pH-dependent permeation of amino acids through isolated ivy cuticles is affected by cuticular water sorption and hydration shell size of the solute

The permeabilities of amino acids for isolated cuticular membranes of ivy (Hedera helix L.) were measured at different pH. Cuticular permeances were lowest for the zwitterionic form at pH 6, followed by the cationic form at pH 1. Highest permeances were obtained for the anionic form at pH 11. Permeances were not correlated with octanol/water partition coefficients and decreased at a given pH with increasing molar volume of the solute. This finding suggests that permeation takes place in the polar cuticular pathways. The effect of pH on the cuticular transport properties was analysed according to the porous membrane model considering the polyelectrolytic character of the cuticle in terms of porosity, tortuosity, and size selectivity of the aqueous cuticular pathway which is altered by pH. An increase of water content and permeability of the cuticular membrane was caused by the dissociation of weak acidic groups with increasing pH leading to a swelling of the cuticle induced by fixed negative charges. In addition, the pH-dependent size of the hydration shell of the amino acids was identified as a secondary factor explaining the variability of cuticular permeances

SPINE20 recommendations 2021: spine care for people's health and prosperity

PURPOSE: The focus of SPINE20 is to develop evidence-based policy recommendations for the G20 countries to work with governments to reduce the burden of spine disease, and disability. METHODS: On September 17-18, 2021, SPINE20 held its annual meeting in Rome, Italy. Prior to the meeting, the SPINE20 created six proposed recommendations. These recommendations were uploaded to the SPINE20 website 10 days before the meeting and opened to the public for comments. The recommendations were discussed at the meeting allowing the participants to object and provide comments. RESULTS: In total, 27 societies endorsed the following recommendations. SPINE20 calls upon the G20 countries: (1) to expand telehealth for the access to spine care, especially in light of the current situation with COVID-19. (2) To adopt value-based interprofessional spine care as an approach to improve patient outcomes and reduce disability. (3) To facilitate access and invest in the development of a competent rehabilitation workforce to reduce the burden of disability related to spine disorders. (4) To adopt a strategy to promote daily physical activity and exercises among the elderly population to maintain an active and independent life with a healthy spine, particularly after COVID-19 pandemic. (5) To engage in capacity building with emerging countries and underserved communities for the benefit of spine patients. (6) To promote strategies to transfer evidence-based advances into patient benefit through effective implementation processes. CONCLUSIONS: SPINE20's initiatives will make governments and decision makers aware of efforts to reduce needless suffering from disabling spine pain through education that can be instituted across the globe

The permeation barrier of plant cuticles: uptake of active ingredients is limited by very long-chain aliphatic rather than cyclic wax compounds

BACKGROUND: The barrier to diffusion of organic solutes across the plant cuticle is composed of waxes consisting of very long-chain aliphatic (VLCA) and, to varying degrees, cyclic compounds like pentacyclic triterpenoids. The roles of both fractions in controlling cuticular penetration by organic solutes, e.g. the active ingredients (AI) of pesticides, are unknown to date. We studied thepermeabilityof isolated leaf cuticularmembranes from Garcinia xanthochymus andPrunus laurocerasus for lipophilic azoxystrobin and theobromine as model compounds for hydrophilic AIs. RESULTS: The wax of P. laurocerasus consists of VLCA (12%) and cyclic compounds (88%), whereas VLCAs make up 97% of the wax of G. xanthochymus.We showthat treating isolated cuticles with methanol almost quantitatively releases the cyclic fraction while leaving the VLCA fraction essentially intact. All VLCAs were subsequently removed using chloroform. In both species, the permeance of the two model compounds did not change significantly after methanol treatment, whereas chloroform extraction had a large effect on organic solute permeability. CONCLUSION: The VLCA wax fractionmakes up the permeability barrier for organic solutes, whereas cyclic compounds even in high amounts have a negligible role. This is of significance when optimizing the foliar uptake of pesticides

Developmental pattern of grapevine (Vitis vinifera L.) berry cuticular wax: Differentiation between epicuticular crystals and underlying wax.

The grapevine berry surface is covered by a cuticle consisting of cutin and various lipophilic wax compounds. The latter build the main barrier for transpirational water loss and protect the fruit against environmental factors e.g. pests, mechanical impacts or radiation. The integrety of the fruit surface is one important key factor for post-harvest quality and storage of fruits. Nonetheless, the developmental pattern of cuticular wax was so far only investigated for a very limited number of fruits. Therefore, we performed comparative investigations on the compositional and morphological nature of epicuticular wax crystals and underlying wax during fruit development in Vitis vinifera. The main compound oleanolic acid belongs to the pentacyclic triterpenoids, which occur very early in the development in high amounts inside the cuticle. The amount increases until veraison and decreases further during ripening. In general, very-long chain aliphatic (VLCA) compounds are present in much smaller amounts and alcohols and aldehydes follow the same trend during development. In contrast, the amount of fatty acids constantly increases from fruit set to ripening while wax esters only occur in significant amount at veraison and increase further. Wax crystals at the fruit surface are solely composed of VLCAs and the morphology changes during development according to the compositional changes of the VLCA wax compounds. The remarkable compositional differences between epicuticular wax crystals and the underlying wax are important to understand in terms of studying grape-pest interactions or the influence of environmental factors, since only wax crystals directly face the environment

The Mode of Action of AdjuvantsRelevance of Physicochemical Properties for Effects on the Foliar Application, Cuticular Permeability, and Greenhouse Performance of Pinoxaden

We comprehensively studied the complexity of the mode of action of adjuvants by uncoupling the parameters contributing to the spray process during foliar application of agrochemicals. The ethoxylated sorbitan esters Tween 20 and Tween 80 improved the efficiency of pinoxaden (PXD) in controlling grass-weed species in greenhouse experiments by aiding retention, having humectant properties, maintaining the bioavailability, and increasing the cuticular penetration of PXD. The nonethoxylated sorbitan esters Span 20 and Span 80 showed minimal effects on retention, droplet hydration, or cuticular penetration, resulting in reduced PXD effects in the greenhouse. Tris­(2-ethylhexyl)­phosphate (TEHP) does not contribute much to retention and spreading but strongly enhances the diffusion of PXD across isolated <i>P. laurocerasus</i> cuticular membranes. As TEHP was most efficient in controlling the growth of grass-weed species, we propose that the direct effect of penetration aids on cuticular permeation plays a key role in the efficiency of foliar-applied agrochemicals

Genetic enhancement of microsomal epoxide hydrolase improves metabolic detoxification but impairs cerebral blood flow regulation

Microsomal epoxide hydrolase (mEH) is a detoxifying enzyme for xenobiotic compounds. Enzymatic activity of mEH can be greatly increased by a point mutation, leading to an E404D amino acid exchange in its catalytic triad. Surprisingly, this variant is not found in any vertebrate species, despite the obvious advantage of accelerated detoxification. We hypothesized that this evolutionary avoidance is due to the fact that the mEH plays a dualistic role in detoxification and control of endogenous vascular signaling molecules. To test this, we generated mEH E404D mice and assessed them for detoxification capacity and vascular dynamics. In liver microsomes from these mice, turnover of the xenobiotic compound phenanthrene-9,10-oxide was four times faster compared to WT liver microsomes, confirming accelerated detoxification. mEH E404D animals also showed faster metabolization of a specific class of endogenous eicosanoids, arachidonic acid-derived epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). Significantly higher DHETs/EETs ratios were found in mEH E404D liver, urine, plasma, brain and cerebral endothelial cells compared to WT controls, suggesting a broad impact of the mEH mutant on endogenous EETs metabolism. Because EETs are strong vasodilators in cerebral vasculature, hemodynamics were assessed in mEH E404D and WT cerebral cortex and hippocampus using cerebral blood volume (CBV)-based functional magnetic resonance imaging (fMRI). Basal CBV0 levels were similar between mEH E404D and control mice in both brain areas. But vascular reactivity and vasodilation in response to the vasodilatory drug acetazolamide were reduced in mEH E404D forebrain compared to WT controls by factor 3 and 2.6, respectively. These results demonstrate a critical role for mEH E404D in vasodynamics and suggest that deregulation of endogenous signaling pathways is the undesirable gain of function associated with the E404D variant

Water Sorption Isotherms of Surfactants: A Tool To Evaluate Humectancy

Fundamental experimental data for moisture absorption of non-ionic polydisperse surfactants with differing ethylene oxide (EO) content and variable aliphatic portions were measured at relative humidities between 0 and 95% at 25 °C. Remarkable differences in moisture absorption were observed between surfactant classes but also within one series of surfactants differing in either EO content or the long-chain aliphatic fraction. Both the EO units as well as the entire molecular structure, including also the lipophilic domain, were discussed to account for the humectant activity of surfactants. Water sorption isotherms showed an exponential shape, which was argued to be associated with the formation of a “free” water domain. These humectant properties might be relevant to the behavior of a foliar-applied spray droplet of agrochemical formulation products because the uptake of active ingredients will be enhanced as a result of deferred crystal precipitation

Identification of a naturally processed NY-ESO-1 peptide recognized by CD8+ T cells in the context of HLA-B51

NY-ESO-1 is one of the most immunogenic cancer antigens known to date, inducing humoral and cellular immune responses in a high proportion of patients with advanced NY-ESO-1-expressing cancers. The assessment of spontaneous and vaccine-induced CD8+ T cell responses has been limited to a small number of known NY-ESO-1 epitopes presented by MHC class I alleles. Recently, a new method to monitor NY-ESO-1-specific CD8+ T cell responses was introduced that does not depend on the individual MHC class I status and on predefined peptide epitopes. Antigen-presenting cells transduced with recombinant adenoviral vectors encoding NY-ESO-1 were used to stimulate CD8+ selected NY-ESO-1-specific T cells. Effector cells were tested for recognition of autologous B cell targets transfected with NY-ESO-1 using a recombinant vaccinia virus construct. Using a modified approach we identified the NY-ESO-1 p94-102 peptide as being recognized by CD8+ T cells in the context of HLA- B51. NY-ESO-1 p94-102 specific CD8+ T cells recognized naturally processed NY-ESO-1 presented by HLA-B51+ monocyte-derived dendritic and tumor cells. Transfection of target cells with NY-ESO-1 combined with different HLA class I alleles confirmed that the NY-ESO-1 peptide was naturally processed and recognized by HLA-B51-restricted CD8+ T cell lines and clones. Therefore, NY-ESO-1 p94-102 is a new candidate peptide antigen for cancer immunotherapy and for the monitoring of spontaneous and vaccine-induced NY-ESO-1-specific T cell responses in HLA- B51+ patients with NY-ESO-1 expressing malignancies