Ultraperformance liquid chromatography (UPLC) and ion mobility (IM) spectrometry were interfaced with mass spectrometry (MS) and tandem mass spectrometry (MS/MS) to characterize a complex nonionic ...surfactant mixture. The surfactant was composed of a glycerol core, functionalized with poly(ethylene oxide) units (PEO n ) that were partially esterified by caprylic and/or capric acid. Reversed-phase UPLC classified the blend based on polarity into four groups of eluates, corresponding to compounds with zero, one, two, or three fatty acid residues. Additional separation within each eluate group was achieved according to the length of the fatty acid chains. Coeluting molecules of similar polarity were dispersed in the gas phase by their collision cross section in the IM dimension. Performed in series, UPLC and IM allowed for the separation and detection of several isomeric and isobaric blend constituents, thereby enabling their isolation for conclusive MS/MS analysis to confirm or elucidate their primary structures and architectures (overall four-dimensional, 4D, characterization).
Cells contain multiple F-actin assembly pathways, including the Arp2/3 complex, formins, and Ena/VASP, which have largely been analyzed separately. They collectively generate the bulk of F-actin from ...a common pool of G-actin; however, the interplay and/or competition between these pathways remains poorly understood. Using fibroblast lines derived from an Arpc2 conditional knockout mouse, we established matched-pair cells with and without the Arp2/3 complex. Arpc2−/− cells lack lamellipodia and migrate more slowly than WT cells but have F-actin levels indistinguishable from controls. Actin assembly in Arpc2−/− cells was resistant to cytochalasin-D and was highly dependent on profilin-1 and Ena/VASP but not formins. Profilin-1 depletion in WT cells increased F-actin and Arp2/3 complex in lamellipodia. Conversely, addition of exogenous profilin-1 inhibited Arp2/3 complex actin nucleation in vitro and in vivo. Antagonism of the Arp2/3 complex by profilin-1 in cells appears to maintain actin homeostasis by balancing Arp2/3 complex-dependent and -independent actin assembly pathways.
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•Arpc2 conditional knockout mice are used to derive cells lacking the Arp2/3 complex•Arpc2−/− and wild-type cells show similar ratios of F-actin to G-actin•Actin assembly without Arp2/3 complex relies on profilin and Ena/VASP, not formins•Profilin-1 inhibits Arp2/3 complex-dependent actin nucleation in wild-type cells
Rotty et al. find that cells lacking a functional Arp2/3 complex compensate by enhancing profilin-dependent F-actin polymerization through Ena/VASP. They also present evidence that profilin-1 inhibits nucleation of actin branches by the Arp2/3 complex, suggesting that cytosolic actin polymerization is achieved, in part, by balancing Arp2/3-dependent and profilin-dependent pathways.
Predicting the impacts of ocean acidification on coastal ecosystems requires an understanding of the effects on macroalgae and their grazers, as these underpin the ecology of rocky shores. Whilst ...calcified coralline algae (Rhodophyta) appear to be especially vulnerable to ocean acidification, there is a lack of information concerning calcified brown algae (Phaeophyta), which are not obligate calcifiers but are still important producers of calcium carbonate and organic matter in shallow coastal waters. Here, we compare ecological shifts in subtidal rocky shore systems along CO₂ gradients created by volcanic seeps in the Mediterranean and Papua New Guinea, focussing on abundant macroalgae and grazing sea urchins. In both the temperate and tropical systems the abundances of grazing sea urchins declined dramatically along CO₂ gradients. Temperate and tropical species of the calcifying macroalgal genus Padina (Dictyoaceae, Phaeophyta) showed reductions in CaCO₃ content with CO₂ enrichment. In contrast to other studies of calcified macroalgae, however, we observed an increase in the abundance of Padina spp. in acidified conditions. Reduced sea urchin grazing pressure and significant increases in photosynthetic rates may explain the unexpected success of decalcified Padina spp. at elevated levels of CO₂. This is the first study to provide a comparison of ecological changes along CO₂ gradients between temperate and tropical rocky shores. The similarities we found in the responses of Padina spp. and sea urchin abundance at several vent systems increases confidence in predictions of the ecological impacts of ocean acidification over a large geographical range.
We show that light-pulse atom interferometry with atomic point sources and spatially resolved detection enables multiaxis (two rotation, one acceleration) precision inertial sensing at long ...interrogation times. Using this method, we demonstrate a light-pulse atom interferometer for 87Rb with 1.4 cm peak wave packet separation and a duration of 2T=2.3 s. The inferred acceleration sensitivity of each shot is 6.7×10(-12)g, which improves on previous limits by more than 2 orders of magnitude. We also measure Earth's rotation rate with a precision of 200 nrad/s.
We developed PolyA-seq, a strand-specific and quantitative method for high-throughput sequencing of 3' ends of polyadenylated transcripts, and used it to globally map polyadenylation (polyA) sites in ...24 matched tissues in human, rhesus, dog, mouse, and rat. We show that PolyA-seq is as accurate as existing RNA sequencing (RNA-seq) approaches for digital gene expression (DGE), enabling simultaneous mapping of polyA sites and quantitative measurement of their usage. In human, we confirmed 158,533 known sites and discovered 280,857 novel sites (FDR < 2.5%). On average 10% of novel human sites were also detected in matched tissues in other species. Most novel sites represent uncharacterized alternative polyA events and extensions of known transcripts in human and mouse, but primarily delineate novel transcripts in the other three species. A total of 69.1% of known human genes that we detected have multiple polyA sites in their 3'UTRs, with 49.3% having three or more. We also detected polyadenylation of noncoding and antisense transcripts, including constitutive and tissue-specific primary microRNAs. The canonical polyA signal was strongly enriched and positionally conserved in all species. In general, usage of polyA sites is more similar within the same tissues across different species than within a species. These quantitative maps of polyA usage in evolutionarily and functionally related samples constitute a resource for understanding the regulatory mechanisms underlying alternative polyadenylation.
A large fraction of engineered nanomaterials in consumer and commercial products will reach natural ecosystems. To date, research on the biological impacts of environmental nanomaterial exposures has ...largely focused on high-concentration exposures in mechanistic lab studies with single strains of model organisms. These results are difficult to extrapolate to ecosystems, where exposures will likely be at low-concentrations and which are inhabited by a diversity of organisms. Here we show adverse responses of plants and microorganisms in a replicated long-term terrestrial mesocosm field experiment following a single low dose of silver nanoparticles (0.14 mg Ag kg(-1) soil) applied via a likely route of exposure, sewage biosolid application. While total aboveground plant biomass did not differ between treatments receiving biosolids, one plant species, Microstegium vimeneum, had 32 % less biomass in the Slurry+AgNP treatment relative to the Slurry only treatment. Microorganisms were also affected by AgNP treatment, which gave a significantly different community composition of bacteria in the Slurry+AgNPs as opposed to the Slurry treatment one day after addition as analyzed by T-RFLP analysis of 16S-rRNA genes. After eight days, N2O flux was 4.5 fold higher in the Slurry+AgNPs treatment than the Slurry treatment. After fifty days, community composition and N2O flux of the Slurry+AgNPs treatment converged with the Slurry. However, the soil microbial extracellular enzymes leucine amino peptidase and phosphatase had 52 and 27% lower activities, respectively, while microbial biomass was 35% lower than the Slurry. We also show that the magnitude of these responses was in all cases as large as or larger than the positive control, AgNO3, added at 4-fold the Ag concentration of the silver nanoparticles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ...ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke.
We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes (
,
, and
) with any stroke, ischemic stroke, and hemorrhagic stroke.
CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 95% CI, 1.03-1.27;
=0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 95% CI, 1.01-1.51;
=0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results,
showed the strongest association with total stroke and ischemic stroke, whereas
and
were each associated with increased risk of hemorrhagic stroke.
CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.
Objective
In recent years there has been increasing clinical and empirical interest in neurocognitive functioning in eating disorders (EDs), which has resulted in numerous quantitative and ...qualitative reviews. However, there has yet to be a comprehensive synthesis or critical review of this literature to identify future directions to advance the field in this area. Therefore the aim of this systematic review of systematic reviews was to (a) characterize the existing literature on neurocognitive functioning in EDs based on recent reviews (i.e., published since 2010), (b) describe related limitations, and (c) suggest avenues for future research to address gaps in the current literature.
Method
Electronic databases were queried for reviews of neurocognitive domains (i.e., inhibitory control, decision‐making, central coherence, set‐shifting, working memory, and attention bias) in EDs, which identified 28 systematic and meta‐analytic reviews.
Results
Broadly, the literature indicates deficits across these neurocognitive domains in EDs, though heterogeneity was noted in the magnitude of these effects, which varied to some extent across ED subtypes, sample characteristics, and methodological approaches.
Discussion
While these reviews have generally suggested varying patterns of neurocognitive deficits across EDs, there remain critical limitations regarding the methodological quality of these studies (e.g., the lack of prospective designs, consideration of confounding influences, or examination of interrelationships between neurocognitive domains and relationships between neurocognition and other relevant behavioral constructs). Specifically, we outline 10 key areas that are imperative to address in future research in this area in order to move our field forward.
Resumen
Objetivo: En años recientes ha habido un incremento en el interés clínico y empírico de las funciones neurocognitivas en los trastornos de la conducta alimentaria (TCAs) lo que ha dado lugar a numerosas revisiones cuantitativas y cualitativas. Sin embargo, todavía no se ha realizado una síntesis exhaustiva o una revisión crítica de la literatura para identifcar las direcciones futuras para avanzar en el campo en esta área. Por lo tanto, el objetivo de esta revisión sistemática de revisiones sistemáticas fue (1) caracterizar la literatura existente sobre el funcionamiento neurocognitivo en los TCAs basado en revisiones recientes (por ejemplo, publicadas desde 2010), (2) describir las limitaciones relacionadas, y (3) sugerir vías para investigación futura que aborden las lagunas que hay en la literatura actual.
Método
Se consultaron las bases de datos electrónicas para revisar los dominios neurocognitivos (es decir, control inhibitorio, toma de decisiones, coherencia central, cambio de escenario, memoria de trabajo y sesgo de atención) en los TCAs, que identificaron 28 revisiones sistemáticas y metaanalíticas.
Resultados
En general, la literatura indica déficits en todos estos dominios neurocognitivos en los TCAs, aunque se observó heterogeneidad en la magnitud de estos efectos, que variaron en cierta medida entre los subtipos de TCAs, las características de la muestra y los enfoques metodológicos.
Discusión
Si bien estas revisiones generalmente sugieren patrones variables de déficits neurocognitivos en TCAs, aún existen limitaciones críticas con respecto a la calidad metodológica de estos estudios (por ejemplo, la falta de diseños prospectivos, consideración de influencias de confusión o examen de interrelaciones entre dominios neurocognitivos y relaciones entre la neurocognición y otros constructos conductuales relevantes). Específicamente, describimos diez áreas clave que son imprescindibles de abordar en futuras investigaciones en esta área para poder avanzar en nuestro campo.
Roux-en-Y gastric bypass has been considered the gold standard bariatric procedure for decades. The surgical technique for Roux-en-Y gastric bypass and perioperative management for patients who ...undergo the procedure are still being improved for better clinical outcomes, shorter hospitalization, and faster return to normal activity. In the past 15 years there have been similar improvements and further development of novel surgical weight loss procedures. As data on other surgical alternatives emerge, the data need to be compared with Roux-en-Y gastric bypass to determine noninferiority. Further long-term investigations are needed to determine superiority of one bariatric procedure over another.
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