Ceramic Microchips for Capillary Electrophoresis-electrochemistry

A capillary electrophoresis–electrochemistry chip constructed from low-temperature co-fired ceramic (LTCC) tape is presented. This is the first report of such a chip constructed in this manner using these materials. Electroosmotic flow at pH 7 is demonstrated by the migration of a neutral marker, catechol. The separation and detection of two phenolic compounds are presented

The effects of food safety education on adolescents' hand hygiene behavior: an analysis of stages of change

The hand hygiene behavior of 400 middle school students (grades 1-3) in Seoul and Gyeonggi-Do was studied to determine how stages of change were affected by food safety education, focusing on hand hygiene and general food safety. Subjects were 51.3% male and 44.3% of study subjects were first graders of middle school. Approximately 40% of subjects were at the stage of action, 42.7% were at the stage of contemplation, and 16.4% were at pre-contemplation. The most important factor that influenced proper hand washing was self efficacy (P < 0.001). Proper hand washing was also correlated significantly with positive belief (P < 0.01) and stages of change (P < 0.01). After food safety education by high-school mentors, middle-school students who were in the stages of pre-contemplation (11.1%) and contemplation (88.9%) showed significant progression toward the action stage (P < 0.001). Proper hand washing (P < 0.01) and food safety knowledge (P < 0.05) were also significantly increased after educational intervention

Stability and mobility of supported Nin (n = 1–10) clusters on ZrO2(111) and YSZ(111) surfaces: a density functional theory study

The performance of supported metal catalysts, such as nickel nanoparticles decorating yttria-stabilized zirconia (YSZ), depends on their microstructure and the metal–support interface. Here, we have used spin polarized density functional theory (DFT) to evaluate different Ni cluster geometries and determined the electronic structure of the most stable configurations. We have described the interaction of Nin (n = 1–10) clusters supported on the cubic ZrO2(111) and YSZ(111) surfaces, which show a preference for pyramidal shapes rather than flat structures wetting the surface. The interfacial interaction is characterized by charge transfer from the cluster to the surface. We also show how yttrium, present in YSZ, affects the Ni–Ni interaction. Through analysing the difference between the cohesive energy and the clustering energy, we show the preference of Ni–Ni bond formation over Ni-surface interaction; this energy difference decreases with the increase of the Nin cluster size. From the evaluation of the Ni atomic hopping rates on YSZ, we have demonstrated that under different temperature conditions, Ni atoms aggregate with other atoms and clusters, which affects the cluster size stability

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

During inflammation, dysregulated neutrophil behaviour can play a major role in a range of chronic inflammatory diseases, for many of which current treatments are generally ineffective. Recently, specific naturally occurring tanshinones have shown promising anti-inflammatory effects by targeting neutrophils in vivo, yet such tanshinones, and moreover, their isomeric isotanshinone counterparts, are still a largely underexplored class of compounds, both in terms of synthesis and biological effects. To explore the anti-inflammatory effects of isotanshinones, and the tanshinones more generally, a series of substituted tanshinone and isotanshinone analogues was synthesised, alongside other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of neutrophilic inflammation revealed differential anti-inflammatory profiles in vivo, with a number of compounds exhibiting promising effects. Several compounds reduce initial neutrophil recruitment and/or promote resolution of neutrophilic inflammation, of which two also result in increased apoptosis of human neutrophils. In particular, the methoxy-substituted tanshinone 39 specifically accelerates resolution of inflammation without affecting the recruitment of neutrophils to inflammatory sites, making this a particularly attractive candidate for potential pro-resolution therapeutics, as well as a possible lead for future development of functionalised tanshinones as molecular tools and/or chemical probes. The structurally related β-lapachones promote neutrophil recruitment but do not affect resolution. We also observed notable differences in toxicity profiles between compound classes. Overall, we provide new insights into the in vivo anti-inflammatory activities of several novel tanshinones, isotanshinones, and structurally related compounds

Multi-ancestry genome-wide study in &gt;2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,289 independent association signals at genome-wide significance (P&lt;5×10 - 8 ) that map to 611 loci, of which 145 loci are previously unreported. We define eight non-overlapping clusters of T2D signals characterised by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial, and enteroendocrine cells. We build cluster-specific partitioned genetic risk scores (GRS) in an additional 137,559 individuals of diverse ancestry, including 10,159 T2D cases, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned GRS are more strongly associated with coronary artery disease and end-stage diabetic nephropathy than an overall T2D GRS across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings demonstrate the value of integrating multi-ancestry GWAS with single-cell epigenomics to disentangle the aetiological heterogeneity driving the development and progression of T2D, which may offer a route to optimise global access to genetically-informed diabetes care. </p

Apophis planetary defense campaign

We describe results of a planetary defense exercise conducted during the close approach to Earth by the near-Earth asteroid (99942) Apophis during 2020 December–2021 March. The planetary defense community has been conducting observational campaigns since 2017 to test the operational readiness of the global planetary defense capabilities. These community-led global exercises were carried out with the support of NASA's Planetary Defense Coordination Office and the International Asteroid Warning Network. The Apophis campaign is the third in our series of planetary defense exercises. The goal of this campaign was to recover, track, and characterize Apophis as a potential impactor to exercise the planetary defense system including observations, hypothetical risk assessment and risk prediction, and hazard communication. Based on the campaign results, we present lessons learned about our ability to observe and model a potential impactor. Data products derived from astrometric observations were available for inclusion in our risk assessment model almost immediately, allowing real-time updates to the impact probability calculation and possible impact locations. An early NEOWISE diameter measurement provided a significant improvement in the uncertainty on the range of hypothetical impact outcomes. The availability of different characterization methods such as photometry, spectroscopy, and radar provided robustness to our ability to assess the potential impact risk

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain