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ObjectiveThis study aimed to explore the genetic causes of probands who were diagnosed with Waardenburg syndrome (WS) or congenital sensorineural hearing loss.MethodsA detailed physical and audiological examinations were carried out to make an accurate diagnosis of 14 patients from seven unrelated families. We performed whole-exome sequencing in probands to detect the potential genetic causes and further validated them by Sanger sequencing in the probands and their family members.ResultsThe genetic causes for all 14 patients with WS or congenital sensorineural hearing loss were identified. A total of seven heterozygous variants including c.1459C > T, c.123del, and c.959-409_1173+3402del of PAX3 gene (NM_181459.4), c.198_262del and c.529_556del of SOX10 gene (NM_006941.4), and c.731G > A and c.970dup of MITF gene (NM_000248.3) were found for the first time. Of these mutations, we had confirmed two (c.1459C > T and c.970dup) are de novo by Sanger sequencing of variants in the probands and their parents.ConclusionWe revealed a total of seven novel mutations in PAX3, SOX10, and MITF, which underlie the pathogenesis of WS. The clinical and genetic characterization of these families with WS elucidated high heterogeneity in Chinese patients with WS. This study expands the database of PAX3, SOX10, and MITF mutations and improves our understanding of the causes of WS.

Glucose uptake by peripheral organs is essential for maintaining blood glucose levels within normal range. Impaired glucose uptake is a hallmark of type 2 diabetes (T2D) and metabolic syndrome and is characterized by insulin resistance. Male sex is an independent risk factor for the development of T2D. We tested whether sex and diet are independent variables for differential glucose uptake by various organs. Here, in a longitudinal study, we used 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET) to determine baseline differences in whole-body glucose uptake in young male and female mice on chow and high-fat diets. We report that sex and diet are important independent variables that account for differential glucose uptake in brown fat, skeletal muscle, liver, heart, kidney, and the stomach, but not the brain, lungs, pancreas, small intestine, or perigonadal adipose. Of the seven organs analyzed, two organs, namely brown fat, and the heart had the highest concentrations of FDG, followed by the brain, kidneys, and skeletal muscle on chow diet. Young female mice had 47% greater FDG uptake in the brown fat compared to male mice, whereas skeletal muscle FDG uptake was 49% greater in male mice. The high-fat diet inhibited FDG uptake in brown fat, skeletal muscle, and the heart, three major organs involved in uptake, whereas brain uptake was enhanced in both sexes. These foundational and groundbreaking findings suggest that mechanisms of glucose homeostasis are context- and organ-dependent and highlight the need to study sex-specific outcomes and mechanisms for diseases such as T2D, obesity, and metabolic syndrome.

Skin is an attractive site for drug administration partly because of its easy accessibility and favorable properties (e.g., less invasiveness and high patient compliance) over some other common routes of administration. Despite this, the efficiency in transdermal drug delivery has been largely limited by poor skin permeation. To address this problem, this study reports the generation of oleic acid-containing vesicles, which can enhance the drug delivery efficiency while showing good stability and limited skin disruption. Upon being loaded into a complex gel, along with the incorporation of the polymer blending technique, a delivery system exhibiting tunable transdermal flux of 2,3,5,4′-tetrahydroxystilbene 2-O-β-D-glucoside is reported. Taking the good biocompatibility and tunable delivery performance into account, our system warrants further development and optimization for future applications in the treatment of skin diseases.

Post-fire recovery success after fires that occur outside of the historical fire season varies between fire response traits, which may impact long term ecosystem composition under changing fire regimes, according to a global systematic meta-analysis.

In this comment we examine a recent study published in Environmental Research Letters that analysed fire history data from forests in Western Australia to suggest that changes in forest structure result in a long-term reduction of fire risk after 56 years since last fire. We examine the data underpinning this study and find that its strongly skewed sample size distribution creates a bias to the extent that the analytical approach would find a pattern of declining fire risk even when there was no decline. Moreover, the very small sample sizes of the longest unburned forests mean that fire mapping errors as small as 1–2 ha can reverse key findings. With documented mapping errors orders of magnitude larger, the dataset is not robust to analysis at this level of precision. An appropriate conclusion, taking into account these detection and sensitivity issues, would be that likelihood of subsequent wildfire is reduced in the first ∼6 years following fire, and remains fairly consistent at a higher level for at least the next 3 decades, with no evidence for a long-term reduction of fire risk. This is relevant given that many fire and forest management decisions are made based on scientific literature. Rather than wildfire risk reducing with increasing time since fire, our projections indicate that ceasing active fire management in the sampled forests could result in landscape wildfire extent 25%–65% above current levels. We recommend further steps that would help provide sound, evidence-based knowledge to inform science, management, and policy.

Changes in fire regimes due to climate change and fire management practices are affecting the timing, length, and distribution of vegetation fires throughout the year. Plant species responses and tolerances to fire differ from season to season and are influenced by species-specific phenological processes. The ability of seeds to tolerate extreme temperatures associated with fire is one of these processes, with survival linked to seed moisture content at the time of exposure. As fire is more often occurring outside historic dry fire seasons, the probability of fire occurring when seeds are hydrated may also be increasing. In this study, we set out to understand the seasonal dynamics of seed hydration for seeds of Banksia woodland species, and how certain seed traits interact with environmental conditions to influence survival of high temperatures associated with fire. We measured the moisture content of seeds buried to 2 cm in the soil seed bank for four common native species and one invasive species on a weekly basis throughout 2017, along with soil moisture content and environmental correlates. We determined water sorption isotherms at 20°C for seeds of each species and used these functions to model weekly variation in seed water activity and predict when seeds are most sensitive to soil heating. Using Generalised additive models (GAMs), we were able to describe approximately 67% of the weekly variance in seed water activity and explored differences in seed hydration dynamics between species. Seed water activity was sufficiently high (i.e., ≥ 0.85 aw) so as to have created an increased risk of mortality if a fire had occurred during an almost continuous period between May and November in the study period (i.e., 2017). There were brief windows when seeds may have been in a dry state during early winter and late spring, and also when they may have been in a wet state during summer and late autumn. These data, and the associated analyses, provide an opportunity to develop approaches to minimize seed mortality during fire and maximize the seed bank response.