Article
Multidisciplinary Sciences
Xenofon Strakosas, Hanne Biesmans, Tobias Abrahamsson, Karin Hellman, Malin Silvera Ejneby, Mary J. Donahue, Peter Ekstrom, Fredrik Ek, Marios Savvakis, Martin Hjort, David Bliman, Mathieu Linares, Caroline Lindholm, Eleni Stavrinidou, Jennifer Y. Gerasimov, Daniel T. Simon, Roger Olsson, Magnus Berggren
Summary: Interfacing electronics with neural tissue is crucial for understanding complex biological functions, but traditional bioelectronics are not compatible with living systems. To overcome this, researchers developed a method to create conducting materials within the biological environment using endogenous metabolites. This approach allows for the formation of conducting polymer gels with long-range conductivity, paving the way for fully integrated, in vivo-fabricated electronics within the nervous system.
Article
Multidisciplinary Sciences
Antoine Gagelin, Corentin Largeau, Sandrine Masscheleyn, Mathilde S. S. Piel, Daniel Calderon-Mora, Frederic Bouillaud, Jerome Henin, Bruno Miroux
Summary: By combining molecular dynamic simulations with in vivo functional assays, Gagelin et al. uncovered the molecular features of UCP1 that are essential for its inhibition by nucleotides. The study focused on understanding how purine nucleotides inhibit the respiration uncoupling activity of UCP1. Through simulations and assays, the authors identified specific residues and interactions that play a crucial role in the selective inhibition of UCP1 by purine nucleotides.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Erik A. Richter
Summary: Exercise in humans greatly increases muscle glucose uptake, but the translocation of GLUT4 to the cell membrane only doubles, indicating a significant disparity. This could be due to underestimated measurements or an increase in GLUT4 intrinsic activity during exercise.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Jin-Yong Lee, Maki Tokumoto, Masahiko Satoh
Summary: Cadmium exerts its cytotoxicity through the inhibition of MEF2A activity and suppression of GLUT4 expression, leading to reduced cellular glucose concentration and ATP levels. This study provides a crucial breakthrough in understanding the mechanism of Cd toxicity in renal cells.
Article
Nutrition & Dietetics
Amy Zheng, Haiyan Wang, Edward B. Arias, Gengfu Dong, Jiahui Zhao, Gregory D. Cartee
Summary: The effects of calorie restriction on female wildtype and Akt substrate of 160 kDa knockout rats were evaluated. The results showed that calorie restriction increased muscle glucose uptake and GLUT4 protein abundance, and AS160 expression was essential for these increases.
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM
(2023)
Article
Multidisciplinary Sciences
Vincent Chaptal, Veronica Zampieri, Benjamin Wiseman, Cedric Orelle, Juliette Martin, Kim-Anh Nguyen, Alexia Gobet, Margot Di Cesare, Sandrine Magnard, Waqas Javed, Jad Eid, Arnaud Kilburg, Marine Peuchmaur, Julien Marcoux, Luca Monticelli, Martin Hogbom, Guy Schoehn, Jean-Michel Jault, Ahcene Boumendjel, Pierre Falson
Summary: This study resolved three outward-facing conformations of BmrA, a multidrug ABC transporter, using x-ray crystallography and cryo-electron microscopy. It was found that two R6G molecules bind to the drug-binding cavity, inducing a rearrangement of TM1-2 and highlighting local flexibility. Simulations showed that in the absence of R6G, the cavity quickly closed after drug release, while in the presence of R6G, the cavity remained open.
Article
Neurosciences
Stewart W. C. Masson, Jonathan S. T. Woodhead, Randall F. D'Souza, Sophie C. Broome, Caitlin MacRae, Hyun C. Cho, Robert D. Atiola, Tumanu Futi, Jessica R. Dent, Peter R. Shepherd, Troy L. Merry
Summary: Beta-catenin plays a crucial role in regulating glucose uptake during exercise/contraction, potentially through facilitating actin cytoskeleton remodelling to support glucose transport.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Endocrinology & Metabolism
Yosuke Masubuchi, Jinhui Ma, Tomohiro Suzuki, Itaru Kojima, Takeshi Inagaki, Hiroshi Shibata
Summary: T1R3 receptor plays a non-gustatory role in adipocytes by negatively regulating insulin action of glucose transport through G alpha s-dependent microtubule disassembly.
Article
Biochemistry & Molecular Biology
Marzieh Dehghan Shasaltaneh, Elmira Naghdi, Zahra Moosavi-Nejad
Summary: This study investigates the interactions between RNase A and cCMP through molecular docking and molecular dynamics simulation. The results indicate that cCMP-RNase A complexes are stabilized through hydrophobic interaction, hydrogen bonding, and π-π stacking interaction. The enzyme-ligand docking study shows three phases of binding modes, and experimental methods confirm the activation and inhibition of substrate at different concentrations of cCMP.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Cell Biology
Dorota Rogacka, Patrycja Rachubik, Irena Audzeyenka, Tomasz Kulesza, Maria Szrejder, Dorota Myslinska, Stefan Angielski, Agnieszka Piwkowska
Summary: A decrease in intracellular levels of cGMP is linked to the progression of diabetic nephropathy. Hyperglycemia inhibits pathway activity in the kidney, leading to glomerular damage and proteinuria. Selective inhibitors, such as tadalafil, can enhance pathway activity by inhibiting PDE5A.
CELLULAR SIGNALLING
(2023)
Article
Nanoscience & Nanotechnology
Christopher Maffeo, Lauren Quednau, James Wilson, Aleksei Aksimentiev
Summary: Flowing fluid past chiral objects has been used to power rotary motion in man-made machines for centuries. In nanoscale biological or chemical systems, rotary motion is generated by biasing Brownian motion through cyclic chemical reactions. In this study, we demonstrate that a chiral biological molecule (DNA or RNA duplex) rotates unidirectionally at billions of revolutions per minute when an electric field is applied along the duplex, with the rotation direction determined by the duplex's chirality. The rotation is powered by the drag force of the electro-osmotic flow, mimicking the operating principle of a macroscopic turbine at the nanoscale.
NATURE NANOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Samaneh Eickelschulte, Sonja Hartwig, Ben Leiser, Stefan Lehr, Viola Joschko, Manopriya Chokkalingam, Alexandra Chadt, Hadi Al-Hasani
Summary: TBC1D4 is a multidomain Rab GTPase-activating protein that plays a role in GLUT4 trafficking. Phosphorylation by AKT and AMPK does not affect enzymatic activity but disrupts interaction with other proteins. Insulin and contraction regulate TBC1D4 primarily by disrupting recruitment to GLUT4 vesicles.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Beth A. Griesel, Satoshi Matsuzaki, Albert Batushansky, Timothy M. Griffin, Kenneth M. Humphries, Ann Louise Olson
Summary: This study using 3T3-L1 adipocytes as a model system found that an increase in glucose uptake during the first 3 days of differentiation promoted the expansion of the adipocyte metabolome and proteome. The positive effects were specifically due to increased expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), highlighting its critical role in regulating cellular metabolic remodeling for adipocyte differentiation and maturation.
Article
Endocrinology & Metabolism
Yosuke Masubuchi, Jinhui Ma, Tomohiro Suzuki, Itaru Kojima, Takeshi Inagaki, Hiroshi Shibata
Summary: T1R3, expressed in adipocytes, negatively regulates insulin-induced glucose transport via Gαs-dependent microtubule disassembly. Activation of T1R3 also inhibits insulin-induced GLUT4 translocation to the plasma membrane.
Review
Biochemistry & Molecular Biology
Shujin Wang, Yinying Han, Miranda Nabben, Dietbert Neumann, Joost J. F. P. Luiken, Jan F. C. Glatz
Summary: The heart can utilize a variety of substrates for energy provision, with balanced substrate preference being crucial for cardiac function. Imbalance or chronic shift towards a single type of energy substrate is linked with cardiac dysfunction.
Review
Hematology
Ishnoor Sidhu, Sonali P. Barwe, Anilkumar Gopalakrishnapillai
Summary: This article discusses the importance of hematopoietic stem cells and the bone marrow microenvironment in hematologic malignancies, as well as the impact of genetic mutations in this process. It also mentions the role of the extracellular matrix in promoting the evolution of hematologic cancers, although its precise role is not fully understood.
Article
Biochemistry & Molecular Biology
Shabir Ahmad Ganai, Pappu Srinivasan, Sundaraj Rajamanikandan, Basit Amin Shah, Suma Mohan, Mudasir Gani, Bilal Ahmad Padder, Raies A. Qadri, M. A. Bhat, Zahoor Ahmad Baba, Manzoor Ahmad Yatoo
Summary: The study investigated the binding affinity, interaction mode, pharmacophoric features, and stability of SFN-NAC towards HDAC2 using various molecular modeling techniques. Furthermore, density functional theory (DFT) study was conducted on SFN-NAC and entinostat in complex state with HDAC2. The results revealed higher binding affinity of entinostat for HDAC2 and its broad spectrum cytotoxicity compared to SFN-NAC.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Biochemistry & Molecular Biology
Basit Amin Shah, Shabir Ahmad Ganai, Aabid M. Koul, Suma Mohan, Asif Amin, Zubair Wani, Umer Majeed, Sundaraj Rajamanikandan, Faizah Farooq, Firdose Ahmad Malik, Naveed Nazir Shah, Raies A. Qadri
Summary: DEPTOR plays a critical role in promoting tumor growth by inhibiting mTORC1, and targeting the DEPTOR-mTOR interaction with small molecules may be an effective strategy for combating cancer. In this study, a top-down approach was used to identify three novel molecules that may disrupt DEPTOR-mTOR interaction effectively. Through molecular docking experiments and molecular dynamics simulations, three promising molecules were selected as potential candidates for anticancer therapy.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Hematology
Emily B. Heikamp, Jill A. Henrich, Florian Perner, Eric M. Wong, Charles Hatton, Yanhe Wen, Sonali P. Barwe, Anilkumar Gopalakrishnapillai, Haiming Xu, Hannah J. Uckelmann, Sumiko Takao, Yaniv Kazansky, Yana Pikman, Gerard M. McGeehan, Edward A. Kolb, Alex Kentsis, Scott A. Armstrong
Summary: Translocations involving the NUP98 gene are associated with poor prognosis in acute myeloid leukemia (AML). In this study, the efficacy of therapeutic blockade of the menin-MLL1 interaction in NUP98-fusion leukemia models was investigated. The results showed that menin-MLL1 inhibition can effectively suppress the growth of NUP98-fusion-driven leukemia cells and promote their differentiation. Furthermore, in vivo experiments using patient-derived xenograft (PDX) models demonstrated that menin-MLL1 inhibition significantly prolongs the survival of mice with NUP98-fusion-driven AML. These findings suggest that menin-MLL1 inhibition could be a promising targeted therapy for patients with NUP98-rearranged leukemias.
Article
Genetics & Heredity
Saleem Farooq, Shabir Ahmad Ganai, Bashir Ahmad Ganai, Suma Mohan, Baba Uqab, Ruqeya Nazir
Summary: Lipases from Pseudomonas species, particularly a cold-active lipase isolated from a Himalayan glacier bacterium, were studied for their structure, catalytic properties, and binding affinity towards different substrates. Molecular docking experiments revealed the lipase's higher affinity for tributyrin compared to oleic acid, indicating its potential application in biocatalysis.
Article
Oncology
Anilkumar Gopalakrishnapillai, Colin E. Correnti, Kristina Pilat, Ida Lin, Man Kid Chan, Ashok D. Bandaranayake, Christopher Mehlin, Anne Kisielewski, Darcy Hamill, Allison J. Kaeding, Soheil Meshinchi, James M. Olson, Edward Anders Kolb, Sonali P. Barwe
Summary: Development of immunotherapy for pediatric AML has been slow, but targeting mesothelin with bispecific antibodies has shown promising results in preclinical models, suggesting a potential new treatment option for pediatric AML patients.
Article
Medicine, General & Internal
Sonali P. Barwe, Anne Kisielewski, Ezio Bonvini, John Muth, Jan Davidson-Moncada, Edward Anders Kolb, Anilkumar Gopalakrishnapillai
Summary: CD123 x CD3 dual-affinity retargeting antibody MGD006 shows efficacy in killing pediatric AML cells, and combination treatment with cytarabine does not interfere with MGD006 activity.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Sonali P. Barwe, Fei Huang, Edward Anders Kolb, Anilkumar Gopalakrishnapillai
Summary: Imetelstat has been shown to specifically kill leukemia stem cells (LSCs) in pediatric AML cells and mouse models, and it can extend animal survival when used as a single agent or in combination with chemotherapy or azacitidine.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Joshua R. Faust, Darcy Hamill, Edward Anders Kolb, Anilkumar Gopalakrishnapillai, Sonali P. Barwe
Summary: This review summarizes the function of mesothelin, its role in cancer, and opportunities for targeted immunotherapy. Current research focuses on designing targeted cancer therapies utilizing mesothelin, including various immunotherapeutic methods. Studies highlight the potential impact of this approach as a unique opportunity to treat hard-to-cure acute myeloid leukemia.
Article
Chemistry, Multidisciplinary
Fasil Ali, Usma Manzoor, Reshmee Bhattacharya, Aniket Kumar Bansal, Kempohalli Sayanna Chandrashekharaiah, Laishram Rajendrakumar Singh, Suma Mohan Saraswati, Vladimir Uversky, Tanveer Ali Dar
Summary: There is a strong correlation between brain metabolite accumulation and oxidative stress in Alzheimer's disease. Myo-inositol (MI) inhibits catalase, an essential antioxidant enzyme, leading to increased cellular H2O2 levels and decreased cell viability.
Article
Biochemistry & Molecular Biology
Akhila Pudipeddi, Sahana Vasudevan, Karthi Shanmugam, Suma S. Mohan, Pothiappan Vairaprakash, Prasanna Neelakantan, Alex Stanley Balraj, Adline Princy Solomon
Summary: Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate-resistant Staphylococcus aureus (VRSA) are high priority pathogens according to the WHO. This study focuses on the urgent need for new classes of anti-MRSA drugs and targets the GyrB subunit of bacterial DNA Gyrase. Through structure-based virtual screening and de novo ligand design, the most promising ligand qsl-304 was identified. In vitro experiments showed qsl-304's activity against the novobiocin resistant clinical isolate, Staphylococcus aureus sa-P2003, and its bacteriostatic nature with reduced resistance recurrence.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Jananishree Sathiyamoorthy, Sudarshan Singh Rathore, Suma Mohan, C. Uma Maheshwari, Jayapradha Ramakrishnan
Summary: In the era of antiretroviral therapy, the prevalence of Cryptococcal infection among HIV patients in developed countries has decreased considerably. However, C. neoformans ranks top among the critical priority pathogen that affects a wide range of immunocompromised individuals. The threat of C. neoformans is because of its incredibly multifaceted intracellular survival capabilities.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Hematology
Anthony Quagliano, Anilkumar Gopalakrishnapillai, Sonali P. Barwe
Summary: Despite advancements in treating hematologic malignancies, relapse remains an ongoing issue, largely due to the bone marrow microenvironment protecting malignant cells. The role of transmembrane 4 superfamily (tetraspanins; TSPANs) in mediating bone marrow interactions and potential therapeutic targeting opportunities in hematologic malignancies are discussed in this review.
Article
Chemistry, Multidisciplinary
Fasil Ali, Usma Manzoor, Reshmee Bhattacharya, Aniket Kumar Bansal, Kempohalli Sayanna Chandrashekharaiah, Laishram Rajendrakumar Singh, Suma Mohan Saraswati, Vladimir Uversky, Tanveer Ali Dar
Summary: A strong correlation between brain metabolite accumulation and oxidative stress in Alzheimer's disease (AD) patients has been observed. This study demonstrates the inhibitory effect of myo-inositol (MI) on the essential antioxidant enzyme catalase, leading to increased cellular H2O2 levels and decreased cell viability. MI also induces structural changes in catalase, further contributing to the inactivation of the antioxidant defense system during oxidative stress-induced pathogenesis of AD. Regulating MI levels during the early stages of AD may serve as a potential therapeutic strategy for this disease.
Article
Materials Science, Biomaterials
Ishnoor Sidhu, Sonali P. Barwe, Kristi L. Kiick, E. Anders Kolb, Anilkumar Gopalakrishnapillai
Summary: The study established a synthetic 3D iPSC culture system to model Transient Myeloproliferative Disorder (TMD), utilizing a chemically cross-linkable PEG hydrogel to promote hematopoietic differentiation of iPSCs with higher yield of early HSPCs, thus mimicking TMD characteristics.
BIOMATERIALS SCIENCE
(2021)