Article
Biochemistry & Molecular Biology
Christian Fernandez, Andres Burgos, Diego Morales, Roberto Rosales-Rojas, Javiera Canelo, Ariela Vergara-Jaque, Gabriel Viliod Vieira, Rodrigo Alberto Alves da Silva, Katiuchia Uzzun Sales, Michael J. Conboy, Eun Ji Bae, Kang-Sik Park, Vicente A. Torres, Mauricio Garrido, Oscar Cerda, Irina M. Conboy, Monica Caceres
Summary: TMPRSS11a is an age-specific protein that plays a role in skin wound healing, with levels increasing with age. Overexpression of TMPRSS11a inhibits cell migration and spreading, leading to cellular senescence.
Article
Pathology
George Lambrinos, Vivian Cristofaro, Kristine Pelton, Alexander Bigger-Allen, Claire Doyle, Evalynn Vasquez, Diane R. Bielenberg, Maryrose P. Sullivan, Rosalyn M. Adam
Summary: Appropriate coordination of smooth muscle contraction and relaxation is crucial for normal colonic motility. This study discovered that neuropilin 2 (Nrp2) is highly expressed in colonic smooth muscle in mice and humans. Deletion of Nrp2 in smooth muscle resulted in increased contractility and enhanced colonic motility. These findings highlight the potential of Nrp2 as a novel target for conditions characterized by abnormal colonic motility.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Susana Lechuga, Alexander X. Cartagena-Rivera, Afshin Khan, Bert Crawford, Vani Narayanan, Daniel E. Conway, Jaakko Lehtimaki, Pekka Lappalainen, Florian Rieder, Michelle S. Longworth, Andrei I. Ivanov
Summary: The actomyosin cytoskeleton plays a crucial role in maintaining and remodeling epithelial barriers. UNC-45A, a cytoskeletal chaperone, is found to be important in the assembly of myosin structures and the protection of the intestinal epithelial barrier. Decreased expression of UNC-45A in patients with ulcerative colitis may contribute to barrier disruption and worsen the symptoms of the disease.
Article
Biochemistry & Molecular Biology
Haiqiong Liu, Huaqiang Mo, Chaobo Yang, Xiheng Mei, Xudong Song, Weizhe Lu, Hua Xiao, Jianyun Yan, Xianbao Wang, Jing Yan, Tao Luo, Yuhao Lin, Daojun Wen, Guiming Chen, Aihua Chen, Yuanna Ling
Summary: In this study, ATF3 was identified as a vital regulator of ferroptosis in myocardial ischemia/reperfusion (I/R) injury. The results showed that ATF3 inhibits cardiomyocyte ferroptotic death and this effect may be related to the regulation of FANCD2.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Multidisciplinary Sciences
Hong-bin Chen, Jorge Carlos Pineda Garcia, Shinako Arizono, Tomoki Takeda, Ren-shi Li, Yukiko Hattori, Hiroe Sano, Yuu Miyauchi, Yuko Hirota, Yoshitaka Tanaka, Yuji Ishii
Summary: The study found that DAPL1 expression in the testes is higher than in other tissues, and its loss leads to significantly elevated testosterone levels in mice. Experimental results indicate that DAPL1 regulates steroidogenesis in Leydig cells by affecting the transcription of critical proteins.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Angela Bononi, Qian Wang, Alicia A. Zolondick, Fang Bai, Mika Steele-Tanji, Joelle S. Suarez, Sandra Pastorino, Abigail Sipes, Valentina Signorato, Angelica Ferro, Flavia Novelli, Jin-Hee Kim, Michael Minaai, Yasutaka Takinishi, Laura Pellegrini, Andrea Napolitano, Ronghui Xu, Christine Farrar, Chandra Goparaju, Cristian Bassi, Massimo Negrini, Ian Pagano, Greg Sakamoto, Giovanni Gaudino, Harvey I. Pass, Jose N. Onuchic, Haining Yang, Michele Carbone
Summary: This study investigates the paradoxical finding that individuals with germline BAP1 mutations develop less aggressive mesotheliomas. The research shows that biallelic BAP1 mutations result in a reduction of HIF-1 alpha activity in mesothelioma cells and hypoxic tissues, leading to reduced aggressiveness and improved survival in these patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Jun-Ho Lee, So-Yeon Choi, Soo-Yeoun Park, Nam-Chul Jung, Kyung-Eun Noh, Ji-Hee Nam, Ji-Soo Oh, Hyun-Ji Choi, Ji-Su Jang, Ji-Young Yoo, Jie-Young Song, Han Geuk Seo, Dae-Seog Lim
Summary: The study investigated the biological effects of Enpp2 on dendritic cells (DCs) and found that Enpp2 is essential for the migration capacity of mature DCs (mDCs) to lymph nodes, enhancing our understanding of DC biology. Regulating Enpp2 may improve DC migration to lymph nodes, thereby enhancing the effectiveness of cancer vaccines based on DCs.
Article
Oncology
Anna Adamiok-Ostrowska, Malgorzata Grzanka, Barbara Czarnocka
Summary: This study found that AGRN is significantly increased in different subtypes of thyroid cancer and promotes tumorigenic phenotypes of cancer cells. AGRN expression is associated with immune infiltration in thyroid tumors. These findings suggest that AGRN may be a potential target for future cancer therapy.
Article
Dermatology
Shen Yan, Raphael Ripamonti, Hiroshi Kawabe, Maya Ben-Yehuda Greenwald, Sabine Werner
Summary: The ubiquitin ligase NEDD4-1 plays crucial roles in various aspects of skin function, including keratinocyte proliferation, differentiation, and wound repair. Lack of NEDD4-1 in keratinocytes leads to impaired migration and proliferation, resulting in delayed re-epithelialization of wounds. This study highlights the importance of NEDD4-1 in skin homeostasis and identifies its involvement in mitogenic and motogenic signaling pathways.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Immunology
Nicholas A. Schmitz, Ritesh P. Thakare, Chun-Shiang Chung, Chang-Min Lee, Jack A. Elias, Chun Geun Lee, Brian W. LeBlanc
Summary: The study found that Chit1 plays a counterproductive role in interfering with fungal clearance, with chitobiose potentially impairing neutrophil function and increasing the burden of Candida in the kidney.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Sundary Sormendi, Mathieu Deygas, Anupam Sinha, Mathilde Bernard, Anja Krueger, Ioannis Kourtzelis, Gregoire Le Lay, Pablo J. Saez, Michael Gerlach, Kristin Franke, Ana Meneses, Martin Kraeter, Alessandra Palladini, Jochen Guck, Uenal Coskun, Triantafyllos Chavakis, Pablo Vargas, Ben Wielockx
Summary: Activation of hypoxia-inducible factor 2 (HIF2 alpha) due to deficiency in HIF prolyl hydroxylase domain protein 2 (PHD2) enhances neutrophil migration through highly confined microenvironments, leading to massive tissue accumulation in models of acute local inflammation. RhoA, a cytoskeleton organizer, is identified as the central downstream factor mediating HIF2 alpha-dependent neutrophil motility. This novel PHD2-HIF2 alpha-RhoA axis is crucial in promoting neutrophil movement through highly confined tissue landscapes during the initial stages of inflammation.
Article
Cell Biology
Ji-Ung Jung, Anwesha B. Ghosh, Svetlana Earnest, Staci L. Deaton, Melanie H. Cobb
Summary: The protein kinase WNK1 is involved in maintaining cellular ion homeostasis and its accumulation can lead to familial hypertension. This study investigates the degradation pathways of WNK1 and identifies UBR5 as a regulator of WNK1 protein stability that leads to lysosomal degradation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jean-Philippe Leduc-Gaudet, Anais Franco-Romero, Marina Cefis, Alaa Moamer, Felipe E. Broering, Giulia Milan, Roberta Sartori, Tomer Jordi Chaffer, Maude Dulac, Vincent Marcangeli, Dominique Mayaki, Laurent Huck, Anwar Shams, Jose A. Morais, Elise Duchesne, Hanns Lochmuller, Marco Sandri, Sabah N. A. Hussain, Gilles Gouspillou
Summary: MYTHO (Macroautophagy and YouTH Optimizer) is a novel FoxO-dependent gene that plays a critical role in regulating muscle mass, function, and integrity. Up-regulation of MYTHO is observed in various mouse models of skeletal muscle atrophy. MYTHO overexpression triggers muscle atrophy, while MYTHO knockdown leads to an increase in muscle mass and sustained activation of the mTORC1 signaling pathway. MYTHO is a key regulator of muscle autophagy and integrity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Fengyan Meng, Yuping Wu, Yu Yu, Guixian Bu, Xiaogang Du, Qiuxia Liang, Xiaohan Cao, Anqi Huang, Xianyin Zeng, Linyan Huang, Fanli Kong, Yunkun Li, Xingfa Han
Summary: In this study, we cloned the full-length cDNA of SPX2 in chicken and found that it is widely expressed in various tissues, especially in the hypothalamus. It was upregulated in the hypothalamus after food deprivation and could suppress feeding behavior when peripheral injected. Mechanistically, cSPX2 acts as a satiety factor by upregulating CART and downregulating AGRP in the hypothalamus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Varsha D. Shiragannavar, Nirmala G. Sannappa Gowda, Divya P. Kumar, Faridoddin Mirshahi, Prasanna K. Santhekadur
Summary: Withaferin A exhibits anti-proliferative, anti-migratory, anti-invasive, and anti-anchorage-independent growth effects on HCC cells by activating LXR-α to inhibit NF-κB transcriptional activity. This suggests that Withaferin A may be a useful anticancer compound for the treatment of HCC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Sachin Kumar, Kalpana J. Nattamai, Aishlin Hassan, Amanda Amoah, Rebekah Karns, Cuiping Zhang, Ying Liang, Akiko Shimamura, M. Carolina Florian, Ute Bissels, Martha Luevano, Andreas Bosio, Stella M. Davies, Medhanie Mulaw, Hartmut Geiger, Kasiani C. Myers
Summary: The research discovered that SDS patients have lower Cdc42 activity in their HSCs, and the extent of HSC depletion is related to the level of apolarity in HSCs. Exogenously provided Wnt5a or GDF11 can restore polarity in SDS HSCs and increase the number of HSCs.
Letter
Allergy
Jaclyn W. McAlees, Theresa Baker, Lauren Houshel, Christopher McKnight, Andrew Lindsley, Richard T. Strait, Xue Zhang, Angela Cannata, Jocelyn M. Biagini, Melinda Butsch Kovacic, Ian P. Lewkowich
CLINICAL AND EXPERIMENTAL ALLERGY
(2022)
Review
Immunology
Apurwa Singhal, Sachin Kumar
Summary: Neutrophil-centered inflammation and flawed clearance processes can lead to various pathological conditions. Neutrophils exhibit high turnover rates in both steady-state and stress conditions. While they play a role in defending against pathogens, they can also trigger pro-inflammatory responses, and their death pathways can have different impacts on the body.
Article
Cell Biology
Apurwa Singhal, Shubhi Yadav, Tulika Chandra, Shrikant R. Mulay, Anil Nilkanth Gaikwad, Sachin Kumar
Summary: Neutrophil extracellular traps (NETs) are associated with various diseases and their identification and quantification methods have limitations. In this study, an imaging and computational algorithm using high content screening (HCS)-cellomics platform was developed for easy, rapid, and specific detection and analysis of NETs. The method utilized DNA dyes and automated algorithm-driven single-cell analysis to accurately detect NET-forming cells without user bias. Addition of Annexin V staining allowed differentiation between NETs, apoptosis, and necrosis. This high throughput imaging-based method provides a good platform for discovering inhibitors of NET formation and agents to modulate neutrophil death to enhance inflammation resolution.
Article
Hematology
Roberto Avellino, Roger Mulet-Lazaro, Marije Havermans, Remco Hoogenboezem, Leonie Smeenk, Nathan Salomonis, Rebekka K. Schneider, Elwin Rombouts, Eric Bindels, Lee Grimes, Ruud Delwel
Summary: The transcription factor C/EBPa plays a key role in initiating the gene expression program of neutrophils in the bone marrow. Knockouts of the Cebpa gene or its +37kb enhancer in mice result in decreased neutrophil count and reduced numbers of long-term hematopoietic stem cells (LT-HSCs). The reduction in LT-HSC numbers is proportional to the degree of neutropenia, suggesting an extrinsic effect. Transplantation experiments demonstrated that deletion of the +37kb enhancer leads to cell-autonomous neutropenia and disruption of HSC quiescence, impairing the hematopoietic process systemically.
Review
Allergy
Archana Shankar, Jaclyn W. McAlees, Ian P. Lewkowich
Summary: Abnormal activation of CD4 T(H)2 cells and excessive production of T(H)2 cytokines IL-4 and IL-13 are implicated in the development of allergic diseases. IL-4 and IL-13 utilize JAK/STAT signaling pathways for induction of inflammatory gene expression and disease pathology. However, there are alternative signaling cascades activated by IL-4 and IL-13, contributing to specific aspects of IL-4/IL-13-associated responses. A better understanding of these signaling pathways is important for designing targeted therapies for uncommon disease endotypes.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Imke Lingel, Adrienne N. Wilburn, Julie Hargis, Jaclyn W. McAlees, Yves Laumonnier, Claire A. Chougnet, Hitesh Deshmukh, Peter Koenig, Ian P. Lewkowich, Inken Schmudde
Summary: Changes in microbiome contribute to severity of allergic asthma. Prenatal antibiotic-induced dysbiosis leads to long-term immunological effects in offspring and increases asthma severity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Zaigham Abbas Rizvi, Prabhakar Babele, Srikanth Sadhu, Upasna Madan, Manas Ranjan Tripathy, Sandeep Goswami, Shailendra Mani, Sachin Kumar, Amit Awasthi, Madhu Dikshit
Summary: This study investigates the efficacy of Glycyrrhiza glabra (GG) extract as an immunomodulator against SARS-CoV-2 infection in hamsters. The results show that GG provides protection against weight loss and lung viral load decrease, along with reduced lung pathology in the hamster model. GG acts as an immunomodulator by reducing pro-inflammatory cytokine expression and regulating immune cell activity. This study provides evidence for the protective efficacy of GG against COVID-19 and its potential mechanisms through immunomodulation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Adrienne N. Wilburn, Jaclyn W. McAlees, David B. Haslam, Simon Graspeuntner, Inken Schmudde, Yves Laumonnier, Jan Rupp, Claire A. Chougnet, Hitesh Deshmukh, William J. Zacharias, Peter Konig, Ian P. Lewkowich
Summary: Delaying microbial maturation in neonates promotes the development of more severe asthma by increasing Th17 frequency, even if allergen exposure is initiated weeks after microbial diversity is normalized. In addition, IL-17A-aggravated asthma is associated with increased expression of IL-13-induced genes in mesenchymal, but not epithelial cells.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Deepika Awasthi, Sheela Nagarkoti, Samreen Sadaf, Hobby Aggarwal, Sonu Kumar Gupta, Tulika Chandra, Yashwant Kumar, Sachin Kumar, Madhu Dikshit
Summary: Neutrophil extracellular trap formation is a unique form of active cell death that plays a role in fighting pathogens and inflammation. This study used metabolomics to investigate the metabolic changes during PMA-induced NETosis in human neutrophils and found alterations in carbohydrate metabolism, redox-related metabolites, nucleic acid metabolism, and amino acid metabolism. The pentose phosphate pathway and glutathione metabolism were highlighted as important in PMA-induced NETosis. Analysis also identified glutathionylated proteins and activation of signaling proteins involved in metabolic regulation. Overall, a balance between reactive oxygen species and glutathione metabolism appears to regulate glycolytic enzyme activity during PMA-induced NETosis in a time-dependent manner.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Immunology
Chanchal Sur Chowdhury, Elizabeth Wareham, Juying Xu, Sachin Kumar, Matthew Kofron, Sribalaji Lakshmikanthan, Magdalena Chrzanowska, Marie-Dominique Filippi
Summary: This study discovers that neutrophil acidity plays a critical role in their function, and acidification leads to abnormal behavior, increased invasiveness, transcellular migration, and vascular leakage. Inhibiting acidity can selectively suppress the infiltration and inflammatory response of pathogenic neutrophils.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sachin Kumar, Jeffrey D. Vassallo, Kalpana J. Nattamai, Aishlin Hassan, Rebekah Karns, Angelika Vollmer, Karin Soller, Vadim Sakk, Mehmet Sacma, Travis Nemkov, Angelo D'Alessandro, Hartmut Geiger
Summary: It has been found that culturing hematopoietic stem cells (HSCs) at a pH of 6.9 for 2 days can maintain their potential, unlike cultivation at the commonly used pH of 7.4. These HSCs maintained at pH 6.9 exhibit smaller size, lower metabolic activity, weaker proliferation, and enhanced reconstitution ability upon transplantation compared to those cultivated at pH 7.4. This is due to the attenuation of the polyamine pathway in HSCs cultured at pH 6.9. Inhibiting the polyamine pathway in HSCs cultured at pH 7.4 with DFMO mimics the phenotypes and potential of HSCs cultured at pH 6.9. Exposing HSCs to a pH of 6.9 ex vivo positively regulates their function by reducing polyamines. These findings have the potential to improve short-term cultivation protocols for HSC transplantation and gene therapy interventions.
Article
Neurosciences
E. Allgire, R. A. Ahlbrand, N. Nawreen, A. Ajmani, C. Hoover, J. W. Mcalees, I. P. Lewkowich, R. Sah
Summary: There is a growing interest in studying the impact of chronic inflammation, especially lung inflammation, on the brain and behavior. This study investigated the effects of Th2-skewed airway inflammation on fear extinction in mice and found that it may promote fear extinction, highlighting beneficial interactions with fear regulatory circuits.
Editorial Material
Multidisciplinary Sciences
Xuan Zhang, H. Leighton Grimes
Summary: A novel strategy using multiplex single-cell genomic and immunophenotypic analysis is able to detect minimal residual disease (MRD) and differentiate leukemic and preleukemic subpopulations.
Article
Biochemical Research Methods
Kyle Ferchen, Nathan Salomonis, H. Leighton Grimes
Summary: Conventional flow cytometry is limited in its ability to detect markers, while new strategies like Infinity Flow can generate and impute hundreds of markers in millions of cells. This study introduces a Python workflow, pyInfinityFlow, for analyzing Infinity Flow data, allowing for the efficient analysis of millions of cells without down-sampling. The workflow accurately identifies both common and rare cell populations and can nominate novel markers for flow cytometry gating strategies.
