Review
Cell Biology
Mei Jiang, Se Eun Jang, Li Zeng
Summary: In the mammalian brain, neurogenesis occurs mainly in the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles, as well as other nonclassic neurogenic areas. Neural stem cells (NSCs) differentiate into neurons and integrate into existing neural networks during prenatal and early postnatal development. Impairments in neurogenesis can lead to brain dysfunction and neurological disorders. This review summarizes the properties and mechanisms of neurogenic niches, discusses the influence of extrinsic and intrinsic factors on neurogenesis, and explores the impact of SARS-CoV-2 infection on neurological sequelae.
Article
Biochemistry & Molecular Biology
Saifeng Cheng, Markus Mittnenzweig, Yoav Mayshar, Aviezer Lifshitz, Marko Dunjic, Yoach Rais, Raz Ben-Yair, Stephanie Gehrs, Elad Chomsky, Zohar Mukamel, Hernan Rubinstein, Katharina Schlereth, Netta Reines, Ayelet-Hashahar Orenbuch, Amos Tanay, Yonatan Stelzer
Summary: By using temporal single-cell atlases, this study reveals that the loss of TET genes in mice leads to embryonic developmental failure. Tet-mutant cells can retain near-complete differentiation potential when developing within a wild-type embryo, but embryos solely composed of mutant cells exhibit defects in epiblast to ectoderm transition and degenerated mesoderm potential.
Article
Materials Science, Multidisciplinary
Hong Li, Qing-Xiang Pei, Zhen-Dong Sha, Paulo S. Branicio
Summary: The study investigates the fracture toughness of metallic glasses, finding that cooling rate and strain rate play a crucial role in increasing toughness. Additionally, the fracture toughness decreases as temperature increases.
MECHANICS OF MATERIALS
(2021)
Article
Multidisciplinary Sciences
Chatchai Phoomak, Wei Cui, Thomas J. Hayman, Seok-Ho Yu, Peng Zhao, Lance Wells, Richard Steet, Joseph N. Contessa
Summary: This study demonstrates that cells lacking the SSR3 or SSR4 subunits can restore N-glycosylation over time and reduce the transcriptional signature of ER stress. The protein levels of the SSR3 subunit are dependent on ER stress and UBE2J1, coordinating upstream N-glycosylation proficiency with downstream ER-associated degradation and proteostasis. The TRAP complex plays a regulatory role in maintaining ER glycoprotein quality control under stress conditions in both non-transformed and tumor cells.
Article
Chemistry, Multidisciplinary
Jialin Liu, Bo Cheng, Xinqi Fan, Xinyue Zhou, Jiankun Wang, Wen Zhou, Hengyu Li, Wenfeng Zeng, Pengyuan Yang, Xing Chen
Summary: Proteins are extensively modified with glycans of different structures, making it challenging to map the protein glycosylation landscape. This study presents Click-iG, a method that enables the simultaneous enrichment and profiling of three types of intact glycopeptides using metabolic labeling of glycans, optimized mass spectrometry, and tailored software analysis. Click-iG was able to identify thousands of intact glycosites in cell lines and living mice, providing comprehensive coverage of the protein glycosylation landscape and laying the foundation for investigating crosstalk between different glycosylation pathways.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Kaipamangalath Aswathi, R. Neenu Lekshmi, Matjaz Valant, Mojca Vrcon Mihelj, Manoj R. Varma
Summary: The perovskite Pr2CuMnO6 exhibits an orthorhombic crystal structure with high resistivity and semiconductor-like temperature behavior. Magnetic ordering occurs at 55 K followed by a cluster glass phase below 22 K. The conduction process follows variable range hopping of polarons.
JOURNAL OF ALLOYS AND COMPOUNDS
(2021)
Article
Chemistry, Inorganic & Nuclear
Hongwei Ming, Chen Zhu, Tao Chen, Shuhuan Yang, Yong Chen, Hongxing Xin, Jian Zhang, Di Li, Xiaoying Qin
Summary: Current understanding of the intrinsic point defects and potential extrinsic dopants in p-type Cu2SnSe3 is limited. The dominant intrinsic defects in Cu(2)SnSe(3) are Cu-Sn and V-Cu under different chemical conditions. The substitution of Al, Ga, In, Cd, Zn, Fe, and Mn for Sn can inhibit the formation of V-Cu, while introducing Cu-Sn, Fe-Sn, Mn-Sn, and Ni-Cu defects can enhance electronic density of states. Introducing Ag-Cu, Al-Sn, Zn-Sn, Ge-Sn, and Mn-Sn defects can lower lattice thermal conductivity remarkably, providing insights for improving the thermoelectric properties.
INORGANIC CHEMISTRY
(2023)
Article
Materials Science, Multidisciplinary
Xingyu Wang, Chunlin Ma, Xiaoxiong Wang, Weiping Zhou, Weishi Tan
Summary: The magnetic properties of N-implanted MgO single crystals were studied, revealing that the enhanced ferromagnetism is attributed to the synergistic effects of Mg vacancies and N-related defects in the samples. First principle calculations also suggest that ferromagnetism mainly originates from specific defect configurations.
MATERIALS RESEARCH EXPRESS
(2021)
Article
Immunology
Benjamin Samuel Haslund-Gourley, Stephane Grauzam, Anand S. Mehta, Brian Wigdahl, Mary Ann Comunale
Summary: In this study, the researchers found that the glycosylation profile of IgG changes during acute Lyme disease infection, which is different from the classic proinflammatory IgG glycan signature. Additionally, IgG glycans detected during acute Lyme disease infection can effectively distinguish between control, acute, and treated cohorts.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Astronomy & Astrophysics
Eileen Sophie Giesel, Basundhara Ghosh, Bjoern Malte Schaefer
Summary: This paper generalizes the linear model of galaxy intrinsic alignments to include intrinsic flexions. The model links the third moments of brightness distribution with distortions of elliptical galaxies caused by third derivatives of the gravitational potential or gradients of the tidal gravitational fields. The study finds that the spectra of intrinsic flexions are typically an order of magnitude smaller than lensing flexions and shows a negative cross-correlation between intrinsic and extrinsic gravitational flexions. The observability of intrinsic and extrinsic flexions is also quantified using the Fisher formalism, with the findings suggesting that intrinsic flexions are challenging to measure and may only be detectable under highly optimistic conditions.
MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY
(2022)
Article
Materials Science, Multidisciplinary
Da-Kun Zhou, Zhi-Fan Zhang, Xiao-Qin Yu, Zhen-Gang Zhu, Gang Su
Summary: This theoretical study investigates the intrinsic and extrinsic differences between nonlinear thermal Hall effects in the presence of disorder, finding distinct dependencies on temperature that allow for easy differentiation between the two types of contributions.
Article
Materials Science, Multidisciplinary
Zheng-Yang Zhuang, Zhongbo Yan
Summary: Three-dimensional Hopf insulators are a new class of topological phases. At the critical point of the transition between two distinct Hopf insulators with rotational symmetry, point Berry dipoles with unique Berry curvature structures lead to special quantization of Berry flux. Near the Berry-dipole transitions, the extrinsic and intrinsic nonlinear Hall conductivity tensors are characterized by universal functions and are proportional to the change in Hopf invariant. Our work establishes a correspondence between nonlinear Hall effects and Hopf invariants.
Article
Materials Science, Multidisciplinary
Seung-Hwan Do, Joseph A. M. Paddison, Gabriele Sala, Travis J. Williams, Koji Kaneko, Keitaro Kuwahara, Andrew F. May, Jiaqiang Yan, Michael A. McGuire, Matthew B. Stone, Mark D. Lumsden, Andrew D. Christianson
Summary: This article introduces a critical step in determining and explaining the presence of a gap at a magnon crossing point to characterize the topological properties of a material. Through neutron scattering measurements of CrCl3, the study finds that the scattering intensity near the crossing point is highly sensitive to experimental conditions, affecting the apparent topological gap size. The study provides an explanation for discrepancies between spectroscopic and first-principles estimates of gap sizes and offers guidelines for accurately measuring topological magnon gaps.
Article
Chemistry, Medicinal
Matthew C. Chan, Diwakar Shukla
Summary: Membrane transporters of the SLC6 family play important roles in physiological processes. This study investigated the impact of glycosylation on the dynamics of these transporters through molecular dynamics simulations. The results suggest that glycosylation affects the dynamics of the glycosylated extracellular loop and surrounding regions, but has no significant effect on the structure and conformational dynamics associated with substrate transport.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemical Research Methods
Jaclyn Gowen Kalmar, Kenneth P. Garrard, David C. Muddiman
Summary: Glycans play important roles in biological activities, but their diverse and complex structures require multiple analytical techniques to solve glycomics problems. The development of various chemical derivatization strategies and bioinformatic software has led to significant analytical advances in the field of glycomics, such as the INLIGHT strategy.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Multidisciplinary Sciences
Xin Jiang, Richard Labaudiniere, Joel N. Buxbaum, Cecilia Monteiro, Marta Novais, Teresa Coelho, Jeffery W. Kelly
Summary: This study investigated the diagnosis and treatment methods for TTR amyloidoses, highlighting the use of NNTTR in diagnosing FAP and the significant reduction of NNTTR levels in patients receiving treatment, even in nonresponders. High levels of NNTTR were associated with poor clinical response to the treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Nicholas L. Yan, Diogo Santos-Martins, Reji Nair, Alan Chu, Ian A. Wilson, Kristen A. Johnson, Stefano Forli, Gareth J. Morgan, H. Michael Petrassi, Jeffery W. Kelly
Summary: The study identified drugs that could stabilize immunoglobulin light chains, suppressing protein aggregation through enhanced affinity. Analysis revealed potential stabilizers, which could improve the stability of the light chains, with some showing significant enhancement in affinity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Maziar S. Ardejani, Louis Noodleman, Evan T. Powers, Jeffery W. Kelly
Summary: The study demonstrates that stereoelectronic effects play a role in stabilizing protein-N-glycan interactions, with enthalpy-entropy compensation depending on the electronics of interacting side chains. Models using quantum mechanical calculations and machine learning can explain up to 79% and 97% of the experimental interaction energy variability.
Article
Multidisciplinary Sciences
Dorit Trudler, Kristopher L. Nazor, Yvonne S. Eisele, Titas Grabauskas, Nima Dolatabadi, James Parker, Abdullah Sultan, Zhenyu Zhong, Marshall S. Goodwin, Yona Levites, Todd E. Golde, Jeffery W. Kelly, Michael R. Sierks, Nicholas J. Schork, Michael Karin, Rajesh Ambasudhan, Stuart A. Lipton
Summary: Parkinson's disease is associated with the accumulation of alpha-synuclein and activation of microglia, potentially leading to neuronal death. This study shows that alpha-synuclein can activate NLRP3 inflammasome in human microglia and that alpha-synuclein-antibody complexes can exacerbate inflammation in a human context.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
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)
Review
Biochemistry & Molecular Biology
Gabriel M. Kline, Karina Nugroho, Jeffery W. Kelly
Summary: In this review, we examine the application of Inverse Drug Discovery method using organic compounds of intermediate complexity harboring Sulfur(VI)-fluoride exchange (SuFEx) electrophiles to expand the cellular proteins that can be targeted covalently.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Meng Wang, Edmund Cotter, Ya-Juan Wang, Xu Fu, Angela L. Whittsette, Joseph W. Lynch, R. Luke Wiseman, Jeffery W. Kelly, Angelo Keramidas, Ting-Wei Mu
Summary: This study demonstrates that pharmacologically enhancing endoplasmic reticulum (ER) proteostasis can increase the assembly, trafficking, and surface expression of variant GABA(A) receptors, offering a potential opportunity to mitigate pathology associated with genetic epilepsy and other disease-associated variant ion channels.
CELL AND BIOSCIENCE
(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
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
Biochemistry & Molecular Biology
Felix J. Tsai, Marcus Jaeger, Teresa Coelho, Evan T. Powers, Jeffery W. Kelly
Summary: This study investigates whether adding tafamidis to cerebrospinal fluid (CSF) stabilizes the TTR protein in healthy donors and patients with hereditary transthyretin amyloidosis (ATTRv). The results show that tafamidis can stabilize the TTR protein in CSF to a clinically meaningful extent.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Gabriel M. Kline, Ryan J. Paxman, Chung-Yon Lin, Nicole Madrazo, Leonard Yoon, Julia M. D. Grandjean, Kyunga Lee, Karina Nugroho, Evan T. Powers, R. Luke Wiseman, Jeffery W. Kelly
Summary: AA132 activates the unfolded protein response (UPR) by metabolically activating and covalently modifying proteins, particularly PDIs, more extensively than AA147. The lower reactivity of activated AA132 allows it to persist longer and modify more proteins, leading to a global UPR activation.
ACS CHEMICAL BIOLOGY
(2023)