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Table of Contents Alert: EMBO reports, Vol. 20, No. 10, 04 October 2019

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Cover Image EMBO reports
Volume 20, Issue 10

04 October 2019

News & Views

A snapshot of membrane protein insertion
Yoshiki Tanaka, Tomoya Tsukazaki

EMBO Rep (2019) 20: e49034 | First Published: 13 September 2019

The SecYEG translocon provides the major route for co‐translational membrane protein insertion in bacteria. A cryo‐electron microscopy structure of SecYEG in lipid nanodiscs bound to a translating ribosome reveals an intermediate stage of protein insertion.

The ubiquitin E2 enzyme UBE2QL1 mediates lysophagy
Noboru Mizushima

EMBO Rep (2019) 20: e49104 | First Published: 15 September 2019

The autophagic clearance of damaged lysosomes with ruptured membranes involves their extensive ubiquitination. A study in this issue identifies the E2 enzyme UBE2QL1 as an important player in lysophagy and lysosomal homeostasis.

Science & Society

The limits of machine intelligence : Despite progress in machine intelligence, artificial general intelligence is still a major challenge
Henry Shevlin, Karina Vold, Matthew Crosby, Marta Halina

EMBO Rep (2019) 20: e49177 | First Published: 18 September 2019

Despite recent breakthroughs in machine learning, current artificial systems lack key features of biological intelligence. Whether the current limitations can be overcome is an open question, but critical to answer, given the implications for society.

Open Access
Preparing biomedical students for the unknown : Some unusual challenges for students to help them understand the fundamentals of empirical research
Adolfo Rivero‐Müller, Matthias Nees

EMBO Rep (2019) 20: e49004 | First Published: 15 September 2019

Make teaching challenging again: a pedagogic approach to educate students on how to do science rather than learn about it.

Why control an experiment? : From empiricism, via consciousness, toward Implicate Order
John S Torday, František Baluška

EMBO Rep (2019) 20: e49110 | First Published: 03 September 2019

Empirical research is based on observation and experimentation. Yet, experimental controls are essential for overcoming our sensory limits and generating reliable, unbiased and objective results.

Illuminating human disease : The potential of in vivo imaging for preclinical research and diagnostics
Philip Hunter

EMBO Rep (2019) 20: e49195 | First Published: 16 September 2019

New in vivo imaging technologies, including optical methods to observe biological processes in real time, show great promise for preclinical research and diagnostics of human diseases.


Open Access
Mitochondria orchestrate proteostatic and metabolic stress responses
Claes Andréasson, Martin Ott, Sabrina Büttner

EMBO Rep (2019) 20: e47865 | First Published: 18 September 2019

The eukaryotic cell consists of an interconnected network of organelles that need to communicate and orchestrate their response to cellular stresses and aging. This review discusses the regulatory pathways that sense and control metabolism and sub‐cellular proteostasis systems with a focus on mitochondria‐to‐nucleus signaling.


Open Access
Partially inserted nascent chain unzips the lateral gate of the Sec translocon
Lukas Kater, Benedikt Frieg, Otto Berninghausen, Holger Gohlke, Roland Beckmann, Alexej Kedrov

EMBO Rep (2019) 20: e48191 | First Published: 05 August 2019

Cryo‐electron microscopy and atomistic simulations of SecYEG in the lipid environment reveal an early stage of membrane protein insertion. The flexible nascent chain triggers a conformational change that pre‐opens the translocon.

Open Access
PPM1G forms a PPP‐type phosphatase holoenzyme with B56δ that maintains adherens junction integrity
Parveen Kumar, Prajakta Tathe, Neelam Chaudhary, Subbareddy Maddika

EMBO Rep (2019) 20: e46965 | First Published: 21 August 2019

PPM family phosphatases are thought to act as monomers. This study shows that PPM1G forms a distinct holoenzyme complex with the PP2A regulatory subunit B56δ in the cytoplasm that functions in adherens junction assembly.

Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment
Federica De Leo, Giacomo Quilici, Mario Tirone, Francesco De Marchis, Valeria Mannella, Chiara Zucchelli, Alessandro Preti, Alessandro Gori, Maura Casalgrandi, Rosanna Mezzapelle, Marco E Bianchi, Giovanna Musco

EMBO Rep (2019) 20: e47788 | First Published: 14 August 2019

Diflunisal, which is a drug in use in the clinic, selectively inhibits the chemotactic activity of HMGB1/CXCL12 complex.

Pannexin‐1 limits the production of proinflammatory cytokines during necroptosis
Tiphaine Douanne, Gwennan André‐Grégoire, Kilian Trillet, An Thys, Antonin Papin, Magalie Feyeux, Philippe Hulin, David Chiron, Julie Gavard, Nicolas Bidère

EMBO Rep (2019) 20: e47840 | First Published: 14 August 2019

The activation of MLKL by RIPK3 controls the execution of necroptosis. During the early stages of necroptotic cell death, MLKL oligomers promote the activation of Pannexin‐1 channels, which constricts the production of proinflammatory cytokines.

CDK12 drives breast tumor initiation and trastuzumab resistance via WNT and IRS1‐ErbB‐PI3K signaling
Hee‐Joo Choi, Sora Jin, Hani Cho, Hee‐Young Won, Hee Woon An, Ga‐Young Jeong, Young‐Un Park, Hyung‐Yong Kim, Mi Kyung Park, Taekwon Son, Kyueng‐Whan Min, Ki‐Seok Jang, Young‐Ha Oh, Jeong‐Yeon Lee, Gu Kong

EMBO Rep (2019) 20: e48058 | First Published: 30 August 2019

CDK12, a RNA polymerase II kinase, promotes breast cancer stem cell‐like properties mediated by WNT and ErbB‐PI3K signaling. Targeting CDK12 improves trastuzumab therapy in breast cancers characterised by HER2/CDK12 co‐amplification.


Open Access
The ubiquitin‐conjugating enzyme UBE2QL1 coordinates lysophagy in response to endolysosomal damage
Lisa Koerver, Chrisovalantis Papadopoulos, Bin Liu, Bojana Kravic, Giulia Rota, Lukas Brecht, Tineke Veenendaal, Mira Polajnar, Anika Bluemke, Michael Ehrmann, Judith Klumperman, Marja Jäättelä, Christian Behrends, Hemmo Meyer

EMBO Rep (2019) 20: e48014 | First Published: 21 August 2019

Lysophagy, the selective autophagy of permeabilized lysosomes, requires extensive ubiquitination of the damaged organelle. The ubiquitin‐conjugating enzyme UBE2QL1 is a key coordinator of lysosome ubiquitination and lysophagy after lysosomal damage.

Open Access
Targeting of early endosomes by autophagy facilitates EGFR recycling and signalling
Jane Fraser, Joanne Simpson, Rosa Fontana, Chieko Kishi‐Itakura, Nicholas T Ktistakis, Noor Gammoh

EMBO Rep (2019) 20: e47734 | First Published: 26 August 2019

Targeting of damaged organelles by autophagy is crucial for cell homeostasis. This study identifies a novel function of the autophagy machinery in recognising damaged early endosomes, the absence of which compromises EGFR trafficking and signalling.

Open Access
Dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis
Yi‐Hsiang Wang, Jo‐Ting Huang, Wen‐Ling Chen, Rong‐Hsuan Wang, Ming‐Chien Kao, Yan‐Ru Pan, Shih‐Hsuan Chan, Kuo‐Wang Tsai, Hsing‐Jien Kung, Kai‐Ti Lin, Lu‐Hai Wang

EMBO Rep (2019) 20: e45986 | First Published: 29 August 2019

Cystathionine‐γ‐lyase (CTH) and its catalyzed product hydrogen sulfide, a known gaseous transmitter, are dysregulated in prostate cancer. Increased CTH activity promotes cancer progression and metastasis via the sulfhydration of the NF‐κB subunit p65.

S‐acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate cell adhesion
Keith T Woodley, Mark O Collins

EMBO Rep (2019) 20: e47472 | First Published: 12 August 2019

Cell membrane localized DHHC5 palmitoylates components of desmosomes and promotes cell adhesion.

Open Access
TDP2 negatively regulates axon regeneration by inducing SUMOylation of an Ets transcription factor
Yoshiki Sakai, Hiroshi Hanafusa, Strahil Iv Pastuhov, Tatsuhiro Shimizu, Chun Li, Naoki Hisamoto, Kunihiro Matsumoto

EMBO Rep (2019) 20: e47517 | First Published: 08 August 2019

The Mxl‐1 transcription factor promotes axon regeneration in C. elegans via inhibition of TDPT‐1, which reduces ETS‐4 SUMOylation and increases svh‐2 transcription.

Rab35 controls cilium length, function and membrane composition
Stefanie Kuhns, Cecília Seixas, Sara Pestana, Bárbara Tavares, Renata Nogueira, Raquel Jacinto, José S Ramalho, Jeremy C Simpson, Jens S Andersen, Arnaud Echard, Susana S Lopes, Duarte C Barral, Oliver E Blacque

EMBO Rep (2019) 20: e47625 | First Published: 21 August 2019

Rab35 at the mammalian and zebrafish cilium regulates cilium length and left‐right asymmetry, and controls the ciliary levels of PI(4,5)P2 and regulators of the Sonic hedgehog pathway.

Trehalose‐6‐phosphate signaling regulates thermoresponsive hypocotyl growth in Arabidopsis thaliana
Geonhee Hwang, Sara Kim, Jae‐Yong Cho, Inyup Paik, Jeong‐Il Kim, Eunkyoo Oh

EMBO Rep (2019) 20: e47828 | First Published: 08 August 2019

Trehalose‐6‐phosphate is a signaling molecule coordinating endogenous sugar availability and plant growth at high temperatures.

Open Access
Robotic platform for microinjection into single cells in brain tissue
Gabriella Shull, Christiane Haffner, Wieland B Huttner, Suhasa B Kodandaramaiah, Elena Taverna

EMBO Rep (2019) 20: e47880 | First Published: 30 August 2019

This study reports the Autoinjector, a robotic tool that enables microinjection of hundreds of cells within a single organotypic slice. The robot is validated in brain tissues and renders microinjection a broadly accessible high‐performance cell manipulation technique.

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