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In a previous study, we optimized the acidic treatment of brown algae to facilitate the efficient sequential extraction of fucoidans and alginates, using a sample of the brown alga Ecklonia radiata . Here, we applied the optimized process to other brown algae feedstocks from South Australia, in order to assess their potential for valorization and to determine whether the process was effective when using different feedstocks. The starting materials included samples of Macrocystis pyrifera , Durvillaea potatorum , Seirococcus axillaris , and two more samples of E. radiata collected from different sites and at different periods. The initial feedstock sample (as used for optimization) was also included for comparison. In terms of product yields, the sequential process appeared to perform similarly for all feedstocks (30–40 % of total available fucoidans and 80–94 % of total available alginates), with the exception of Seirococcus axillaris (5.5 and 74 %, respectively). The remainder of the fucoidans either resisted extraction or were hydrolyzed by the acid treatment. The fucoidan extracts had sulfate contents of 10 to 30 % by weight and fucose contents of 12–30 % by weight and exhibited antioxidant potential, to which the presence of phlorotannins contributed. The quality of the alginates varied, with M. pyrifera yielding the most viscous (599 mPa s) and colorless alginates, while the alginates from S. axillaris had the lowest mannuronic to guluronic acid ratio (0.54), indicating the strongest gel-forming capability.

This book finds that, in many ways, Northern Ireland stands out internationally with its thoughtfully designed evaluation and assessment framework. The major components are well developed, in particular policies for student assessment, school evaluation and school system evaluation. It has been developed using the majority of key design principles recommended by the OECD. The approach to evaluation and assessment combines: central control over policy development and standard setting; transparency over procedures and reporting of results; an increasing responsibility for the implementation of evaluation and assessment among teachers and schools; and central mechanisms to monitor the effectiveness of implementation. For example, while schools and their Boards of Governors are accountable for their educational quality and are accountable to their communities, school development planning processes are also monitored as part of external school evaluation by a central inspectorate. Teachers play a central role in student assessment and their assessment of pupil progress against central standards is moderated by a central agency which engages working teachers in the process. Teachers in primary schools are offered central diagnostic tests to support their assessment of pupil progress. Only teacher appraisal remains entirely school based, but there is a set of common competence standards for teachers.

A bstract Modular Berry transport is a useful way to understand how geometric bulk information is encoded in the boundary CFT: the modular curvature is directly related to the bulk Riemann curvature. We extend this approach by studying modular transport in the presence of a non-trivial quantum extremal surface. Focusing on JT gravity on an AdS background coupled to a non-gravitating bath, we compute the modular curvature of an interval in the bath in the presence of an island: the Quantum Extremal Modular Curvature (QEMC). We highlight some important properties of the QEMC, most importantly that it is non-local in general. In an OPE limit, the QEMC becomes local and probes the bulk Riemann curvature in regions with an island. Our work gives a new approach to probe physics behind horizons.

Peptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that sense PG fragments. However, only a few PG biosynthetic enzymes are direct kinase substrates. Here, we identify the conserved ReoM protein as a novel PASTA-eSTK substrate in the Gram-positive pathogen Listeria monocytogenes. Our data show that the phosphorylation of ReoM is essential as it controls ClpCP-dependent proteolytic degradation of the essential enzyme MurA, which catalyses the first committed step in PG biosynthesis. We also identify ReoY as a second novel factor required for degradation of ClpCP substrates. Collectively, our data imply that the first committed step of PG biosynthesis is activated through control of ClpCP protease activity in response to signals of PG homeostasis imbalance.

Sexual and reproductive health are significant aspects of quality of life. Healthcare often fails to provide adequate support for young cancer survivors in this area, hence the need to develop more effective interventions. The present study aimed to describe experiences of participating in a web-based psycho-educational intervention focusing on sexual dysfunction and fertility distress after cancer, and to explore these experiences within the theoretical frame of the basic psychological needs for competence, relatedness and autonomy according to self-determination theory. Individual semi-structured interviews with 24 women and 4 men, age 19-40, were abductively analyzed using the Framework approach for qualitative content analysis. Participant experiences corresponded well with the three main deductive themes competence, relatedness and autonomy, divided into a total of nine subthemes illustrating varying degrees of basic need satisfaction with considerable nuance but not without ambiguity. While satisfaction of the need for competence could be linked to the amount of information in relation to participants' cognitive capacity, satisfaction of the need for relatedness seemed to be of special importance for these young adults with cancer experience. Invitation to the program meant a chance at alleviating loneliness and normalizing problems, symptoms and concerns. Participants' descriptions of perceived autonomy support were more challenging and ambiguous, because of the many contradictions in participants' responses to their variable situations. Basic psychological needs were confirmed as flexible positions along a continuum rather than discrete and mutually exclusive qualities. Understanding the variety of basic need satisfaction may enhance the design of future web-based interventions to be even more inclusive, tailorable and autonomy-supportive. Further research is warranted to determine the role of basic need satisfaction as a possible mediator for web-based psychoeducational interventions in cancer survivorship care.

Loss-of-function (LOF) mutations in the endothelial cell (EC)-enriched gene endoglin ( ENG) cause the human disease hereditary haemorrhagic telangiectasia-1, characterized by vascular malformations promoted by vascular endothelial growth factor A (VEGFA). How ENG deficiency alters EC behaviour to trigger these anomalies is not understood. Mosaic ENG deletion in the postnatal mouse rendered Eng LOF ECs insensitive to flow-mediated venous to arterial migration. Eng LOF ECs retained within arterioles acquired venous characteristics and secondary ENG-independent proliferation resulting in arteriovenous malformation (AVM). Analysis following simultaneous Eng LOF and overexpression (OE) revealed that ENG OE ECs dominate tip-cell positions and home preferentially to arteries. ENG knockdown altered VEGFA-mediated VEGFR2 kinetics and promoted AKT signalling. Blockage of PI(3)K/AKT partly normalized flow-directed migration of ENG LOF ECs in vitro and reduced the severity of AVM in vivo . This demonstrates the requirement of ENG in flow-mediated migration and modulation of VEGFR2 signalling in vascular patterning. Two studies by Sugden et al. and Jin et al. show that endoglin regulates endothelial cell migration through VEGFR2 signalling and controls blood vessel diameter in response to blood flow.

ObjectiveNecrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother’s own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC.DesignWe performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644).ResultsConcentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of Bifidobacterium longum and higher relative abundance of Enterobacter cloacae in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by Bifidobacterium spp and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or having NEC.ConclusionThese results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification and novel avenues for supplements that may prevent life-threatening disease.

Alzheimer’s disease (AD) is characterized by synapse loss due to mechanisms that remain poorly understood. We show that the neural cell adhesion molecule 2 (NCAM2) is enriched in synapses in the human hippocampus. This enrichment is abolished in the hippocampus of AD patients and in brains of mice overexpressing the human amyloid-β (Aβ) precursor protein carrying the pathogenic Swedish mutation. Aβ binds to NCAM2 at the cell surface of cultured hippocampal neurons and induces removal of NCAM2 from synapses. In AD hippocampus, cleavage of the membrane proximal external region of NCAM2 is increased and soluble extracellular fragments of NCAM2 (NCAM2-ED) accumulate. Knockdown of NCAM2 expression or incubation with NCAM2-ED induces disassembly of GluR1-containing glutamatergic synapses in cultured hippocampal neurons. Aβ-dependent disassembly of GluR1-containing synapses is inhibited in neurons overexpressing a cleavage-resistant mutant of NCAM2. Our data indicate that Aβ-dependent disruption of NCAM2 functions in AD hippocampus contributes to synapse loss. Understanding how ß-amyloid contributes to synapse loss and dysfunction is a central goal of Alzheimer’s disease research. Here, Leshchyns’ka et al. identify a novel mechanism by which Aß disassembles hippocampal glutamatergic synapses via cleavage of a neural cell adhesion molecule 2 (NCAM2).

Amyloid-β (Aβ) toxicity in Alzheimer's disease (AD) is considered to be mediated by phosphorylated tau protein. In contrast, we found that, at least in early disease, site-specific phosphorylation of tau inhibited Aβ toxicity. This specific tau phosphorylation was mediated by the neuronal p38 mitogen-activated protein kinase p38γ and interfered with postsynaptic excitotoxic signaling complexes engaged by Aβ. Accordingly, depletion of p38γ exacerbated neuronal circuit aberrations, cognitive deficits, and premature lethality in a mouse model of AD, whereas increasing the activity of p38γ abolished these deficits. Furthermore, mimicking site-specific tau phosphorylation alleviated Aβ-induced neuronal death and offered protection from excitotoxicity. Our work provides insights into postsynaptic processes in AD pathogenesis and challenges a purely pathogenic role of tau phosphorylation in neuronal toxicity.

Emphasizing the co-benefits of climate policy can motivate action across ideological, age and gender divides regardless of existing levels of concern about climate change, as global survey data shows. Personal and political action on climate change is traditionally thought to be motivated by people accepting its reality and importance. However, convincing the public that climate change is real faces powerful ideological obstacles 1 , 2 , 3 , 4 , and climate change is slipping in public importance in many countries 5 , 6 . Here we investigate a different approach, identifying whether potential co-benefits of addressing climate change 7 could motivate pro-environmental behaviour around the world for both those convinced and unconvinced that climate change is real. We describe an integrated framework for assessing beliefs about co-benefits 8 , distinguishing social conditions (for example, economic development, reduced pollution or disease) and community character (for example, benevolence, competence). Data from all inhabited continents (24 countries; 6,196 participants) showed that two co-benefit types, Development (economic and scientific advancement) and Benevolence (a more moral and caring community), motivated public, private and financial actions to address climate change to a similar degree as believing climate change is important. Critically, relationships were similar for both convinced and unconvinced participants, showing that co-benefits can motivate action across ideological divides. These relationships were also independent of perceived climate change importance, and could not be explained by political ideology, age, or gender. Communicating co-benefits could motivate action on climate change where traditional approaches have stalled.