Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling

The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions,including cell morphology,elasticity,migration,organelle localization,and resistance against mechanical or pathological stress.Currently available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the nucleus.Effective tools for long-term manipulation of vimentin network dispersion in living cells are still lacking,limiting in-depth studies on vimentin function and potential therapeutic applications.Here,we verified that a commercially available small molecule,trametinib,is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or Translational regulation.Further evidence confirmed its low cytotoxicity and similar effects on different cell types.Importantly,Trametinib has no impact on the other two cytoskeletal systems,actin filaments and the microtubule network.Moreover,Trametinib regulates vimentin network dispersion rapidly and efficiently,with effects persisting for up to 48 h after drug withdrawal.We also ruled out the possibility that Trametinib directly affects the phosphorylation level of vimentin.In summary,we identified an unprecedented regulator Trametinib,which is capable of spreading the vimentin network toward the cell periphery,and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.

High-resolution sea surface wind speeds of Super Typhoon Lekima (2019) retrieved by Gaofen-3 SAR

Gaofen-3(GF-3)is the first Chinese spaceborne multi-polarization synthetic aperture radar(SAR)instrument at C-band(5.43 GHz).In this paper,we use data collected from GF-3 to observe Super Typhoon Lekima(2019)in the East China Sea.Using a VH-polarized wide ScanSAR(WSC)image,ocean surface wind speeds at 100m horizontal resolution are obtained at 21:56:59 UTC on 8 August 2019,with the maximum wind speed,38.9 m·s^(-1).Validating the SAR-retrieved winds with buoymeasured wind speeds,we find that the root mean square error(RMSE)is 1.86 m·s^(-1),and correlation coefficient,0.92.This suggests that wind speeds retrieved from GF-3 SAR are reliable.Both the European Centre for MediumRange Weather Forecasts(ECMWF)fine grid operational forecast products with spatial resolution,and China Global/Regional Assimilation and Prediction Enhance System(GRAPES)have good performances on surface wind prediction under weak wind speed condition(<24 m·s^(-1)),but underestimate the maximum wind speed when the storm is intensified as a severe tropical storm(>24m·s^(-1)).With respect to SAR-retrieved wind speeds,the RMSEs are 5.24 m·s^(–1) for ECMWF and 5.17 m·s^(–1) for GRAPES,with biases of 4.16 m·s^(–1) for ECMWF and 3.84 m·s^(-1)for GRAPES during Super Typhoon Lekima(2019).

Key elements for designing and performing a CRISPR/Cas9-based genetic screen

Reverse genetic screens are invaluable for uncovering gene functions, but are traditionally hampered by some technical limitations. Over the past few years, since the advent of the revolutionary CRISPR/Cas9 technology, its power in genome editing has been harnessed to overcome the traditional limitations in reverse genetic screens, with successes in various biological contexts. Here, we outline these CRISPR/Cas9-based screens, provide guidance on the design of effective screens and discuss the potential future directions of development of this field.

Tropical Cyclone Ocean Winds and Structure Parameters Retrieved from Cross-Polarized SAR Measurements

Spaceborne synthetic aperture radar(SAR)can provide unique capabilities to measure ocean surface winds under tropical cyclones(TCs),on synoptic scales,and at a very high spatial resolution.In this paper,we first discuss the accuracy and reliability of SAR-retrieved TC marine winds.The results show that wind retrievals from SAR images are in good agreement with Stepped Frequency Microwave Radiometer(SFMR)measurements,with root-mean-square error(RMSE)and correlation coefficient(CC)of 3.52 m s^(−1) and 0.91,respectively.Based on the marine winds retrieved from SAR images,a relatively simple method is applied to extract the storm intensity(maximum wind speed)and wind radii(R34,R50,and R64)from 234 cross-polarized SAR images,in the Northwest Pacific Ocean from 2015 to 2023.The SAR-retrieved TC wind radii and intensities are compared with the best-track reports,with RMSEs for R34,R50,and R64 being 48.32,41.88,and 38.51 km,and CCs being 0.87,0.83,and 0.65,respectively.In terms of TC intensity,the RMSE and bias between SAR estimates and best-track data are 7.32 and 0.38 m s^(−1),respectively.For TC Surigae(2023),we found that employing a combination of multiplatform SARs,acquired within a short time interval,has the potential to simultaneously measure the intensity and wind structure parameters.In addition,for a storm with a long life cycle,the multitemporal synergistic SARs can be used to investigate fine-scale features of the TC ocean winds,as well as the evolution of TC surface wind intensities and wind structures.