Article
Neurosciences
George P. Cribaro, Elena Saavedra-Lopez, Leire Romarate, Izaskun Mitxitorena, Laura R. Diaz, Paola V. Casanova, Meritxell Roig-Martinez, Jose M. Gallego, Ana Perez-Valles, Carlos Barcia
Summary: This study provides an in-depth analysis of the cellular composition and microenvironment of human glioblastoma, revealing its structural and biological characteristics. The critical association between tumor cells and neo-vascular niche, as well as the relationship between T cell infiltration and tumor proliferation, were highlighted. The research also discovered distinct cell phenotypes in tumor nests and surrounding tissues.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Andrew F. Jarnuczak, Hanna Najgebauer, Mitra Barzine, Deepti J. Kundu, Fatemeh Ghavidel, Yasset Perez-Riverol, Irene Papatheodorou, Alvis Brazma, Juan Antonio Vizcaino
Summary: Utilizing 11 proteomics datasets from the PRIDE database, a reference expression map was constructed for 191 cancer cell lines and 246 clinical tumor samples, revealing unique peptides in tumor samples and highlighting the correlation between baseline expression in cell lines and tumors. Integration of proteomics and transcriptomics data showed a median correlation of 0.58 across cell lines, indicating that mRNA levels are often a poor predictor of changes in protein abundance. This study represents the first meta-analysis focusing on cancer-related public proteomics datasets, emphasizing the shortcomings and limitations of such studies.
Article
Multidisciplinary Sciences
Musalula Sinkala
Summary: This study analyzes the genomic sequences of 20,331 primary tumors, identifying driver mutations in 727 known cancer genes and revealing significant variations in mutation frequency and co-occurrence in different cancer types. The study also finds that patients with tumors displaying different combinations of gene mutation patterns have variable survival outcomes, providing new insights into the genetic landscape and mechanisms of cancer development.
SCIENTIFIC REPORTS
(2023)
Article
Plant Sciences
Jenny L. McCune, Christina J. Frendo, Mohammed Ramadan, Lyn K. Baldwin
Summary: This study examines the impact of landscape context on vascular plants and bryophytes in human-dominated landscapes. The results show that landscape context significantly affects the species richness and community composition of vascular plants, while bryophytes appear to be less sensitive overall. However, disturbance-intolerant perennial stayer bryophytes may decline in response to increased road density and loss of forest cover over the past four decades.
JOURNAL OF VEGETATION SCIENCE
(2021)
Article
Oncology
Yun Lu, Xiangyu Li, Kai Zhao, Peng Qiu, Zhengdong Deng, Wei Yao, Jianming Wang
Summary: This study provides the first comprehensive investigation of K-hib modification and identified a range of proteins and sites modified by K-hib. Bioinformatics analysis revealed that K-hib modified proteins are primarily located in the cytoplasm and are involved in multiple metabolic pathways. In addition, compared to succinylation and acetylation, lysine 2-hydroxyisobutyrylation is associated with a larger number of proteins and sites. Furthermore, a compound identified as a Tip60 inhibitor significantly reduced K-hib modification levels in pancreatic cancer and suppressed cancer proliferation and migration.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chong Chu, Eric W. Lin, Antuan Tran, Hu Jin, Natalie Ho, Alexander Veit, Isidro Cortes-Ciriano, Kathleen H. Burns, David T. Ting, Peter J. Park
Summary: This study identified polymorphic SVA insertions from more than 150 diverse populations by analyzing 3646 whole-genome sequencing samples, and constructed a reference catalog for these polymorphic SVA insertions. The study also characterized the structural features and activity differences of SVA sequences in different subfamilies and human populations, and developed a module for annotating SVA insertions.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Luke Funk, Kuan-Chung Su, Jimmy Ly, David Feldman, Avtar Singh, Brittania Moodie, Paul C. Blainey, Iain M. Cheeseman
Summary: Understanding the roles of essential genes in cellular processes is crucial for understanding cellular growth, proliferation, and function. This study used CRISPR-Cas9-based screening and microscopy imaging to identify the contributions of over 5,000 genes to cellular organization and morphology. Analysis of millions of cells revealed measurable phenotypes for over 90% of gene knockouts, providing insights into specific cellular processes. Clustering of phenotypic similarities further revealed co-functional genes and predicted gene functions and associations. The study also identified genes with functional contributions to chromosome segregation. This work provides a detailed resource exploring the consequences of disrupting core cellular processes.
Article
Biotechnology & Applied Microbiology
Maxime Tarabichi, Jonas Demeulemeester, Annelien Verfaillie, Adrienne M. Flanagan, Peter Van Loo, Tomasz Konopka
Summary: In this study, genomic variants in cancers from the PCAWG cohort were annotated with links to similar sites across the human genome. A machine learning model was trained to call somatic events in non-unique regions using signals from multiple genomic sites. This approach uncovered hidden mutations in coding sequences and regulatory elements, providing a systematic summary of mutation events in non-unique regions across various human cancers.
NATURE BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Wen Zhong, Swapnali Barde, Nicholas Mitsios, Csaba Adori, Per Oksvold, Kalle von Feilitzen, Liam O'Learyd, Laszlo Csiba, Tibor Hortobagyi, Peter Szocsics, Naguib Mechawar, Zsofia Magloczky, Eva Renner, Miklos Palkovits, Mathias Uhlen, Jan Mulder, Tomas Hokfelt
Summary: This study provides an overview of the distribution of peptidergic systems in the human prefrontal cortex (hPFC) and identifies unique peptide/transmitter-related profiles in different subregions of the hPFC. The results suggest the involvement of neuropeptide signaling in stabilizing circuit connectivity and modulating hPFC functions during health and disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Ming Zheng, Yi-Ming Li, Zhen-Yu Liu, Xin Zhang, Yinghui Zhou, Jian-Li Jiang, Ping Zhu, Xiang-Min Yang, Juan Tang, Zhi-Nan Chen
Summary: Immunotherapy targeting tumor-infiltrating lymphocytes has shown promising potential as a treatment for various cancers, but its efficacy varies across different cancer types and patients. The distribution of TIL-T and TIL-B cells and their interactions with the tumor microenvironment play a crucial role in determining the clinical outcomes. Understanding the prognostic significance of these factors can have important implications for cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Microbiology
Maxwell T. White, Cynthia L. Sears
Summary: This review discusses the significant role of the gut microbiota in the development of colorectal cancer (CRC) and the mechanisms by which specific microorganisms and complex microbial communities contribute to CRC pathogenesis. Despite advancements in understanding the microbiota-CRC relationship, there are substantial gaps in current research that need to be addressed.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Oncology
Viola Fanfani, Luca Citi, Adrian L. Harris, Francesco Pezzella, Giovanni Stracquadanio
Summary: This study developed a new statistical method, BAGHERA, to identify genes associated with cancer heritability, finding that SNPs and certain genes can explain a significant proportion of the heritable risk of cancer. The identified cancer heritability genes (CHGs) were involved in key processes and included tumor suppressors, providing insights for identifying high-risk subgroups and strategies for early detection and cancer surveillance using germline and somatic mutation information.
Article
Immunology
Erin F. McCaffrey, Michele Donato, Leeat Keren, Zhenghao Chen, Alea Delmastro, Megan B. Fitzpatrick, Sanjana Gupta, Noah F. Greenwald, Alex Baranski, William Graf, Rashmi Kumar, Marc Bosse, Christine Camacho Fullaway, Pratista K. Ramdial, Erna Forgo, Vladimir Jojic, David Van Valen, Smriti Mehra, Shabaana A. Khader, Sean C. Bendall, Matt van de Rijn, Daniel Kalman, Deepak Kaushal, Robert L. Hunter, Niaz Banaei, Adrie J. C. Steyn, Purvesh Khatri, Michael Angelo
Summary: This study used MIBI-TOF technology to map the immune responses within human tuberculosis granulomas, revealing the presence of local spatially coordinated immunoregulatory programs that may have implications for disease progression and treatment response.
Article
Biochemistry & Molecular Biology
Chen Lyu, Lili Wang, Birgit Stadlbauer, Alexander Buchner, Heike Pohla
Summary: Emerging evidence suggests that ABCG2, a protein involved in drug resistance, plays a significant role in the development of multidrug resistance in various types of cancers. This study aims to investigate the therapeutic potential of ABCG2 across 33 different tumors by analyzing multiple databases. The results show that ABCG2 expression is generally lower in cancer cells and acts as a protective factor. Distinct associations between ABCG2 expression and various factors related to the tumor microenvironment and genetic characteristics were observed. The study also highlights the impact of ABCG2 mutations on patient prognosis in particular cancer types. Furthermore, the functionality of ABCG2 and its related genes is found to be associated with transmembrane transport activity and hormone biosynthesis. Overall, this pan-cancer study provides a comprehensive understanding of ABCG2's multifunctionality and sheds light on its potential therapeutic role in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Zhongwei Xin, Mingjie Lin, Zhixing Hao, Di Chen, Yongyuan Chen, Xiaoke Chen, Xia Xu, Jinfan Li, Dang Wu, Ying Chai, Pin Wu
Summary: In this study, the developmental pattern of intra-tumoral T-cells in human thymic epithelial tumors (TET) was analyzed by single cell analysis. Three types of TETs were identified based on the characteristics of tumor cells and their effects on T-cell development. The molecular subtypes of TETs were found to determine their tumor immune microenvironment, and GNB3 and CHI3L1 might serve as predictors for the immunological behavior and prognosis of these tumors.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Bettina Kunze, Moritz Middelhoff, H. Carlo Maurer, Tatiana Agibalova, Akanksha Anand, Anne-Marie Buhrer, Hsin-Yu Fang, Theresa Baumeister, Katja Steiger, Julia Strangmann, Roland M. Schmid, Timothy C. Wang, Michael Quante
Summary: Activation of the Notch signaling pathway in Dclk1-positive tuft cells accelerates the development of BE, while genetic ablation of Notch receptor 2 in Dclk1-positive cells delays BE progression and leads to increased secretory cell differentiation. This suggests that Notch activation plays a role in BE development.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Katja Peschke, Hannah Jakubowsky, Arlett Schaefer, Carlo Maurer, Sebastian Lange, Felix Orben, Raquel Bernad, Felix N. Harder, Matthias Eiber, Rupert Oellinger, Katja Steiger, Melissa Schlitter, Wilko Weichert, Ulrich Mayr, Veit Phillip, Christoph Schlag, Roland M. Schmid, Rickmer F. Braren, Bo Kong, Ihsan Ekin Demir, Helmut Friess, Roland Rad, Dieter Saur, Gunter Schneider, Maximilian Reichert
Summary: This article introduces a longitudinal precision oncology platform based on functional model systems to identify chemotherapy-induced vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). It is found that treatment-induced tumor cell plasticity distinctly changes responsiveness to targeted therapies.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Yeqiao Zhou, Jelena Petrovic, Jingru Zhao, Wu Zhang, Ashkan Bigdeli, Zhen Zhang, Shelley L. Berger, Warren S. Pear, Robert B. Faryabi
Summary: This study systematically examined the chromatin structures in therapy-sensitive and therapy-resistant T-ALL using sequencing and imaging data. They found widespread alterations in successive layers of chromatin organization upon the emergence of therapy resistance, including spatial compartments, contact domain boundaries, and enhancer positioning. These changes in chromatin structures coincide with the reorganization of chromatin activity and redistribution of architectural proteins.
Article
Oncology
Yogev Sela, Jinyang Li, Shivahamy Maheswaran, Robert Norgard, Salina Yuan, Maimon Hubbi, Miriam Doepner, Jimmy P. Xu, Elaine S. Ho, Clementina Mesaros, Colin Sheehan, Grace Croley, Alexander Muir, Ian A. Blair, Ophir Shalem, Chi V. Dang, Ben Z. Stanger
Summary: Solid tumors have heterogeneous metabolic microenvironments, with some regions being rich in oxygen and nutrients, while others are scarce. Cancer cells in the arid regions exhibit a slow-cycling state and are resistant to chemotherapy. Bcl-xL plays a central role in the adaptation of cancer cells to nutrient and oxygen deprivation. Combining traditional cancer therapies that target rapidly cycling cells with those that target quiescent, chemoresistant cells associated with nutrient and oxygen deprivation could improve treatment efficacy and patient survival.
Article
Neurosciences
Alfredo Lucas, Ravi Prakash Reddy Nanga, Peter Hadar, Stephanie Chen, Adam Gibson, Kelly Oechsel, Mark A. Elliott, Joel M. Stein, Sandhitsu Das, Ravinder Reddy, John A. Detre, Kathryn A. Davis
Summary: Glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) can effectively differentiate sclerotic and non-sclerotic hippocampi in mesial temporal lobe epilepsy, even when traditional MRI assessments do not show evidence of sclerosis. This method is valuable in presurgical epilepsy evaluation.
HUMAN BRAIN MAPPING
(2023)
Article
Oncology
Hongru Zhang, Vivek S. Tomar, Jinyang Li, Raghavendra Basavaraja, Fangxue Yan, Jun Gui, Noreen McBrearty, Tara Lee Costich, Daniel P. Beiting, M. Andres Blanco, Jose R. Conejo-Garcia, Gurpanna Saggu, Allison Berger, Yulia Nefedova, Dmitry Gabrilovich, Serge Y. Fuchs
Summary: This study reveals a mechanism by which intratumoral regulatory T (Treg) cells retain their immunosuppressive activities by downregulating the IFNAR1 chain of the type I interferon (IFN1) receptor. The downregulation of IFNAR1 mediated by p38α kinase protects Treg cells from fragility and maintains NRP1 levels, which are crucial for immune suppression. Inhibition of p38α or stabilization of IFNAR1 induces fragility in Treg cells and inhibits their immune suppressive and protumorigenic functions. These findings provide insights into the mechanisms of immune regulation in the tumor microenvironment and suggest strategies for enhancing the efficacy of immunotherapies by inducing Treg cell fragility.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Medicine, Research & Experimental
Niklas Krebs, Lukas Klein, Florian Wegwitz, Elisa Espinet, Hans Carlo Maurer, Mengyu Tu, Frederike Penz, Stefan Kueffer, Xingbo Xu, Hanibal Bohnenberger, Silke Cameron, Marius Brunner, Albrecht Neesse, Uday Kishore, Elisabeth Hessmann, Andreas Trumpp, Philipp Stroebel, Rolf A. Brekken, Volker Ellenrieder, Shiv K. Singh
Summary: Metastatic pancreatic cancer has a poor clinical outcome, and recent research has identified two distinct subtypes, one with poor prognosis and therapy resistance. Through experiments and patient biopsies, we found that the axon guidance receptor ROBO3 promotes the metastatic program in one of the subtypes. Silencing ROBO3 can halt metastasis and enhance therapy sensitivity.
Article
Clinical Neurology
Eli J. J. Cornblath, Alfredo Lucas, Caren Armstrong, Adam S. S. Greenblatt, Joel M. M. Stein, Peter N. N. Hadar, Ramya Raghupathi, Eric Marsh, Brian Litt, Kathryn A. A. Davis, Erin C. C. Conrad
Summary: Variability in brain state and stimulation technique could impact the use of cortico-cortical evoked potentials (CCEPs) for epilepsy localization. CCEPs show systematic variability across trials and their amplitudes depend on the timing of stimulation relative to low-frequency oscillations.
Article
Microbiology
H. Carlo Maurer, David Schult, Plamena Koyumdzhieva, Sandra Reitmeier, Moritz Middelhoff, Sebastian Rasch, Markus List, Klaus-Peter Janssen, Katja Steiger, Ulrike Protzer, Roland M. Schmid, Klaus Neuhaus, Dirk Haller, Michael Quante, Tobias Lahmer
Summary: This study investigates the potential association between severe CAPA and alterations in the gut and bronchial microbial composition. The results suggest that COVID-19 patients with CAPA exhibit reduced gut microbial diversity and an increased abundance of Staphylococcus epidermidis in the gut, which may influence the host's immunological response. The analysis of bronchial samples did not yield significant results.
Article
Oncology
Emily K. W. Lo, Brian M. Mears, H. Carlo Maurer, Adrian Idrizi, Kasper D. Hansen, Elizabeth D. Thompson, Ralph H. Hruban, Kenneth P. Olive, Andrew P. Feinberg
Summary: Pancreatic ductal adenocarcinoma (PDAC) arises from the accumulation of somatic mutations and is frequently associated with pancreatic intraepithelial neoplasia (PanIN) lesions. The debate on whether PanINs and PDACs in humans originate from acinar or ductal cells still exists. DNA methylation changes during pancreatic neoplasia can provide insights into the cell type-of-origin of PanINs and PDACs.
Article
Clinical Neurology
Alfredo Lucas, Eli J. J. Cornblath, Nishant Sinha, Peter Hadar, Lorenzo Caciagli, Simon S. S. Keller, Leonardo Bonilha, Russell T. T. Shinohara, Joel M. M. Stein, Sandhitsu Das, Ezequiel Gleichgerrcht, Kathryn A. A. Davis
Summary: This study used network neuroscience to investigate the interictal whole-brain network of bilateral temporal lobe epilepsy (BiTLE). The study found that compared to unilateral temporal lobe epilepsy (UTLE), BiTLE patients had a higher level of network segregation, and these differences can assist in non-invasively identifying this patient population prior to invasive procedures.
Letter
Endocrinology & Metabolism
Abhijeet R. Patil, Jonathan Schug, Ali Naji, Klaus H. Kaestner, Robert B. Faryabi, Golnaz Vahedi
Article
Clinical Neurology
D. J. Doss, G. W. Johnson, S. Narasimhan, J. S. Shless, J. W. Jiang, H. F. J. Gonzaez, D. L. Paulo, A. Lucas, K. A. Davis, C. Chang, V. L. Morgan, C. Constantinidis, B. M. Dawant, D. J. Englot
Summary: This study developed a deep learning network for automatic and accurate patient-specific segmentation of the nucleus basalis of Meynert on 3T MR imaging. The model showed improved segmentation results compared to the standard probabilistic atlas and decreased centroid distance in patients.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Review
Oncology
Jingru Zhao, Robert B. Faryabi
Summary: This review discusses the structure and complexity of promoter-enhancer hubs in cancer, as well as the underlying mechanisms and functional role in disease pathogenesis. Understanding the role of promoter-enhancer hubs in transcriptional dysregulation is crucial for developing new therapeutic approaches.
Article
Oncology
Fangxue Yan, Jinyang Li, Jelena Milosevic, Ricardo Petroni, Suying Liu, Zhennan Shi, Salina Yuan, Janice M. Reynaga, Yuwei Qi, Joshua Rico, Sixiang Yu, Yiman Liu, Susumu Rokudai, Neil Palmisiano, Sara E. Meyer, Pamela J. Sung, Liling Wan, Fei Lan, Benjamin A. Garcia, Ben Z. Stanger, David B. Sykes, M. Andres Blanco
Summary: The study identified histone acetyltransferase KAT6A as a key epigenetic regulator of AML cell differentiation. Mechanistically, KAT6A cooperates with ENL in an epigenetic transcriptional control module, revealing a new epigenetic dependency and therapeutic opportunity in AML.