• All you need to know about sperm RNAs

      Santiago, Joana; Silva, Joana; Howl, John; Santos, Manuel; Fardilha, Margarida (Oxford University Press, 2021-10-08)
      Background: Spermatogenesis generates a small and highly specialized type of cell that is apparently incapable of transcription and translation. For many years, this dogma was supported by the assumption that (i) the compact sperm nucleus, resulting from the substitution of histones by protamine during spermatogenesis, renders the genome inaccessible to the transcriptional machinery; and (ii) the loss of most organelles, including endoplasmic reticulum and ribosomes, limits or prevents translational activity. Despite these observations, several types of coding and non-coding RNAs have been identified in human sperm. Their functional roles, particularly during fertilization and embryonic development, are only now becoming apparent. Objective and rationale: This review aimed to summarize current knowledge of the origin, types, and functional roles of sperm RNAs, and to evaluate the clinical benefits of employing these transcripts as biomarkers of male fertility and reproductive outcomes. The possible contribution of sperm RNAs to both intergenerational and transgenerational phenotypic inheritance is also addressed. Search methods: A comprehensive literature search on PubMed was conducted using the search terms ‘sperm’ AND ‘RNA’. Searches focussed upon articles written in English and published prior to August 2020. Outcomes: The development of more sensitive and accurate RNA technologies, including RNA-seq, has enabled the identification and characterization of numerous transcripts in human sperm. Though a majority of these RNAs likely arise during spermatogenesis, other data support an epididymal origin of RNA transmitted to maturing sperm by extracellular vesicles. A minority may also be synthesized by de novo transcription in mature sperm, since a small portion of the sperm genome remains packed by histones. This complex RNA population has important roles in paternal chromatin packaging, sperm maturation and capacitation, fertilization, early embryogenesis, and developmental maintenance. In recent years, additional lines of evidence from animal models support a role for sperm RNAs in intergenerational and transgenerational inheritance, modulating both the genotype and phenotype of progeny. Importantly, several reports indicate that the sperm RNA content of fertile and infertile men differs considerably, and is strongly modulated by the environment, lifestyle, and pathological states. Wider implications: Transcriptional profiling has considerable potential for the discovery of fertility biomarkers. Understanding the role of sperm transcripts and comparing the sperm RNA fingerprint of fertile and infertile men could help to elucidate the regulatory pathways contributing to male factor infertility. Such data might also provide a molecular explanation for several causes of idiopathic male fertility. Ultimately, transcriptional profiling may be employed to optimize ART procedures and overcome some of the underlying causes of male infertility, ensuring the birth of healthy children
    • Atmin mediates kidney morphogenesis by modulating Wnt signaling

      Goggolidou, P.; Hadjirin, N.F.; Bak, A.; Papakrivopoulou, E.; Hilton, H.; Norris, D.P.; Dean, C.H. (Oxford University Press, 2014-05-22)
      The DNA damage protein and transcription factor Atmin (Asciz) is required for both lung tubulogenesis and ciliogenesis. Like the lungs, kidneys contain a tubular network that is critical for their function and in addition, renal ciliary dysfunction has been implicated in the pathogenesis of cystic kidney disease. Using the Atmin mouse mutant Gasping6 (Gpg6), we investigated kidney development and found it severely disrupted with reduced branching morphogenesis, resulting in fewer epithelial structures being formed. Unexpectedly, transcriptional levels of key cilia associated genes were not altered in Atmin(Gpg6/Gpg6) kidneys. Instead, Gpg6 homozygous kidneys exhibited altered cytoskeletal organization and modulation of Wnt signaling pathway molecules, including β-catenin and non-canonical Wnt/planar cell polarity (PCP) pathway factors, such as Daam2 and Vangl2. Wnt signaling is important for kidney development and perturbation of Wnt signaling pathways can result in cystic, and other, renal abnormalities. In common with other PCP pathway mutants, Atmin(Gpg6/Gpg6) mice displayed a shortened rostral-caudal axis and mis-oriented cell division. Moreover, intercrosses between Atmin(Gpg6/+) and Vangl2(Lp/+) mice revealed a genetic interaction between Atmin and Vangl2. Thus we show for the first time that Atmin is critical for normal kidney development and we present evidence that mechanistically, Atmin modifies Wnt signaling pathways, specifically placing it as a novel effector molecule in the non-canonical Wnt/PCP pathway. The identification of a novel modulator of Wnt signaling has important implications for understanding the pathobiology of renal disease.
    • Authorship and citation gender trends in immunology and microbiology

      Thelwall, Michael (Oxford University Press, 2020-02-06)
      Immunology and microbiology research are essential for human and animal health. Unlike many other health fields, they do not usually centre around the curing or helping individual patients but focus on the microscopic scale instead. These fields are interesting from a gender perspective because two theories seeking to explain gender differences in career choices in the USA (people/things and communal/agentic goals) might produce conflicting expectations about their gender balances. This article assesses the gender shares of journal articles and gendered citation rates of five subfields of the Scopus Immunology and Microbiology broad category 1996-2014/18, for research with solely US author affiliations. Only Applied Microbiology and Biotechnology (38% female) had not reached gender parity in publishing by 2018. There was a female first author citation advantage in Parasitology but a disadvantage in Immunology. Immunology, Parasitology and Virology, had female last author citation disadvantages, but all gender effects were much smaller (<5%) than that of an extra author (10%-56%). Citation differences cannot therefore account for the current underrepresentation of women in senior roles.
    • Confronting taxonomic vandalism in biology: conscientious community self-organization can preserve nomenclatural stability

      Wüster, Wolfgang; Thomson, Scott A; O'Shea, Mark; Kaiser, Hinrich (Oxford University Press, 2021-04-20)
      Self-published taxon descriptions, bereft of a basis of evidence, are a long-standing problem in taxonomy. The problem derives in part from the Principle of Priority in the International Code of Zoological Nomenclature, which forces the use of the oldest available nomen irrespective of scientific merit. This provides a route to ‘immortality’ for unscrupulous individuals through the mass-naming of taxa without scientific basis, a phenomenon referred to as taxonomic vandalism. Following a flood of unscientific taxon namings, in 2013 a group of concerned herpetologists organized a widely supported, community-based campaign to treat these nomina as lying outside the permanent scientific record, and to ignore and overwrite them as appropriate. Here, we review the impact of these proposals over the past 8 years. We identified 59 instances of unscientific names being set aside and overwritten with science-based names (here termed aspidonyms), and 1087 uses of these aspidonyms, compared to one instance of preference for the overwritten names. This shows that when there is widespread consultation and agreement across affected research communities, setting aside certain provisions of the Code can constitute an effective last resort defence against taxonomic vandalism and enhance the universality and stability of the scientific nomenclature.
    • Cost-effective design of the alkaline electrolyser for enhanced electrochemical performance and reduced electrode degradation

      Symes, Daniel; Al-Duri, Bushra; Bujalski, Waldemar; Dhir, Aman (Oxford University Press, 2013-03)
      An alkaline electrolyser was developed and characterized. Three different metals, working as the electrode, were analysed using electrochemical methods to determine the best electrochemical performance. The performance of the Stainless Steel (SS316) electrode and the nickel electrode is much better than that of the conventional iron electrode. Degradation analysis of the electrode materials highlighted the need for the material to be durable and resistant to corrosion from an alkaline environment. Through SEM and mass analysis, it is shown that Nickel exhibits the strongest long-term resistance to surface and electrochemical performance degradation, when compared with Mild Steel (Iron) and SS316.
    • Endemic, endangered, and evolutionarily significant: Cryptic lineages in Seychelles’ frogs (Anura: Sooglossidae)

      Labisko, Jim; Griffiths, Richard A.; Chong-Seng, Lindsay; Bunbury, Nancy; Maddock, Simon T; Bradfield, Kay S.; Taylor, Michelle L. (Oxford University Press, 2019-01-12)
      Cryptic diversity corresponding with island of origin has been previously reported in the endemic, geographically restricted sooglossid frogs of the Seychelles archipelago. The evolutionary pattern behind this has not been fully explored, and given current amphibian declines and the increased extinction risk faced by island species, we sought to identify evolutionarily significant units (ESUs) to address conservation concerns for these highly threatened anurans. We obtained genetic data for two mitochondrial (mtDNA) and four nuclear (nuDNA) genes from all known populations of sooglossid frog (on the islands of Mahé, Praslin and Silhouette) for phylogenetic analyses and to construct nuDNA haplotype networks. Bayesian and maximum likelihood analyses of mtDNA support the monophyly and molecular differentiation of populations in all species that occur on multiple islands. Haplotype networks using statistical parsimony revealed multiple high-frequency haplotypes shared between islands and taxa, in addition to numerous geographically distinct (island-specific) haplotypes for each species. We consider each island-specific population of sooglossid frog as an ESU and advise conservation managers to do likewise. Furthermore, our results identify each island lineage as a candidate species, evidence for which is supported by analyses of mtDNA based on Bayesian Poisson tree processes, and independent analyses of mtDNA and nuDNA using the multispecies coalescent. Our findings add to the growing understanding of the biogeography and hidden diversity within this globally important region.
    • Iron deficiency, immunology and colorectal cancer

      Omar, Hafid; Phipps, Oliver; Brookes, Matthew (Oxford University Press, 2020-07-17)
      Excessive gut luminal iron contributes to the initiation and progression of colorectal cancer. However, emerging evidence suggests that reduced iron intake and low systemic iron levels are also associated with the pathogenesis of colorectal cancer. This is important because patients with colorectal cancer often present with iron deficiency. Iron is necessary for appropriate immunological functions; hence, iron deficiency may hinder cancer immunosurveillance and potentially modify the tumor immune microenvironment, both of which may assist cancer development. This is supported by studies showing that patients with colorectal cancer with iron deficiency have inferior outcomes and reduced response to therapy. Here, we provide an overview of the immunological consequences of iron deficiency and suggest ensuring adequate iron therapy to limit these outcomes.
    • Microcavities

      Kavokin, Alexey V; Baumberg, Jeremy J; Laussy, Fabrice; Malpuech, Guillaume (Oxford University Press, 2017)
    • PDBe: improved findability of macromolecularstructure data in the PDB

      Clark, Alice; Armstrong, David; Berrisford, John; Conroy, Matthew; Gutmanas, Aleksandras; Anyango, Stephen; Choudhary, Preeti; Dana, Jose; Haslam, Pauline; Koca, Jaroslav; et al. (Oxford University Press, 2019-11-06)
      The Protein Data Bank in Europe (PDBe), a founding member of the Worldwide Protein Data Bank (wwPDB), actively participates in the deposition, curation, validation, archiving and dissemination of macromolecular structure data. PDBe supports diverse research communities in their use of macromolecular structures by enriching the PDB data and by providing advanced tools and services for effective data access, visualization and analysis. This paper details the enrichment of data at PDBe, including mapping of RNA structures to Rfam, and identification of molecules that act as cofactors. PDBe has developed an advanced search facility with ∼100 data categories and sequence searches. New features have been included in the LiteMol viewer at PDBe, with updated visualization of carbohydrates and nucleic acids. Small molecules are now mapped more extensively to external databases and their visual representation has been enhanced. These advances help users to more easily find and interpret macromolecular structure data in order to solve scientific problems.
    • PDBe: towards reusable data delivery infrastructure at protein data bank in Europe

      Mir, Saqib; Alhroub, Younes; Anyango, Stephen; Armstrong, David R; Berrisford, John M; Clark, Alice R; Conroy, Matthew J; Dana, Jose M; Deshpande, Mandar; Gupta, Deepti; et al. (Oxford University Press, 2017-11-06)
      The Protein Data Bank in Europe (PDBe, pdbe.org) is actively engaged in the deposition, annotation, remediation, enrichment and dissemination of macromolecular structure data. This paper describes new developments and improvements at PDBe addressing three challenging areas: data enrichment, data dissemination and functional reusability. New features of the PDBe Web site are discussed, including a context dependent menu providing links to raw experimental data and improved presentation of structures solved by hybrid methods. The paper also summarizes the features of the LiteMol suite, which is a set of services enabling fast and interactive 3D visualization of structures, with associated experimental maps, annotations and quality assessment information. We introduce a library of Web components which can be easily reused to port data and functionality available at PDBe to other services. We also introduce updates to the SIFTS resource which maps PDB data to other bioinformatics resources, and the PDBe REST API.
    • Sternal Gland Scent-Marking Signals Sex, Age, Rank, and Group Identity in Captive Mandrills.

      Vaglio, Stefano; Minicozzi, Pamela; Romoli, Riccardo; Boscaro, Francesca; Pieraccini, Giuseppe; Moneti, Gloriano; Moggi-Cecchi, Jacopo (Oxford University Press, 2016-02)
      Mandrills are one of the few Old World primates to show scent-marking. We combined ethological and chemical approaches to improve our understanding of this behavior in 3 zoo-managed groups. We observed the olfactory behavior performed by adults and adolescents (N = 39) for 775h. We investigated the volatile components of sternal scent-marks using gas chromatography-mass spectrometry and compared volatile profiles with traits of the signaler. Males marked more than females and within each sex the frequency of scent-marking was related to age and dominance status, but alpha males scent-marked most frequently and particularly in specific areas at the enclosure boundaries. We identified a total of 77 volatile components of sternal gland secretion, including compounds functioning as male sex pheromones in other mammals, in scent-marks spontaneously released on filter paper by 27 male and 18 female mandrills. We confirmed our previous findings that chemical profiles contain information including sex, male age and rank, and we also found that odor may encode information about group membership in mandrills. Our results support the hypotheses that scent-marking signals the status of the dominant male as well as playing territorial functions but also suggest that it is part of sociosexual communication.