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Takashi Namba, Samir Vaid, Wieland Huttner
Primate neocortex development and evolution: Conserved versus evolved folding.
J Comp Neurol, 527(10) 1621-1632 (2019)
PubMed Source   

The neocortex, the seat of higher cognitive functions, exhibits a key feature across mammalian species-a highly variable degree of folding. Within the neocortex, two distinct subtypes of cortical areas can be distinguished, the isocortex and the proisocortex. Here, we have compared specific spatiotemporal aspects of folding between the proisocortex and the isocortex in 13 primates, including human, chimpanzee, and various Old World and New World monkeys. We find that folding at the boundaries of the dorsal isocortex and the proisocortex, which gives rise to the cingulate sulcus (CiS) and the lateral fissure (LF), is conserved across the primates studied and is therefore referred to as conserved folding. In contrast, the degree of folding within the dorsal isocortex exhibits huge variation across these primates, indicating that this folding, which gives rise to gyri and sulci, is subject to major changes during primate evolution. We therefore refer to the folding within the dorsal isocortex as evolved folding. Comparison of fetal neocortex development in long-tailed macaque and human reveals that the onset of conserved folding precedes the onset of evolved folding. Moreover, the analysis of infant human neocortex exhibiting lissencephaly, a developmental malformation thought to be mainly due to abnormal neuronal migration, shows that the evolved folding is perturbed more than the conserved folding. Taken together, our study presents a two-step model of folding that pertains to primate neocortex development and evolution. Specifically, our data imply that the conserved folding and the evolved folding constitute two distinct, sequential events.
@article{Namba7305,
author={Takashi Namba, Samir Vaid, Wieland Huttner},
title={Primate neocortex development and evolution: Conserved versus evolved folding.},
journal ={The Journal of comparative neurology},
volume={527},
issue ={10},
pages={1621--1632},
year=2019
}

Aniruddha Mitra, Marc Suñé, Stefan Diez, José M Sancho, David Oriola, Jaume Casademunt
A Brownian Ratchet Model Explains the Biased Sidestepping of Single-Headed Kinesin-3 KIF1A.
Biophys J, 116(12) 2266-2274 (2019)
PubMed Source   

The kinesin-3 motor KIF1A is involved in long-ranged axonal transport in neurons. To ensure vesicular delivery, motors need to navigate the microtubule lattice and overcome possible roadblocks along the way. The single-headed form of KIF1A is a highly diffusive motor that has been shown to be a prototype of a Brownian motor by virtue of a weakly bound diffusive state to the microtubule. Recently, groups of single-headed KIF1A motors were found to be able to sidestep along the microtubule lattice, creating left-handed helical membrane tubes when pulling on giant unilamellar vesicles in vitro. A possible hypothesis is that the diffusive state enables the motor to explore the microtubule lattice and switch protofilaments, leading to a left-handed helical motion. Here, we study the longitudinal rotation of microtubules driven by single-headed KIF1A motors using fluorescence-interference contrast microscopy. We find an average rotational pitch of ≃1.5μm, which is remarkably robust to changes in the gliding velocity, ATP concentration, microtubule length, and motor density. Our experimental results are compared to stochastic simulations of Brownian motors moving on a two-dimensional continuum ratchet potential, which quantitatively agree with the fluorescence-interference contrast experiments. We find that single-headed KIF1A sidestepping can be explained as a consequence of the intrinsic handedness and polarity of the microtubule lattice in combination with the diffusive mechanochemical cycle of the motor.
@article{Mitra7406,
author={Aniruddha Mitra, Marc Suñé, Stefan Diez, José M Sancho, David Oriola, Jaume Casademunt},
title={A Brownian Ratchet Model Explains the Biased Sidestepping of Single-Headed Kinesin-3 KIF1A.},
journal ={Biophysical journal},
volume={116},
issue ={12},
pages={2266--2274},
year=2019
}

João P L Castro, Michelle N Yancoskie, Marta Marchini, Stefanie Belohlavy, Layla Hiramatsu, Marek Kučka, William H Beluch, Ronald Naumann, Isabella Skuplik, John Cobb, Nick H Barton, Campbell Rolian, Yingguang Frank Chan
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice.
Elife, 8 Art. No. doi: 10.7554/eLife.42014 (2019)
PubMed Source   

Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.
@article{Castro7408,
author={João P L Castro, Michelle N Yancoskie, Marta Marchini, Stefanie Belohlavy, Layla Hiramatsu, Marek Kučka, William H Beluch, Ronald Naumann, Isabella Skuplik, John Cobb, Nick H Barton, Campbell Rolian, Yingguang Frank Chan},
title={An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice.},
journal ={eLife},
volume={8},
pages={1--1},
year=2019
}

Titus Franzmann, Simon Alberti
Protein Phase Separation as a Stress Survival Strategy.
Cold Spring Harb Perspect Biol, 11(6) Art. No. a034058 (2019)
PubMed Source   

Cells under stress must adjust their physiology, metabolism, and architecture to adapt to the new conditions. Most importantly, they must down-regulate general gene expression, but at the same time induce synthesis of stress-protective factors, such as molecular chaperones. Here, we investigate how the process of phase separation is used by cells to ensure adaptation to stress. We summarize recent findings and propose that the solubility of important translation factors is specifically affected by changes in physical-chemical parameters such temperature or pH and modulated by intrinsically disordered prion-like domains. These stress-triggered changes in protein solubility induce phase separation into condensates that regulate the activity of the translation factors and promote cellular fitness. Prion-like domains play important roles in this process as environmentally regulated stress sensors and modifier sequences that determine protein solubility and phase behavior. We propose that protein phase separation is an evolutionary conserved feature of proteins that cells harness to regulate adaptive stress responses and ensure survival in extreme environmental conditions.
@article{Franzmann7321,
author={Titus Franzmann, Simon Alberti},
title={Protein Phase Separation as a Stress Survival Strategy.},
journal ={Cold Spring Harbor perspectives in biology},
volume={11},
issue ={6},
pages={null--null},
year=2019
}

Dimitrios Papadopoulos, Pavel Tomancak
Gene Regulation: Analog to Digital Conversion of Transcription Factor Gradients.
Curr Biol, 29(11) 422-424 (2019)
PubMed Source   

Transcription factor gradients trigger differential transcriptional responses based on concentration. But how, in some cases, do target genes maintain uniform transcription across portions of the gradient? Lessons from Drosophila demonstrate that organization of transcription into 'hubs' can lead to local increases in transcription factor concentration.
@article{Papadopoulos7404,
author={Dimitrios Papadopoulos, Pavel Tomancak},
title={Gene Regulation: Analog to Digital Conversion of Transcription Factor Gradients.},
journal ={Current biology : CB},
volume={29},
issue ={11},
pages={422--424},
year=2019
}

Ivana Viktorinová, Robert Haase, Tobias Pietzsch, Ian Henry, Pavel Tomancak
Analysis of Actomyosin Dynamics at Local Cellular and Tissue Scales Using Time-lapse Movies of Cultured Drosophila Egg Chambers.
J Vis Exp, 148 Art. No. e58587 (2019)
PubMed Source   

Drosophila immature eggs are called egg chambers, and their structure resembles primitive organs that undergo morphological changes from a round to an ellipsoid shape during development. This developmental process is called oogenesis and is crucial to generating functional mature eggs to secure the next fly generation. For these reasons, egg chambers have served as an ideal and relevant model to understand animal organ development. Several in vitro culturing protocols have been developed, but there are several disadvantages to these protocols. One involves the application of various covers that exert an artificial pressure on the imaged egg chambers in order to immobilize them and to increase the imaged acquisition plane of the circumferential surface of the analyzed egg chambers. Such an approach may negatively influence the behavior of the thin actomyosin machinery that generates the power to rotate egg chambers around their longer axis. Thus, to overcome this limitation, we culture Drosophila egg chambers freely in the media in order to reliably analyze actomyosin machinery along the circumference of egg chambers. In the first part of the protocol, we provide a manual detailing how to analyze the actomyosin machinery in a limited acquisition plane at the local cellular scale (up to 15 cells). In the second part of the protocol, we provide users with a new Fiji-based plugin that allows the simple extraction of a defined thin layer of the egg chambers' circumferential surface. The following protocol then describes how to analyze actomyosin signals at the tissue scale (>50 cells). Finally, we pinpoint the limitations of these approaches at both the local cellular and tissue scales and discuss its potential future development and possible applications.
@article{Viktorinová7407,
author={Ivana Viktorinová, Robert Haase, Tobias Pietzsch, Ian Henry, Pavel Tomancak},
title={Analysis of Actomyosin Dynamics at Local Cellular and Tissue Scales Using Time-lapse Movies of Cultured Drosophila Egg Chambers.},
journal ={Journal of visualized experiments : JoVE},
volume={148},
pages={1--1},
year=2019
}

Eugenia Marbach-Breitrück, Madlen Matz-Soja, Ute Abraham, Wolfgang Schmidt-Heck, Susanne Sales, Christiane Rennert, Matthias Kern, Susanne Aleithe, Luise Spormann, Carlo Thiel, Raffaele Gerlini, Katrin Arnold, Nora Klöting, Reinhard Guthke, Damjana Rozman, Raffaele Teperino, Andrej Shevchenko, Achim Kramer, Rolf Gebhardt
Tick-tock hedgehog-mutual crosstalk with liver circadian clock promotes liver steatosis.
J Hepatol, 70(6) 1192-1202 (2019)
PubMed Source   

The mammalian circadian clock controls various aspects of liver metabolism and integrates nutritional signals. Recently, we described Hedgehog (Hh) signaling as a novel regulator of liver lipid metabolism. Herein, we investigated crosstalk between hepatic Hh signaling and circadian rhythm.
@article{Marbach-Breitrück7353,
author={Eugenia Marbach-Breitrück, Madlen Matz-Soja, Ute Abraham, Wolfgang Schmidt-Heck, Susanne Sales, Christiane Rennert, Matthias Kern, Susanne Aleithe, Luise Spormann, Carlo Thiel, Raffaele Gerlini, Katrin Arnold, Nora Klöting, Reinhard Guthke, Damjana Rozman, Raffaele Teperino, Andrej Shevchenko, Achim Kramer, Rolf Gebhardt},
title={Tick-tock hedgehog-mutual crosstalk with liver circadian clock promotes liver steatosis.},
journal ={Journal of hepatology},
volume={70},
issue ={6},
pages={1192--1202},
year=2019
}

Volker Hartenstein, Michaela Yuan, Amelia Younossi-Hartenstein, Aanavi Karandikar, F Javier Bernardo-Garcia, Simon Sprecher, Elisabeth Knust
Serial electron microscopic reconstruction of the drosophila larval eye: Photoreceptors with a rudimentary rhabdomere of microvillar-like processes.
Dev Biol, Art. No. doi: 10.1016/j.ydbio.2019.05.017 (2019)
PubMed Source   

Photoreceptor cells (PRCs) across the animal kingdom are characterized by a stacking of apical membranes to accommodate the high abundance of photopigment. In arthropods and many other invertebrate phyla PRC membrane stacks adopt the shape of densely packed microvilli that form a structure called rhabdomere. PRCs and surrounding accessory cells, including pigment cells and lens-forming cells, are grouped in stereotyped units, the ommatidia. In larvae of holometabolan insects, eyes (called stemmata) are reduced in terms of number and composition of ommatidia. The stemma of Drosophila (Bolwig organ) is reduced to a bilateral cluster of subepidermal PRCs, lacking all other cell types. In the present paper we have analyzed the development and fine structure of the Drosophila larval PRCs. Shortly after their appearance in the embryonic head ectoderm, PRC precursors delaminate and lose expression of apical markers of epithelial cells, including Crumbs and several centrosome-associated proteins. In the early first instar larva, PRCs show an expanded, irregularly shaped apical surface that is folded into multiple horizontal microvillar-like processes (MLPs). Apical PRC membranes and MLPs are covered with a layer of extracellular matrix. MLPs are predominantly aligned along an axis that extends ventro-anteriorly to dorso-posteriorly, but vary in length, diameter, and spacing. Individual MLPs present a "beaded" shape, with thick segments (0.2-0.3 μm diameter) alternating with thin segments (>0.1 μm). We show that loss of the glycoprotein Chaoptin, which is absolutely essential for rhabdomere formation in the adult PRCs, does not lead to severe abnormalities in larval PRCs.
@article{Hartenstein7405,
author={Volker Hartenstein, Michaela Yuan, Amelia Younossi-Hartenstein, Aanavi Karandikar, F Javier Bernardo-Garcia, Simon Sprecher, Elisabeth Knust},
title={Serial electron microscopic reconstruction of the drosophila larval eye: Photoreceptors with a rudimentary rhabdomere of microvillar-like processes.},
journal ={Developmental biology},
volume={},
pages={1--1},
year=2019
}

Steven W Poser, Oliver Otto, Carina Arps-Forker, Yan Ge, Maik Herbig, Cordula Andree, Konrad Gruetzmann, Melissa F Adasme, Szymon Stodolak, Polyxeni Nikolakopoulou, Deric M Park, Alan Mcintyre, Mathias Lesche, Andreas Dahl, Petra Lennig, Stefan R. Bornstein, Evelin Schroeck, Barbara Klink, Ronen R Leker, Marc Bickle, George P Chrousos, Michael Schroeder, Carlo Vittorio Cannistraci, Jochen Guck, Andreas Androutsellis-Theotokis
Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery.
FASEB J, Art. No. doi: 10.1096/fj.201802603RR (2019)
PubMed Source   

Cancer cells can switch between signaling pathways to regulate growth under different conditions. In the tumor microenvironment, this likely helps them evade therapies that target specific pathways. We must identify all possible states and utilize them in drug screening programs. One such state is characterized by expression of the transcription factor Hairy and Enhancer of Split 3 (HES3) and sensitivity to HES3 knockdown, and it can be modeled in vitro. Here, we cultured 3 primary human brain cancer cell lines under 3 different culture conditions that maintain low, medium, and high HES3 expression and characterized gene regulation and mechanical phenotype in these states. We assessed gene expression regulation following HES3 knockdown in the HES3-high conditions. We then employed a commonly used human brain tumor cell line to screen Food and Drug Administration (FDA)-approved compounds that specifically target the HES3-high state. We report that cells from multiple patients behave similarly when placed under distinct culture conditions. We identified 37 FDA-approved compounds that specifically kill cancer cells in the high-HES3-expression conditions. Our work reveals a novel signaling state in cancer, biomarkers, a strategy to identify treatments against it, and a set of putative drugs for potential repurposing.-Poser, S. W., Otto, O., Arps-Forker, C., Ge, Y., Herbig, M., Andree, C., Gruetzmann, K., Adasme, M. F., Stodolak, S., Nikolakopoulou, P., Park, D. M., Mcintyre, A., Lesche, M., Dahl, A., Lennig, P., Bornstein, S. R., Schroeck, E., Klink, B., Leker, R. R., Bickle, M., Chrousos, G. P., Schroeder, M., Cannistraci, C. V., Guck, J., Androutsellis-Theotokis, A. Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery.
@article{Poser7403,
author={Steven W Poser, Oliver Otto, Carina Arps-Forker, Yan Ge, Maik Herbig, Cordula Andree, Konrad Gruetzmann, Melissa F Adasme, Szymon Stodolak, Polyxeni Nikolakopoulou, Deric M Park, Alan Mcintyre, Mathias Lesche, Andreas Dahl, Petra Lennig, Stefan R. Bornstein, Evelin Schroeck, Barbara Klink, Ronen R Leker, Marc Bickle, George P Chrousos, Michael Schroeder, Carlo Vittorio Cannistraci, Jochen Guck, Andreas Androutsellis-Theotokis},
title={Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery.},
journal ={FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume={},
pages={null--null},
year=2019
}

Mareike A Jordan, Gaia Pigino
In situ cryo-electron tomography and subtomogram averaging of intraflagellar transport trains
Methods Cell Biol, Art. No. doi: 10.1016/bs.mcb.2019.04.005 (2019)
Source  

@article{Jordan7409,
author={Mareike A Jordan, Gaia Pigino},
title={In situ cryo-electron tomography and subtomogram averaging of intraflagellar transport trains},
journal ={Methods in cell biology},
volume={},
pages={1--1},
year=2019
}