Stemness of the Organ of Corti Relates to the Epigenetic Status of Sox2 Enhancers

In the adult mammalian auditory epithelium, the organ of Corti, loss of sensory hair cells results in permanent hearing loss. The underlying cause for the lack of regenerative response is the depletion of otic progenitors in the cell pool of the sensory epithelium. Here, we show that an increase in the sequence-specific methylation of the otic Sox2 enhancers NOP1 and NOP2 is correlated with a reduced self-renewal potential in vivo and in vitro; additionally, the degree of methylation of NOP1 and NOP2 is correlated with the dedifferentiation potential of postmitotic supporting cells into otic stem cells. Thus, the stemness the organ of Corti is related to the epigenetic status of the otic Sox2 enhancers. These observations validate the continued exploration of treatment strategies for dedifferentiating or reprogramming of differentiated supporting cells into progenitors to regenerate the damaged organ of Corti

Parallel Expansions of Sox Transcription Factor Group B Predating the Diversifications of the Arthropods and Jawed Vertebrates

Group B of the Sox transcription factor family is crucial in embryo development in the insects and vertebrates. Sox group B, unlike the other Sox groups, has an unusually enlarged functional repertoire in insects, but the timing and mechanism of the expansion of this group were unclear. We collected and analyzed data for Sox group B from 36 species of 12 phyla representing the major metazoan clades, with an emphasis on arthropods, to reconstruct the evolutionary history of SoxB in bilaterians and to date the expansion of Sox group B in insects. We found that the genome of the bilaterian last common ancestor probably contained one SoxB1 and one SoxB2 gene only and that tandem duplications of SoxB2 occurred before the arthropod diversification but after the arthropod-nematode divergence, resulting in the basal repertoire of Sox group B in diverse arthropod lineages. The arthropod Sox group B repertoire expanded differently from the vertebrate repertoire, which resulted from genome duplications. The parallel increases in the Sox group B repertoires of the arthropods and vertebrates are consistent with the parallel increases in the complexity and diversification of these two important organismal groups

Boron isotopes in foraminifera : systematics, biomineralisation, and CO2 reconstruction

Funding: Fellowship from University of St Andrews, $100 (pending) from Richard Zeebe, UK NERC grants NE/N003861/1 and NE/N011716/1.The boron isotope composition of foraminifera provides a powerful tracer for CO2 change over geological time. This proxy is based on the equilibrium of boron and its isotopes in seawater, which is a function of pH. However while the chemical principles underlying this proxy are well understood, its reliability has previously been questioned, due to the difficulty of boron isotope (δ11B) analysis on foraminferal samples and questions regarding calibrations between δ11B and pH. This chapter reviews the current state of the δ11B-pH proxy in foraminfera, including the pioneering studies that established this proxy’s potential, and the recent work that has improved understanding of boron isotope systematics in foraminifera and applied this tracer to the geological record. The theoretical background of the δ11B-pH proxy is introduced, including an accurate formulation of the boron isotope mass balance equations. Sample preparation and analysis procedures are then reviewed, with discussion of sample cleaning, the potential influence of diagenesis, and the strengths and weaknesses of boron purification by column chromatography versus microsublimation, and analysis by NTIMS versus MC-ICPMS. The systematics of boron isotopes in foraminifera are discussed in detail, including results from benthic and planktic taxa, and models of boron incorporation, fractionation, and biomineralisation. Benthic taxa from the deep ocean have δ11B within error of borate ion at seawater pH. This is most easily explained by simple incorporation of borate ion at the pH of seawater. Planktic foraminifera have δ11B close to borate ion, but with minor offsets. These may be driven by physiological influences on the foraminiferal microenvironment; a novel explanation is also suggested for the reduced δ11B-pH sensitivities observed in culture, based on variable calcification rates. Biomineralisation influences on boron isotopes are then explored, addressing the apparently contradictory observations that foraminifera manipulate pH during chamber formation yet their δ11B appears to record the pH of ambient seawater. Potential solutions include the influences of magnesium-removal and carbon concentration, and the possibility that pH elevation is most pronounced during initial chamber formation under favourable environmental conditions. The steps required to reconstruct pH and pCO2 from δ11B are then reviewed, including the influence of seawater chemistry on boron equilibrium, the evolution of seawater δ11B, and the influence of second carbonate system parameters on δ11B-based reconstructions of pCO2. Applications of foraminiferal δ11B to the geological record are highlighted, including studies that trace CO2 storage and release during recent ice ages, and reconstructions of pCO2 over the Cenozoic. Relevant computer codes and data associated with this article are made available online.Publisher PDFPeer reviewe

Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs

Scrub typhus ecology: a systematic review of Orientia in vectors and hosts

Abstract Scrub typhus, caused by Orientia tsutsugamushi, is an important and neglected vector-borne zoonotic disease with an expanding known distribution. The ecology of the disease is complex and poorly understood, impairing discussion of public health interventions. To highlight what we know and the themes of our ignorance, we conducted a systematic review of all studies investigating the pathogen in vectors and non-human hosts. A total of 276 articles in 7 languages were included, with 793 study sites across 30 countries. There was no time restriction for article inclusion, with the oldest published in 1924. Seventy-six potential vector species and 234 vertebrate host species were tested, accounting for over one million trombiculid mites (‘chiggers’) and 83,000 vertebrates. The proportion of O. tsutsugamushi positivity was recorded for different categories of laboratory test and host species. Vector and host collection sites were geocoded and mapped. Ecological data associated with these sites were summarised. A further 145 articles encompassing general themes of scrub typhus ecology were reviewed. These topics range from the life-cycle to transmission, habitats, seasonality and human risks. Important gaps in our understanding are highlighted together with possible tools to begin to unravel these. Many of the data reported are highly variable and inconsistent and minimum data reporting standards are proposed. With more recent reports of human Orientia sp. infection in the Middle East and South America and enormous advances in research technology over recent decades, this comprehensive review provides a detailed summary of work investigating this pathogen in vectors and non-human hosts and updates current understanding of the complex ecology of scrub typhus. A better understanding of scrub typhus ecology has important relevance to ongoing research into improving diagnostics, developing vaccines and identifying useful public health interventions to reduce the burden of the disease.</jats:p

Lessons from non-canonical splicing

Recent improvements in experimental and computational techniques that are used to study the transcriptome have enabled an unprecedented view of RNA processing, revealing many previously unknown non-canonical splicing events. This includes cryptic events located far from the currently annotated exons and unconventional splicing mechanisms that have important roles in regulating gene expression. These non-canonical splicing events are a major source of newly emerging transcripts during evolution, especially when they involve sequences derived from transposable elements. They are therefore under precise regulation and quality control, which minimizes their potential to disrupt gene expression. We explain how non-canonical splicing can lead to aberrant transcripts that cause many diseases, and also how it can be exploited for new therapeutic strategies

New Myobiidae (Acarina: Trombidiformes) from Philippine Mammals(Taxonomy and Systematics)

Volume: 8Start Page: 157End Page: 16

Boric acid and borate incorporation in inorganic calcite inferred from B/Ca, boron isotopes and surface kinetic modeling

The boron concentration (B/Ca ratio) and isotopic composition (δ11B) of biogenic calcite are widely applied to reconstruct past changes in seawater carbonate chemistry. Knowledge of B incorporation pathways into calcite is critical for these applications and for improving the theoretical basis of B proxies. While the canonical interpretation of δ11B holds that B in calcite predominantly derives from dissolved borate anion in seawater, recent studies of the B content, coordination, and isotopic composition in calcite suggest more complex B incorporation pathways. To provide new insights into these pathways, here we present δ11B of inorganic calcite precipitated from saline solutions of varying pH, calcium and dissolved inorganic carbon (DIC) concentration for which B/Ca data were previously reported by Uchikawa et al. (2015). Results show that calcite δ11B significantly increases with increasing pH and decreases with increasing [Ca2+] and [DIC]. In combination, these experiments show that the difference in δ11B between solid calcite and aqueous borate linearly decreases with increasing calcite precipitation rate. To interpret these data, we present the first application of surface kinetic modeling (SKM) to boron incorporation. The SKM can simultaneously explain rate-dependent B/Ca and δ11B patterns observed in our and previously published inorganic calcite precipitation experiments when both aqueous borate and boric acid contribute to boron in inorganic calcite. If the B incorporation mechanism shown here for inorganic calcite is applicable to biogenic calcite, precipitation rate variations could modify δ11B patterns by changing the contributions of aqueous boric acid and borate to boron in calcite. However, better knowledge of biogenic calcite precipitation mechanisms and rates is needed to assess the importance of this effect for applications of B proxies in biogenic carbonates