Non-coding RNAs to treat vascular smooth muscle cell dysfunction.

Vascular smooth muscle cell (vSMC) dysfunction is a critical contributor to cardiovascular diseases, including atherosclerosis, restenosis and vein graft failure. Recent advances have unveiled a fascinating range of non-coding RNAs (ncRNAs) that play a pivotal role in regulating vSMC function. This review aims to provide an in-depth analysis of the mechanisms underlying vSMC dysfunction and the therapeutic potential of various ncRNAs in mitigating this dysfunction, either preventing or reversing it. We explore the intricate interplay of microRNAs, long-non-coding RNAs and circular RNAs, shedding light on their roles in regulating key signalling pathways associated with vSMC dysfunction. We also discuss the prospects and challenges associated with developing ncRNA-based therapies for this prevalent type of cardiovascular pathology.

Intragenic meiotic recombination in Schizosaccharomyces pombe is sensitive to environmental temperature changes.

Changes in environmental temperature influence cellular processes and their dynamics, and thus affect the life cycle of organisms that are unable to control their cell/body temperature. Meiotic recombination is the cellular process essential for producing healthy haploid gametes by providing physical links (chiasmata) between homologous chromosomes to guide their accurate segregation. Additionally, meiotic recombination-initiated by programmed DNA double-strand breaks (DSBs)-can generate genetic diversity and, therefore, is a driving force of evolution. Environmental temperature influencing meiotic recombination outcome thus may be a crucial determinant of reproductive success and genetic diversity. Indeed, meiotic recombination frequency in fungi, plants and invertebrates changes with temperature. In most organisms, these temperature-induced changes in meiotic recombination seem to be mediated through the meiosis-specific chromosome axis organization, the synaptonemal complex in particular. The fission yeast Schizosaccharomyces pombe does not possess a synaptonemal complex. Thus, we tested how environmental temperature modulates meiotic recombination frequency in the absence of a fully-fledged synaptonemal complex. We show that intragenic recombination (gene conversion) positively correlates with temperature within a certain range, especially at meiotic recombination hotspots. In contrast, crossover recombination, which manifests itself as chiasmata, is less affected. Based on our observations, we suggest that, in addition to changes in DSB frequency, DSB processing could be another temperature-sensitive step causing temperature-induced recombination rate alterations.

DNA sequence differences are determinants of meiotic recombination outcome.

Meiotic recombination is essential for producing healthy gametes, and also generates genetic diversity. DNA double-strand break (DSB) formation is the initiating step of meiotic recombination, producing, among other outcomes, crossovers between homologous chromosomes (homologs), which provide physical links to guide accurate chromosome segregation. The parameters influencing DSB position and repair are thus crucial determinants of reproductive success and genetic diversity. Using Schizosaccharomyces pombe, we show that the distance between sequence polymorphisms across homologs has a strong impact on meiotic recombination rate. The closer the sequence polymorphisms are to each other across the homologs the fewer recombination events were observed. In the immediate vicinity of DSBs, sequence polymorphisms affect the frequency of intragenic recombination events (gene conversions). Additionally, and unexpectedly, the crossover rate of flanking markers tens of kilobases away from the sequence polymorphisms was affected by their relative position to each other amongst the progeny having undergone intragenic recombination. A major regulator of this distance-dependent effect is the MutSα-MutLα complex consisting of Msh2, Msh6, Mlh1, and Pms1. Additionally, the DNA helicases Rqh1 and Fml1 shape recombination frequency, although the effects seen here are largely independent of the relative position of the sequence polymorphisms.

XMaS @ the ESRF.

This paper describes the motivation for the design and construction of a beamline at the European Synchrotron Radiation Facility (ESRF) for the use of UK material scientists. Although originally focused on the study of magnetic materials, the beamline has been running for 20 years and currently supports a very broad range of science as evidenced by the research topics highlighted in this article. We describe how the beamline will adapt to align with the ESRF's upgrade to a diffraction limited storage ring. This article is part of the theme issue 'Fifty years of synchrotron science: achievements and opportunities'.

Immediately restored single implants in the aesthetic zone of the maxilla using a novel design: 5-year results from a prospective single-arm clinical trial.

BACKGROUND: Single implant crowns have become the preferred rehabilitation treatment option for replacing a missing tooth. PURPOSE: This study evaluates 5-year clinical success of using tilted implants placed immediately after extraction followed by rehabilitation with all-ceramic crowns. MATERIALS AND METHODS: Twenty-seven participants requiring 28 single implant crowns in the aesthetic zone of maxilla were recruited to participate in a single-arm clinical trial. All participants were rehabilitated according to immediate implant placement using CP grade 4 titanium implants with roughened surfaces and a 12°-angled platform. Provisional implant crowns were connected within 4 hours of implant placement and loaded according to progressive loading protocol. At 8 weeks (baseline), definitive screw-retained crowns fabricated using densely sintered zirconia abutments with the veneering porcelain were delivered. Participants were followed up to 5 years and 16 participants with 17 single implant crowns attended Year 5 recall. Data collection included changes in marginal bone levels (MBLs), mid-buccal mucosal levels (MBMLs), implant stability quotient (ISQ) values, and any prosthodontic maintenance issues. RESULTS: The mean changes in MBLs at each recall was bone fill of 0.5 ± 1.18 mm (surgery-baseline), increase of 0.1 ± 0.57 mm (baseline-Year 1), and marginal bone loss of 0.1 ± 0.25 mm (Years 1-5). A minimal change occurred with the MBMLs during the observation period. The mean ISQ value at each time point increased from 65.1 (implant placement), to 67.4 (baseline) and 69.9 (Years 1 and 5). Prosthodontic maintenance issues occurred only during the first year which included fracture of veneering ceramic and zirconia abutment as well as aesthetic concerns. CONCLUSIONS: Within the limitations of this study, the data collected would suggest that replacing a single missing tooth using titanium oral implants with 12° platform tilt and zirconia abutments can be a successful rehabilitation option in the esthetically demanding zone of anterior maxilla.

Quantitative Disentanglement of the Spin Seebeck, Proximity-Induced, and Ferromagnetic-Induced Anomalous Nernst Effect in Normal-Metal-Ferromagnet Bilayers.

We identify and investigate thermal spin transport phenomena in sputter-deposited Pt/NiFe_{2}O_{x} (4≥x≥0) bilayers. We separate the voltage generated by the spin Seebeck effect from the anomalous Nernst effect (ANE) contributions and even disentangle the ANE in the ferromagnet (FM) from the ANE produced by the Pt that is spin polarized due to its proximity to the FM. Further, we probe the dependence of these effects on the electrical conductivity and the band gap energy of the FM film varying from nearly insulating NiFe_{2}O_{4} to metallic Ni_{33}Fe_{67}. A proximity-induced ANE could only be identified in the metallic Pt/Ni_{33}Fe_{67} bilayer in contrast to Pt/NiFe_{2}O_{x} (x>0) samples. This is verified by the investigation of static magnetic proximity effects via x-ray resonant magnetic reflectivity.

Single-step Marker Switching in Schizosaccharomyces pombe Using a Lithium Acetate Transformation Protocol.

The ability to utilize different selectable markers for tagging or mutating multiple genes in Schizosaccharomyces pombe is hampered by the historical use of only two selectable markers, ura4+ and kanMX6; the latter conferring resistance to the antibiotic G418 (geneticin). More markers have been described recently, but introducing these into yeast cells often requires strain construction from scratch. To overcome this problem we and other groups have created transformation cassettes with flanking homologies to ura4+ and kanMX6 which enable an efficient and time-saving way to exchange markers in existing mutated or tagged fission yeast strains. Here, we present a protocol for single-step marker switching by lithium acetate transformation in fission yeast, Schizosaccharomyces pombe. In the following we describe how to swap the ura4+ marker to a kanMX6, natMX4, or hphMX4 marker, which provide resistance against the antibiotics G418, nourseothricin (clonNAT) or hygromycin B, respectively. We also detail how to exchange any of the MX markers for nutritional markers, such as arg3+, his3+, leu1+ and ura4+ .

X-ray spectroscopy for chemistry in the 2-4 keV energy regime at the XMaS beamline: ionic liquids, Rh and Pd catalysts in gas and liquid environments, and Cl contamination in γ-Al2O3.

The 2-4 keV energy range provides a rich window into many facets of materials science and chemistry. Within this window, P, S, Cl, K and Ca K-edges may be found along with the L-edges of industrially important elements from Y through to Sn. Yet, compared with those that cater for energies above ca. 4-5 keV, there are relatively few resources available for X-ray spectroscopy below these energies. In addition, in situ or operando studies become to varying degrees more challenging than at higher X-ray energies due to restrictions imposed by the lower energies of the X-rays upon the design and construction of appropriate sample environments. The XMaS beamline at the ESRF has recently made efforts to extend its operational energy range to include this softer end of the X-ray spectrum. In this report the resulting performance of this resource for X-ray spectroscopy is detailed with specific attention drawn to: understanding electrostatic and charge transfer effects at the S K-edge in ionic liquids; quantification of dilution limits at the Cl K- and Rh L3-edges and structural equilibria in solution; in vacuum deposition and reduction of [Rh(I)(CO)2Cl]2 to γ-Al2O3; contamination of γ-Al2O3 by Cl and its potential role in determining the chemical character of supported Rh catalysts; and the development of chlorinated Pd catalysts in `green' solvent systems. Sample environments thus far developed are also presented, characterized and their overall performance evaluated.

Immediately restored single implants in the aesthetic zone of the maxilla using a novel design: 1-year report.

OBJECTIVES: To evaluate immediate placement and immediate restoration of a novel implant with a 12°-angled prosthodontic platform, in fresh extraction sockets of the aesthetic zone of the maxilla. MATERIALS AND METHODS: Tapered, roughened surface implants of 4 mm (n=15) or 5 mm (n=13) diameter were placed in 27 participants (mean age: 47.1 years; range: 21-71 years) requiring an immediate replacement of single anterior maxillary teeth. Provisional screw-retained all-ceramic crowns were placed within 4 h following optical impressions. At 8 weeks (baseline), definitive screw-retained all-ceramic crowns were placed in occlusion. RESULTS: Twenty-six of the 28 implants met the inclusion criteria at surgery. Marginal bone levels revealed bone gain between surgery and baseline, and between baseline and 1 year of 0.2 mm (SD 0.75) and 0.78 mm (SD 2.45). Mean mid-buccal mucosal margins showed gains of 0.2 mm (SD 0.44). Prosthodontic maintenance and the aesthetics of the screw-retained implant crowns were facilitated by the external hex 12°-angled prosthodontic platform on the novel implant design, re-orientating the access cavity to the palatal or occlusal surfaces. All-ceramic implant crowns showed a high success rate with low maintenance issues over 1 year. CONCLUSION: Tapered, roughened-surfaced implants with a novel 12°-angled prosthodontic platform immediately placed in fresh extraction sockets, immediately restored with provisional crowns and subsequent definitive crowns at 8 weeks were successful for 1 year.