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Diatoms are major contributors to global primary production and their populations in the modern oceans are affected by availability of iron, nitrogen, phosphate, silica, and other trace metals, vitamins, and infochemicals. However, little is known about the role of phosphorylation in diatoms and its role in regulation and signaling. We report a total of 2759 phosphorylation sites on 1502 proteins detected in Phaeodactylum tricornutum. Conditionally phosphorylated peptides were detected at low iron (n = 108), during the diel cycle (n = 149), and due to nitrogen availability (n = 137). Through a multi-omic comparison of transcript, protein, phosphorylation, and protein homology, we identify numerous proteins and key cellular processes that are likely under control of phospho-regulation. We show that phosphorylation regulates: (1) carbon retrenchment and reallocation during growth under low iron, (2) carbon flux towards lipid biosynthesis after the lights turn on, (3) coordination of transcription and translation over the diel cycle and (4) in response to nitrogen depletion. We also uncover phosphorylation sites for proteins that play major roles in diatom Fe sensing and utilization, including flavodoxin and phytotransferrin (ISIP2A), as well as identify phospho-regulated stress proteins and kinases. These findings provide much needed insight into the roles of protein phosphorylation in diel cycling and nutrient sensing in diatoms.

Aim: To infer species identity, population isolation, and geographical variation in inter-specific hybridization among corals of the genus Pontes from the central and eastern tropical Pacific, with a focus on the timing of separation between populations of P. evermanni and P. lobata divided by the Eastern Pacific Barrier. Location: Hawaii, American Samoa, Panama and the Galapagos Islands of Ecuador. Methods: Maximum likelihood gene trees were obtained for mitochondrial DNA (COI), the internal transcribed spacer (ITS), and 5 single-copy nuclear (SCN) gene regions. Allelic networks were used to group multi-locus sen data into species clusters despite some alíele sharing. Coalescent analyses (IMa2) of the 5 sen markers were used to estimate the time of population divergence and test for introgression between P. evermanni and P. lobata. Results: Allelic networks based on sen gene sequences agreed with mtCOI and ITS designations. Divergence times between Hawaiian and eastern Pacific populations are consistent with an early Pleistocene recolonization of the eastern Pacific by P. evermanni followed by a more recent arrival of P. lobata. The two species were fully isolated in Hawaii/American Samoa populations, but introgression from P. evermanni into P. lobata was evident in the eastern Pacific. Main conclusions: These results are consistent with a scenario where a bout of introgression with P. evermanni> an early-arriving colonizer of the eastern Pacific suited to marginal environmental conditions, facilitated the later colonization of the more sensitive P. lobata.

The ocean is the largest reservoir of mobile carbon over decadal to centennial time scales, absorbing approximately 41% of cumulative anthropogenic CO sub(2) emissions (Sabine and Tanhua, 2010). Various geoengineering solutions seek to exploit this uptake capacity (see Vaughan and Lenton, 2011, for a review), including CO sub(2) injection (Marchetti, 1977), iron fertilization (Martin et al., 1994), and artificial upwelling (Lovelock and Rapley, 2007). The ubiquity of social media- allowing anyone to \"self-publish\"-and funding from crowd-sources and private foundations have allowed some proposals to gain traction outside of the peer-reviewed scientific literature. A recent example is the proposal by theoretical neurobiologist W.H. Calvin (2013) to construct a massive array of push-pull pump systems to enhance the ocean's natural biological pump to sequester atmospheric CO sub(2).

LEDs offer a wide range of spectral output with high efficiencies. However, the efficiencies of solid-state LEDs with green and yellow wavelengths are rather low due to the lack of suitable direct bandgap materials. Here, we introduce and develop perylene-enhanced green LEDs that produce a higher wall-plug efficiency of 48% compared to 38% for a solid-state green LED. While the wall-plug efficiency of the perylene-enhanced red LED is still lower than that of a solid-state red LED, we demonstrate that remote phosphor colour converters are effective solutions for targeted spectral tuning across the visible spectrum for horticultural lighting. In this work, we retrofit existing white LEDs and augment photosynthesis via spectral output tuning to achieve a higher red-to-blue ratio. Our results show a significant improvement in plant growth by up to 39%, after a 4-month growth cycle. We observe no visible degradation of the colour converter even under continuous illumination with a current of 400 mA. This opens up new opportunities for using perylene-based colour converters for tuneable illumination with high brightness.

Macrophytes can be crucial for maintaining clear water conditions in temperate shallow lakes. However, their restorative potential and role in regulating phytoplankton remains uncertain in tropical lakes. We investigated the effects of emergent (Ludwigia adscendens and Persicaria barbata) and submerged (Vallisneria spiralis) macrophytes on the phytoplankton community of a turbid tropical reservoir. Through two in situ mesocosm experiments (~ 1000 l capacity) lasting 4 weeks, we (1) determined the effects of macrophyte density on phytoplankton biomass and composition, and (2) compared these effects between emergent and submerged macrophytes. In Experiment 1, macrophyte treatments reduced phytoplankton biomass and increased water clarity in a density-dependent manner. Only the ‘high density’ treatment (300 g/m2 emergent and 650 g/m2 submerged macrophytes) induced a taxonomic and functional shift from an initial community dominated by turbid water-adapted filamentous cyanobacteria to one dominated by clear water-adapted green algae and cryptophytes. In Experiment 2, emergent and submerged macrophytes reduced phytoplankton biomass and distinctly altered taxonomic and functional composition, with submerged macrophytes inhibiting Microcystis and stimulating cryptophyte taxa. Our results indicate that macrophytes can induce substantial phytoplankton community shifts in turbid tropical lakes, demonstrating the potential to assist in the reversal from turbid to clear water states during restoration efforts.

Alveolar macrophages (AM) must perform three seemingly opposing roles including homeostasis, driving inflammation, and facilitating tissue repair. Whilst there is now consensus (supported by a large body of human single cell RNA sequencing (scRNA-seq) data) that the cell subsets that perform these tasks can readily be found based on their transcriptome, their ontogeny has remained unclear. Moreover, there is agreement that in all types of pulmonary fibrosis (PF) there is an expanded population of profibrotic AM that may aberrantly drive PF. From a therapeutic viewpoint, there is great appeal in the notion that the transcriptional program in different AM subsets is not fixed but remains plastic and amenable to pharmacological reprogramming. Accordingly, this study addresses this question by performing scRNA-seq on human AM following treatment with drugs or perturbagens including pioglitazone, trametinib, nintedanib, lipopolysaccharide and the natural compound endiandrin A. Each treatment induced a unique global transcriptional change, driving the cells towards distinct subsets, further supported by trajectory analysis, confirming a high level of plasticity. Confirmatory experiments using qPCR demonstrated that single exposure to a compound induced a relatively stable transcriptome, whereas serial exposure to a different compound allowed the cells to be reprogrammed yet again to a different phenotype. These findings add new insight into the biology of AM and support the development of novel therapies to treat PF.

Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of the interstitial pneumonias. The cause of the disease is unknown, and new therapies that stop or reverse disease progression are desperately needed. Recent advances in next-generation sequencing have led to an abundance of freely available, clinically relevant, organ-and-disease-specific, single-cell transcriptomic data, including studies from patients with IPF. We mined data from published IPF data sets and identified gene signatures delineating pro-fibrotic or antifibrotic macrophages and then used the Enrichr platform to identify compounds with the potential to drive the macrophages toward the antifibrotic transcriptotype. We then began testing these compounds in a novel in vitro phenotypic drug screening assay utilising human lung macrophages recovered from whole-lung lavage of patients with silicosis. As predicted by the Enrichr tool, glitazones potently modulated macrophage gene expression towards the antifibrotic phenotype. Next, we assayed a subset of the NatureBank pure compound library and identified the cyclobutane lignan, endiandrin A, which was isolated from the roots of the endemic Australian rainforest plant, Endiandra anthropophagorum, with a similar antifibrotic potential to the glitazones. These methods open new avenues of exploration to find treatments for lung fibrosis.

Infectious diseases of the central nervous system (CNS) remain common and life-threatening, especially in developing countries. Knowledge of the aetiological agents responsible for these infections is essential to guide empiric therapy and develop a rational public health policy. To date most data has come from patients admitted to tertiary referral hospitals in Asia and there is limited aetiological data at the provincial hospital level where most patients are seen. We conducted a prospective Provincial Hospital-based descriptive surveillance study in adults and children at thirteen hospitals in central and southern Viet Nam between August 2007-April 2010. The pathogens of CNS infection were confirmed in CSF and blood samples by using classical microbiology, molecular diagnostics and serology. We recruited 1241 patients with clinically suspected infection of the CNS. An aetiological agent was identified in 640/1241 (52%) of the patients. The most common pathogens were Streptococcus suis serotype 2 in patients older than 14 years of age (147/617, 24%) and Japanese encephalitis virus in patients less than 14 years old (142/624, 23%). Mycobacterium tuberculosis was confirmed in 34/617 (6%) adult patients and 11/624 (2%) paediatric patients. The acute case fatality rate (CFR) during hospital admission was 73/617 (12%) in adults and to 42/624 (7%) in children. Zoonotic bacterial and viral pathogens are the most common causes of CNS infection in adults and children in Viet Nam.

We report the case of a 69‐year‐old man five‐month post double lung transplant for idiopathic pulmonary fibrosis (IPF) who presented with progressive breathlessness, loss of lung function, and diffuse ground glass shadowing on the chest computed tomography. Transbronchial lung biopsy revealed foamy macrophages, hyperplasia of type II pneumocytes, and eosinophilic material in the alveolar space. Video thoracic lung biopsy was performed, and histology confirmed pulmonary alveolar proteinosis. Anti‐granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) antibodies were negative. Bilateral sequential whole lung lavage (WLL) was performed. Lavage fluid recovered during WLL was notably dark brown in colour and upon analysis was shown to contain heavily oxidized protein (lipofuscin), giant lipofuscin‐engorged macrophages, and a highly pro‐inflammatory gene expression profile. Following WLL, the patient's symptoms, lung function, and radiology appearance improved. His repeat bronchoalveolar lavage (BAL) fluid analysis showed reduced lipofuscin and normalized macrophage size and gene expression. Here, we report a case of secondary pulmonary alveolar proteinosis (PAP) after double lung transplantation with highly oxidized protein and pro‐inflammatory gene expression in whole lung lavage (WLL) fluid. Our patient was successfully treated with WLL. His repeat bronchoalveolar lavage (BAL) fluid analysis showed reduced lipofuscin and normalized macrophage size and gene expression.

IntroductionRecent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening.Methods and analysisA multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population.Ethics and disseminationEthics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences.Trial registration numbersNCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).