{"title":"Postdocs are doing it for themselves: peer mentorship and why it matters","authors":"Peter S Myers, Catherine R. Hoyt","doi":"10.36069/jols/20220301","DOIUrl":"https://doi.org/10.36069/jols/20220301","url":null,"abstract":"","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42522355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher B Erickson, Ryan Hill, Donna Pascablo, Galateia Kazakia, Kirk Hansen, Chelsea Bahney
While most bones fully self-heal, certain diseases require bone allograft to assist with fracture healing. Bone allografts offer promise as treatments for such fractures due to their osteogenic properties. However, current bone allografts made of decellularized bone extracellular matrix (ECM) have high failure rates, and thus grafts which improve fracture healing outcomes are needed. Understanding specific changes to the ECM proteome during normal fracture healing would enable the identification of key proteins that could be used enhance osteogenicity of bone allograft. Here, we performed a timeseries analysis of the fracture callus in mice to investigate proteomic and mineralization changes to the ECM at key stages of fracture healing. We found that changes to the ECM proteome largely coincide with the distinct phases of fracture healing. Basement membrane proteins (AGRN, COL4, LAMA), cartilage proteins (COL2A1, ACAN), and collagen crosslinking enzymes (LOXL, PLOD, ITIH) were initially upregulated, followed by bone specific proteoglycans and collagens (IBSP, COL1A1). Various tissue proteases (MMP2, 9, 13, 14; CTSK, CTSG, ELANE) were expressed at different levels throughout fracture healing. These changes coordinated with mineralization of the fracture callus, which increased steeply during the initial stages of healing. Interestingly the later timepoint was characterized by a response to wound healing and high expression of clotting factors (F2, 7, 9, 10). We identified ELANE and ITIH2 as tissue remodeling enzymes having no prior known involvement with fracture healing. This data can be further mined to identify regenerative proteins for enhanced bone graft design.
{"title":"A timeseries analysis of the fracture callus extracellular matrix proteome during bone fracture healing.","authors":"Christopher B Erickson, Ryan Hill, Donna Pascablo, Galateia Kazakia, Kirk Hansen, Chelsea Bahney","doi":"10.36069/JoLS/20220601","DOIUrl":"https://doi.org/10.36069/JoLS/20220601","url":null,"abstract":"<p><p>While most bones fully self-heal, certain diseases require bone allograft to assist with fracture healing. Bone allografts offer promise as treatments for such fractures due to their osteogenic properties. However, current bone allografts made of decellularized bone extracellular matrix (ECM) have high failure rates, and thus grafts which improve fracture healing outcomes are needed. Understanding specific changes to the ECM proteome during normal fracture healing would enable the identification of key proteins that could be used enhance osteogenicity of bone allograft. Here, we performed a timeseries analysis of the fracture callus in mice to investigate proteomic and mineralization changes to the ECM at key stages of fracture healing. We found that changes to the ECM proteome largely coincide with the distinct phases of fracture healing. Basement membrane proteins (AGRN, COL4, LAMA), cartilage proteins (COL2A1, ACAN), and collagen crosslinking enzymes (LOXL, PLOD, ITIH) were initially upregulated, followed by bone specific proteoglycans and collagens (IBSP, COL1A1). Various tissue proteases (MMP2, 9, 13, 14; CTSK, CTSG, ELANE) were expressed at different levels throughout fracture healing. These changes coordinated with mineralization of the fracture callus, which increased steeply during the initial stages of healing. Interestingly the later timepoint was characterized by a response to wound healing and high expression of clotting factors (F2, 7, 9, 10). We identified ELANE and ITIH2 as tissue remodeling enzymes having no prior known involvement with fracture healing. This data can be further mined to identify regenerative proteins for enhanced bone graft design.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"3 4","pages":"1-30"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236279/pdf/nihms-1812454.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40403570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reactive oxygen species is one of the most common cellular RNA damaging agents in living organisms. A growing number of studies show a strong correlation between oxidatively damaged RNA and human diseases, predominantly age-related neurodegenerative disorders. Oxidized RNAs impair the fundamental cellular processes including gene regulatory activities and protein synthesis. Molecular characterization of oxidized RNA such as understanding the sources of RNA oxidation, their mechanism of action, and cellular consequences may help to unravel their involvement in the pathogenesis of human diseases. Several proteins and factors with potential function to control RNA oxidation have been identified. Here, we will discuss the role of oxidized RNA binding protein polynucleotide phosphorylase (PNPase) in the quality control of oxidized RNA. PNPase is an evolutionarily conserved 3’-5’ exoribonuclease having multifaceted RNA regulatory roles. Apart from binding to oxidized RNA, PNPase reduces the level of RNA oxidation and protects cells during oxidative stress. In this review, we discuss RNA oxidation and its quality control process with a specific focus on PNPase in regulating oxidized RNA.
{"title":"RNA oxidation: Role of polynucleotide phosphorylase in the quality control of oxidized RNA","authors":"Sulochan Malla, Alexander Kwakye","doi":"10.36069/jols/20210603","DOIUrl":"https://doi.org/10.36069/jols/20210603","url":null,"abstract":"Reactive oxygen species is one of the most common cellular RNA damaging agents in living organisms. A growing number of studies show a strong correlation between oxidatively damaged RNA and human diseases, predominantly age-related neurodegenerative disorders. Oxidized RNAs impair the fundamental cellular processes including gene regulatory activities and protein synthesis. Molecular characterization of oxidized RNA such as understanding the sources of RNA oxidation, their mechanism of action, and cellular consequences may help to unravel their involvement in the pathogenesis of human diseases. Several proteins and factors with potential function to control RNA oxidation have been identified. Here, we will discuss the role of oxidized RNA binding protein polynucleotide phosphorylase (PNPase) in the quality control of oxidized RNA. PNPase is an evolutionarily conserved 3’-5’ exoribonuclease having multifaceted RNA regulatory roles. Apart from binding to oxidized RNA, PNPase reduces the level of RNA oxidation and protects cells during oxidative stress. In this review, we discuss RNA oxidation and its quality control process with a specific focus on PNPase in regulating oxidized RNA.","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47570667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer heterogeneity and development of resistance is the main limiting factor for the management and treatment of the disease. However, major technological innovations in precision medicine and immunebased therapies have renewed faith in having a cure for different types of cancers. Classical cancer treatment options include chemotherapy, radiotherapy, and immunotherapy. Emergence of novel tumor targeting bacteria could open up new therapeutic avenues. Bacteriotherapy alone or in conjunction with classical cancer therapies has given promising results on local tumor regression and distant metastasis. Moreover, bacteria exhibit direct anti-cancer effects that subsequently aid in the activation of innate and adaptive anti-tumor immune responses. Overall, genetically reprogrammed bacterial vectors holds great potential for the specific targeting of cancers as delivery vehicles. In this review article, we have reviewed the therapeutic potential of bacteriotherapy as monotherapy or combination therapy and discussed its benefits, challenges, and future directions.
{"title":"Bacteria: our ally in the fight against cancer","authors":"B. Kushwaha, Manish Charan","doi":"10.36069/jols/20210601","DOIUrl":"https://doi.org/10.36069/jols/20210601","url":null,"abstract":"Cancer heterogeneity and development of resistance is the main limiting factor for the management and treatment of the disease. However, major technological innovations in precision medicine and immunebased therapies have renewed faith in having a cure for different types of cancers. Classical cancer treatment options include chemotherapy, radiotherapy, and immunotherapy. Emergence of novel tumor targeting bacteria could open up new therapeutic avenues. Bacteriotherapy alone or in conjunction with classical cancer therapies has given promising results on local tumor regression and distant metastasis. Moreover, bacteria exhibit direct anti-cancer effects that subsequently aid in the activation of innate and adaptive anti-tumor immune responses. Overall, genetically reprogrammed bacterial vectors holds great potential for the specific targeting of cancers as delivery vehicles. In this review article, we have reviewed the therapeutic potential of bacteriotherapy as monotherapy or combination therapy and discussed its benefits, challenges, and future directions.","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47151087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Balkrishna, P. Thakur, Shivam Singh, Namita Singh, A. Tanwar, R. Sharma
SARS-CoV-2 causes COVID-19, a life-threatening respiratory illness with high rates of morbidity and mortality. As of date, there is no specific medicine to treat COVID-19. Therefore, there is an acute need to identify evidence-based holistic and safe mitigators. The present study aims to screen phytochemicals based on bioprospection analysis and subsequently predicting their binding potential to SARS-CoV-2 proteins in silico. The drug likeliness and ADMETox descriptors of 24 phytoligands were computationally predicted. Docking studies were further conducted with those phytoligands that qualified the drug likeliness parameters. Docking studies suggested that the herbal moiety, namely, gamma-glutamyl-S-allylcysteine demonstrated highly significant binding energies with viral spike glycoprotein, endoribonuclease, and main protease (binding energy ≥ -490 kcal/mol for all the tested target viral proteins). Gamma-glutamyl-S-allylcysteine demonstrated more significant binding potential as compared to the known chemical analog, i.e., hydroxychloroquine, as observed in the computational docking studies. This study serves to present pre-eminent information for further clinical studies highlighting the utility of herbal ligands as probable lead molecules for mitigating novel Coronavirus infection.
SARS-CoV-2会导致COVID-19,这是一种危及生命的呼吸系统疾病,发病率和死亡率都很高。到目前为止,还没有治疗COVID-19的特异性药物。因此,迫切需要确定以证据为基础的全面和安全的缓解措施。本研究旨在基于生物前景分析筛选植物化学物质,并随后预测其与SARS-CoV-2蛋白的结合潜力。对24种植物配体的药物似然性和ADMETox描述符进行了计算预测。进一步与符合药物似然参数的植物配体进行对接研究。对接研究表明,草药部分,即γ -谷氨酰胺- s -丙氨酸半胱氨酸与病毒刺突糖蛋白、核糖核酸内切酶和主要蛋白酶的结合能非常显著(所有测试的目标病毒蛋白的结合能均≥-490 kcal/mol)。在计算对接研究中观察到,与已知的化学类似物,即羟氯喹相比,γ -谷氨酰- s -丙氨酸半胱氨酸表现出更显著的结合潜力。本研究为进一步的临床研究提供了卓越的信息,突出了草药配体作为减轻新型冠状病毒感染的可能铅分子的效用。
{"title":"In silico screening for investigating the potential activity of phytoligands against SARS-CoV-2","authors":"A. Balkrishna, P. Thakur, Shivam Singh, Namita Singh, A. Tanwar, R. Sharma","doi":"10.36069/JOLS/20210302","DOIUrl":"https://doi.org/10.36069/JOLS/20210302","url":null,"abstract":"SARS-CoV-2 causes COVID-19, a life-threatening respiratory illness with high rates of morbidity and mortality. As of date, there is no specific medicine to treat COVID-19. Therefore, there is an acute need to identify evidence-based holistic and safe mitigators. The present study aims to screen phytochemicals based on bioprospection analysis and subsequently predicting their binding potential to SARS-CoV-2 proteins in silico. The drug likeliness and ADMETox descriptors of 24 phytoligands were computationally predicted. Docking studies were further conducted with those phytoligands that qualified the drug likeliness parameters. Docking studies suggested that the herbal moiety, namely, gamma-glutamyl-S-allylcysteine demonstrated highly significant binding energies with viral spike glycoprotein, endoribonuclease, and main protease (binding energy ≥ -490 kcal/mol for all the tested target viral proteins). Gamma-glutamyl-S-allylcysteine demonstrated more significant binding potential as compared to the known chemical analog, i.e., hydroxychloroquine, as observed in the computational docking studies. This study serves to present pre-eminent information for further clinical studies highlighting the utility of herbal ligands as probable lead molecules for mitigating novel Coronavirus infection.","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42851039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T cells are an integral component of the adaptive immune response via the recognition of peptides by the cell surface-expressed T cell receptor (TCR). Rearrangement of the TCR genes results in a highly polymorphic repertoire on the T cells within a given individual. Although the diverse repertoire is beneficial for immune responses to foreign pathogens, recognition of self-peptides by T cells can contribute to the development of autoimmune disorders. Increasing evidence supports a pathogenic role for T cells in autoimmune pathology, and it is of interest to determine the TCR repertoires involved in autoimmune disease development. In this review, we summarize methodologies and advancements in the TCR sequencing field and discuss recent studies focused on TCR sequencing in a variety of autoimmune conditions. The rapidly evolving methodology of TCR sequencing has the potential to allow for a better understanding of autoimmune disease pathogenesis, identify disease-specific biomarkers, and aid in developing therapies to prevent and treat a number of these disorders.
{"title":"T cell receptor sequencing in autoimmunity.","authors":"Angela M Mitchell, Aaron W Michels","doi":"10.36069/jols/20201203","DOIUrl":"https://doi.org/10.36069/jols/20201203","url":null,"abstract":"<p><p>T cells are an integral component of the adaptive immune response via the recognition of peptides by the cell surface-expressed T cell receptor (TCR). Rearrangement of the TCR genes results in a highly polymorphic repertoire on the T cells within a given individual. Although the diverse repertoire is beneficial for immune responses to foreign pathogens, recognition of self-peptides by T cells can contribute to the development of autoimmune disorders. Increasing evidence supports a pathogenic role for T cells in autoimmune pathology, and it is of interest to determine the TCR repertoires involved in autoimmune disease development. In this review, we summarize methodologies and advancements in the TCR sequencing field and discuss recent studies focused on TCR sequencing in a variety of autoimmune conditions. The rapidly evolving methodology of TCR sequencing has the potential to allow for a better understanding of autoimmune disease pathogenesis, identify disease-specific biomarkers, and aid in developing therapies to prevent and treat a number of these disorders.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"2 4","pages":"38-58"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757640/pdf/nihms-1652253.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38752722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lysosomes, membrane-bound organelles, play important roles in cellular processes including endocytosis, phagocytosis, and autophagy. Lysosomes maintain cellular homeostasis by generating a highly acidic environment of pH 4.5 - 5.0 and by housing hydrolytic enzymes that degrade engulfed biomolecules. Impairment of lysosomal function, especially in its acidification, is a driving force in the pathogenesis of diseases including neurodegeneration, cancer, metabolic disorders, and infectious diseases. Therefore, lysosomal pH is an attractive and targetable site for therapeutic intervention. Currently, there is a dearth of strategies or materials available to specifically modulate lysosomal acidification. This review focuses on the key aspects of how lysosomal pH is implicated in various diseases and discusses design strategies and molecular or nanoscale agents for lysosomal pH modulation, with the ultimate goal of developing novel therapeutic solutions.
{"title":"Modulating lysosomal pH: a molecular and nanoscale materials design perspective.","authors":"Jialiu Zeng, Orian S Shirihai, Mark W Grinstaff","doi":"10.36069/jols/20201204","DOIUrl":"10.36069/jols/20201204","url":null,"abstract":"<p><p>Lysosomes, membrane-bound organelles, play important roles in cellular processes including endocytosis, phagocytosis, and autophagy. Lysosomes maintain cellular homeostasis by generating a highly acidic environment of pH 4.5 - 5.0 and by housing hydrolytic enzymes that degrade engulfed biomolecules. Impairment of lysosomal function, especially in its acidification, is a driving force in the pathogenesis of diseases including neurodegeneration, cancer, metabolic disorders, and infectious diseases. Therefore, lysosomal pH is an attractive and targetable site for therapeutic intervention. Currently, there is a dearth of strategies or materials available to specifically modulate lysosomal acidification. This review focuses on the key aspects of how lysosomal pH is implicated in various diseases and discusses design strategies and molecular or nanoscale agents for lysosomal pH modulation, with the ultimate goal of developing novel therapeutic solutions.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"2 4","pages":"25-37"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781074/pdf/nihms-1652255.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38785683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tau oligomers have recently emerged as the principal toxic species in Alzheimer's disease (AD) and tauopathies. Tau oligomers are spontaneously self-assembled soluble tau proteins that are formed prior to fibrils, and they have been shown to play a central role in neuronal cell death and in the induction of neurodegeneration in animal models. As the therapeutic paradigm shifts to targeting toxic tau oligomers, this suggests the focus to study tau oligomerization in species that are less susceptible to fibrillization. While truncated and mutation containing tau as well as the isolated repeat domains are particularly prone to fibrillization, the wild-type (WT) tau proteins have been shown to be resistant to fibril formation in the absence of aggregation inducers. In this review, we will summarize and discuss the toxicity of WT tau both in vitro and in vivo, as well as its involvement in tau oligomerization and cell-to-cell propagation of pathology. Understanding the role of WT tau will enable more effective biomarker development and therapeutic discovery for treatment of AD and tauopathies.
Tau 低聚物最近已成为阿尔茨海默病(AD)和tau病的主要毒性物质。Tau 寡聚体是一种自发自组装的可溶性 Tau 蛋白,在形成纤维之前就已形成,它们已被证明在动物模型中神经细胞死亡和诱导神经退行性变中发挥了核心作用。随着治疗范式转向靶向毒性 tau 低聚物,这表明研究重点应放在不易纤维化的物种中的 tau 低聚物化。虽然含有截短和突变的 tau 蛋白以及孤立的重复结构域特别容易发生纤维化,但野生型(WT)tau 蛋白已被证明在没有聚集诱导剂的情况下能抵抗纤维的形成。在本综述中,我们将总结并讨论WT tau在体外和体内的毒性,以及它在tau寡聚化和细胞间病理传播中的参与。了解WT tau的作用将有助于更有效地开发生物标记物和发现治疗AD和tau病的疗法。
{"title":"The role of wild-type tau in Alzheimer's disease and related tauopathies.","authors":"Chih Hung Lo, Jonathan N Sachs","doi":"10.36069/jols/20201201","DOIUrl":"10.36069/jols/20201201","url":null,"abstract":"<p><p>Tau oligomers have recently emerged as the principal toxic species in Alzheimer's disease (AD) and tauopathies. Tau oligomers are spontaneously self-assembled soluble tau proteins that are formed prior to fibrils, and they have been shown to play a central role in neuronal cell death and in the induction of neurodegeneration in animal models. As the therapeutic paradigm shifts to targeting toxic tau oligomers, this suggests the focus to study tau oligomerization in species that are less susceptible to fibrillization. While truncated and mutation containing tau as well as the isolated repeat domains are particularly prone to fibrillization, the wild-type (WT) tau proteins have been shown to be resistant to fibril formation in the absence of aggregation inducers. In this review, we will summarize and discuss the toxicity of WT tau both in vitro and in vivo, as well as its involvement in tau oligomerization and cell-to-cell propagation of pathology. Understanding the role of WT tau will enable more effective biomarker development and therapeutic discovery for treatment of AD and tauopathies.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"2 4","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929479/pdf/nihms-1652260.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25433435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The hippocampus is the key site for learning and memory and for processing of spatial information in the brain. It is divided into three main subregions: the dentate gyrus (DG), the CA3 area, and the CA1 region, which are linearly interconnected to form a so-called trisynaptic circuit. Thus, the DG sits in a strategic position to gate the flow of information from the neocortex into the hippocampal network. The granule cells (GCs), the main cell type in the DG, receive 'where' and 'what' information from the medial and lateral entorhinal cortex, respectively. How they process this mixed information remains enigmatic. By characterizing the spatial information encoded by the excitatory postsynaptic potentials (EPSPs) in GCs, we demonstrated that the majority of GCs received spatially tuned synaptic input. However, only a minority of GCs successfully converted spatially tuned input to spatially tuned output. Furthermore, we found that mature GCs were highly heterogeneous in terms of their dendritic morphology and intrinsic excitability, which contributes to the sparse and heterogeneous firing of GCs. Finally, we discuss the possible origin of this neural heterogeneity and its potential role in enlarging the computational power of the DG, facilitating pattern separation in this network.
{"title":"Integration of spatial and non-spatial information by heterogeneous dentate gyrus granule cells.","authors":"Xiaomin Zhang, Peter Jonas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The hippocampus is the key site for learning and memory and for processing of spatial information in the brain. It is divided into three main subregions: the dentate gyrus (DG), the CA3 area, and the CA1 region, which are linearly interconnected to form a so-called trisynaptic circuit. Thus, the DG sits in a strategic position to gate the flow of information from the neocortex into the hippocampal network. The granule cells (GCs), the main cell type in the DG, receive 'where' and 'what' information from the medial and lateral entorhinal cortex, respectively. How they process this mixed information remains enigmatic. By characterizing the spatial information encoded by the excitatory postsynaptic potentials (EPSPs) in GCs, we demonstrated that the majority of GCs received spatially tuned synaptic input. However, only a minority of GCs successfully converted spatially tuned input to spatially tuned output. Furthermore, we found that mature GCs were highly heterogeneous in terms of their dendritic morphology and intrinsic excitability, which contributes to the sparse and heterogeneous firing of GCs. Finally, we discuss the possible origin of this neural heterogeneity and its potential role in enlarging the computational power of the DG, facilitating pattern separation in this network.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"2 4","pages":"19-24"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116553/pdf/EMS107988.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39138457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitochondria are the major consumer of oxygen in eukaryotic cells, owing to the requirement of oxygen to generate ATP through the mitochondrial respiratory chain (MRC) and the oxidative phosphorylation system (OXPHOS). This aerobic energy transduction is more efficient than anaerobic processes such as glycolysis. Hypoxia, a condition in which environmental or intracellular oxygen levels are below the standard range, triggers an adaptive signaling pathway within the cell. When oxygen concentrations are low, hypoxia-inducible factors (HIFs) become stabilized and activated to mount a transcriptional response that triggers modulation of cellular metabolism to adjust to hypoxic conditions. Mitochondrial aerobic metabolism is one of the main targets of the hypoxic response to regulate its functioning and efficiency in the presence of decreased oxygen levels. During evolution, eukaryotic cells and tissues have increased the plasticity of their mitochondrial OXPHOS system to cope with metabolic needs in different oxygen contexts. In mammalian mitochondria, two factors contribute to this plasticity. First, several subunits of the multimeric MRC complexes I and IV exist in multiple tissue-specific and condition-specific isoforms. Second, the MRC enzymes can coexist organized as individual entities or forming supramolecular structures known as supercomplexes, perhaps in a dynamic manner to respond to environmental conditions and cellular metabolic demands. In this review, we will summarize the information currently available on oxygen-related changes in MRC composition and organization and will discuss gaps of knowledge and research opportunities in the field.
{"title":"Mitochondrial respiratory chain composition and organization in response to changing oxygen levels.","authors":"Alba Timón-Gómez, Antoni Barrientos","doi":"10.36069/JoLS/20200601","DOIUrl":"https://doi.org/10.36069/JoLS/20200601","url":null,"abstract":"<p><p>Mitochondria are the major consumer of oxygen in eukaryotic cells, owing to the requirement of oxygen to generate ATP through the mitochondrial respiratory chain (MRC) and the oxidative phosphorylation system (OXPHOS). This aerobic energy transduction is more efficient than anaerobic processes such as glycolysis. Hypoxia, a condition in which environmental or intracellular oxygen levels are below the standard range, triggers an adaptive signaling pathway within the cell. When oxygen concentrations are low, hypoxia-inducible factors (HIFs) become stabilized and activated to mount a transcriptional response that triggers modulation of cellular metabolism to adjust to hypoxic conditions. Mitochondrial aerobic metabolism is one of the main targets of the hypoxic response to regulate its functioning and efficiency in the presence of decreased oxygen levels. During evolution, eukaryotic cells and tissues have increased the plasticity of their mitochondrial OXPHOS system to cope with metabolic needs in different oxygen contexts. In mammalian mitochondria, two factors contribute to this plasticity. First, several subunits of the multimeric MRC complexes I and IV exist in multiple tissue-specific and condition-specific isoforms. Second, the MRC enzymes can coexist organized as individual entities or forming supramolecular structures known as supercomplexes, perhaps in a dynamic manner to respond to environmental conditions and cellular metabolic demands. In this review, we will summarize the information currently available on oxygen-related changes in MRC composition and organization and will discuss gaps of knowledge and research opportunities in the field.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302114/pdf/nihms-1597826.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38060532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}