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JOURNAL ARTICLE
Hisato Nagano, Naoaki Mizuno, Hideyuki Sato, Eiji Mizutani, Ayaka Yanagida, Mayuko Kano, Mariko Kasai, Hiromi Yamamoto, Motoo Watanabe, Fabian Suchy, Hideki Masaki, Hiromitsu Nakauchi
Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with pluripotent stem cell-derived epidermis with appendages on p63 knockout embryos' dermis...
April 29, 2024: Nature Communications
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JOURNAL ARTICLE
Roberta Filograna, Jule Gerlach, Hae-Na Choi, Giovanni Rigoni, Michela Barbaro, Mikael Oscarson, Seungmin Lee, Katarina Tiklova, Markus Ringnér, Camilla Koolmeister, Rolf Wibom, Sara Riggare, Inger Nennesmo, Thomas Perlmann, Anna Wredenberg, Anna Wedell, Elisa Motori, Per Svenningsson, Nils-Göran Larsson
Loss-of-function variants in the PRKN gene encoding the ubiquitin E3 ligase PARKIN cause autosomal recessive early-onset Parkinson's disease (PD). Extensive in vitro and in vivo studies have reported that PARKIN is involved in multiple pathways of mitochondrial quality control, including mitochondrial degradation and biogenesis. However, these findings are surrounded by substantial controversy due to conflicting experimental data. In addition, the existing PARKIN-deficient mouse models have failed to faithfully recapitulate PD phenotypes...
April 29, 2024: NPJ Parkinson's Disease
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JOURNAL ARTICLE
Saori Yoshimura, Ryuki Shimada, Koji Kikuchi, Soichiro Kawagoe, Hironori Abe, Sakie Iisaka, Sayoko Fujimura, Kei-Ichiro Yasunaga, Shingo Usuki, Naoki Tani, Takashi Ohba, Eiji Kondoh, Tomohide Saio, Kimi Araki, Kei-Ichiro Ishiguro
Meiotic prophase progression is differently regulated in males and females. In males, pachytene transition during meiotic prophase is accompanied by robust alteration in gene expression. However, how gene expression is regulated differently to ensure meiotic prophase completion in males remains elusive. Herein, we identify HSF5 as a male germ cell-specific heat shock transcription factor (HSF) for meiotic prophase progression. Genetic analyzes and single-cell RNA-sequencing demonstrate that HSF5 is essential for progression beyond the pachytene stage under non-stress conditions rather than heat stress...
April 29, 2024: Nature Communications
#24
JOURNAL ARTICLE
Haruko Miyazaki, Saki Nishioka, Tomoyuki Yamanaka, Manabu Abe, Yukio Imamura, Tomohiro Miyasaka, Nobuto Kakuda, Toshitaka Oohashi, Tomomi Shimogori, Kazuhiro Yamakawa, Masahito Ikawa, Nobuyuki Nukina
Golli-myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli-myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli-myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli-myelin basic protein knockout through the generation of conditional knockout mice (Golli-myelin basic proteinsfl/fl ; E3CreN), in which Golli-myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli-myelin basic proteins are expressed abundantly in wild-type mice...
April 29, 2024: Transgenic Research
#25
JOURNAL ARTICLE
Ruqaia Abbas, Oliver Hartmann, Dorin Theodora Asiss, Rabab Abbas, Julia Kagan, Hyoung-Tae Kim, Moshe Oren, Markus Diefenbacher, Amir Orian, Sarit Larisch
Mutations resulting in decreased activity of p53 tumor suppressor protein promote tumorigenesis. P53 protein levels are tightly regulated through the Ubiquitin Proteasome System (UPS). Several E3 ligases were shown to regulate p53 stability, including MDM2. Here we report that the ubiquitin E3 ligase XIAP (X-linked Inhibitors of Apoptosis) is a direct ligase for p53 and describe a novel approach for modulating the levels of p53 by targeting the XIAP pathway. Using in vivo (live-cell) and in vitro (cell-free reconstituted system) ubiquitylation assays, we show that the XIAP-antagonist ARTS regulates the levels of p53 by promoting the degradation of XIAP...
April 29, 2024: Apoptosis: An International Journal on Programmed Cell Death
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JOURNAL ARTICLE
Carolina Maschietto Pucinelli, Raquel Assed Bezerra da Silva, Paulo Nelson-Filho, Ricardo Barbosa Lima, Marília Pacífico Lucisano, Julie Teresa Marchesan, Léa Assed Bezerra da Silva
OBJECTIVE: To evaluate the effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis (AP) induced in mice. METHODS: The experimental AP was induced by pulpal exposure. To evaluate NLRP3-specific inhibitor medication (MCC950), WT mice received intraperitoneal injections, while the control received PBS (n = 10). In addition, to evaluate NLRP3 knockout, 35 wild-type (WT) and 35 NLRP3-/- mice were divided into a control group (without pulpal exposure, n = 5) and three experimental groups: after 2, 14 and 42 days after pulpal exposure (n = 10)...
April 30, 2024: Clinical Oral Investigations
#27
JOURNAL ARTICLE
Yuhei Nishimura
The primary cilium, an antenna-like structure of cell membrane, detects various signals and regulates cellular functions such as proliferation and differentiation. The impairment of primary cilium is associated with the etiologies of diseases including cancer, obesity, and congenital anomalies. In this review, novel functions of trichoplein, a suppressor of ciliogenesis, on the regulation of adipose progenitors and fibro-adipogenic progenitors are focused. Trichoplein-knockout mice show resistance to high-fat diet-induced obesity and accelerated regeneration after skeletal muscle injury...
April 26, 2024: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
#28
JOURNAL ARTICLE
Daniel Matúš, Jaybree M Lopez, Richard C Sando, Thomas C Südhof
Latrophilin-1 (Lphn1, a.k.a. CIRL1 and CL1; gene symbol Adgrl1 ) is an Adhesion GPCR that has been implicated in excitatory synaptic transmission as a candidate receptor for α-latrotoxin. Here we analyzed conditional knockin/knockout mice for Lphn1 that contain an extracellular myc-epitope tag. Mice of both sexes were used in all experiments. Surprisingly, we found that Lphn1 is localized in cultured neurons to synaptic nanoclusters that are present in both excitatory and inhibitory synapses. Conditional deletion of Lphn1 in cultured neurons failed to elicit a detectable impairment in excitatory synapses but produced a decrease in inhibitory synapse numbers and synaptic transmission that was most pronounced for synapses close to the neuronal soma...
April 29, 2024: Journal of Neuroscience
#29
JOURNAL ARTICLE
Philipp M Roessner, Isabelle Seufert, Vicente Chapaprieta, Ruparoshni Jayabalan, Hannah Briesch, Ramon Massoni-Badosa, Pavle Boskovic, Julian Beckendorff, Tobias Roider, Lavinia Arseni, Mariana Coelho, Supriya Chakraborty, Alicia Vaca, Mariela Sivina, Markus Muckenhuber, Sonia Rodriguez-Rodriguez, Alice Bonato, Sophie A Herbst, Marc Zapatka, Clare Sun, Helene Kretzmer, Thomas Naake, Peter-Martin Bruch, Felix Czernilofsky, Elisa Ten Hacken, Martin Schneider, Dominic Helm, Deyan Yordanov Yosifov, Joseph Kauer, Alexey V Danilov, Moritz Bewarder, Kristina Heyne, Christof Schneider, Stephan Stilgenbauer, Adrian Wiestner, Jan-Philipp Mallm, Jan A Burger, Dimitar G Efremov, Peter Lichter, Sascha Dietrich, José Ignacio Martín-Subero, Karsten Rippe, Martina Seiffert
The T-box transcription factor T-bet is known as a master regulator of T-cell response but its role in malignant B cells is not sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with genetic knockout of TBX21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate. NF-κB activity induced by inflammatory signals provided by the microenvironment, triggered T-bet expression which impacted on promoter proximal and distal chromatin co-accessibility and controlled a specific gene signature by mainly suppressing transcription...
April 29, 2024: Blood
#30
JOURNAL ARTICLE
Huidong Wang, Jing Song, Benjamin J Hunt, Kairan Zuo, Huiru Zhou, Angela Hayward, Bingbing Li, Yajuan Xiao, Xing Geng, Chris Bass, Shutang Zhou
Phytophagous insects have evolved sophisticated detoxification systems to overcome the antiherbivore chemical defenses produced by many plants. However, how these biotransformation systems differ in generalist and specialist insect species and their role in determining insect host plant range remains an open question. Here, we show that UDP-glucosyltransferases (UGTs) play a key role in determining the host range of insect species within the Spodoptera genus. Comparative genomic analyses of Spodoptera species that differ in host plant breadth identified a relatively conserved number of UGT genes in generalist species but high levels of UGT gene pseudogenization in the specialist Spodoptera picta ...
May 7, 2024: Proceedings of the National Academy of Sciences of the United States of America
#31
JOURNAL ARTICLE
Paramesha Bugga, Michael W Stoner, Janet R Manning, Bellina Mushala, Nisha Bhattarai, Maryam Sharifi-Sanjani, Bradley R Webster, Dharendra Thapa, Iain Scott
GCN5L1, also known as BLOC1S1 and BLOS1, is a small intracellular protein involved in a number of key biological processes. Over the last decade, GCN5L1 has been implicated in the regulation of protein lysine acetylation, energy metabolism, endo-lysosomal function, and cellular immune pathways. An increasing number of published papers have used commercially-available reagents to interrogate GCN5L1 function. However, in many cases these reagents have not been rigorously validated, leading to potentially misleading results...
April 29, 2024: Biochemical Journal
#32
JOURNAL ARTICLE
Anil Upreti, Thanh V Hoang, Minghua Li, Jared A Tangeman, David S Dierker, Brad D Wagner, Panagiotis A Tsonis, Chun Liang, Salil A Lachke, Michael L Robinson
PURPOSE: Despite strong evidence demonstrating that normal lens development requires regulation governed by microRNAs (miRNAs), the functional role of specific miRNAs in mammalian lens development remains largely unexplored. METHODS: A comprehensive analysis of miRNA transcripts in the newborn mouse lens, exploring both differential expression between lens epithelial cells and lens fiber cells and overall miRNA abundance, was conducted by miRNA sequencing. Mouse lenses lacking each of three abundantly expressed lens miRNAs (miR-184, miR-26, and miR-1) were analyzed to explore the role of these miRNAs in lens development...
April 1, 2024: Investigative Ophthalmology & Visual Science
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JOURNAL ARTICLE
Yaxin Ding, Wenjie Sun, Mingwei Han, Ziyu Liu, Huarui Kang, Xiaohan Ma, Jiayu Wang, Hongrui Mu, Yuxiao Huang, Shiyuan Hou, Danni Sun, Xing Shen, Xingan Wu, Rongrong Liu
Colorectal cancer (CRC) is a prevalent and aggressive malignancy with high mortality rates and significant risks to human well-being. Population-wide screening for tumor suppressor genes and oncogenes shows promise for reducing the incidence and fatality of CRC. Recent studies have suggested that NLRX1, an innate immunity suppressor, may play a role in regulating chronic inflammation and tumorigenesis. However, further investigation is needed to understand the specific role of NLRX1 in CRC. To evaluate the impact of NLRX1 on migration, invasion, and metastasis, two human colon cancer cell lines were studied in vitro...
April 29, 2024: Medical Oncology
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JOURNAL ARTICLE
Irene Bodega-Mayor, Pablo Delgado-Wicke, Alejandro Arrabal, Estíbaliz Alegría-Carrasco, Ana Nicolao-Gómez, Marta Jaén-Castaño, Cristina Espadas, Ana Dopazo, Enrique Martín-Gayo, María Luisa Gaspar, Belén de Andrés, Elena Fernández-Ruiz
Tyrosine kinase 2 (TYK2) is involved in type I interferon (IFN-I) signaling through IFN receptor 1 (IFNAR1). This signaling pathway is crucial in the early antiviral response and remains incompletely understood on B cells. Therefore, to understand the role of TYK2 in B cells, we studied these cells under homeostatic conditions and following in vitro activation using Tyk2-deficient (Tyk2-/- ) mice. Splenic B cell subpopulations were altered in Tyk2-/- compared to wild type (WT) mice. Marginal zone (MZ) cells were decreased and aged B cells (ABC) were increased, whereas follicular (FO) cells remained unchanged...
April 29, 2024: Cellular and Molecular Life Sciences: CMLS
#35
JOURNAL ARTICLE
Michael Kunzler, Rudolf O Schlechter, Lukas Schreiber, Mitja N P Remus-Emsermann
Here, we demonstrate the beneficial effect of surfactant-producing pseudomonads on Pantoea eucalypti 299R. We conducted a series of experiments in environments of increasing complexity. P. eucalypti 299R (Pe299R), and Pseudomonas sp. FF1 (Pff1) or Pe299R and surfactant-production deficient Pseudomonas sp. FF1::ΔviscB (Pff1ΔviscB) were co-inoculated in broth, on swarming agar plates, and on plants. In broth, there were no differences in the growth dynamics of Pe299R when growing in the presence of Pff1 or Pff1ΔviscB...
April 29, 2024: Microbial Ecology
#36
JOURNAL ARTICLE
Rui Min Liu, Shan Huang, Di Hu, Lingjuan Liu, Hui Chao Sun, Jie Tian, Bo Pan
In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co-factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS-eGFP-GST and NLS-mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5-decline-related impaired cardiac autophagy...
May 2024: Journal of Cellular and Molecular Medicine
#37
JOURNAL ARTICLE
Sarah Michaelis, Tong Chen, Camille Schmid, Hubert Hilbi
UNLABELLED: The causative agent of Legionnaires' disease, Legionella pneumophila , is an environmental bacterium, that replicates in macrophages, parasitizes amoeba, and forms biofilms. L. pneumophila employs the Legionella quorum sensing (Lqs) system and the transcription factor LvbR to control various bacterial traits, including virulence and biofilm architecture. LvbR negatively regulates the nitric oxide (NO) receptor Hnox1, linking quorum sensing to NO signaling. Here, we assessed the response of L...
April 29, 2024: MBio
#38
JOURNAL ARTICLE
Yan Chu Cheung, Xing Guo, Xuemei Yang, Ruohan Wei, Edward Waichi Chan, Xuechen Li, Sheng Chen
Pseudaminic acid (Pse) is found in the polysaccharide structures of the cell surface of various Gram-negative pathogenic bacteria including Acinetobacter baumannii and considered as an important component of cell surface glycans including oligosaccharides and glycoproteins. However, the glycosyltransferase that is responsible for the Pse glycosylation in A. baumannii remains unknown yet. In this study, through comparative genomics analysis of Pse-positive and negative A. baumannii clinical isolates, we identified a potential glycosyltransferase, KpsS1, located right downstream of the Pse biosynthesis genetic locus...
April 29, 2024: Chemistry: a European Journal
#39
JOURNAL ARTICLE
Michael R Odom, Francis M Hughes, NiQuava Pope, Huixia Jin, J Todd Purves
BACKGROUND: Diabetic bladder dysfunction (DBD) is driven in part by inflammation which dysregulates prostaglandin release in the bladder. Precise inflammatory mechanisms responsible for such dysregulation have been elusive. Since prostaglandins impact bladder contractility, elucidating these mechanisms may yield potential therapeutic targets for DBD. In female Type 1 diabetic Akita mice, inflammation mediated by the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome is responsible for DBD...
April 18, 2024: Frontiers in Bioscience (Landmark Edition)
#40
JOURNAL ARTICLE
Qiulei Liu, Peng Wang, Zhao Yang, Yue Dai, Sheng Wang
BACKGROUND: The endogenous metabolism of polyunsaturated fatty acids is regulated by the fatty acid desaturase (FADS) gene cluster and is strongly associated with diseases such as atherosclerosis, dyslipidemia, and type 2 diabetes. However, the association between FADS and atherosclerosis remains a subject of debate. METHODS: In this study, we specifically investigated the physiological role of Δ-5 fatty acid desaturase (FADS1) in aortic and peripheral vessel (namely, the femoral artery) atherosclerosis by targeting the selective knockdown of hepatic Fads1 in apolipoprotein E-null (ApoE-/-) mice with antisense oligonucleotides (ASOs)...
March 29, 2024: Frontiers in Bioscience (Landmark Edition)
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