Veronika Uhrova, Helena Parova, Zuzana Cervinkova, Otto Kucera, Vladimir Palicka
The selection of proper reference genes and materials is critical in the design of PCR experiments, especially for differential expression studies. In this study, we propose a method to identify robust endogenous control miRNAs in the visceral adipose tissue of C57BL/6J mice with non-alcoholic fatty liver disease induced by alternating Western and control diets. This study outlines a comprehensive methodology for the analysis of microRNA endogenous controls using microfluidic cards in conjunction with miRNA profiling through small RNA sequencing and subsequent validation by quantitative PCR and the RefFinder algorithm. Criteria included were fold change, p-value, reads per million, and gene stability assessment. A set of six putative endogenous microRNAs was identified (miR-331-3p, let-7a-5p, miR-1839-5p, miR-151a-5p, let-7d-5p, and let-7c-5p). Subsequent validation and analysis using the RefFinder algorithm assessed the stability of the selected genes, and a combination of the three most stable endogenous miRNA controls (miR-331-3p, let-7a- 5p, and miR-1839-5p) exhibiting consistent expression patterns with minimal variability was set. Given the absence of universal endogenous controls, individual evaluation of normalizers for each experiment is imperative for accurate miRNA expression measurements. This approach, which combines multiple techniques and assessments, provides a reliable strategy for identifying and validating endogenous controls in miRNA studies.
{"title":"Optimal endogenous controls for microRNA analysis of visceral adipose tissue in the NAFLD mouse model.","authors":"Veronika Uhrova, Helena Parova, Zuzana Cervinkova, Otto Kucera, Vladimir Palicka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The selection of proper reference genes and materials is critical in the design of PCR experiments, especially for differential expression studies. In this study, we propose a method to identify robust endogenous control miRNAs in the visceral adipose tissue of C57BL/6J mice with non-alcoholic fatty liver disease induced by alternating Western and control diets. This study outlines a comprehensive methodology for the analysis of microRNA endogenous controls using microfluidic cards in conjunction with miRNA profiling through small RNA sequencing and subsequent validation by quantitative PCR and the RefFinder algorithm. Criteria included were fold change, p-value, reads per million, and gene stability assessment. A set of six putative endogenous microRNAs was identified (miR-331-3p, let-7a-5p, miR-1839-5p, miR-151a-5p, let-7d-5p, and let-7c-5p). Subsequent validation and analysis using the RefFinder algorithm assessed the stability of the selected genes, and a combination of the three most stable endogenous miRNA controls (miR-331-3p, let-7a- 5p, and miR-1839-5p) exhibiting consistent expression patterns with minimal variability was set. Given the absence of universal endogenous controls, individual evaluation of normalizers for each experiment is imperative for accurate miRNA expression measurements. This approach, which combines multiple techniques and assessments, provides a reliable strategy for identifying and validating endogenous controls in miRNA studies.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Synapses are specialized intercellular connections where neurons transfer information, and they are funda mental for complex brain functions. Synaptic assembly is precisely regulated, and its dysfunction often leads to neurodevelopmental disorders. Previously, we demonstrated that O-GlcNAc transferase (OGT-1) is required for synaptic development in C. elegans. However, the underlying molecular mechanisms remain largely unknown. In this study, we found that OGT-1, the C. elegans homolog of mammalian OGT, regulates presynaptic assembly in AIY interneurons in a catalysis-independent manner. Mechanistically, OGT-1 acts upstream of a specific isoform of the transcription factor DAF-16/FOXO in the insulin signaling pathway. Finally, we found that OGT-1 regulates presynaptic assembly in a subset of neurons and is required for associative learning. Our findings provide insights into the role of OGT-1 in synaptic assembly.
{"title":"O-GlcNAc transferase promotes synaptic assembly independent of catalytic activity in <i>C. elegans</i>.","authors":"Mengting Wu, Huihui Jiang, Qian Li, Yunhe Liu, Hongjun Zhang, Zhiyong Shao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Synapses are specialized intercellular connections where neurons transfer information, and they are funda mental for complex brain functions. Synaptic assembly is precisely regulated, and its dysfunction often leads to neurodevelopmental disorders. Previously, we demonstrated that O-GlcNAc transferase (OGT-1) is required for synaptic development in <i>C. elegans</i>. However, the underlying molecular mechanisms remain largely unknown. In this study, we found that OGT-1, the <i>C. elegans</i> homolog of mammalian OGT, regulates presynaptic assembly in AIY interneurons in a catalysis-independent manner. Mechanistically, OGT-1 acts upstream of a specific isoform of the transcription factor DAF-16/FOXO in the insulin signaling pathway. Finally, we found that OGT-1 regulates presynaptic assembly in a subset of neurons and is required for associative learning. Our findings provide insights into the role of OGT-1 in synaptic assembly.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autoimmunity has been explored in various viral infections, and its relevance to respiratory viruses deserves more attention, especially its immune derangement during these infections, which could potentially trigger relapse and induction of many new cases. Our study aimed to utilize publicly available transcriptomic respiratory viral datasets of rhinovirus, influenza virus, respiratory syncytial virus, and COVID-19 to understand their autoimmune activation. Antibodies produced against the autoantigens associated with respiratory viruses resulted in the identification of three biomarker genes: TRIM21, ELANE, and CTSG. These genes are reported to be involved in the pathways of neuroactive ligand-receptor interaction, neutrophil extracellular trap formation, apoptosis, amebiasis, renin-angiotensin system, and lysosome, commonly triggering the systemic lupus erythematosus (SLE) pathway in genetically susceptible SLE patients. These results emphasize that the key genes are enriched mainly in the immune system process linking SLE pathogenesis. Literature sources suggest that the biomarkers induce autoreactivity through bystander activation and molecular mimicry which results in aberrant B-cell activation and the formation of neutrophil extracellular traps leading to autoimmunity. Thus, these key biomarkers indicate a new direction for early diagnosis, risk assessment, and treatment of respiratory virus infections and SLE pathogenesis.
{"title":"Respiratory viruses and systemic lupus erythematosus: Biomarkers and mechanisms leading to autoimmunity.","authors":"Aruna Rajalingam, Sekar Kanagaraj, Anjali Ganjiwale","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Autoimmunity has been explored in various viral infections, and its relevance to respiratory viruses deserves more attention, especially its immune derangement during these infections, which could potentially trigger relapse and induction of many new cases. Our study aimed to utilize publicly available transcriptomic respiratory viral datasets of rhinovirus, influenza virus, respiratory syncytial virus, and COVID-19 to understand their autoimmune activation. Antibodies produced against the autoantigens associated with respiratory viruses resulted in the identification of three biomarker genes: <i>TRIM21, ELANE,</i> and <i>CTSG</i>. These genes are reported to be involved in the pathways of neuroactive ligand-receptor interaction, neutrophil extracellular trap formation, apoptosis, amebiasis, renin-angiotensin system, and lysosome, commonly triggering the systemic lupus erythematosus (SLE) pathway in genetically susceptible SLE patients. These results emphasize that the key genes are enriched mainly in the immune system process linking SLE pathogenesis. Literature sources suggest that the biomarkers induce autoreactivity through bystander activation and molecular mimicry which results in aberrant B-cell activation and the formation of neutrophil extracellular traps leading to autoimmunity. Thus, these key biomarkers indicate a new direction for early diagnosis, risk assessment, and treatment of respiratory virus infections and SLE pathogenesis.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cantekin Dursun, Kamil Candan, Elif YıLDıRıM Caynak, Yusuf Kumlutaş, Çetin Ilgaz, Serkan Gül
The aim of the present study was to obtain information on certain life history traits such as life span and age of sexual maturity of individuals of the species Mediodactylus heterocercus using the method of skeletochronology. A total of 31 specimens (12 males, 19 females) was aged from a population located in Güzelköy (Haliliye, Şanlıurfa, Türkiye). The age of male individuals ranged from 4 to 9 years, while that of females ranged from 3 to 10 years, with mean values of 6.25±1.60 and 5.21±1.55 years, respectively. The age of sexual maturity was 3 years for both sexes. The mean age of individuals in the population did not show a statistically significant difference between the sexes. The calculated mean values of snout-vent length (SVL) were 41.90±4.31 mm (33.53-46.69 mm) for males and 39.16±5.05 mm (30.18-48.29 mm) for females. It was concluded that the difference in SVL measurements between the sexes was not statistically significant, but a significant relationship between age and SVL was found. The species M. heterocercus does not follow Bergmann's rule with regard to climatic or topographic heterogeneity.
本研究的目的是利用骨骼年代学的方法,获得异ococcus (Mediodactylus heterocercus)个体的寿命和性成熟年龄等生活史特征。在Güzelköy (Haliliye, Şanlıurfa, t kiye)的种群中采集了31只标本(雄性12只,雌性19只)。雄性个体年龄4 ~ 9岁,雌性个体年龄3 ~ 10岁,平均年龄分别为6.25±1.60岁和5.21±1.55岁。两性性成熟年龄均为3岁。人口中个体的平均年龄在性别之间没有统计学上的显著差异。计算得出的鼻口长度(SVL)均值男性为41.90±4.31 mm (33.53 ~ 46.69 mm),女性为39.16±5.05 mm (30.18 ~ 48.29 mm)。结果表明,SVL测量值的性别差异无统计学意义,但年龄与SVL之间存在显著关系。在气候或地形异质性方面,异ococcus不遵循Bergmann规则。
{"title":"Life history traits and spatial characteristics of an Asia Minor thin-toed gecko population (<i>Mediodactylus heterocercus</i> Blanford, 1874).","authors":"Cantekin Dursun, Kamil Candan, Elif YıLDıRıM Caynak, Yusuf Kumlutaş, Çetin Ilgaz, Serkan Gül","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of the present study was to obtain information on certain life history traits such as life span and age of sexual maturity of individuals of the species <i>Mediodactylus heterocercus</i> using the method of skeletochronology. A total of 31 specimens (12 males, 19 females) was aged from a population located in Güzelköy (Haliliye, Şanlıurfa, Türkiye). The age of male individuals ranged from 4 to 9 years, while that of females ranged from 3 to 10 years, with mean values of 6.25±1.60 and 5.21±1.55 years, respectively. The age of sexual maturity was 3 years for both sexes. The mean age of individuals in the population did not show a statistically significant difference between the sexes. The calculated mean values of snout-vent length (SVL) were 41.90±4.31 mm (33.53-46.69 mm) for males and 39.16±5.05 mm (30.18-48.29 mm) for females. It was concluded that the difference in SVL measurements between the sexes was not statistically significant, but a significant relationship between age and SVL was found. The species <i>M. heterocercus</i> does not follow Bergmann's rule with regard to climatic or topographic heterogeneity.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji-Seon Lee, You-Rin Kim, Dogeon Yoon, Ji Hye Park, Ga Eun You, Wook Chun
Inhalation burns, especially when combined with thermal burns, can be fatal and significantly increase mortality rate through inhaling hazardous gas. However, there is no specific treatment for inhalation burns except for relieving bronchospasm and cleaning the airways. In particular, inhaled sulfur dioxide (SO2), a major component of inhalation burns, can easily be hydrated in the respiratory tract to produce sulfurous acid, which subsequently dissociates to form bisulfite and sulfite derivatives. In this study, we intend to assess whether human adipose-derived stem cell (ASC) exosomes rescue respiratory system-related cells damaged by exposure to SO2 derivatives. We found that the uptake of ASC exosomes was high in human respiratory systemrelated cells and they rescue decreased proliferation of cells damaged by treatment with SO2 derivatives. In human pulmonary endothelial cells (HPMECs), total tubule length was increased by pre-treatment of ASC exosomes through an in vitro angiogenesis assay. Besides, we confirmed that ASC exosomes alleviate increased expression of inflammation-related genes by treatment of SO2 derivatives in primary respiratory epithelial cells. Taken together, these results suggest that ASC exosomes have potential in regeneration of human respiratory system-related cells damaged by inhalation burns, which currently lack specific treatment methods.
{"title":"Human adipose-derived stem cell exosomes alleviate human respiratory system-related cells damaged by exposure to SO<sub>2</sub> derivatives.","authors":"Ji-Seon Lee, You-Rin Kim, Dogeon Yoon, Ji Hye Park, Ga Eun You, Wook Chun","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Inhalation burns, especially when combined with thermal burns, can be fatal and significantly increase mortality rate through inhaling hazardous gas. However, there is no specific treatment for inhalation burns except for relieving bronchospasm and cleaning the airways. In particular, inhaled sulfur dioxide (SO<sub>2</sub>), a major component of inhalation burns, can easily be hydrated in the respiratory tract to produce sulfurous acid, which subsequently dissociates to form bisulfite and sulfite derivatives. In this study, we intend to assess whether human adipose-derived stem cell (ASC) exosomes rescue respiratory system-related cells damaged by exposure to SO<sub>2</sub> derivatives. We found that the uptake of ASC exosomes was high in human respiratory systemrelated cells and they rescue decreased proliferation of cells damaged by treatment with SO<sub>2</sub> derivatives. In human pulmonary endothelial cells (HPMECs), total tubule length was increased by pre-treatment of ASC exosomes through an in vitro angiogenesis assay. Besides, we confirmed that ASC exosomes alleviate increased expression of inflammation-related genes by treatment of SO<sub>2</sub> derivatives in primary respiratory epithelial cells. Taken together, these results suggest that ASC exosomes have potential in regeneration of human respiratory system-related cells damaged by inhalation burns, which currently lack specific treatment methods.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Plant phenology encompasses the study of periodic events in the biological life cycles of plants and the influence of seasonal changes in weather and other environmental factors. In order to understand the role of the environment and changing climate on the life cycle of plants, long-term records are required to establish baselines against which significant future deviations can be discerned. This study aimed to analyze the spatial flowering pattern of the plant species Bombax ceiba, Butea monosperma, and Cassia fistula across India using publicly available images from citizen science portals and social media platforms. Citizen science is rapidly emerging as a reliable source of supplementary scientific information that can be effectively used to examine large-scale patterns of tree phenology. We found that for all three species, the flowering period is longer and begins earlier in the southern latitudes as compared with the northern latitudes. We conclude that publicly available images of flowering trees and citizen science data can serve as valuable resources to supplement existing information on tree phenology across India.
{"title":"Latitudinal patterns of flowering phenology of three widespread tropical species from public media and data repositories.","authors":"Bhavya Kriti, Sidharth Mahesh, Geetha Ramaswami","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Plant phenology encompasses the study of periodic events in the biological life cycles of plants and the influence of seasonal changes in weather and other environmental factors. In order to understand the role of the environment and changing climate on the life cycle of plants, long-term records are required to establish baselines against which significant future deviations can be discerned. This study aimed to analyze the spatial flowering pattern of the plant species <i>Bombax ceiba, Butea monosperma</i>, and <i>Cassia fistula</i> across India using publicly available images from citizen science portals and social media platforms. Citizen science is rapidly emerging as a reliable source of supplementary scientific information that can be effectively used to examine large-scale patterns of tree phenology. We found that for all three species, the flowering period is longer and begins earlier in the southern latitudes as compared with the northern latitudes. We conclude that publicly available images of flowering trees and citizen science data can serve as valuable resources to supplement existing information on tree phenology across India.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The dystrophin protein plays a critical role not only in muscles but also in the central nervous system. The absence of and mutations in the Duchenne muscular dystrophy gene (the dystrophin gene) (DMD), which encodes the dystrophin protein, lead to progressive muscle degeneration. In addition, these deficiencies result in impaired brain functions with varying clinical outcomes. Several studies have shown that patients with DMD have an IQ one standard deviation lower than that of the general population. Although the neurological and cognitive manifestations of the absence of or mutations in the dystrophin gene have been known for more than two decades, the therapeutic approach has remained primarily focused on neuromuscular manifestations. In this review, we summarize the studies exploring the associations between DMD mutations or absence and cognitive impairment. First, we review the mouse models available to study various dystrophin gene mutations. Then, we provide an overview of the localization of different dystrophin isoforms in the brain. Further, we summarize the diagnostic tools for assessing cognitive impairment in patients with DMD and modern therapies that could be used to ameliorate these cognitive impairments. This review describes recent advances in our understanding of the role of dystrophin in the brain, exploring its involvement in synaptic plasticity, neurotransmission, and brain morphology. Understanding the brain-related consequences of dystrophin deficiency is critical for elucidating the neuropathogenesis of muscular dystrophies and designing targeted therapies aimed at improving both muscle and cognitive function in DMD patients. We conclude that a holistic approach is needed in diagnosing cognitive impairment in DMD patients. We also highlight the importance of modern therapies in addressing this unmet need.
{"title":"Brain dystrophinopathies and cognitive impairment: Pathogenesis, diagnosis, and therapies.","authors":"Aadi Saluja, Kyriloss Gad, Phillipa Iyede, Praveen Parkali, Narendra Chirmule","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The dystrophin protein plays a critical role not only in muscles but also in the central nervous system. The absence of and mutations in the Duchenne muscular dystrophy gene (the dystrophin gene) (<i>DMD</i>), which encodes the dystrophin protein, lead to progressive muscle degeneration. In addition, these deficiencies result in impaired brain functions with varying clinical outcomes. Several studies have shown that patients with DMD have an IQ one standard deviation lower than that of the general population. Although the neurological and cognitive manifestations of the absence of or mutations in the dystrophin gene have been known for more than two decades, the therapeutic approach has remained primarily focused on neuromuscular manifestations. In this review, we summarize the studies exploring the associations between <i>DMD</i> mutations or absence and cognitive impairment. First, we review the mouse models available to study various dystrophin gene mutations. Then, we provide an overview of the localization of different dystrophin isoforms in the brain. Further, we summarize the diagnostic tools for assessing cognitive impairment in patients with DMD and modern therapies that could be used to ameliorate these cognitive impairments. This review describes recent advances in our understanding of the role of dystrophin in the brain, exploring its involvement in synaptic plasticity, neurotransmission, and brain morphology. Understanding the brain-related consequences of dystrophin deficiency is critical for elucidating the neuropathogenesis of muscular dystrophies and designing targeted therapies aimed at improving both muscle and cognitive function in DMD patients. We conclude that a holistic approach is needed in diagnosing cognitive impairment in DMD patients. We also highlight the importance of modern therapies in addressing this unmet need.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145633870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The transcription factors PAX6 and LHX2 play fundamental roles in mammalian cerebral cortical development. Loss of either factor causes depletion of the cortical progenitor pool and reduction of neurogenesis of later-born cortical neurons. We compared the chromatin occupancy of PAX6 and LHX2 and transcriptional dysregulation upon loss of each factor to analyze whether they function via common gene regulatory networks. We identified common direct and indirect targets that were dysregulated either concordantly or discordantly, based on whether their expression showed similar up- or downregulation upon loss of either factor. Finally, we examined single-cell RNA-seq datasets from neocortical progenitors to identify the cell types within which each common direct/indirect and concordantly/discordantly regulated target gene is expressed as cortical progenitors undergo neurogenesis. Our analysis shows that PAX6 and LHX2 have several common targets that suggest similar pathways for progenitor maintenance, but the regulation of neurogenesis may occur via at least partially non-overlapping pathways. Furthermore, each factor functions to suppress the expression of a set of common Cajal-Retzius cell-specific and interneuron-specific genes which are not normally expressed by cortical progenitors. Together, our analysis offers experimentally testable hypotheses for how PAX6 and LHX2 may execute their critical roles.
{"title":"Analysis of downstream targets of PAX6 and LHX2, fundamental regulators of the developing mammalian neocortex.","authors":"Mansi Srivastava, Varun Suresh, Shubha Tole","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The transcription factors PAX6 and LHX2 play fundamental roles in mammalian cerebral cortical development. Loss of either factor causes depletion of the cortical progenitor pool and reduction of neurogenesis of later-born cortical neurons. We compared the chromatin occupancy of PAX6 and LHX2 and transcriptional dysregulation upon loss of each factor to analyze whether they function via common gene regulatory networks. We identified common direct and indirect targets that were dysregulated either concordantly or discordantly, based on whether their expression showed similar up- or downregulation upon loss of either factor. Finally, we examined single-cell RNA-seq datasets from neocortical progenitors to identify the cell types within which each common direct/indirect and concordantly/discordantly regulated target gene is expressed as cortical progenitors undergo neurogenesis. Our analysis shows that PAX6 and LHX2 have several common targets that suggest similar pathways for progenitor maintenance, but the regulation of neurogenesis may occur via at least partially non-overlapping pathways. Furthermore, each factor functions to suppress the expression of a set of common Cajal-Retzius cell-specific and interneuron-specific genes which are not normally expressed by cortical progenitors. Together, our analysis offers experimentally testable hypotheses for how PAX6 and LHX2 may execute their critical roles.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
How does a single neuron type shape both short- and long-term behavior? A study reveals how co-transmission by two hermaphrodite-specific neurons (HSNs) of Caenorhabditis elegans produces both transient and long-lasting effects on its egg-laying behavior. A key question in neuroscience is how neurons and circuits integrate information to drive behavior. In the nematode C. elegans, locomotion, feeding, defecation and egg-laying motor programs are all generated by a simple nervous system consisting of 302 neurons whose connectivity patterns are fully described (White et al. 1986). Egg-laying behavior allows dispersal of eggs in the most appropriate locations. The egg-laying circuit consists of two hermaphrodite-specific serotonergic neurons (HSNs) and six ventral cholinergic C-neurons (VCs) connected to the vulval muscle. In addition, uv1 neuroendocrine cells mechanically respond to egg laying by the release of tyramine and neuropeptides. Together, they produce a rhythmic behavior modulated by environmental cues that alternates between egg-laying phases and resting periods (Hardaker et al. 2001; Ringstad and Horvitz 2008; Fenk and de Bono 2015). How can such a simple circuit generate rhythmic and regulated behavior?
单一类型的神经元是如何塑造短期和长期行为的?一项研究揭示了秀丽隐杆线虫(Caenorhabditis elegans)的两个雌雄同体特异性神经元(hsn)如何共同传播对其产卵行为产生短暂和持久的影响。神经科学的一个关键问题是神经元和电路如何整合信息来驱动行为。在线虫中,运动、进食、排便和产卵运动程序都是由一个由302个神经元组成的简单神经系统产生的,这些神经元的连接模式得到了完整的描述(White et al. 1986)。产卵行为允许蛋散布在最合适的位置。产卵回路由两个两性特异性血清素能神经元(HSNs)和6个连接外阴肌的腹侧胆碱能c神经元(VCs)组成。此外,uv1神经内分泌细胞通过释放酪胺和神经肽来机械地响应产卵。它们共同产生一种受环境因素调节的有节奏的行为,在产卵期和休息期之间交替(Hardaker et al. 2001;Ringstad and Horvitz 2008;Fenk and de Bono 2015)。这样一个简单的电路是如何产生有节奏和有规律的行为的?
{"title":"A jack of all trades: Hermaphrodite-specific serotonergic neuron in <i>C. elegans</i>.","authors":"Patrick Laurent","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>How does a single neuron type shape both short- and long-term behavior? A study reveals how co-transmission by two hermaphrodite-specific neurons (HSNs) of <i>Caenorhabditis elegans</i> produces both transient and long-lasting effects on its egg-laying behavior. A key question in neuroscience is how neurons and circuits integrate information to drive behavior. In the nematode <i>C. elegans</i>, locomotion, feeding, defecation and egg-laying motor programs are all generated by a simple nervous system consisting of 302 neurons whose connectivity patterns are fully described (White <i>et al</i>. 1986). Egg-laying behavior allows dispersal of eggs in the most appropriate locations. The egg-laying circuit consists of two hermaphrodite-specific serotonergic neurons (HSNs) and six ventral cholinergic C-neurons (VCs) connected to the vulval muscle. In addition, <i>uv1</i> neuroendocrine cells mechanically respond to egg laying by the release of tyramine and neuropeptides. Together, they produce a rhythmic behavior modulated by environmental cues that alternates between egg-laying phases and resting periods (Hardaker <i>et al</i>. 2001; Ringstad and Horvitz 2008; Fenk and de Bono 2015). How can such a simple circuit generate rhythmic and regulated behavior?</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell therapy using autologous, ex vivo expanded chondrocytes from surgically removed disc tissues has emerged as a promising treatment option for patients with degenerated intervertebral discs. One critical aspect of this is the requirement to culture cells in a good manufacturing practice (GMP)-compliant tissue culture facility. Given the potential for delays during the transportation of disc tissue to a centralized cell culture facility, our study aimed to assess the stability of surgically removed disc tissues stored appropriately for varying durations. Surgically removed disc tissues, stored in normal saline at 4°C for different durations, were cultured in vitro in Dulbecco's Modified Eagle medium (DMEM) supplemented with human platelet lysate. Immunophenotyping was performed using a panel of reported chondrocyte-specific antibodies, including cluster of differentiation 73 (CD73), CD90, CD105, CD166, CD14, human leukocyte antigen DR (HLA-DR), and CD34, for validation. We report that more than 80% of the tissues remained viable up to the 24-h time point as evidenced by cell growth, after which the success of culturing the chondrocytes fell to almost 30% when stored for up to 96 h. The immunophenotype of the cells was identical at all time points. For cell therapy, surgically removed disc tissue should preferably be expanded ex vivo within 24 h post surgery, although all successfully cultured cells, irrespective of the storage duration, expressed the same phenotypic markers. This study will help in planning autologous chondrocyte cell therapy for back pain where the tissue has to be transported to distant GMP facilities.
{"title":"<i>Ex vivo</i> expansion of human disc chondrocytes from surgically removed disc tissue: Post-operative tissue stability.","authors":"Ankita Bendre, Rohini Lad, Sharwani Dole, Saurabh Vaishnav, Onkar Sudame, Sunil Nadkarni, Rita Mulherkar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cell therapy using autologous, <i>ex vivo</i> expanded chondrocytes from surgically removed disc tissues has emerged as a promising treatment option for patients with degenerated intervertebral discs. One critical aspect of this is the requirement to culture cells in a good manufacturing practice (GMP)-compliant tissue culture facility. Given the potential for delays during the transportation of disc tissue to a centralized cell culture facility, our study aimed to assess the stability of surgically removed disc tissues stored appropriately for varying durations. Surgically removed disc tissues, stored in normal saline at 4°C for different durations, were cultured <i>in vitro</i> in Dulbecco's Modified Eagle medium (DMEM) supplemented with human platelet lysate. Immunophenotyping was performed using a panel of reported chondrocyte-specific antibodies, including cluster of differentiation 73 (CD73), CD90, CD105, CD166, CD14, human leukocyte antigen DR (HLA-DR), and CD34, for validation. We report that more than 80% of the tissues remained viable up to the 24-h time point as evidenced by cell growth, after which the success of culturing the chondrocytes fell to almost 30% when stored for up to 96 h. The immunophenotype of the cells was identical at all time points. For cell therapy, surgically removed disc tissue should preferably be expanded <i>ex vivo</i> within 24 h post surgery, although all successfully cultured cells, irrespective of the storage duration, expressed the same phenotypic markers. This study will help in planning autologous chondrocyte cell therapy for back pain where the tissue has to be transported to distant GMP facilities.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}