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Conformational inhibitors of protein aggregation
Curr Opin Struct Biol. 2023 Sep 15;83:102700. doi: 10.1016/j.sbi.2023.102700. Online ahead of print.ABSTRACTAmyloidoses are fatal conditions associated with the aggregation of proteins into amyloid fibrils that deposit systemically and/or locally. Possibly because the causal mechanism of protein aggregation and deposition is not fully understood, this group of diseases remains uncurable. Advances in structural biology, such as the use of nuclear magnetic resonance and cryo-electron microscopy, have enabled the study of the structures and the conformational nature of the proteins whose aggregation is associated with the und...
Source: Current Opinion in Structural Biology - September 17, 2023 Category: Biology Authors: Mar ía Del Carmen Fernández Ramírez Shumaila Afrin Lorena Saelices Source Type: research
Asiatic acid protects against pressure overload-induced heart failure in mice by inhibiting mitochondria-dependent apoptosis
CONCLUSIONS: Our findings suggest that AA effectively combats chronic TAC-induced and hydrogen peroxide-induced cardiomyocyte apoptosis through a mitochondria-dependent mechanism. AA reduces cellular levels of oxidative stress and inhibits the activation of the JNK pathway, highlighting its potential therapeutic value in the treatment of HF.PMID:37717794 | DOI:10.1016/j.freeradbiomed.2023.09.015
Source: Free Radical Biology and Medicine - September 17, 2023 Category: Biology Authors: Junjie Du Dongmin Yu Jinghang Li Linjie Si Dawei Zhu Ben Li Yizhou Gao Lifu Sun Xufeng Wang Xiaowei Wang Source Type: research
Luteolin exhibits synergistic therapeutic efficacy with erastin to induce ferroptosis in colon cancer cells through the HIC1-mediated inhibition of GPX4 expression
This study aimed to examine the synergistic therapeutic impact of combining erastin with a bioactive flavonoid compound luteolin on the ferroptosis-mediated suppression of colon cancer. Human colon cancer HCT116 and SW480 cells were used for the in vitro studies and a xenograft of colon cancer model in BALB/c nude mice was established for the in vivo experiments. The results showed that combinative treatment of luteolin and erastin effectively inhibited the viability and proliferation of colon cancer cells. Luteolin and erastin cotreatment synergistically induced ferroptosis, concomitant with a reduction in glutathione and...
Source: Free Radical Biology and Medicine - September 17, 2023 Category: Biology Authors: Yinli Zheng Leyan Li Haipeng Chen Yuting Zheng Xuanjing Tan Guiyu Zhang Ruidi Jiang Hong Yu Senyi Lin Yijie Wei Ying Wang Rong Zhang Zhongqiu Liu Jinjun Wu Source Type: research
Hydroxyl radical generations form the physiologically relevant Fenton-like reactions
Free Radic Biol Med. 2023 Sep 15:S0891-5849(23)00637-8. doi: 10.1016/j.freeradbiomed.2023.09.013. Online ahead of print.ABSTRACTIron(II) species can participate in the Fenton and Fenton-like reactions to generate the hydroxyl radical that can oxidatively damage biomolecules and induce oxidative stress in biological systems. Many diseases, including neurodegeneration, cardiovascular disease and cancer, are associated with oxidative stress. However, it is proposed recently that hydroxyl radical would not be generated from the Fenton reaction under physiological conditions and thus would not cause oxidative stress in biologic...
Source: Free Radical Biology and Medicine - September 17, 2023 Category: Biology Authors: Zhongwei Zhao Source Type: research
Multi-element Exposure and Cognitive Function in Rural Elderly Chinese
Biol Trace Elem Res. 2023 Sep 16. doi: 10.1007/s12011-023-03774-1. Online ahead of print.ABSTRACTTo investigate the relationship between selenium (Se) based multi-element combined exposure and cognitive function in rural elderly individuals, a cross-sectional study was conducted. The study involved 416 older adults aged 60 and above, residing in four different areas of Enshi county, China, with varying soil Se levels. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to measure the concentrations of Se, copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), magnesium (Mg), cadmium (Cd), arsenic (As), and lead (P...
Source: Biological Trace Element Research - September 16, 2023 Category: Biology Authors: Lidan Duan Liqin Su Xiaohong He Yegang Du Yanying Duan Ning Xu Rangpeng Wu Yunfeng Zhu Ranqi Shao Frederick W Unverzagt Ann M Hake Yinlong Jin Sujuan Gao Source Type: research
Convergent reductive evolution and host adaptation in Mycoavidus bacterial endosymbionts of Mortierellaceae fungi
Fungal Genet Biol. 2023 Sep 14:103838. doi: 10.1016/j.fgb.2023.103838. Online ahead of print.ABSTRACTIntimate associations between fungi and intracellular bacterial endosymbionts are becoming increasingly well understood. Phylogenetic analyses demonstrate that bacterial endosymbionts of Mucoromycota fungi are related either to free-living Burkholderia or Mollicutes species. The so-called Burkholderia-related endosymbionts or BRE comprise Mycoavidus, Mycetohabitans and Candidatus Glomeribacter gigasporarum. These endosymbionts are marked by genome contraction thought to be associated with intracellular selection. However, t...
Source: Fungal Genetics and Biology - September 16, 2023 Category: Biology Authors: Kevin Amses Alessandro Desir ó Abigail Bryson Igor Grigoriev Stephen Mondo Anna Lipzen Kurt LaButti Robert Riley Vasanth Singan Paris Salazar-Hamm Jason King Elizabeth Ballou Teresa Pawlowska Rasheed Adeleke Gregory Bonito Jessie Uehling Source Type: research
Computing allostery: from the understanding of biomolecular regulation and the discovery of cryptic sites to molecular design
Curr Opin Struct Biol. 2023 Sep 14;83:102702. doi: 10.1016/j.sbi.2023.102702. Online ahead of print.ABSTRACTThe concept of allostery has become a central tenet in the study of biological systems. In parallel, the discovery of allosteric drugs is generating new opportunities to selectively modulate difficult targets involved in pathologic mechanisms. Molecular simulations can provide atomistically detailed insight into the processes involved in allosteric regulation and signaling, and at the same time, they have the potential to unveil regulatory hotspots or cryptic sites that are not immediately evident from the analysis o...
Source: Current Opinion in Structural Biology - September 16, 2023 Category: Biology Authors: Giorgio Colombo Source Type: research
Time resolved applications for Cryo-EM; approaches, challenges and future directions
Curr Opin Struct Biol. 2023 Sep 14;83:102696. doi: 10.1016/j.sbi.2023.102696. Online ahead of print.ABSTRACTDevelopments within the cryo-EM field have allowed us to generate higher-resolution "static" structures and pull out different conformational states which exist at equilibrium within the sample. Moreover, to trap non-equilibrium states and determine conformations that are present after a defined period of time (typically in the ms time frame) new approaches have been developed for the application of time-resolved cryo-EM. Here we give an overview of these different approaches and the limitations and strengths of each...
Source: Current Opinion in Structural Biology - September 16, 2023 Category: Biology Authors: David P Klebl Louie Aspinall Stephen P Muench Source Type: research
Conformational entropy in molecular recognition of intrinsically disordered proteins
Curr Opin Struct Biol. 2023 Sep 14;83:102697. doi: 10.1016/j.sbi.2023.102697. Online ahead of print.ABSTRACTBroad conformational ensembles make intrinsically disordered proteins or regions entropically intriguing. Although methodologically challenging and understudied, emerging studies into their changes in conformational entropy (ΔS°conf) upon complex formation have provided both quantitative and qualitative insight. Recent work based on thermodynamics from isothermal titration calorimetry and NMR spectroscopy uncovers an expanded repertoire of regulatory mechanisms, where ΔS°conf plays roles in partner selection, sta...
Source: Current Opinion in Structural Biology - September 16, 2023 Category: Biology Authors: Karen Skriver Frederik Friis Theisen Birthe B Kragelund Source Type: research
Progressive computational approaches to facilitate decryption of allosteric mechanism and drug discovery
Curr Opin Struct Biol. 2023 Sep 14;83:102701. doi: 10.1016/j.sbi.2023.102701. Online ahead of print.ABSTRACTAllostery is a ubiquitous biological phenomenon where perturbation at topologically distal areas of a protein serves as a trigger to fine-tune the orthosteric site and thus regulate protein function. The investigation of allosteric regulation greatly enhances our understanding of human diseases and broadens avenue for drug discovery. For decades, owing to the difficulty in allostery characterization through serendipitous experimental screening, researchers have developed several innovative computational approaches, w...
Source: Current Opinion in Structural Biology - September 16, 2023 Category: Biology Authors: Xun Lu Xiaobing Lan Shaoyong Lu Jian Zhang Source Type: research
Trade liberalization and nutrition transition: Evidence from China
Econ Hum Biol. 2023 Sep 9;51:101304. doi: 10.1016/j.ehb.2023.101304. Online ahead of print.ABSTRACTWe examine the impact of trade liberalization on the nutrition transition between 1997 and 2011. Our findings demonstrate that the reduction in tariff rates has had a significant effect on the dietary patterns of both rural and urban residents in the country. With the decrease in tariffs, there has been a noticeable increase in the consumption of animal products (such as meat and aquatic products), vegetables, beans and nuts, as well as packaged and processed foods. Simultaneously, there has been a decrease in the demand for ...
Source: Economics and Human Biology - September 16, 2023 Category: Biology Authors: Xu Tian Faqin Lin Source Type: research
Genome and transcriptome of Selaginella kraussiana reveal evolution of root apical meristems in vascular plants
Curr Biol. 2023 Sep 6:S0960-9822(23)01141-7. doi: 10.1016/j.cub.2023.08.061. Online ahead of print.ABSTRACTThe evolution of roots allowed vascular plants to adapt to land environments. Fossil evidence indicates that roots evolved independently in euphyllophytes (ferns and seed plants) and lycophytes, the two lineages of extant vascular plants. Based on a high-quality genome assembly, mRNA sequencing (mRNA-seq) data, and single-cell RNA-seq data for the lycophyte Selaginella kraussiana, we show that the two root origin events in lycophytes and euphyllophytes adopted partially similar molecular modules in the regulation of r...
Source: Current Biology - September 16, 2023 Category: Biology Authors: Wu Liu Gui Cai Ning Zhai Hua Wang Tengfei Tang Yuyun Zhang Zhiyao Zhang Lijun Sun Yijing Zhang Tom Beeckman Lin Xu Source Type: research
Orbitofrontal cortex conveys stimulus and task information to the auditory cortex
Curr Biol. 2023 Sep 12:S0960-9822(23)01139-9. doi: 10.1016/j.cub.2023.08.059. Online ahead of print.ABSTRACTAuditory cortical neurons modify their response profiles in response to numerous external factors. During task performance, changes in primary auditory cortex (A1) responses are thought to be driven by top-down inputs from the orbitofrontal cortex (OFC), which may lead to response modification on a trial-by-trial basis. While OFC neurons respond to auditory stimuli and project to A1, the function of OFC projections to A1 during auditory tasks is unknown. Here, we observed the activity of putative OFC terminals in A1 ...
Source: Current Biology - September 16, 2023 Category: Biology Authors: Jonah K Mittelstadt Patrick O Kanold Source Type: research
Microtubule detyrosination by VASH1/SVBP is regulated by the conformational state of tubulin in the lattice
Curr Biol. 2023 Sep 5:S0960-9822(23)01001-1. doi: 10.1016/j.cub.2023.07.062. Online ahead of print.ABSTRACTTubulin, a heterodimer of α- and β-tubulin, is a GTPase that assembles into microtubule (MT) polymers whose dynamic properties are intimately coupled to nucleotide hydrolysis. In cells, the organization and dynamics of MTs are further tuned by post-translational modifications (PTMs), which control the ability of MT-associated proteins (MAPs) and molecular motors to engage MTs. Detyrosination is a PTM of α-tubulin, wherein its C-terminal tyrosine residue is enzymatically removed by either the vasohibin (VASH) or MT-...
Source: Current Biology - September 16, 2023 Category: Biology Authors: Yang Yue Takashi Hotta Takumi Higaki Kristen J Verhey Ryoma Ohi Source Type: research
Genome and transcriptome of Selaginella kraussiana reveal evolution of root apical meristems in vascular plants
Curr Biol. 2023 Sep 6:S0960-9822(23)01141-7. doi: 10.1016/j.cub.2023.08.061. Online ahead of print.ABSTRACTThe evolution of roots allowed vascular plants to adapt to land environments. Fossil evidence indicates that roots evolved independently in euphyllophytes (ferns and seed plants) and lycophytes, the two lineages of extant vascular plants. Based on a high-quality genome assembly, mRNA sequencing (mRNA-seq) data, and single-cell RNA-seq data for the lycophyte Selaginella kraussiana, we show that the two root origin events in lycophytes and euphyllophytes adopted partially similar molecular modules in the regulation of r...
Source: Current Biology - September 16, 2023 Category: Biology Authors: Wu Liu Gui Cai Ning Zhai Hua Wang Tengfei Tang Yuyun Zhang Zhiyao Zhang Lijun Sun Yijing Zhang Tom Beeckman Lin Xu Source Type: research
