Article
Biotechnology & Applied Microbiology
Stephen Richer, Yuan Tian, Stefan Schoenfelder, Laurence Hurst, Adele Murrell, Giuseppina Pisignano
Summary: This study investigates the differences in three-dimensional chromatin conformation between heterozygous loci, taking into consideration parent-of-origin differences and genome-wide allele-specific chromatin conformation associations. A bioinformatic pipeline called HiCFlow is developed for haplotype assembly and visualization of parental chromatin architecture. The study identifies stable allele-specific interactions at specific gene loci and detects allele-specific differences in A/B compartmentalization. The findings highlight the widespread differences in chromatin conformation and provide insights into allele-specific expressed genes, including previously unidentified ones.
Article
Biochemistry & Molecular Biology
Ashley Pacheco, Aaron Issaian, Jonathan Davis, Nathan Anderson, Travis Nemkov, Natasia Paukovich, Morkos A. Henen, Beat Vögeli, James M. Sikela, Kirk Hansen
Summary: Olduvai protein domains, which show the greatest increase in copy number in humans, are closely related to human brain evolution and cognitive diseases. These domains are processed by furin protease and are found in NBPF genes, forming Olduvai triplets. The correlation between Olduvai copy number and brain size, along with the furin data, suggests that the primary role of Olduvai in human brain expansion is through the increased dosage of autonomously functioning Olduvai triplet proteins.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Cell Biology
Sarah E. Gilbertson, Hannah C. Walter, Katherine Gardner, Spencer N. Wren, Golnaz Vahedi, Amy S. Weinmann
Summary: Distinguishing between conserved and divergent regulatory mechanisms is crucial for translating preclinical research from mice to humans. Evolutionary genome rearrangements disrupt TAD boundaries, enabling sequence-conserved enhancer elements from divergent genomic locations between species to create unique regulatory modules.
Article
Clinical Neurology
Aurora Veteleanu, Sarah Pape, Kate Davies, Eleftheria Kodosaki, Abdul Hye, Wioleta M. Zelek, Andre Strydom, B. Paul Morgan
Summary: Complement dysregulation is present in individuals with Down syndrome, likely indicating a generalized immune dysregulation state; complement biomarkers differ in individuals with Down syndrome with and without Alzheimer's disease and may be used for diagnosis and/or prediction.
ALZHEIMERS & DEMENTIA
(2023)
Review
Immunology
Howard Chung, Peter H. R. Green, Timothy C. Wang, Xiao-Fei Kong
Summary: Down syndrome is a genetic disease caused by an extra copy of chromosome 21, which may result in mild interferonopathy in individuals with DS. Despite lack of direct evidence linking this interferonopathy to illnesses in individuals with DS, further research is needed to clarify the impact.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Multidisciplinary Sciences
Claudia Cannavo, Karen Cleverley, Cheryl Maduro, Paige Mumford, Dale Moulding, Elizabeth M. C. Fisher, Frances K. Wiseman
Summary: Individuals with Down syndrome are at high risk of developing Alzheimer's disease. Mouse embryonic fibroblasts from a Down syndrome mouse model are used to study endosome and APP cell biology, and it is found that APP dosage does not affect endosome and APP processing in this cellular model.
Review
Clinical Neurology
Alessia Filippone, Domenico Pratico
Summary: Intracellular protein trafficking through the endosomes is crucial for normal neuronal function. Dysfunctions in the endosome system, particularly through the recycling, degradation, and retrograde pathways, are common in neurodegenerative diseases like Alzheimer's and Down syndrome. Two major routes, mediated by the retromer complex and the newly discovered retriever system, play key roles in endosomal transport and could be potential therapeutic targets in these diseases.
ANNALS OF NEUROLOGY
(2021)
Article
Pharmacology & Pharmacy
Albert Martinez-Pinteno, Patricia Gasso, Llucia Prohens, Alex G. Segura, Mara Parellada, Jeronimo Saiz-Ruiz, Manuel J. Cuesta, Miguel Bernardo, Amalia Lafuente, Sergi Mas, Natalia Rodriguez
Summary: This study identified EP300 as a key gene involved in the metabolic abnormalities induced by antipsychotic drugs. Modulating EP300 levels may be beneficial in mitigating treatment side effects. However, further research is needed to determine the exact role of this gene in the mechanism of action of medications.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Fisheries
Hao Li, Yuehong Zhao, Xiaoli Zhang, Hui Zhao, Weiwei Li, Qun Wang
Summary: In this study, the transcriptional response of Eriocheir sinensis to different forms of Dscam ICDs was investigated. The results showed that different forms of Dscam ICDs can affect key immune, metabolic, and cell proliferation-regulated genes and pathways.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2022)
Article
Reproductive Biology
Yanqiu Dong, Lanjie Jin, Xiaoqian Liu, Dongjie Li, Weina Chen, Haonan Huo, Cui Zhang, Shijie Li
Summary: The study assessed the allelic expression of bovine IMPACT, OSBPL1A, and HRH4 genes and examined the differentially methylated regions (DMRs) associated with these genes. The results revealed isoform-specific monoallelic expression of IMPACT and OSBPL1A genes in bovine adult tissues, while HRH4 gene showed biallelic expression. Additionally, DMRs were identified in the promoter region of OSBPL1A gene and DNA methylation seemed to be correlated with the expression of HRH4 gene in tissues.
Article
Neurosciences
Zohreh Farsi, Ally Nicolella, Sean K. Simmons, Sameer Aryal, Nate Shepard, Kira Brenner, Sherry Lin, Linnea Herzog, Sean P. Moran, Katherine J. Stalnaker, Wangyong Shin, Vahid Gazestani, Bryan J. Song, Kevin Bonanno, Hasmik Keshishian, Steven A. Carr, Jen Q. Pan, Evan Z. Macosko, Sandeep Robert Datta, Borislav Dejanovic, Eunjoon Kim, Joshua Z. Levin, Morgan Sheng
Summary: This study reveals gene expression changes, altered brain activity, enhanced dopamine signaling, and abnormal locomotor behavior in Grin2a mutant mice, providing support for the hypo-glutamate and hyperdopamine hypotheses of schizophrenia.
Article
Multidisciplinary Sciences
Jasper J. van Gemst, Nathalie J. H. G. Passmann, Angelique L. W. M. M. Rops, Toin H. van Kuppevelt, Jo H. Berden, Markus A. Loeven, Ton J. Rabelink, Bart Smeets, Johan van der Vlag
Summary: Despite not altering the final outcome of experimental glomerulonephritis induced by anti-GBM, injection of anti-HS antibodies led to transient effects, potentially through temporarily altered glycocalyx and/or PMN function. Further research is needed to explore alternative strategies targeting HS domains in inflammatory processes during glomerulonephritis.
Article
Mathematics
Leandro Arosio, Gian Maria Dall'Ara, Matteo Fiacchi
Summary: We demonstrate that Worm domains are not Gromov hyperbolic in terms of the Kobayashi distance.
JOURNAL OF GEOMETRIC ANALYSIS
(2023)
Article
Multidisciplinary Sciences
Mitsunori Miyazaki, Michito Shimozuru, Yu Kitaoka, Kenya Takahashi, Toshio Tsubota
Summary: During hibernation, the skeletal muscles of black bears undergo minimal changes, likely as an adaptive strategy to minimize energy wasting.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Chiara Migliore, Anna Vendramin, Shane McKee, Paolo Prontera, Francesca Faravelli, Rani Sachdev, Patricia Dias, Martina Mascaro, Danilo Licastro, Germana Meroni
Summary: Opitz G/BBB syndrome is a rare genetic developmental condition characterized by congenital defects along the midline of the body. Mutations in the MID1 gene and the SPECC1L gene have been associated with the X-linked and autosomal dominant forms of the disease, respectively. This study focused on screening for SPECC1L gene mutations in cases of sporadic OS with excluded MID1 gene mutations. The identified missense variants have been reported in variant databases, but their pathogenic significance remains unclear. The study also confirmed that patients diagnosed with OS, mainly characterized by hypospadias and laryngo-tracheo-esophageal defects, do not carry pathogenic SPECC1L mutations. These findings provide insights into the classification of SPECC1L syndrome.
Editorial Material
Developmental Biology
James Briscoe, Seema Grewal
Editorial Material
Developmental Biology
James Briscoe, Seema Grewal
Article
Cell Biology
Robert Blassberg, Harshil Patel, Thomas Watson, Mina Gouti, Vicki Metzis, M. Joaquina Delas, James Briscoe
Summary: This study reveals that the level of transcription factor SOX2 determines the chromatin occupancy of TCF/β-catenin, thus regulating the cell fate and gene expression during embryonic development.
NATURE CELL BIOLOGY
(2022)
Correction
Multidisciplinary Sciences
Anny Devoy, Georgia Price, Francesca De Giorgio, Rosie Bunton-Stasyshyn, David Thompson, Samanta Gasco, Alasdair Allan, Gemma F. Codner, Remya R. Nair, Charlotte Tibbit, Ross McLeod, Zeinab Ali, Judith Noda, Alessandro Marrero-Gagliardi, Jose M. Brito-Armas, Muhammet M. Ozturk, Michelle Simon, Edward O'Neill, Sam Bryce-Smith, Jackie Harrison, Gemma Atkins, Silvia Corrochano, Michelle Stewart, Lydia Teboul, Abraham Acevedo-Arozena, Elizabeth M. C. Fisher, Thomas J. Cunningham
Editorial Material
Developmental Biology
Kristina S. Stapornwongkul, James Briscoe
Article
Neurosciences
Paige Mumford, Justin Tosh, Silvia Anderle, Eleni Gkanatsiou Wikberg, Gloria Lau, Sue Noy, Karen Cleverley, Takashi Saito, Takaomi C. Saido, Eugene Yu, Gunnar Brinkmalm, Erik Portelius, Kaj Blennow, Henrik Zetterberg, Victor Tybulewicz, Elizabeth M. C. Fisher, Frances K. Wiseman
Summary: This study found that in individuals with Down syndrome (DS), early onset Alzheimer's disease (AD) is associated with multiple copies of the APP gene on chromosome 21, while three copies of other genes on chromosome 21 can partially alleviate the accumulation of AP in the brain. This provides critical mechanistic insight into disease development and explains the typically later age of onset of dementia in DS individuals compared to those with familial AD caused by triplication of APP.
JOURNAL OF NEUROSCIENCE
(2022)
Editorial Material
Developmental Biology
James Briscoe, Katherine Brown
Article
Cell Biology
M. Joaquina Delas, Christos M. Kalaitzis, Tamara Fawzi, Madeleine Demuth, Isabel Zhang, Hannah T. Stuart, Elena Costantini, Kenzo Ivanovitch, Elly M. Tanaka, James Briscoe
Summary: In many developing tissues, graded secreted signals organize the patterns of gene expression that assign cell fate. Cis-regulatory elements (CREs) interpret these signals to regulate gene expression, but the mechanism is poorly understood. In the neural tube, a gradient of the morphogen sonic hedgehog (Shh) determines the pattern of neural progenitors. This study identifies distinct ways in which CREs translate graded Shh into differential gene expression in mouse neural progenitors, identifying potential conserved roles for the pioneer factor FOXA2 across tissues.
DEVELOPMENTAL CELL
(2023)
Article
Developmental Biology
Yushi Redhead, Dorota Gibbins, Eva Lana-Elola, Sheona Watson-Scales, Lisa Dobson, Matthias Krause, Karen J. Liu, Elizabeth M. C. Fisher, Jeremy B. A. Green, Victor L. J. Tybulewicz
Summary: Down syndrome (DS) is a common human chromosomal abnormality that leads to various phenotypic features, including craniofacial dysmorphology. Through analysis of a DS mouse model and genetic mapping, it was found that four regions on mouse chromosome 16, which correspond to Hsa21 in humans, contain dosage-sensitive genes that contribute to DS craniofacial abnormalities, with Dyrk1a identified as one of the causative genes. The study revealed that the earliest and most severe defects in the DS mouse skulls occur in bones of neural crest origin, and that abnormal mineralization of the skull base synchondroses is present. Additionally, increased dosage of Dyrk1a was found to result in decreased proliferation of neural crest cells and a reduction in size and cellularity of the frontal bone primordia.
Editorial Material
Developmental Biology
James Briscoe, Katherine Brown, Steve Wilson
Article
Cell Biology
Kourtney Sloan, Jared Thomas, Matthew Blackwell, Deanna Voisard, Eva Lana-Elola, Sheona Watson-Scales, Daniel L. Roper, Joseph M. Wallace, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Randall J. Roper
Summary: This study investigates the effects of triplicated genes on mouse skeletal phenotypes and finds that they can both improve and worsen bone deficits.
DISEASE MODELS & MECHANISMS
(2023)
Review
Neurosciences
Elizabeth M. C. Fisher, Linda Greensmith, Andrea Malaspina, Pietro Fratta, Michael G. Hanna, Giampietro Schiavo, Adrian M. Isaacs, Richard W. Orrell, Thomas J. Cunningham, Abraham Acevedo Arozena
Summary: Amyotrophic lateral sclerosis (ALS) is a complex disorder with mostly unknown cause, but around 10% of cases are familial and caused by mutations in over 30 different genes. Mouse models exist for many genetic forms of ALS, but there is currently no model for the majority of ALS cases that are sporadic. The development of potential therapies has primarily relied on limited mouse models and has been tested on patients with different etiologies. The use of complex mouse models and patient stratification in clinical trials has proven successful in cancer research, and adopting a similar approach could lead to better understanding of ALS pathologies and faster translation of research findings into effective therapies.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biology
Alexandre P. Thiery, Ailin Leticia Buzzi, Eva Hamrud, Chris Cheshire, Nicholas M. Luscombe, James Briscoe, Andrea Streit
Summary: The vertebrate neural plate border is a transient territory that contains precursors for all ectodermal derivatives. Through single cell RNA sequencing, this study explores the diversity and heterogeneity of cells in the neural plate border and reveals the dynamic expression patterns and fate enrichment of genes previously classified as neural plate border specifiers. Furthermore, the study suggests that individual cells in the neural plate border co-express competing transcriptional programs, indicating their undecided fate.
Article
Biochemistry & Molecular Biology
Alberto Pezzotta, James Briscoe
Summary: This article describes the mechanism of morphogen-driven cell fate decisions in developing tissues. An alternative framework using optimal control theory is developed to tackle the problem of morphogen patterning. This approach recovers experimentally observed properties of patterning strategies and offers insight into design principles that produce timely, precise, and reproducible morphogen patterning.
Review
Biology
M. Saez, J. Briscoe, D. A. Rand
Summary: Cellular diversity during development can be described using quantitative dynamical models, where cell fate decisions can be represented by a small number of decision structures with only two distinct ways of making a binary choice between two fates. This approach allows for quantitative predictions about cellular differentiation.
