Article
Genetics & Heredity
Mohan Rajeshwari, Sellamuthu Karthi, Reetu Singh, Stephanie Efthymiou, Vykuntaraju K. Gowda, Perumal Varalakshmi, Varunvenkat M. Srinivasan, Henry Houlden, Markus A. Keller, William B. Rizzo, Balasubramaniem Ashokkumar
Summary: The study identified several novel mutations causing Sjogren-Larsson syndrome (SLS) and revealed the diverse clinical manifestations of this neuro-ichthyotic condition. Asymmetric distribution of nonclassical traits and a novel neurological phenotype were observed in the study. Genetic testing confirmed that the identified mutations may disrupt enzyme activity and lead to SLS.
Article
Biotechnology & Applied Microbiology
Jean-Philippe Kanter, Philipp Jakob Honold, David Lueke, Sven Heiles, Bernhard Spengler, Marco Alexander Fraatz, Christoph Harms, Jakob Peter Ley, Holger Zorn, Andreas Klaus Hammer
Summary: Aldehydes can be produced by converting fatty acids with enzymes from the alpha-dioxygenase pathway. The enzymes alpha-dioxygenase (alpha-DOX) from Crocosphaera subtropica and fatty aldehyde dehydrogenase (FALDH) from Vibrio harveyi were used in a tandem repetitive reaction to achieve high aldehyde yields. The method was then applied to sea buckthorn pulp oil to produce flavoring/fragrance ingredients. The resulting aldehydes were identified, characterized, and analyzed for their odor impressions.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hongying Daisy Dai, Fang Qiu, Kimberly Jackson, Marcus Fruttiger, William B. Rizzo
Summary: Sjogren-Larsson syndrome (SLS) is a rare inherited neurocutaneous disease characterized by ichthyosis, spastic diplegia or tetraplegia, intellectual disability and a distinctive retinopathy. SLS is caused by bi-allelic mutations in ALDH3A2, which results in abnormal lipid metabolism. The biochemical abnormalities in SLS and the pathogenic mechanisms leading to symptoms are still unclear.
Article
Biochemistry & Molecular Biology
Koki Nojiri, Shuhei Fudetani, Ayami Arai, Takuya Kitamura, Takayuki Sassa, Akio Kihara
Summary: Sjogren-Larsson syndrome is a genetic neurocutaneous disorder caused by mutations in the ALDH3A2 gene. Research has found that the pathology mainly involves a decrease in acylceramide production. Experiments with double-knockout mice and human immortalized keratinocytes lacking ALDH3A2 demonstrated reduced acylceramide levels, providing insight into the development of the disease.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Che-Hong Chen, Benjamin R. Kraemer, Lucia Lee, Daria Mochly-Rosen
Summary: Human ALDH is a multigene family with 19 functional members involved in detoxification and biotransformation. Genetic mutations can lead to toxic aldehyde accumulation and human pathologies. The physiological functions and substrate specificity of many ALDH genes are still unknown.
Article
Health Care Sciences & Services
Tsuo-Hsuan Chien, Chih-Lang Lin, Li-Wei Chen, Cheng-Hung Chien, Ching-Chih Hu
Summary: Patients with non-alcoholic fatty liver disease (NAFLD) may have similar pathophysiologies to those with alcoholic liver disease. Certain genetic polymorphisms related to alcohol metabolism enzymes, such as ADH1B and ALDH2, may be associated with the pathophysiology of NAFLD. This study evaluated the association between ADH1B/ALDH2 gene polymorphisms and various metabolic factors, body fat composition, and liver steatosis/fibrosis status in NAFLD patients. The results showed that the mutant-type ADH1B/ALDH2 alleles were present in a high proportion of NAFLD patients, and these patients had higher levels of alanine aminotransferase (ALT) compared to those with the wild-type alleles. However, no significant associations were found between the gene polymorphisms and body mass index, serum metabolic factors, or liver steatosis/fibrosis.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Agriculture, Multidisciplinary
Jean-Philippe Kanter, Philipp Jakob Honold, David Luh, Sven Heiles, Bernhard Spengler, Marco Alexander Fraatz, Holger Zorn, Andreas Klaus Hammer
Summary: Odor-active fatty aldehydes are important compounds for the flavor and fragrance industry. These aldehydes, obtained from the biotransformation of margaroleic acid [17:1(9Z)], have unique odor profiles including citrus-like, soapy, herbaceous, and savory notes. By optimizing cultivation conditions of Mortierella hyalina, the production of the uncommon fatty acid 17:1(9Z) was significantly increased, and its lipid extract can be biotransformed into a complex aldehyde mixture with a high yield. The sensory evaluation of this aldehyde mixture revealed intense citrus-like, green, and soapy odor impressions.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Health Care Sciences & Services
Ren-Long Jan, Chung-Han Ho, Jhi-Joung Wang, Sung-Huei Tseng, Yuh-Shin Chang
Summary: This study found a strong association between Sjogren syndrome, post ocular surgery, systemic infection disease, systemic autoimmune disease, and scleritis.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Medicine, General & Internal
K. J. Srilakshmi, Muhammad Daniyal Waheed, Saima Batool, Shaniah S. Holder, Yadelys Rodriguez Reyes, Manisha Guntha
Summary: Sjogren-Larsson syndrome is a rare inherited disorder characterized by spastic diplegic paralysis, congenital ichthyotic hyperkeratosis, and mental retardation. It is caused by a deficiency or absence of microsomal fatty aldehyde dehydrogenase (FALDH), leading to the accumulation of fatty aldehydes and fatty alcohols, particularly in the skin. Educating patients about dry skin management and offering genetic counseling are essential for optimal care.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Yi-Cheng Chang, Hsiao-Lin Lee, Wenjin Yang, Meng-Lun Hsieh, Cai-Cin Liu, Tung-Yuan Lee, Jing-Yong Huang, Jiun-Yi Nong, Fu-An Li, Hsiao-Li Chuang, Zhi-Zhong Ding, Wei-Lun Su, Li-Yun Chueh, Yi-Ting Tsai, Che-Hong Chen, Daria Mochly-Rosen, Lee-Ming Chuang
Summary: Obesity and type 2 diabetes are global pandemics. Mutations in the ALDH2 gene result in reduced enzymatic activity, leading to metabolic disorders. Activating ALDH2 can improve diet-induced obesity, fatty liver, and glucose homeostasis.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Zili Zhai, Takeshi Yamauchi, Sarah Shangraw, Vincent Hou, Akiko Matsumoto, Mayumi Fujita
Summary: Acetaldehyde (AcAH), a carcinogenic byproduct of ethanol metabolism, has been linked to the development of malignancies in the upper gastrointestinal tract as well as cutaneous melanoma. This review examines the sources of ethanol and AcAH in the skin, their metabolic pathways, and the role of dysfunctional ethanol and AcAH metabolizing enzymes in melanoma development and progression. Data analysis also shows reduced activity of alcohol and AcAH metabolizing enzymes in melanoma tissues.
Article
Biochemistry & Molecular Biology
Zhiping Feng, Marisa E. Hom, Thomas E. Bearrood, Zachary C. Rosenthal, Daniel Fernandez, Alison E. Ondrus, Yuchao Gu, Aaron K. McCormick, Madeline G. Tomaske, Cody R. Marshall, Toni Kline, Che-Hong Chen, Daria Mochly-Rosen, Calvin J. Kuo, James K. Chen
Summary: Aldehyde dehydrogenases (ALDHs) are potential cancer drug targets, specifically certain isoforms essential for the survival of stem-like tumor cells. Selective inhibitors of ALDH1B1 have been identified, an enzyme essential for promoting colorectal and pancreatic cancer. Bicyclic imidazoliums and guanidines that target the ALDH1B1 active site have been described, with comparable molecular interactions and potencies. These inhibitors effectively suppress ALDH1B1 function in cells, with guanidines avoiding off-target mitochondrial toxicity observed with imidazoliums. A lead isoform-selective guanidinyl antagonist of ALDHs demonstrates proteome-wide target specificity and selectively hinders the growth of colon cancer spheroids and organoids. The ALDH1B1-dependent transcriptome, involving genes regulating mitochondrial metabolism and ribosomal function, has been elucidated through genetic and chemical perturbations. The importance of ALDH1B1 in colorectal cancer is supported, offering molecular probes for ALDH1B1 studies and potential leads for targeted therapies.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
In Jung Kim, Yannik Brack, Thomas Bayer, Uwe T. Bornscheuer
Summary: This study identified and characterized two novel alpha-DOX enzymes from cyanobacteria, showcasing their heme-dependent catalytic behavior towards medium carbon fatty acids. The findings not only contribute to the understanding of alpha-DOX molecular function, but also present potential industrial applications in fatty aldehyde biosynthesis.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Neil D. Butler, Shelby R. Anderson, Roman M. Dickey, Priyanka Nain, Aditya M. Kunjapur
Summary: Aldehydes are important chemical targets for flavors and fragrances industry and synthetic intermediates due to their ability to form C-C bonds. This study identifies and addresses unexpected oxidation of aromatic aldehydes, and demonstrates that it can be slowed down by inactivating certain aldehyde dehydrogenase genes in E. coli. The newly engineered E. coli ROAR strain shows reduced oxidation and improved product titers in biocatalysis reactions involving aldehydes.
METABOLIC ENGINEERING
(2023)
Article
Biology
Sien-Sing Yang, Yi-Hsun Chen, Jui-Ting Hu, Ching-Feng Chiu, Shao-Wen Hung, Yi-Chih Chang, Chien-Chao Chiu, Hsiao-Li Chuang
Summary: ALDH2, a critical enzyme in ethanol clearance, plays a key role in protecting the liver. The ALDH2*2 mutation decreases acetaldehyde scavenging capacity, leading to acetaldehyde accumulation. ALDH2 reportedly has protective properties on myocardial damage, stroke, and diabetic retina damage. This study highlights the role of ALDH2 in high-fat-diet-induced metabolic syndrome in mice, particularly in male mice where it exacerbates liver diseases.
Article
Immunology
Bettina Nothegger, Norbert Reider, Claudia E. Covaciu, Valentina Cova, Linda Ahammer, Reiner Eidelpes, Jana Unterhauser, Stefan Platzgummer, Elisabeth Raffeiner, Martin Tollinger, Thomas Letschka, Klaus Eisendle
Summary: Immunotherapy by daily apple consumption showed clinical efficacy in treating birch pollen allergy and pollen-related food allergies to apples. It increased patients' tolerance to apples, decreased skin reactivity to apples, and reduced oral allergy syndrome to other birch pollen-related foods.
IMMUNITY INFLAMMATION AND DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Sabrina Sailer, Stefan Coassin, Katharina Lackner, Caroline Fischer, Eileen McNeill, Gertraud Streiter, Christian Kremser, Manuel Maglione, Catherine M. Green, Daniela Moralli, Alexander R. Moschen, Markus A. Keller, Georg Golderer, Gabriele Werner-Felmayer, Irmgard Tegeder, Keith M. Channon, Benjamin Davies, Ernst R. Werner, Katrin Watschinger
Summary: A gene segment tandem duplication event occurred during homologous recombination in the Agmo gene of mice, which was not detected by routine PCR genotyping but could be resolved by qPCR, targeted locus amplification sequencing, and nanopore sequencing. Despite the duplication, the Agmo knockout mouse model lacks AGMO enzyme activity for studying its physiological role. Nanopore sequencing provides a cost-effective method for detecting underrated off-target effects in gene editing.
CELL AND BIOSCIENCE
(2021)
Article
Genetics & Heredity
Mohan Rajeshwari, Sellamuthu Karthi, Reetu Singh, Stephanie Efthymiou, Vykuntaraju K. Gowda, Perumal Varalakshmi, Varunvenkat M. Srinivasan, Henry Houlden, Markus A. Keller, William B. Rizzo, Balasubramaniem Ashokkumar
Summary: The study identified several novel mutations causing Sjogren-Larsson syndrome (SLS) and revealed the diverse clinical manifestations of this neuro-ichthyotic condition. Asymmetric distribution of nonclassical traits and a novel neurological phenotype were observed in the study. Genetic testing confirmed that the identified mutations may disrupt enzyme activity and lead to SLS.
Article
Endocrinology & Metabolism
Gregor Oemer, Jakob Koch, Yvonne Wohlfarter, Katharina Lackner, Rita E. M. Gebert, Stephan Geley, Johannes Zschocke, Markus A. Keller
Summary: Tafazzin deficiency in Barth syndrome leads to severe symptoms including cardiomyopathy, neutropenia, myopathy, and short stature, with significant changes in cardiolipin composition. The composition of cardiolipins strongly depends on the surrounding lipid environment, and variations in nutritional lipid pools can affect phospholipid profiles. Future research will focus on the metabolic implications of different lipid states and tafazzin function on cardiolipin and phospholipid homeostasis.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Lisa Bartenbach, Thomas Karall, Jakob Koch, Markus Andreas Keller, Herbert Oberacher, Sabine Scholl-Buergi, Daniela Karall, Gregor Oemer, Daniela Baumgartner, Katharina Meinel, Safwat Aly, Irena Odri-Komazec, Ralf Geiger, Miriam Michel
Summary: The study analyzed amino acid and lipid metabolic pathways in Marfan syndrome (MFS) patients and found significant differences in serum levels between patients and healthy controls, with some metabolites associated with cardiovascular risk and deterioration of myocardial function. The results showed that patients had a higher risk of cardiac diseases and exhibited alterations in amino acid and lipid metabolic pathways.
Editorial Material
Genetics & Heredity
Johannes Zschocke, Peter H. Byers, Andrew O. M. Wilkie
Summary: The concepts of dominance and recessiveness are crucial for understanding the relationship between genotype and phenotype in diploid organisms, even though they originated at a time when the basic molecular and cellular elements of inheritance were not yet identified.
NATURE REVIEWS GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Sebastian Fuehrer, Jana Unterhauser, Ricarda Zeindl, Reiner Eidelpes, Monica L. Fernandez-Quintero, Klaus R. Liedl, Martin Tollinger
Summary: PR-10 proteins are a major cause of food allergic reactions. This study analyzes the structural flexibility of thirteen PR-10 proteins from prevalent plant food sources and reveals that they have inherently flexible protein backbones in solution, with protein-specific extent of flexibility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Martina Witsch-Baumgartner, Gunda Schwaninger, Simon Schnaiter, Franziska Kollmann, Silja Burkhard, Rebekka Groebner, Beatrix Muehlegger, Esther Schamschula, Peter Kirchmeier, Johannes Zschocke
Summary: In this study, we examined the diagnostic value of genotyping arrays and found that they have high analytical sensitivity and specificity. We also identified ethical and legal concerns, as well as cost and time considerations. Overall, genotyping arrays have great potential in medical diagnostics.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Yvonne Wohlfarter, Reiner Eidelpes, Ryan D. Yu, Sabrina Sailer, Jakob Koch, Daniela Karall, Sabine Scholl-Buergi, Albert Amberger, Hauke S. Hillen, Johannes Zschocke, Markus A. Keller
Summary: Multifunctional protein HSD10 has been shown to be involved in disease pathomechanisms. Recent studies have suggested that HSD10 might have phospholipase C-like activity towards cardiolipins, but experimental results have shown no physiologically relevant role of HSD10 in cardiolipid metabolism.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Letter
Clinical Neurology
Fabian Leys, Sabine Eschlbock, Nicole Campese, Philipp Mahlknecht, Marina Peball, Georg Goebel, Victoria Sidoroff, Roberta Granata, Vincenzo Bonifati, Johannes Zschocke, Stefan Kiechl, Werner Poewe, Klaus Seppi, Gregor K. Wenning, Alessandra Fanciulli
MOVEMENT DISORDERS
(2022)
Article
Food Science & Technology
Linda Ahammer, Jana Unterhauser, Reiner Eidelpes, Christina Meisenbichler, Bettina Nothegger, Claudia E. Covaciu, Valentina Cova, Anna S. Kamenik, Klaus R. Liedl, Kathrin Breuker, Klaus Eisendle, Norbert Reider, Thomas Letschka, Martin Tollinger
Summary: The protein Mal d 1, responsible for most allergic reactions to apples in the northern hemisphere, can be chemically modified by ascorbic acid, which attenuates IgE binding in apple-allergic patients by partially masking an antibody binding site on the allergen.
Article
Multidisciplinary Sciences
Hyeong Jin Kim, Mazzen Black, Ross A. Edwards, Flora Peillard-Fiorente, Rashmi Panigrahi, David Klinger, Reiner Eidelpes, Ricarda Zeindl, Shiyun Peng, Jikun Su, Ayat R. Omar, Andrew M. MacMillan, Christoph Kreutz, Martin Tollinger, Xavier Charpentier, Laetitia Attaiech, J. N. Mark Glover
Summary: This study investigates the structural basis for RNA recognition by ProQ/FinO proteins and the importance of this recognition in repressing the uptake of environmental DNA in L. pneumophila. The authors also discover that other ProQ/FinO domains recognize transcriptional terminators with different specificities for the length of the 3' ssRNA tail.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Endocrinology & Metabolism
Shamima Rahman, Marc Patterson, Verena Peters, Eva Morava, Johannes Zschocke, Matthias Baumgartner
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Genetics & Heredity
Johannes Zschocke, Peter H. Byers, Andrew O. M. Wilkie
Summary: Understanding the consequences of genotype for phenotype is crucial in genetic diagnostics, but current measures of deleteriousness have limitations for predicting clinical outcomes. Knowing the reasons why some alleles are harmful in heterozygous state while others require biallelic pathogenic presence is important in dealing with rare genetic alterations identified by high throughput DNA sequencing. Knowledge of specific variant effects and allelic interactions is necessary for accurate diagnosis, treatment, and counseling of individuals with genetic disorders.
NATURE REVIEWS GENETICS
(2023)