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  • Mckee Palm posted an update 5 days, 10 hours ago

    A tandem Bischler-Napieralski/semipinacol rearrangement reaction has been developed for the purpose of assembling a bis(spirocyclic) indole framework, a privileged structural unit of aspidofractinine-type monoterpenoid indole alkaloids, and was used in combination with a subsequent Mannich reaction to expeditiously construct the central bridged bicyclo[2.2.1]heptane ring system of these molecules with contiguous quaternary centers. The development of this novel strategy culminated in the collective total synthesis of four aspidofractinine alkaloids.The PUF60 gene encodes a ubiquitously expressed essential splicing factor that is recruited to the U2snRNA complex. The complex binds to the 3′ splice site of exons in specific target genes and regulates the inclusion or exclusion of such exons. Recently, pathogenic variants of PUF60 have been shown to cause a relatively specific and potentially recognizable pattern of malformation referred to as Verheij syndrome. Here, we report a 12-year-old female patient with a de novo mutation in PUF60 whose phenotype was representative of the milder end of the phenotypic spectrum of Verheij syndrome; the de novo mutation was a frameshift mutation p.(Ser558Cysfs*21) that resulted in the addition of 21 extra amino acids at the carboxy end of the protein. Among the frequent features of Verheij syndrome, the patient exhibited coloboma, cervical spinal segmentation defects, and borderline intellectual functioning, but lacked cardiac abnormalities, deafness, and urogenital abnormalities. The results of RNA analysis using peripheral blood showed the escape of the mutant allele from nonsense-mediated mRNA decay, possibly accounting for the mild phenotype in the presently reported patient. Based on our clinical observations, we inferred that two embryologic processes, closure of the ocular plate and cervical spinal segmentation, are particularly susceptible to deficient PUF60-mediated splicing regulation, compared with other embryogenetic processes leading to the central nervous system, heart, ear, and kidney.This study investigated the structure-activity relationships of 4-phenylpyridin-2-one and 6-phenylpyrimidin-4-one M1 muscarinic acetylcholine receptor (M1 mAChRs) positive allosteric modulators (PAMs). The presented series focuses on modifications to the core and top motif of the reported leads, MIPS1650 (1) and MIPS1780 (2). Profiling of our novel analogues showed that these modifications result in more nuanced effects on the allosteric properties compared to our previous compounds with alterations to the biaryl pendant. Further pharmacological characterisation of the selected compounds in radioligand binding, IP1 accumulation and β-arrestin 2 recruitment assays demonstrated that, despite primarily acting as affinity modulators, the PAMs displayed different pharmacological properties across the two cellular assays. The novel PAM 7 f is a potential lead candidate for further development of peripherally restricted M1 PAMs, due to its lower blood-brain-barrier (BBB) permeability and improved exposure in the periphery compared to lead 2.Presentations to emergency departments (EDs) for non-fatal suicidal behaviour (NFSB) are increasing in Australia and overseas. Our understanding of the factors contributing to this trend remains unclear. In this qualitative phenomenological study, we explored patient perceptions of their ED experience and the interventions provided. The study group comprised 10 adults who had had 3 or more presentations to the ED in a 12-week period for NFSB. Individual interviews were conducted in person with participants and transcribed verbatim. Three broad themes emerged from analysis of the transcripts ED – a safety net; ‘treatment – what treatment!’; and maintaining ED dependence. The findings highlight a failure to understand the needs of those with NFSB and establish better ED treatment strategies and models of aftercare for this sub-group of patients. The findings have implications for mental health nurses working with consumers in the ED and in broader case management roles.The decomposition of urea into ammonia by urease-producing bacterium shows an elevation in the pH level, which can lead to incontinence-associated dermatitis (IAD). This study aimed to examine the efficacy of a combination of antiseptic and urease inhibitor in inhibiting the decomposition of urea by the urease-producing bacterium Proteus mirabilis. We performed in vitro assays to compare the effects of a combination of antiseptic and urease inhibitor, antiseptic only, urease inhibitor only, and an untreated control with the effects of a urea-containing solution. Cultured P. check details mirabilis was mixed with urea-containing solution, followed by the addition of antiseptic and/or urease inhibitor. The main outcome used to assess the efficacy of the different treatments was ammonia concentration at 4-hours post-treatment initiation, and multiple comparison analysis was performed using Dunnett’s test to compare the results between groups. Ammonia concentrations in samples treated with either antiseptic or urease inhibitor were lower than those in the untreated control, while the combination of antiseptic and urease inhibitor resulted in decreased ammonia concentrations compared with either treatment alone. Therefore, the application of both urease inhibitor and antiseptic is more effective for the inhibition of urea decomposition by urease-producing bacteria. Novel preventive strategies using these reagents may be effective for preventing IAD.Metallic zinc (Zn) is considered to be a safe and low-cost anode for rechargeable batteries. Thus, several zinc metal batteries (ZMBs) have been well developed, i. e., zinc silver batteries, Zn-MnO2 batteries, nickel-zinc batteries, zinc-air batteries and other kinds of zinc ion batteries. ZMBs are strongly correlated with electrochemistry, electrodes, electrolytes and battery structures. To support the development of this field, we herein invite some famous research experts to write this roadmap for giving some guidance in future research. The roadmap will include their research status, challenge, opportunities, and the technology advance in their fields. We expect this roadmap will produce active influence in developing green, low-cost, safe ZMBs for our bright life in future.

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