DNA glycosylases promote genomic stability by initiating base excision repair (BER) in both the nuclear and mitochondrial genomes. Several of these enzymes have overlapping substrate recognition, through which a degree of redundancy in lesion recognition is achieved. For example, OGG1 and NEIL1 both recognize and release the imidazole-ring-fragmented guanine, FapyGua as part of a common overall pathway to cleanse the genome of damaged bases. However, these glycosylases have many differences, including their differential breadth of substrate specificity, the contrasting chemistries through which base release occurs, the subsequent steps required to complete the BER pathway, and the identity of specific protein-binding partners. Beyond these differences, the complexities and differences of their in vivo biological roles have been primarily elucidated in studies of murine models harboring a knockout of Neil1 or Ogg1, with the diversity of phenotypic manifestations exceeding what might have been anticipated for a DNA glycosylase deficiency. Pathologies associated with deficiencies in nuclear DNA repair include differential cancer susceptibilities, where Ogg1-deficient mice are generally refractory to carcinogenesis, while deficiencies in Neil1-deficient mice confer cancer susceptibility. In contrast to NEIL1, OGG1 functions as a key transcription factor in regulating inflammation and other complex gene cascades. With regard to phenotypes attributed to mitochondrial repair, knockout of either of these genes results in age- and diet-induced metabolic syndrome. The adverse health consequences associated with metabolic syndrome can be largely overcome by expression of a mitochondrial-targeted human OGG1 in both wild-type and Ogg1-deficient mice. The goal of this review is to compare the roles that NEIL1 and OGG1 play in maintaining genomic integrity, with emphasis on insights gained from not only the diverse phenotypes that are manifested in knockout and transgenic mice, but also human disease susceptibility associated with polymorphic variants.
{"title":"Complex Roles of NEIL1 and OGG1: Insights Gained from Murine Knockouts and Human Polymorphic Variants","authors":"A. Basu, Deyu Li, R. Lloyd","doi":"10.3390/dna2040020","DOIUrl":"https://doi.org/10.3390/dna2040020","url":null,"abstract":"DNA glycosylases promote genomic stability by initiating base excision repair (BER) in both the nuclear and mitochondrial genomes. Several of these enzymes have overlapping substrate recognition, through which a degree of redundancy in lesion recognition is achieved. For example, OGG1 and NEIL1 both recognize and release the imidazole-ring-fragmented guanine, FapyGua as part of a common overall pathway to cleanse the genome of damaged bases. However, these glycosylases have many differences, including their differential breadth of substrate specificity, the contrasting chemistries through which base release occurs, the subsequent steps required to complete the BER pathway, and the identity of specific protein-binding partners. Beyond these differences, the complexities and differences of their in vivo biological roles have been primarily elucidated in studies of murine models harboring a knockout of Neil1 or Ogg1, with the diversity of phenotypic manifestations exceeding what might have been anticipated for a DNA glycosylase deficiency. Pathologies associated with deficiencies in nuclear DNA repair include differential cancer susceptibilities, where Ogg1-deficient mice are generally refractory to carcinogenesis, while deficiencies in Neil1-deficient mice confer cancer susceptibility. In contrast to NEIL1, OGG1 functions as a key transcription factor in regulating inflammation and other complex gene cascades. With regard to phenotypes attributed to mitochondrial repair, knockout of either of these genes results in age- and diet-induced metabolic syndrome. The adverse health consequences associated with metabolic syndrome can be largely overcome by expression of a mitochondrial-targeted human OGG1 in both wild-type and Ogg1-deficient mice. The goal of this review is to compare the roles that NEIL1 and OGG1 play in maintaining genomic integrity, with emphasis on insights gained from not only the diverse phenotypes that are manifested in knockout and transgenic mice, but also human disease susceptibility associated with polymorphic variants.","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45416663","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}
DNA damage is induced by exogenous and endogenous sources, creating a variety of lesions. However, the cellular repair machinery that addresses and corrects this damage must contend with the fact that genomic DNA is sequestered in the nucleoprotein complex of chromatin. As the minimal unit of DNA compaction, the nucleosome core particle (NCP) is a major determinant of repair and poses unique barriers to DNA accessibility. This review outlines how the base excision repair (BER) pathway is modulated by the NCP and describes the structural and dynamic factors that influence the ability of BER enzymes to find and repair damage. Structural characteristics of the NCP such as nucleobase positioning and occupancy will be explored along with factors that impact the dynamic nature of NCPs to increase mobilization of nucleosomal DNA. We will discuss how altering the dynamics of NCPs initiates a domino effect that results in the regulation of BER enzymes.
{"title":"The Domino Effect: Nucleosome Dynamics and the Regulation of Base Excision Repair Enzymes","authors":"Julia C. Cook, S. Delaney","doi":"10.3390/dna2040018","DOIUrl":"https://doi.org/10.3390/dna2040018","url":null,"abstract":"DNA damage is induced by exogenous and endogenous sources, creating a variety of lesions. However, the cellular repair machinery that addresses and corrects this damage must contend with the fact that genomic DNA is sequestered in the nucleoprotein complex of chromatin. As the minimal unit of DNA compaction, the nucleosome core particle (NCP) is a major determinant of repair and poses unique barriers to DNA accessibility. This review outlines how the base excision repair (BER) pathway is modulated by the NCP and describes the structural and dynamic factors that influence the ability of BER enzymes to find and repair damage. Structural characteristics of the NCP such as nucleobase positioning and occupancy will be explored along with factors that impact the dynamic nature of NCPs to increase mobilization of nucleosomal DNA. We will discuss how altering the dynamics of NCPs initiates a domino effect that results in the regulation of BER enzymes.","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45189783","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}
We introduce a new DNA tile self-assembly model: the Surface Flexible Tile Assembly Model (SFTAM), where 2D tiles are placed on host 3D surfaces made of axis-parallel unit cubes glued together by their faces, called polycubes. The bonds are flexible, so that the assembly can bind on the edges of the polycube. We are interested in the study of SFTAM self-assemblies on 3D surfaces which are not always embeddable in the Euclidean plane, in order to compare their different behaviors and to compute the topological properties of the host surfaces. We focus on a family of polycubes called cuboids. Order-0 cuboids are polycubes that have six rectangular faces, and order-1 cuboids are made from two order-0 cuboids by substracting one from the other. Thus, order-1 cuboids can be of genus 0 or of genus 1 (then they contain a tunnel). We are interested in the genus of these structures, and we present a SFTAM tile assembly system that determines the genus of a given order-1 cuboid. The SFTAM tile assembly system which we design, contains a specific set $Y$ of tile types with the following properties. If the assembly is made on a host order-1 cuboid $C$ of genus 0, no tile of $Y$ appears in any producible assembly, but if $C$ has genus 1, every terminal assembly contains at least one tile of $Y$. Thus, we are able to distinguish the host surfaces according to their genus, by the tiles used in the assembly. This system is specific to order-1 cuboids but the techniques we use should be generalizable to other families of shapes.
{"title":"DNA Tile Self-Assembly for 3D-Surfaces: Towards Genus Identification","authors":"Florent Becker, Shahrzad Heydarshahi","doi":"10.4230/LIPIcs.DNA.29.2","DOIUrl":"https://doi.org/10.4230/LIPIcs.DNA.29.2","url":null,"abstract":"We introduce a new DNA tile self-assembly model: the Surface Flexible Tile Assembly Model (SFTAM), where 2D tiles are placed on host 3D surfaces made of axis-parallel unit cubes glued together by their faces, called polycubes. The bonds are flexible, so that the assembly can bind on the edges of the polycube. We are interested in the study of SFTAM self-assemblies on 3D surfaces which are not always embeddable in the Euclidean plane, in order to compare their different behaviors and to compute the topological properties of the host surfaces. We focus on a family of polycubes called cuboids. Order-0 cuboids are polycubes that have six rectangular faces, and order-1 cuboids are made from two order-0 cuboids by substracting one from the other. Thus, order-1 cuboids can be of genus 0 or of genus 1 (then they contain a tunnel). We are interested in the genus of these structures, and we present a SFTAM tile assembly system that determines the genus of a given order-1 cuboid. The SFTAM tile assembly system which we design, contains a specific set $Y$ of tile types with the following properties. If the assembly is made on a host order-1 cuboid $C$ of genus 0, no tile of $Y$ appears in any producible assembly, but if $C$ has genus 1, every terminal assembly contains at least one tile of $Y$. Thus, we are able to distinguish the host surfaces according to their genus, by the tiles used in the assembly. This system is specific to order-1 cuboids but the techniques we use should be generalizable to other families of shapes.","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":"1 1","pages":"2:1-2:21"},"PeriodicalIF":0.0,"publicationDate":"2022-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46313622","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}
Genetic instability can result from increases in DNA damage and/or alterations in DNA repair proteins and can contribute to disease development. Both exogenous and endogenous sources of DNA damage and/or alterations in DNA structure (e.g., non-B DNA) can impact genome stability. Multiple repair mechanisms exist to counteract DNA damage. One key DNA repair protein complex is ERCC1-XPF, a structure-specific endonuclease that participates in a variety of DNA repair processes. ERCC1-XPF is involved in nucleotide excision repair (NER), repair of DNA interstrand crosslinks (ICLs), and DNA double-strand break (DSB) repair via homologous recombination. In addition, ERCC1-XPF contributes to the processing of various alternative (i.e., non-B) DNA structures. This review will focus on the processing of alternative DNA structures by ERCC1-XPF.
{"title":"Multi-Faceted Roles of ERCC1-XPF Nuclease in Processing Non-B DNA Structures","authors":"Tonia T. Li, K. Vasquez","doi":"10.3390/dna2040017","DOIUrl":"https://doi.org/10.3390/dna2040017","url":null,"abstract":"Genetic instability can result from increases in DNA damage and/or alterations in DNA repair proteins and can contribute to disease development. Both exogenous and endogenous sources of DNA damage and/or alterations in DNA structure (e.g., non-B DNA) can impact genome stability. Multiple repair mechanisms exist to counteract DNA damage. One key DNA repair protein complex is ERCC1-XPF, a structure-specific endonuclease that participates in a variety of DNA repair processes. ERCC1-XPF is involved in nucleotide excision repair (NER), repair of DNA interstrand crosslinks (ICLs), and DNA double-strand break (DSB) repair via homologous recombination. In addition, ERCC1-XPF contributes to the processing of various alternative (i.e., non-B) DNA structures. This review will focus on the processing of alternative DNA structures by ERCC1-XPF.","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45621009","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}
The integrity of DNA replication is under constant threat from various exogenous and endogenous factors along with some epigenetic factors. When there is damage to the genome, cells respond to the damage in two major ways, DNA damage repair and DNA damage tolerance. One of the major mechanisms for DNA damage tolerance is DNA lesion bypass, which is performed by specific DNA polymerases called Y-family DNA polymerases including DNA polymerase eta (polη). Ever since the discovery of polη’s unique role in bypassing cyclobutane pyrimidine dimer (CPD), a wide range of DNA lesions have been experimentally shown to be bypassed by polη. The structural study of polη was greatly boosted by the first elucidation of the N-terminal catalytic domain of polη by X-ray crystallography in 2010. Ever since, a lot of polη catalytic domain crystal structures have been published, which were complexed with an incoming nucleotide and a lesion containing DNA including pyrimidine dimers, cisplatin GpG adduct, 8-oxoguanine (oxoG), 8-oxoadenine (oxoA), N7-methylguanine (N7mG), O6-methylguanine (O6mG), hypoxanthine (HX), and many others. Though polη’s active site is known to be rigid with few conformational changes, there are several contributing factors that could facilitate the lesion bypass such as catalytic metals, syn–anti conformational equilibrium, tautomerization, and specific residues of polη. Each of these components are discussed in detail in this review.
{"title":"Contributing Factors for Mutagenic DNA Lesion Bypass by DNA Polymerase Eta (polη)","authors":"Hunmin Jung","doi":"10.3390/dna2040015","DOIUrl":"https://doi.org/10.3390/dna2040015","url":null,"abstract":"The integrity of DNA replication is under constant threat from various exogenous and endogenous factors along with some epigenetic factors. When there is damage to the genome, cells respond to the damage in two major ways, DNA damage repair and DNA damage tolerance. One of the major mechanisms for DNA damage tolerance is DNA lesion bypass, which is performed by specific DNA polymerases called Y-family DNA polymerases including DNA polymerase eta (polη). Ever since the discovery of polη’s unique role in bypassing cyclobutane pyrimidine dimer (CPD), a wide range of DNA lesions have been experimentally shown to be bypassed by polη. The structural study of polη was greatly boosted by the first elucidation of the N-terminal catalytic domain of polη by X-ray crystallography in 2010. Ever since, a lot of polη catalytic domain crystal structures have been published, which were complexed with an incoming nucleotide and a lesion containing DNA including pyrimidine dimers, cisplatin GpG adduct, 8-oxoguanine (oxoG), 8-oxoadenine (oxoA), N7-methylguanine (N7mG), O6-methylguanine (O6mG), hypoxanthine (HX), and many others. Though polη’s active site is known to be rigid with few conformational changes, there are several contributing factors that could facilitate the lesion bypass such as catalytic metals, syn–anti conformational equilibrium, tautomerization, and specific residues of polη. Each of these components are discussed in detail in this review.","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41946895","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}
As the coronavirus struck the globe, we were all affected, and cytogenetic conferences were no exception [...]
随着冠状病毒袭击全球，我们都受到了影响，细胞遗传学会议也不例外[…]
{"title":"The Joint Meeting of the 23rd International Chromosome Conference (ICC) and the 24th International Colloquium in Animal Cytogenetics and Genomics (ICACG)","authors":"D. Griffin","doi":"10.3390/dna2030014","DOIUrl":"https://doi.org/10.3390/dna2030014","url":null,"abstract":"As the coronavirus struck the globe, we were all affected, and cytogenetic conferences were no exception [...]","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49350986","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}
Anthropological and linguistic studies place the first settlement of Austronesian speaking Taiwanese (AN_Tw) in the mid-Holocene era. However, geneticists have revealed exclusive diversity among the Bunun indigenous people, implying that their ancestral origin needs further study. The mitochondrial DNA (mtDNA) polymorphism of the Bunun shows a homogeneous relationship with other AN_Tw. However, the Y-chromosome polymorphism shows two major haplogroups, O1a2-M50 (60.7%), also seen to a lesser extent among the Northern AN_Tw, and O1b1a1a1a1a1-M88 (37.5%), scarce among all other AN and non-AN groups in Taiwan, but prevailing in Southeast Asia (SEA) and Mainland Southeast Asia (MSEA). While the present-day mtDNA profile of the Bunun typifies the long-term demographic standard for all AN_Tw since the Neolithic era, their Y-chromosome profile suggests an arrival of male settlers in the last two to three millennia from SEA or MSEA, who mixed exclusively with the Bunun indigenous people.
{"title":"Origin of the Bunun Indigenous People of Taiwan, a Review of Published Material Using Y-Chromosome and Mitochondrial DNA Gene Systems","authors":"J. Trejaut","doi":"10.3390/dna2030013","DOIUrl":"https://doi.org/10.3390/dna2030013","url":null,"abstract":"Anthropological and linguistic studies place the first settlement of Austronesian speaking Taiwanese (AN_Tw) in the mid-Holocene era. However, geneticists have revealed exclusive diversity among the Bunun indigenous people, implying that their ancestral origin needs further study. The mitochondrial DNA (mtDNA) polymorphism of the Bunun shows a homogeneous relationship with other AN_Tw. However, the Y-chromosome polymorphism shows two major haplogroups, O1a2-M50 (60.7%), also seen to a lesser extent among the Northern AN_Tw, and O1b1a1a1a1a1-M88 (37.5%), scarce among all other AN and non-AN groups in Taiwan, but prevailing in Southeast Asia (SEA) and Mainland Southeast Asia (MSEA). While the present-day mtDNA profile of the Bunun typifies the long-term demographic standard for all AN_Tw since the Neolithic era, their Y-chromosome profile suggests an arrival of male settlers in the last two to three millennia from SEA or MSEA, who mixed exclusively with the Bunun indigenous people.","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42164320","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}
M. Ogata, F. Shams, Yuri Yoshimura, T. Ezaz, I. Miura
The Y or W sex chromosome of a heteromorphic pair is usually heterochromatinised and degenerated. However, whether chromosome degeneration constantly proceeds toward an extreme end is not fully understood. Here, we present a case of intermittent evolution of W chromosomes caused by interpopulation hybridisation in the Japanese soil-frog, Glandirana rugosa. This species includes two heteromorphic sex chromosome systems, which are separated into geographic populations, namely the XY and ZW groups. In this study, to uncover the evolutionary mechanisms of the heterogeneous W chromosomes, we genetically investigated the geographic differentiation of the ZW populations along with the closely located XY populations. Analysis of mitochondrial cytochrome b sequences detected three distinct clades, named ZW1, ZW2, and ZW3. High throughput analyses of nuclear genomic DNA showed that autosomal alleles of XY populations were deeply introgressed into the ZW3 sub-group. Based on the genotypes of sex-linked single nucleotide polymorphisms, W-borne androgen receptor gene expression, and WW developmental mortality, we concluded that the X chromosomes were recycled to W chromosomes. Upon inclusion of two cases from another group, Neo-ZW, we observed that the X chromosomes were recycled independently at least four times to the new W chromosomes: a repetition of degeneration and resurrection.
{"title":"W Chromosome Evolution by Repeated Recycling in the Frog Glandirana rugosa","authors":"M. Ogata, F. Shams, Yuri Yoshimura, T. Ezaz, I. Miura","doi":"10.3390/dna2030012","DOIUrl":"https://doi.org/10.3390/dna2030012","url":null,"abstract":"The Y or W sex chromosome of a heteromorphic pair is usually heterochromatinised and degenerated. However, whether chromosome degeneration constantly proceeds toward an extreme end is not fully understood. Here, we present a case of intermittent evolution of W chromosomes caused by interpopulation hybridisation in the Japanese soil-frog, Glandirana rugosa. This species includes two heteromorphic sex chromosome systems, which are separated into geographic populations, namely the XY and ZW groups. In this study, to uncover the evolutionary mechanisms of the heterogeneous W chromosomes, we genetically investigated the geographic differentiation of the ZW populations along with the closely located XY populations. Analysis of mitochondrial cytochrome b sequences detected three distinct clades, named ZW1, ZW2, and ZW3. High throughput analyses of nuclear genomic DNA showed that autosomal alleles of XY populations were deeply introgressed into the ZW3 sub-group. Based on the genotypes of sex-linked single nucleotide polymorphisms, W-borne androgen receptor gene expression, and WW developmental mortality, we concluded that the X chromosomes were recycled to W chromosomes. Upon inclusion of two cases from another group, Neo-ZW, we observed that the X chromosomes were recycled independently at least four times to the new W chromosomes: a repetition of degeneration and resurrection.","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42618826","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}
Hyaluronic acid (HA)-binding is reported to predict the fertilising capacity of spermatozoa, while HA-bound sperm selection is reported to reduce the incidence of miscarriage. However, the clinical effectiveness of these techniques remains uncertain. This work investigated the prognostic value of sperm-HA binding (HAB) as a predictor of treatment outcomes, and whether HAB-sperm selection for Invitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) improves clinical outcomes or reduces miscarriage rates. A systematic review of the literature was carried out. A modified version of the Downs and Black Checklist was used to assess bias and study quality on eleven selected studies. No significant correlations were found between HAB score and fertilisation, clinical pregnancy, or live birth rates (low-quality evidence). Three studies reported a significant reduction in the incidence of miscarriage, including a Cochrane review (low-quality evidence). While the prognostic value of HAB scores is currently undetermined, there is evidence that HAB-sperm selection prior to insemination reduces the incidence of miscarriage following ART. Moreover, there are no reports of detrimental effects of HAB-sperm selection on treatment outcomes when compared with conventional IVF or ICSI. Therefore, it is unclear why it is assigned as a treatment “add-on” with a red light by the HFEA, and why its routine use is not recommended.
{"title":"The Efficacy of Hyaluronic Acid Binding (HAB) in the Treatment of Male Infertility: A Systematic Review of the Literature","authors":"Róisín Ní Dhuifin, D. Griffin, T. Moodley","doi":"10.3390/dna2030011","DOIUrl":"https://doi.org/10.3390/dna2030011","url":null,"abstract":"Hyaluronic acid (HA)-binding is reported to predict the fertilising capacity of spermatozoa, while HA-bound sperm selection is reported to reduce the incidence of miscarriage. However, the clinical effectiveness of these techniques remains uncertain. This work investigated the prognostic value of sperm-HA binding (HAB) as a predictor of treatment outcomes, and whether HAB-sperm selection for Invitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) improves clinical outcomes or reduces miscarriage rates. A systematic review of the literature was carried out. A modified version of the Downs and Black Checklist was used to assess bias and study quality on eleven selected studies. No significant correlations were found between HAB score and fertilisation, clinical pregnancy, or live birth rates (low-quality evidence). Three studies reported a significant reduction in the incidence of miscarriage, including a Cochrane review (low-quality evidence). While the prognostic value of HAB scores is currently undetermined, there is evidence that HAB-sperm selection prior to insemination reduces the incidence of miscarriage following ART. Moreover, there are no reports of detrimental effects of HAB-sperm selection on treatment outcomes when compared with conventional IVF or ICSI. Therefore, it is unclear why it is assigned as a treatment “add-on” with a red light by the HFEA, and why its routine use is not recommended.","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42853175","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}
Pub Date : 2022-06-14DOI: 10.48550/arXiv.2206.06594
Xiang Huang, Rachel N. Huls
Bournez, Fraigniaud, and Koegler defined a number in [0,1] as computable by their Large-Population Protocol (LPP) model, if the proportion of agents in a set of marked states converges to said number over time as the population grows to infinity. The notion, however, restricts the ordinary differential equations (ODEs) associated with an LPP to have only finitely many equilibria. This restriction places an intrinsic limitation on the model. As a result, a number is computable by an LPP if and only if it is algebraic, namely, not a single transcendental number can be computed under this notion. In this paper, we lift the finitary requirement on equilibria. That is, we consider systems with a continuum of equilibria. We show that essentially all numbers in [0,1] that are computable by bounded general-purpose analog computers (GPACs) or chemical reaction networks (CRNs) can also be computed by LPPs under this new definition. This implies a rich series of numbers (e.g., the reciprocal of Euler's constant, $pi/4$, Euler's $gamma$, Catalan's constant, and Dottie number) are all computable by LPPs. Our proof is constructive: We develop an algorithm that transfers bounded GPACs/CRNs into LPPs. Our algorithm also fixes a gap in Bournez et al.'s construction of LPPs designed to compute any arbitrary algebraic number in [0,1].
{"title":"Computing Real Numbers with Large-Population Protocols Having a Continuum of Equilibria","authors":"Xiang Huang, Rachel N. Huls","doi":"10.48550/arXiv.2206.06594","DOIUrl":"https://doi.org/10.48550/arXiv.2206.06594","url":null,"abstract":"Bournez, Fraigniaud, and Koegler defined a number in [0,1] as computable by their Large-Population Protocol (LPP) model, if the proportion of agents in a set of marked states converges to said number over time as the population grows to infinity. The notion, however, restricts the ordinary differential equations (ODEs) associated with an LPP to have only finitely many equilibria. This restriction places an intrinsic limitation on the model. As a result, a number is computable by an LPP if and only if it is algebraic, namely, not a single transcendental number can be computed under this notion. In this paper, we lift the finitary requirement on equilibria. That is, we consider systems with a continuum of equilibria. We show that essentially all numbers in [0,1] that are computable by bounded general-purpose analog computers (GPACs) or chemical reaction networks (CRNs) can also be computed by LPPs under this new definition. This implies a rich series of numbers (e.g., the reciprocal of Euler's constant, $pi/4$, Euler's $gamma$, Catalan's constant, and Dottie number) are all computable by LPPs. Our proof is constructive: We develop an algorithm that transfers bounded GPACs/CRNs into LPPs. Our algorithm also fixes a gap in Bournez et al.'s construction of LPPs designed to compute any arbitrary algebraic number in [0,1].","PeriodicalId":77708,"journal":{"name":"DNA (Mary Ann Liebert, Inc.)","volume":"1 1","pages":"7:1-7:22"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43434089","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：