Discovery of new epigenomics-based biomarkers and the early diagnosis of neurodegenerative diseases

Treatment options for many neurodegenerative diseases are limited due to the lack of early diagnostic procedures that allow timely delivery of therapeutic agents to affected neurons prior to cell death. While notable advances have been made in neurodegenerative disease biomarkers, whether or not the biomarkers discovered to date are useful for early diagnosis remains an open question. Additionally, the reliability of these biomarkers has been disappointing, due in part to the large dissimilarities between the tissues traditionally used to source biomarkers and primarily diseased neurons. In this article, we review the potential viability of atypical epigenetic and/or consequent transcriptional alterations (ETAs) as biomarkers of early-stage neurodegenerative disease, and present our perspectives on the discovery and practical use of such biomarkers in patient-derived neural samples using single-cell level analyses, thereby greatly enhancing the reliability of biomarker application. © 2020 The Authors1

Variation of quercetin glycoside derivatives in three onion (Allium cepa L.) varieties

AbstractThe aim of this study was to quantify the contents of individual quercetin glycosides in red, yellow and chartreuse onion by High Performance Liquid Chromatography (HPLC) analysis. Acid hydrolysis of individual quercetin glycosides using 6M hydrochloric acid guided to identify and separate quercetin 7,4′-diglucoside, quercetin 3-glucoside, quercetin 4′-glucoside, and quercetin. The contents of total quercetin glycosides varied extensively among three varieties (ranged from 16.10 to 103.93mg/g DW). Quercetin was the predominant compound that accounted mean 32.21mg/g DW in red onion (43.6% of the total) and 127.92mg/g DW in chartreuse onion (78.3% of the total) followed by quercetin 3-glucoside (28.83 and 24.16mg/g DW) respectively. Quercetin 3-glucoside levels were much higher in yellow onion (43.85mg/g DW) followed by quercetin 30.08mg/g DW. Quercetin 4′-glucoside documented the lowest amount that documented mean 2.4% of the total glycosides. The varied contents of glycosides present in the different onion varieties were significant

YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5

AbstractProgrammed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA. Upon genotoxic stress response, YAF2 promotes TP53 activation via association with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally, impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses

Genome shotgun sequencing and development of microsatellite markers for gerbera (Gerbera hybrida H.) by 454 GS-FLX

The objective of this research was to develop and characterize microsatellite markers for gerbera. We used shotgun sequencing with Roche 454 GS-FLX Titanium technology to identify microsatellite loci in gerbera genomic DNA (Gerbera hybrida). The total length of non-redundant sequences obtained was 22,527,019 bp, which consisted of 3,085 contigs and 28,249 singletons. We assembled 61,958 reads into 3,085 contigs, of which 114 (3.70%) contained microsatellite repeats. The average G+C content was 39.3%. Functional annotation to known sequences yielded 14.7% unigenes in the ‘Raon’ cultivar. Analysis of the gerbera genome DNA (‘Raon’) general library showed that sequences of (AT), (AG), (AAG) and (AAT) repeats appeared most often, whereas (AC), (AAC) and (ACC) were the least frequent. Primer pairs were designed for 80 loci. Only eight primer pairs produced reproducible polymorphic bands in the 28 gerbera accessions analyzed. A total of 30 alleles were identified from the eight polymorphic SSR loci, with two to eight alleles per locus (average level of 3.75). These markers will be useful for investigating genetic diversity and differentiation in gerbera. Keywords: Genetic diversity, genomics, microsatellite isolation, pyrosequencing, SSRs. African Journal of Biotechnology Vol. 11(29), pp. 7388-7396, 10 April, 201

Angiographic analysis of the lateral intercostal artery perforator of the posterior intercostal artery: anatomic variation and clinical significance

PURPOSEKnowledge of the anatomic variations of the posterior intercostal artery (PICA) and its major branches is important during transthoracic procedures and surgery. We aimed to identify the anatomic features and variations of the lateral intercostal artery perforator (LICAP) of the PICA with selective PICA arteriography.METHODSWe retrospectively evaluated 353 PICAs in 75 patients with selective PICA arteriography for the following characteristics: incidence, length (as number of traversed intercostal spaces), distribution at the hemithorax (medial half vs. lateral half), and size as compared to the collateral intercostal artery of the PICA.RESULTSThe incidence of LICAPs was 35.9% (127/353). LICAPs were most commonly observed in the right 8th–11th intercostal spaces (33%, 42/127) and in the medial half of the hemithorax (85%, 108/127). Most LICAPs were as long as two (35.4%, 45/127) or three intercostal spaces (60.6%, 77/127). Compared to the collateral intercostal artery, 42.5% of LICAPs were larger (54/127), with most of these observed in the right 4th–7th intercostal spaces (48.8%, 22/54).CONCLUSIONWe propose the clinical significance of the LICAP as a potential risk factor for iatrogenic injury during posterior transthoracic intervention and thoracic surgery. For example, skin incisions must be as superficial as possible and directed vertically at the right 4th–7th intercostal spaces and the medial half of the thorax. Awareness of the anatomical variations of the LICAPs of the PICA will allow surgeons and interventional radiologists to avoid iatrogenic arterial injuries during posterior transthoracic procedures and surgery

Evaluation of factors related to Anaesthesia-induced Lens opacity in experimental mice

To investigate conditions that cause temporal lens opacity, we tested chemical and physical factors, such as anaesthesia dose, ocular surface dryness, and infrared (IR) light exposure in anaesthetised C57BL/6 N mice. Mice were anaesthetised with a low (80%; tiletamine/zolazepam 32 mg/kg and xylazine 8 mg/kg, intraperitoneal injection) or high (120%; 48 mg/kg and 12 mg/kg) dose of anaesthetic and examined every 5 min from 10 to 30 min after anaesthesia was induced. Lens opacity levels were assessed and graded (1–6) using the standard classification system. Regardless of the anaesthetic dose, lens opacity grade was 1–2 in moisturised eyes with application of 0.5% carboxymethylcellulose, and 5–6 in dry ocular surface conditions. Lens opacity in mice with high-dose anaesthetic in the dry ocular surface condition was not different from that of mice with low-dose anaesthetic. Lens opacity grade 1–2 was noted in eyes in the wet ocular surface condition, regardless of IR light exposure. During IR light exposure in eyes in the dry ocular surface condition, lens opacity (grade 6) in mice with high-dose anaesthetic was not different from that (grade 6) in mice with low-dose anaesthetic. We demonstrated that ocular surface dryness might be a relevant factor for the formation and progression of lens opacity in anesthetized C57BL/6 N mice. Anaesthesia dose and IR light exposure did not strongly influence lens opacity formation. Furthermore, eyes with corneal dryness-induced lens opacity recovered to normal status without additional intervention.This research was supported by Korea Mouse Phenotyping Project (NRF2013M3A9D5072551) of the Ministry of Science and ICT through the National Research Foundation

High-yield exfoliation of three-dimensional graphite into two-dimensional graphene-like sheets

Edge-functionalized graphite (EFG) is prepared via a "direct'' covalent attachment of organic molecular wedges. The EFG is dispersed in N-methyl-2-pyrrolidone with a concentration as high as 0.27 mg mL(-1), leading to high-yield exfoliation of the three-dimensional graphite into two-dimensional graphene-like sheets.close464