NANOG is required to establish the competence for germ-layer differentiation in the basal tetrapod axolotl.

Pluripotency defines the unlimited potential of individual cells of vertebrate embryos, from which all adult somatic cells and germ cells are derived. Understanding how the programming of pluripotency evolved has been obscured in part by a lack of data from lower vertebrates; in model systems such as frogs and zebrafish, the function of the pluripotency genes NANOG and POU5F1 have diverged. Here, we investigated how the axolotl ortholog of NANOG programs pluripotency during development. Axolotl NANOG is absolutely required for gastrulation and germ-layer commitment. We show that in axolotl primitive ectoderm (animal caps; ACs) NANOG and NODAL activity, as well as the epigenetic modifying enzyme DPY30, are required for the mass deposition of H3K4me3 in pluripotent chromatin. We also demonstrate that all 3 protein activities are required for ACs to establish the competency to differentiate toward mesoderm. Our results suggest the ancient function of NANOG may be establishing the competence for lineage differentiation in early cells. These observations provide insights into embryonic development in the tetrapod ancestor from which terrestrial vertebrates evolved.

Characteristics of gelatin from lizardfish (Saurida micropectoralis) and threadfin bream (Nemipterus hexodon) skins as influenced by extraction conditions.

Gelatins from lizardfish and threadfin bream skins were extracted using distilled water at 45 and 60 °C and 4, 8 and 12 h. Gelatin recovered from both lizardfish and threadfin bream skins was in the range of 63.96-91.46%. As extraction temperature and duration increased, the turbidity of gelatin solution from both species increased. Gelatins isolated from either lizardfish or threadfin bream skins at 45 °C for 4 and 8 h showed the maximum bloom strength (245.03-320.85 g), which were also greater than commercial gelatin from bovine (208.55 g) (P < 0.05). The gelatin gels (6.67%, w/v) could set at 4 °C within 3 min and were able to set at room temperatures within 51.83 min. Gelatins extracted from both fish skins contained α1-, ß- and γ-chains as predominant protein components. The lightness of all gelatin gels faintly declined with an increase in extraction temperature and time. Among the various production conditions explored, lizardfish/threadfin bream skin gelatin developed at 45 °C and 8 h was found to be highly comparable to commercial bovine gelatin. Based on the results obtained, gelatin from both fish species could be used as a replacement for land animal counterparts and can be used in many different food and pharmaceutical products.

Genome-Wide Association Study Identifies Risk Loci for Cluster Headache.

OBJECTIVE: This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways. METHODS: We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort. The 2 cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene-set enrichment, functional variant annotation, prediction and pathway analyses, were performed. RESULTS: Initial independent analysis identified 2 replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 × 10-17 , odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.37-1.66) and rs4519530 (p = 6.98 × 10-17 , OR = 1.47, 95% CI = 1.34-1.61) on chromosome 2, rs12121134 on chromosome 1 (p = 1.66 × 10-8 , OR = 1.36, 95% CI = 1.22-1.52), and rs11153082 (p = 1.85 × 10-8 , OR = 1.30, 95% CI = 1.19-1.42) on chromosome 6. Downstream analyses implicated immunological processes in the pathogenesis of cluster headache. INTERPRETATION: We identified and replicated several genome-wide significant associations supporting a genetic predisposition in cluster headache in a genome-wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to, for example, treatment response and cluster headache subtypes, could provide unprecedented insights into genotype-phenotype correlations and the pathophysiological pathways underlying cluster headache. ANN NEUROL 2021;90:193-202.

Evaluation of the Preservation and Digestion of Seal Meat Processed with Heating and Antioxidant Seal Meat Hydrolysates.

Seal meat is of high nutritive value but is not highly exploited for human food due to ethical issues, undesirable flavors, and loss of nutrients during the processing/cooking step. In this work, commercially available processed seal meat was treated with its hydrolysates as preservatives with the aim of improving nutrient bioavailability. The contents of the nutrients were analyzed after digestion using a simulated dynamic digestion model, and the effects of different processing conditions, i.e., low-temperature processing and storage (25 °C) and high-temperature cooking (100 °C), of seal meat were investigated. Hydrolysates with antioxidant activity decreased the amounts of the less desirable Fe3+ ions in the seal meat digests. After treatment with hydrolysates at room temperature, a much higher total Fe content of 781.99 mg/kg was observed compared to other treatment conditions. The release of amino acids increased with temperature and was 520.54 mg/g for the hydrolysate-treated sample versus 413.12 mg/g for the control seal meat sample treated in buffer. Overall, this study provides useful data on the potential use of seal meat as a food product with high nutritive value and seal meat hydrolysates with antioxidant activity as preservatives to control oxidation in food.

Conspicuity of prostate cancer on multiparametric magnetic resonance imaging: A cross-disciplinary translational hypothesis.

Pre-biopsy multiparametric magnetic resonance imaging (mpMRI) has transformed the risk stratification and diagnostic approach for suspected prostate cancer. The majority of clinically significant prostate cancers are visible on pre-biopsy mpMRI, however, there are a subset of significant tumors that are not detected by mpMRI. The radiobiological mechanisms underpinning mpMRI-visibility and invisibility of these cancers remain uncertain. Emerging evidence suggests that mpMRI-visible tumors are enriched with molecular features associated with increased disease aggressivity and poor clinical prognosis, which is supported by short-term endpoints, such as biochemical recurrence following surgery. Furthermore, at the histopathological level, mpMRI-visible tumors appear to exhibit increased architectural and vascular density compared to mpMRI-invisible disease. It seems probable that the genomic, pathological, radiological, and clinical features of mpMRI-visible and mpMRI-invisible prostate cancers are interrelated. Here, we propose a novel cross-disciplinary theory that links genomic and molecular evidence with cellular and histopathological appearances, elucidating both the mpMRI visibility and clinical status of significant prostate cancer.

Understanding the influence of left ventricular assist device inflow cannula alignment and the risk of intraventricular thrombosis.

BACKGROUND: Adverse neurological events associated with left ventricular assist devices (LVADs) have been suspected to be related to thrombosis. This study aimed to understand the risks of thrombosis with variations in the implanted device orientation. A severely dilated pulsatile patient-specific left ventricle, modelled with computational fluid dynamics, was utilised to identify the risk of thrombosis for five cannulation angles. With respect to the inflow cannula axis directed towards the mitral valve, the other angles were 25° and 20° towards the septum and 20° and 30° towards the free wall. RESULTS: Inflow cannula angulation towards the free wall resulted in longer blood residence time within the ventricle, slower ventricular washout and reduced pulsatility indices along the septal wall. Based on the model, the ideal inflow cannula alignment to reduce the risk of thrombosis was angulation towards the mitral valve and up to parallel to the septum, avoiding the premature clearance of incoming blood. CONCLUSIONS: This study indicates the potential effects of inflow cannulation angles and may guide optimised implantation configurations; however, the ideal approach will be influenced by other patient factors and is suspected to change over the course of support.

Effect of lactic fermentation on soy protein digestive pattern assessed by an in vitro dynamic gastrointestinal digestion model and the influence on human faecal microbiota.

BACKGROUND: The aim of this study was to investigate the effect of lactic fermentation on soy protein gastrointestinal digestive pattern and the influence of protein digesta on human faecal microbiota. Soymilk and soy yogurt were prepared in this study and a novel in vitro dynamic gastrointestinal model was employed to simulate gastric and duodenum digestions. Particle size, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and peptide content were monitored at the end of duodenum tract. RESULTS: Ingestion of soy yogurt allowed a rapid drop in pH from 7.0 to 5.0 at simulated duodenal digestion (0-30 min), and resulted in a loss in soluble protein content compared to that of soymilk. The electrophoretic pattern between soymilk and soy yogurt exerted distinctive differences at early stages of duodenal digestion (0-60 min) and resulted in different peptide contents (180 min). Soy yogurt duodenal digesta collected at 180 min (D180), by co-fermentation with human intestinal flora distribution, allowed a higher population in Bifidobacterium spp., Lactobacillus/Enterococcus spp. and Streptococcus/Lactococcus spp., whereas soy yogurt D30 resulted in lower population in Clostridium and Escherichia coli compared to samples co-fermented with soymilk digesta. CONCLUSION: The results demonstrated lactic fermentation of soy protein modulated human intestinal microflora and might relate to the different protein digestive behaviours. © 2020 Society of Chemical Industry.

Comparison of physicochemical properties of recombinant buckwheat trypsin inhibitor (rBTI) and soybean trypsin inhibitor (SBTI).

The inhibitory activities of buckwheat trypsin inhibitor (rBTI) towards trypsin were compared with soybean trypsin inhibitor (SBTI) in terms of their sensitivities to temperature, pH, salt ions and organic solvents. Both rBTI and SBTI were stable over a broad pH range of 2.0-12.0. rBTI exhibited higher thermal stability than SBTI. The inhibitory activity of rBTI was decreased by Zinc ions (Zn2+), KSCN, vitamin C and urea, while that of SBTI remained unchanged. However, H2O2, Mg2+ and Cu2+ ions had no significant effects on the inhibitory activities of rBTI and SBTI. Acetonitrile enhanced the inhibitory activity of rBTI, but had no effect on SBTI, while dimethylacetamide (DMAC) increased the inhibitory effect of both rBTI and SBTI. On the contrary, the inhibitory activities of rBTI and SBTI were reduced by isopropyl alcohol and methanol. The inhibition constants Ki of rBTI and SBTI were calculated to be 7.41 × 10-9 M and 6.52 × 10-9 M, respectively.

Food-related transglutaminase obtained from fish/shellfish.

In the past two decades, there has been an upsurge of interest in transglutaminase (TGase) research due to their immense value in food applications to improve the quality as well as functional and nutritional attributes of food. Besides, TGases have been involved in new biomaterial development and shown to have potential in various biomedical applications. Presently, TGases from microbial sources (and some animal sources) are the main forms of the enzyme used in industrial applications. Nonetheless, there are disadvantages with the commercial TGases currently in use for food processing, such as the low activity, low yield, high cost, consumer aversions on their safety, and difficult in activity recovery, among others. Fish and shellfish TGases are promising alternatives for use in food industries due to their cheap sources, high yield and special characteristics such as cold activity and thermal-lability. This review presents at the onset, the catalytic mechanism of TGase based on updated research; compares the enzymatic properties of fish/shellfish TGases with their animal, plant and microbial counterparts; summarizes the unique properties of fish/shellfish TGases related with food usage; and discusses the current and potential applications of fish/shellfish TGases in foods.

Prevalence of familial cluster headache: a systematic review and meta-analysis.

INTRODUCTION: The population rate of familial cluster headache (CH) has been reported to be as high as 20% however this varies considerably across studies. To obtain a true estimate of family history in CH, we conducted a systematic review and meta-analysis of previously published data. METHODS: Our systematic review involved a search of electronic databases (Medline, EMBASE, PubMed, CINAHL) to identify and appraise studies of interest utilising the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. To further ameliorate the accuracy of our analysis we included an additional unpublished cohort of CH patients recruited at a tertiary referral centre for headache, who underwent detailed family history with diagnostic verification in relatives. Data was extracted and meta-analysis conducted to provide a true estimation of family history. RESULTS: In total, we identified 7 studies which fulfilled our inclusion criteria. The estimated true prevalence of CH patients with a positive family history was 6.27% (95% CI:4.65-8.40%) with an overall I2 of 73%. Fitted models for gender subgroups showed higher estimates 9.26% (95% CI: 6.29-13.43%) in females. However the I2 for the female model was 58.42% and significant (p = 0.047). CONCLUSION: Our findings estimate a rate of family history in CH to be approximately 6.27% (95% CI: 4.65-8.40%). While estimates were larger for female probands, we demonstrated high heterogeneity in this subgroup. These findings further support a genetic role in the aetiology of CH.

Health Insurance Portability and Accountability Act Noncompliance in Patient Photograph Management in Plastic Surgery.

BACKGROUND: Today, plastic surgeons have largely transitioned to digital photography. This shift has introduced new risks to daily workflows, notably data theft and Health Insurance Portability and Accountability Act (HIPAA) violations. METHODS: We performed a national survey of digital photograph management patterns among members of the American Society of Plastic Surgery and trainees in Accreditation Council for Graduate Medical Education-accredited plastic surgery programs. RESULTS: Our findings showed that attendings preferred the use of stand-alone digital cameras (91.4%), whereas trainees preferred the use of smartphones (96.1%) for capturing patient photographs. The rate of noncompliance was nearly identical; 82.8% of attendings were HIPAA noncompliant when using stand-alone digital cameras compared with 90.2% of trainees using smartphones. Both groups also breached HIPAA rules when using other photographic management modalities. CONCLUSIONS: This is the first study to quantify the prevalence of noncompliance with regard to an entire digital photograph management workflow. These findings were consistent with previous studies that reported that younger physicians tend to embrace newer technologies, whereas older attendings are more reluctant. The findings also suggest that HIPAA noncompliance in digital photograph security and management is a significant problem within the plastic surgery community.

Phaseolus vulgaris lectins: A systematic review of characteristics and health implications.

Legume lectins are carbohydrate-binding proteins of non-immune origin. Significant amounts of lectins have been found in Phaseolus vulgaris beans as far back as in the last century; however, many questions about their potential biological roles still remain obscure. Studies have shown that lectins are anti-nutritional factors that can cause intestinal disorders. Owing to their ability to act as toxic allergens and hemagglutinins, the Phaseolus vulgaris lectins are of grave concern for human health and safety. Nonetheless, their potential beneficial health effects, such as anti-cancer, anti-human immunodeficiency virus (anti-HIV), anti-microbial infection, preventing mucosal atrophy, reducing type 2 diabetes and obesity, promoting nutrients absorption and targeting drugs, are of immense interest. The significance of Phaseolus vulgaris lectins in biological researches and the potential biomedical applications have placed tremendous emphasis on the development of purification strategies to obtain the protein in pure and stable forms. These purification strategies entail considerations such as effects of proteolysis, heating, gamma radiation, and high-hydrostatic-pressure that can have crucial outcomes in either eliminating or improving bioactivities of the lectins. Thus, up-to-date research findings of Phaseolus vulgaris lectins on different aspects such as anti-nutritional and health impacts, purification strategies and novel processing trends, are systematically reviewed.

The Influence of Rotary Blood Pump Speed Modulation on the Risk of Intraventricular Thrombosis.

Rotary left ventricular assist devices (LVADs) are commonly operated at a constant speed, attenuating blood flow pulsatility. Speed modulation of rotary LVADs has been demonstrated to improve vascular pulsatility and pump washout. The effect of LVAD speed modulation on intraventricular flow dynamics is not well understood, which may have an influence on thromboembolic events. This study aimed to numerically evaluate intraventricular flow characteristics with a speed modulated LVAD. A severely dilated anatomical left ventricle was supported by a HeartWare HVAD in a three-dimensional multiscale computational fluid dynamics model. Three LVAD operating scenarios were evaluated: constant speed and sinusoidal co- and counter-pulsation. In all operating scenarios, the mean pump speed was set to restore the cardiac output to 5.0 L/min. Co- and counter-pulsation was speed modulated with an amplitude of 750 rpm. The risk of thrombosis was evaluated based on blood residence time, ventricular washout, kinetic energy densities, and a pulsatility index map. Blood residence time for co-pulsation was on average 1.8 and 3.7% lower than constant speed and counter-pulsation mode, respectively. After introducing fresh blood to displace preexisting blood for 10 cardiac cycles, co-pulsation had 1.5% less old blood in comparison to counter-pulsation. Apical energy densities were 84 and 27% higher for co-pulsation in comparison to counter-pulsation and constant speed mode, respectively. Co-pulsation had an increased pulsatility index around the left ventricular outflow tract and mid-ventricle. Improved flow dynamics with co-pulsation was caused by increased E-wave velocities which minimized blood stasis. In the studied scenario and from the perspective of intraventricular flow dynamics, co-pulsation of rotary LVADs could minimize the risk of intraventricular thrombosis.

Extraction of gelatin from salmon (Salmo salar) fish skin using trypsin-aided process: optimization by Plackett-Burman and response surface methodological approaches.

Gelatin from salmon (Salmo salar) skin with high molecular weight protein chains (α-chains) was extracted using trypsin-aided process. Response surface methodology was used to optimise the extraction parameters. Yield, hydroxyproline content and protein electrophoretic profile via sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of gelatin were used as responses in the optimization study. The optimum conditions were determined as: trypsin concentration at 1.49 U/g; extraction temperature at 45 °C; and extraction time at 6 h 16 min. This response surface optimized model was significant and produced an experimental value (202.04 ± 8.64%) in good agreement with the predicted value (204.19%). Twofold higher yields of gelatin with high molecular weight protein chains were achieved in the optimized process with trypsin treatment when compared to the process without trypsin.

Effect of catechin and its derivatives on inhibition of polyphenoloxidase and melanosis of Pacific white shrimp.

This study aimed to investigate the effect of tea catechin (C) and 4 of its derivatives on the Pacific white shrimp PPO inhibition and melanosis during refrigerated storage. Epigallocatechin gallate (EGCG) exhibited the highest inhibition towards PPO, followed by C. Inhibitory activity of all compounds tested was in a dose dependent manner (0.1-2.0 mM). Based on activity staining, EGCG most effectively inhibited PPO. For inhibition kinetic studies, C and epicatechin (EC) showed uncompetitive type, whereas epicatechin gallate (ECG), epigallocatechin (EGC) and EGCG exhibited mixed type inhibition. When whole shrimps were treated with EGCG solution at various concentrations (0.25-0.75%), those treated with 0.5 or 0.75% EGCG had lower melanosis scores throughout storage for 10 days at 4 °C, compared with the control and the 1.25% sodium metabisulfite treated samples (P < 0.05). Therefore, EGCG could be used as a potential inhibitor for melanosis in raw Pacific white shrimp during refrigerated storage.

Numerical prediction of thrombus risk in an anatomically dilated left ventricle: the effect of inflow cannula designs.

BACKGROUND: Implantation of a rotary blood pump (RBP) can cause non-physiological flow fields in the left ventricle (LV) which may trigger thrombosis. Different inflow cannula geometry can affect LV flow fields. The aim of this study was to determine the effect of inflow cannula geometry on intraventricular flow under full LV support in a patient specific model. METHODS: Computed tomography angiography imaging of the LV was performed on a RBP candidate to develop a patient-specific model. Five inflow cannulae were evaluated, which were modelled on those used clinically or under development. The inflow cannulae are described as a crown like tip, thin walled tubular tip, large filleted tip, trumpet like tip and an inferiorly flared cannula. Placement of the inflow cannula was at the LV apex with the central axis intersecting the centre of the mitral valve. Full support was simulated by prescribing 5 l/min across the mitral valve. Thrombus risk was evaluated by identifying regions of stagnation. Rate of LV washout was assessed using a volume of fluid model. Relative haemolysis index and blood residence time was calculated using an Eulerian approach. RESULTS: The inferiorly flared inflow cannula had the lowest thrombus risk due to low stagnation volumes. All cannulae had similar rates of LV washout and blood residence time. The crown like tip and thin walled tubular tip resulted in relatively higher blood damage indices within the LV. CONCLUSION: Changes in intraventricular flow due to variances in cannula geometry resulted in different stagnation volumes. Cannula geometry does not appreciably affect LV washout rates and blood residence time. The patient specific, full support computational fluid dynamic model provided a repeatable platform to investigate the effects of inflow cannula geometry on intraventricular flow.

Techno-functional characterization of salad dressing emulsions supplemented with pea, lentil and chickpea flours.

BACKGROUND: Salad dressings supplemented with pulse flours are novel products. A three-factor face-centered central composite design (CCD) was used to determine the effect of pulse flour concentration (3.5%, 7%, 10.5% w/w), egg yolk concentration (3%, 5%, 7% w/w) and oil concentration (20%, 35%, 50% w/w) on the rheological and color characteristics of salad dressings supplemented with pulse flours. RESULTS: The consistency coefficient m, plateau modulus G(N)(0), recoverable strain Q(t) and color values were all affected by the concentrations of pulse flours used. Scanning electron microscopy showed that dressings with lower oil and egg yolk contents had a less densely packed network compared with dressings with higher oil and egg yolk contents. Sensory results were most promising for salad dressings supplemented with the whole green lentil, yellow pea with low flour content, and chickpea with high oil content. CONCLUSION: This study should be useful for designing novel types of salad dressings to meet market requirements as well as helping to increase pulse consumption.