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ement published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).Rice is a major food crop to approximately half of the human population. Unfortunately, the starchy endosperm, which is the remaining portion of the seed after polishing, contains limited amounts of micronutrients. Here, it is shown that this is particularly the case for thiamin (vitamin B1). Therefore, a tissue-specific metabolic engineering approach was conducted, aimed at enhancing the level of thiamin specifically in the endosperm. To achieve this, three major thiamin biosynthesis genes, THIC, THI1 and TH1, controlled by strong endosperm-specific promoters, were employed to obtain engineered rice lines. The metabolic engineering approaches included ectopic expression of THIC alone, in combination with THI1 (bigenic) or combined with both THI1 and TH1 (trigenic). Determination of thiamin and thiamin biosynthesis intermediates reveals the impact of the engineering approaches on endosperm thiamin biosynthesis. The results show an increase of thiamin in polished rice up to threefold compared to WT, and stable upon cooking. These findings confirm the potential of metabolic engineering to enhance de novo thiamin biosynthesis in rice endosperm tissue and aid in steering future biofortification endeavours.Per- and polyfluoroalkyl substances (PFAS) are widespread, persistent environmental pollutants known to elicit a wide range of negative effects on wildlife species. There is scarce information regarding the toxicity of PFAS on amphibians, but amphibians may be highly susceptible because of their permeable skin and dependence on fresh water. Acute toxicity studies are a first step toward understanding responses to PFAS exposure, providing benchmarks for species-specific tolerances, informing ecological risk assessment (ERA), and designing chronic toxicity studies. We conducted standardized 96-h lethal concentration (LC50) toxicity tests for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) with 9 widely distributed amphibian species native to eastern and central North America. We also conducted LC50 tests with perfluorohexane sulfonate (PFHxS) for 2 species and determined whether toxicity of PFOS and PFOA varied between life stages for 3 species. Acute toxicity varied among PFAS and speciesnd help predict influences on amphibian communities, thereby informing future ERAs for PFAS. Integr Environ Assess Manag 2021;17684-689. © 2021 SETAC.

Serglycin (SRGN) is an intragranular, sulfated proteoglycan in hematopoietic cells that affects granule composition and function.

To understand how SRGN affects platelet granule packaging, cargo release, and extra-platelet microenvironments.

Platelets and megakaryocytes from SRGN

mice were assayed for secretion kinetics, cargo levels, granule morphology upon activation, and receptor shedding.

Metabolic,

SO

labeling identified SRGN as a major sulfated macromolecule in megakaryocytes. SRGN colocalized with α-granule markers (platelet factor 4 [PF4], von Willebrand factor [VWF], and P-selectin), but its deletion did not affect α-granule morphology or number. Platelet α-granule composition was altered, with a reduction in basic proteins (pI ≥8; e.g., PF4, SDF-1, angiogenin) and constitutive release of PF4 from SRGN

megakaryocytes. P-Selectin, VWF, and fibrinogen were unaffected. Serotonin (5-HT) uptake and β-hexosaminidase (HEXB) were slightly elevated. Thrombin-induced exocytosis of PF4 from platelets was defective; however, release of RANTES/CCL5 was normal and osteopontin secretion was more rapid. Release of 5-HT and HEXB (from dense granules and lysosomes, respectively) were unaffected. Ultrastructural studies showed distinct morphologies in activated platelets. The α-granule lumen of SRGN

platelet had a grainy staining pattern, whereas that of wild-type granules had only fibrous material remaining. α-Granule swelling and decondensation were reduced in SRGN

platelets. Upon stimulation of platelets, a SRGN/PF4 complex was released in a time- and agonist-dependent manner. Shedding of GPVI from SRGN

platelets was modestly enhanced. Shedding of GP1b was unaffected.

The polyanionic proteoglycan SRGN influences α-granule packaging, cargo release, and shedding of platelet membrane proteins.

The polyanionic proteoglycan SRGN influences α-granule packaging, cargo release, and shedding of platelet membrane proteins.Proof-of-concept is provided that a large estate of 16-membered macrolide antibiotics can be reached by a "unified" approach. The key building block was formed on scale by an asymmetric vinylogous Mukaiyama aldol reaction; its alkene terminus was then converted either into the corresponding methyl ketone by Wacker oxidation or into a chain-extended aldehyde by catalyst-controlled branch-selective asymmetric hydroformylation. These transformations ultimately opened access to two structurally distinct series of macrolide targets. Notable late-stage maneuvers comprise a rare example of a ruthenium-catalyzed redox isomerization of an 1,3-enyne-5-ol into a 1,3-diene-5-one derivative, as well as the elaboration of a tertiary propargylic alcohol into an acyloin by trans-hydrostannation/Chan-Lam-type coupling. Moreover, this case study illustrates the underutilized possibility of forging complex macrolactone rings by transesterification under essentially neutral conditions.Fasting has been shown to decrease chemotherapy-associated adverse events (AEs), in part through insulin-like growth factor (IGF-1) reduction, and may induce a protective effect on normal cells during chemotherapy treatment in mice and people. The purpose of this study was to evaluate the effect of fasting on constitutional, bone marrow and gastrointestinal (GI) AEs, and serum glucose, IGF-1 and insulin levels in dogs receiving vincristine. The study was a prospective, crossover clinical trial in tumour-bearing dogs. Dogs were randomized to be fasted for 24 to 28 hours prior to and 6 hours following their first or second vincristine treatment, and fed normally for the alternate dose. A significant reduction in nausea, anorexia, lethargy and serum insulin was observed when dogs were fasted; however, no significant differences were found in other GI symptoms, neutrophil count, serum glucose or IGF-1. Fasting prior to vincristine therapy is a safe and effective treatment modality that helped mitigate constitutional and GI AEs in tumour-bearing dogs.

Managing the alliance is considered to be a core competency and central therapeutic change process during cognitive analytic therapy (CAT). This study examined latent trajectories of change in the alliance and their relationship to depression treatment outcomes.

Secondary analysis of a randomized controlled trial.

A sample of N=79 depressed participants completed standardized alliance (WAI-SF) and depression symptom measures (PHQ-9) every session during an 8-session CAT intervention. Growth mixture modelling was applied to model alliance trajectories and to classify cases into different latent classes. Associations between alliance class and post-treatment PHQ-9 scores were examined using hierarchical linear regression, controlling for confounders.

There were two classes of alliance trajectories. The majority class (91%) displayed stable alliance trajectories, whilst a minority class (9%) had initially poor alliance ratings that significantly improved during treatment. Baseline severity and early change in depression symptoms significantly predicted treatment outcomes, but early alliance and longitudinal alliance change did not.

Alliance trajectories did not significantly predict depression treatment outcomes after controlling for initial symptom severity and early change. An important limitation concerns the small sample size, so future replication in larger samples is necessary.

Alliance trajectories did not significantly predict depression treatment outcomes after controlling for initial symptom severity and early change. An important limitation concerns the small sample size, so future replication in larger samples is necessary.Climate change scenarios predict tropical cyclones will increase in both frequency and intensity, which will escalate the amount of terrestrial run-off and mechanical disruption affecting coastal ecosystems. Bacteria are key contributors to ecosystem functioning, but relatively little is known about how they respond to extreme storm events, particularly in nearshore subtropical regions. In this study, we combine field observations and mesocosm experiments to assess bacterial community dynamics and changes in physicochemical properties during early- and late-season tropical cyclones affecting Okinawa, Japan. Storms caused large and fast influxes of freshwater and terrestrial sediment - locally known as red soil pollution - and caused moderate increases of macronutrients, especially SiO2 and PO4 3-, with up to 25 and 0.5 μM respectively. A-1210477 manufacturer We detected shifts in relative abundances of marine and terrestrially derived bacteria, including putative coral and human pathogens, during storm events. Soil input alone did not substantially affect marine bacterial communities in mesocosms, indicating that other components of run-off or other storm effects likely exert a larger influence on bacterial communities. The storm effects were short-lived and bacterial communities quickly recovered following both storm events. The early- and late-season storms caused different physicochemical and bacterial community changes, demonstrating the context-dependency of extreme storm responses in a subtropical coastal ecosystem.The prevalence of inter-arm BP difference is high in hypertension and is associated with adverse cardiovascular outcomes. We performed a retrospective chart review of prevalent patients in the Ottawa Hospital Hypertension Center to assess for prevalence, risk factors, and whether finding of inter-arm BP difference >10 mmHg leads to investigations of the aorta and aortic arch. Inter-arm BP difference among 493 patients was present in 16.2% (95% confidence interval [CI]13.3-19.9%), and it was associated with presence of peripheral arterial disease. Physicians did not investigate ascending aorta and aortic arch for causes of the clinically significant inter-arm BP difference.The front cover artwork is provided by Julián Valero and Marko Škugor from Aarhus University and University of Bonn. The image shows an ad libitum representation of a new class of artificial molecular motors, coined as DNA walkers, on an athletic track testing their performance i.e. speed, directionality and progressivity. Read the full text of the Review at 10.1002/cphc.202000235.

To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability.

Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs).