Article
Clinical Neurology
Parthiv Haldipur, Silvia Bernardo, Kimberly A. Aldinger, Tarika Sivakumar, Jake Millman, Alexandria H. Sjoboen, Derek Dang, Danilo Dubocanin, Mei Deng, Andrew E. Timms, Brian D. Davis, Jasmine T. Plummer, Kshitij Mankad, Ozgur Oztekin, Lucia Manganaro, Fabien Guimiot, Homa Adle-Biassette, Rosa Russo, Joseph R. Siebert, Debora Kidron, Giulia Petrilli, Nathalie Roux, Ferechte Razavi, Ian A. Glass, Cira Di Gioia, Evelina Silvestri, Kathleen J. Millen
Summary: Dandy-Walker malformation (DWM) and Cerebellar vermis hypoplasia (CVH) are common cerebellar malformations diagnosed through ultrasound and MRI. Histopathological analysis showed reduced foliation and inferior vermian hypoplasia in DWM cases. Disruption of the rhombic lip, with reduced proliferation and altered vasculature, is key in the pathogenesis of DWM.
ACTA NEUROPATHOLOGICA
(2021)
Article
Biology
Alexa N. Wimberly, Graham J. Slater, Michael C. Granatosky
Summary: The study utilized internet videos to study the gait evolution of vertebrates, finding an ancestral lateral-sequence diagonal-couplet gait in quadrupedal gnathostomes. Mammals overcame this constraint with a wider range of phase values. The diagonal-sequence diagonal-couplet gait in mammals is significantly associated with arboreality.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Article
Robotics
Baxi Chong, Yasemin Ozkan Aydin, Chaohui Gong, Guillaume Sartoretti, Yunjin Wu, Jennifer M. Rieser, Haosen Xing, Perrin E. Schiebel, Jeffery W. Rankin, Krijn B. Michel, Alfredo Nicieza, John R. Hutchinson, Daniel Goldman, Howie Choset
Summary: This study investigates the coordination between body bending and limb movement in quadrupedal locomotion, using a geometric approach to quantify gait performance and optimize coordination patterns for systems dominated by damping forces. The effectiveness of lateral undulation coordinated with leg movement in robot motion is demonstrated, with theoretical results validated through numerical simulations and robophysical experiments. The study not only focuses on robotics, but also accurately predicts optimal body bending of a living salamander.
INTERNATIONAL JOURNAL OF ROBOTICS RESEARCH
(2021)
Article
Cell Biology
Anastasia P. Grigorenko, Maria S. Protasova, Alexandra A. Lisenkova, Denis A. Reshetov, Tatiana V. Andreeva, Gilberto De Lima Garcias, Maria Da Graca Martino Roth, Andreas Papassotiropoulos, Evgeny I. Rogaev
Summary: This article describes a genetic cause of an involution phenotype and identifies a gene deletion associated with this condition in a Brazilian family. The study also investigates the evolutionary trajectory of the GRID2 gene and finds potential human-specific mutations that may contribute to the observed phenotype.
Article
Biochemistry & Molecular Biology
Urszula Slawinska, Henryk Majczynski, Anna Kwasniewska, Krzysztof Miazga, Anna M. Cabaj, Marek Bekisz, Larry M. Jordan, Malgorzata Zawadzka
Summary: The study found that blockade of 5-HT7 receptors in rats leads to an asynchronous stepping pattern between forelimbs and hindlimbs during quadrupedal locomotion, while blockade of 5-HT2A receptors does not. This suggests that 5-HT7 receptors play an important role in coordination of limb movements and may regulate it through interneurons in the spinal cord.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Emanuel Andrada, Gregor Hildebrandt, Hartmut Witte, Martin S. Fischer
Summary: Research has found that dogs prefer walking at lower speeds and trotting at speeds ranging from 0.5 to 3 times their preferred walking speed. This study analyzed the global dynamics of dogs' limbs during walking and trotting, showing that dogs' pelvic and thoracic limbs have different functions and absorb energy differently. Ground reaction forces formed virtual pivot points for the limbs, and these pivot points' positions were influenced by gait and leg length but not always breed-specific. The study also found that torque profiles in the scapulothoracic joint were likely between breeds, while hip torque profiles were size-related.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Chenfei Lyu, Chencen Yu, Guanglong Sun, Yue Zhao, Ruolan Cai, Hao Sun, Xintai Wang, Guoqiang Jia, Lingzhu Fan, Xi Chen, Lin Zhou, Ying Shen, Lixia Gao, Xinjian Li
Summary: The cerebellum is involved in encoding balance, posture, speed, and gravity during locomotion. The study found that cerebellar activity is specifically enhanced during uphill and downhill locomotion. Chemogenetic inactivation of lobule V of the vermis impaired uphill locomotion.
Article
Biology
Delyle T. Polet
Summary: Research suggests that the normalization of pitch moment of inertia (MOI) has opposite effects on walking and running energetics in quadrupedal mammals. While simultaneous forelimb and hindlimb contacts during walking can dampen pitching energy, the pitching required for a four-beat walk becomes more expensive as the Murphy number increases. Rotation dynamics play a central role in gait selection for animals like dogs, horses, giraffes, and elephants.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2021)
Article
Automation & Control Systems
Jiawei Chen, Kun Xu, Xilun Ding
Summary: Inspired by human roller-skating, a new dynamic roller-skating gait for a typical mammalian quadrupedal robot with passive wheels is proposed to improve mobile efficiency. By imitating human roller-skating, this dynamic gait based on bilateral symmetry can achieve linear and turning motion, with higher speed and efficiency compared to conventional trotting.
IEEE-ASME TRANSACTIONS ON MECHATRONICS
(2021)
Article
Biology
Francois Druelle, Anthony Supiot, Silke Meulemans, Niels Schouteden, Pablo Molina-Vila, Brigitte Rimbaud, Peter Aerts, Gilles Berillon
Summary: The study found that olive baboons can rely on an inverted pendulum-like energy exchange when walking on the ground using a diagonal sequence gait, while adjustments in kinematics and muscles are needed when walking on a suspended branch. Different footfall patterns and substrates influence muscular effort and efficiency.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2021)
Article
Automation & Control Systems
Jiawei Chen, Kun Xu, Ripeng Qin, Xilun Ding
Summary: A new quadruped robot with passive wheels is designed for roller-skating and walking, utilizing a double parallel four-bar linkage for configuration switching. A dynamics controller based on the center of inertia on SE(3) is developed to achieve roller-skating and walking, alongside a new method of internal force distribution and a floating coordinate system. Experimental results show that the proposed controller successfully enables roller-skating, walking, and configuration switching for the quadrupedal robot.
IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS
(2023)
Article
Biology
Richard A. Warren, Qianyun Zhang, Judah R. Hoffman, Edward Y. Li, Y. Kate Hong, Randy M. Bruno, Nathaniel B. Sawtell
Summary: By using machine learning for high-resolution kinematic analysis, researchers uncovered the logic behind sensory-guided locomotion in mice, showing that mice choose different kinematic strategies depending on whisker-derived estimate of obstacle location and body position and velocity. While mice rely on whiskers for obstacle avoidance, lesions of primary whisker sensory cortex have minimal impact, while manipulations of motor cortex affect the execution of chosen strategy but the decision-making process remains intact. This study highlights the potential of machine learning in analyzing naturalistic behaviors and shows that subcortical brain structures are sufficient for mediating sophisticated sensorimotor decisions.
Article
Biology
Baruch Haimson, Yoav Hadas, Nimrod Bernat, Artur Kania, Monica A. Daley, Yuval Cinnamon, Aharon Lev-Tov, Avihu Klar
Summary: Peripheral and intraspinal feedback are crucial for shaping and updating spinal networks that control motor behavior. dI2 spinal interneurons in chicks receive synaptic input from afferents and premotor neurons, and are involved in local spinal circuits and lumbo-brachial coupling. Silencing these neurons results in destabilized stepping and wide-base walking gait in hatchlings, indicating their contribution to bipedal gait stabilization.
Article
Robotics
Jeeseop Kim, Randall T. Fawcett, Vinay R. Kamidi, Aaron D. Ames, Kaveh Akbari Hamed
Summary: This article presents a layered control approach for real-time trajectory planning and control of robust cooperative locomotion by two holonomically constrained quadrupedal robots. The approach utilizes an interconnected network of reduced-order models and proposes centralized and distributed model predictive control (MPC) algorithms. Distributed nonlinear controllers are developed for tracking the full-order dynamics. Extensive simulations and experiments show the effectiveness of the approach, with the distributed MPC achieving similar performance as the centralized MPC but with significantly reduced computation time.
IEEE TRANSACTIONS ON ROBOTICS
(2023)
Article
Pediatrics
Hao Huang, Jieyuan Jin, Liping Wu, Huifen Wu, Huichun Pi, Yi Dong, Rong Xiang
Summary: This study reports the first case in Asia of brain malformation and lung lobulation defects caused by a variant in NFIB. These findings are important for genetic diagnosis, family counseling, and our understanding of NFIB mutations and brain and lung development.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Guido Vogt, Sarah Verheyen, Sarina Schwartzmann, Nadja Ehmke, Cornelia Potratz, Anette Schwerin-Nagel, Barbara Plecko, Manuel Holtgrewe, Dominik Seelow, Jasmin Blatterer, Michael R. Speicher, Uwe Kornak, Denise Horn, Stefan Mundlos, Bjorn Fischer-Zirnsak, Felix Boschann
Summary: Pathogenic variants in the ATP9A gene cause a novel autosomal recessive neurodevelopmental disorder characterized by postnatal microcephaly. ATP9A plays a crucial role in endosomal transport, with variants leading to a reduction in mRNA expression and altered gene expression of components related to endosomes.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Cell Biology
Juliane Glaser, Stefan Mundlos
Summary: One of the fundamental questions in developmental biology is how a fertilized cell develops into a fully mature organism and how gene regulation governs this process. Precise spatiotemporal gene expression is crucial for development, achieved through a complex interplay of sequence-specific information, epigenetic modifications, trans-acting factors, and chromatin folding.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Review
Clinical Neurology
R. Mertens, M. Graupera, H. Gerhardt, A. Bersano, E. Tournier-Lasserve, M. A. Mensah, S. Mundlos, P. Vajkoczy
Summary: Moyamoya disease is a rare cerebrovascular disease characterized by progressive bilateral occlusion of the intracranial internal cerebral arteries. Clinical presentation varies depending on age and population, with hemorrhage and ischemic infarcts leading to severe neurological dysfunction or death. Surgical revascularization is currently the only established treatment for MMD.
TRANSLATIONAL STROKE RESEARCH
(2022)
Article
Immunology
Julia Koerholz, Anastasia Gabrielyan, John M. Sowerby, Felix Boschann, Lan-Sun Chen, Diana Paul, David Brandt, Janina Kleymann, Martin Kolditz, Nicole Toepfner, Ralf Knoefler, Eva-Maria Jacobsen, Christine Wolf, Karsten Conrad, Nadja Roeber, Min Ae Lee-Kirsch, Kenneth G. C. Smith, Stefan Mundlos, Reinhard Berner, Alexander H. Dalpke, Catharina Schuetz, William Rae
Summary: SOCS1 haploinsufficiency is a pleiotropic monogenic IEI, leading to diverse clinical manifestations in patients due to dysregulation of multiple immune cell pathways.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Behavioral Sciences
Helle Lybaek, Michael Robson, Nicole de Leeuw, Jayne Y. Hehir-Kwa, Aaron Jeffries, Bjorn Ivar Haukanes, Siren Berland, Diederik de Bruijn, Stefan Mundlos, Malte Spielmann, Gunnar Houge
Summary: LRFN5 is involved in synaptic development and is located in a large genomic locus with complex structure and high conservation. Specific locus structural changes are associated with increased autism susceptibility in males, potentially explaining the higher prevalence of higher-functioning autism in males. The dysregulation of LRFN5 could be an epigenetic cause of autism.
Article
Biochemistry & Molecular Biology
Marie Coutelier, Manuel Holtgrewe, Marten Jaeger, Ricarda Floettman, Martin A. Mensah, Malte Spielmann, Peter Krawitz, Denise Horn, Dieter Beule, Stefan Mundlos
Summary: Copy Number Variants (CNVs) are deletions, duplications, or insertions larger than 50 base pairs that contribute to normal genome variation and have significant implications in human pathology. While traditional array-based approaches have been used for CNV detection, whole-genome sequencing (WGS) offers the potential for comprehensive exploration of CNVs and smaller variants. This study evaluates practical calling options for CNV detection from WGS data, highlighting the need to strike a balance between sensitivity and sensibility. Combining multiple callers and tools like SV2 shows promising results in terms of computation time and accuracy compared to array-based methods like aCGH.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Felix Boschann, Daniel Acero Moreno, Martin A. Mensah, Henrike L. Sczakiel, Karolina Skipalova, Manuel Holtgrewe, Stefan Mundlos, Bjoern Fischer-Zirnsak
Summary: This study identified a complex interchromosomal insertion in a large family with seven affected males using WGS. The inserted fragment originated from chromosome 10q21.3 and was inserted inversionally into the intergenic chromosomal region Xq27.1. The patterns found at the breakpoint junctions resembled characteristics that arise in replication-based mechanisms with long-distance template switching. This research demonstrates the importance of WGS as a powerful diagnostic test in unsolved genetic diseases.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Rutger A. F. Gjaltema, Till Schwaemmle, Pauline Kautz, Michael Robson, Robert Schoepflin, Liat Ravid Lustig, Lennart Brandenburg, Ilona Dunkel, Carolina Vechiatto, Evgenia Ntini, Verena Mutzel, Vera Schmiedel, Annalisa Marsico, Stefan Mundlos, Edda G. Schulz
Summary: Developmental genes like Xist are regulated by complex cis regulatory landscapes, which decode multiple signals to establish specific expression patterns. In this study, functional enhancer elements of Xist were identified during random X inactivation. X-dosage controls the promoter-proximal region, while differentiation cues activate several distal enhancers. A previously unannotated enhancer cluster associated with Xist-enhancing regulatory transcript, named Xert, was also discovered. The study helps to understand how multiple regulatory elements interact to generate complex expression patterns in mammals.
Article
Genetics & Heredity
Tzung-Chien Hsieh, Aviram Bar-Haim, Shahida Moosa, Nadja Ehmke, Karen W. Gripp, Jean Tori Pantel, Magdalena Danyel, Martin Atta Mensah, Denise Horn, Stanislav Rosnev, Nicole Fleischer, Guilherme Bonini, Alexander Hustinx, Alexander Schmid, Alexej Knaus, Behnam Javanmardi, Hannah Klinkhammer, Hellen Lesmann, Sugirthan Sivalingam, Tom Kamphans, Wolfgang Meiswinkel, Frederic Ebstein, Elke Krueger, Sebastien Kuery, Stephane Bezieau, Axel Schmidt, Sophia Peters, Hartmut Engels, Elisabeth Mangold, Martina Kreiss, Kirsten Cremer, Claudia Perne, Regina C. Betz, Tim Bender, Kathrin Grundmann-Hauser, Tobias B. Haack, Matias Wagner, Theresa Brunet, Heidi Beate Bentzen, Luisa Averdunk, Kimberly Christine Coetzer, Gholson J. Lyon, Malte Spielmann, Christian P. Schaaf, Stefan Mundlos, Markus M. Noethen, Peter M. Krawitz
Summary: GestaltMatcher utilizes deep convolutional neural network to improve recognition of rare disorders based on facial morphology, aiding in discovery of new disease genes by detecting similarities among patients with previously unseen syndromes. This approach assists physicians in recognizing characteristic facial morphology associated with monogenic disorders through training on thousands of patient photographs. By developing an encoder based on deep convolutional neural network, GestaltMatcher allows matching of patients even with ultra-rare disorders that were not part of the training set. Combined with mutation data, it can accelerate clinical diagnosis and enable delineation of new phenotypes.
Article
Endocrinology & Metabolism
Ralf Oheim, Elena Tsourdi, Lothar Seefried, Gisela Beller, Max Schubach, Eik Vettorazzi, Julian Sturznickel, Tim Rolvien, Nadja Ehmke, Alena Delsmann, Franca Genest, Ulrike Krueger, Tomasz Zemojtel, Florian Barvencik, Thorsten Schinke, Franz Jakob, Lorenz C. Hofbauer, Stefan Mundlos, Uwe Kornak
Summary: The impact of genetic testing on the differential diagnosis of adult LBMD was investigated in this study. Clinical criteria for predicting monogenic forms were also defined. The results showed that genetic testing can easily distinguish overlapping spectra of monogenic adult LBMD, and the proposed clinical criteria can help maximize the diagnostic yield.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Evolutionary Biology
Francisca M. Real, Miguel Lao-Perez, Miguel Burgos, Stefan Mundlos, Dario G. Lupianez, Rafael Jimenez, Francisco J. Barrionuevo
Summary: In species with seasonal breeding, male specimens undergo substantial testicular regression during the nonbreeding period of the year. However, the molecular mechanisms that control this biological process are largely unknown. Here, we report a transcriptomic analysis on the Iberian mole, Talpa occidentalis, in which the desquamation of live, nonapoptotic germ cells is the major cellular event responsible for testis regression. Our study advances in the knowledge of the molecular mechanisms associated to gonadal seasonal breeding, highlighting the existence of a conserved transcriptional program of testis involution across mammalian clades.
JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION
(2023)
Article
Multidisciplinary Sciences
Katerina Kraft, Kathryn E. Yost, Sedona E. Murphy, Andreas Magg, Yicheng Long, M. Ryan Corces, Jeffrey M. Granja, Lars Wittler, Stefan Mundlos, Thomas R. Cech, Alistair N. Boettiger, Howard Y. Chang
Summary: Polycomb-group proteins are involved in gene silencing through H3K27me3 deposition and chromatin compaction. This study investigates the distribution of long-range Polycomb-associated DNA loops in mouse ESCs and human induced pluripotent stem cells, and finds that H3K27me3 loop anchors are enriched for Polycomb nucleation points and coincide with key developmental genes. Furthermore, the study demonstrates that RNA binding is crucial for PRC2 occupancy and Polycomb-associated DNA looping. These findings reveal the importance of developmental gene loci in Polycomb spreading and provide insights into the regulation of gene silencing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Uwe Kornak, Namrata Saha, Boris Keren, Alexander Neumann, Ana Lisa Taylor Tavares, Juliette Piard, Johannes Kopp, Joao Guilherme Rodrigues Alves, Miguel Rodriguez de los Santos, Naji El Choubassi, Nadja Ehmke, Marten Jaeger, Malte Spielmann, Jean Tori Pantel, Elodie Lejeune, Beatrix Fauler, Thorsten Mielke, Jochen Hecht, David Meierhofer, Tim M. Strom, Vincent Laugel, Alexis Brice, Stefan Mundlos, Aida Bertoli-Avella, Peter Bauer, Florian Heyd, Odile Boute, Juliette Dupont, Christel Depienne, Lionel Van Maldergem, Bjoern Fischer-Zirnsak
Summary: This study successfully identified a rare progressive multisystem disease with prominent lipodystrophy and revealed the molecular genetic cause associated with the disease. The findings showed that the alternative splice product of the BUD13 gene converts a loss-of-function into a hypomorphic allele, potentially determining the severity of the disease and the survival of affected individuals.
GENETICS IN MEDICINE
(2022)
Article
Multidisciplinary Sciences
Martin A. Mensah, Henri Niskanen, Alexandre P. Magalhaes, Shaon Basu, Martin Kircher, Henrike L. Sczakiel, Alisa M. V. Reiter, Jonas Elsner, Peter Meinecke, Saskia Biskup, Brian H. Y. Chung, Gregor Dombrowsky, Christel Eckmann-Scholz, Marc Phillip Hitz, Alexander Hoischen, Paul-Martin Holterhus, Wiebke Huelsemann, Kimia Kahrizi, Vera M. Kalscheuer, Anita Kan, Mandy Krumbiegel, Ingo Kurth, Jonas Leubner, Ann Carolin Longardt, Joerg D. Moritz, Hossein Najmabadi, Karolina Skipalova, Lot Snijders Blok, Andreas Tzschach, Eberhard Wiedersberg, Martin Zenker, Carla Garcia-Cabau, Rene Buschow, Xavier Salvatella, Matthew L. Kraushar, Stefan Mundlos, Almuth Caliebe, Malte Spielmann, Denise Horn, Denes Hnisz
Summary: A study found that thousands of genetic variants in protein-coding genes are associated with diseases. However, the functional impact of these variants is largely unknown because they occur in poorly defined functional regions of intrinsically disordered proteins. It was discovered that certain disease-associated variants in intrinsically disordered regions alter phase separation, causing misplacement in the nucleolus and disrupting nucleolar function.
Article
Biotechnology & Applied Microbiology
Jakob Hertzberg, Stefan Mundlos, Martin Vingron, Giuseppe Gallone
Summary: Functional annotation-based prioritization of pathogenic CNVs is a promising approach to support clinical diagnostics and further the understanding of mechanisms controlling the disease impact of larger genomic alterations. Our method, TADA, demonstrates accurate prediction of pathogenic CNVs, outperforming current alternative methods, and producing a well-calibrated pathogenicity score.