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Assessing the degree to which climate explains the spatial distributions of different taxonomic and functional groups is essential for anticipating the effects of climate change on ecosystems. Most effort so far has focused on above-ground organisms, which offer only a partial view on the response of biodiversity to environmental gradients. Here including both above- and below-ground organisms, we quantified the degree of topoclimatic control on the occurrence patterns of >1,500 taxa and phylotypes along a c. 3,000 m elevation gradient, by fitting species distribution models. Higher model performances for animals and plants than for soil microbes (fungi, bacteria and protists) suggest that the direct influence of topoclimate is stronger on above-ground species than on below-ground microorganisms. Accordingly, direct climate change effects are predicted to be stronger for above-ground than for below-ground taxa, whereas factors expressing local soil microclimate and geochemistry are likely more important to explain and forecast the occurrence patterns of soil microbiota. Pelabresib purchase Detailed mapping and future scenarios of soil microclimate and microhabitats, together with comparative studies of interacting and ecologically dependent above- and below-ground biota, are thus needed to understand and realistically forecast the future distribution of ecosystems.Mutations in GJB2 encoding Connexin 26 (CX26) are associated with hearing loss and hyperproliferative skin disorders of differing severity including keratitis-ichthyosis-deafness (KID) and Vohwinkel syndrome. A 6-year-old Caucasian girl who presented with recurrent skin rashes and sensorineural hearing loss harboured a heterozygous point mutation in GJB2 (c.424T > C; p.F142L). To characterize the impact of CX26F142L on cellular events. Plasmids CX26WT, CX26F142L, CX26G12R (KID) or CX26D66H (Vohwinkel) were transfected into HeLa cells expressing Cx26 or Cx43 or into HaCaT cells, a model keratinocyte cell line. Confocal microscopy determined protein localization. MTT assays assessed cell viability in the presence or absence of carbenoxolone, a connexin-channel blocker. Co-immunoprecipitation/Western blot analysis determined Cx43Cx26 interactions. Quantitative real-time polymerase chain reaction assessed changes in gene expression of ER stress markers. Dye uptake assays determined Connexin-channel functionality. F142L and G12R were restricted to perinuclear areas. Collapse of the microtubule network, rescued by co-treatment with paclitaxel, occurred. ER stress was not involved. Cell viability was reduced in cells expressing F142L and G12R but not D66H. Unlike G12R that forms "leaky" hemichannels, F142L had restricted permeability. Cell viability of F142L and G12R transfected cells was greater in HeLa cells expressing Cx43 than in native Cx-free HeLa cells. Co-immunoprecipitation suggested a possible interaction between Cx43 and the three mutations. Expression of CX26F142L and G12R results in microtubule collapse, rescued by interaction with Cx43. The GJB2 mutations interacted with Cx43 suggesting that unique Cx43Cx26 channels are central to the diverse phenotype of CX26 skin-related channelopathies.Up to three million skin cancers occur worldwide annually, with an increasing burden over time1 . Melanomas, accounting for 4% of skin cancers, are responsible for 75% of deaths1,2 . An estimated 86% of melanomas in the UK are preventable3 . Self-monitoring, earlier detection and improvement in survival from melanoma are therefore of interest. Algorithm based smartphone applications (apps) are based on artificial intelligence algorithms trained on images of diagnosed skin cancer. They have the potential to facilitate early detection of otherwise aggressive life-threatening skin cancers, thus prompting users to seek timely medical attention and improve survival.

Limited research has examined the impact of peanut allergy (PA) on children using validated instruments to assess psychosocial burden and the factors influencing burden.

The PAPRIQUA study aimed to assess the caregiver-reported impact of living with PA on children's health-related quality of life (HRQL), correlations between PA severity and child's sex, and associations of caregivers' sex and anxiety with the proxy report of their child's HRQL and to identify significant predictors of a child's HRQL.

A cross-sectional survey of caregivers of children with mild, moderate and severe PA, based on caregiver perception, was conducted in the United Kingdom. Participants were recruited through a survey recruitment panel; a maximum quota of 20% who rated their child's PA as mild was set to ensure population diversity; however, the quota was not required as few participants considered their child's PA mild. The survey, funded by Aimmune Therapeutics, included sociodemographic and clinical questions, the EQ-5D-Y,iety and reaction frequency may help reduce the child's burden. Self-report studies in children with PA would help confirm these findings.

Caregivers report that children with PA experience high levels of psychosocial burden, particularly those with more severe PA and a reaction history. Interventions to decrease caregiver anxiety and reaction frequency may help reduce the child's burden. Self-report studies in children with PA would help confirm these findings.

Chronic wounds, a common morbidity in recessive dystrophic epidermolysis bullosa (RDEB), lack definitive therapies.

To assess allogeneic epidermal skin grafts in terms of wound healing and durability over time.

In a prospective, open-label clinical trial for postallogeneic haematopoietic cell transplantation (post-alloHCT) patients with RDEB, up to nine chronic wounds per patient were grafted over 1year. Epidermal grafts measuring 5 cm

were obtained from related alloHCT donors in the outpatient setting using the CELLUTOME

Epidermal Harvesting System. Wounds were photographed and symptom inventories completed at baseline and 6, 12 and 52weeks after grafting. The trial was registered at ClinicalTrials.gov (NCT02670837).

Between August 2016 and January 2019, eight patients with RDEB received a total of 35 epidermal allografts at a median of 1157days (range 548-2884) post-alloHCT. The median (interquartile range) percentage reductions in wound surface area were 75% (52-94), 95% (72-100) and 100% (97-100) at 6, 12 and 52weeks postgraft, respectively, each significantly reduced from baseline (P<0·001).

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