Neuromatch Academy: a 3-week, online summer school in computational neuroscience

Neuromatch Academy (https://academy.neuromatch.io; (van Viegen et al., 2021)) was designed as an online summer school to cover the basics of computational neuroscience in three weeks. The materials cover dominant and emerging computational neuroscience tools, how they complement one another, and specifically focus on how they can help us to better understand how the brain functions. An original component of the materials is its focus on modeling choices, i.e. how do we choose the right approach, how do we build models, and how can we evaluate models to determine if they provide real (meaningful) insight. This meta-modeling component of the instructional materials asks what questions can be answered by different techniques, and how to apply them meaningfully to get insight about brain function

Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

11 páginas, 2 figuras, 1 tablaInappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.I. Comas was supported by PID2019-104477RB-I00 from the Spanish Science Ministry and by ERC (CoG 101001038)Peer reviewe

Synergistic effect of combined protopanaxatiol and ginsenoside Rh2 on antiproliferative activity in MDA-MB-231 human breast cancer cells in vitro

Breast cancer is the most common cancer in women worldwide. The antiproliferative activities of protopanaxatiol (PPT) and ginsenoside Rh2 was measured by evaluating the inhibition of MDA-MB-231 human breast cancer cell proliferation. The two-way combination of PPT and Rh2 was conducted. In the two-way combination, the EC50 values of PPT and Rh2 were 2.3- and 2.2-fold lower, respectively, than those of PPT and Rh2 alone. The combination index (CI) values were 0.55 ± 0.09, 0.65 ± 0.10, 0.79 ± 0.12, and 0.91 ± 0.14 at 50% and 95% inhibition rates. Combined PPT and Rh2 also increased the inhibition of cell invasion and migration compared with individual compounds tested in cell lines. Intracellular signalling array analysis demonstrated that phosphorylated BAD, p53, and p38 proteins were increased. The results indicate that combined PPT and Rh2 exhibits a synergistic effect in MDA-MB-231 cell proliferation

Auxin Response Factors Are Ubiquitous in Plant Growth and Development, and Involved in Crosstalk between Plant Hormones: A Review

Auxin response factors (ARFs) are an important family of transcription factors involved in the exertion of auxin in plants and play a key role in regulating the growth and development of plant nutritional and reproductive organs such as roots, stems, leaves, flowers, fruits, and seeds. Foods of plant origin occupy an important place in the nutritional structure of the human diet, and the main edible parts of different plants vary. In this paper, we review recent research reports on ARFs and summarize its role in the regulation of leaf, flower, root, and fruit growth, as well as other important life activities. We also present the challenges and opportunities that ARFs will present in the future. It will be important to deepen our understanding of the mechanisms by which ARFs interact with other proteins or genes. In addition, it is worth considering that more technical tools should be put into the study of ARFs and that the research should be oriented towards solving practical problems. In the future, it is expected that the nutrition and function of plant-derived foods can be improved through gene editing and other means

Oleuropein Protects Cardiomyocyte against Apoptosis via Activating the Reperfusion Injury Salvage Kinase Pathway In Vitro

Oleuropein, the main glycoside present in olives, has been reported to have cardioprotective effect, but the exact mechanism has not been clearly elucidated. This study attempted to clarify the cardioprotective effect of oleuropein against simulated ischemia/reperfusion- (SI/R-) induced cardiomyocyte injury in vitro and further explore the underlying mechanism. Here we confirmed that oleuropein reduced the cell injury in neonatal rat cardiomyocyte induced by SI/R evidenced by decreasing MTT dye reduction and LDH activity in the culture medium. Meanwhile, the compound also inhibited reactive oxygen species excessive generation and stabilized mitochondrial membrane potential after SI/R. The flow cytometry assessment results indicated the inhibition of cellular apoptosis with oleuropein treatment. Furthermore, western blot analysis showed that oleuropein attenuated the expression of Cyt-C, c-caspase-3, and c-caspase-9, increased the Bcl-2/Bax ratio, and enhanced the phosphorylation of ERK1/2 and Akt after SI/R. However, the phosphorylation enhancement was partially abolished in the presence of LY294002 (PI3K inhibitor) and U0126 (ERK inhibitor). All these findings indicate that oleuropein has the protective potential against SI/R-induced injury and its protective effect may be partly due to the attenuation of apoptosis via the activation of the PI3K/Akt and ERK1/2 signaling pathways

Dihydromyricetin Attenuates TNF-α-Induced Endothelial Dysfunction through miR-21-Mediated DDAH1/ADMA/NO Signal Pathway

Accumulating studies demonstrate that dihydromyricetin (DMY), a compound extracted from Chinese traditional herb, Ampelopsis grossedentata, attenuates atherosclerotic process by improvement of endothelial dysfunction. However, the underlying mechanism remains poorly understood. Thus, the aim of this study is to investigate the potential mechanism behind the attenuating effects of DMY on tumor necrosis factor alpha- (TNF-α-) induced endothelial dysfunction. In response to TNF-α, microRNA-21 (miR-21) expression was significantly increased in human umbilical vein endothelial cells (HUVECs), in line with impaired endothelial dysfunction as evidenced by decreased tube formation and migration, endothelial nitric oxide synthase (eNOS) (ser1177) phosphorylation, dimethylarginine dimethylaminohydrolases 1 (DDAH1) expression and metabolic activity, and nitric oxide (NO) concentration as well as increased asymmetric dimethylarginine (ADMA) levels. In contrast, DMY or blockade of miR-21 expression ameliorated endothelial dysfunction in HUVECs treated with TNF-α through downregulation of miR-21 expression, whereas these effects were abolished by overexpression of miR-21. In addition, using a nonspecific NOS inhibitor, L-NAME, also abrogated the attenuating effects of DMY on endothelial dysfunction. Taken together, these data demonstrated that miR-21-mediated DDAH1/ADMA/NO signal pathway plays an important role in TNF-α-induced endothelial dysfunction, and DMY attenuated endothelial dysfunction induced by TNF-α in a miR-21-dependent manner