BUSCADOR RECOLECTA

Compiled RNAseq data from HCT-116 cells treated with BTM-3528., DLBCL are aggressive, rapidly proliferating tumors that critically depend on the ATF4-mediated integrated stress response (ISR) to adapt to stress caused by uncontrolled growth, such as hypoxia, amino acid deprivation, and accumulation of misfolded proteins. Here, we show that ISR hyperactivation is a targetable liability in DLBCL. We describe a novel class of compounds represented by BTM-3528 and BTM-3566, which activate the ISR through the mitochondrial protease OMA1. Treatment of tumor cells with compound leads to OMA1-dependent cleavage of DELE1 and OPA1, mitochondrial fragmentation, activation of the eIF2α-kinase HRI, cell growth arrest, and apoptosis. Activation of OMA1 by BTM-3528 and BTM-3566 is mechanistically distinct from inhibitors of mitochondrial electron transport, as the compounds induce OMA1 activity in the absence of acute changes in respiration. We further identify the mitochondrial protein FAM210B as a negative regulator of BTM-3528 and BTM-3566 activity. Overexpression of FAM210B prevents both OMA1 activation and apoptosis. Notably, FAM210B expression is nearly absent in healthy germinal center B-lymphocytes and in derived B-cell malignancies, revealing a fundamental molecular vulnerability which is targeted by BTM compounds. Both compounds induce rapid apoptosis across diverse DLBCL lines derived from activated B-cell, germinal center B-cell, and MYC-rearranged lymphomas. Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first-of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL., Peer reviewed

DLBCL are aggressive, rapidly proliferating tumors that critically depend on the ATF4-mediated integrated stress response (ISR) to adapt to stress caused by uncontrolled growth, such as hypoxia, amino acid deprivation, and accumulation of misfolded proteins. Here, we show that ISR hyperactivation is a targetable liability in DLBCL. We describe a novel class of compounds represented by BTM-3528 and BTM-3566, which activate the ISR through the mitochondrial protease OMA1. Treatment of tumor cells with compound leads to OMA1-dependent cleavage of DELE1 and OPA1, mitochondrial fragmentation, activation of the eIF2α-kinase HRI, cell growth arrest, and apoptosis. Activation of OMA1 by BTM-3528 and BTM-3566 is mechanistically distinct from inhibitors of mitochondrial electron transport, as the compounds induce OMA1 activity in the absence of acute changes in respiration. We further identify the mitochondrial protein FAM210B as a negative regulator of BTM-3528 and BTM-3566 activity. Overexpression of FAM210B prevents both OMA1 activation and apoptosis. Notably, FAM210B expression is nearly absent in healthy germinal center B-lymphocytes and in derived B-cell malignancies, revealing a fundamental molecular vulnerability which is targeted by BTM compounds. Both compounds induce rapid apoptosis across diverse DLBCL lines derived from activated B-cell, germinal center B-cell, and MYC-rearranged lymphomas. Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first-of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL., Peer reviewed

DLBCL are aggressive, rapidly proliferating tumors that critically depend on the ATF4-mediated integrated stress response (ISR) to adapt to stress caused by uncontrolled growth, such as hypoxia, amino acid deprivation, and accumulation of misfolded proteins. Here, we show that ISR hyperactivation is a targetable liability in DLBCL. We describe a novel class of compounds represented by BTM-3528 and BTM-3566, which activate the ISR through the mitochondrial protease OMA1. Treatment of tumor cells with compound leads to OMA1-dependent cleavage of DELE1 and OPA1, mitochondrial fragmentation, activation of the eIF2α-kinase HRI, cell growth arrest, and apoptosis. Activation of OMA1 by BTM-3528 and BTM-3566 is mechanistically distinct from inhibitors of mitochondrial electron transport, as the compounds induce OMA1 activity in the absence of acute changes in respiration. We further identify the mitochondrial protein FAM210B as a negative regulator of BTM-3528 and BTM-3566 activity. Overexpression of FAM210B prevents both OMA1 activation and apoptosis. Notably, FAM210B expression is nearly absent in healthy germinal center B-lymphocytes and in derived B-cell malignancies, revealing a fundamental molecular vulnerability which is targeted by BTM compounds. Both compounds induce rapid apoptosis across diverse DLBCL lines derived from activated B-cell, germinal center B-cell, and MYC-rearranged lymphomas. Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first-of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL., Peer reviewed

DLBCL are aggressive, rapidly proliferating tumors that critically depend on the ATF4-mediated integrated stress response (ISR) to adapt to stress caused by uncontrolled growth, such as hypoxia, amino acid deprivation, and accumulation of misfolded proteins. Here, we show that ISR hyperactivation is a targetable liability in DLBCL. We describe a novel class of compounds represented by BTM-3528 and BTM-3566, which activate the ISR through the mitochondrial protease OMA1. Treatment of tumor cells with compound leads to OMA1-dependent cleavage of DELE1 and OPA1, mitochondrial fragmentation, activation of the eIF2α-kinase HRI, cell growth arrest, and apoptosis. Activation of OMA1 by BTM-3528 and BTM-3566 is mechanistically distinct from inhibitors of mitochondrial electron transport, as the compounds induce OMA1 activity in the absence of acute changes in respiration. We further identify the mitochondrial protein FAM210B as a negative regulator of BTM-3528 and BTM-3566 activity. Overexpression of FAM210B prevents both OMA1 activation and apoptosis. Notably, FAM210B expression is nearly absent in healthy germinal center B-lymphocytes and in derived B-cell malignancies, revealing a fundamental molecular vulnerability which is targeted by BTM compounds. Both compounds induce rapid apoptosis across diverse DLBCL lines derived from activated B-cell, germinal center B-cell, and MYC-rearranged lymphomas. Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first-of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL., Peer reviewed

Supplementary Figures (1-10), Tables (1-5), Notes (1-2) and References., Peer reviewed

[Description of methods used for collection/generation of data] ATACseq and RNAseq methodology in different developmental stages, Analysis of the transcriptomes and chromatin accessibility of multiple developmental stages of the indirect-developing hemichordate Ptychodera flava. After the individual analysis of each sample, integration of ATACseq and RNAseq data was performed in order to reconstruct genetic and regulatory networks. These data were also compared to other species, what could shed light on deuterostome evolution., Ministerio de Ciencia e Innovación (grant PID2022-141288NB-I00)., supp_data_01.xlsx supp_data_02.xlsx supp_data_03.xlsx supp_data_04.xlsx supp_data_05.xlsx supp_data_06.xlsx supp_data_07.xlsx supp_data_08.xlsx supp_data_09.bed supp_data_10.tsv supp_data_11.tsv.gz supp_data_12.tsv.gz supp_data_13.xlsx supp_data_14.xlsx supp_data_15.xlsx supp_data_16.xlsx, Peer reviewed

Quantum-dot (QD) solids are being widely exploited as a solution-processable technology to develop photovoltaic, light-emission, and photodetection devices. Charge transport in these materials is the result of a compromise between confinement at the individual QD level and electronic coupling among the different nanocrystals in the ensemble. While this is commonly achieved by ligand engineering in colloidal-based systems, ligand-free QD assemblies have recently emerged as an exciting alternative where nanostructures can be directly grown into porous matrices with optical quality as well as control over their connectivity and, hence, charge transport properties. In this context, we present a complete photophysical study comprising fluence- and temperature-dependent timeresolved spectroscopy to study carrier dynamics in ligand-free QD networks with gradually varying degrees of interconnectivity, which we achieve by changing the average distance between the QDs. Analysis of the photoluminescence and absorption properties of the QD assemblies, involving both static and timeresolved measurements, allows us to identify the weight of the different recombination mechanisms, both radiative and nonradiative, as a function of QD connectivity. We propose a picture where carrier diffusion, which is needed for any optoelectronic application and implies interparticle transport, gives rise to the exposure of carriers to a larger defect landscape than in the case of isolated QDs. The use of a broad range of fluences permits extracting valuable information for applications demanding either low- or high-carrier-injection levels and highlighting the relevance of a judicious design to balance recombination and diffusion., HM is thankful for the financial support of the Spanish Ministry of Science and Innovation under grant PID2020-116593RB-I00, funded by MCIN/AEI/10.13039/501100011033, and of the Junta de Andalucía under grant P18-RT-2291 (FEDER/UE). HM, JFGL, and DOT acknowledge financial support from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 956270 (Persephone). ARSK acknowledges the start-up funds provided by Wake Forest University and funding from the Center for Functional Materials and the Office of Research and Sponsored Programs at WFU., (Folder > File.txt) Figure 1 Figure_1c(norm. Abs).txt Figure_1d(PL).txt Figure_1e(PLQY).txt Figure 2 Figure_2a (TRPL_raw_bulk).txt Figure_2b (TRPL_raw_30per).txt Figure_2c (TRPL_raw_20per).txt Figure_2d (TRPL_raw_10per).txt Figure_2e (TRPL_raw_5per).txt Figure_2i (TRPL_photon_flux_bulk).txt Figure_2j (TRPL_photon_flux_30per).txt Figure_2k (TRPL_photon_flux_20per).txt Figure_2l (TRPL_photon_flux_10per).txt Figure_2m (TRPL_photon_flux_5per).txt Figure 3 Figure_3a (PLQY_bulk).txt Figure_3b (rel_PLQY_Tdep_30per).txt Figure_3c (rel_PLQY_Tdep_20per).txt Figure_3d (rel_PLQY_Tdep_10per).txt Figure_3e (rel_PLQY_Tdep_5per).txt Figure 4 Figure_4a (30per_norm_PL_80K).txt Figure_4b (5per_norm_PL_80K).txt Figure_4c (30per_TA_77K_N=15d5).csv Figure_4d (5per_TA_77K_N=11d1).csv Figure 5 Figure 5a (30per_GSB_decay).txt Figure 5b (5per_GSB_decay).txt Figure 5c (30per_GSB_decay_derivative).txt Figure 5d (5per_GSB_decay_biexciton_fit_all).txt, Peer reviewed

DLBCL are aggressive, rapidly proliferating tumors that critically depend on the ATF4-mediated integrated stress response (ISR) to adapt to stress caused by uncontrolled growth, such as hypoxia, amino acid deprivation, and accumulation of misfolded proteins. Here, we show that ISR hyperactivation is a targetable liability in DLBCL. We describe a novel class of compounds represented by BTM-3528 and BTM-3566, which activate the ISR through the mitochondrial protease OMA1. Treatment of tumor cells with compound leads to OMA1-dependent cleavage of DELE1 and OPA1, mitochondrial fragmentation, activation of the eIF2α-kinase HRI, cell growth arrest, and apoptosis. Activation of OMA1 by BTM-3528 and BTM-3566 is mechanistically distinct from inhibitors of mitochondrial electron transport, as the compounds induce OMA1 activity in the absence of acute changes in respiration. We further identify the mitochondrial protein FAM210B as a negative regulator of BTM-3528 and BTM-3566 activity. Overexpression of FAM210B prevents both OMA1 activation and apoptosis. Notably, FAM210B expression is nearly absent in healthy germinal center B-lymphocytes and in derived B-cell malignancies, revealing a fundamental molecular vulnerability which is targeted by BTM compounds. Both compounds induce rapid apoptosis across diverse DLBCL lines derived from activated B-cell, germinal center B-cell, and MYC-rearranged lymphomas. Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first-of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL., Peer reviewed

Supplementary material to DESI's publication "Target Selection for the DESI Peculiar Velocity Survey" to comply with the data management plan. Contains data for: Figure 1: color-color diagram, comparing truth catalogues to data from the survey. Data contains all observational colors to construct the heatmap and the colors of the two truth catalogues shown in the left and right panel respectively. Figure 2: Sersic index for different morphological types. Data contains relative number counts to reproduce the histogram. Figure 3 consists of images, hence not included here. Figure 4: quality metrics for ETG classification. Data includes the various metrics as a function of elliptical probability. Figure 5: Success rate for different magnitudes. Data contains all the plotted data points as a function of magnitude. Figure 6: pPXF example for ETG: Data contains the plotted spectrum and model. Figure 7: quality metrics for LTG classification. Data includes the various metrics as a function of spiral probability. Figure 8: example for TF measurements: Data contains the two spectra shown in the figure. Figure 9: example of rotation curves from MaNGA: Data contains the individual measurements, fit, and shown example. Figures 10 + 11: comparison between the observed rotational velocities and calculated one. Data contains DESI and MaNGA measurements as well as expected values from the fit. Figure 12: Sky distribution of PV surveys. Data contains the coordinates of the targets of all the surveys shown. Figure 13: Redshift distribution of different PV surveys and our targets. Data contains the number counts to reproduce the histogram. Figure 14: Forecast for f-sigma8 constraints. Data contains the predictions from different theories and the forecast for DESI (PV and/or BGS). Figure 15: Forecasts for measurements of the velocity power spectrum. Data contains the forecast for the DESI., Australian Laureate Fellowships - Grant ID: FL180100168 FL180100168 Australian Research Council, Peer reviewed

Gene level data for Venn Diagram figure of Cell line screening data, DLBCL are aggressive, rapidly proliferating tumors that critically depend on the ATF4-mediated integrated stress response (ISR) to adapt to stress caused by uncontrolled growth, such as hypoxia, amino acid deprivation, and accumulation of misfolded proteins. Here, we show that ISR hyperactivation is a targetable liability in DLBCL. We describe a novel class of compounds represented by BTM-3528 and BTM-3566, which activate the ISR through the mitochondrial protease OMA1. Treatment of tumor cells with compound leads to OMA1-dependent cleavage of DELE1 and OPA1, mitochondrial fragmentation, activation of the eIF2α-kinase HRI, cell growth arrest, and apoptosis. Activation of OMA1 by BTM-3528 and BTM-3566 is mechanistically distinct from inhibitors of mitochondrial electron transport, as the compounds induce OMA1 activity in the absence of acute changes in respiration. We further identify the mitochondrial protein FAM210B as a negative regulator of BTM-3528 and BTM-3566 activity. Overexpression of FAM210B prevents both OMA1 activation and apoptosis. Notably, FAM210B expression is nearly absent in healthy germinal center B-lymphocytes and in derived B-cell malignancies, revealing a fundamental molecular vulnerability which is targeted by BTM compounds. Both compounds induce rapid apoptosis across diverse DLBCL lines derived from activated B-cell, germinal center B-cell, and MYC-rearranged lymphomas. Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first-of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL., Peer reviewed