Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I3-4.10994
Dora Markulin
CRISPR-Cas adaptive immune systems are present in many bacteria and archaea and provide protection against invading DNA such as phages and plasmids. These systems are very versatile and complex in their gene composition and genomic architecture. CRISPR-Cas systems are classified into 2 classes, 6 types and 33 subtypes although this number is not definitive and the research is ongoing. All CRISPR-Cas systems have been thoroughly investigated in order to better understand the mechanism of CRISPR immunity enabling its use as a tool in genome editing and other biotechnological applications. However, regulation of the CRISPR-Cas system is also very complex and still not fully understood; it must provide optimal protection without introducing harmful consequences to the host. In this review, we give an overview on the regulation of the CRISPR-Cas system Class 1 Type I-E in Escherichia coli with the emphasis on the role of temperature in the regulation of the CRISPR-Cas activity and the interplay of the key regulators H-NS and StpA repressors and LeuO antirepressor in regulation of cas gene expression and HtpG chaperone in maintaining functional levels of Cas3.
CRISPR-Cas适应性免疫系统存在于许多细菌和古菌中，并提供对入侵DNA（如噬菌体和质粒）的保护。这些系统在基因组成和基因组结构方面非常通用和复杂。CRISPR-Cas系统分为2类、6种类型和33种亚型，尽管这一数字尚不明确，研究仍在进行中。为了更好地了解CRISPR免疫的机制，使其能够作为基因组编辑和其他生物技术应用的工具，所有CRISPR-Cas系统都经过了彻底的研究。然而，CRISPR-Cas系统的调节也非常复杂，仍然没有完全理解；它必须在不给主机带来有害后果的情况下提供最佳保护。在这篇综述中，我们概述了CRISPR-Cas系统Class 1 Type I-E在大肠杆菌中的调节，重点介绍了温度在CRISPR-Cas活性调节中的作用，以及关键调节因子H-NS和StpA阻遏物和LeuO抗阻遏物在Cas基因表达调节中的相互作用，以及HtpG伴侣在维持Cas3功能水平中的作用。
{"title":"CRISPR-Cas in Escherichia coli: regulation by H-NS, LeuO and temperature","authors":"Dora Markulin","doi":"10.18054/PB.V121-122I3-4.10994","DOIUrl":"https://doi.org/10.18054/PB.V121-122I3-4.10994","url":null,"abstract":"CRISPR-Cas adaptive immune systems are present in many bacteria and archaea and provide protection against invading DNA such as phages and plasmids. These systems are very versatile and complex in their gene composition and genomic architecture. CRISPR-Cas systems are classified into 2 classes, 6 types and 33 subtypes although this number is not definitive and the research is ongoing. All CRISPR-Cas systems have been thoroughly investigated in order to better understand the mechanism of CRISPR immunity enabling its use as a tool in genome editing and other biotechnological applications. However, regulation of the CRISPR-Cas system is also very complex and still not fully understood; it must provide optimal protection without introducing harmful consequences to the host. In this review, we give an overview on the regulation of the CRISPR-Cas system Class 1 Type I-E in Escherichia coli with the emphasis on the role of temperature in the regulation of the CRISPR-Cas activity and the interplay of the key regulators H-NS and StpA repressors and LeuO antirepressor in regulation of cas gene expression and HtpG chaperone in maintaining functional levels of Cas3.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":" ","pages":""},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47405784","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I1-2.10268
T. Zemunik
Background and purpose: The aim of this study was to investigate thyroid volume (TV) and its determinants in healthy young adults without present or previous thyroid disease. Materials and methods: The study was performed in a sample of 145 healthy young participants aged 19–29 years, living in an iodine-sufficient area of Dalmatia. Dimensions of the thyroid gland were obtained by ultrasound and used to determine TV. Anthropometric data was collected, and measurements of serum TSH, fT4, Tg, TgAb, and TPOAb levels were determined. Correlations between TV and other continuous variables were determined using the Pearson correlation test, while multivariate linear regression analysis was used to determine the associations of the potential predictors for the TV. Results: TV in men was larger than in women (p = 3.53 × 10–8) and was positively correlated with anthropometric measurements, with the highest correlation coefficient for height (r = 0.53, p = 6.36 × 10–12), then body surface area, BSA (r = 0.48, p = 1.68 × 10–9), weight (r = 0.43, p = 8.28 × 10–8) and body mass index, BMI (r = 0.17, p = 0.04). Age and cigarette smoking did not appear to be significantly associated with TV (p = 0.13 and p = 0.95, respectively). Univariate analysis showed TV correlated with fT4 plasma levels (b = 0.79, p = 1.73 × 10–5), while multivariate analysis showed height and fT4 levels to be important parameters with a significant role in TV. Conclusions: We confirmed previously observed association of TV with sex and anthropometric parameters and reported a significant correlation between TV and fT4 levels. Furthermore, fT4 levels and height were found to be the important parameters for predicting TV.
{"title":"Determinants of thyroid volume in healthy young adults of Dalmatia","authors":"T. Zemunik","doi":"10.18054/PB.V121-122I1-2.10268","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10268","url":null,"abstract":"Background and purpose: The aim of this study was to investigate thyroid volume (TV) and its determinants in healthy young adults without present or previous thyroid disease. Materials and methods: The study was performed in a sample of 145 healthy young participants aged 19–29 years, living in an iodine-sufficient area of Dalmatia. Dimensions of the thyroid gland were obtained by ultrasound and used to determine TV. Anthropometric data was collected, and measurements of serum TSH, fT4, Tg, TgAb, and TPOAb levels were determined. Correlations between TV and other continuous variables were determined using the Pearson correlation test, while multivariate linear regression analysis was used to determine the associations of the potential predictors for the TV. Results: TV in men was larger than in women (p = 3.53 × 10–8) and was positively correlated with anthropometric measurements, with the highest correlation coefficient for height (r = 0.53, p = 6.36 × 10–12), then body surface area, BSA (r = 0.48, p = 1.68 × 10–9), weight (r = 0.43, p = 8.28 × 10–8) and body mass index, BMI (r = 0.17, p = 0.04). Age and cigarette smoking did not appear to be significantly associated with TV (p = 0.13 and p = 0.95, respectively). Univariate analysis showed TV correlated with fT4 plasma levels (b = 0.79, p = 1.73 × 10–5), while multivariate analysis showed height and fT4 levels to be important parameters with a significant role in TV. Conclusions: We confirmed previously observed association of TV with sex and anthropometric parameters and reported a significant correlation between TV and fT4 levels. Furthermore, fT4 levels and height were found to be the important parameters for predicting TV.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":" ","pages":""},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49649805","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I3-4.10802
K. Dolinar
Chronic inflammatory rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus, increase the risk of developing insulin resistance, metabolic syndrome, and/or type 2 diabetes. While inflammation is thought to be a major mechanism underlying metabolic dysregulation in rheumatic diseases, antirheumatic drugs that exert direct metabolic effects in addition to suppressing inflammation, might be particularly useful to prevent metabolic complications. Here we review antirheumatic drugs, such as methotrexate, that inhibit ATIC, the final enzyme in the de novo purine biosynthesis, responsible for conversion of ZMP to IMP. Inhibition of ATIC results in accumulation of ZMP, thus promoting activation of AMP-activated protein kinase (AMPK), a major regulator of cellular energy metabolism and one of the most promising targets for the treatment of insulin resistance and type 2 diabetes. We focus especially on ATIC inhibition and AMPK activation in skeletal muscle as this is the largest and one of the most metabolically active tissues with a major role in glucose homeostasis. As an important site of insulin resistance, skeletal muscle is also one of the main target tissues for pharmacological therapy of type 2 diabetes. Finally, we review the metabolic effects of ATIC-inhibiting antirheumatic drugs and discuss whether these drugs might improve systemic glucose homeostasis by inhibiting ATIC and activating AMPK in skeletal muscle.
{"title":"ATIC as a link between antirheumatic drugs and regulation of energy metabolism in skeletal muscle","authors":"K. Dolinar","doi":"10.18054/PB.V121-122I3-4.10802","DOIUrl":"https://doi.org/10.18054/PB.V121-122I3-4.10802","url":null,"abstract":"Chronic inflammatory rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus, increase the risk of developing insulin resistance, metabolic syndrome, and/or type 2 diabetes. While inflammation is thought to be a major mechanism underlying metabolic dysregulation in rheumatic diseases, antirheumatic drugs that exert direct metabolic effects in addition to suppressing inflammation, might be particularly useful to prevent metabolic complications. Here we review antirheumatic drugs, such as methotrexate, that inhibit ATIC, the final enzyme in the de novo purine biosynthesis, responsible for conversion of ZMP to IMP. Inhibition of ATIC results in accumulation of ZMP, thus promoting activation of AMP-activated protein kinase (AMPK), a major regulator of cellular energy metabolism and one of the most promising targets for the treatment of insulin resistance and type 2 diabetes. We focus especially on ATIC inhibition and AMPK activation in skeletal muscle as this is the largest and one of the most metabolically active tissues with a major role in glucose homeostasis. As an important site of insulin resistance, skeletal muscle is also one of the main target tissues for pharmacological therapy of type 2 diabetes. Finally, we review the metabolic effects of ATIC-inhibiting antirheumatic drugs and discuss whether these drugs might improve systemic glucose homeostasis by inhibiting ATIC and activating AMPK in skeletal muscle.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":"1 1","pages":"129-145"},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48803388","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I1-2.11506
T. Balog
T entire volume of Periodicum biologorum is dedicated to molecular life sciences with two papers written by the Spiridion Brusina Medal laureates and 14 papers as an overview of the scientific topics presented at the HDBMB2019 “Crossroads in Life Sciences” that was held in Lovran, Croatia from 25 to 28 September 2019. We are pleased that Periodicum biologorum will serve as a support to disseminate scientific achievements of this Congress, and we are honoured to give assistance as guest editors. This collaboration between HDBMB and Periodicum biologorum has proven successful in 2016 when an issue was dedicated to the 40th Anniversary of the Croatian Society for Biochemistry and Molecular Biology (HDBMB). We also hope to continue down this road and justify the trust given by the readers.
{"title":"Crossroads in Life Sciences","authors":"T. Balog","doi":"10.18054/PB.V121-122I1-2.11506","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.11506","url":null,"abstract":"T entire volume of Periodicum biologorum is dedicated to molecular life sciences with two papers written by the Spiridion Brusina Medal laureates and 14 papers as an overview of the scientific topics presented at the HDBMB2019 “Crossroads in Life Sciences” that was held in Lovran, Croatia from 25 to 28 September 2019. We are pleased that Periodicum biologorum will serve as a support to disseminate scientific achievements of this Congress, and we are honoured to give assistance as guest editors. This collaboration between HDBMB and Periodicum biologorum has proven successful in 2016 when an issue was dedicated to the 40th Anniversary of the Croatian Society for Biochemistry and Molecular Biology (HDBMB). We also hope to continue down this road and justify the trust given by the readers.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":" ","pages":""},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43410760","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I1-2.10867
T. Čadež, Z. Kovarik
Butyrylcholinesterase (BChE) is a serine hydrolase present in plasma and other mammalian tissues. As a target of organophosphorous pesticides and warfare nerve agents, BChE acts as their stoichiometric bioscavenger. However, so far it has been a significant challenge to produce BChE at large scales and low cost. For decades, numerous research efforts have been directed first at isolation from human volunteers and later at production of BChE in eukaryotic and prokaryotic expression systems. In this review we focused on recent studies on recombinant BChE discussing reasons why the efficient, economically sensible expression system for recombinant BChE is hard to develop. We also bring the most recent advancements in the use of expression of human BChE in vivo as an effective prophylactic against organophosphate poisoning.
{"title":"Advancements in recombinant technology for production of butyrylcholinesterase, a bioscavenger of nerve agent","authors":"T. Čadež, Z. Kovarik","doi":"10.18054/PB.V121-122I1-2.10867","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10867","url":null,"abstract":"Butyrylcholinesterase (BChE) is a serine hydrolase present in plasma and other mammalian tissues. As a target of organophosphorous pesticides and warfare nerve agents, BChE acts as their stoichiometric bioscavenger. However, so far it has been a significant challenge to produce BChE at large scales and low cost. For decades, numerous research efforts have been directed first at isolation from human volunteers and later at production of BChE in eukaryotic and prokaryotic expression systems. In this review we focused on recent studies on recombinant BChE discussing reasons why the efficient, economically sensible expression system for recombinant BChE is hard to develop. We also bring the most recent advancements in the use of expression of human BChE in vivo as an effective prophylactic against organophosphate poisoning.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":" ","pages":""},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46241855","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I1-2.10571
E. Šatović
Genome compartments known to carry out very important biological functions (e.g. centromeres and telomeres) are mostly constituted of repetitive sequences. At the same time, regions of the genomes enriched in repetitive sequences have always presented great technical challenges for sequence alignments and genome assemblies. Fast evolving sequencing technologies and the increasing accessibility of genomic datasets have opened the opportunity to gain new insights into poorly explored genome fractions, built of repetitive DNA. Comprehensive and accurate annotation and characterization of these sequences is therefore an important contribution to the understanding of genomic architecture and function as a whole. In order to attend the emerging needs in repeat analysis and characterization, many bioinformatics tools, databases and pipelines have been generated. This review is intended to draw attention to the problems encountered in the genomic studies of repetitive sequences and to provide an overview of a spectrum of most prominent bioinformatics tools used for gaining better insight into these important genomic components. Some of the described assets are focused on detection of a wide range of repeats while the others are focused on a specific type of repetitive DNA sequences, generated as an answer to specific research interests and needs of the scientific community. REPETITIVE SEQUENCES IN EUKARYOTIC
{"title":"Tools and databases for solving problems in detection and identification of repetitive DNA sequences","authors":"E. Šatović","doi":"10.18054/PB.V121-122I1-2.10571","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10571","url":null,"abstract":"Genome compartments known to carry out very important biological functions (e.g. centromeres and telomeres) are mostly constituted of repetitive sequences. At the same time, regions of the genomes enriched in repetitive sequences have always presented great technical challenges for sequence alignments and genome assemblies. Fast evolving sequencing technologies and the increasing accessibility of genomic datasets have opened the opportunity to gain new insights into poorly explored genome fractions, built of repetitive DNA. Comprehensive and accurate annotation and characterization of these sequences is therefore an important contribution to the understanding of genomic architecture and function as a whole. In order to attend the emerging needs in repeat analysis and characterization, many bioinformatics tools, databases and pipelines have been generated. This review is intended to draw attention to the problems encountered in the genomic studies of repetitive sequences and to provide an overview of a spectrum of most prominent bioinformatics tools used for gaining better insight into these important genomic components. Some of the described assets are focused on detection of a wide range of repeats while the others are focused on a specific type of repetitive DNA sequences, generated as an answer to specific research interests and needs of the scientific community. REPETITIVE SEQUENCES IN EUKARYOTIC","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":" ","pages":""},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45726487","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I3-4.11132
A. Peris
Background and purpose: Inflammation is a common pathogenesis in infection, injury, cancer, and many chronic diseases. Macrophages are among the main cells involved in generation of inflammation. The aim of the present study was to investigate the effects of molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible a 2-aminoethanol linker, on the in vitro inflammatory responses to lipopolysaccharides (LPS) induced inflammation in the RAW 264.7 cells. Materials and methods: To determine effects of seven quinoline-arylamidine hybrids on the growth of the murine macrophage-like (RAW 264.7) cells MTT assay was used. Inflammatory reactions in the RAW264.7 cells were induced using E. coli lipopolysaccharides (LPS). Levels of nitric oxide (NO) and malondialdehyde (MDA) were determined by spectrophotometry methods. Intracellular production of reactive oxygen species (ROS) was measured by flow cytometry. Antioxidant capacity of tested compounds was tested by 2,2’-azino-bis(3-ethybenzthiazoline-6-sulfonic acid (ABTS) radical cation method. Results: Tested hybrid compounds differentially influenced proliferation of non-stimulated and LPS-stimulated RAW 264.7 cells. The hybrid compounds have not presented ABTS radical-scavenger activity. In the LPSstimulated RAW 264.7 cells 10 μM compounds slightly decreased production of NO and ROS and significantly modulated LPS-induced lipid peroxidation. Conclusions: Molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible 2-aminoethanol linker markedly decreased accumulation of lipid peroxidation products in the LPS-stimulated RAW 264.7 cells. Further studies are necessary to determine their mechanism of anti-inflammatory action in more details.
{"title":"Effects of quinoline-arylamidine hybrids on LPS-induced inflammation in RAW 264.7 cells","authors":"A. Peris","doi":"10.18054/PB.V121-122I3-4.11132","DOIUrl":"https://doi.org/10.18054/PB.V121-122I3-4.11132","url":null,"abstract":"Background and purpose: Inflammation is a common pathogenesis in infection, injury, cancer, and many chronic diseases. Macrophages are among the main cells involved in generation of inflammation. The aim of the present study was to investigate the effects of molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible a 2-aminoethanol linker, on the in vitro inflammatory responses to lipopolysaccharides (LPS) induced inflammation in the RAW 264.7 cells. Materials and methods: To determine effects of seven quinoline-arylamidine hybrids on the growth of the murine macrophage-like (RAW 264.7) cells MTT assay was used. Inflammatory reactions in the RAW264.7 cells were induced using E. coli lipopolysaccharides (LPS). Levels of nitric oxide (NO) and malondialdehyde (MDA) were determined by spectrophotometry methods. Intracellular production of reactive oxygen species (ROS) was measured by flow cytometry. Antioxidant capacity of tested compounds was tested by 2,2’-azino-bis(3-ethybenzthiazoline-6-sulfonic acid (ABTS) radical cation method. Results: Tested hybrid compounds differentially influenced proliferation of non-stimulated and LPS-stimulated RAW 264.7 cells. The hybrid compounds have not presented ABTS radical-scavenger activity. In the LPSstimulated RAW 264.7 cells 10 μM compounds slightly decreased production of NO and ROS and significantly modulated LPS-induced lipid peroxidation. Conclusions: Molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible 2-aminoethanol linker markedly decreased accumulation of lipid peroxidation products in the LPS-stimulated RAW 264.7 cells. Further studies are necessary to determine their mechanism of anti-inflammatory action in more details.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":" ","pages":""},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46919423","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I1-2.10627
Nikolina Prtenjaca
Mutations in optineurin have been linked to amyotrophic lateral sclerosis (ALS) a decade ago, but its exact role in the neurodegenerative process is still unclear. As a lysine 63 (K63)and methionine (M1)-linked polyubiquitin-binding protein, optineurin has been reported to act as an adaptor in inflammatory signaling pathways mediated via nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 3 (IRF3), as well as in membrane-associated trafficking events including autophagy, maintenance of the Golgi apparatus, and exocytosis. Other studies have demonstrated its role in other processes such as regulation of mitosis, transcription, necroptosis and apoptosis. However, many of the reported effects in cell models have been proven difficult to reproduce in optineurin animal models, demonstrating the challenges of extrapolation between model systems. Knowing that multifunctional proteins present a “nightmare” for researchers, to help navigating through this field, we address the most common controversies, open questions, and artefacts related to optineurin and its role in pathogenesis of ALS and other neurodegenerative diseases.
{"title":"Optineurin Dysfunction in Amyotrophic Lateral Sclerosis: Why So Puzzling?","authors":"Nikolina Prtenjaca","doi":"10.18054/PB.V121-122I1-2.10627","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10627","url":null,"abstract":"Mutations in optineurin have been linked to amyotrophic lateral sclerosis (ALS) a decade ago, but its exact role in the neurodegenerative process is still unclear. As a lysine 63 (K63)and methionine (M1)-linked polyubiquitin-binding protein, optineurin has been reported to act as an adaptor in inflammatory signaling pathways mediated via nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 3 (IRF3), as well as in membrane-associated trafficking events including autophagy, maintenance of the Golgi apparatus, and exocytosis. Other studies have demonstrated its role in other processes such as regulation of mitosis, transcription, necroptosis and apoptosis. However, many of the reported effects in cell models have been proven difficult to reproduce in optineurin animal models, demonstrating the challenges of extrapolation between model systems. Knowing that multifunctional proteins present a “nightmare” for researchers, to help navigating through this field, we address the most common controversies, open questions, and artefacts related to optineurin and its role in pathogenesis of ALS and other neurodegenerative diseases.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":" ","pages":""},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46083604","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I1-2.10603
R. Odžak
Quaternary ammonium compounds (QACs) have a long-known application as antiseptics and disinfectants applied in various industries such as pharmaceutical, agricultural and food industry. Given the alarming number of QACs resistant bacteria, there is an urgent need to develop new QACs with broad-spectrum antimicrobial activities and low tendency to trigger bacterial resistance. One recently proposed approach to develop new QACs is based on quaternization of natural products, which proved to be successful. Quinuclidine is an interesting natural precursor find to be a part of the structure of biologically active cinchona alkaloids. In addition to the well-established medicinal and pharmaceutical potential of 3-substituted quinuclidines, QACs based on 3-substituted quinuclidines, have only recently been shown to exhibit a significant antimicrobial activity. Most importantly, these compounds exhibit low toxicity toward normal human cell lines, which opens up a new chapter in the QACs field ensuring further investigation of possible therapeutic application of 3-substituted quinuclidine based QACs.
{"title":"Biological activity of monoquaternary ammonium compounds based on 3-substituted quinuclidine: A short review","authors":"R. Odžak","doi":"10.18054/PB.V121-122I1-2.10603","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10603","url":null,"abstract":"Quaternary ammonium compounds (QACs) have a long-known application as antiseptics and disinfectants applied in various industries such as pharmaceutical, agricultural and food industry. Given the alarming number of QACs resistant bacteria, there is an urgent need to develop new QACs with broad-spectrum antimicrobial activities and low tendency to trigger bacterial resistance. One recently proposed approach to develop new QACs is based on quaternization of natural products, which proved to be successful. Quinuclidine is an interesting natural precursor find to be a part of the structure of biologically active cinchona alkaloids. In addition to the well-established medicinal and pharmaceutical potential of 3-substituted quinuclidines, QACs based on 3-substituted quinuclidines, have only recently been shown to exhibit a significant antimicrobial activity. Most importantly, these compounds exhibit low toxicity toward normal human cell lines, which opens up a new chapter in the QACs field ensuring further investigation of possible therapeutic application of 3-substituted quinuclidine based QACs.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":"1 1","pages":"15-21"},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45133550","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}
Pub Date : 2020-12-30DOI: 10.18054/PB.V121-122I3-4.10547
A. Zandona, M. Katalinić
The communication between the nervous and other systems in the organism is carried out by the transmission of nerve impulses. Diverse neurotransmitters are released into the synaptic cleft and bind to the specific receptors at the neighbouring cell to transmit the signal further. One of such receptors are nicotinic acetylcholine receptors (nAChR), integrated membrane proteins (ligand-gated ion channels) activated by the binding of a neurotransmitter acetylcholine. nAChR’s main characteristic is their diversity, as they consist of five of the same or mutually different subunits, which contribute to the specific receptors properties and biological activity. During the assembly of a pentameric protein structure, various combinations of subunits are linked together. After the discovery of nAChR’s involvement in various diseases, they became an important therapeutic target, for example in the treatment of neurodegenerative diseases (Alzheimer’s and Parkinson’s) and in the treatment of organophosphorus compound poisoning. This paper presents an overview of current knowledge on nicotinic receptors and an accompanying discussion on diseases, poisonings, potential drugs and treatments is given.
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