A whole-genome RNAi screen identifies an 8q22 gene cluster that inhibits death receptor-mediated apoptosis.

Deregulation of apoptosis is a common occurrence in cancer, for which emerging oncology therapeutic agents designed to engage this pathway are undergoing clinical trials. With the aim of uncovering strategies to activate apoptosis in cancer cells, we used a pooled shRNA screen to interrogate death receptor signaling. This screening approach identified 16 genes that modulate the sensitivity to ligand induced apoptosis, with several genes exhibiting frequent overexpression and/or copy number gain in cancer. Interestingly, two of the top hits, EDD1 and GRHL2, are found 50 kb apart on chromosome 8q22, a region that is frequently amplified in many cancers. By using a series of silencing and overexpression studies, we show that EDD1 and GRHL2 suppress death-receptor expression, and that EDD1 expression is elevated in breast, pancreas, and lung cancer cell lines resistant to death receptor-mediated apoptosis. Supporting the relevance of EDD1 and GRHL2 as therapeutic candidates to engage apoptosis in cancer cells, silencing the expression of either gene sensitizes 8q22-amplified breast cancer cell lines to death receptor induced apoptosis. Our findings highlight a mechanism by which cancer cells may evade apoptosis, and therefore provide insight in the search for new targets and functional biomarkers for this pathway.

Semantic reconstruction of continuous language from non-invasive brain recordings.

A brain-computer interface that decodes continuous language from non-invasive recordings would have many scientific and practical applications. Currently, however, non-invasive language decoders can only identify stimuli from among a small set of words or phrases. Here we introduce a non-invasive decoder that reconstructs continuous language from cortical semantic representations recorded using functional magnetic resonance imaging (fMRI). Given novel brain recordings, this decoder generates intelligible word sequences that recover the meaning of perceived speech, imagined speech and even silent videos, demonstrating that a single decoder can be applied to a range of tasks. We tested the decoder across cortex and found that continuous language can be separately decoded from multiple regions. As brain-computer interfaces should respect mental privacy, we tested whether successful decoding requires subject cooperation and found that subject cooperation is required both to train and to apply the decoder. Our findings demonstrate the viability of non-invasive language brain-computer interfaces.

Corrigendum: QUaRTM: A Quadcopter with Unactuated Rotor Tilting Mechanism capable of faster, more agile, and more efficient flight.

[This corrects the article DOI: 10.3389/frobt.2022.1033715.].

Brain encoding models based on multimodal transformers can transfer across language and vision.

Encoding models have been used to assess how the human brain represents concepts in language and vision. While language and vision rely on similar concept representations, current encoding models are typically trained and tested on brain responses to each modality in isolation. Recent advances in multimodal pretraining have produced transformers that can extract aligned representations of concepts in language and vision. In this work, we used representations from multimodal transformers to train encoding models that can transfer across fMRI responses to stories and movies. We found that encoding models trained on brain responses to one modality can successfully predict brain responses to the other modality, particularly in cortical regions that represent conceptual meaning. Further analysis of these encoding models revealed shared semantic dimensions that underlie concept representations in language and vision. Comparing encoding models trained using representations from multimodal and unimodal transformers, we found that multimodal transformers learn more aligned representations of concepts in language and vision. Our results demonstrate how multimodal transformers can provide insights into the brain's capacity for multimodal processing.

A natural language fMRI dataset for voxelwise encoding models.

Speech comprehension is a complex process that draws on humans' abilities to extract lexical information, parse syntax, and form semantic understanding. These sub-processes have traditionally been studied using separate neuroimaging experiments that attempt to isolate specific effects of interest. More recently it has become possible to study all stages of language comprehension in a single neuroimaging experiment using narrative natural language stimuli. The resulting data are richly varied at every level, enabling analyses that can probe everything from spectral representations to high-level representations of semantic meaning. We provide a dataset containing BOLD fMRI responses recorded while 8 participants each listened to 27 complete, natural, narrative stories (~6 hours). This dataset includes pre-processed and raw MRIs, as well as hand-constructed 3D cortical surfaces for each participant. To address the challenges of analyzing naturalistic data, this dataset is accompanied by a python library containing basic code for creating voxelwise encoding models. Altogether, this dataset provides a large and novel resource for understanding speech and language processing in the human brain.

QUaRTM: A Quadcopter with Unactuated Rotor Tilting Mechanism capable of faster, more agile, and more efficient flight.

We present QUaRTM - a novel quadcopter design capable of tilting the propellers into the forward flight direction, which reduces the drag area and therefore allows for faster, more agile, and more efficient flight. The vehicle can morph between two configurations in mid-air, including the untilted configuration and the tilted configuration. The vehicle in the untilted configuration has a higher pitch torque capacity and a smaller vertical dimension. The vehicle in the tilted configuration has a lower drag area, leading to a higher top speed, higher agility at high speed, and better flight efficiency. The morphing is accomplished without any additional actuators beyond the four motors of a quadcopter. The rigid connections between the quadcopter frame and the quadcopter arms are replaced with sprung hinges. This allows the propellers to be tilted when high thrusts are produced, and recover to the untilted configuration when the thrusts are brought low. The effectiveness of such a vehicle is demonstrated by running experiments on a prototype vehicle with a shape similar to a regular quadcopter. Through the use of tilting, the vehicle is shown to have a 12.5% higher maximum speed, better high-speed agility as the maximum crash-free cruise speed increased by 7.5%, and a better flight efficiency as the power consumption has dropped by more than 20% in the speed range of 15-20 m s-1.

Cathode Material Development in the Past Decade for H2 Production from Microbial Electrolysis Cells.

Cathode materials are critical for microbial electrolysis cell (MEC) development and its contribution to achieving a circular hydrogen economy. There are numerous reports on the progress in MEC cathode development during the past decade, but a comprehensive review on the quantitative comparisons and critical assessments of these works is lacking. This Review summarizes and analyzes the published literature on MEC cathode and catalyst development in the past decade, providing an overview of new materials examined during this time period and quantitative analyses on system performance and trends in materials development. Collected data indicate that hybrid materials have become the most popular catalyst candidate while nickel materials also attract increasing interest and exploration. However, the dilemma between higher H2 production rate and larger MEC volume remains and still requires more investigation of novel MEC cathode catalysts and configurations to offer a solution.

A mouse knockout library for secreted and transmembrane proteins.

Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.

Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers.

The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene has been identified as an oncogene in a subset of non-small cell lung cancers (NSCLC). We used profiling of cancer genomes on an exon array to develop a novel computational method for the global search of gene rearrangements. This approach led to the detection of EML4-ALK fusion in breast and colorectal carcinomas in addition to NSCLC. Screening of a large collection of patient tumor samples showed the presence of EML4-ALK fusion in 2.4% of breast (5 of 209), 2.4% of colorectal (2 of 83), and in 11.3% of NSCLC (12 of 106). Besides previously known EML4-ALK variants 1 (E13; A20) and 2 (E20; A20), a novel variant E21; A20 was found in colorectal carcinoma. The presence of an EML-ALK rearrangement was verified by identifying genomic fusion points in tumor samples representative of breast, colon, and NSCLC. EML4-ALK translocation was also confirmed by fluorescence in situ hybridization assay, which revealed its substantial heterogeneity in both primary tumors and tumor-derived cell lines. To elucidate the functional significance of EML4-ALK, we examined the growth of cell lines harboring the fusion following EML4 and ALK silencing by small interfering RNA. Significant growth inhibition was observed in some but not all cell lines, suggesting their variable dependence on ALK-mediated cell survival signaling. Collectively, these findings show the recurrence of EML4-ALK fusion in multiple solid tumors and further substantiate its role in tumorigenesis.