Article
Biochemistry & Molecular Biology
Ying Zou, Jiaqi Zhang, Jiawei Xu, Lanya Fu, Yizhou Xu, Xianghai Wang, Zhenlin Li, Lixin Zhu, Hao Sun, Hui Zheng, Jiasong Guo
Summary: SIRT6 plays a crucial role in macrophage function following peripheral nerve injury, with its inhibition impairing migration, phagocytosis, and M2 polarization of macrophages, thus suggesting it as a potential therapeutic target for peripheral nerve injury.
CELL AND BIOSCIENCE
(2021)
Article
Biochemical Research Methods
Mark Jayson Cortez, Hyukpyo Hong, Boseung Choi, Jae Kyoung Kim, Kresimir Josic
Summary: This study proposes a non-Markovian, hierarchical Bayesian inference framework for quantifying the variability of cellular processes within and across cells in a population. By using a delayed birth-death process, the proposed hierarchical framework is shown to be robust and leads to improved estimates compared to its non-hierarchical counterpart when applied to in silico and experimental data. The mean delays in protein production are reported to be larger than previously thought, with a coefficient of variation of around 0.2 across the population, and not strongly correlated with protein production or growth rates.
Review
Biochemistry & Molecular Biology
Yuichi Shichino, Shintaro Iwasaki
Summary: Many human diseases are caused by harmful protein production, and selectively suppressing protein synthesis can provide a unique path for drug development. The use of ribosome profiling technique uncovers the selectivity of translation repression by small molecules, facilitating rational drug design.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Neurosciences
Ran Wang, Tiantian Li, Sihao Diao, Chao Chen
Summary: This study demonstrates that PTP sigma inhibition can improve neurodevelopmental outcomes, promote white matter development, and modulate neuroinflammation and microglia/macrophage phenotype in a mouse model of preterm white matter injury (WMI).
EXPERIMENTAL NEUROLOGY
(2023)
Article
Chemistry, Multidisciplinary
Zhi Guo, Xun Zhang, Shihua Zhou
Summary: The output state of a sequential logic circuit is determined by both the input signal at that time and the original state of the circuit, so the ability of the sequential logic circuit to unveil history-dependent signals will contribute to our understanding of the ordered expression of genes. Here, we show a sequential logic circuit built on lambda exonuclease, capable of detecting the relative sequence between inputs and inhibiting the second signal response when the first signal activates the corresponding output signal.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Neurosciences
Elliot J. Glotfelty, Shih-Chang Hsueh, Quia Clayborne, Alicia Bedolla, Katherine O. Kopp, Tonya Wallace, Binhai Zheng, Yu Luo, Tobias E. Karlsson, Ross A. McDevitt, Lars Olson, Nigel H. Greig
Summary: Nogo proteins are negative regulators of CNS neurite outgrowth and repair. Recent research suggests a relationship between Nogo proteins and inflammation. In this study, microglial-specific Nogo knockout mice showed decreased tissue inflammation and altered behavior following traumatic brain injury.
Article
Oncology
Alexander Drilon, Manish R. Sharma, Melissa L. Johnson, Timothy A. Yap, Shirish Gadgeel, Dale Nepert, Gang Feng, Micaela B. Reddy, Allison S. Harney, Mohamed Elsayed, Adam W. Cook, Christina E. Wong, Ronald J. Hinklin, Yutong Jiang, Eric N. Brown, Nickolas A. Neitzel, Ellen R. Laird, Wen - Wu, Anurag Singh, Ping Wei, Keith A. Ching, John J. Gaudino, Patrice A. Lee, Dylan P. Hartley, S. Michael Rothenberg
Summary: PF-07284892, an allosteric SHP2 inhibitor, combined with various oncogenic driver inhibitors, overcame bypass-signaling-mediated resistance in clinical settings. This combination therapy showed significant tumor and circulating tumor DNA responses, extending the duration of overall clinical benefit in patients with targeted therapy resistance in lung, colorectal, ovarian, and pancreatic cancer.
Article
Immunology
Xiaowen Bi, Baolin Jiang, Jinyi Zhou, Xirui Fan, Xintong Yan, Juanjuan Liang, Lan Luo, Zhimin Yin
Summary: Inhibition of CBP bromodomain effectively blocks HMGB1-mediated inflammatory responses and reduces its pro-inflammatory activity. SGC-CBP30 down-regulates the activation of relevant signaling pathways to decrease the inflammatory effects of HMGB1.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Aidan Levine, Erika Liktor-Busa, Kelly L. Karlage, Luigi Giancotti, Daniela Salvemini, Todd W. Vanderah, Tally M. Largent-Milnes
Summary: Recent findings suggest that Clinical Endocannabinoid Deficiency is associated with pain disorders, and targeted regulation of the endocannabinoid system may induce headache pain. Inhibition of specific biosynthetic enzymes could lead to headache-like pain and photophobia, providing a valuable addition to headache models.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Payton L. Marshall, Nadine Nagy, Gernot Kaber, Graham L. Barlow, Amrit Ramesh, Bryan J. Xie, Miles H. Linde, Naomi L. Haddock, Colin A. Lester, Quynh-Lam Tran, Christiaan R. de Vries, Aviv Hargil, Andrey V. Malkovskiy, Irina Gurevich, Hunter A. Martinez, Hedwich F. Kuipers, Koshika Yadava, Xiangyue Zhang, Stephen P. Evanko, John A. Gebe, Xi Wang, Robert B. Vernon, Carol de la Motte, Thomas N. Wight, Edgar G. Engleman, Sheri M. Krams, Everett H. Meyer, Paul L. Bollyky
Summary: Treatment with 4-methylumbelliferone (4MU) reduces pericellular hyaluronan, disrupts interactions between DC and T-cells, and inhibits T-cell proliferation. 4MU can delay rejection of allogeneic pancreatic islet and cardiac transplants, as well as suppress allogeneic T-cell activation.
Article
Medicine, Research & Experimental
Elena Abbotto, Caterina Miro, Francesco Piacente, Annalisa Salis, Melania Murolo, Annarita Nappi, Enrico Millo, Eleonora Russo, Elena Cichero, Laura Sturla, Alberto Del Rio, Antonio De Flora, Alessio Nencioni, Monica Dentice, Santina Bruzzone
Summary: SIRT6 plays a critical role in cutaneous Squamous Cell Carcinoma (cSCC), with its silencing promoting cell differentiation and deletion preventing skin tumorigenesis. However, SIRT6 acts as a tumor suppressor in cSCC by enhancing glycolysis. The study investigated the pharmacological modulation of SIRT6 deacetylase activity using S6 (inhibitor) and MDL-800 (activator), with S6 recreating the effects of SIRT6 silencing and MDL-800 showing the opposite trend. In a mouse model, S6 treatment reduced the number and size of papillomas, while MDL-800 had an opposite effect.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Colin Carlock, Yunpeng Bai, Allison Paige-Hood, Qinglin Li, Frederick Nguele Meke, Zhong-Yin Zhang
Summary: Overexpression of PRL2 and reduced PTEN protein are frequently observed in patients with acute myeloid leukemia (AML). Inhibiting PRL2 can prolong animal survival and slow the accumulation of leukemia blasts in the bone marrow niche. This study provides evidence for the viability of PRL2 inhibition as a therapeutic strategy for improving clinical outcomes in AML and other PTEN-deficient cancers.
Article
Chemistry, Physical
Anika J. Friedman, Evan T. Liechty, Levi Kramer, Ankur Sarkar, Jerome M. Fox, Michael R. Shirts
Summary: Protein tyrosine phosphatases (PTPs) are potential drug targets for various diseases, but the design of selective therapeutics is complicated. This study investigates the allosteric inhibition of PTP1B by AD, an unusually selective inhibitor. Molecular dynamics simulations suggest that AD stably interacts with the allosterically influential region of PTP1B. The binding requires a disordered alpha 7 helix, contributing to the selectivity of AD. The findings indicate the potential of AD as a scaffold for building allosteric inhibitors of PTP1B.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemical Research Methods
Preeyanut Butmee, Gamolwan Tumcharern, Chomphunuch Songsiriritthigul, Marie Jose Durand, Gerald Thouand, Margaret Kerr, Kurt Kalcher, Anchalee Samphao
Summary: This study fabricated a novel enzymatic electrochemical biosensor for detecting glyphosate-based acid phosphatase inhibition. The biosensor functioned by measuring oxidation current through enzymatic reactions, and was successfully applied for selective analysis of glyphosate in actual samples.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2021)
Review
Cell Biology
Fernando Maestu, Willem de Haan, Marc Aurel Busche, Javier DeFelipe
Summary: Our incomplete understanding of the link between Alzheimer's Disease pathology and symptomatology hinders therapeutic success. Disturbance of neuronal activity, particularly an imbalance in underlying excitation/inhibition (E/I), plays a central role in connecting structural brain pathology and cognitive dysfunction in AD. While there are emerging options to influence this imbalance, the complexity of human brain dynamics complicates identification of an optimal approach.
AGEING RESEARCH REVIEWS
(2021)
Article
Plant Sciences
Julia Hartmann, Lisa Silbernagl, Gerald M. Schneeweiss, Michael H. J. Barfuss, Hanna Weiss-Schneeweiss, Peter Schoenswetter
Summary: The study aimed to address two questions related to the systematics of small-flowering Euphrasia species from the Eastern Alps. The research failed to find new populations of diploid E. inopinata, but discovered a new diploid species in the eastern Ortler/Ortles mountain range, which was named E. ultima. Based on the study, E. ultima was found to be morphologically and genetically distinct from tetraploid widespread E. minima and E. inopinata.
Review
Plant Sciences
Dennis J. Larsson, Da Pan, Gerald M. Schneeweiss
Summary: This review outlines the evolution of phylogeography studies of alpine plants in the past two decades, focusing on the recent approach of integrative distributional, demographic and coalescent (iDDC) modeling. By integrating distributional data with spatially explicit demographic modeling and subsequent coalescent simulations, the history of alpine species can be inferred and hypotheses can be effectively tested. Future prospects and improvements of iDDC are also discussed.
Article
Biochemistry & Molecular Biology
Fabrizio Chiti, Jeffery W. Kelly
Summary: Protein misfolding diseases are caused by structural abnormalities in proteins, and specific small molecules have been approved to stabilize the folded state of these proteins, providing a promising approach to treat such diseases.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aglaia Szukala, Jessica Lovegrove-Walsh, Hirzi Luqman, Simone Fior, Thomas M. Wolfe, Bozo Frajman, Peter Schoenswetter, Ovidiu Paun
Summary: Parallel evolution provides a powerful framework to study the evolutionary potential, constraints, repeatability, and predictability of populations. This study investigates gene expression and functional parallelism in different ecotypes of Heliosperma pusillum. The findings reveal a polygenic architecture for diverged adaptive traits, suggesting that polygenic traits play a key role in widening the adaptive potential of organisms.
Article
Chemistry, Medicinal
Nicholas L. Yan, Reji Nair, Alan Chu, Ian A. Wilson, Kristen A. Johnson, Gareth J. Morgan, Jeffery W. Kelly
Summary: This study investigates the potential of finding small molecule kinetic stabilizers in immunoglobulin light chain amyloidosis, identifying coumarin-based compounds with potential therapeutic effects. Structural-activity relationship data reveals that these compounds bind at different sites in the LC dimer, exerting unique stabilizing effects on LCs.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Ecology
Pau Carnicero, Johannes Wessely, Dietmar Moser, Xavier Font, Stefan Dullinger, Peter Schoenswetter
Summary: Besides bedrock preference, habitat specialization and dispersal ability also influence the postglacial expansion patterns of high-elevation plants. Species occupying a broad range of habitats are able to rapidly expand their ranges, while species with high habitat specialization exhibit slower expansion.
JOURNAL OF BIOGEOGRAPHY
(2022)
Article
Multidisciplinary Sciences
Philipp Kirschner, Manolo F. Perez, Eliska Zaveska, Isabel Sanmartin, Laurent Marquer, Birgit C. Schlick-Steiner, Nadir Alvarez, Florian M. Steiner, Peter Schoenswetter
Summary: Quaternary climatic oscillations had a significant impact on European biogeography, particularly on the Eurasian steppe biome. Through the analysis of plant and insect species, consistent demographic responses of expansion during cold stages and contraction during warm stages were observed. Climate was identified as a driving force underlying genetic variance patterns at the biome level.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Jaleh S. Mesgarzadeh, Isabelle C. Romine, Ethan M. Smith-Cohen, Julia M. D. Grandjean, Jeffery W. Kelly, Joseph C. Genereux, R. Luke Wiseman
Summary: This study identified ER proteostasis factors involved in ATF6-dependent reductions in destabilized TTR secretion through a mass-spectrometry-based interactomics approach. Activation of ATF6 reduces the secretion and subsequent aggregation of amyloidogenic TTR through increased interactions with ATF6-regulated ER proteostasis factors including BiP and PDIA4. PDIA4 retains destabilized TTR in the ER through a redox-independent mechanism. These findings provide a mechanistic basis for the therapeutic targeting of ATF6 activation to improve treatments for TTR-related amyloid diseases.
Article
Plant Sciences
Guillaume Wos, Erwann Arc, Karl Huelber, Veronika Konecna, Adam Knotek, Doubravka Pozarova, Clara Bertel, Dominik Kaplenig, Terezie Mandakova, Gilbert Neuner, Peter Schoenswetter, Ilse Kranner, Filip Kolar
Summary: Parallel local adaptation, when different genetic lineages independently adapt to the same selective environment, was investigated in Arabidopsis arenosa populations from four distinct mountain regions. The study found that the populations exhibited similar adaptive responses to elevation difference, indicating parallel local adaptation. The results highlight the role of divergent selection and provide experimental support for the repeatability of adaptive evolution.
JOURNAL OF ECOLOGY
(2022)
Article
Geriatrics & Gerontology
Mathew S. Maurer, Dia Smiley, Eli Simsolo, Fabrizio Remotti, Angela Bustamante, Sergio Teruya, Stephen Helmke, Andrew J. Einstein, Ronald Lehman, Jon T. Giles, Jeffery W. Kelly, Felix Tsai, William S. Blaner, Pierre-Jacques Brun, Ron Riesenburger, James Kryzanski, Cindy Varga, Ayan R. Patel
Summary: Lumbar spinal stenosis (LSS) is a common reason for spine surgery in older adults, with amyloid detected in over one third of patients, especially in those over 75 years old. Age, clinical symptoms, cardiac biomarkers, and other parameters did not differ significantly between patients with and without amyloid.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Cecilia Monteiro, Jaleh S. Mesgarzadeh, Joao Anselmo, Joana Fernandes, Marta Novais, Carla Rodrigues, David L. Powers, Evan T. Powers, Teresa Coelho, Jeffery W. Kelly
Summary: This study explored the relationship between TTR stabilization markers and clinical efficacy of tafamidis treatment. The results showed an increase in native TTR concentration and a decrease in non-native TTR concentration. However, changes in native and non-native TTR levels were not correlated with clinical response to tafamidis. Successful tafamidis therapy requires moderate TTR stabilization, and male patients may benefit from higher doses of tafamidis.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Felix J. J. Tsai, Luke T. T. Nelson, Gabriel M. M. Kline, Marcus Jager, John L. L. Berk, Yoshiki Sekijima, Evan T. T. Powers, Jeffery W. Kelly
Summary: This study investigated the plasma concentrations of diflunisal and its efficacy in treating TTR polyneuropathy, finding that at a certain concentration, diflunisal can effectively slow down TTR dissociation rate and inhibit aggregation.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Biodiversity Conservation
Jalil Noroozi, Masoud Minaei, Sina Khalvati, Akram Kaveh, Hanieh Nafisi, Behnaz Nazari, Golshan Zare, Ernst Vitek, Karl Huelber, Gerald M. Schneeweiss
Summary: This study aims to investigate the biodiversity hotspots and conservation status of subalpine-alpine habitats in Southwest Asia. Using distribution data of subalpine vascular plant species, the researchers identified hotspots and conservation gaps. The results show that a large proportion of these hotspots are unprotected, highlighting the need for new nature reserves in these areas.
DIVERSITY AND DISTRIBUTIONS
(2023)
Article
Biochemistry & Molecular Biology
Pau Carnicero, Joelle Kroell, Peter Schoenswetter
Summary: Hybridization and polyploidy play significant roles in plant evolution. Homoploid hybridization can generate new species or modify existing lineages. Although well-known, the evolutionary role of autopolyploidy may have been underestimated. Through studying saxifrages in the Pyrenees, this research aims to understand the evolutionary consequences and origin of hybridization and polyploidy. The results reveal multiple homoploid hybridization events and differentiate the tetraploid populations from their diploid parent. Additionally, the study confirms that S. pubescens and S. iratiana should be treated as separate species.
MOLECULAR PHYLOGENETICS AND EVOLUTION
(2023)
Article
Plant Sciences
Spela Pungarsek, Jasna Dolenc Koce, Martina Bacic, Michael H. J. Barfuss, Peter Schoenswetter, Bozo Frajman
Summary: This study examined the relationships among different species of Luzula sect. Luzula in the Eastern Alps using relative genome size and karyotype estimations, as well as AFLP fingerprinting. The study found the co-occurrence of multiple ploidies and species at the same localities, with partial fragmentation of chromosomes leading to the recurrent formation of agmatoploid individuals. Further research is needed to determine if this pattern is common in Luzula sect. Luzula and if ecological niche segregation supports the frequent co-occurrence of closely related cytotypes in mixed populations.
