ve as potential therapeutic strategies for rotator cuff healing.Our understanding of the interactions between the nuclear and mitochondrial genomes is becoming increasingly important as they are extensively involved in establishing early development and developmental progression. Evidence from various biological systems indicates the interdependency between the genomes, which requires a high degree of compatibility and synchrony to ensure effective cellular function throughout development and in the resultant offspring. During development, waves of DNA demethylation, de novo methylation, and maintenance methylation act on the nuclear genome and typify oogenesis and pre- and postimplantation development. At the same time, significant changes in mitochondrial DNA copy number influence the metabolic status of the developing organism in a typically cell-type-specific manner. Collectively, at any given stage in development, these actions establish genomic balance that ensures each developmental milestone is met and that the organism’s program for life is established.Antimicrobial resistance (AMR) is a threat to animal and human health. Antimicrobial use has been identified as a major driver of AMR, and reductions in use are a focal point of interventions to reduce resistance. Accordingly, stakeholders in human health and livestock production have implemented antimicrobial stewardship programs aimed at reducing use. Thus far, these efforts have yielded variable impacts on AMR. Furthermore, scientific advances are prompting an expansion and more nuanced appreciation of the many nonantibiotic factors that drive AMR, as well as how these factors vary across systems, geographies, and contexts. Given these trends, we propose a framework to prioritize AMR interventions. We use this framework to evaluate the impact of interventions that focus on antimicrobial use. We conclude by suggesting that priorities be expanded to include greater consideration of host-microbial interactions that dictate AMR, as well as anthropogenic and environmental systems that promote dissemination of AMR.Purpose The experiment reported here compared two hypotheses for the poor statistical and artificial grammar learning often seen in children and adults with developmental language disorder (DLD; also known as specific language impairment). The procedural learning deficit hypothesis states that implicit learning of rule-based input is impaired, whereas the sequential pattern learning deficit hypothesis states that poor performance is only seen when learners must implicitly compute sequential dependencies. The current experiment tested learning of an artificial grammar that could be learned via feature activation, as observed in an associatively organized lexicon, without computing sequential dependencies and should therefore be learnable on the sequential pattern learning deficit hypothesis, but not on the procedural learning deficit hypothesis. Method Adults with DLD and adults with typical language development (TD) listened to consonant-vowel-consonant-vowel familiarization words from one of two artificial picit hypothesis.In most organisms, fecundity and longevity are negatively associated and the molecular regulation of these two life-history traits is highly interconnected. In addition, nutrient intake often has opposing effects on lifespan and reproduction. In contrast to solitary insects, the main reproductive individual of social hymenopterans, the queen, is also the most long-lived. During development, queen larvae are well-nourished, but we are only beginning to understand the impact of nutrition on the queens’ adult life and the molecular regulation and connectivity of fecundity and longevity. Here, we used two experimental manipulations to alter queen fecundity in the ant Temnothorax rugatulus and investigated associated changes in fat body gene expression. Egg removal triggered a fecundity increase, leading to expression changes in genes with functions in fecundity such as oogenesis and body maintenance. Dietary restriction lowered the egg production of queens and altered the expression of genes linked to autophagy, Toll signalling, cellular homeostasis and immunity. Our study reveals that an experimental increase in fecundity causes the co-activation of reproduction and body maintenance mechanisms, shedding light on the molecular regulation of the link between longevity and fecundity in social insects.Processionary caterpillars of Thaumetopoea pityocampa (in Europe) and Ochrogaster lunifer (in Australia) (Lepidoptera Notodontidae) form single files of larvae crawling head-to-tail when moving to feeding and pupation sites. We investigated if the processions are guided by polarization vision. The heading orientation of processions could be manipulated with linear polarizing filters held above the leading caterpillar. Exposure to changes in the angle of polarization around the caterpillars resulted in corresponding changes in heading angles. Anatomical analysis indicated specializations for polarization vision of stemma I in both species. Stemma I has a rhabdom with orthogonal and aligned microvilli, and an opaque and rugged surface, which are optimizations for skylight polarization vision, similar to the dorsal rim of adult insects. Stemmata II-VI have a smooth and shiny surface and lobed rhabdoms with non-orthogonal and non-aligned microvilli; they are thus optimized for general vision with minimal polarization sensitivity. Behavioural and anatomical evidence reveal that polarized light cues are important for larval orientation and can be robustly detected with a simple visual system.The East Asian experience in tackling COVID-19 has been highly praised, but this high-level generalisation neglects variation in pandemic response measures adopted across countries as well as the socio-political factors that shaped them. This paper compares the early pandemic response in Singapore and Hong Kong, two Asian city-states of similar sizes, a shared history of SARS, and advanced medical systems. Although both were able to contain the virus, they did so using two very different approaches. Drawing upon data from a cross-national, probability sample Internet survey conducted in May 2020 as well as media and mobility data, we argue that the different approaches were the result of the relative strength of civil society vs. the state at the outset of the outbreak. In protest-ridden Hong Kong, low governmental trust bolstered civil society, which focused on self-mobilisation and community mutual-help. In Singapore, a state-led response model that marginalised civil society brought early success but failed to stem an outbreak among its segregated migrant population. Our findings show that an active civil society is pivotal to effective outbreak response and that trust in government may not have been as important as a factor in these contexts.Purpose This scoping study sought to establish a baseline for how well the needs of children with cortical visual impairment (CVI) who use augmentative and alternative communication (AAC) are currently aligned with the services available to them. CVI is the most common cause of visual impairment in children today, and AAC methods rely heavily on vision. Yet, the prevalence of CVI in children who use AAC methods is not yet known, and there is virtually no research concerning use of AAC with children with CVI. Our overarching goals were to identify barriers and suggest priorities for improving outcomes for these children. Method Surveys were distributed anonymously online to professionals from multiple disciplines in different school-based settings and to parents of children with CVI who use AAC. Results School-based professionals identified many barriers, including a lack of knowledge and skills about CVI and about AAC, limited access to training and experts, and concerns about services being delivered in isolated silos with limited time allotted for interprofessional collaboration and planning. Parent reported that their children (M age = 11 years) continued to rely predominantly on body-based forms of communication and lacked access to symbolic language, which, in AAC, is primarily visually based. Conclusions The barriers to services identified by school-based professionals indicate a need to develop and disseminate reliable information about CVI and AAC, both at a preservice and in-service level and, while doing so, to respect the diversity of stakeholders who need this information, including parents. Future research on what types of AAC approaches support the development of language and communication skills for children with CVI is essential.

Three-dimensional computed tomography (3D-CT) is commonly used for the evaluation of cam deformity; however, it does not display the cam border directly.

To compare the efficacy of the best-fit sphere (BFS) method and the alpha angle marking (AAM) method in 3D-CT evaluation for the cam border.

Cohort study (Diagnosis); Level of evidence, 3.

Twenty-six cases of cam deformity, confirmed during hip arthroscopy, were included in this study. All patients underwent a CT scan before surgery. Using multiplanar reconstruction, we obtained reformatted CT images of oblique axial, oblique coronal, and radial views. The alpha angle and femoral head-neck offset ratio (hnoR) were measured on the reformatted CT images. The cam area on 3D-CT was displayed in 4 different ways by importing the markers from the reformatted CT images of the oblique axial view (cam-oa), the oblique coronal view (cam-oc), or the radial view (cam-r) using the AAM method, or by using the BFS method (cam-bfs). The sizes and locations of the dilique axial, oblique coronal, and radial views, with the radial view showing the greatest area.

The cam area displayed by the BFS method on 3D-CT was larger than those evaluated by the AAM method. In the reformatted CT, the sizes and locations of cam deformity differed among the oblique axial, oblique coronal, and radial views, with the radial view showing the greatest area.The cytosolic metalloenzyme leukotriene A4 hydrolase (LTA4H) is the final and rate-limiting enzyme in the biosynthesis of pro-inflammatory leukotriene B4 (LTB4). Preclinical studies have validated this enzyme as an attractive drug target in chronic inflammatory diseases. Despite several attempts, no LTA4H inhibitor has reached the market, yet. Herein, we disclose the discovery and preclinical profile of LYS006, a highly potent and selective LTA4H inhibitor. A focused fragment screen identified hits that could be cocrystallized with LTA4H and inspired a fragment merging. Further optimization led to chiral amino acids and ultimately to LYS006, a picomolar LTA4H inhibitor with exquisite whole blood potency and long-lasting pharmacodynamic effects. Due to its high selectivity and its ability to fully suppress LTB4 generation at low exposures in vivo, LYS006 has the potential for a best-in-class LTA4H inhibitor and is currently investigated in phase II clinical trials in inflammatory acne, hidradenitis suppurativa, ulcerative colitis, and NASH.The development of novel synthetic methods remains a cornerstone in simplifying complex molecule synthesis. Progress in the field of transition metal catalysis has enabled new mechanistic strategies to achieve difficult chemical transformations, increased the value of abundant chemical building blocks, and pushed the boundaries of creative and strategic route design to improve step economy in multistep synthesis. Methodologies to introduce an olefin into saturated molecules continue to be essential transformations because of the plethora of reactions available for alkene functionalization. Of particular importance are dehydrogenation reactions adjacent to electron-withdrawing groups such as carbonyls, which advantageously provide activated olefins that can be regioselectively manipulated. Palladium catalysis occupies a central role in the most widely adopted carbonyl dehydrogenation reactions, but limits to the scope of these protocols persist.In this Account, we describe our group’s contributions to the area of transition-metal-catalyzed dehydrogenation using palladium catalysis and more sustainable and economical nickel catalysis.