Article
Multidisciplinary Sciences
Moshe Giladi, Michal Lisnyansky Bar-El, Pavla Vankova, Alisa Ferofontov, Emelia Melvin, Suha Alkaderi, Daniel Kavan, Boris Redko, Elvira Haimov, Reuven Wiener, Petr Man, Yoni Haitin
Summary: Isoprenoids are synthesized by the prenyltransferase superfamily, and the correlation between active site volume and product length is not observed in long-chain products and rubber synthases. In the human cis-prenyltransferase complex, elongating products exit through an outlet, and product elongation is closely correlated with membrane association.
Article
Biochemistry & Molecular Biology
Jia-Jin Liu, Po-Huang Liang
Summary: This study investigates the differences in dolichol synthesis between plants and animals by studying the homologues of dehydrodolichyl diphosphate synthases (DHDDSs) and cis-prenyltransferases (cis-PTs) in Cinnamomum kanehirae. The researchers discovered that plants have multiple cis-PT homologues, which can either pair or stand alone to produce different chain-length products. Additionally, the study reveals the possible evolutionary paths of these proteins based on their roles in polyprenol and dolichol biosynthesis and sequence motifs.
Article
Microbiology
Urszula Perlinska-Lenart, Sebastian Graczyk, Sebastian Pilsyk, Jacek Lenart, Agata Lipko, Ewa Swiezewska, Przemyslaw Bernat, Joanna S. S. Kruszewska
Summary: In this study, Trichoderma atroviride strains with improved antifungal activity were created by expressing the RER2 gene from Saccharomyces cerevisiae. The enhanced synthesis of dolichyl phosphate resulted in increased activities of dolichyl-dependent enzymes and stimulated glycosylation of secretory proteins. The transformed strains showed higher levels of cellulase secretion and were more effective against the plant pathogen Pythium ultimum.
Review
Biochemistry & Molecular Biology
Steven J. Fliesler, Sriganesh Ramachandra Rao, Mai N. Nguyen, Mahmoud Tawfik KhalafAllah, Steven J. Pittler
Summary: This review focuses on the phenotypic characteristics and genetic mutations of RP59 models and patients. The ocular phenotypes are particularly emphasized. The findings address knowledge gaps in the underlying pathobiology mechanism of RP59 and have potential implications for developing therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Carolina Courage, Karen L. Oliver, Eon Joo Park, Jillian M. Cameron, Kariona A. Grabinska, Mikko Muona, Laura Canafoglia, Antonio Gambardella, Edith Said, Zaid Afawi, Betul Baykan, Christian Brandt, Carlo di Bonaventura, Hui Bein Chew, Chiara Criscuolo, Leanne M. Dibbens, Barbara Castellotti, Patrizia Riguzzi, Angelo Labate, Alessandro Filla, Anna T. Giallonardo, Geza Berecki, Christopher B. Jackson, Tarja Joensuu, John A. Damiano, Sara Kivity, Amos Korczyn, Aarno Palotie, Pasquale Striano, Davide Uccellini, Loretta Giuliano, Eva Andermann, Ingrid E. Scheffer, Roberto Michelucci, Melanie Bahlo, Silvana Franceschetti, William C. Sessa, Samuel F. Berkovic, Anna-Elina Lehesjoki
Summary: Progressive myoclonus epilepsies (PMEs) are a group of clinically and genetically heterogeneous rare diseases, with over 70% of cases now molecularly solved. By performing whole-exome sequencing on unsolved PME-affected individuals, novel disease-causing variants were identified, particularly in cases studied with additional family members. A variety of new genes related to lysosomal and endosomal function were discovered, shedding light on the genetic complexity of PME.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Nuno Maia, Sven Potelle, Hamide Yildirim, Sandrine Duvet, Shyam K. Akula, Celine Schulz, Elsa Wiame, Alexander Gheldof, Katherine O'Kane, Abbe Lai, Karen Sermon, Maia Proisy, Philippe Loget, Tania Attie-Bitach, Chloe Quelin, Ana Maria Fortuna, Ana Rita Soares, Arjan P. M. de Brouwer, Emile Van Schaftingen, Marie-Cecile Nassogne, Christopher A. Walsh, Katrien Stouffs, Paula Jorge, Anna C. Jansen, Francois Foulquier
Summary: This study reports on six individuals, including two fetuses, with bi-allelic pathogenic variants in MAN2C1 gene from four different families. These individuals exhibit dysmorphic features, congenital anomalies, and brain abnormalities. The pathogenicity of MAN2C1 variants is confirmed, and it is demonstrated that these variants lead to accumulation and delay in the processing of fOSs in cells.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Floranne Boulogne, Laura R. Claus, Henry Wiersma, Roy Oelen, Floor Schukking, Niek de Klein, Shuang Li, Harm-Jan Westra, Bert van der Zwaag, Franka van Reekum, Dana Sierks, Ria Schoenauer, Zhigui Li, Emilia K. Bijlsma, Willem Jan W. Bos, Jan Halbritter, Nine V. A. M. Knoers, Whitney Besse, Patrick Deelen, Lude Franke, Albertien M. van Eerde
Summary: Researchers have developed KidneyNetwork, a method that utilizes tissue-specific expression to prioritize candidate genes for kidney diseases. By integrating kidney RNA-sequencing co-expression network with a multi-tissue network, KidneyNetwork predicts genes related to kidney disease phenotypes using expression patterns and gene-phenotype associations. Applying KidneyNetwork to patients with undiagnosed kidney disease, it accurately predicts kidney-specific gene functions and identifies ALG6 as a plausible candidate gene for kidney and liver cysts.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Review
Endocrinology & Metabolism
Congli Chen, Yanmei Sang
Summary: Congenital hyperinsulinemia (CHI) is a clinically diverse disorder that causes persistent and recurrent hypoglycemia in infancy and childhood. There are 16 subtypes of CHI-related genes, with phosphomannomutase 2 hyperinsulinemia (PMM2-HI) being an extremely rare subtype. This review highlights the genetic pathogenesis, and current diagnostic and therapeutic advances of PMM2-HI to raise awareness among clinicians.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Wei Shi, Angel P. Scialdone, James I. Emerson, Liu Mei, Lauren K. Wasson, Haley A. Davies, Christine E. Seidman, Jonathan G. Seidman, Jeanette G. Cook, Frank L. Conlon
Summary: This study reveals that the CHD4 mutation can cause ventricular wall defects, and that ADAMTS1 can improve this defect by regulating the function of CHD4. This research enhances our understanding of heart development and provides a new therapeutic strategy for treating heart diseases.
CIRCULATION RESEARCH
(2023)
Article
Hematology
Shijie Zhou, Xi Wu, Ying Song, Lei Li, Chunli Shi, Zhe Lai, Qiulan Ding, Wenman Wu, Jing Dai, Xuefeng Wang, Yeling Lu
Summary: This study identified a heterozygous mutation in the PROC gene of a thrombosis patient, which affects the anticoagulant function of protein C. The mutation introduces a new glycosylation site that impairs the activation and anticoagulant activity of protein C, leading to thrombosis in the patient.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biology
Shaoyi Mei, Yi Wu, Yan Wang, Yubo Cui, Miao Zhang, Tong Zhang, Xiaosheng Huang, Sejie Yu, Tao Yu, Jun Zhao
Summary: Through our study on a Chinese family, we identified a potential variant in the PIKFYVE gene, which is involved in the pathogenesis of congenital cataract. We demonstrated that the loss of PIKFYVE function causes congenital cataract and identified a potential treatment using Baf-A1.
Article
Clinical Neurology
Serena Galosi, Ban H. Edani, Simone Martinelli, Hana Hansikova, Erik A. Eklund, Caterina Caputi, Laura Masuelli, Nicole Corsten-Janssen, Myriam Srour, Renske Oegema, Danielle G. M. Bosch, Colin A. Ellis, Louise Amlie-Wolf, Andrea Accogli, Isis Atallah, Luisa Averdunk, Kristin W. Baranano, Roberto Bei, Irene Bagnasco, Alfredo Brusco, Scott Demarest, Anne-Sophie Alaix, Carlo Di Bonaventura, Felix Distelmaier, Frances Elmslie, Ziv Gan-Or, Jean-Marc Good, Karen Gripp, Erik-Jan Kamsteeg, Ellen Macnamara, Carlo Marcelis, Noelle Mercier, Joseph Peeden, Simone Pizzi, Luca Pannone, Marwan Shinawi, Camilo Toro, Nienke E. Verbeek, Sunita Venkateswaran, Patricia G. Wheeler, Lucie Zdrazilova, Rong Zhang, Giovanna Zorzi, Renzo Guerrini, William C. Sessa, Dirk Lefeber, Marco Tartaglia, Fadi F. Hamdan, Kariona A. Grabinska, Vincenzo Leuzzi
Summary: This study investigated the variants in the DHDDS gene and found that they are associated with a new neurodegenerative disorder characterized by symptoms such as neurodevelopmental disorders, epilepsy, myoclonus, and cognitive decline. The study also revealed dysfunctional lysosomal enzymatic scavenger machinery.
Article
Multidisciplinary Sciences
May E. Montasser, Cristopher V. Van Hout, Lawrence Miloscio, Alicia D. Howard, Avraham Rosenberg, Myrasol Callaway, Biao Shen, Ning Li, Adam E. Locke, Niek Verweij, Tanima De, Manuel A. Ferreira, Luca A. Lotta, Aris Baras, Thomas J. Daly, Suzanne A. Hartford, Wei Lin, Yuan Mao, Bin Ye, Derek White, Guochun Gong, James A. Perry, Kathleen A. Ryan, Qing Fang, Gannie Tzoneva, Evangelos Pefanis, Charleen Hunt, Yajun Tang, Lynn Lee, Carole Sztalryd-Woodle, Braxton D. Mitchell, Matthew Healy, Elizabeth A. Streeten, Simeon Taylor, Jeffrey R. O'Connell, Aris N. Economides, Giusy Della Gatta, Alan R. Shuldiner
Summary: Increased blood levels of LDL-C and fibrinogen are independent risk factors for cardiovascular disease. A missense variant in the B4GALT1 gene was associated with lower LDL-C and fibrinogen levels, as well as decreased risk of coronary artery disease. This suggests that targeting protein galactosylation could be a potential therapeutic approach for reducing cardiovascular disease risk.
Review
Genetics & Heredity
Julien H. Park, Thorsten Marquardt
Summary: Despite limited treatment options for congenital disorders like CDG, significant advances have been made in recent years in developing new therapies aimed at addressing both the causal defect and secondary disease manifestations, providing more possibilities for treatment.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Silvia Radenkovic, Diego Martinelli, Yuebo Zhang, Graeme J. Preston, Arianna Maiorana, Alessandra Terracciano, Maria Lisa Dentici, Elisa Pisaneschi, Antonio Novelli, Wasantha Ranatunga, Anna N. Ligezka, Bart Ghesquiere, David R. Deyle, Tamas Kozicz, Filippo Pinto e Vairo, Peter Witters, Eva Morava
Summary: This study identified associations between TRAPPC9 deficiency and intellectual disability, dysmorphic features, and abnormal glycosylation, suggesting that TRAPPC9 deficiency may lead to a congenital disorder of glycosylation (CDG). These findings are highly relevant for diagnosis, further elucidation of the pathophysiology, and management of the disease.
GENETICS IN MEDICINE
(2022)
Article
Urology & Nephrology
Jakub Sikora, Tereza Kmochova, Dita Musalkova, Michal Pohludka, Petr Prikryl, Hana Hartmannova, Katerina Hodanova, Helena Treslova, Lenka Noskova, Lenka Mrazova, Viktor Stranecky, Mariia Lunova, Milan Jirsa, Eva Honsova, Surendra Dasari, Ellen D. McPhail, Nelson Leung, Martina Zivna, Anthony J. Bleyer, Ivan Rychlik, Romana Rysava, Stanislav Kmoch
Summary: Amyloid A amyloidosis is a serious clinical condition characterized by the deposition of amyloid A originating from serum amyloid A proteins. This study describes a family with primary amyloid A amyloidosis caused by a mutation in the SAA1 promoter gene. The mutation leads to increased serum amyloid A levels and the development of kidney disease.
KIDNEY INTERNATIONAL
(2022)
Article
Clinical Neurology
Sarah L. Stenton, Marketa Tesarova, Natalia L. Sheremet, Claudia Catarino, Valerio Carelli, Elzbieta Ciara, Kathryn Curry, Martin Engvall, Leah R. Fleming, Peter Freisinger, Katarzyna Iwanicka-Pronicka, Elzbieta Jurkiewicz, Thomas Klopstock, Mary K. Koenig, Hana Kolarova, Bohdan Kousal, Tatiana Krylova, Chiara La Morgia, Lenka Noskova, Dorota Piekutowska-Abramczuk, Sam N. Russo, Viktor Stranecky, Iveta Tothova, Frank Traisk, Holger Prokisch
Summary: The study identified 28 previously unreported individuals carrying the DNAJC30 variant, expanding the spectrum of Leber hereditary optic neuropathy and Leigh syndrome. The findings confirmed sex-dependent incomplete penetrance of the homozygous variant and the association of DNAJC30 with Leigh syndrome.
Article
Biochemistry & Molecular Biology
Hanadi Ananbeh, Jaromir Novak, Stefan Juhas, Jana Juhasova, Jiri Klempir, Kristyna Doleckova, Irena Rysankova, Karolina Turnovcova, Jaroslav Hanus, Hana Hansikova, Petr Vodicka, Helena Kupcova Skalnikova
Summary: This study characterizes HTT and mHTT forms/fragments found in blood plasma derived EVs in porcine models of HD and HD patients, representing a valuable step towards identifying HD biomarkers. A specific mutant HTT fragment was observed in the TgHD pig model, indicating potential disease relevance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Lucie Zdrazilova, Hana Hansikova, Erich Gnaiger
Summary: In this study, we compared the respiration differences between attached and suspended cells using multiple measurement platforms. The results showed no differences in ROUTINE and LEAK respiration between attached and suspended cells. The O2k platform had a higher electron transfer capacity than the XF24, which was possibly due to the limitations of uncoupler titrations in the XF24 platform leading to underestimation. Short-term suspension did not affect respiratory activity and coupling control.
Article
Microscopy
Marie Vanisova, Hana Stufkova, Michaela Kohoutova, Tereza Rakosnikova, Jana Krizova, Jiri Klempir, Irena Rysankova, Jan Roth, Jiri Zeman, Hana Hansikova
Summary: This study investigates mitochondrial structure and function in skin fibroblasts from HD patients and finds disruptions in mitochondrial structure, function, and signs of apoptosis. These findings suggest that energy metabolism damage in HD is not limited to the central nervous system but also plays a role in peripheral tissues. Skin fibroblasts can serve as a suitable cellular model for understanding HD pathobiochemical processes and identifying potential targets for new therapies.
ULTRASTRUCTURAL PATHOLOGY
(2022)
Article
Genetics & Heredity
Hana Stufkova, Hana Kolarova, Katerina Lokvencova, Tomas Honzik, Jiri Zeman, Hana Hansikova, Marketa Tesarova
Summary: In this study, a new pathogenic variant in mitochondrial DNA was discovered, associated with symptoms including myoclonus, epilepsy, muscle weakness, and hearing impairment. The variant was found in the MTTK gene with a mutation load ranging from 71% to >96% in tested tissues. The study also revealed decreased respiratory chain complex activities in muscle mitochondria. This finding expands the spectrum of MTTK variants associated with mitochondrial encephalopathies in adults.
Article
Pharmacology & Pharmacy
Veronika Talianova, Zdenek Kejik, Robert Kaplanek, Katerina Vesela, Nikita Abramenko, Lukas Lacina, Karolina Strnadova, Barbora Dvorankova, Pavel Martasek, Michal Masarik, Magdalena Houdova Megova, Petr Busek, Jana Krizova, Lucie Zdrazilova, Hana Hansikova, Erik Vlcak, Vlada Filimonenko, Aleksi Sedo, Karel Smetana, Milan Jakubek
Summary: IL-6 signaling plays a crucial role in the pathogenesis of serious diseases such as chronic inflammation and cancer. Two newly designed bis-pentamethinium salts compounds showed potential in binding IL-6 receptor and inhibiting mitochondrial metabolism in cancer cells.
Article
Biochemistry & Molecular Biology
Michael Pasak, Marie Vanisova, Lucie Tichotova, Jana Krizova, Taras Ardan, Yaroslav Nemesh, Jana Cizkova, Anastasiia Kolesnikova, Ruslan Nyshchuk, Natasha Josifovska, Lyubomyr Lytvynchuk, Miriam Kolko, Jan Motlik, Goran Petrovski, Hana Hansikova
Summary: This study investigates the changes in mitochondrial parameters in the neuroretina, retinal pigment epithelium (RPE), and choroid in a porcine model of retinal ischemia (RI). The findings suggest that mitochondrial dysfunction and alterations in mitochondrial proteins may play a role in the pathophysiology of RI.
Article
Endocrinology & Metabolism
An N. Dang Do, Irene J. Chang, Xutian Jiang, Lynne A. Wolfe, Bobby G. Ng, Christina Lam, Rhonda E. Schnur, Katrina Allis, Hana Hansikova, Nina Ondruskova, Shawn D. O'Connor, Amarilis Sanchez-Valle, Arve Vollo, Raymond Y. Wang, Zoe Wolfenson, John Perreault, Daniel S. Ory, Hudson H. Freeze, J. Lawrence Merritt, Forbes D. Porter
Summary: Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are metabolic errors that can present with severe liver disease and other symptoms. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are biomarkers that can be used for screening NPC. In this study, an infant with ATP6AP1-CDG was found to have elevated oxysterols and bile acid, mimicking NPC. Further investigation showed elevated PPCS in patients with ATP6AP1-, ALG1-, ALG8-, and PMM2-CDG, but not the bile acid derivative TCG. These findings emphasize the importance of considering CDG as a differential diagnosis in children with early-onset liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Genetics & Heredity
Marketa Vlckova, Darina Prchalova, Pavel Zimmermann, Jana Haberlova, Sarka Bendova, Veronika Moslerova, Viktor Stranecky, Zdenek Sedlacek, Miroslava Hancarova
Summary: Congenital myasthenic syndromes (CMS) are characterized by hypotonia, muscle weakness and fatigue. CMS20, caused by variants in SLC5A7, is a rare disorder associated with neurodevelopmental disorders (NDDs). This study identified two SLC5A7 variants in a 12-year-old boy with CMS20 and NDDs, highlighting the importance of genetic analysis in understanding rare diseases.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Joseph Wayne M. Fowler, Nabil E. Boutagy, Rong Zhang, Daiki Horikami, Michael B. Whalen, Casey E. Romanoski, William C. Sessa
Summary: The transcription factor SREBP2 is the main regulator of cholesterol homeostasis and has been implicated in leukocyte immune responses. In this study, the role of SREBP2 in endothelial cells was investigated, revealing its impact on inflammatory chemokine production and interferon response genes.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Multidisciplinary Sciences
Wenping Zhou, Wenxue Li, Shisheng Wang, Barbora Salovska, Zhenyi Hu, Bo Tao, Yi Di, Ujwal Punyamurtula, Benjamin E. E. Turk, William C. C. Sessa, Yansheng Liu
Summary: The authors used optogenetics and mass spectrometry-based phosphoproteomics to study the effects of different intensities, durations, and patterns of Akt1 activation on phosphorylation circuits, revealing downstream signaling outcomes of Akt1. The study showed that different intensities, durations, and patterns of Akt1 activation lead to distinct phosphorylation profiles in vascular endothelial cells, and also revealed the interaction between Akt1 signaling and growth factor signaling in these cells. The resulting dataset provides an important resource for future studies on AKT signaling and dynamics.
NATURE COMMUNICATIONS
(2023)
Review
Gastroenterology & Hepatology
Michele A. Rodrigues, Dawidson A. Gomes, Romina Fiorotto, Mateus T. Guerra, Jittima Weerachayaphorn, Tao Bo, William C. Sessa, Mario Strazzabosco, Michael H. Nathanson
Summary: Fluid and bicarbonate secretion in cholangiocytes is regulated by ITPR3, which localizes to the apical region. This localization is dependent on intact lipid rafts and interactions with CAV1 and MYH9. Disruption of lipid rafts or knockdown of CAV1 or MYH9 impairs ITPR3 localization and secretion.
HEPATOLOGY COMMUNICATIONS
(2022)
Review
Medicine, Research & Experimental
Nabil E. Boutagy, Abhishek K. Singh, William C. Sessa
Summary: Obesity is a major contributor to insulin resistance and type 2 diabetes, increasing the risk of cardiovascular disease. Metabolic changes caused by obesity negatively affect the vasculature, exacerbating disease progression. Understanding the cellular and molecular processes is crucial for optimizing medical therapies.
JOURNAL OF CLINICAL INVESTIGATION
(2022)