Article
Neurosciences
Pankaj Patyal, Daniel Fil, Hamdan Hamdan, Patricia A. Wight
Summary: By using transgenic animal models, researchers have gained insights into the mechanisms that control the developmental expression of the PLP1 gene. They analyzed the expression of transgenes containing PLP1 genomic DNA from humans or mice, and observed differences in their expression patterns. The findings suggest that the differences between human and mouse PLP1 sequences play a critical role in gene expression.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Seung Koo Lee, Zhenhua Shen, Myung Shin Han, Ching-Hsuan Tung
Summary: A methylene blue-based beta-galactosidase activatable molecule, Gal-MB, has been developed for senescence imaging and light-triggered senolysis. Gal-MB becomes fluorescent when in contact with LacZ beta-gal or senescence-associated beta-gal (SA-beta-gal). It also selectively induces phototoxicity in LacZ beta-gal expressing cells and drug-induced senescent cells, which express SA-beta-gal, after light illumination at 665 nm.
Article
Biochemistry & Molecular Biology
Lorenzo Badenetti, Rosa Manzoli, Michela Rubin, Giorgio Cozza, Enrico Moro
Summary: Among cytoprotective mechanisms, eukaryotic cells rely on the Nrf2 transcription factor to initiate a complex transcriptional program during biological stressors, including oxidative stress. Nrf2 has recently been found to play a crucial role in various research fields, such as cancer, inflammatory disorders, and age-related neurological diseases. In this study, a novel Nrf2/ARE pathway biosensor fish was generated and characterized, demonstrating spatiotemporal expression during early development. This transgenic fish shows responsiveness to Nrf2 pathway modulators and Edaravone, which has not been seen in any live transgenic fish models before. The activated reporter in this fish is also shown to be faithful during fin regeneration and slightly affected in a glucocerebrosidase morphant zebrafish model. Therefore, this innovative transgenic fish can serve as a valuable tool for studying zebrafish models of human diseases and primary high-throughput drug screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Hien Thi-Thu Ngo, Dinh-Huy Nguyen, Sung-Hwan You, Khuynh Van Nguyen, So-Young Kim, Yeongjin Hong, Jung-Joon Min
Summary: In this study, a doxycycline-inducible gene switch system was successfully developed in attenuated S. typhimurium, which triggered the expression of cargo genes in tumor tissues. The results demonstrated that bacteria carrying this gene switch system effectively suppressed tumor growth and prolonged survival in mice models, even after just one doxycycline induction.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Article
Biochemical Research Methods
David Romero-Suarez, Tune Wulff, Yixin Rong, Tadas Jakociunas, Satoshi Yuzawa, Jay D. Keasling, Michael K. Jensen
Summary: Protein misfolding and aggregation are associated with neurodegenerative diseases and suboptimal protein expression in biotechnology. A promoter-reporter system based on yeast response to misfolded protein was developed to monitor protein aggregates, showing a 12-fold output dynamic range and the ability to distinguish different protein states. Optimization of promoters and culture conditions improved the performance of the reporter system.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Plant Sciences
Ramona Persad-Russell, Mitra Mazarei, Tayler Marie Schimel, Lana Howe, Manuel J. Schmid, Tayebeh Kakeshpour, Caitlin N. Barnes, Holly Brabazon, Erin M. Seaberry, D. Nikki Reuter, Scott C. Lenaghan, C. Neal Stewart
Summary: The study demonstrated the amplification of plant sensor signals using a synthetic transcription factor gene to achieve rapid detection of pathogenic bacterial infection, leading to successful identification of specific pathogens within the plant family.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemical Research Methods
Manuela Sauter, Reinhard J. Sauter, Marcus Olbrich, Martin Thunemann, Susanne Feil, Robert Feil, Harald F. Langer
Summary: In this article, an in vivo approach to visualize CD11c+ cells in atherosclerosis is described. The authors use X-Gal staining to analyze plaque composition and cell-specific molecules as an alternative method. By breeding mice with LacZ knockin and CD11ccre recombinase onto an ApoE-/- background, the interested cell type in the plaques can be visualized by X-Gal staining. This approach allows for the examination of various immune cells in atherogenesis.
Article
Engineering, Chemical
Somphot Saoin, Chatikorn Boonkrai, Trairak Pisitkun, Chiraphat Kloypan, Sawitree Nangola
Summary: NGAL is considered a promising biomarker for early prediction of acute kidney injury. This study successfully expressed recombinant NGAL protein under a Tet-On inducible system, providing an efficient strategy for producing other recombinant proteins secreted from mammalian cells.
Article
Neurosciences
F. De Winter, I. Francos Quijorna, E. Burnside, B. Hobo, R. Eggers, S. A. Hoyng, H. P. Mulder, R. C. Hoeben, E. M. Muir, E. J. Bradbury, J. Verhaagen
Summary: This study developed a chimeric transactivator with an immune-advantage, which can promote spinal cord regeneration and show better expression and survival characteristics in vivo.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Biochemical Research Methods
Natascha Goedecke, Sabrina Herrmann, Viola Weichelt, Dagmar Wirth
Summary: Synthetic expression cassettes enable control of transgene expression in animal models, and their performance is influenced by chromosomal integration sites and epigenetic status. In this study, the effect of UCOE HNRPA2B1-CBX3 and its subfragments on doxycycline-controlled expression modules was investigated. Results showed that CBX3 facilitated expression and supported external control, suggesting a strategy for overcoming epigenetic constraints and enabling transgene expression in mice.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Keishi Ishida, Kanoko Tatsumi, Yoshiki Minamigawa, Kazuma Mori, Daisuke Matsumaru, Hisamitsu Nagase, Yasunari Kanda, Kazuhiro Takuma, Tsuyoshi Nakanishi
Summary: Current routine tests for chemical risk assessment lack a simple, quantitative, and objective method to detect the potential developmental neurotoxicity (DNT) of chemicals. In this study, transgenic mice expressing reporter genes were developed as a potential tool for streamlined detection of chemical-induced DNT in the developing mammalian brain.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Abu Zaffar Shibly, Abdullah Md. Sheikh, Makoto Michikawa, Shatera Tabassum, Abul Kalam Azad, Xiaojing Zhou, Yuchi Zhang, Shozo Yano, Atsushi Nagai
Summary: Amyloid beta (A beta) peptide is deposited in the brains of sporadic Alzheimer's disease (AD) due to impaired vessel-dependent clearance. Time-dependent cerebrovascular changes were found in AD model mice, with A beta appearing in vessels from 3 months and vessel density decreasing at 9 months in J20 mice. Decreased claudin-5 and increased VEGF expression were observed throughout the study.
Article
Biochemistry & Molecular Biology
Rajiv Kumar Sah, Noor Bahadar, Fatoumata Binta Bah, Salah Adlat, Zin Mar Oo, Luqing Zhang, Fawad Ali, M. S. Zobaer, Xuechao Feng, Yaowu Zheng
Summary: Dip2B, a member of the Dip2 superfamily, plays a crucial role in axonal outgrowth during embryogenesis and is highly expressed in various somatic tissues in adults. Its broad and intense expression patterns in neuronal, reproductive, and vascular tissues, as well as in organs such as the kidneys, heart, liver, and lungs, suggest its involvement in numerous physiological functions.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Myrian Thiago Pruschinski Fernandes, Jeniffer Farias dos Santos, Bruna Leticia Freitas, Gustavo Roncoli Reigado, Fernanda Antunes, Nayara Gusmao Tessarollo, Felipe Santiago Chambergo, Bryan Eric Strauss, Viviane Abreu Nunes
Summary: A reporter system was developed to assess the transdifferentiation of umbilical cord mesenchymal stem cells (MSCs) into keratinocytes. By monitoring specific markers and enzymatic activities, the transdifferentiation of MSCs was confirmed. This method opens up new possibilities for studying skin biology and regenerative medicine.
Article
Biotechnology & Applied Microbiology
Natalia Klimova, Siwei Chu, Bernard Turcotte
Summary: Researcher created a synthetic reporter gene derived from the Vibrio cholerae lacZ gene to study gene expression in the human fungal pathogen Candida albicans. The synthetic lacZ reporter showed high beta-galactosidase activity, making it a useful tool for analyzing promoter activity in C. albicans.
FEMS YEAST RESEARCH
(2021)
Article
Behavioral Sciences
Fabian Kreilaus, Magdalena Przybyla, Lars Ittner, Tim Karl
Summary: This study investigated the therapeutic effects of CBD on transgenic mice and found that CBD can improve behavioural deficits and cognitive impairments associated with FTD and AD.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Daryl Ariawan, Carol Au, Esmeralda Paric, Thomas Fath, Yazi D. Ke, Michael Kassiou, Janet van Eersel, Lars M. Ittner
Summary: The LIMK family, including LIMK1 and LIMK2, plays a key role in regulating actin cytoskeleton dynamics. By designing and synthesizing analogues with different stereochemistry, the study aimed to improve selectivity for different LIMK isoforms. Changes in stereochemistry were found to impact LIMK isoform selectivity, with docking studies predicting interactions with the target.
FRONTIERS IN CHEMISTRY
(2021)
Review
Clinical Neurology
Jared S. Katzeff, Fiona Bright, Katherine Phan, Jillian J. Kril, Lars M. Ittner, Michael Kassiou, John R. Hodges, Olivier Piguet, Matthew C. Kiernan, Glenda M. Halliday, Woojin Scott Kim
Summary: This study explores and evaluates potential biomarkers for distinguishing frontotemporal dementia and amyotrophic lateral sclerosis, aiming to improve diagnosis and treatment for patients. The two diseases share common genetic and molecular features, with a lack of sensitive and specific biomarkers for diagnostic and disease surveillance purposes.
Article
Multidisciplinary Sciences
Prita R. Asih, Anne Poljak, Michael Kassiou, Yazi D. Ke, Lars M. Ittner
Summary: The translocator protein (TSPO) plays a role in mitochondrial cholesterol transport, brain inflammation, and other mitochondrial functions. A common A147T polymorphism in TSPO reduces ligand binding and is associated with increased risk of neuropsychiatric disorders. This study found that the A147T polymorphism has fewer binding partners compared to the wild-type TSPO, suggesting a loss of function in mitochondrial protein networks.
Article
Clinical Neurology
Yuanyuan Deng, Mian Bi, Fabien Delerue, Shelley L. Forrest, Gabriella Chan, Julia van der Hoven, Annika van Hummel, Astrid F. Feiten, Seojin Lee, Ivan Martinez-Valbuena, Tim Karl, Gabor G. Kovacs, Grant Morahan, Yazi D. Ke, Lars M. Ittner
Summary: In Alzheimer's disease, hyperexcitation of neuronal networks is an underlying disease mechanism. The study identifies LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations.
ACTA NEUROPATHOLOGICA
(2022)
Article
Cell Biology
Ann-Na Cho, Fiona Bright, Nicolle Morey, Carol Au, Lars M. Ittner, Yazi D. Ke
Summary: Cortical organoids derived from human stem cells are three-dimensional structures capable of better simulating the human brain. Adeno-associated viruses (AAVs) have emerged as a vector of choice for gene therapy targeting the central nervous system. In this study, AAVs were compared to traditional methods for gene expression in cortical organoids, and it was demonstrated that AAVs can easily generate disease models through the expression of different variants of the central gene TDP-43, implicated in neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Hei W. A. Cheng, Timothy B. Callis, Andrew P. Montgomery, Jonathan J. Danon, William T. Jorgensen, Yazi D. Ke, Lars M. Ittner, Eryn L. Werry, Michael Kassiou
Summary: The use of cellular models in drug discovery for ALS and FTD is common, but there is currently no consensus on the most accurate model to replicate key pathological features. This study characterized two TDP-43 proteinopathy cellular models and found that different effects were observed when small molecule probes were exposed to these models. The study highlights the challenges of using cellular models in lead development and emphasizes the need for evaluations of novel therapeutics across various cell lines and aetiological models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Nicolle Morey, Magdalena Przybyla, Julia van der Hoven, Yazi D. Ke, Fabien Delerue, Janet van Eersel, Lars M. Ittner
Summary: Hyperphosphorylated tau protein is involved in various neurological disorders, while site-specific phosphorylation of tau at T205 by p38y kinase can protect against Alzheimer's disease. Delivery of p38y through gene transfer reduces seizure susceptibility, restores normal neuronal activity, improves behavioral deficits, and prevents epilepsy-induced deaths. Additionally, p38y-mediated phosphorylation of tau at T205 plays a crucial role in protecting against epilepsy.
Article
Clinical Neurology
Shelley L. Forrest, Seojin Lee, Nasna Nassir, Ivan Martinez-Valbuena, Valerie Sackmann, Jun Li, Awab Ahmed, Maria Carmela Tartaglia, Lars M. Ittner, Anthony E. Lang, Mohammed Uddin, Gabor G. Kovacs
Summary: MAPT protein aggregates in neurons, astrocytes and oligodendrocytes in neurodegenerative diseases, and this study found that cytopathology of tau does not compromise MAPT expression. The results suggest a dual approach to therapy by decreasing cellular MAPT expression and targeting removal of misfolded tau.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Annika van Hummel, Miheer Sabale, Magdalena Przybyla, Julia van der Hoven, Gabriella Chan, Astrid F. Feiten, Roger S. Chung, Lars M. Ittner, Yazi D. Ke
Summary: This study developed the first mouse models expressing wild-type and mutant human CCNF genes to replicate the key clinical and neuropathological features of ALS and FTD linked to CCNF disease variants. The results showed that these mice exhibited behavioral abnormalities similar to FTD patients, as well as memory deficits. Furthermore, the study found altered CCNF-mediated pathways and abnormal TDP-43 neuropathology, which are key hallmarks of FTD/ALS pathology.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Annika van Hummel, Goce Taleski, Jean-Marie Sontag, Astrid Feentje Feiten, Yazi D. Ke, Lars M. Ittner, Estelle Sontag
Summary: Experimental evidence shows that dietary supplementation with L-methylfolate, choline, and betaine can reduce phosphorylation of tau protein and alleviate associated behavioral and learning deficits. This change is associated with increased methylation of protein phosphatase 2A and decreased levels of Fyn, a tau tyrosine kinase. Enhancing one-carbon metabolism may be a potential treatment for tauopathies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Annika van Hummel, Goce Taleski, Jean-Marie Sontag, Astrid Feentje Feiten, Yazi D. Ke, Lars M. Ittner, Estelle Sontag
Summary: In this study, it was found that dietary supplementation with L-methylfolate, choline, and betaine can reduce phosphorylation of tau protein and associated behavioral phenotypes in the TAU58/2 mouse model. These findings provide experimental evidence that boosting one-carbon metabolism may be a potential therapeutic strategy for tauopathies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Review
Materials Science, Biomaterials
Daryl Ariawan, Janet van Eersel, Adam D. Martin, Yazi D. Ke, Lars M. Ittner
Summary: This paper summarizes different self-adjuvant structures, including self-assembly peptides, lipids, glycolipids, and polymers, which enhance the immune response to peptide or small molecule antigens.
BIOMATERIALS SCIENCE
(2022)
