Article
Fisheries
Paulina Bustos, Paulina Schmitt, Donald I. Brown, Rodolfo Farlora
Summary: Nuclear receptors play a crucial role in the treatment of parasitic diseases. The study investigates the diversity, expression, and localization of nuclear receptors in the parasitic copepod Caligus rogercresseyi. The functional knock-down of the Cr-RXR gene resulted in delayed egg string production, reduced fecundity, and abnormal gonad and embryo development.
Article
Endocrinology & Metabolism
Rebeca Ortega, Luisa Hueso, Esther Benito, Joaquin Ortega, Miguel Civera, Maria-Jesus Sanz, Jose T. Real, Laura Piqueras
Summary: ROR alpha expression is higher in omental AT compared to subcutaneous AT, positively correlated with BMI and insulin resistance. Inflammation marker release in omental fat from diabetic patients was reduced significantly by ROR alpha blockade, along with improvement in protein kinase B signaling. The study suggests that ROR alpha blockade could be a potential therapy for preventing AT dysfunction and inflammation in human obesity.
INTERNATIONAL JOURNAL OF OBESITY
(2021)
Review
Biochemistry & Molecular Biology
Catherine Cerutti, Jing-Ru Shi, Jean-Marc Vanacker
Summary: Estrogen-related receptors (ERR alpha, beta and gamma) are orphan members of the nuclear receptor superfamily acting as transcription factors. They play various roles in normal and pathological contexts, such as bone homeostasis, energy metabolism, and cancer progression. Unlike other nuclear receptors, ERRs are not controlled by a natural ligand but rely on the availability of transcriptional co-regulators. This review focuses on ERR alpha, discussing the variety of co-regulators and their target genes, highlighting the combinatorial specificity of transcriptional regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Soumita Mukherjee, Subrata Dasgupta, Sujit Sankar Panja, Utpal Adhikari
Summary: The RXR alpha-THR beta heterodimer plays a crucial role in human growth and development. This heterodimer interacts with DNA through conserved/semiconserved water molecules, which mediate the interaction between amino acid residues and DNA sequences.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Genetics & Heredity
Arthur Stefanski, Eduardo Perez-Palma, Marko Mrdjen, Megan McHugh, Costin Leu, Dennis Lal
Summary: This study investigated the association between large deletions causing monogenic disorders and loss-of-function (LOF)-intolerant genes. The results showed that large deletions frequently affected additional LOF-intolerant genes, potentially leading to more complex phenotypes. The impact was dependent on the size of the deletion. Further research is needed to improve clinical care and the efficacy of targeted therapies by understanding the influence of these disease-relevant genes.
GENETICS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Eyal Ben-David, Pinelopi Pliota, Sonya A. Widen, Alevtina Koreshova, Tzitziki Lemus-Vergara, Philipp Verpukhovskiy, Sridhar Mandali, Christian Braendle, Alejandro Burga, Leonid Kruglyak
Summary: The study reveals the presence of maternal-effect TAs in C. tropicalis and C. briggsae, causing significant intraspecific incompatibility. The identification of new TAs genes and their role in larval development suggests TAs are widespread in Caenorhabditis species, and their spreading in populations is affected by balancing selection.
Article
Immunology
David E. Phelan, Masahiko Shigemura, Sarah Aldhafiri, Catarina Mota, Thomas J. Hall, Jacob I. Sznajder, Evelyn P. Murphy, Daniel Crean, Eoin P. Cummins
Summary: The NR4A family members NR4A2 and NR4A3 have distinct and common roles in transcriptional regulation in monocytes, with NR4A2 associated with antigen presentation and MHC genes, and NR4A3 linked to viral response pathways. Functional studies suggest preferential roles for NR4A2 in antigen processing and common roles for both NR4A2 and NR4A3 in cell migration. This study provides new insights into the mechanisms of action of NR4A2 and NR4A3 in monocytes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yun Chen, Shu-Ping Zhang, Wei-Wei Gong, Yang-Yang Zheng, Jie-Ru Shen, Xiao Liu, Yun-Hui Gu, Jia-Hai Shi, Guo-Liang Meng
Summary: This review summarizes the understanding and potential effects of retinoid-related orphan receptor alpha (ROR alpha) in the cardiovascular system, as well as current advances, limitations, challenges, and future strategies for ROR alpha-related drugs in cardiovascular diseases. ROR alpha influences various physiological and pathological processes in the cardiovascular system and is involved in the regulation of inflammation, apoptosis, autophagy, oxidative stress, ER stress, and mitochondrial function. Synthetic ROR alpha agonists or antagonists have been developed in addition to natural ligands. The review highlights the protective roles and possible mechanisms of ROR alpha against cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Food Science & Technology
J. Abraham Dominguez-Avila
Summary: This article summarizes the recent evidence of the effects of phenolic compounds on liver X receptor (LXR) and retinoid X receptor (RXR), two important nuclear receptors. The data shows that these compounds can modify gene expression and exert various bioactivities, particularly in lipid metabolism and processes like cell proliferation and vitamin D metabolism. The findings suggest a promising and novel research area linking diet and health.
Article
Neurosciences
Teng Zhao, Rui Zhong, Xinyue Zhang, Guangjian Li, Chunkui Zhou, Shaokuan Fang, Ying Ding, Weihong Lin
Summary: In this study, a mouse model of hyperthermic seizure was constructed, and in vitro and in vivo electrophysiological and behavioral studies were conducted to elucidate the pathogenic characteristics and mechanism of the GluN2A/GRIN2A-V685G mutation. The mutant mice showed no significant change in the expression of NMDAR compared to the wild type mice. The mutation resulted in altered excitatory/inhibitory balance of neural networks and increased susceptibility to seizures, which could be reversed by treatment with EFV.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Baixue Li, Shi-Ying Cai, James L. Boyer
Summary: Retinoic acid receptors (RARs) and retinoid X receptors (RXRs), activated by retinoids, play crucial roles in various biological processes such as embryo development, homeostasis, cell proliferation, differentiation and death. In liver physiology, RAR/RXR heterodimers regulate lipid and bile acid synthesis and metabolism, cholesterol transport in macrophages, and fibrogenesis in hepatic stellate cells. Specific genes carrying out these functions are regulated by RAR/RXR in liver cells, providing a mechanistic understanding of their roles in liver physiology. Still, detailed signaling mechanisms of RAR/RXR in regulating liver gene expression remain to be fully elucidated in future studies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Neurosciences
Qi Zeng, Ying Yang, Jing Duan, Xueyang Niu, Yi Chen, Dan Wang, Jing Zhang, Jiaoyang Chen, Xiaoling Yang, Jinliang Li, Zhixian Yang, Yuwu Jiang, Jianxiang Liao, Yuehua Zhang
Summary: This study analyzes the phenotypic spectrum, treatment, and prognosis of 72 Chinese children with SCN2A variants. The results show that SCN2A variants are associated with various types of epilepsy phenotypes, and most patients have developmental delay. Oxcarbazepine and valproate are effective drugs, but sodium channel blockers may worsen seizures in patients with onset beyond 1 year of age.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Oncology
Jyoti Kashyap, Rakesh K. Tyagi
Summary: Mitosis is a crucial process for cell self-renewal, and recent studies have shown that some transcription factors remain attached to chromatin during cell division, ensuring the reactivation of necessary transcription factors. This study confirms Vitamin D Receptor (VDR) as a mitotic bookmarking factor that plays a crucial role in maintaining cell identity and genome bookmarking.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Clinical Neurology
Antonella Morea, G. Boero, V. Demaio, T. Francavilla, A. La Neve
Summary: Eyelid myoclonia with absences, a childhood epileptic syndrome recently classified, may have a genetic origin and is triggered by eyes closure in a well-lit room causing EEG abnormalities. Patients with this syndrome often exhibit intellectual disability and attention deficit hyperactivity disorder (ADHD).
NEUROLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Carlos Roma-Mateo, Sheila Lorente-Pozo, Lucia Marquez-Thibaut, Mireia Moreno-Estelles, Concepcion Garces, Dayme Gonzalez, Marcos Lahuerta, Carmen Aguado, Jose Luis Garcia-Gimenez, Pascual Sanz, Federico V. V. Pallardo
Summary: Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by intracellular accumulation of abnormal polyglucosan granules. Experimental mouse models deficient in laforin or malin proteins provide evidence of molecular and cellular alterations in neural tissue. Overexpression of miR-155 and miR-146a in an age-dependent manner and altered gene expression in brain extracts indicate their potential role as biomarkers for disease progression in LD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Roberta Celli, Pasquale Striano, Rita Citraro, Luisa Di Menna, Milena Cannella, Tiziana Imbriglio, Mahmoud Koko, Euro Epinomics-Cogie Euro Epinomics-Cogie Consortium, Giovambattista De Sarro, James A. Monn, Giuseppe Battaglia, Gilles van Luijtelaar, Ferdinando Nicoletti, Emilio Russo, Antonio Leo
Summary: Previous studies suggest that modulation of mGlu3 receptors may be a potential treatment for absence epilepsy. This study found that mGlu3 receptor expression and signaling were decreased in the somatosensory cortex and thalamus of epileptic rats, and selective activation of mGlu3 receptors reduced seizures and depressive-like behavior. However, no association was found between genetic variants of GRM3 and absence epilepsy.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Clinical Neurology
Tobias Brunger, Eduardo Perez-Palma, Ludovica Montanucci, Michael Nothnagel, Rikke S. Moller, Stephanie Schorge, Sameer Zuberi, Joseph Symonds, Johannes R. Lemke, Andreas Brunklaus, Stephen F. Traynelis, Patrick May, Dennis Lal
Summary: This study aimed to systematically identify biological features associated with variant pathogenicity in ion-channel genes and found that these features are correlated with clinical phenotypes and molecular measurements in patients with neurodevelopmental disorders. The results suggest the feasibility of clinical decision support algorithms that can predict variant pathogenicity and function in the future.
Article
Clinical Neurology
Kelly G. Knupp, Ingrid E. Scheffer, Berten Ceulemans, Joseph Sullivan, Katherine C. Nickels, Lieven Lagae, Renzo Guerrini, Sameer M. Zuberi, Rima Nabbout, Kate Riney, Anupam Agarwal, Michael Lock, David Dai, Gail M. Farfel, Bradley S. Galer, Arnold R. Gammaitoni, Shikha Polega, Ronald Davis, Antonio Gil-Nagel
Summary: Long-term use of fenfluramine showed sustained reduction in drop seizure frequency in LGS patients, with significant reduction in the frequency of GTCS and tonic seizures. The drug was generally well tolerated with minimal adverse effects and no significant cardiac side effects observed. Fenfluramine may serve as an important long-term treatment option for patients with LGS.
Article
Biochemistry & Molecular Biology
Antony Kaspi, Michael S. Hildebrand, Victoria E. Jackson, Ruth Braden, Olivia van Reyk, Tegan Howell, Simone Debono, Mariana Lauretta, Lottie Morison, Matthew J. Coleman, Richard Webster, David Coman, Himanshu Goel, Mathew Wallis, Gabriel Dabscheck, Lilian Downie, Emma K. Baker, Bronwyn Parry-Fielder, Kirrie Ballard, Eva Harrold, Shaun Ziegenfusz, Mark F. Bennett, Erandee Robertson, Longfei Wang, Amber Boys, Simon E. Fisher, David J. Amor, Ingrid E. Scheffer, Melanie Bahlo, Angela T. Morgan
Summary: This study identified new candidate genes associated with childhood apraxia of speech (CAS) through genome sequencing and bioinformatic analysis. The findings highlight the roles of chromatin organization and gene regulation in CAS, and confirm co-expression of CAS-related genes during brain development.
MOLECULAR PSYCHIATRY
(2023)
Article
Clinical Neurology
Helena Martins Custodio, Lisa M. Clayton, Ravishankara Bellampalli, Susanna Pagni, Katri Silvennoinen, Richard Caswell, John C. Ambrose, Andreas Brunklaus, Renzo Guerrini, Bobby P. C. Koeleman, Johannes R. Lemke, Rikke S. Moler, Ingrid E. Scheffer, Sarah Weckhuysen, Federico Zara, Sameer Zuberi, Karoline Kuchenbaecker, Simona Balestrini, James D. Mills, Sanjay M. Sisodiya
Summary: Dravet syndrome, a rare severe epilepsy caused by SCN1A variants, shows phenotypic heterogeneity that cannot be fully explained by the causal variant or clinical factors. In this study, additional genomic variation and rare variants in epilepsy-related genes were found to contribute to the phenotypic diversity of adults with SCN1A-related Dravet syndrome. The study also revealed differences in polygenic risk scores for intelligence and longevity between Dravet syndrome and epilepsy controls, suggesting that genetic background plays a role in the syndrome's phenotype and mortality risk.
Article
Clinical Neurology
Alice M. Donnan, Amy L. Schneider, Sophie Russ-Hall, Leonid Churilov, Ingrid E. Scheffer
Summary: This study aims to describe the proportions of patients with commonly encountered genetic developmental and epileptic encephalopathies (DEEs) who developed convulsive status epilepticus (CSE), nonconvulsive status epilepticus (NCSE), and sudden unexplained death in epilepsy (SUDEP). The findings showed that the proportions of these serious presentations vary for different genetic DEEs. These results have important implications for early diagnosis, management, and disease-specific counseling for this high-risk group of conditions.
Article
Clinical Neurology
Rebekah V. Harris, Karen L. Oliver, Piero Perucca, Pasquale Striano, Angelo Labate, Antonella Riva, Bronwyn E. Grinton, Joshua Reid, Jessica Hutton, Marian Todaro, Terence J. O'Brien, Patrick Kwan, Lynette G. Sadleir, Saul A. Mullen, Emanuela Dazzo, Douglas E. Crompton, Ingrid E. Scheffer, Melanie Bahlo, Carlo Nobile, Antonio Gambardella, Samuel F. Berkovic
Summary: This study analyzed 134 families with familial mesial temporal lobe epilepsy (FMTLE) and found that FMTLE is a generally mild drug-responsive syndrome with the main symptom being déjà vu. Unlike monogenic focal epilepsy syndromes, molecular data supports a polygenic basis for FMTLE. The polygenic risk score (PRS) data suggests that sub-genome-wide significant focal epilepsy genome-wide association study single nucleotide polymorphisms are important risk variants for FMTLE.
ANNALS OF NEUROLOGY
(2023)
Article
Biology
N. Dirkx, Wout J. J. Weuring, E. De Vriendt, N. Smal, J. van de Vondervoort, Ruben van 't Slot, M. Koetsier, N. Zonnekein, Tim De Pooter, S. Weckhuysen, B. P. C. Koeleman
Summary: This study demonstrates improved editing rates in hiPSC using EF-1 & alpha;-driven sncRNA pAIO-PE plasmids, especially after FACS sorting. Optimizing these sncRNA PE systems will be important for future therapeutic in vivo use, where accuracy is crucial.
Article
Clinical Neurology
Sterre Van der Veen, Gabrielle T. W. Tse, Alessandro Ferretti, Giacomo Garone, Bart Post, Nicola Specchio, Victor S. C. Fung, Marina Trivisano, Ingrid E. Scheffer
Summary: In patients with genetic DEEs, a variety of MDs are present, with stereotypies and dystonia being the most common. Different biological mechanisms may lead to different types of MDs.
Editorial Material
Clinical Neurology
Zimeng Ye, Sufang Lin, Xia Zhao, Mathew Wallis, Xinyi Gao, Li Sun, Jiarui Wu, Jing Duan, Yi Yao, Lin Li, Li Chen, Dezhi Cao, Zhanqi Hu, Victor W. Zhang, Samuel F. Berkovic, Ingrid E. Scheffer, Jianxiang Liao, Michael S. Hildebrand
PEDIATRIC NEUROLOGY
(2024)
Article
Neurosciences
Benedetta Kassabian, Christina Duhring Fenger, Marjolaine Willems, Angel Aledo-Serrano, Tarja Linnankivi, Pamela Pojomovsky McDonnell, Laina Lusk, Birgit Susanne Jepsen, Michael Bayat, Anja Kattentidt, Anna Abuli Vidal, Gabriel Valero-Lopez, Helena Alarcon-Martinez, Kimberly Goodspeed, Marjon van Slegtenhorst, Tahsin Stefan Barakat, Rikke S. Moller, Katrine M. Johannesen, Guido Rubboli
Summary: The phenotypic spectrum of SLC6A1-related neurodevelopmental disorders (SLC6A1-NDD) includes intellectual disability (ID), autistic spectrum disorders (ASD), epilepsy, developmental delay, and other neurological features. Our study aimed to investigate intrafamilial phenotypic variability in families with SLC6A1 variants and found that relatives presented with a less severe phenotype compared to probands.
FRONTIERS IN NEUROSCIENCE
(2023)
Correction
Neurosciences
Benedetta Kassabian, Christina Duhring Fenger, Marjolaine Willems, Angel Aledo-Serrano, Tarja Linnankivi, Pamela Pojomovsky Mcdonnell, Laina Lusk, Birgit Susanne Jepsen, Michael Bayat, Anja A. Kattentidt-Mouravieva, Anna Abuli Vidal, Gabriel Valero-Lopez, Helena Alarcon-Martinez, Kimberly Goodspeed, Marjon van Slegtenhorst, Tahsin Stefan Barakat, Rikke S. Moller, Katrine M. Johannesen, Guido Rubboli
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Katrine M. Johannesen, Jimmi Nielsen, Anne Sabers, Bertrand Isidor, Anja A. Kattentidt-Mouravieva, Dominik Zieglgaensberger, Alexis R. Heidlebaugh, Kathryn F. Oetjens, Anna Abuli Vidal, Jakob Christensen, Jacob Tiller, Amber N. Freed, Rikke S. Moller, Guido Rubboli
Summary: SLC6A1 is a common genetic cause of epilepsy and neurodevelopmental disorders. Adult patients with SLC6A1 variants show similar phenotypic characteristics to pediatric patients, including intellectual disability, epilepsy, and behavioral disorders.
FRONTIERS IN NEUROSCIENCE
(2023)
Correction
Clinical Neurology
Fanny Mochel, AgnSs Rastetter, Berten Ceulemans, Konrad Platzer, Sandra Yang, Deepali N. Shinde, Katherine L. Helbig, Diego Lopergolo, Francesca Mari, Alessandra Renieri, Elisa Benetti, Roberto Canitano, Quinten Waisfisz, Astrid S. Plomp, Sylvia A. Huisman, Golder N. Wilson, Sara S. Cathey, Raymond J. Louie, Daniela Del Gaudio, Darrel Waggoner, Shawn Kacker, Kimberly M. Nugent, Elizabeth R. Roeder, Ange-Line Bruel, Julien Thevenon, Nadja Ehmke, Denise Horn, Manuel Holtgrewe, Frank J. Kaiser, Susanne B. Kamphausen, Rami Abou Jamra, Sarah Weckhuysen, Carine Dalle, Christel Depienne
Article
Medicine, General & Internal
Hang Lyu, Christian M. Bosselmann, Katrine M. Johannesen, Mahmoud Koko, Juan Dario Ortigoza-Escobar, Sergio Aguilera-Albesa, Deyanira Garcia -Navas Nunez, Tarja Linnankivi, Eija Gaily, Henriette J. A. van Ruiten, Ruth Richardson, Cornelia Betzler, Gabriella Horvath, Eva Brilstra, Niels Geerdink, Daniele Orsucci, Alessandra Tessa, Elena Gardella, Zofia Fleszar, Ludger Schoels, Holger Lerche, Rikke S. Moller, Yuanyuan Liu
Summary: SCN8A variants are associated with a spectrum of ataxias, including chronic progressive and episodic ataxia. Variants causing chronic ataxia exhibit a more pronounced loss-of-function effect, while variants causing episodic ataxia show mixed gain-and loss-of function effects. Sodium channel blockers should be avoided in individuals with SCN8A-related ataxias.