Redirecting E3 ligases to neo-substrates, leading to their proteasomal disassembly, known as targeted protein degradation (TPD), has emerged as a promising alternative to traditional, occupancy-driven pharmacology. Although the field has expanded tremendously over the past years, the choice of E3 ligases remains limited, with an almost exclusive focus on CRBN and VHL. Here, we report the discovery of novel ligands to the PRY-SPRY domain of TRIM58, a RING ligase that is specifically expressed in erythroid precursor cells.
View Article and Find Full Text PDFRNA deaminases are powerful tools for base editing and RNA molecular recording. However, the enzymes used in currently available RNA molecular recorders such as TRIBE, DART or STAMP have limitations due to RNA structure and sequence dependence. We designed a platform for directed evolution of RNA molecular recorders.
View Article and Find Full Text PDFBackground: Physical activity is associated with health benefits and has been shown to reduce mortality risk. However, exposure to high levels of ambient fine particulate matter (PM) during exercise can potentially reduce the health benefits of physical activity. This study aims to assess and compare the PM concentrations of different exercise venues in Singapore by their location attributes and time of day.
View Article and Find Full Text PDFHuman body sodium is regulated by the kidneys and extrarenal mechanisms. Stored skin and muscle tissue sodium accumulation is associated with kidney function decline, hypertension, and a pro-inflammatory and cardiovascular disease profile. In this chapter, we describe the use of sodium-hydrogen magnetic resonance imaging (Na/H MRI) to dynamically quantify tissue sodium concentration in the lower limb of humans.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
August 2023
Background: Anorexia of aging is characterized by an age-associated reduction of appetite, whose aetiology in most cases is multifactorial and which often triggers malnutrition. The Simplified Nutritional Appetite Questionnaire (SNAQ) is an established screening tool. This study aimed to investigate reliability, validity, and feasibility of its telephone administration (T-SNAQ) in German community-dwelling older adults.
View Article and Find Full Text PDFHeart failure remains a leading cause of morbidity and mortality worldwide. Current treatment for patients with heart failure include drugs targeting G protein-coupled receptors such as β-adrenoceptor antagonists (β-blockers) and angiotensin II type 1 receptor antagonists (or angiotensin II receptor blockers). However, many patients progress to advanced heart failure with persistent symptoms, despite treatment with available therapeutics that have been shown to reduce mortality and mortality.
View Article and Find Full Text PDFThe adenosine A receptor is a therapeutic target based on its ability to provide cardioprotection during episodes of myocardial ischemia and reperfusion injury. However, the clinical translation of AR agonists has been hindered by dose-limiting adverse effects (bradycardia and hypotension). Previously, we demonstrated that the bitopic agonist VCP746 (), consisting of an adenosine pharmacophore linked to an allosteric moiety, can stimulate cardioprotective AR signaling effects in the absence of unwanted bradycardia.
View Article and Find Full Text PDFACS Appl Mater Interfaces
April 2022
A novel type of all-ceramic SiC aerogel was fabricated by freeze casting and carbothermal reduction reaction processes using graphene oxide (GO) doped SiC nanowires suspensions as starting materials. The effect of GO addition (0, 1, 2, and 4 mg/mL) on the porous morphologies, chemical composition, and the electromagnetic (EM) performance of the SiC aerogels were investigated. The optimum all-ceramic SiC aerogel exhibits effective whole X-band attenuation (>90%) at a fixed thickness of 3.
View Article and Find Full Text PDFBackground: Obesity is a risk factor for tracheostomy-related complications. We aimed to investigate whether obesity was associated with a risk of unplanned tracheostomy dislodgement or decannulation (DD).
Methods: Retrospective review of patients undergoing tracheostomy at a single institution from 2013 to 2019 was performed.
DDX3 is an RNA chaperone of the DEAD-box family that regulates translation. Ded1, the yeast ortholog of DDX3, is a global regulator of translation, whereas DDX3 is thought to preferentially affect a subset of mRNAs. However, the set of mRNAs that are regulated by DDX3 are unknown, along with the relationship between DDX3 binding and activity.
View Article and Find Full Text PDFThis study used an online survey of a sample of sexual minority Vietnamese women ( = 302, Mean = 21.23) who self-identified as lesbian (48.7%), bisexual (42.
View Article and Find Full Text PDFAcross the world billions of dollars of damage are attributed to rodents, resulting in them being classified collectively as the biggest animal pest in the world. At a commercial scale most pest control companies employ the labour intensive approach of deploying and manually monitoring rodenticide bait stations. In this paper was present, , a visual, low-power bait station monitoring system which wirelessly reports both on bait station levels and intruders entering the bait station.
View Article and Find Full Text PDFBackground: Studying well-being at work and how it is related to employees' work-home interactions has been of great concern to both researchers and policy-makers in recent years. The aim of this study is to investigate the status of well-being at work of young Vietnamese employees working in Hanoi city and how dimensions of their work-home interaction contribute to their well-being at work.
Participants And Procedure: A self-administered questionnaire survey was conducted on 675 Vietnamese employees whose age was under 35 years.
Background: The M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2) is one of the key components in the Warburg effect, and an important regulator of cancer cell metabolism. Elevated PKM2 expression is a hallmark of numerous tumor types, making it a promising target for cancer therapy.
Methods: Migration of H1299 lung tumor cells treated with synthetic oleanane triterpenoid derivatives CDDO-Me and CDDO-Im was monitored using scratch and transwell assays.
Aquaculture production of the Pacific white shrimp is the largest in the world for crustacean species. Crucial to the sustainable global production of this important seafood species is a fundamental understanding of the shrimp gut microbiota and its relationship to the microbial ecology of shrimp pond. This is especially true, given the recently recognized role of beneficial microbes in promoting shrimp nutrient intake and in conferring resistance against pathogens.
View Article and Find Full Text PDFThe unusually high demand for metals in the brain, along with insufficient understanding of how their dysregulation contributes to neurological diseases, motivates the study of how inorganic chemistry influences neural circuitry. We now report that the transition metal copper is essential for regulating rest-activity cycles and arousal. Copper imaging and gene expression analysis in zebrafish identifies the locus coeruleus-norepinephrine (LC-NE) system, a vertebrate-specific neuromodulatory circuit critical for regulating sleep, arousal, attention, memory and emotion, as a copper-enriched unit with high levels of copper transporters CTR1 and ATP7A and the copper enzyme dopamine β-hydroxylase (DBH) that produces NE.
View Article and Find Full Text PDFCopper is essential for eukaryotic life, and animals must acquire this nutrient through the diet and distribute it to cells and organelles for proper function of biological targets. Indeed, mutations in the central copper exporter ATP7A contribute to a spectrum of diseases, including Menkes disease, with symptoms ranging from neurodegeneration to lax connective tissue. As such, a better understanding of the fundamental impacts of ATP7A mutations on in vivo copper distributions is of relevance to those affected by these diseases.
View Article and Find Full Text PDFThe capacity of G protein-coupled receptors to modulate mechanistic target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell surface receptors with cell survival. Cardiomyocyte viability is linked to signalling pathways involving Akt and mTOR, as well as increased glucose uptake and utilization. Our aim was to determine whether the α-adrenoceptor (AR) couples to these protective pathways, and increased glucose uptake.
View Article and Find Full Text PDFThe marine clam Lutraria rhynchaena is gaining popularity as an aquaculture species in Asia. Lutraria populations are present in the wild throughout Vietnam and several stocks have been established and translocated for breeding and aquaculture grow-out purposes. In this study, we demonstrate the feasibility of utilising Illumina next-generation sequencing technology to streamline the identification and genotyping of microsatellite loci from this clam species.
View Article and Find Full Text PDFJ Opt Soc Am A Opt Image Sci Vis
May 2015
We present a hemispherical reflectance model for simulating passive images in an outdoor environment where illumination is provided by natural sources such as the sun and the clouds. While the bidirectional reflectance distribution function (BRDF) accurately produces radiance from any objects after the illumination, using the BRDF in calculating radiance requires double integration. Replacing the BRDF by hemispherical reflectance under the natural sources transforms the double integration into a multiplication.
View Article and Find Full Text PDFMitochondrial DNA A DNA Mapp Seq Anal
October 2016
The complete mitochondrial genome of the commercially important snout otter clam Lutraria rhynchaena was obtained from low-coverage shotgun sequencing data on the MiSeq platform. The L. rhynchaena mitogenome has 16,927 base pairs (69% A + T content) and made up of 12 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs, and a 953 bp non-coding AT-rich region.
View Article and Find Full Text PDFEpithelial-to-mesenchymal transition (EMT) is controlled by cellular signaling pathways that trigger the loss of cell-cell adhesion and lead to the restructuring of the cell cytoskeleton. Transforming growth factor β (TGF-β) has been shown to regulate cell plasticity through the phosphorylation of Par6 on a conserved serine residue (S345) by the type II TGF-β receptor. We show here that atypical protein kinase C (aPKC) is an essential component to this signaling pathway in non-small-cell lung cancer (NSCLC) cells.
View Article and Find Full Text PDFIEEE Trans Syst Man Cybern B Cybern
October 2012
Color textures contain a large amount of spectral and spatial structure that can be exploited for recognition. Recent work has demonstrated that spatial filters offer a convenient means of extracting illumination-invariant spatial information from a color image. In this paper, we address the problem of deriving optimal filters for illumination-invariant color texture discrimination.
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