tbuckley/cabot-search huggingface dataset:
Molecular and functional convergences associated with complex multicellularity in Eukarya
Authors: Francisco Pereira Lobo, Dalbert Benjamim da Costa, Thieres Tayroni Martins da Silva, Maycon Douglas de Oliveira
Journal: Molecular Biology and Evolution (2025)

Abstract A key trait of Eukarya is the independent evolution of complex multicellular (CM) in animals, plants, fungi, brown algae and red algae. This phenotype is characterized by the initial exaptation of cell-cell adhesion genes followed by the emergence of mechanisms for cell-cell communication, together with the expansion of transcription factor gene families responsible for cell and tissue identity. The number of cell types (NCT) is commonly used as a quantitative proxy for biological complexity in comparative genomics studies. While expansions of individual gene families have been associated with NCT variation within individual CM lineages, the molecular and functional roles responsible for the independent evolution of CM across Eukarya remain poorly understood. We employed a phylogeny-aware strategy to conduct a genomic-scale search for associations between NCT and the abundance of genomic components across a phylogenetically diverse set of 81 eukaryotic species, including species from all CM lineages. Our annotation schemas represent two complimentary aspects of genomic information: homology – represented by conserved sequences – and function – represented by Gene Ontology (GO) terms. We found many gene families sharing common biological themes that define CM to be independently expanded in two or more CM lineages, such as components of the extracellular matrix, cell-cell communication mechanisms, and developmental pathways. Additionally, we describe many previously unknown associations of biological themes and biological complexity, such as mechanisms for wound response, immunity, cell migration, regulatory processes, and response to natural rhythms. Together, our findings unveil a set of functional and molecular convergences independently expanded in CM lineages likely due to the common selective pressures in their lifestyles.
Microneedle Array‐Based Dermal Interstitial Fluid Biopsy for Cancer Diagnosis: Advances and Challenges
Authors: Chaima Merzougui, Xi Yang, Dianhuai Meng, Yan Huang, Xiangwei Zhao
Journal: Advanced Healthcare Materials (2025)

Abstract Current early cancer diagnostic technologies, such as imaging, molecular tests, endoscopic techniques, and biopsies, face considerable challenges in low‐and middle‐income countries (LMICs) due to high costs, procedural complexity, and limited resource access. Microneedle‐based liquid biopsy for skin interstitial fluid (ISF) offers a practical and minimally invasive alternative for cancer diagnosis in these settings. This review systematically examines ISF liquid biopsy methods for their effectiveness in capturing cancer biomarkers directly from the skin and assesses their potential to address diagnostic needs in low‐resource environments. Recent innovations in microneedle design and ISF underscore their potential in enabling early, accessible cancer detection tailored to LMICs' needs. Additionally, integrating artificial intelligence (AI) for data interpretation is proposed as a way to enhance diagnostic accuracy and enable real‐time point‐of‐care (POC) applications. Collectively, these advances illustrate a flexible, scalable model for accessible cancer diagnostics, with significant implications for improving early detection and healthcare quality in resource‐limited environments.
Receptor-ligand interactions for optimized endocytosis in targeted therapies
Authors: Yejin Sung, Youngjin Choi, Eun Sun Kim, Ju Hee Ryu, Ick Chan Kwon
Journal: Journal of Controlled Release (2025)

Receptor-mediated endocytosis plays a crucial role in the success of numerous therapies and remains central to advancing drug development. This process begins with ligand binding to specific receptors, triggering the internalization and intracellular trafficking of receptor-ligand complexes. These complexes are subsequently directed into distinct routes, either toward lysosomal degradation or recycling to the cell surface, with implications for therapeutic outcomes. This review examines receptor-ligand interactions as key modulators of endocytosis, emphasizing their role in shaping therapeutic design and efficacy. Advances in selecting receptor-ligand pairs and engineering ligands with optimized properties have enabled precise control over internalization, endosomal sorting, and trafficking, providing tailored solutions for diverse therapeutic applications. Leveraging these insights, strategies such as RNA-based therapies, antibody-drug conjugates (ADCs), and targeted protein degradation (TPD) platforms have been refined to selectively avoid or promote lysosomal degradation, thereby enhancing therapeutic efficacy. By bridging fundamental mechanisms of receptor-mediated endocytosis with innovative therapeutic approaches, this review offers a framework for advancing precision medicine.
Cotadutide reversible self-assembly based long-acting injectable depot for sustained delivery of GLP-1 glucagon receptor agonists with controlled burst release
Authors: Bin Yang, Durga Devalla, Silvia Sonzini, Mikael Boberg, Sashi Gopaul, Monika Sundqvist, Iain Grant, Christopher Jones, Stephanie Brookes, Cindy Weidauer, Eleonora Paladino, Najet Mahmoudi, Jason van Rooyen, Ana Gomes Dos Santos, Johanna Laru, Andy Campbell, Lutz Jermutus, Annette Bak
Journal: Journal of Controlled Release (2025)
Chaperoning a Cure: Unexpected Role of CD74 in Cutaneous T-cell lymphoma
Authors: Robert Gniadecki
Journal: British Journal of Dermatology (2025)

Journal Article Accepted manuscript Chaperoning a Cure: Unexpected Role of CD74 in Cutaneous T-cell lymphoma Get access Robert Gniadecki Robert Gniadecki Division of Dermatology, University of Alberta, Canada Email:[email protected] Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljaf040, https://doi.org/10.1093/bjd/ljaf040 Published: 29 January 2025 Article history Received: 20 January 2025 Accepted: 21 January 2025 Published: 29 January 2025
Microneedle-delivered adeno-associated virus vaccine amplified anti-viral immunity by improving antigen-presenting cells infection
Authors: Penghui He, Chunting He, Fuhua Wu, Yangsen Ou, Shuang Luo, Yongshun Zhang, Yu Chang, Zhaofei Guo, Xue Tang, Yuanhao Zhao, Yanhua Xu, Hairui Wang, Shuting Bai, Guangsheng Du, Xun Sun
Journal: Journal of Controlled Release (2025)
tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells
Authors: Shan Miao, Hao Li, Xiaohan Song, Yongbo Liu, Gaoyang Wang, Chen Kan, Youqiong Ye, Ru-Juan Liu, Hua-Bing Li
Journal: The Journal of Experimental Medicine (2024)

Activation of CD8+ T cells necessitates rapid metabolic reprogramming to fulfill the substantial biosynthetic demands of effector functions. However, the posttranscriptional mechanisms underpinning this process remain obscure. The transfer RNA (tRNA) N1-methyladenine (m1A) modification, essential for tRNA stability and protein translation, has an undefined physiological function in CD8+ T cells, particularly in antitumor responses. Here, we demonstrate that the tRNA m1A "writer" gene Trmt61a enhances the tumor-killing capacity of CD8+ T cells by regulating cholesterol biosynthesis. Deletion of Trmt61a in CD8+ T cells leads to a compromised tumor-killing function in both in vivo and in vitro assays. Mechanistically, tRNA m1A promotes antitumor immunity in CD8+ T cells by enhancing the translation of ATP citrate lyase, a key enzyme for cholesterol biosynthesis. Cholesterol supplementation rescues the impaired tumor-killing function and proliferation of TRMT61A-deficient CD8+ T cells. Our findings highlight tRNA m1A modification as a regulatory checkpoint in cholesterol metabolism in CD8+ T cells, suggesting potential novel strategies for cancer immunotherapy.
Career framework is needed to help more doctors into clinical research, says report
Authors: Carla Delgado
Journal: BMJ (2025)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Career framework is needed to help more doctors into clinical research, says report Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
<i>Lachnospiraceae-bacterium</i> alleviates ischemia-reperfusion injury in steatotic donor liver by inhibiting ferroptosis via the Foxo3-Alox15 signaling pathway
Authors: Shenghe Deng, Huan Cao, Tongxi Li, Xueling Wang, Junpeng Meng, Teng Zeng, Di Zhang, Shuhua Zhang, Guoliang Wang, Ran Liu, Tianhao Zou, Mao Cai, Ren Lang, Di Lu, Jinyang Gu
Journal: Gut Microbes (2025)

Ischemia-reperfusion injury (IRI) is a major obstacle in liver transplantation, especially with steatotic donor livers. Dysbiosis of the gut microbiota has been implicated in modulating IRI, and Lachnospiraceae plays a pivotal role in regulating host inflammatory and immune responses, but its specific role in liver transplantation IRI remains unclear. This study explores whether Lachnospiraceae can mitigate IRI and its underlying mechanisms. We found Lachnospiraceae-bacterium (Lachn.) abundance was significantly reduced in rats with liver cirrhosis. Lachn.-treated rats exhibited improved intestinal permeability, reduced IRI severity in both normal and steatotic donor livers, and decreased levels of neutrophil and macrophage infiltration, and inflammatory cytokines. Multi-omics analysis revealed elevated pyruvate levels in transplanted livers after Lachn. treatment, alongside reduced Alox15 and Foxo3 expression. Mechanistically, Lachn.-derived pyruvate inhibited Alox15 expression and reduced ferroptosis in normal and steatotic donor livers. Furthermore, reduced nuclear translocation of Foxo3 further suppressed Alox15 expression, alleviating IRI, especially in steatotic donor livers. Clinical samples confirmed reduced donor livers IRI in cirrhotic recipients with high Lachn. abundance after liver transplantation. In conclusion, Lachn. alleviates IRI in steatotic donor liver transplantation by inhibiting ferroptosis via the Foxo3-Alox15 axis, providing a potential therapeutic strategy to modulate gut microbiota to alleviate IRI following liver transplantation.
Lewy body diseases and the gut
Authors: Timothy R. Sampson, Malú Gámez Tansey, Andrew B. West, Rodger A. Liddle
Journal: Molecular Neurodegeneration (2025)

Abstract Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation. Experimental LBD models have implicated important contributions from the intrinsic gut microbiome, the intestinal immune system, and environmental toxicants, acting as triggers and modifiers to GI pathologies. Here, we review the primary clinical observations that link GI dysfunctions to LBDs. We first provide an overview of GI anatomy and the cellular repertoire relevant for disease, with a focus on luminal-sensing cells of the intestinal epithelium including enteroendocrine cells that express ⍺-syn and make direct contact with nerves. We describe interactions within the GI tract with resident microbes and exogenous toxicants, and how these may directly contribute to ⍺-syn pathology along with related metabolic and immunological responses. Finally, critical knowledge gaps in the field are highlighted, focusing on pivotal questions that remain some 200 years after the first descriptions of GI tract dysfunction in LBDs. We predict that a better understanding of how pathophysiologies in the gut influence disease risk and progression will accelerate discoveries that will lead to a deeper overall mechanistic understanding of disease and potential therapeutic strategies targeting the gut-brain axis to delay, arrest, or prevent disease progression.
Comparative population genomics unveils congruent secondary suture zone in Southwest Pacific Hydrothermal Vents
Authors: Adrien Tran Lu Y, Stéphanie Ruault, Claire Daguin-Thiébaut, Anne-Sophie Le Port, Marion Ballenghien, Jade Castel, Pierre-Alexandre Gagnaire, Nicolas Bierne, Sophie Arnaud-Haond, Camille Poitrimol, Eric Thiébaut, François H Lallier, Thomas Broquet, Didier Jollivet, François Bonhomme, Stéphane Hourdez
Journal: Molecular Biology and Evolution (2025)

Abstract How the interplay of biotic and abiotic factors shapes current genetic diversity at the community level remains an open question, particularly in the deep sea. Comparative phylogeography of multiple species can reveal the influence of past climatic events, geographic barriers, and species life history traits on spatial patterns of genetic structure across lineages. To shed light on the factors that shape community-level genetic variation and to improve our understanding of deep-sea biogeographic patterns, we conducted a comparative population genomics study on seven hydrothermal vent species co-distributed in the Back-Arc Basins (BABs) of the Southwest Pacific region. Using ddRAD-seq, we compared the range-wide distribution of genomic diversity across species and discovered a shared phylogeographic break. Demogenetic inference revealed shared histories of lineage divergence and a secondary contact. Low levels of asymmetric gene flow probably occurred in most species between the Woodlark and North Fiji basins, but the exact location of contact zones varied from species to species. For two species, we found individuals from the two lineages co-occurring in sympatry in Woodlark Basin. Although species exhibit congruent patterns of spatial structure (Eastern vs Western sites), they also show variation in the degree of divergence among lineages across the suture zone. Our results also show heterogeneous gene flow across the genome, indicating possible partial reproductive isolation between lineages and early speciation. Our comparative study highlights the pivotal role of historical and contemporary factors, underscoring the need for a comprehensive approach—especially in addressing knowledge gaps on the life history traits of deep-sea species.
New Therapeutic Perspectives in Type B Insulin Resistance Syndrome: Efficacy of a Multitarget Therapy With Obinutuzumab and Mycophenolate Mofetil in Two Patients With Insulin Receptor Autoantibodies and Systemic Lupus Erythematosus
Authors: Vincent Jachiet, Philippine Vuillaume, Jérôme Hadjadj, Noémie Abisror, Martine Auclair, Olivier Fain, Corinne Vigouroux, Camille Vatier
Journal: Diabetes Care (2025)
Blocking the CD39/CD73 pathway synergizes with anti-CD20 bispecific antibody in nodal B-cell lymphoma
Authors: Clara Kolbe, Joseph Kauer, Berit Brinkmann, Peter Dreger, Wolfgang Huber, Carsten Müller-Tidow, Sascha Dietrich, Tobias Roider
Journal: Journal for ImmunoTherapy of Cancer (2025)

Bispecific antibodies (BsAb) have emerged as a leading treatment modality in patients suffering from B-cell non-Hodgkin’s lymphoma (B-NHL). However, treatment failure is common and may potentially be attributed to pre-existing or emerging T-cell exhaustion. CD39 catalyzes—together with CD73—the hydrolysis of immunogenic ATP into immunosuppressive adenosine and thus actively promotes an immunosuppressive micromilieu. Previously, we and others demonstrated that CD39 + T-cell subsets may have an adverse impact on the efficacy of T-cell-engaging immunotherapies. In this study, we applied an autologous ex vivo culture model of primary lymph node-derived T cells to investigate the potential of anti-CD39 or anti-CD73 blocking antibodies as T-cell enhancing combination partners of an anti-CD20 BsAb. Existing single-cell data of patient samples examined in this study were used to detect potential biomarkers predicting combination benefits. Combining anti-CD20 BsAb with anti-CD39 or anti-CD73 blocking antibodies induced synergistic effects on tumor cell killing, T-cell expansion and secretion of cytokines, including granzyme B, perforin, interleukin-10, interferon-γ, and tumor necrosis factor-α. We discovered that blockade of the CD39/CD73 pathway was particularly effective in patients with a high proportion of Programmed cell death protein 1 (PD-1) + T-cell immunoglobulin and mucin-domain containing-3 (TIM3) + exhausted T cells. Also, expression of CD39 in effector memory T cells indicated superior treatment benefit ex vivo. In summary, our study holds significant relevance as it introduces the combination of bispecific and anti-CD39 or anti-CD73 antibodies as a synergistic treatment approach in B-NHL, while also suggesting potential indicators to identify patients that might benefit from this treatment.
Extracellular Vesicles Released by Glioblastoma Cancer Cells Drive Tumor Invasiveness via Connexin-43 Gap Junctions
Authors: Matteo Tamborini, Valentino Ribecco, Elisabetta Stanzani, Arianna Sironi, Monica Tambalo, Davide Franzone, Elena Florio, Edoardo Fraviga, Chiara Saulle, Maria C Gagliani, Marco Pizzocri, Milena Mattioli, Katia Cortese, Jean X Jiang, Giuseppe Martano, Letterio S Politi, Marco Riva, Federico Pessina, Davide Pozzi, Simona Lodato, Lorena Passoni, Michela Matteoli
Journal: Neuro-Oncology (2025)

Abstract Background Although invasiveness is one of the major determinants of the poor glioblastoma (GBM) outcome, the mechanisms of GBM invasion are only partially understood. Among the intrinsic and environmental processes promoting cell-to-cell interaction processes, eventually driving GBM invasion, we focused on the pro-invasive role played by Extracellular Vesicles (EVs), a heterogeneous group of cell-released membranous structures containing various bioactive cargoes, which can be transferred from donor to recipient cells. Methods EVs isolated from patient-derived GBM cell lines and surgical aspirates were assessed for their pro-migratory competence by spheroid migration assays, calcium imaging, and PYK-2/FAK phosphorylation. Brain invasiveness was investigated in human cortical organoids-based assembloids and in vivo orthotopic xenografts. EV molecular features were specified by multiplex bead-based flow cytometry. Results Results unveil a self-sustaining mechanism triggering migration through autocrine release and engagement of a specific population of EVs of large size (L-EVs), isolated from either patient-derived cell lines or surgical aspirates. L-EVs act through modulation of calcium transients via Connexin 43-Gap Junctions (Cx43-GJ) and phospho-activation of PYK2. Pre-incubation with blocking antibodies targeting Cx43 hemichannels demonstrated a dose-dependent inhibition of the L-EV-mediated GBM migration. By exploiting patients’ surgical aspirates, we show that only L-EVs deriving from tumoral cells, and not those with immune origin, promote tumor migration, impacting more prominently the tumoral cells with mesenchymal subtype. Conclusions We demonstrate that L-EVs released by GBM cells, but not by the immune cells of the tumor microenvironment, represent a relevant and unique autocrine pro-migratory input for the tumor.
Tumor cells upregulate neurotransmitter GABA in the choroid plexus through STAT6-Bestrophin1 signaling, promoting leptomeningeal dissemination
Authors: Diganta Das, Mukund Iyer, Brooke Nakamura, Saman Sedighi, Angela Hsu, Camelia Danilov, Peter S LaViolette, Jennifer Connelly, Frances Chow, Josh Neman
Journal: Neuro-Oncology (2025)

Abstract Background Leptomeningeal dissemination (LMD) occurs when tumor cells interact with choroid plexus epithelium (CPE) to gain access to cerebrospinal fluid (CSF) in the brain’s meninges and ventricular system. This disease is particularly devastating for patients due to our limited understanding and few therapeutic options. The leptomeningeal CSF is a nutritionally deprived microenvironment for tumor cells. Despite this, LMD tumor cells survive by taking up and metabolizing the neurotransmitter GABA from the CSF. However, we currently lack evidence on how CSF-GABA levels are altered and how tumor cells communicate with the choroid plexus epithelium to increase GABA levels in the LMD microenvironment. Herein, we examined the interactions between CPEs and tumor cells that make CSF more hospitable to LMD growth. Methods We utilized primary choroid plexus, breast cancer cell and patient-derived breast and lung to brain metastatic cells along with in-vivo modeling along with STAT6 inhibitor and IL13 gene knockdown. Results We show breast and lung cancer cells derived-IL13 activates STAT6 signaling in choroid plexus. Subsequently, choroid plexus upregulates GABA-synthesizing enzyme GAD67 and GABA-permeable channel Bestrophin-1, all leading to elevated neurotransmitter GABA levels in the cerebrospinal fluid. Moreover, we show a significant reduction of Bestrophin1 in choroid plexus when tumor-derived IL13 is knocked down or when treated with brain permeable STAT6 specific inhibitor AS1517499, leading to increased survival. Conclusions Overall, these findings reveal a novel STAT6-Bestrophin1-GABA axis in choroid plexus and its therapeutic targeting can lead to favorable outcomes in leptomeningeal disease.
Up-regulated matrix metalloproteinase activity in soil-transmitted helminth–tuberculosis co-infection is associated with increased lung pathology
Authors: Maria-Cristina I Loader, Sory Vasquez Alves, Robert H Gilman, Jorge Coronel, Carmen Taquiri, Neusa Vasquez Alves, Fabiola Díaz-Soria, Salomón Durand, Sean T Kelleher, Teresa Jacob, William H Elson, Daniela E Kirwan, Jon S Friedland
Journal: European Respiratory Journal (2025)
Concerns in Interpretation of Results In the Identification of Immune Checkpoint Inhibitor–Induced Diabetes—Reply
Authors: Karina N. Ruiz-Esteves, Aaron J. Deutsch, Michelle Rengarajan
Journal: JAMA Oncology (2025)

In Reply We read with interest the Letter to the Editor in response to our recent publication on immune checkpoint inhibitor (ICI)–induced diabetes,1 and we appreciate the opportunity to address the concerns raised by Akturk and Michels.
Ten Years After Diagnosis
Authors: Judith Redwing Keyssar
Journal: JAMA Oncology (2025)

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