NUAK: never underestimate a kinase.

NUAK1 and NUAK2 belong to a family of kinases related to the catalytic α-subunits of the AMP-activated protein kinase (AMPK) complexes. Despite canonical activation by the tumour suppressor kinase LKB1, both NUAKs exhibit a spectrum of activities that favour tumour development and progression. Here, we review similarities in structure and function of the NUAKs, their regulation at gene, transcript and protein level, and discuss their phosphorylation of specific downstream targets in the context of the signal transduction pathways and biological activities regulated by each or both NUAKs.

Advances in Legume Systematics 14. Classification of Caesalpinioideae. Part 2: Higher-level classification.

Caesalpinioideae is the second largest subfamily of legumes (Leguminosae) with ca. 4680 species and 163 genera. It is an ecologically and economically important group formed of mostly woody perennials that range from large canopy emergent trees to functionally herbaceous geoxyles, lianas and shrubs, and which has a global distribution, occurring on every continent except Antarctica.

Kinase signalling adaptation supports dysfunctional mitochondria in disease.

Mitochondria form a critical control nexus which are essential for maintaining correct tissue homeostasis. An increasing number of studies have identified dysregulation of mitochondria as a driver in cancer. However, which pathways support and promote this adapted mitochondrial function? A key hallmark of cancer is perturbation of kinase signalling pathways.

Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response.

Mitochondrial outer membrane permeabilisation (MOMP) is often essential for apoptosis, by enabling cytochrome c release that leads to caspase activation and rapid cell death. Recently, MOMP has been shown to be inherently pro-inflammatory with emerging cellular roles, including its ability to elicit anti-tumour immunity. Nonetheless, how MOMP triggers inflammation and how the cell regulates this remains poorly defined.

Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.

Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking.

Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma.

Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration.

Phylogenomics reveals extreme gene tree discordance in a lineage of dominant trees: hybridization, introgression, and incomplete lineage sorting blur deep evolutionary relationships despite clear species groupings in Eucalyptus subgenus Eudesmia.

Eucalypts are a large and ecologically important group of plants on the Australian continent, and understanding their evolution is important in understanding evolution of the unique Australian flora. Previous phylogenies using plastome DNA, nuclear-ribosomal DNA, or random genome-wide SNPs, have been confounded by limited genetic sampling or by idiosyncratic biological features of the eucalypts, including widespread plastome introgression. Here we present phylogenetic analyses of Eucalyptus subgenus Eudesmia (22 species from western, northern, central and eastern Australia), in the first study to apply a target-capture sequencing approach using custom, eucalypt-specific baits (of 568 genes) to a lineage of Eucalyptus.

Treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs: British Society for Rheumatology guideline scope.

Pharmacological management has advanced considerably since the 2015 British Society for Rheumatology axial spondyloarthritis (axSpA) guideline to incorporate new classes of biologic DMARDs (bDMARDs, including biosimilars), targeted synthetic DMARDs (tsDMARDs) and treatment strategies such as drug tapering. The aim of this guideline is to provide an evidence-based update on pharmacological management of adults with axSpA (including AS and non-radiographic axSpA) using b/tsDMARDs. This guideline is aimed at health-care professionals in the UK who care directly for people with axSpA, including rheumatologists, rheumatology specialist nurses, allied health professionals, rheumatology specialty trainees and pharmacists; people living with axSpA; and other stakeholders, such as patient organizations and charities.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

NUAK1 governs centrosome replication in pancreatic cancer via MYPT1/PP1β and GSK3β-dependent regulation of PLK4.

The AMP-activated protein kinase (AMPK)-related kinase NUAK1 (NUAK family SNF1-like kinase 1) has emerged as a potential vulnerability in MYC-dependent cancer but the biological roles of NUAK1 in different settings are poorly characterised, and the spectrum of cancer types that exhibit a requirement for NUAK1 is unknown. Unlike canonical oncogenes, NUAK1 is rarely mutated in cancer and appears to function as an obligate facilitator rather than a cancer driver per se. Although numerous groups have developed small-molecule NUAK inhibitors, the circumstances that would trigger their use and the unwanted toxicities that may arise as a consequence of on-target activity are thus undetermined.

Symptomatic Myocardial Bridging in D-Transposition of the Great Arteries Post-Arterial Switch.

We present Stanford's experience with patients post-arterial switch operation presenting with chest pain found to have hemodynamically significant myocardial bridging. The evaluation of symptomatic patients post-arterial switch should not only include assessment for coronary ostial patency but also for nonobstructive coronary conditions such as myocardial bridging. ().

Precipitation is the main axis of tropical plant phylogenetic turnover across space and time.

Early natural historians-Comte de Buffon, von Humboldt, and De Candolle-established environment and geography as two principal axes determining the distribution of groups of organisms, laying the foundations for biogeography over the subsequent 200 years, yet the relative importance of these two axes remains unresolved. Leveraging phylogenomic and global species distribution data for Mimosoid legumes, a pantropical plant clade of c. 3500 species, we show that the water availability gradient from deserts to rain forests dictates turnover of lineages within continents across the tropics.

Phylogeny and classification of the Australasian and Indomalayan mimosoid legumes and (Leguminosae, subfamily Caesalpinioideae, mimosoid clade).

The morphologically variable genus is the second largest mimosoid legume genus from the Indomalayan-Australasian region, yet it has not been well represented in phylogenetic studies. Phylogenies that have included multiple representatives of suggest it may not be monophyletic, and the same applies to , another understudied genus of the Archidendron clade. The most comprehensive phylogeny of and to date is presented, based on four nuclear markers (ITS, ETS, SHMT and RBPCO).

Phylogenomic analysis of 997 nuclear genes reveals the need for extensive generic re-delimitation in Caesalpinioideae (Leguminosae).

Subfamily Caesalpinioideae with ca. 4,600 species in 152 genera is the second-largest subfamily of legumes (Leguminosae) and forms an ecologically and economically important group of trees, shrubs and lianas with a pantropical distribution. Despite major advances in the last few decades towards aligning genera with clades across Caesalpinioideae, generic delimitation remains in a state of considerable flux, especially across the mimosoid clade.

Can 10 000 Healthy Steps a Day Slow Aortic Root Dilation in Pediatric Patients With Marfan Syndrome?

Background Stiffer aortas are associated with a faster rate of aortic root (AoR) dilation and higher risk of aortic dissection in patients with Marfan syndrome. We have previously shown that mild aerobic exercise reduces aortic stiffness and rate of AoR dilation in a Marfan mouse model. In this study, we investigated if these results could be translated to pediatric patients with Marfan syndrome.

Hepatic glutamine synthetase controls N-methylglutamine in homeostasis and cancer.

Glutamine synthetase (GS) activity is conserved from prokaryotes to humans, where the ATP-dependent production of glutamine from glutamate and ammonia is essential for neurotransmission and ammonia detoxification. Here, we show that mammalian GS uses glutamate and methylamine to produce a methylated glutamine analog, N-methylglutamine. Untargeted metabolomics revealed that liver-specific GS deletion and its pharmacological inhibition in mice suppress hepatic and circulating levels of N-methylglutamine.

A genome resource for Acacia, Australia's largest plant genus.

Acacia (Leguminosae, Caesalpinioideae, mimosoid clade) is the largest and most widespread genus of plants in the Australian flora, occupying and dominating a diverse range of environments, with an equally diverse range of forms. For a genus of its size and importance, Acacia currently has surprisingly few genomic resources. Acacia pycnantha, the golden wattle, is a woody shrub or tree occurring in south-eastern Australia and is the country's floral emblem.

Long-read assemblies reveal structural diversity in genomes of organelles - an example with .

Organelle genomes are typically represented as single, static, circular molecules. However, there is evidence that the chloroplast genome exists in two structural haplotypes and that the mitochondrial genome can display multiple circular, linear or branching forms. We sequenced and assembled chloroplast and mitochondrial genomes of the Golden Wattle, , using long reads, iterative baiting to extract organelle-only reads, and several assembly algorithms to explore genomic structure.

Navigating through chemical space and evolutionary time across the Australian continent in plant genus Eremophila.

Eremophila is the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological diversity across the Australian continent. The Australian Aboriginal Peoples recognize many Eremophila species as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic studies have revealed complex evolutionary relationships between Eremophila and related genera in the tribe.