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In Huntington's disease (HD), a key pathological feature includes the development of inclusion-bodies of fragments of the mutant huntingtin protein in the neurons of the striatum and hippocampus. To examine the molecular changes associated with inclusion-body formation, we applied MALDI-mass spectrometry imaging and deuterium pulse labelling to determine lipid levels and synthesis rates in the hippocampus of a transgenic mouse model of HD (R6/1 line). The R6/1 HD mice lacked inclusions in the hippocampus at 6 weeks of age (pre-symptomatic), whereas inclusions were pervasive by 16 weeks of age (symptomatic). Hippocampal subfields (CA1, CA3 and DG), which formed the highest density of inclusion formation in the mouse brain showed a reduction in the relative abundance of neuron-enriched lipids that have roles in neurotransmission, synaptic plasticity, neurogenesis, and ER-stress protection. Lipids involved in the adaptive response to ER stress (phosphatidylinositol, phosphatidic acid, and ganglioside classes) displayed increased rates of synthesis in HD mice relative to WT mice at all the ages examined, including prior to the formation of the inclusion bodies. Our findings, therefore, support a role for ER stress occurring pre-symptomatically and potentially contributing to pathological mechanisms underlying HD.

Non-alcoholic steatohepatitis (NASH), characterized as the joint presence of steatosis, hepatocellular ballooning and lobular inflammation, and liver fibrosis are strong contributors to liver-related and overall mortality. Despite the high global prevalence of NASH and the substantial healthcare burden, there are currently no FDA-approved therapies for preventing or reversing NASH and/or liver fibrosis. Importantly, despite nearly 200 pharmacotherapies in different phases of pre-clinical and clinical assessment, most therapeutic approaches that succeed from pre-clinical rodent models to the clinical stage fail in subsequent Phase I-III trials. In this respect, one major weakness is the lack of adequate mouse models of NASH that also show metabolic comorbidities commonly observed in NASH patients, including obesity, type 2 diabetes and dyslipidaemia. This study provides an in-depth comparison of NASH pathology and deep metabolic profiling in eight common inbred mouse strains (A/J, BALB/c, C3H/HeJ, C57BL/6J, CBA/CaH, DBA/2J, FVB/N and NOD/ShiLtJ) fed a western-style diet enriched in fat, sucrose, fructose and cholesterol for eight months. Combined analysis of histopathology and hepatic lipid metabolism, as well as measures of obesity, glycaemic control and insulin sensitivity, dyslipidaemia, adipose tissue lipolysis, systemic inflammation and whole-body energy metabolism points to the FVB/N mouse strain as the most adequate diet-induced mouse model for the recapitulation of metabolic (dysfunction) associated fatty liver disease (MAFLD) and NASH. With efforts in the pharmaceutical industry now focussed on developing multi-faceted therapies; that is, therapies that improve NASH and/or liver fibrosis, and concomitantly treat other metabolic comorbidities, this mouse model is ideally suited for such pre-clinical use.

Nonalcoholic fatty liver disease (NAFLD) and impaired glycemic control are closely linked; however, the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. The high secretory capacity of the liver and impairments in protein secretion in NAFLD suggest that endocrine changes in the liver are likely to contribute to glycemic defects. We identify hexosaminidase A (HEXA) as an NAFLD-induced hepatokine in both mice and humans. HEXA regulates sphingolipid metabolism, converting GM2 to GM3 gangliosides-sphingolipids that are primarily localized to cell-surface lipid rafts. Using recombinant murine HEXA protein, an enzymatically inactive HEXA(R178H) mutant, or adeno-associated virus vectors to induce hepatocyte-specific overexpression of HEXA, we show that HEXA improves blood glucose control by increasing skeletal muscle glucose uptake in mouse models of insulin resistance and type 2 diabetes, with these effects being dependent on HEXA's enzymatic action. Mechanistically, HEXA remodels muscle lipid raft ganglioside composition, thereby increasing IGF-1 signaling and GLUT4 localization to the cell surface. Disrupting lipid rafts reverses these HEXA-mediated effects. In this study, we identify a pathway for intertissue communication between liver and skeletal muscle in the regulation of systemic glycemic control.

We conducted a lipidomic analysis of the whole body of female Aedes aegypti mosquitoes at different time points over the course of feeding and reproduction. There were temporal biphasic increases of more than 80% of lipids identified at the time of feeding and from 16 h to 30 h post blood meal (PBM). During these two increases, the abundance of many lipids dropped while body weight remained stable, probably reflecting blood lipid digestion and the synthesis of vitellogenin in this period. A concerted temporal pattern was particularly strong at the second peak for membrane and signalling lipids such as phosphatidylethanolamine (PE), phosphatidylinositol (PI), cardiolipin (CL), hexosylceramide (HexCer) and lyso-phosphatidic acid (LPA). Lyso-glycerophospholipids showed three distinct change patterns that are functionally related: Lyso-PE and Lyso-phosphatidylcholine (LPC), which are membrane lipids, showed little change; LPA, a signalling lipid, showed a significant increase from 16 to 30 h PBM; Lyso-PI, a bioactive lipid, and both lyso-phosphatidylglycerol (LPG) and lyso-phosphatidylserine (LPS), which are bacterial membrane lipids, showed one significant increase from the time of feeding to 16 h post blood meal. The result of our study on the anautogenous insect Ae. aegypti point to specific lipids likely to be important in the reproductive process with a role in the formation and growth of ovarian follicles.

Fungal pathogens pose a major threat to Cannabis sativa production, requiring safe and effective management procedures to control disease. Chitin and chitosan are natural molecules that elicit plant defense responses. Investigation of their effects on C. sativa will advance understanding of plant responses towards elicitors and provide a potential pathway to enhance plant resistance against diseases. Plants were grown in the in vitro Root-TRAPR system and treated with colloidal chitin and chitosan. Plant morphology was monitored, then plant tissues and exudates were collected for enzymatic activity assays, phytohormone quantification, qPCR analysis and proteomics profiling. Chitosan treatments showed increased total chitinase activity and expression of pathogenesis-related (PR) genes by 3-5 times in the root tissues. In the exudates, total peroxidase and chitinase activities and levels of defense proteins such as PR protein 1 and endochitinase 2 were increased. Shoot development was unaffected, but root development was inhibited after chitosan exposure. In contrast, chitin treatments had no significant impact on any defense parameters, including enzymatic activities, hormone quantities, gene expression levels and root secreted proteins. These results indicate that colloidal chitosan, significantly enhancing defense responses in C. sativa root system, could be used as a potential elicitor, particularly in hydroponic scenarios to manage crop diseases.

Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5'-monophosphate-mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid-sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5'-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite Plasmodium falciparum, namely tyrosine RS (PfYRS). ML901 exerts whole-life-cycle-killing activity with low nanomolar potency and single-dose efficacy in a mouse model of malaria. X-ray crystallographic studies of plasmodium and human YRSs reveal differential flexibility of a loop over the catalytic site that underpins differential susceptibility to reaction hijacking by ML901.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is linked to impaired lipid metabolism and systemic insulin resistance, which is partly mediated by altered secretion of liver proteins known as hepatokines. Regular physical activity can resolve NAFLD and improve its metabolic comorbidities, however, the effects of exercise training on hepatokine secretion and the metabolic impact of exercise-regulated hepatokines in NAFLD remain unresolved. Herein, we examined the effect of endurance exercise training on hepatocyte secreted proteins with the aim of identifying proteins that regulate metabolism and reduce NAFLD severity. METHODS: C57BL/6 mice were fed a high-fat diet for six weeks to induce NAFLD. Mice were exercise trained for a further six weeks, while the control group remained sedentary. Hepatocytes were isolated two days after the last exercise bout, and intracellular and secreted proteins were detected using label-free mass spectrometry. Hepatocyte secreted factors were applied to skeletal muscle and liver ex vivo and insulin action and fatty acid metabolism were assessed. Syndecan-4 (SDC4), identified as an exercise-responsive hepatokine, was overexpressed in the livers of mice using adeno-associated virus. Whole-body energy homeostasis was assessed by indirect calorimetry and skeletal muscle and liver metabolism was assessed using radiometric techniques. RESULTS: Proteomics analysis detected 2657 intracellular and 1593 secreted proteins from mouse hepatocytes. Exercise training remodelled the hepatocyte proteome, with differences in 137 intracellular and 35 secreted proteins. Bioinformatic analysis of hepatocyte secreted proteins revealed enrichment of tumour suppressive proteins and proteins involved in lipid metabolism and mitochondrial function, and suppression of oncogenes and regulators of oxidative stress. Hepatocyte secreted factors from exercise trained mice improved insulin action in skeletal muscle and increased hepatic fatty acid oxidation. Hep

Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, yet the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. Using proteomic approaches, we interrogate hepatocyte protein secretion in two models of murine NASH to understand how liver-derived factors modulate lipid metabolism and insulin sensitivity in peripheral tissues. We reveal striking hepatokine remodelling that is associated with insulin resistance and maladaptive lipid metabolism, and identify arylsulfatase A (ARSA) as a hepatokine that is upregulated in NASH and type 2 diabetes. Mechanistically, hepatic ARSA reduces sulfatide content and increases lysophosphatidylcholine (LPC) accumulation within lipid rafts and suppresses LPC secretion from the liver, thereby lowering circulating LPC and lysophosphatidic acid (LPA) levels. Reduced LPA is linked to improvements in skeletal muscle insulin sensitivity and systemic glycemic control. Hepatic silencing of Arsa or inactivation of ARSA's enzymatic activity reverses these effects. Together, this study provides a unique resource describing global changes in hepatokine secretion in NASH, and identifies ARSA as a regulator of liver to muscle communication and as a potential therapeutic target for type 2 diabetes.

Eukaryotic cells respond to heat shock through several regulatory processes including upregulation of stress responsive chaperones and reversible shutdown of cellular activities through formation of protein assemblies. However, the underlying regulatory mechanisms of the recovery of these heat-induced protein assemblies remain largely elusive. Here, we measured the proteome abundance and solubility changes during recovery from heat shock in the mouse Neuro2a cell line. We found that prefoldins and translation machinery are rapidly down-regulated as the first step in the heat shock response. Analysis of proteome solubility reveals that a rapid mobilization of protein quality control machineries, along with changes in cellular energy metabolism, translational activity, and actin cytoskeleton are fundamental to the early stress responses. In contrast, longer term adaptation to stress involves renewal of core cellular components. Inhibition of the Hsp70 family, pivotal for the heat shock response, selectively and negatively affects the ribosomal machinery and delays the solubility recovery of many nuclear proteins. ProteomeXchange: PXD030069.

Parasitic roundworms (nematodes) cause destructive diseases, and immense suffering in humans and other animals around the world. The control of these parasites relies heavily on anthelmintic therapy, but treatment failures and resistance to these drugs are widespread. As efforts to develop vaccines against parasitic nematodes have been largely unsuccessful, there is an increased focus on discovering new anthelmintic entities to combat drug resistant worms. Here, we employed thermal proteome profiling (TPP) to explore hit pharmacology and to support optimisation of a hit compound (UMW-868), identified in a high-throughput whole-worm, phenotypic screen. Using advanced structural prediction and docking tools, we inferred an entirely novel, parasite-specific target (HCO_011565) of this anthelmintic small molecule in the highly pathogenic, blood-feeding barber's pole worm, and in other socioeconomically important parasitic nematodes. The "hit-to-target" workflow constructed here provides a unique prospect of accelerating the simultaneous discovery of novel anthelmintics and associated parasite-specific targets.

BACKGROUND: A lack of clear trial evidence often hampers clinical decision-making during support of the preterm lung at birth. Protein biomarkers have been used to define acute lung injury phenotypes and improve patient selection for specific interventions in adult respiratory distress syndrome. The objective of the study was to use proteomics to provide a deeper biological understanding of acute lung injury phenotypes resulting from different aeration strategies at birth in the preterm lung. METHODS: Changes in protein abundance against an unventilated group (n = 7) were identified via mass spectrometry in a biobank of gravity dependent and non-dependent lung tissue from preterm lambs managed with either a Sustained Inflation (SI, n = 20), Dynamic PEEP (DynPEEP, n = 19) or static PEEP (StatPEEP, n = 11). Ventilation strategy-specific pathways and functions were identified (PANTHER and WebGestalt Tool) and phenotypes defined using integrated analysis of proteome, physiological and clinical datasets (MixOmics package). RESULTS: 2372 proteins were identified. More altered proteins were identified in the non-dependent lung, and in SI group than StatPEEP and DynPEEP. Different inflammation, immune system, apoptosis and cytokine pathway enrichment were identified for each strategy and lung region. Specific integration maps of clinical and physiological outcomes to specific proteins could be generated for each strategy. CONCLUSIONS: Proteomics mapped the molecular events initiating acute lung injury and identified detailed strategy-specific phenotypes. This study demonstrates the potential to characterise preterm lung injury by the direct aetiology and response to lung injury; the first step towards true precision medicine in neonatology.

Background: Olanzapine is used to treat schizophrenia and bipolar disorder in women of childbearing age. Continuation of psychotropic medications throughout pregnancy and lactation is often required as cessation could be dangerous for both mother and child. However, there is a lack of information on the transfer of these drugs into the developing brain. Methods: Sprague Dawley rats at three developmental ages: embryonic day E19, postnatal day P4 and non-pregnant adult females were administered unlabelled or radiolabelled ( 3H) olanzapine (0.15 mg/kg) either as monotherapy or in combination with each of seven other common medications. Similar injections were administered to pregnant E19 females to investigate placental transfer. Olanzapine in plasma, cerebrospinal fluid (CSF) and brain was measured by liquid scintillation counting after a single dose (acute) or following 5 days of treatment (prolonged). Results: Olanzapine entry into brain and CSF was not age-dependent. Prolonged olanzapine treatment reduced placental transfer from 53% to 46% (p<0.05). Co-administration of digoxin or lamotrigine with olanzapine increased its entry into the fetal brain, whereas paracetamol decreased its entry into the CSF. Placental transfer of olanzapine was increased by co-treatment with cimetidine and digoxin, whereas co-treatment with lamotrigine, paracetamol or valproate led to a substantial decrease. Repeated co-treatment of digoxin and olanzapine increased olanzapine transfer into the brain and CSF, but not across the placenta. Overall entry of olanzapine from maternally administered drugs into the fetal brain was higher after combination therapy with cimetidine and digoxin. Conclusions: Co-administration of olanzapine with some commonly used drugs affected its entry into the fetus and its developing brain to a greater extent than in adults. It appears that protection of the fetal brain for these drugs primarily comes from the placenta rather than from the fetal brain barriers.

The coupled data assimilation (CDA) system consisting of ocean, sea‐ice, and atmosphere data assimilation components with the Beijing Climate Center (BCC) Climate System Model has been developed to provide reliable analyses of the atmosphere, ocean, and sea‐ice states. It incorporates ocean temperature/salinity profiles, sea surface temperature, sea level height, and sea‐ice concentration observations at a daily frequency, and atmosphere reanalysis at a 6‐hourly frequency. Results show that the system is capable of realistically reproducing the climatology and variability of ocean, sea‐ice, and atmosphere. The performances in analyzing ocean component are comparable to those of well‐known ocean reanalyses that were once used to initialize the BCC model for climate predictions. A series of experiments with and without sea‐ice observations in the CDA framework are designed to explore the role of sea‐ice data assimilation (DA). The addition of sea‐ice DA exerts very small influence to the analysis of upper ocean temperature over the Arctic area, but leads to an evident reduction of temperature error in the upper 1000 m of ocean south of 60ºS. Particularly, only the inclusion of sea‐ice DA can make the ocean/ocean‐atmosphere DA effective in providing skillful analysis in the high‐latitude Southern Ocean. Furthermore, we find that only on the basis of ocean DA, can the addition of sea‐ice concentration assimilation improve the analysis of tropical tropospheric atmosphere, along with a better analysis of mid‐ and high‐latitude stratospheric atmosphere. These results address the importance of coordination of sea‐ice observations and ocean observations in CDA. Plain Language Summary Developing coupled data assimilation (CDA) technique has become an important task for many operational and research centers. Although CDA consisting of multiple assimilation components has made great progress in the past years, the impacts of each individual component, especially the sea‐ice dat

Due to their sessile nature, plants rely on root systems to mediate many biotic and abiotic cues. To overcome these challenges, the root proteome is shaped to specific responses. Proteome-wide reprogramming events are magnified in meristems due to their active protein production. Using meristems as a test system, here, we study the major rewiring that plants undergo during cold acclimation. We performed tandem mass tag-based bottom-up quantitative proteomics of two consecutive segments of barley seminal root apexes subjected to suboptimal temperatures. After comparing changes in total and ribosomal protein (RP) fraction-enriched contents with shifts in individual protein abundances, we report ribosome accumulation accompanied by an intricate translational reprogramming in the distal apex zone. Reprogramming ranges from increases in ribosome biogenesis to protein folding factors and suggests roles for cold-specific RP paralogs. Ribosome biogenesis is the largest cellular investment; thus, the vast accumulation of ribosomes and specific translation-related proteins during cold acclimation could imply a divergent ribosomal population that would lead to a proteome shift across the root. Consequently, beyond the translational reprogramming, we report a proteome rewiring. First, triggered protein accumulation includes spliceosome activity in the root tip and a ubiquitous upregulation of glutathione production and S-glutathionylation (S-GSH) assemblage machineries in both root zones. Second, triggered protein depletion includes intrinsically enriched proteins in the tip-adjacent zone, which comprise the plant immune system. In summary, ribosome and translation-related protein accumulation happens concomitantly to a proteome reprogramming in barley root meristems during cold acclimation. The cold-accumulated proteome is functionally implicated in feedbacking transcript to protein translation at both ends and could guide cold acclimation.

Silicon dioxide (SiO2) has played a critical role in the development of high-efficiency silicon (Si)-based photovoltaic devices. Recently, it has experienced a renaissance as an interlayer in many of the new contact passivating structures. Studies have extensively investigated the recombination process at the Si–SiO2 interface, however, only little is known about the impact of temperature on the surface recombination. In this study, we investigate the recombination at the Si–SiO2 interface by varying the temperature, excess carrier density, and dielectric fixed charge. An improved lifetime is observed with increasing temperature. A forming gas anneal is used to improve the passivation quality, however, at higher temperatures, the hydrogenated interface passivation degrades due to increased surface state density. The degradation is stronger for corona-charged SiO2, due to the instability of the corona charge within the dielectric. Using the extended Shockley-Read Hall recombination model, the Si–SiO2 interface defects’ parameters are extracted. Most importantly, we determine the value and the temperature-dependence of the capture cross-sections at this interface.

Lipidomics is a relatively recent molecular research field, and explores lipids (fats) and their biology using advanced mass spectrometry technologies. Although this field has expanded significantly in biomedical and biotechnological disciplines, it is still in its infancy in molecular parasitology. Our goal here is to review and discuss technical aspects of MS-based lipidomics and its recent applications to parasitic worms, as well as challenges and future directions for worm lipid research. In a multi-omic paradigm, we expect that the exploration of lipidomic data for parasitic worms will yield important insights into lipid-associated biological pathways and processes, including the regulation of essential signalling pathways, parasite invasion, establishment, adaptation and development.

Insulin-like peptide 5 (INSL5), the natural ligand for the relaxin family peptide receptor 4 (RXFP4), is a gut hormone that is exclusively produced by colonic L-cells. We have recently developed an analogue of INSL5, INSL5-A13, that acts as an RXFP4 agonist in vitro and stimulates colorectal propulsion in wild-type mice but not in RXFP4-knockout mice. These results suggest that INSL5 may have a physiological role in the control of colorectal motility. To investigate this possibility, in this study we designed and developed a novel INSL5 analogue, INSL5-A13NR. This compound is a potent antagonist, without significant agonist activity, in two in vitro assays. We report here for the first time that this novel antagonist peptide blocks agonist-induced increase in colon motility in mice that express RXFP4. Our data also show that colorectal propulsion induced by intracolonic administration of bacterial products (short-chain fatty acids, SCFAs) is antagonized by INSL5-A13NR. Therefore, INSL5-A13NR is an important research tool and potential drug lead for the treatment of colon motility disorders, such as bacterial diarrheas.

Introduction: Asthma and allergy occur frequently among seafood processing workers, with the highest prevalence seen in the crustacean processing industry. In this study we established for the first time the prevalence of allergic sensitization in the Norwegian king- and edible crab processing industry and characterized the IgE-reactive proteins. Materials and Methods: Two populations of crab processing workers participated; 119 king crab and 65 edible crab workers. The investigation included information on work tasks and health through a detailed questionnaire. Allergic sensitization was investigated by crab-specific IgE quantification and skin prick tests (SPT) to four in-house prepared crab extracts; raw meat, cooked meat, raw intestines and raw shell. Allergen-specific IgE binding patterns were analyzed by IgE immunoblotting to the four allergen extracts using worker serum samples. Total proteins in crab SPT extracts and immunoblot-based IgE binding proteins were identified by mass spectrometric analysis. Results: Positive SPTs were established in 17.5% of king- and 18.1% of edible crab workers, while elevated IgE to crab were demonstrated in 8.9% of king- and 12.2% of edible crab processing workers. There was no significant difference between the king and edible crab workers with respect to self-reported respiratory symptoms, elevated specific IgE to crab or SPT results. Individual workers exhibited differential IgE binding patterns to different crab extracts, with most frequent binding to tropomyosin and arginine kinase and two novel IgE binding proteins, hemocyanin and enolase, identified as king- and edible crab allergens. Conclusions: Occupational exposure to king- and edible crabs may frequently cause IgE mediated allergic sensitization. Future investigations addressing the diagnostic value of crab allergens including tropomyosin and arginine kinase and the less well-known IgE-binding proteins hemocyanin and enolase in a component-resolved diagnostic appro

Background: Women with epilepsy face difficult choices whether to continue antiepileptic drug treatment during pregnancy, as uncontrolled seizures carry great risk to mother and fetus but continuing treatment may have adverse effects on baby's development. This study aimed at evaluating antiepileptic drug entry into developing brain. Methods: Anaesthetised pregnant, non-pregnant adult females, postnatal and fetal rats were injected intraperitoneally with different doses, single or in combinations, of valproate and lamotrigine, within clinical range. Injectate included 3H-labelled drug. After 30min, CSF, blood and brain samples were obtained; radioactivity measured using liquid scintillation counting. Some animals were also exposed to valproate in feed throughout pregnancy and into neonatal period. Drug levels measured by liquid chromatography coupled to mass spectrometry (LC-MS). Results given as CSF or tissue/plasma% as index of drug entry. Results: Entry of valproate into brain and CSF was higher at E19 and P4 compared to adult and was dose-dependent except at E19; placental transfer increased significantly at highest dose of 100mg/kg. Lamotrigine entry into the brain was dose dependent only at E19. Chronic valproate treatment, or combination of valproate and lamotrigine had little effect on either drug entry, except for reduced valproate brain entry in adult brain with chronic treatment. Placental transfer decreased significantly after chronic valproate treatment. LC-MS measurement of valproate in adults confirmed that rat plasma values were within the clinical range and CSF/plasma and brain/plasma ratios for LC-MS and 3H-valproate were similar. Conclusion: Results suggest that entry of valproate may be higher in developing brain, the capacity of barrier mechanism is mostly unaffected by doses within the clinical range, with or without addition of lamotrigine. Chronic valproate exposure may result in upregulation in cellular mechanisms restricting its entry int

Due to their sessile nature, plants rely on root systems to mediate many biotic and abiotic cues. To overcome these challenges, the root proteome is shaped to specific responses. Proteome-wide reprogramming events are magnified in meristems due to their active protein production. Using meristems as a test system, here, we study the major rewiring that plants undergo during cold acclimation. We performed tandem mass tag-based bottom-up quantitative proteomics of two consecutive segments of barley seminal root apexes subjected to suboptimal temperatures. After comparing changes in total and ribosomal protein (RP) fraction-enriched contents with shifts in individual protein abundances, we report ribosome accumulation accompanied by an intricate translational reprogramming in the distal apex zone. Reprogramming ranges from increases in ribosome biogenesis to protein folding factors and suggests roles for cold-specific RP paralogs. Ribosome biogenesis is the largest cellular investment; thus, the vast accumulation of ribosomes and specific translation-related proteins during cold acclimation could imply a divergent ribosomal population that would lead to a proteome shift across the root. Consequently, beyond the translational reprogramming, we report a proteome rewiring. First, triggered protein accumulation includes spliceosome activity in the root tip and a ubiquitous upregulation of glutathione production and S-glutathionylation (S-GSH) assemblage machineries in both root zones. Second, triggered protein depletion includes intrinsically enriched proteins in the tip-adjacent zone, which comprise the plant immune system. In summary, ribosome and translation-related protein accumulation happens concomitantly to a proteome reprogramming in barley root meristems during cold acclimation. The cold-accumulated proteome is functionally implicated in feedbacking transcript to protein translation at both ends and could guide cold acclimation.

Adenosine triphosphate binding cassette (ABC) transporters transfer lipid-soluble molecules across cellular interfaces either directly or after enzymatic metabolism. RNAseq analysis identified transcripts for ABC transporters and enzymes in rat E19, P5 and adult brain and choroid plexus and E19 placenta. Their functional capacity to efflux small molecules was studied by quantitative analysis of paracetamol (acetaminophen) and its metabolites using liquid scintillation counting, autoradiography and ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Animals were treated acutely (30 min) and chronically (5 days, twice daily) with paracetamol (15 mg/kg) to investigate ability of brain and placenta barriers to regulate ABC transport functionality during extended treatment. Results indicated that transcripts of many efflux-associated ABC transporters were higher in adult brain and choroid plexus than at earlier ages. Chronic treatment upregulated certain transcripts only in adult brain and altered concentrations of paracetamol metabolites in circulation of pregnant dams. Combination of changes to metabolites and transport system transcripts may explain observed changes in paracetamol entry into adult and fetal brains. Analysis of lower paracetamol dosing (3.75 mg/kg) indicated dose-dependent changes in paracetamol metabolism. Transcripts of ABC transporters and enzymes at key barriers responsible for molecular transport into the developing brain showed alterations in paracetamol pharmacokinetics in pregnancy following different treatment regimens.

Background Diagnostic tests for fish allergy are hampered by the large number of under-investigated fish species. Four salmon allergens are well-characterized and registered with the WHO/IUIS while no catfish allergens have been described so far. In 2008, freshwater-cultured catfish production surpassed that of salmon, the globally most-cultured marine species. We aimed to identify, quantify, and compare all IgE-binding proteins in salmon and catfish. Methods Seventy-seven pediatric patients with clinically confirmed fish allergy underwent skin prick tests to salmon and catfish. The allergen repertoire of raw and heated protein extracts was evaluated by immunoblotting using five allergen-specific antibodies and patients' serum followed by mass spectrometric analyses. Results Raw and heated extracts from catfish displayed a higher frequency of IgE-binding compared to those from salmon (77% vs 70% and 64% vs 53%, respectively). The major fish allergen parvalbumin demonstrated the highest IgE-binding capacity (10%-49%), followed by triosephosphate isomerase (TPI; 19%-34%) in raw and tropomyosin (6%-32%) in heated extracts. Six previously unidentified fish allergens, including TPI, were registered with the WHO/IUIS. Creatine kinase from salmon and catfish was detected by IgE from 14% and 10% of patients, respectively. Catfish L-lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, and glucose-6-phosphate isomerase showed IgE-binding for 6%-13% of patients. In salmon, these proteins could not be separated successfully. Conclusions We detail the allergen repertoire of two highly farmed fish species. IgE-binding to fish tropomyosins and TPIs was demonstrated for the first time in a large patient cohort. Tropomyosins, in addition to parvalbumins, should be considered for urgently needed improved fish allergy diagnostics.

Due to their sessile nature, plants rely on root systems to mediate many biotic and abiotic cues. To overcome these challenges, the root proteome is shaped to specific responses. Proteome-wide reprogramming events are magnified in meristems due to their active protein production. Using meristems as a test system, here, we study the major rewiring that plants undergo during cold acclimation. We performed tandem mass tag-based bottom-up quantitative proteomics of two consecutive segments of barley seminal root apexes subjected to suboptimal temperatures. After comparing changes in total and ribosomal protein (RP) fraction-enriched contents with shifts in individual protein abundances, we report ribosome accumulation accompanied by an intricate translational reprogramming in the distal apex zone. Reprogramming ranges from increases in ribosome biogenesis to protein folding factors and suggests roles for cold-specific RP paralogs. Ribosome biogenesis is the largest cellular investment; thus, the vast accumulation of ribosomes and specific translation-related proteins during cold acclimation could imply a divergent ribosomal population that would lead to a proteome shift across the root. Consequently, beyond the translational reprogramming, we report a proteome rewiring. First, triggered protein accumulation includes spliceosome activity in the root tip and a ubiquitous upregulation of glutathione production and S-glutathionylation (S-GSH) assemblage machineries in both root zones. Second, triggered protein depletion includes intrinsically enriched proteins in the tip-adjacent zone, which comprise the plant immune system. In summary, ribosome and translation-related protein accumulation happens concomitantly to a proteome reprogramming in barley root meristems during cold acclimation. The cold-accumulated proteome is functionally implicated in feedbacking transcript to protein translation at both ends and could guide cold acclimation.

The coupled data assimilation (CDA) system consisting of ocean, sea‐ice, and atmosphere data assimilation components with the Beijing Climate Center (BCC) Climate System Model has been developed to provide reliable analyses of the atmosphere, ocean, and sea‐ice states. It incorporates ocean temperature/salinity profiles, sea surface temperature, sea level height, and sea‐ice concentration observations at a daily frequency, and atmosphere reanalysis at a 6‐hourly frequency. Results show that the system is capable of realistically reproducing the climatology and variability of ocean, sea‐ice, and atmosphere. The performances in analyzing ocean component are comparable to those of well‐known ocean reanalyses that were once used to initialize the BCC model for climate predictions. A series of experiments with and without sea‐ice observations in the CDA framework are designed to explore the role of sea‐ice data assimilation (DA). The addition of sea‐ice DA exerts very small influence to the analysis of upper ocean temperature over the Arctic area, but leads to an evident reduction of temperature error in the upper 1000 m of ocean south of 60ºS. Particularly, only the inclusion of sea‐ice DA can make the ocean/ocean‐atmosphere DA effective in providing skillful analysis in the high‐latitude Southern Ocean. Furthermore, we find that only on the basis of ocean DA, can the addition of sea‐ice concentration assimilation improve the analysis of tropical tropospheric atmosphere, along with a better analysis of mid‐ and high‐latitude stratospheric atmosphere. These results address the importance of coordination of sea‐ice observations and ocean observations in CDA. Plain Language Summary Developing coupled data assimilation (CDA) technique has become an important task for many operational and research centers. Although CDA consisting of multiple assimilation components has made great progress in the past years, the impacts of each individual component, especially the sea‐ice dat

The coupled data assimilation (CDA) system consisting of ocean, sea‐ice, and atmosphere data assimilation components with the Beijing Climate Center (BCC) Climate System Model has been developed to provide reliable analyses of the atmosphere, ocean, and sea‐ice states. It incorporates ocean temperature/salinity profiles, sea surface temperature, sea level height, and sea‐ice concentration observations at a daily frequency, and atmosphere reanalysis at a 6‐hourly frequency. Results show that the system is capable of realistically reproducing the climatology and variability of ocean, sea‐ice, and atmosphere. The performances in analyzing ocean component are comparable to those of well‐known ocean reanalyses that were once used to initialize the BCC model for climate predictions. A series of experiments with and without sea‐ice observations in the CDA framework are designed to explore the role of sea‐ice data assimilation (DA). The addition of sea‐ice DA exerts very small influence to the analysis of upper ocean temperature over the Arctic area, but leads to an evident reduction of temperature error in the upper 1000 m of ocean south of 60ºS. Particularly, only the inclusion of sea‐ice DA can make the ocean/ocean‐atmosphere DA effective in providing skillful analysis in the high‐latitude Southern Ocean. Furthermore, we find that only on the basis of ocean DA, can the addition of sea‐ice concentration assimilation improve the analysis of tropical tropospheric atmosphere, along with a better analysis of mid‐ and high‐latitude stratospheric atmosphere. These results address the importance of coordination of sea‐ice observations and ocean observations in CDA. Plain Language Summary Developing coupled data assimilation (CDA) technique has become an important task for many operational and research centers. Although CDA consisting of multiple assimilation components has made great progress in the past years, the impacts of each individual component, especially the sea‐ice dat

As exemplified by the growing interest in the quantum anomalous Hall effect, the research on topology as an organizing principle of quantum matter is greatly enriched from the interplay with magnetism. In this vein, we present a combined electrical and thermoelectrical transport study on the magnetic Weyl semimetal EuCd2As2. Unconventional contribution to the anomalous Hall and anomalous Nernst effects were observed both above and below the magnetic transition temperature of EuCd2As2, indicating the existence of significant Berry curvature. EuCd2As2 represents a rare case in which this unconventional transverse transport emerges both above and below the magnetic transition temperature in the same material. The transport properties evolve with temperature and field in the antiferromagnetic phase in a different manner than in the paramagnetic phase, suggesting different mechanisms to their origin. Our results indicate EuCd2As2 is a fertile playground for investigating the interplay between magnetism and topology, and potentially a plethora of topologically nontrivial phases rooted in this interplay.

A topological superconductor (TSC) is a new type of superconductor with non-trivial topology in its bulk electronic structure, which has great potential in both fundamental research and application. However, despite the intensive research efforts worldwide, to date only a few intrinsic (non-heterostructures) materials have been proposed as TSC candidates. In this work, following the theoretical prediction, we experimentally studied a newly proposed TSC candidate, TaSe3. The topological non-trivial surface states were directly observed by using angle-resolved photoemission spectroscopy, while the superconductivity of the compound was examined by both transport and scanning tunneling microscopy measurement. Therefore, TaSe3 was proved to be a promising candidate as a TSC, and a promising research platform for the related novel physics phenomena.

© 2011-2012 IEEE. In this article, we present a method to obtain implied open-circuit voltage images of silicon wafers and cells at different temperatures. The proposed method is then demonstrated by investigating the temperature coefficients of various regions across multicrystalline silicon wafers and cells from different heights of two bricks with different dislocation densities. Interestingly, both low and high temperature coefficients are found in dislocated regions on the wafers. A large spread of temperature coefficient is observed at regions with similar performance at 298 K. Reduced temperature sensitivity is found to be correlated with the increasing brick height and is exhibited by both wafers and cells. This may indicate that cells made from the top of the brick, although having higher defect concentration, actually suffer relatively less degradation in the performance at higher temperatures.

Ascaris is a soil-transmitted nematode that causes ascariasis, a neglected tropical disease affecting predominantly children and adolescents in the tropics and subtropics. Approximately 0.8 billion people are affected worldwide, equating to 0.86 million disability-adjusted life-years (DALYs). Exploring the molecular biology of Ascaris is important to gain a better understanding of the host-parasite interactions and disease processes, and supports the development of novel interventions. Although advances have been made in the genomics, transcriptomics and proteomics of Ascaris, its lipidome has received very limited attention. Lipidomics is an important sub-discipline of systems biology, focused on exploring lipids profiles in tissues and cells, and elucidating their biological and metabolic roles. Here, we characterised the lipidomes of key developmental stages and organ systems of Ascaris of porcine origin via high throughput LC-MS/MS. In total, > 500 lipid species belonging to 18 lipid classes within three lipid categories were identified and quantified–in precise molar amounts in relation to the dry weight of worm material–in different developmental stages/sexes and organ systems. The results showed substantial differences in the composition and abundance of lipids with key roles in cellular processes and functions (e.g. energy storage regulation and membrane structure) among distinct stages and among organ systems, likely reflecting differing demands for lipids, depending on stage of growth and development as well as the need to adapt to constantly changing environments within and outside of the host animal. This work provides the first step toward understanding the biology of lipids in Ascaris, with possibilities to work toward designing new interventions against ascariasis.

Porphyromonas gingivalis and Tannerella forsythia use the type IX secretion system to secrete cargo proteins to the cell surface where they are anchored via glycolipids. In P. gingivalis, the glycolipid is anionic lipopolysaccharide (A-LPS), of partially known structure. Modified cargo proteins were deglycosylated using trifluoromethanesulfonic acid and digested with trypsin or proteinase K. The residual modifications were then extensively analyzed by tandem mass spectrometry. The C terminus of each cargo protein was amide-bonded to a linking sugar whose structure was deduced to be 2-N-seryl, 3-N-acetylglucuronamide in P. gingivalis and 2-N-glycyl, 3-N-acetylmannuronic acid in T. forsythia The structures indicated the involvement of the Wbp pathway to produce 2,3-di-N-acetylglucuronic acid and a WbpS amidotransferase to produce the uronamide form of this sugar in P. gingivalis The wbpS gene was identified as PGN_1234 as its deletion resulted in the inability to produce the uronamide. In addition, the P. gingivalisvimA mutant which lacks A-LPS was successfully complemented by the T. forsythiavimA gene; however, the linking sugar was altered to include glycine rather than serine. After removal of the acetyl group at C-2 by the putative deacetylase, VimE, VimA presumably transfers the amino acid to complete the biosynthesis. The data explain all the enzyme activities required for the biosynthesis of the linking sugar accounting for six A-LPS-specific genes. The linking sugar is therefore the key compound that enables the attachment of cargo proteins in P. gingivalis and T. forsythia We propose to designate this novel linking sugar biosynthetic pathway the Wbp/Vim pathway.IMPORTANCEPorphyromonas gingivalis and Tannerella forsythia, two pathogens associated with severe gum disease, use the type IX secretion system (T9SS) to secrete and attach toxic arrays of virulence factor proteins to their cell surfaces. The proteins are tethered to the outer membrane via glycolipid a

BACKGROUND: Lipids play essential structural and functional roles in the biology of animals. Studying the composition and abundance of lipids in parasites should assist in gaining a better understanding of their molecular biology, biochemistry and host-parasite interactions. METHODS: Here, we used a combination of high-performance liquid chromatography and mass spectrometric analyses, combined with bioinformatics, to explore the lipid composition and abundance in the reproductive (Rt) and alimentary (At) tracts of Haemonchus contortus. RESULTS: We identified and quantified 320 unique lipid species representing four categories: glycerolipids, glycerophospholipids, sphingolipids and steroid lipids. Glycerolipids (i.e. triradylglycerols) and glycerophospholipids (i.e. glycerophosphocholines) were the most commonly and abundant lipid classes identified and were significantly enriched in Rt and At, respectively. We propose that select parasite-derived lipids in Rt and At of adult female H. contortus are required as an energy source (i.e. triradylglycerol) or are involved in phospholipid biosynthesis (i.e. incorporated fatty acids) and host-parasite interactions (i.e. phospholipids and lysophospholipids). CONCLUSIONS: This work provides a first foundation to explore lipids at the organ-specific and tissue-specific levels in nematodes, and to start to unravel aspects of lipid transport, synthesis and metabolism, with a perspective on discovering new intervention targets.

A topological superconductor (TSC) is a new type of superconductor with non-trivial topology in its bulk electronic structure, which has great potential in both fundamental research and application. However, despite the intensive research efforts worldwide, to date only a few intrinsic (non-heterostructures) materials have been proposed as TSC candidates. In this work, following the theoretical prediction, we experimentally studied a newly proposed TSC candidate, TaSe3. The topological non-trivial surface states were directly observed by using angle-resolved photoemission spectroscopy, while the superconductivity of the compound was examined by both transport and scanning tunneling microscopy measurement. Therefore, TaSe3 was proved to be a promising candidate as a TSC, and a promising research platform for the related novel physics phenomena.

Here, we discovered an endogenous dafachronic acid (DA) in the socioeconomically important parasitic nematode Haemonchus contortus. We demonstrate that DA promotes larval exsheathment and development in this nematode via a relatively conserved nuclear hormone receptor (DAF-12). This stimulatory effect is dose- and time-dependent, and relates to a modulation of dauer-like signalling, and glycerolipid and glycerophospholipid metabolism, likely via a negative feedback loop. Specific chemical inhibition of DAF-9 (cytochrome P450) was shown to significantly reduce the amount of endogenous DA in H. contortus; compromise both larval exsheathment and development in vitro; and modulate lipid metabolism. Taken together, this evidence shows that DA plays a key functional role in the developmental transition from the free-living to the parasitic stage of H. contortus by modulating the dauer-like signalling pathway and lipid metabolism. Understanding the intricacies of the DA-DAF-12 system and associated networks in H. contortus and related parasitic nematodes could pave the way to new, nematode-specific treatments.

Endothelial dysfunction induced by bubbles plays an important role in decompression sickness (DCS), but the mechanism of which has not been clear. The present study was to investigate the role of autophagy in bubble-induced endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with bubbles, autophagy markers and endothelial injury indices were determined, and relationship strengths were quantified. Effects of autophagy inhibitor 3-methyladenine (3-MA) were observed. Bubble contact for 1, 5, 10, 20 or 30 minutes induced significant autophagy with increases in LC3-II/I ratio and Beclin-1, and a decrease in P62, which correlated with bubble contact duration. Apoptosis rate, cytochrome C and cleaved caspase-3 increased, and cell viability decreased following bubble contact for 10, 20 or 30 minutes, but not for 1 or 5 minutes. Injuries in HUVECs were correlated with LC3-II/I ratio and partially reversed by 3-MA in 10, 20 or 30 minutes contact, but worsened in 1 or 5 minutes. Bubble pre-conditioning for 1 minutes resulted in increased cell viability and decreased apoptosis rate compared with no pre-conditioning, and 30-minutes pre-conditioning induced opposing changes, all of which were inhibited by 3-MA. In conclusion, autophagy was involved and played a biphasic role in bubble-induced endothelial injury.

The benefits of adult stem cells for repair of the heart have been attributed to the repertoire of salutary paracrine activities they appear to exert. We previously isolated human W8B2+ cardiac stem cells (CSCs) and found they powerfully influence cardiomyocytes and endothelial cells to collectively promote cardiac repair and regeneration. Here, the complexity of the W8B2+ CSC secretomes was characterised and examined in more detail. Using ion exchange chromatography to separate soluble proteins based on their net surface charge, the secreted factors responsible for the pro-survival activity of W8B2+ CSCs were found within the low and medium cation fractions. In addition to the soluble proteins, extracellular vesicles generated from W8B2+ CSCs not only exhibited pro-survival and pro-angiogenic activities, but also promoted proliferation of neonatal cardiomyocytes. These extracellular vesicles contain a cargo of proteins, mRNA and primary microRNA precursors that are enriched in exosomes and are capable of modulating collectively many of the cellular pathways involved in protein metabolism, cell growth, as well as cellular responses to stress and organisation of the extracellular matrix. Thus the W8B2+ CSC secretome contains a multitude of bioactive paracrine factors we have now characterised, that might well be harnessed for therapeutic application for cardiac repair and regeneration.

The benefits of adult stem cells for repair of the heart have been attributed to the repertoire of salutary paracrine activities they appear to exert. We previously isolated human W8B2+ cardiac stem cells (CSCs) and found they powerfully influence cardiomyocytes and endothelial cells to collectively promote cardiac repair and regeneration. Here, the complexity of the W8B2+ CSC secretomes was characterised and examined in more detail. Using ion exchange chromatography to separate soluble proteins based on their net surface charge, the secreted factors responsible for the pro-survival activity of W8B2+ CSCs were found within the low and medium cation fractions. In addition to the soluble proteins, extracellular vesicles generated from W8B2+ CSCs not only exhibited pro-survival and pro-angiogenic activities, but also promoted proliferation of neonatal cardiomyocytes. These extracellular vesicles contain a cargo of proteins, mRNA and primary microRNA precursors that are enriched in exosomes and are capable of modulating collectively many of the cellular pathways involved in protein metabolism, cell growth, as well as cellular responses to stress and organisation of the extracellular matrix. Thus the W8B2+ CSC secretome contains a multitude of bioactive paracrine factors we have now characterised, that might well be harnessed for therapeutic application for cardiac repair and regeneration.

Item does not contain fulltext, OBJECTIVES: The aim of this study was to assess calcium growth with fused grayscale intravascular ultrasound (IVUS), IVUS-virtual histology, and optical coherence tomography (OCT) from baseline to 5-year follow-up in patients treated with bioresorbable vascular scaffolds. BACKGROUND: IVUS and OCT have individual strengths in assessing plaque composition and volume. Fusion of images obtained using these methods could potentially aid in coronary plaque assessment. METHODS: Anatomic landmarks and endoluminal radiopaque markers were used to fuse OCT and IVUS images and match baseline and follow-up. RESULTS: Seventy-two IVUS-virtual histology and OCT paired matched cross-sectional in- and out-scaffold segments were fused at baseline and follow-up. In total, 46 calcified plaques at follow-up were detected using the fusion method (33 in-scaffold, 13 out-scaffold), showing either calcium progression (52.2%) or de novo calcifications (47.8%). On OCT, calcification volume increased from baseline to follow-up by 2.3 +/- 2.4 mm(3) (p = 0.001). The baseline virtual histologic tissue precursors of dense calcium at follow-up were necrotic core in 73.9% and fibrous or fibrofatty plaque in 10.9%. In 15.2%, calcium was already present at baseline. Precursors on OCT were lipid pool in 71.2%, fibrous plaque in 4.3%, and fibrocalcific plaque in 23.9%. CONCLUSIONS: The use of OCT and IVUS fusion imaging shows similar calcium growth in- and out-scaffold segments. Necrotic core is the most frequent precursor of calcification. The scaffold resorption process creates a tissue layer that re-caps the calcified plaques. (Absorb Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

Item does not contain fulltext, OBJECTIVES: The aim of this study was to assess calcium growth with fused grayscale intravascular ultrasound (IVUS), IVUS-virtual histology, and optical coherence tomography (OCT) from baseline to 5-year follow-up in patients treated with bioresorbable vascular scaffolds. BACKGROUND: IVUS and OCT have individual strengths in assessing plaque composition and volume. Fusion of images obtained using these methods could potentially aid in coronary plaque assessment. METHODS: Anatomic landmarks and endoluminal radiopaque markers were used to fuse OCT and IVUS images and match baseline and follow-up. RESULTS: Seventy-two IVUS-virtual histology and OCT paired matched cross-sectional in- and out-scaffold segments were fused at baseline and follow-up. In total, 46 calcified plaques at follow-up were detected using the fusion method (33 in-scaffold, 13 out-scaffold), showing either calcium progression (52.2%) or de novo calcifications (47.8%). On OCT, calcification volume increased from baseline to follow-up by 2.3 +/- 2.4 mm(3) (p = 0.001). The baseline virtual histologic tissue precursors of dense calcium at follow-up were necrotic core in 73.9% and fibrous or fibrofatty plaque in 10.9%. In 15.2%, calcium was already present at baseline. Precursors on OCT were lipid pool in 71.2%, fibrous plaque in 4.3%, and fibrocalcific plaque in 23.9%. CONCLUSIONS: The use of OCT and IVUS fusion imaging shows similar calcium growth in- and out-scaffold segments. Necrotic core is the most frequent precursor of calcification. The scaffold resorption process creates a tissue layer that re-caps the calcified plaques. (Absorb Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Item does not contain fulltext, OBJECTIVES: The aim of this study was to assess calcium growth with fused grayscale intravascular ultrasound (IVUS), IVUS-virtual histology, and optical coherence tomography (OCT) from baseline to 5-year follow-up in patients treated with bioresorbable vascular scaffolds. BACKGROUND: IVUS and OCT have individual strengths in assessing plaque composition and volume. Fusion of images obtained using these methods could potentially aid in coronary plaque assessment. METHODS: Anatomic landmarks and endoluminal radiopaque markers were used to fuse OCT and IVUS images and match baseline and follow-up. RESULTS: Seventy-two IVUS-virtual histology and OCT paired matched cross-sectional in- and out-scaffold segments were fused at baseline and follow-up. In total, 46 calcified plaques at follow-up were detected using the fusion method (33 in-scaffold, 13 out-scaffold), showing either calcium progression (52.2%) or de novo calcifications (47.8%). On OCT, calcification volume increased from baseline to follow-up by 2.3 +/- 2.4 mm(3) (p = 0.001). The baseline virtual histologic tissue precursors of dense calcium at follow-up were necrotic core in 73.9% and fibrous or fibrofatty plaque in 10.9%. In 15.2%, calcium was already present at baseline. Precursors on OCT were lipid pool in 71.2%, fibrous plaque in 4.3%, and fibrocalcific plaque in 23.9%. CONCLUSIONS: The use of OCT and IVUS fusion imaging shows similar calcium growth in- and out-scaffold segments. Necrotic core is the most frequent precursor of calcification. The scaffold resorption process creates a tissue layer that re-caps the calcified plaques. (Absorb Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene signatures and the differences in response to hyperthermia between hyperthermia-sensitive and -resistant cancer cells identified CTGF as a key regulator of sensitivity. CTGF silencing sensitized resistant cells to hyperthermia. CTGF small interfering RNA (siRNA) treatment also sensitized resistant cancers to localized hyperthermia induced by copper sulfide nanoparticles and near-infrared laser in orthotopic ovarian cancer models. CTGF silencing aggravated energy stress induced by hyperthermia and enhanced apoptosis of hyperthermia-resistant cancers.

In this study, multifunctional polyethersulfone (PES) membranes are prepared via in situ cross-linked copolymerization coupled with a liquid-liquid phase separation technique. Acrylic acid (AA) and N-vinylpyrrolidone (VP) are copolymerized in PES solution, and the solution is then directly used to prepare PES membranes. The infrared and X-ray photoelectron spectroscopy testing, scanning electron microscopy, and water contact angle measurements confirm the successful modification of pristine PES membrane. Protein adsorption, platelet adhesion, plasma recalcification time, and activated partial thromboplastin time assays convince that the modified PES membranes have a better biocompatibility than pristine PES membrane. In addition, the modified membranes showed good protein antifouling property and significant adsorption property of cationic dye. The loading of Ag nanoparticles into the modified membranes endows the composite membranes with antibacterial activity., QC 20151214, QC 20160318

Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis