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Stereoselective syntheses of three tricyclic cyclohexenones are described. These compounds were conceived as novel precursors of synthetic conduritols, quercitols, and inositols because they allow diastereoselective C=O reductions, C=C osmylations, and C=C epoxidations to be performed. These functionalizations created up to three uniformly configured oxygenbearing stereocenters. One of the follow-up products was a tricycle that was amenable to successive cleavages of its 1,4-dioxane and 1,3-dioxane rings. This rendered the pentaesters of neo-quercitol, which contain five stereogenic C-O bonds, with ds = 85:15. [ABSTRACT FROM AUTHOR]

The swimming larva represents the dispersal phase of ascidians, marine invertebrates belonging to tunicates. Due to its adhesive papillae, the larva searches the substrate, adheres to it, and undergoes metamorphosis, thereby becoming a sessile filter feeding animal. The larva anatomy has been described in detail in a few species, revealing a different degree of adult structure differentiation, called adultation. In the solitary ascidian Halocynthia roretzi, a species reared for commercial purposes, embryogenesis has been described in detail, but information on the larval anatomy is still lacking. Here, we describe it using a comparative approach, utilizing 3D reconstruction, as well as histological/TEM observations, with attention to its papillae. The larva is comparable to those of other solitary ascidians, such as Ciona intestinalis. However, it displays a higher level of adultation for the presence of the atrium, opened outside by means of the atrial siphon, and the peribranchial chambers. It does not reach the level of complexity of the larva of Botryllus schlosseri, a phylogenetically close colonial ascidian. Our study reveals that the papillae of H. roretzi, previously described as simple and conform, exhibit dynamic changes during settlement. This opens up new considerations on papillae morphology and evolution and deserves to be further investigated. [ABSTRACT FROM AUTHOR]

Background: The 9p21.3 locus is strongly associated with the risk of coronary artery disease (CAD) and with type 2 diabetes (T2D). We investigated the association of 9p21.3 variants with severity of CAD (defined by the number of vessel diseased [VD]) in the presence and absence of T2D. Methods: We tested 11 9p21.3-variants for association in a white Italian study (N = 2,908), and carried out replication in 2 independent white populations, a German study (N = 2,028) and a Canadian Study (N=950). SNP association and permutation analyses were conducted. Results: We identified two 9p21.3-variants, rs4977574 (P < 4×10-4) and rs2383207 (P < 1.5×10²) that were associated with severity of CAD in subjects without T2D. Association of rs4977574 with severity of CAD was confirmed in the Canadian Study. Results from subgroup analysis among patients with T2D showed an interaction between rs10738610 and T2D with P = 4.82×10². Further investigation showed that rs10738610 (P < 1.99×10²) was found to be significantly associated with severity of CAD in subjects with T2D. Conclusions: The 9p21.3 locus is significantly associated with severity of CAD. The number of associations of 9p21.3 variants with severity of CAD is variable to the presence and absence of T2D. In a CAD-susceptible region of 115 kb, there is only one variant associated with the severity of coronary vessel disease in the presence of type 2 diabetes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Colourful residues found in Persepolis were deeply investigated for the first time. • Malachite with green earth represent an evidence of a mixture ready to use. • Red and yellow lumps of pigments are related with Fe-deposits located in Fars area. • Evidence of Egyptian blue manufacturing from bronze scarp and diopside trace. • Confirming of local workshops production according to archaeologists' hypothesis. The microstructure and chemical composition of blue and green pellets, coloured lump pigments and a metal scrap excavated in Persepolis West (Fars, Iran), by the Iranian-Italian Joint Archaeological Mission in Fars in 2008–09, were investigated to clarify their origin and production techniques. The Persepolis West urban area has its eastern limit about five hundred meters away from the Persepolis Terrace and extends for about 1 km in a westward direction. Due to the presence in this area of various kilns and other remains, the existence of a craft zone connected with the construction of imperial and élite buildings in Persepolis was proposed. The colourful residues were submitted to integrated investigations using portable X-ray fluorescence spectrometry, digital and polarized light microscopy, scanning electron microscopy with energy dispersive X-ray spectroscopy, X-ray diffraction, ATR-FTIR and Raman spectroscopy. The integrated analyses allowed to identify azurite, malachite, Egyptian blue, glauconite, yellow and red ochre with hematite, magnetite and goethite. Proteinaceous material was detected only in one red lump. These pigments are in accordance with the palette used to paint the palaces of the Persepolis Terrace, thus supporting the hypothesis that in Persepolis West craft zone, there was a laboratory for production of pigments. The microscopic features of the lumps and their peculiar shape confirmed a local manufacturing process. Moreover, the diopside presence related to the Egyptian blue production, as well as the discovery of a bronze scrap with a crust of Egyptian blue also suggested that this pigment was manufactured locally. [ABSTRACT FROM AUTHOR]

In this work, the authors proposed a novel and interesting animal model for studying human neurodegenerative diseases, Botryllus schlosseri , a small invertebrate inhabiting temperate seas worldwide, which shares remarkable similarities with mammals in the expression of genes involved in pathological aging., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Tunicates, the sister group of vertebrates, offer a unique perspective for evolutionary developmental studies (Evo-Devo) due to their simple anatomical organization. Moreover, the separation of tunicates from vertebrates predated the vertebrate-specific genome duplications. As adults, they include both sessile and pelagic species, with very limited mobility requirements related mainly to water filtration. In sessile species, larvae exhibit simple swimming behaviors that are required for the selection of a suitable substrate on which to metamorphose. Despite their apparent simplicity, tunicates display a variety of mechanoreceptor structures involving both primary and secondary sensory cells ( i.e ., coronal sensory cells). This review encapsulates two decades of research on tunicate mechanoreception focusing on the coronal organ's sensory cells as prime candidates for understanding the evolution of vertebrate hair cells of the inner ear and the lateral line organ. The review spans anatomical, cellular and molecular levels emphasizing both similarity and differences between tunicate and vertebrate mechanoreception strategies. The evolutionary significance of mechanoreception is discussed within the broader context of Evo-Devo studies, shedding light on the intricate pathways that have shaped the sensory system in chordates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Anselmi, Fuller, Stolfi, Groves and Manni.)

Carotenoids play an important role in the stability, freshness, and nutritional value of extra-virgin olive oil (EVOO). However, the carotenoid content in EVOO changes over time as a function of olive ripening and degrading events. A reliable quality marker is the ratio between the two most abundant carotenoids, namely lutein and β-carotene, since the second degrades more rapidly. Thus, to obtain a fast quantification of the lutein/β-carotene ratio in olive oil could deserve a certain interest. Resonant Raman spectroscopy is a rapid and non-destructive technique, widely applied for food chemical characterization. In this work, using high-performance liquid chromatography and UV-vis absorption spectroscopy as calibration techniques, we present a reliable method to assess the lutein/β-carotene ratio in EVOO using a single Raman spectrum. The novel approach deserves several methodological and applicative interests, since it would allow rapid, on-site screening of EVOO quality and authenticity, especially if implemented as a portable system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The role of single nucleotide polymorphisms (SNPs) in the etiopathogenesis of cardiovascular diseases is well known. The effect of SNPs on disease predisposition has been established not only for protein coding genes but also for genes encoding microRNAs (miRNAs). The miR-143/145 cluster is smooth muscle cell-specific and implicated in the pathogenesis of atherosclerosis. Whether SNPs within the genomic sequence of the miR-143/145 cluster are involved in cardiovascular disease development is not known. We thus searched annotated sequence databases for possible SNPs associated with miR-143/145. We identified one SNP, rs41291957 (G > A), located -91 bp from the mature miR-143 sequence, as the nearest genetic variation to this miRNA cluster, with a minor allele frequency > 10%. In silico and in vitro approaches determined that rs41291957 (A) upregulates miR-143 and miR-145, modulating phenotypic switching of vascular smooth cells towards a differentiated/contractile phenotype. Finally, we analysed association between rs41291957 and CAD in two cohorts of patients, finding that the SNP was a protective factor. In conclusion, our study links a genetic variation to a pathological outcome through involvement of miRNAs., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk., Methods: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD., Results: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09)., Conclusions: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Background: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD., Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events., Results: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints., Conclusions: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

Vertebrates have evolved the most sophisticated nervous systems we know. These differ from the nervous systems of invertebrates in several ways, including the evolution of new cell types, and the emergence and elaboration of patterning mechanisms to organise cells in time and space. Vertebrates also generally have many more cells in their central nervous systems than invertebrates, and an increase in neural cell number may have contributed to the sophisticated anatomy of the brain and spinal cord. Here, we study how increased cell number evolved in the vertebrate central nervous system, investigating the regulation of cell proliferation in the lamprey spinal cord. Markers of proliferation show that a ventricular progenitor zone is found throughout the lamprey spinal cord. We show that inhibition of Notch signalling disrupts the maintenance of this zone. When Notch is blocked, progenitor cells differentiate precociously, the proliferative ventricular zone is lost and differentiation markers become expressed throughout the spinal cord. Comparison with other chordates suggests that the emergence of a persistent Notch-regulated proliferative progenitor zone was a crucial step for the evolution of vertebrate spinal cord complexity., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Tunicates, the sister group of vertebrates, possess a mechanoreceptor organ, the coronal organ, which is considered the best candidate to address the controversial issue of vertebrate hair cell evolution. The organ, located at the base of the oral siphon, controls the flow of seawater into the organism and can drive the "squirting" reaction, i.e., the rapid body muscle contraction used to eject dangerous particles during filtration. Coronal sensory cells are secondary mechanoreceptors and share morphological, developmental, and molecular traits with vertebrate hair cells. In the colonial tunicate Botryllus schlosseri, we described coronal organ differentiation during asexual development. Moreover, we showed that the ototoxic aminoglycoside gentamicin caused morphological and mechanosensorial impairment in coronal cells. Finally, fenofibrate had a strong protective effect on coronal sensory cells due to gentamicin-induced toxicity, as occurs in vertebrate hair cells. Our results reinforce the hypothesis of homology between vertebrate hair cells and tunicate coronal sensory cells.

We report a joint experimental and computational study into the spectroscopic properties of a prototypical D5 organic dye, both in solution and adsorbed on a TiO2 surface, with the aim of modeling and quantifying the UV/Vis spectral shifts that occur in the different explored environments. Going from the dye in solution to dye-sensitized TiO2, various factors may shift the position of the UV/Vis absorption maximum, both towards longer and shorter wavelengths. Here we have focused on the effect of dye aggregation on TiO2, surface protonation, and solvent effects. The D5 dye forms stable aggregates on the TiO2 surface that cause spectral blueshifts. We used different sensitization conditions to vary the dye loading and thus the extent of dye aggregation. For each sensitization condition, we explored protonated and native TiO2 films. Computational modeling of different dimeric aggregates with increasing intermolecular interactions and simulation of the associated optical responses also confirm the observed spectral blueshifts. Our results show that both the presence of surface protons and solvent stabilize the excited state of the adsorbed dye molecules, which causes a marked redshift in the absorption maximum and thus moves in the opposite direction to the shift due to the increase in the surface coverage., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Training is a key tool to improve prevention and safety management at the workplace. Few studies have aimed at assessing quality of training and its outcomes., Objectives and Methods: This paper describes the rationale, design, content, and evaluation of an ongoing randomized controlled trial aimed at assessing the effectiveness of a training programme designed to reduce the risk of occupational injuries among employees of the wood processing industry., Discussion and Conclusions: Well designed, targeted training programmes could represent a feasible means of reducing work injuries by improving employers' behaviour and attitudes towards safety; nevertheless, these kinds of interventions have a considerable impact both in terms of human resources and in terms of cost. For these reasons, assessment of effectiveness and knowledge-sharing should be considered as essential phases of injury prevention programmes.