNBC. IL-26 induced dephosphorylation and downmodulation of EphA3 in TNBC, which resulted in increased phosphorylation of AKT and JNK against EGFR-TKI-induced endoplasmic reticulum (ER) stress, leading to tumor growth. Meanwhile, the blockade of IL-26 overcame EGFR-TKI resistance in TNBC. Since the gene encoding IL-26 is absent in mice, we utilized human IL-26 transgenic (hIL-26Tg) mice as a tumor-bearing murine model to characterize the role of IL-26 in the differential effect of EGFR-TKI in human and mice and to confirm our in vitro findings. Our findings indicate that IL-26 activates the bypass pathway of EGFR-TKI, while blockade of IL-26 overcomes EGFR-TKI resistance in TNBC via enhancement of ER stress signaling. Our work provides novel insights into the mechanisms of EGFR-TKI resistance in TNBC via interaction of IL-26 with its newly identified receptor EphA3, while also suggesting IL-26 as a possible therapeutic target in TNBC.Subject terms: Stress signalling, Cell death and immune response, Breast cancer     

Significance of Low Nanomolar Concentration of Zn<Superscript>2+</Superscript> in Artificial Cerebrospinal Fluid

Much less attention has been paid to Zn²⁺ in artificial cerebrospinal fluid (ACSF), i.e., extracellular medium, used for in vitro slice experiments than divalent cations such as Ca²⁺. Approximately 2 mM Ca²⁺ is added to conventional ACSF from essentiality of Ca²⁺ signaling in neurons and glial cells. However, no Zn²⁺ is added to it, even though the importance of Zn²⁺ signaling in them is recognizing. On the other hand, synaptic Zn²⁺ homeostasis is changed during brain slice preparation. Therefore, it is possible that not only neuronal excitation but also synaptic plasticity such as long-term potentiation is modified in ACSF without Zn²⁺, in which original physiology might not appear. The basal (static) levels of intracellular (cytosolic) Zn²⁺ and Ca²⁺ are not significantly different between brain slices prepared with conventional ACSF without Zn²⁺ and pretreated with ACSF containing 20 nM ZnCl₂ for 1 h. In the case of mossy fiber excitation, however, presynaptic activity assessed with FM 4–64 is significantly suppressed in the stratum lucidum of brain slices pretreated with ACSF containing Zn²⁺, indicating that hippocampal excitability is enhanced in brain slices prepared with ACSF without Zn²⁺. The evidence suggests that low nanomolar concentration of Zn²⁺ is necessary for ACSF. Furthermore, exogenous Zn²⁺ has opposite effect on LTP induction between in vitro and in vivo experiments. It is required to pay attention to extracellular Zn²⁺ concentration to understand synaptic function precisely.     

Instability of parasympathetic nerve function evaluated by instantaneous time–frequency analysis in patients with obstructive sleep apnea

Sleep and Biological Rhythms - The purpose was to determine whether the instability of parasympathetic nerve (PN) function is associated with fragmentation of sleep and the instability can be...     

Insights into nitrogen fixing traits and population structure analyses in cowpea (Vigna unguiculata L. Walp) accessions grown in Ghana

Physiology and Molecular Biology of Plants - With legumes, symbiotic N2 fixation can meet the species N demand and reduce the over-reliance on chemical fertilizers in tropical regions where N...