Article
Microbiology
Ana Valades-Alcaraz, Roberto Reinosa, Africa Holguin
Summary: This study provides a comprehensive conservation analysis of gp41/gp36 variants in the largest panel of HIV variants to date, offering valuable information for the rational design of drugs, vaccines, and molecular detection tests targeting the HIV transmembrane glycoprotein.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Camila H. Coelho, Wai Kwan Tang, Martin Burkhardt, Jacob D. Galson, Olga Muratova, Nichole D. Salinas, Thiago Luiz Alves e Silva, Karine Reiter, Nicholas J. MacDonald, Vu Nguyen, Raul Herrera, Richard Shimp, David L. Narum, Miranda Byrne-Steele, Wenjing Pan, Xiaohong Hou, Brittany Brown, Mary Eisenhower, Jian Han, Bethany J. Jenkins, Justin Y. A. Doritchamou, Margery G. Smelkinson, Joel Vega-Rodriguez, Johannes Trueck, Justin J. Taylor, Issaka Sagara, Jonathan P. Renn, Niraj H. Tolia, Patrick E. Duffy
Summary: This study identifies a human monoclonal antibody from Pfs230 vaccinated individuals that can effectively block the transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with the gamete surface.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Li He, Guangyan Zhou, Vladimir Sofiyev, Eddie Garcia, Newton Nguyen, Kathy H. H. Li, Miriam Gochin
Summary: The study investigates the conversion of molecules with better drug-like properties to improve antiviral efficacy. By adding an electrophilic warhead, equilibrium binders can be converted into inhibitors. This method shows promise in inhibiting HIV-1 entry.
Article
Chemistry, Multidisciplinary
Alessandro Piai, Qingshan Fu, Amanda K. Sharp, Beatrice Bighi, Anne M. Brown, James J. Chou
Summary: This study determined the structure of the cytoplasmic tail (CT) of HIV-1 envelope glycoprotein through NMR, and derived a model of the membrane-interacting region, showcasing stability in a viral membrane and compensation for lipid exclusion by the KS-LLP2 region through molecular dynamics simulations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Microbiology
Srividhya Swaminathan, Katie E. Lineburg, George R. Ambalathingal, Pauline Crooks, Emma J. Grant, Sonali Mohan, Jyothy Raju, Archana Panikkar, Laetitia Le Texier, Zheng Wei Marcus Tong, Keng Yih Chew, Michelle A. Neller, Kirsty R. Short, Harsha Gowda, Stephanie Gras, Rajiv Khanna, Corey Smith
Summary: Understanding the immune response to SARS-CoV-2 is crucial for overcoming the COVID-19 pandemic. This study assessed T-cell responses and found that cross-reactive CD8(+) T cells are uncommon in unexposed individuals, suggesting that they play a limited role in providing broad preexisting immunity.
MICROBIOLOGY SPECTRUM
(2022)
Article
Multidisciplinary Sciences
Naba K. Das, Nele M. Hollmann, Jeff Vogt, Spiridon E. Sevdalis, Hasan A. Banna, Manju Ojha, Deepak Koirala
Summary: Researchers have determined the crystal structure of an RNA in complex with an antibody chaperone, which plays a crucial role in initiating genome replication.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Tatiana M. Garcia-Bates, Mariana L. Palma, Renee R. Anderko, Denise C. Hsu, Jintanat Ananworanich, Bette T. Korber, Gaurav D. Gaiha, Nittaya Phanuphak, Rasmi Thomas, Sodsai Tovanabutra, Bruce D. Walker, John W. Mellors, Paolo A. Piazza, Eugene Kroon, Sharon A. Riddler, Nelson L. Michael, Charles R. Rinaldo, Robbie B. Mailliard
Summary: The study demonstrated the efficacy of using MDC1 to selectively elicit CTL responses against conserved and topologically important HIV-1 epitopes. Epigraph and Network antigens showed higher sequence conservation and stronger CTL responses compared to overlapping Gag peptides. Importantly, CTL responses against topologically constrained Gag epitopes were enhanced in Network pool-initiated cultures.
Article
Virology
Soohyun Kim, Maria V. Filsinger V. Interrante, Peter S. S. Kim
Summary: The trimeric glycoprotein Env on the surface of HIV-1 is the target of broadly neutralizing antibodies and vaccine development efforts. Antibodies that target the membrane proximal external region (MPER) of Env show lipid-binding characteristics and increasing their local concentration through binding to the Fc receptor Fc gamma RI can potentiate their ability to prevent viral entry. This study shows that lipid-binding activity and Fc gamma RI-mediated potentiation work together to improve the potency of MPER-directed antibodies by increasing their local concentration near the site of viral fusion.
JOURNAL OF VIROLOGY
(2023)
Article
Biology
Benkun Zou, Michael Goodwin, Danial Saleem, Wei Jiang, Jianguo Tang, Yiwei Chu, Robert S. Munford, Mingfang Lu
Summary: Research shows that acyloxyacyl hydrolase (AOAH) can reduce the pro-inflammatory effects of oxidized phospholipids by removing specific lipid acyl chains and also has protective effects against acute lung injury.
Article
Biochemistry & Molecular Biology
Daria Mezhenskaya, Irina Isakova-Sivak, Tatiana Gupalova, Elena Bormotova, Eugenia Kuleshevich, Tatiana Kramskaya, Galina Leontieva, Larisa Rudenko, Alexander Suvorov
Summary: This study investigates the feasibility of using Enterococcus faecium L3 as a bacterial vector for oral immunization against influenza virus. The results demonstrate that the L3-LAH+4M2e vaccine shows superior immunogenicity and protective potential in mice.
Article
Veterinary Sciences
Zida Zhu, Taisuke Kitano, Masami Morimatsu, Kazuhiko Ochiai, Toshina Ishiguro-Oonuma, Kosuke Oosumi, Xianghui Lin, Koichi Orino, Yasunaga Yoshikawa
Summary: BRCA2 mutations are associated with mammary tumors in dogs and humans. The highly conserved region (HCR) near the BRC repeats of BRCA2 regulates its interaction with RAD51. HCR mutations may contribute to tumorigenesis in both species.
VETERINARY SCIENCES
(2023)
Article
Multidisciplinary Sciences
Aileen J. Lam, Lu Rao, Yuzu Anazawa, Kyoko Okada, Kyoko Chiba, Mariah Dacy, Shinsuke Niwa, Arne Gennerich, Dan W. Nowakowski, Richard J. McKenney
Summary: KIF1A is a critical motor for cargo transport within neurons, and mutations associated with KAND can significantly affect its microtubule-binding rate. The P305L mutation negatively impacts various biophysical parameters of the motor, with the 310 helix playing a crucial role in maintaining a specific K-loop conformation.
Article
Multidisciplinary Sciences
Nicolas Vabret, Valerie Najburg, Alexander Solovyov, Ramya Gopal, Christopher McClain, Petr Sulc, Sreekumar Balan, Yannis Rahou, Guillaume Beauclair, Maxime Chazal, Hugo Varet, Rachel Legendre, Odile Sismeiro, Raul Y. Sanchez David, Lise Chauveau, Nolwenn Jouvenet, Martin Markowitz, Sylvie van der Werf, Olivier Schwartz, Frederic Tangy, Nina Bhardwaj, Benjamin D. Greenbaum, Anastassia V. Komarova
Summary: This study reveals the role of endogenous RNA in antiviral immunity, particularly in interaction with RLRs during different types of RNA virus infections. Specific endogenous RNAs bind to RLRs and induce immune response, indicating the importance of endogenous ligands in PRR activation.
Article
Plant Sciences
Byeong Jun Jeon, Nayeon Yoo, Jeong Do Kim, Jaeyoung Choi
Summary: This study identified highly conserved protein sequence profiles within the genus Streptomyces and discovered a highly conserved sequence with antimicrobial activity against bacterial and fungal plant pathogens. This sequence could be a potential antimicrobial agent for controlling plant diseases.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Abenaya Muralidharan, Caroline Gravel, Greg Harris, Anwar M. Hashem, Wanyue Zhang, David Safronetz, Gary Van Domselaar, Florian Krammer, Simon Sauve, Michael Rosu-Myles, Lisheng Wang, Wangxue Chen, Xuguang Li
Summary: This study investigates the immune protective effect of an antibody (Uni-1) against influenza viruses. The antibody was found to induce strong ADCC in vitro and provide cross-protection against different types of influenza viruses. The results demonstrate that Uni-1 can protect mice from lethal influenza virus infections.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2022)
Review
Cell Biology
Fatima Amer-Sarsour, Alina Kordonsky, Yevgeny Berdichevsky, Gali Prag, Avraham Ashkenazi
Summary: The roles of deubiquitylating enzymes in neuronal function and survival are discussed in this article, providing an updated perspective on their genetics, physiology, structure, and function in neuronal health and disease.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Sandra M. Hill, Lidia Wrobel, Avraham Ashkenazi, Marian Fernandez-Estevez, Keith Tan, Roland W. Burli, David C. Rubinsztein
Summary: VCP is a key regulator in the early initiation of autophagy, playing a role in stabilizing Beclin-1 levels and regulating the activity of the PI3K complex to increase the production of the signaling lipid PI(3)P. Decreased VCP levels or inhibition of its ATPase activity impairs autophagosome formation by limiting downstream recruitment of essential autophagy factors.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Tzah Feldman, Akhiad Bercovich, Yoni Moskovitz, Noa Chapal-Ilani, Amanda Mitchell, Jessie J. F. Medeiros, Tamir Biezuner, Nathali Kaushansky, Mark D. Minden, Vikas Gupta, Michael Milyavsky, Zvi Livneh, Amos Tanay, Liran I. Shlush
Summary: Recurrent deletions in myeloid malignancies are found to be generated by PARP1-dependent microhomology-mediated end joining, originating in pre-leukemic stem cells. The association between POLQ-independent MMEJ and clonal hematopoiesis is demonstrated, shedding light on mutational mechanisms in the early stages of leukemia evolution.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Nili Furer, Nathali Kaushansky, Liran I. Shlush
Article
Clinical Neurology
Yehonatan Sharabi, Gad D. Vatine, Avraham Ashkenazi
Summary: Patients with Parkinson's disease may exhibit signs of dysregulation of the peripheral autonomic nervous system, which could serve as early biomarkers for the disease. Dysfunction of the autonomic nervous system may play a role in the spread of Parkinson's disease pathology, emphasizing the importance of developing early diagnostic tests and strategies to prevent neurodegeneration.
Article
Hematology
Amos Tuval, Yardena Brilon, Hadas Azogy, Yoni Moskovitz, Dena Leshkowitz, Tomer M. Salame, Mark D. Minden, Perry Tal, Varda Rotter, Moshe Oren, Nathali Kaushansky, Liran Shlush
Summary: Pre-leukemic clones carrying DNMT3A mutations have inherent chemoresistance and selective advantage. They also have a dominant pseudo-mutant P53 conformation. Shifting the dynamic equilibrium in favor of the wild-type P53 conformation can eliminate dysfunctional cells.
Editorial Material
Neurosciences
Yehonatan Sharabi, Gad D. Vatine, Avraham Ashkenazi
Editorial Material
Neurosciences
Stav Cohen-Adiv, Avraham Ashkenazi
Summary: A recent study demonstrates that altering the monounsaturated fatty acid equilibrium in neuronal cells can alleviate cellular stress caused by familial alpha-synuclein mutations, indicating the involvement of metabolic perturbation of lipids in the pathogenesis of Parkinson's disease.
TRENDS IN NEUROSCIENCES
(2022)
Article
Multidisciplinary Sciences
Lidia Wrobel, Sandra M. Hill, Alvin Djajadikerta, Marian Fernandez-Estevez, Cansu Karabiyik, Avraham Ashkenazi, Victoria J. Barratt, Eleanna Stamatakou, Anders Gunnarsson, Timothy Rasmusson, Eric W. Miele, Nigel Beaton, Roland Bruderer, Yuehan Feng, Lukas Reiter, M. Paola Castaldi, Rebecca Jarvis, Keith Tan, Roland W. Buerli, David C. Rubinsztein
Summary: Enhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for neurodegenerative diseases, and activating VCP protein can improve the clearance of such proteins through autophagy and proteasome pathways.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Kyoung Ha Kim, TaeHyung Kim, Igor Novitzky-Basso, Hyewon Lee, Youngseok Yoo, Jae-Sook Ahn, Ivan Pasic, Arjun Law, Wilson Lam, Fotios Michelis, Armin Gerbitz, Auro Viswabandya, Jeffrey Lipton, Rajat Kumar, Jonas Mattsson, Zhaolei Zhang, Nathali Kaushansky, Yardena Brilon, Noa Chapal-Ilani, Tamir Biezuner, Liran I. Shlush, Dennis Dong Hwan Kim
Summary: It is unknown whether donor clonal hematopoiesis affects transplant outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, 744 samples from HSCT recipients and corresponding donors were analyzed, and the presence of clonal hematopoiesis with indeterminate potential (CHIP) mutations in donors did not impact overall survival, relapse incidence, non-relapse mortality, graft-versus-host disease rates, or secondary malignancy occurrence following HSCT. These findings suggest that molecular profiling for CHIP mutations may not be necessary for pretransplant evaluation of stem cell donors.
Article
Biology
Margarita Galves, Michal Sperber, Fatima Amer-Sarsour, Ran Elkon, Avraham Ashkenazi
Summary: Nutrient deprivation, induced by fasting and hypercaloric regimens, affects cell and tissue homeostasis in mammals. This study focuses on identifying the gene expression networks involved in the cell survival pathway autophagy as a response to starvation. By analyzing omics datasets, two prominent active modules were identified including stress-induced transcription factors and autophagosome sub-network genes. These findings were validated in fasting mice and provide a resource for future research on autophagy regulation.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
N. Zioni, A. Akhiad Bercovich, N. Chapal-Ilani, Tal Bacharach, N. Rappoport, A. Solomon, R. Avraham, E. Kopitman, Z. Porat, M. Sacma, G. Hartmut, M. Scheller, C. Muller-Tidow, D. Lipka, E. Shlush, M. Minden, N. Kaushansky, Liran Shlush
Summary: The accumulation of fatty bone marrow and somatic mutations in hematopoietic stem cells (HSCs) increases with aging. In preclinical mouse models, it is found that fatty bone marrow can enhance the self-renewal of HSCs and activate inflammatory signaling. The inflammatory cytokines, such as IL-6, in fatty bone marrow promote DNMT3a-driven clonal hematopoiesis, which can be inhibited by blocking the IL-6 pathway.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Aster Legesse, Nathali Kaushansky, Ilana Braunstein, Haddas Saad, Gerardo Lederkremer, Ami Navon, Ariel Stanhill
Summary: Protein quality control is a crucial process to monitor the folding status of proteins. RNF149, a membrane bound E3 ligase, plays a significant role in maintaining cellular functionality by ubiquitinating non-translocated proteins. Dysfunction of RNF149 leads to disruption of cellular quality control and is associated with pathological conditions related to impaired quality control.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Hasan Ishtayeh, Margarita Galves, Tania T. Barnatan, Yevgeny Berdichevsky, Fatima Amer-Sarsour, Metsada Pasmanik-Chor, Itzhak Braverman, Sergiu C. Blumen, Avraham Ashkenazi
Summary: We found that the RNA binding protein HNRNPQ/SYNCRIP plays an important role in the early events of autophagosome biogenesis, specifically by inducing VPS34 kinase through ULK1-mediated beclin 1 phosphorylation. HNRNPQ and PABPN1 form a regulatory network that controls the degradation of specific autophagy-related proteins. We also discovered that oculopharyngeal muscular dystrophy mutations impair the control of ULK1 levels by PABPN1 and HNRNPQ, leading to a switch from autophagosome stimulation to inhibition. Overexpression of HNRNPQ in cells derived from oculopharyngeal muscular dystrophy patients can rescue defective autophagy.
Article
Genetics & Heredity
Tamir Biezuner, Yardena Brilon, Asaf Ben Arye, Barak Oron, Aditee Kadam, Adi Danin, Nili Furer, Mark D. Minden, Dennis Dong Hwan Kim, Shiran Shapira, Nadir Arber, John Dick, Paaladinesh Thavendiranathan, Yoni Moskovitz, Nathali Kaushansky, Noa Chapal-Ilani, Liran Shlush
Summary: Deep targeted sequencing technologies are not widely used in clinical practice due to complexity and cost. In this study, we sequenced a large cohort using Molecular Inversion Probes (MIP) technology and improved its performance in detecting low frequency variants and GC rich regions through statistical model enhancements and biochemical modifications.
NAR GENOMICS AND BIOINFORMATICS
(2022)