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Friederike I Tam, Mathias J. Gerl, Christian Klose, Michal Surma, Joseph A King, Maria Seidel, Kerstin Weidner, Veit Roessner, Kai Simons, Stefan Ehrlich
Adverse Effects of Refeeding on the Plasma Lipidome in Young Individuals With Anorexia Nervosa?
J Am Acad Child Adolesc Psychiatry, 60(12) 1479-1490 (2021)
PubMed Source

Refeeding is the cornerstone of anorexia nervosa (AN) treatment, but little is known regarding the optimal pace and dietary composition or possible adverse effects of current clinical practices. Plasma lipids may be a moderating factor underlying unfavorable refeeding effects in AN, such as an abnormal central body fat distribution. The objective of this study was to analyze the plasma lipidome in the acutely underweight state of AN before and after refeeding.

@article{Tam8011,
author={Friederike I Tam, Mathias J. Gerl, Christian Klose, Michal Surma, Joseph A King, Maria Seidel, Kerstin Weidner, Veit Roessner, Kai Simons, Stefan Ehrlich},
title={Adverse Effects of Refeeding on the Plasma Lipidome in Young Individuals With Anorexia Nervosa?},
journal ={Journal of the American Academy of Child and Adolescent Psychiatry},
volume={60},
issue ={12},
pages={1479--1490},
year=2021
}

Dennis Schifferl, Manuela Scholze-Wittler, Lars Wittler, Jesse V Veenvliet, Frederic Koch^#, Bernhard G Herrmann^#
A 37 kb region upstream of Brachyury comprising a notochord enhancer is essential for notochord and tail development.
Development, Art. No. doi: 10.1242/dev.200059 (2021)
Open Access PubMed Source

The node-streak border region comprising notochord progenitor cells (NPCs) at the posterior node and neuro-mesodermal progenitor cells (NMPs) in the adjacent epiblast is the prime organizing center for axial elongation in mouse embryos. The T-box transcription factor Brachyury (T) is essential for both, formation of the notochord and maintenance of NMPs, and thus is a key regulator of trunk and tail development. The T promoter controlling T expression in NMPs and nascent mesoderm has been characterized in detail. However, control elements for T expression in the notochord have not been identified yet. We have generated a series of deletion alleles by CRISPR/Cas9 genome editing in mESCs, and analyzed their effects in mutant mouse embryos. We identified a 37 kb region upstream of T essential for notochord function and tailbud outgrowth. Within that region we discovered a T binding enhancer required for notochord cell specification and differentiation. Our data reveal a complex regulatory landscape controlling cell type-specific expression and function of T in NMP/nascent mesoderm and node/notochord allowing proper trunk and tail development.

@article{Schifferl8216,
author={Dennis Schifferl, Manuela Scholze-Wittler, Lars Wittler, Jesse V Veenvliet, Frederic Koch, Bernhard G Herrmann},
title={A 37 kb region upstream of Brachyury comprising a notochord enhancer is essential for notochord and tail development.},
journal ={Development (Cambridge, England)},
volume={},
pages={1--1},
year=2021
}

Bharath Kumar Raghuraman, Aliona Bogdanova, HongKee Moon, Ignacy Rzagalinski, Eric R Geertsma, Lena Hersemann, Andrej Shevchenko
Median-Based Absolute Quantification of Proteins Using Fully Unlabeled Generic Internal Standard (FUGIS).
J Proteome Res, Art. No. 10.1021/acs.jproteome.1c00596 (2021)
Open Access PubMed Source

By reporting the molar abundance of proteins, absolute quantification determines their stoichiometry in complexes, pathways, or networks. Typically, absolute quantification relies either on protein-specific isotopically labeled peptide standards or on a semiempirical calibration against the average abundance of peptides chosen from arbitrarily selected proteins. In contrast, a generic protein standard FUGIS (fully unlabeled generic internal standard) requires no isotopic labeling, chemical synthesis, or external calibration and is applicable to quantifying proteins of any organismal origin. The median intensity of the peptide peaks produced by the tryptic digestion of FUGIS is used as a single-point calibrant to determine the molar abundance of any codigested protein. Powered by FUGIS, median-based absolute quantification (MBAQ) outperformed other methods of untargeted proteome-wide absolute quantification.

@article{Raghuraman8215,
author={Bharath Kumar Raghuraman, Aliona Bogdanova, HongKee Moon, Ignacy Rzagalinski, Eric R Geertsma, Lena Hersemann, Andrej Shevchenko},
title={Median-Based Absolute Quantification of Proteins Using Fully Unlabeled Generic Internal Standard (FUGIS).},
journal ={Journal of proteome research},
volume={},
pages={null--null},
year=2021
}

Yukako Oda, Chisato Takahashi, Shota Harada, Shun Nakamura, Daxiao Sun, Kazumi Kiso, Yuko Urata, Hitoshi Miyachi, Yoshinori Fujiyoshi, Alf Honigmann, Seiichi Uchida, Yasushi Ishihama, Fumiko Toyoshima
Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation.
Sci Adv, 7(47) Art. No. eabj6895 (2021)
Open Access PubMed Source

[Figure: see text].

@article{Oda8209,
author={Yukako Oda, Chisato Takahashi, Shota Harada, Shun Nakamura, Daxiao Sun, Kazumi Kiso, Yuko Urata, Hitoshi Miyachi, Yoshinori Fujiyoshi, Alf Honigmann, Seiichi Uchida, Yasushi Ishihama, Fumiko Toyoshima},
title={Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation.},
journal ={Science advances},
volume={7},
issue ={47},
pages={null--null},
year=2021
}

Victor Girard, Florence Jollivet, Oskar Knittelfelder, Marion Celle, Jean-Noel Arsac, Gilles Chatelain, Daan M Van den Brink, Thierry Baron, Andrej Shevchenko, Ronald P Kühnlein, Nathalie Davoust^#, Bertrand Mollereau^#
Abnormal accumulation of lipid droplets in neurons induces the conversion of alpha-Synuclein to proteolytic resistant forms in a Drosophila model of Parkinson's disease.
PLoS Genet, 17(11) Art. No. e1009921 (2021)
Open Access PubMed Source

Parkinson's disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein (αSyn) aggregation and associated with abnormalities in lipid metabolism. The accumulation of lipids in cytoplasmic organelles called lipid droplets (LDs) was observed in cellular models of PD. To investigate the pathophysiological consequences of interactions between αSyn and proteins that regulate the homeostasis of LDs, we used a transgenic Drosophila model of PD, in which human αSyn is specifically expressed in photoreceptor neurons. We first found that overexpression of the LD-coating proteins Perilipin 1 or 2 (dPlin1/2), which limit the access of lipases to LDs, markedly increased triacylglyclerol (TG) loaded LDs in neurons. However, dPlin-induced-LDs in neurons are independent of lipid anabolic (diacylglycerol acyltransferase 1/midway, fatty acid transport protein/dFatp) and catabolic (brummer TG lipase) enzymes, indicating that alternative mechanisms regulate neuronal LD homeostasis. Interestingly, the accumulation of LDs induced by various LD proteins (dPlin1, dPlin2, CG7900 or KlarsichtLD-BD) was synergistically amplified by the co-expression of αSyn, which localized to LDs in both Drosophila photoreceptor neurons and in human neuroblastoma cells. Finally, the accumulation of LDs increased the resistance of αSyn to proteolytic digestion, a characteristic of αSyn aggregation in human neurons. We propose that αSyn cooperates with LD proteins to inhibit lipolysis and that binding of αSyn to LDs contributes to the pathogenic misfolding and aggregation of αSyn in neurons.

@article{Girard8208,
author={Victor Girard, Florence Jollivet, Oskar Knittelfelder, Marion Celle, Jean-Noel Arsac, Gilles Chatelain, Daan M Van den Brink, Thierry Baron, Andrej Shevchenko, Ronald P Kühnlein, Nathalie Davoust, Bertrand Mollereau},
title={Abnormal accumulation of lipid droplets in neurons induces the conversion of alpha-Synuclein to proteolytic resistant forms in a Drosophila model of Parkinson's disease.},
journal ={PLoS genetics},
volume={17},
issue ={11},
pages={null--null},
year=2021
}

Frank Sauer, Anatol Fritsch, Steffen Grosser, Steve Pawlizak, Tobias Kießling, Martin Reiss-Zimmermann, Mehrgan Shahryari, Wolf C Müller, Karl-Titus Hoffmann, J. Käs, Ingolf Sack
Whole tissue and single cell mechanics are correlated in human brain tumors.
Soft Matter, Art. No. 10.1039/d1sm01291f (2021)
PubMed Source

Biomechanical changes are critical for cancer progression. However, the relationship between the rheology of single cells measured ex-vivo and the living tumor is not yet understood. Here, we combined single-cell rheology of cells isolated from primary tumors with in vivo bulk tumor rheology in patients with brain tumors. Eight brain tumors (3 glioblastoma, 3 meningioma, 1 astrocytoma, 1 metastasis) were investigated in vivo by magnetic resonance elastography (MRE), and after surgery by the optical stretcher (OS). MRE was performed in a 3-Tesla clinical MRI scanner and magnitude modulus |G*|, loss angle φ, storage modulus G', and loss modulus G'' were derived. OS experiments measured cellular creep deformation in response to laser-induced step stresses. We used a Kelvin-Voigt model to deduce two parameters related to cellular stiffness (μKV) and cellular viscosity (ηKV) from OS measurements in a time regimen that overlaps with that of MRE. We found that single-cell μKV was correlated with |G*| (R = 0.962, p < 0.001) and G'' (R = 0.883, p = 0.004) but not G' of the bulk tissue. These results suggest that single-cell stiffness affects tissue viscosity in brain tumors. The observation that viscosity parameters of individual cells and bulk tissue were not correlated suggests that collective mechanical interactions (i.e. emergent effects or cellular unjamming) of many cancer cells, which depend on cellular stiffness, influence the mechanical dissipation behavior of the bulk tissue. Our results are important to understand the emergent rheology of active multiscale compound materials such as brain tumors and its role in disease progression.

@article{Sauer8214,
author={Frank Sauer, Anatol Fritsch, Steffen Grosser, Steve Pawlizak, Tobias Kießling, Martin Reiss-Zimmermann, Mehrgan Shahryari, Wolf C Müller, Karl-Titus Hoffmann, J. Käs, Ingolf Sack},
title={Whole tissue and single cell mechanics are correlated in human brain tumors.},
journal ={Soft matter},
volume={},
pages={null--null},
year=2021
}

Byung Ho Lee^✳︎, Irene Seijo-Barandiaran^✳︎, Anne Grapin-Botton
Epithelial morphogenesis in organoids.
Curr Opin Genet Dev, 72 30-37 (2021)
PubMed Source

Epithelial organoids can recapitulate many processes reminiscent of morphogenesis in vivo including lumen and multilayer formation, folding, branching, delamination and elongation. While being noisier in vitro than in vivo, these processes can be monitored live and subjected to interferences, a field that is emerging. We elaborate on the signalling molecules controlling morphogenesis, from the medium and their emergence as signalling centers in the organoids. Further, we discuss how organoid shape is controlled by mechanical cues within the organoid and their interplay with the material properties of the environment.

@article{Lee8213,
author={Byung Ho Lee, Irene Seijo-Barandiaran, Anne Grapin-Botton},
title={Epithelial morphogenesis in organoids.},
journal ={Current opinion in genetics & development},
volume={72},
pages={30--37},
year=2021
}

Thomas J O'Neill^✳︎, Thomas Seeholzer^✳︎, Andreas Gewies^✳︎, Torben Gehring, Florian Giesert, Isabel Hamp, Carina Graß, Henrik Schmidt, Katharina Kriegsmann, Marie J Tofaute, Katrin Demski, Tanja Poth, Marc Rosenbaum, Theresa Schnalzger, Jurgen Ruland, Martin Göttlicher, Mark Kriegsmann, Ronald Naumann, Vigo Heissmeyer, Oliver Plettenburg, Wolfgang Wurst, Daniel Krappmann
TRAF6 prevents fatal inflammation by homeostatic suppression of MALT1 protease.
Sci Immunol, 6(65) Art. No. eabh2095 (2021)
PubMed Source

[Figure: see text].

@article{O'Neill8206,
author={Thomas J O'Neill, Thomas Seeholzer, Andreas Gewies, Torben Gehring, Florian Giesert, Isabel Hamp, Carina Graß, Henrik Schmidt, Katharina Kriegsmann, Marie J Tofaute, Katrin Demski, Tanja Poth, Marc Rosenbaum, Theresa Schnalzger, Jurgen Ruland, Martin Göttlicher, Mark Kriegsmann, Ronald Naumann, Vigo Heissmeyer, Oliver Plettenburg, Wolfgang Wurst, Daniel Krappmann},
title={TRAF6 prevents fatal inflammation by homeostatic suppression of MALT1 protease.},
journal ={Science immunology},
volume={6},
issue ={65},
pages={null--null},
year=2021
}

Aditya Saxena, Virag Sharma, Pushpanathan Muthuirulan, Stanley J Neufeld, Mai P Tran, Haydee L Gutierrez, Kevin D Chen, Joel M Erberich, Amanda Birmingham, Terence D Capellini, John Cobb, Michael Hiller, Kimberly L Cooper
Interspecies transcriptomics identify genes that underlie disproportionate foot growth in jerboas.
Curr Biol, Art. No. 10.1016/j.cub.2021.10.063. (2021)
PubMed Source

Despite the great diversity of vertebrate limb proportion and our deep understanding of the genetic mechanisms that drive skeletal elongation, little is known about how individual bones reach different lengths in any species. Here, we directly compare the transcriptomes of homologous growth cartilages of the mouse (Mus musculus) and bipedal jerboa (Jaculus jaculus), the latter of which has "mouse-like" arms but extremely long metatarsals of the feet. Intersecting gene-expression differences in metatarsals and forearms of the two species revealed that about 10% of orthologous genes are associated with the disproportionately rapid elongation of neonatal jerboa feet. These include genes and enriched pathways not previously associated with endochondral elongation as well as those that might diversify skeletal proportion in addition to their known requirements for bone growth throughout the skeleton. We also identified transcription regulators that might act as "nodes" for sweeping differences in genome expression between species. Among these, Shox2, which is necessary for proximal limb elongation, has gained expression in jerboa metatarsals where it has not been detected in other vertebrates. We show that Shox2 is sufficient to increase mouse distal limb length, and a nearby putative cis-regulatory region is preferentially accessible in jerboa metatarsals. In addition to mechanisms that might directly promote growth, we found evidence that jerboa foot elongation may occur in part by de-repressing latent growth potential. The genes and pathways that we identified here provide a framework to understand the modular genetic control of skeletal growth and the remarkable malleability of vertebrate limb proportion.

@article{Saxena8212,
author={Aditya Saxena, Virag Sharma, Pushpanathan Muthuirulan, Stanley J Neufeld, Mai P Tran, Haydee L Gutierrez, Kevin D Chen, Joel M Erberich, Amanda Birmingham, Terence D Capellini, John Cobb, Michael Hiller, Kimberly L Cooper},
title={Interspecies transcriptomics identify genes that underlie disproportionate foot growth in jerboas.},
journal ={Current biology : CB},
volume={},
pages={null--null},
year=2021
}

Dalileh Nabi, Hauke Drechsler, Johannes Pschirer, Franz Korn, Nadine Schuler, Stefan Diez, Rolf Jessberger^#, Mariola R. Chacón^#
CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes.
Nat Commun, 12(1) Art. No. 6547 (2021)
Open Access PubMed Source

Proper chromosome segregation is essential to avoid aneuploidy, yet this process fails with increasing age in mammalian oocytes. Here we report a role for the scarcely described protein CENP-V in oocyte spindle formation and chromosome segregation. We show that depending on the oocyte maturation state, CENP-V localizes to centromeres, to microtubule organizing centers, and to spindle microtubules. We find that Cenp-V-/- oocytes feature severe deficiencies, including metaphase I arrest, strongly reduced polar body extrusion, increased numbers of mis-aligned chromosomes and aneuploidy, multipolar spindles, unfocused spindle poles and loss of kinetochore spindle fibres. We also show that CENP-V protein binds, diffuses along, and bundles microtubules in vitro. The spindle assembly checkpoint arrests about half of metaphase I Cenp-V-/- oocytes from young adults only. This finding suggests checkpoint weakening in ageing oocytes, which mature despite carrying mis-aligned chromosomes. Thus, CENP-V is a microtubule bundling protein crucial to faithful oocyte meiosis, and Cenp-V-/- oocytes reveal age-dependent weakening of the spindle assembly checkpoint.

@article{Nabi8207,
author={Dalileh Nabi, Hauke Drechsler, Johannes Pschirer, Franz Korn, Nadine Schuler, Stefan Diez, Rolf Jessberger, Mariola R. Chacón},
title={CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes.},
journal ={Nature communications},
volume={12},
issue ={1},
pages={null--null},
year=2021
}

^✳︎ joined first author, ^# joined corresponding author