Article
Clinical Neurology
Leon A. Steiner, Andrea A. Kuhn, Jorg R. P. Geiger, Henrik Alle, Milos R. Popovic, Suneil K. Kalia, Mojgan Hodaie, Andres M. Lozano, William D. Hutchison, Luka Milosevic
Summary: This study aims to explore the local synaptic dynamics in the subthalamic nucleus (STN) and the neighboring substantia nigra pars reticulata (SNr) during external stimulation. The results show that inhibitory input in the STN persists during high frequency stimulation, while it does not occur in the SNr. This indicates a local synaptic mechanism in the STN during high frequency stimulation, which is associated with the regulation of neuronal firing.
Article
Biochemistry & Molecular Biology
Zeshuai Wang, Zhisheng Wu, Hao Wang, Ruoqing Feng, Guanlin Wang, Muxi Li, Shuang-Yin Wang, Xiaoyan Chen, Yiyi Su, Jun Wang, Weiwen Zhang, Yuzhou Bao, Zhenwei Lan, Zhuo Song, Yiheng Wang, Xianyang Luo, Lingyu Zhao, Anli Hou, Shuye Tian, Hongliang Gao, Wenbin Miao, Yingyu Liu, Huilin Wang, Cui Yin, Zhi-Liang Ji, Mingqian Feng, Hongkun Liu, Lianghui Diao, Ido Amit, Yun Chen, Yong Zeng, Florent Ginhoux, Xueqing Wu, Yuanfang Zhu, Hanjie Li
Summary: Macrophages in human development exhibit diversity and developmental dynamics. The study identifies the presence of microglia-like cells in the fetal epidermis and proangiogenic macrophages around fetal organs.
Review
Urology & Nephrology
Dries Deleersnijder, Jasper Callemeyn, Ingrid Arijs, Maarten Naesens, Amaryllis H. Van Craenenbroeck, Diether Lambrechts, Ben Sprangers
Summary: Single-cell RNA sequencing and single-nucleus RNA sequencing are promising tools for understanding the pathophysiology of glomerular diseases, but face technical challenges in isolation and enrichment of glomerular cells from renal biopsy specimens.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Pharmacology & Pharmacy
Zhiwei Xue, Lei Ye, Jianwei Ge, Zhen Lan, Xinxin Zou, Chenglu Mao, Xinyu Bao, Linjie Yu, Yun Xu, Xiaolei Zhu
Summary: In this study, the researchers found that the inhibition of ABHD6 could improve synaptic function and memory impairment in APP/PS1 mice with Alzheimer's disease, without affecting the levels of amyloid-beta and neuroinflammation in the brain. Injection of the ABHD6-specific inhibitor wwl70 enhanced synaptic plasticity and memory function, lowered amyloid-beta levels and neuroinflammation, and promoted the phagocytosis of amyloid-beta by microglia.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Microbiology
Tridib Mahata, Shahar Molshanski-Mor, Moran G. Goren, Miriam Kohen-Manor, Ido Yosef, Oren Avram, Dor Salomon, Udi Qimron
Summary: We have identified a novel phage-encoded inhibitor of the major cytoskeletal protein in bacterial division, FtsZ. The inhibition is shown to confer T5 bacteriophage with a growth advantage in dividing hosts. Our studies demonstrate a strategy in bacteriophages to maximize their progeny number by inhibiting escape of one of the daughter cells of an infected bacterium. They further emphasize that FtsZ is a natural target for bacterial growth inhibition.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Shalva Gurgenidze, Peter Baeuerle, Dietmar Schmitz, Imre Vida, Tengis Gloveli, Tamar Dugladze
Summary: A subset of parvalbumin-positive (PV+) interneurons (INs)-stuttering cells (STUT) with distinct morphological, electrophysiological, and synaptic properties in the medial entorhinal cortex (mEC) are described for the first time. These STUT cells have the ability to modulate gamma activity in the pyramidal cell population of the mEC. Activation of the mu-opioid receptors decreases the GABA release from the PV+ INs onto the STUT, resulting in an increase in network gamma power.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Maria Vazquez Pavon, Sheeja Navakkode, Lik-Wei Wong, Sreedharan Sajikumar
Summary: Alzheimer's disease is a progressive neurodegenerative disease characterized by memory loss and cognitive decline. Synaptic impairment is one of the first events to occur in the progression of this disease. This research demonstrates that Nogo-A acts as a plasticity suppressor in Alzheimer's disease models, and targeting Nogo-A could be a promising strategy to understand and potentially treat the pathology of Alzheimer's disease.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Fengying Wu, Jue Fan, Yayi He, Anwen Xiong, Jia Yu, Yixin Li, Yan Zhang, Wencheng Zhao, Fei Zhou, Wei Li, Jie Zhang, Xiaosheng Zhang, Meng Qiao, Guanghui Gao, Shanhao Chen, Xiaoxia Chen, Xuefei Li, Likun Hou, Chunyan Wu, Chunxia Su, Shengxiang Ren, Margarete Odenthal, Reinhard Buettner, Nan Fang, Caicun Zhou
Summary: This study utilized single-cell RNA sequencing to analyze 42 late-stage NSCLC patients, revealing significant heterogeneity in tumors in terms of cellular composition, chromosomal structure, developmental trajectory, and the identification of rare cell types. The research also highlighted the correlation between tumor heterogeneity and tumor-associated neutrophils.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Song Chen, Caroline Chandra Tjin, Xiang Gao, Yi Xue, Haoyan Jiao, Ruilin Zhang, Mengnan Wu, Zunyu He, Jonathan Ellman, Ya Ha
Summary: Most human cancer cells have mutations in the p53 tumor suppressor gene. Inhibition of PI5P4K alpha and beta disrupts cell energy balance and is selectively toxic towards p53-null tumor cells, indicating the potential for development of novel diabetes and cancer drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Arindam Mondal, Rachel NeMoyer, Mehul Vora, Logan Napoli, Zoya Syed, Elaine Langenfeld, Dongxuan Jia, Youyi Peng, John Gilleran, Jacques Roberge, Christopher Rongo, Salma K. Jabbour, John Langenfeld
Summary: Recent studies have shown that inhibition of BMPR2 destabilizes microtubules, leading to lysosome activation and decreased BMPR2 signaling, ultimately promoting cancer cell death.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Multidisciplinary Sciences
Neeraj Singh, Brati Das, John Zhou, Xiangyou Hu, Riqiang Yan
Summary: This study demonstrates that targeted inhibition of BACE-1 in microglia has unique advantages in the treatment of Alzheimer's disease, including reducing amyloid plaque formation, enhancing Aβ clearance, and promoting the functions of autophagolysosomes and Aβ-induced metabolic reprogramming.
Article
Multidisciplinary Sciences
Nan Xiang, Hao Xu, Zhou Zhou, Junyu Wang, Pengfei Cai, Li Wang, Zhen Tan, Yingbo Zhou, Tianping Zhang, Jiayuan Zhou, Ke Liu, Songwen Luo, Minghao Fang, Guosheng Wang, Zhuo Chen, Chuang Guo, Xiaomei Li
Summary: This study used single-cell RNA sequencing to investigate cellular heterogeneity in patients with primary Sjogren's syndrome (pSS). The findings suggest that downregulated SOX9 in myoepithelial cells might be associated with impaired epithelial regeneration in pSS. Additionally, an expanded ACKR1(+) endothelial population in pSS patients may play a role in lymphocyte migration. The study also identified expanded IGHD(+) naive B cells in the peripheral blood of pSS patients.
Editorial Material
Multidisciplinary Sciences
Jeffrey A. Farrell
Summary: CellOracle, a computational tool, can predict the interaction of gene networks in programming cell identity during embryonic development. This tool will contribute to a better understanding of the regulation of development.
Article
Multidisciplinary Sciences
Kosuke Fukui, Kazushi Arai, Yuka Tanaka, Yuki Aoi, Vandna Kukshal, Joseph M. Jez, Martin F. Kubes, Richard Napier, Yunde Zhao, Hiroyuki Kasahara, Ken-ichiro Hayashi
Summary: The phytohormone auxin, indole-3-acetic acid (IAA), plays a significant role in plant development. The research characterizes a potent GH3 inhibitor called kakeimide that selectively targets IAA-conjugating GH3 proteins. Chemical knockdown experiments demonstrate that auxin turnover is rapid, suggesting that both auxin biosynthesis and inactivation dynamically regulate auxin homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Ilana B. B. Kotliar
Summary: Proteomics, which is the study of proteomes on a large scale, has seen significant advancements in the fields of chemical biology, mass spectrometry, and machine learning. The Proteomics in Cell Biology and Disease Mechanisms conference highlighted the synergy between these advancements and the wide range of biological questions that can now be addressed with proteomics.
Article
Cell Biology
Davor Ivankovic, James Drew, Flavie Lesept, Ian J. White, Guillermo Lopez Domenech, Sharon A. Tooze, Josef T. Kittler
Article
Biochemistry & Molecular Biology
Christian Covill-Cooke, Viktoriya S. Toncheva, James Drew, Nicol Birsa, Guillermo Lopez-Domenech, Josef T. Kittler
Article
Cell Biology
Rosalind Norkett, Flavie Lesept, Josef T. Kittler
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Antonio P. A. Ferreira, Alessandra Casamento, Sara Carrillo Roas, Els F. Halff, James Panambalana, Shaan Subramaniam, Kira Schutzenhofer, Laura Chan Wah Hak, Kieran McGourty, Konstantinos Thalassinos, Josef T. Kittler, Denis Martinvalet, Emmanuel Boucrot
Summary: The authors demonstrate that Cdk5 and GSK3 beta act as negative regulators of fast Endophilin-mediated endocytosis (FEME), playing critical roles in axon elongation, branching, and growth cone formation in hippocampal neurons.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Guillermo Lopez-Domenech, Jack H. Howden, Christian Covill-Cooke, Corinne Morfill, Jigna Patel, Roland Burli, Damian Crowther, Nicol Birsa, Nicholas J. Brandon, Josef T. Kittler
Summary: Research has shown that Miro proteins play a crucial role in mitochondrial turnover and dysfunction may contribute to neurodegenerative diseases. Genetic deletion or inhibition of Miro1 ubiquitination delays Parkin translocation to damaged mitochondria, leading to reduced mitochondrial clearance. Knockout of Miro1 in hippocampus and cortex results in disrupted mitophagy, enlarged mitochondria, and hyperactivation of the integrated stress response, potentially indicating a role in human neurodegenerative disease pathogenesis.
Article
Biology
Georgina Kontou, Pantelis Antonoudiou, Marina Podpolny, Blanka R. Szulc, I. Lorena Arancibia-Carcamo, Nathalie F. Higgs, Guillermo Lopez-Domenech, Patricia C. Salinas, Edward O. Mann, Josef T. Kittler
Summary: The study explores the role of Miro1 in PV+ interneurons and how changes in mitochondrial trafficking could alter network activity in the mouse brain. Impairments in Miro1-directed trafficking in PV+ interneurons altered their mitochondrial distribution and axonal arborization, while PV+ interneuron-mediated inhibition remained intact. These changes were accompanied by an increase in hippocampal gamma-oscillation frequency and promoted anxiolysis. Our findings show that precise regulation of mitochondrial dynamics in PV+ interneurons is crucial for proper neuronal signaling and network synchronization.
Article
Multidisciplinary Sciences
Swati Gupta, Narges Bazargani, James Drew, Jack H. Howden, Souvik Modi, Sana Al Awabdh, Helene Marie, David Attwell, Josef T. Kittler
Summary: This study shows that the surface expression and function of astrocytic GLT-1 can be rapidly modulated through its interaction with Nischarin protein. Nischarin knockout in astrocytes is neuroprotective against glutamate excitotoxicity, suggesting new drug targets for the treatment of neurological disorders.
Article
Clinical Neurology
Chanawee Hirunpattarasilp, Greg James, Jaturon Kwanthongdee, Felipe Freitas, Jiandong Huo, Huma Sethi, Josef T. Kittler, Raymond J. Owens, Laura E. McCoy, David Attwell
Summary: The binding of SARS-CoV-2 to ACE2 on capillary pericytes causes pericyte contraction and capillary constriction, leading to reduced blood flow in the brain, heart, and kidney. The drug losartan can prevent these effects.
Article
Biochemistry & Molecular Biology
Els F. Halff, Saad Hannan, Jaturon Kwanthongdee, Flavie Lesept, Trevor G. Smart, Josef T. Kittler
Summary: A study has found that cAMP-dependent protein kinase (PKA) plays a key role in the synaptic stabilization of neuroligin-2 (NL2). PKA-mediated phosphorylation of NL2 causes its dispersal from the synapse and reduces the amount of synaptic GABA(A)Rs. Enhancing the stability of NL2 at synapses by inhibiting PKA-mediated phosphorylation leads to increased inhibitory signaling.
Article
Cell Biology
Michael J. Devine, Blanka R. Szulc, Jack H. Howden, Guillermo Lopez-Domenech, Arnaud Ruiz, Josef T. Kittler
Summary: This study investigates the role of mitochondria in regulating synaptic transmission and plasticity. The results show that reducing mitochondrial Ca2+ uptake alters synaptic vesicle fusion and enhances long-term potentiation at specific synapses.
JOURNAL OF CELL SCIENCE
(2022)
Review
Neurosciences
Guillermo Lopez-Domenech, Josef T. Kittler
Summary: Brain computation is energetically costly and relies on mitochondria to generate cellular energy. Neurons have specialized mechanisms to regulate mitochondrial function locally, such as controlling mitochondrial transport and dynamics, as well as removing inefficient mitochondria through mitophagy. Signaling pathways coordinate these processes to couple energy expenditure with availability. Failure in these mechanisms can lead to neuropathological conditions like metabolic syndromes or neurodegeneration.
CURRENT OPINION IN NEUROBIOLOGY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Josef Kittler
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Georgina Kontou, Shu Fun Josephine Ng, Ross A. Cardarelli, Jack H. Howden, Catherine Choi, Qiu Ren, Miguel A. Rodriguez Santos, Christopher E. Bope, Jake S. Dengler, Matt R. Kelley, Paul A. Davies, Josef T. Kittler, Nicholas J. Brandon, Stephen J. Moss, Joshua L. Smalley
Summary: KCC2 plays a critical role in maintaining neuronal survival in mature neurons, while having minimal impact on neuronal development and structure. The loss of KCC2 function in mature neurons can rapidly activate the apoptotic pathway. In contrast, ablating KCC2 expression in immature neurons does not significantly affect their subsequent development.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Christian Covill-Cooke, Viktoriya S. Toncheva, Josef T. Kittler
Summary: Peroxisomes are essential organelles involved in metabolic processes, requiring both long- and short-range trafficking for optimal positioning in cells. This review examines the mechanisms of peroxisomal distribution, with a focus on regulatory overlaps between mitochondrial and peroxisomal trafficking, as well as the role of mitochondrial Rho-GTPase Miro in peroxisomal dynamics. Additionally, it discusses pathological and pharmacological conditions affecting peroxisomal positioning, along with highlighting gaps in current knowledge and suggesting future research directions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
J. Kittler
JOURNAL OF NEUROCHEMISTRY
(2019)
