The ascorbic acid content of tomato fruits is associated with the expression of genes involved in pectin degradation

<p>Abstract</p> <p>Background</p> <p>High levels of ascorbic acid (AsA) in tomato fruits provide health benefits for humans and also play an important role in several aspects of plant life. Although AsA metabolism has been characterized in detail, the genetic mechanisms controlling AsA accumulation in tomatoes are poorly understood. The transcriptional control of AsA levels in fruits can be investigated by combining the advanced genetic and genomic resources currently available for tomato. A comparative transcriptomic analysis of fruit tissues was carried out on an introgression line containing a QTL promoting AsA accumulation in the fruit, using a parental cultivar with lower AsA levels as a reference.</p> <p>Results</p> <p>Introgression line IL 12-4 (<it>S. pennellii </it>in a <it>S. lycopersicum </it>background) was selected for transcriptomic analysis because it maintained differences in AsA levels compared to the parental genotypes M82 and <it>S. pennellii </it>over three consecutive trials. Comparative microarray analysis of IL 12-4 and M82 fruits over a 2-year period allowed 253 differentially-expressed genes to be identified, suggesting that AsA accumulation in IL 12-4 may be caused by a combination of increased metabolic flux and reduced utilization of AsA. In particular, the upregulation of a pectinesterase and two polygalacturonases suggests that AsA accumulation in IL12-4 fruit is mainly achieved by increasing flux through the L-galactonic acid pathway, which is driven by pectin degradation and may be triggered by ethylene.</p> <p>Conclusions</p> <p>Based on functional annotation, gene ontology classification and hierarchical clustering, a subset of the 253 differentially-expressed transcripts was used to develop a model to explain the higher AsA content in IL 12-4 fruits in terms of metabolic flux, precursor availability, demand for antioxidants, abundance of reactive oxygen species and ethylene signaling.</p

Minimally invasive aortic valve replacement with a sutureless valve through a right anterior mini-thoracotomy versus transcatheter aortic valve implantation in high-risk patients

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Clinical and pathology characterization of small nerve fiber neuro(no)pathy in cerebellar ataxia with neuropathy and vestibular areflexia syndrome

Background and purpose; Biallelic mutation/expansion of the gene RFC1 has been described in association with a spectrum of manifestations ranging from isolated sensory neuro(no)pathy to a complex presentation as cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Our aim was to define the frequency and characteristics of small fiber neuropathy (SFN) in RFC1 disease at different stages.Methods: RFC1 cases were screened for SFN using the Neuropathic Pain Symptom Inventory and Composite Autonomic Symptom Score 31 questionnaires. Clinical data were retrospectively collected. If available, lower limb skin biopsy samples were evaluated for somatic epidermal and autonomic subepidermal structure innervation and compared to healthy controls (HCs).Results: Forty patients, median age at onset 54 years (interquartile range [IQR] 49-61) and disease duration 10 years (IQR 6-16), were enrolled. Mild-to-moderate positive symptoms (median Neuropathic Pain Symptom Inventory score 12.1/50, IQR 5.5-22.3) and relevant autonomic disturbances (median Composite Autonomic Symptom Score 31 37.0/100, IQR 17.7-44.3) were frequently reported and showed scarce correlation with disease duration. A non-length-dependent impairment in nociception was evident in both clinical and paraclinical investigations. An extreme somatic denervation was observed in all patients at both proximal (fibers/mm, RFC1 cases 0.0 vs. HCs 20.5, p &lt; 0.0001) and distal sites (fibers/mm, RFC1 cases 0.0 vs. HCs 13.1, p &lt; 0.0001); instead only a slight decrease was observed in cholinergic and adrenergic innervation of autonomic structures.Conclusions: RFC1 disease is characterized by a severe and widespread somatic SFN. Skin denervation may potentially represent the earliest feature and drive towards the suspicion of this disorder

Principal molecular axis and transition dipole moment orientations in liquid crystal systems: an assessment based on studies of guest anthraquinone dyes in a nematic host

An assessment of five different definitions of the principal molecular axis along which molecules align in a nematic liquid crystal system has been made by analysing fully atomistic molecular dynamics (MD) simulations of a set of anthraquinone dyes in the cyanobiphenyl-based nematic host mixture E7. Principal molecular axes of the dyes defined by minimum moment of inertia, minimum circumference, minimum area, maximum aspect ratio, and surface tensor models were tested, and the surface tensor model was found to give the best description. Analyses of MD simulations of E7 alone showed that the surface tensor model also gave a good description of the principal molecular axes of the host molecules, suggesting that this model may be applicable more generally. Calculated dichroic order parameters of the guest-host systems were obtained by combining the surface tensor analysis with fixed transition dipole moment (TDM) orientations from time-dependent density functional theory (TD-DFT) calculations on optimised structures of the dyes, and the trend between the dyes generally matched the trend in the experimental values. Additional analyses of the guest-host simulations identified the range of conformers explored by the flexible chromophores within the dyes, and TD-DFT calculations on corresponding model structures showed that this flexibility has a significant effect on the TDM orientations within the molecular frames. Calculated dichroic order parameters that included the effects of this flexibility gave a significantly improved match with the experimental values for the more flexible dyes. Overall, the surface tensor model has been shown to provide a rationale for the experimental alignment trends that is based on molecular shape, and molecular flexibility within the chromophores has been shown to be significant for the guest-host systems: The computational approaches reported here may be used as a general aid in the predictive design of dyes with appropriate molecular shapes and flexibilities for guest-host applications

Application of Δ- and Λ-Isomerism of Octahedral Metal Complexes for Inducing Chiral Nematic Phases

The Δ- and Λ-isomerism of octahedral metal complexes is employed as a source of chirality for inducing chiral nematic phases. By applying a wide range of chiral metal complexes as a dopant, it has been found that tris(β-diketonato)metal(III) complexes exhibit an extremely high value of helical twisting power. The mechanism of induction of the chiral nematic phase is postulated on the basis of a surface chirality model. The strategy for designing an efficient dopant is described, together with the results using a number of examples of Co(III), Cr(III) and Ru(III) complexes with C2 symmetry. The development of photo-responsive dopants to achieve the photo-induced structural change of liquid crystal by use of photo-isomerization of chiral metal complexes is also described

miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators

BACKGROUND: Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance.METHODS: The miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy.RESULTS: miR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor.CONCLUSIONS: Deregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. Video Abstract

Stofnvísitala fyrir rjúpu (Lagopus muta) á Íslandi: greiningar á talningagögnum sem safnað var á vegsniðum

The rock ptarmigan (Lagopus muta) is the most important game bird in Iceland and a keystone species within the terrestrial food web, making monitoring of its population essential to assure a sustainable harvest. One of the population factors monitored is spring density of territorial cocks, surveyed yearly in all parts of Iceland. Since 1999, ptarmigan counts have been conducted also on road transects using the distance sampling technique. The goal of this study is to validate the road transect approach and use the obtained population indices to study rock ptarmigan population dynamics, trends, and synchrony in numbers among populations. The data analysed in this study was collected on 18 road transects for 1999–2020. Comparison of time series derived using road transects and time series from same areas but surveyed with different techniques, confirms the reliability of the road transects approach. The population dynamics were studied using nonlinear time series modelling. Only four of the time series show significant signs of cyclicality (significant autocorrelation at half the dominant period), with a period of 5 (in two cases), 10 and 14 years. Fitted ARX models show no trend in density for nine time series, while three series show a positive trend and two a negative trend. Synchrony among populations is common between adjacent areas, while one-year lag is more common with increasing distance between areas. The derived time series are still relatively short and this should be kept in mind when interpreting the results.Rjúpan (Lagopus muta) er mikilvægasta bráð skotveiðimanna á Íslandi og hún er að auki lykiltegund í fæðuvef á þurrlendi. Vöktun tegundarinnar er stór þáttur í því að tryggja sjálfbæra nýtingu stofnsins. Þéttleiki óðalskarra er einn af þeim stofnþáttum sem vaktaður er árvisst. Frá 1999 hafa rjúpur verið taldar á vegsniðum samkvæmt aðferðafræði sem kölluð er distance sampling. Markmið þessa verkefnis er að sannreyna gildi vegsniða og nota stofnvísitölur byggðar á slíkum talningum til að rannsaka stofnbreytingar hjá rjúpu, leitni í stofnstærð og fylgni á milli svæða í fjölda fugla. Gögnunum var safnað á 18 vegsniðum á árunum 1999–2020. Samanburður á stofnvísitölum, sem fengust með vegsniðum og vísitölum af sömu svæðum en safnað á annan máta, sýnir að vegsnið eru áreiðanleg aðferð til að telja rjúpur. Gangverk stofnbreytinga var rannsakað með ólínulegri tímaraðagreiningu. Aðeins fjórar af tímaröðunum sýna merki um stofnsveiflu (marktækur sjálffylgnistuðull við hálfa lengd sveiflu), sveiflutíminn er 5 ár (tvö tilvik), og 10 og 14 ár. ARX líkön sýna enga leitni í stofnstærð í 9 tilvikum, en þrjár stofnvísitölur gefa til kynna jákvæða leitni og tvær neikvæða leitni í þróun stofnvísitölu. Samsvörun í stofnvísitölu er algeng á milli nálægra talningasvæða, en hliðrun um eitt ár er tíðari með aukinni fjarlægð á milli svæða. Þessar tímaraðir eru enn tiltölulega stuttar og það ber að hafa í huga við túlkun gagna

Effects of induction interactions on the orientational order of solutes in liquid crystals

In a recent paper (di Matteo, A.; Ferrarini, A.; Moro, G. J. J. Phys. Chem. B 2000, 104, 7764) a method to derive a mean field potential for molecules in nematic phases based on their structure and charge distribution has been presented. The potential consists of a shape and a reaction field contribution, accounting for short range and electrostatic intermolecular interactions, respectively. The model is extended here by introducing induction interactions in the reaction field. In the spirit of our approach, aimed at a realistic picture at a semiphenomenological level, an appropriate description is obtained in terms of distributed polarizabilities. The Thole model of interacting damped atom dipoles has been singled out as a suitable one, although also different choices have been considered. The orientational order parameters calculated in this way for a set of typical polar and nonpolar solutes in nematic solvents are reported, and the influence of induction interactions is discussed

A molecular based continuum approach for the dielectric permittivity of liquids and liquid crystals

A method for the calculation of the dielectric permittivity of isotropic and anisotropic homogeneous fluids is presented which, in the framework of the continuum approximation, adopts a realistic description of the molecular features, so overcoming some of the limits of the Onsager model. The Poisson equation for the molecular charge distribution contained in a cavity in a dielectric continuum in the presence of an external field is solved by a boundary element technique, which allows a detailed description of the cavity shape associated with a given molecular structure. The charge distribution is described in terms of point charges derived from ab initio calculations in vacuum, in addition to a set of interacting atom dipoles induced by all the electric fields experienced by the molecule in the condensed phase. The link between molecular features and bulk properties is established in a general way suitable for isotropic liquids and nematic phases, through the orientational distribution function of the molecule interacting with the applied field and the surrounding fluid. Numerical results are reported for the liquid phase of a set of selected organic compounds of different shape and polarity, and for the isotropic and nematic phases of 4-n-pentyl-4(')-cyanobiphenyl (5CB). They show that a realistic description of the molecular features can have dramatic effects in the case of strongly anisometric molecules