Evolutionarily conserved enhancer-associated features within the MYEOV locus suggest a regulatory role for this non-coding DNA region in cancer.

The myeloma overexpressed gene (MYEOV) has been proposed to be a proto-oncogene due to high RNA transcript levels found in multiple cancers, including myeloma, breast, lung, pancreas and esophageal cancer. The presence of an open reading frame (ORF) in humans and other primates suggests protein-coding potential. Yet, we still lack evidence of a functional MYEOV protein. It remains undetermined how MYEOV overexpression affects cancerous tissues. In this work, we show that MYEOV has likely originated and may still function as an enhancer, regulating CCND1 and LTO1. Firstly, MYEOV 3' enhancer activity was confirmed in humans using publicly available ATAC-STARR-seq data, performed on B-cell-derived GM12878 cells. We detected enhancer histone marks H3K4me1 and H3K27ac overlapping MYEOV in multiple healthy human tissues, which include B cells, liver and lung tissue. The analysis of 3D genome datasets revealed chromatin interactions between a MYEOV-3'-putative enhancer and the proto-oncogene CCND1. BLAST searches and multi-sequence alignment results showed that DNA sequence from this human enhancer element is conserved from the amphibians/amniotes divergence, with a 273 bp conserved region also found in all mammals, and even in chickens, where it is consistently located near the corresponding CCND1 orthologues. Furthermore, we observed conservation of an active enhancer state in the MYEOV orthologues of four non-human primates, dogs, rats, and mice. When studying this homologous region in mice, where the ORF of MYEOV is absent, we not only observed an enhancer chromatin state but also found interactions between the mouse enhancer homolog and Ccnd1 using 3D-genome interaction data. This is similar to the interaction observed in humans and, interestingly, coincides with CTCF binding sites in both species. Taken together, this suggests that MYEOV is a primate-specific gene with a de novo ORF that originated at an evolutionarily older enhancer region. This deeply conserved putative enhancer element could regulate CCND1 in both humans and mice, opening the possibility of studying MYEOV regulatory functions in cancer using non-primate animal models.

Prospective validation of a preoperative scoring system for difficult laparoscopy cholecystectomy.

Difficult laparoscopic cholecystectomy (LC) is defined by its surgical outcomes, including operative time, conversion to open surgery, bile duct and/or vascular injury. Difficult LC can be graded based on intraoperative findings. The main objective of this study is to apply and validate the reliability of their proposed risk score to predict the operative difficulty of an LC, based on their own validated intraoperative scale. Single-center prospective cohort study from 01/2020-12-2023. 367 patients > 18 years who underwent LC were included. The preoperative risk scale and intraoperative grading system were registered. Surgical outcomes were determined. Predictive accuracy was evaluated by the Receiver Operator Characteristic curve, sensitivity, specificity, positive, and negative predictive values, and Youden's Index (J). Patients' mean age was 44.1 ± 15.3 years. According to the risk score, 39.5% LC were "low" risk difficulty, 49.3% were "medium" risk, and 11.2% were "high" risk difficult LC. Based on the intraoperative grading system, 31.9% were difficult LC (Nassar grades 3-4) and 68.1% were easy LC (Nassar grades 1-2). There was a statistically significant correlation (0.428, p < 0.05) between the preoperative risk score and the intraoperative grading system. The AUC for the preoperative risk score scale and intraoperative difficult LC was 0.735 (95% CI 0.687-0.779) (J: 0.34). A preoperative risk score > 1.5 had an 83.7% sensitivity and a 50.8% specificity for intraoperative difficult LC. A predictive preoperative score for difficult LC and a routine collection of the intraoperative difficulty should be implemented to improve surgical outcomes and surgical planning.

From 'Farm to Fork': Exploring the Potential of Nutrient-Rich and Stress-Resilient Emergent Crops for Sustainable and Healthy Food in the Mediterranean Region in the Face of Climate Change Challenges.

In the dynamic landscape of agriculture and food science, incorporating emergent crops appears as a pioneering solution for diversifying agriculture, unlocking possibilities for sustainable cultivation and nutritional bolstering food security, and creating economic prospects amid evolving environmental and market conditions with positive impacts on human health. This review explores the potential of utilizing emergent crops in Mediterranean environments under current climate scenarios, emphasizing the manifold benefits of agricultural and food system diversification and assessing the impact of environmental factors on their quality and consumer health. Through a deep exploration of the resilience, nutritional value, and health impacts of neglected and underutilized species (NUS) such as quinoa, amaranth, chia, moringa, buckwheat, millet, teff, hemp, or desert truffles, their capacity to thrive in the changing Mediterranean climate is highlighted, offering novel opportunities for agriculture and functional food development. By analysing how promoting agricultural diversification can enhance food system adaptability to evolving environmental conditions, fostering sustainability and resilience, we discuss recent findings that underscore the main benefits and limitations of these crops from agricultural, food science, and health perspectives, all crucial for responsible and sustainable adoption. Thus, by using a sustainable and holistic approach, this revision analyses how the integration of NUS crops into Mediterranean agrifood systems can enhance agriculture resilience and food quality addressing environmental, nutritional, biomedical, economic, and cultural dimensions, thereby mitigating the risks associated with monoculture practices and bolstering local economies and livelihoods under new climate scenarios.

Decoding the Gut Microbiota-Gestational Diabetes Link: Insights from the Last Seven Years.

The human microbiome, a complex ecosystem of bacteria, viruses, and protozoans living in symbiosis with the host, plays a crucial role in human health, influencing everything from metabolism to immune function. Dysbiosis, or an imbalance in this ecosystem, has been linked to various health issues, including diabetes and gestational diabetes (GD). In diabetes, dysbiosis affects the function of adipose tissue, leading to the release of adipokines and cytokines, which increase inflammation and insulin resistance. During pregnancy, changes to the microbiome can exacerbate glucose intolerance, a common feature of GD. Over the past years, burgeoning insights into the gut microbiota have unveiled its pivotal role in human health. This article comprehensively reviews literature from the last seven years, highlighting the association between gut microbiota dysbiosis and GD, as well as the metabolism of antidiabetic drugs and the potential influences of diet and probiotics. The underlying pathophysiological mechanisms discussed include the impact of dysbiosis on systemic inflammation and the interplay with genetic and environmental factors. By focusing on recent studies, the importance of considering microbial health in the prevention and treatment of GD is emphasized, providing insights into future research directions and clinical applications to improve maternal-infant health outcomes.

Empagliflozin and Dapagliflozin Improve Endothelial Function in Mexican Patients with Type 2 Diabetes Mellitus: A Double-Blind Clinical Trial.

AIM: To assess the acute effect of empagliflozin versus dapagliflozin administration on flow-mediated vasodilation in patients with type 2 diabetes mellitus. DESIGN: A double-blind clinical trial, at the Experimental and Clinical Therapeutics Institute, University Health Sciences Center, at the Universidad de Guadalajara, in inpatients with T2D according to the 2023 ADA criteria. METHODS: Thirty patients (15 males and 15 females), aged between 35 and 65 years, were included in this study, according to the 2023 ADA criteria. The eligible patients were randomly assigned to three groups: empagliflozin 25 mg once daily, dapagliflozin 10 mg once daily, or placebo once daily. Anthropometric parameters were taken using validated techniques. FMD was measured using a high-resolution semiautomatic ultrasound UNEX-EF 38G (UNEX Co., Ltd., Nagoya, Japan). Arterial tension was determined with the OMRON electronic digital sphygmomanometer (HEM 907 XL, Kyoto, Japan). RESULTS: The group of patients who received empagliflozin had a significantly lower baseline flow-mediated dilation (FMD) compared to the group receiving dapagliflozin (p = 0.017); at the end of this study, the empagliflozin group achieved a comparable FMD to the dapagliflozin group (p = 0.88). CONCLUSION: After the treatment period, the empagliflozin and dapagliflozin groups achieved similar FMD, suggesting a class effect.

Impact of the rs822393 Variant on Adiponectin Levels and Metabolic Parameters after Weight Loss Secondary to a High-Fat Hypocaloric Diet with Mediterranean Pattern.

INTRODUCTION: The effects of the rs822393 variant of ADIPOQ gene on metabolic parameters such as insulin resistance and adiponectin levels following weight loss through dietary intervention are still uncertain. The aim of this study was to evaluate the role of rs822393 of ADIPOQ gene on adiponectin levels and metabolic parameters after weight loss with a high-fat hypocaloric diet with Mediterranean pattern during 12 weeks. METHODS: A population of 283 patients with obesity was allocated to a dietary intervention trial with a high-fat hypocaloric diet during 12 weeks. Adiposity and biochemical parameters were determined. rs822393 was assessed with a dominant model analysis (CC vs. CT + TT). RESULTS: These patients had three different genotypes: CC (59.0%), CT (33.6%), and TT (7.4%). The allelic frequencies for C and T were 0.89 and 0.20, respectively. Basal and post-intervention HDL cholesterol, adiponectin levels, and adiponectin/leptin ratio were lower in T-allele than non-T-allele carriers. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin, HOMA-IR, leptin, total cholesterol, and LDL cholesterol levels improved significantly in both genotype groups. Moreover, HDL cholesterol (CC vs. CT + TT) (delta: 8.9 ± 1.1 mg/dL vs. 1.7 ± 0.8 mg/dL; p = 0.02), serum adiponectin in non-T-allele carriers (43.1 ± 5.9 ng/dL vs. 2.8 ± 3 0.0 ng/dL; p = 0.01), and adiponectin/leptin ratio (1.37 ± 0.1 units vs. 0.17 ± 0.08 units; p = 0.02) improved only in non-T-allele carriers after weight loss. CONCLUSION: Individuals with obesity and without the T allele of rs822393 experienced improvements in adiponectin levels, adiponectin/leptin ratio, and HDL cholesterol levels after following a high-fat hypocaloric diet with a Mediterranean pattern.

Boosting Synergistic Antioxidant and Anti-Inflammatory Properties Blending Cereal-Based Nutraceuticals Produced Using Sprouting and Hydrolysis Tools.

Nutraceuticals obtained from sprouted wheat and oat grains and processing by-products (bran and hull, respectively) naturally containing antioxidant and anti-inflammatory compounds were evaluated. The objective of this study was the development of a cereal-based nutraceutical formula combining extracts from sprouts and by-products and the exploration for potential synergetic effects in their bioactive properties. The antioxidant and anti-inflammatory capacities, glycemic index, phytic acid, and ß-glucan of individual wheat bran hydrolysate (EH-WB), sprouted wheat (SW), oat hull hydrolysate (EH-OH), sprouted oat (SO), and combined ingredients (CI 1, CI 2, and CI3) were used to tailor an optimal nutraceutical formula. The three blend ingredients (CI 1, CI2, and CI3) were formulated at different ratios (EH-WB:SW:EH-OH:SO; 1:1:1:1, 2:1:2:1, and 1:2:1:2, w:w:w:w, respectively). The resulting mixtures showed total phenol (TPs) content ranging from 412.93 to 2556.66 µmol GAE 100 g-1 and antioxidant capacity values from 808.14 to 22,152.54 µmol TE 100 g-1 (ORAC) and 1914.05 to 7261.32 µmol TE 100 g-1 (ABTS•+), with Fe3+ reducing ability from 734. 02 to 8674.51 mmol reduced Fe 100 g-1 (FRAP) for the individual ingredients produced from EH-WB and EH-OH, where high antioxidant activity was observed. However, the anti-inflammatory results exhibited an interesting behavior, with a potentially synergistic effect of the individual ingredients. This effect was observed in CI2 and CI3, resulting in a higher ability to inhibit IL-6 and TNF-α than expected based on the anti-inflammatory values of their individual ingredients. Similar to the antioxidant properties, oat-based ingredients significantly contributed more to the anti-inflammatory properties of the overall mixture. This contribution is likely associated with the ß-glucans and avenanthramides present in oats. To ensure the bioaccessibility of these ingredients, further studies including simulated digestion protocols would be necessary. The ingredient formulated with a 2:1 hydrolysate-to-sprout ratio was the most effective combination, reaching higher biological characteristics.

An Entropic Analysis of Social Demonstrations.

Social media has dramatically influenced how individuals and groups express their demands, concerns, and aspirations during social demonstrations. The study of X or Twitter hashtags during those events has revealed the presence of some temporal points characterised by high correlation among their participants. It has also been reported that the connectivity presents a modular-to-nested transition at the point of maximum correlation. The present study aims to determine whether it is possible to characterise this transition using entropic-based tools. Our results show that entropic analysis can effectively find the transition point to the nested structure, allowing researchers to know that the transition occurs without the need for a network representation. The entropic analysis also shows that the modular-to-nested transition is characterised not by the diversity in the number of hashtags users post but by how many hashtags they share.

Genome Engineering by RNA-Guided Transposition for Anabaena sp. PCC 7120.

In genome engineering, the integration of incoming DNA has been dependent on enzymes produced by dividing cells, which has been a bottleneck toward increasing DNA insertion frequencies and accuracy. Recently, RNA-guided transposition with CRISPR-associated transposase (CAST) was reported as highly effective and specific in Escherichia coli. Here, we developed Golden Gate vectors to test CAST in filamentous cyanobacteria and to show that it is effective in Anabaena sp. strain PCC 7120. The comparatively large plasmids containing CAST and the engineered transposon were successfully transferred into Anabaena via conjugation using either suicide or replicative plasmids. Single guide (sg) RNA encoding the leading but not the reverse complement strand of the target were effective with the protospacer-associated motif (PAM) sequence included in the sgRNA. In four out of six cases analyzed over two distinct target loci, the insertion site was exactly 63 bases after the PAM. CAST on a replicating plasmid was toxic, which could be used to cure the plasmid. In all six cases analyzed, only the transposon cargo defined by the sequence ranging from left and right elements was inserted at the target loci; therefore, RNA-guided transposition resulted from cut and paste. No endogenous transposons were remobilized by exposure to CAST enzymes. This work is foundational for genome editing by RNA-guided transposition in filamentous cyanobacteria, whether in culture or in complex communities.

Evolutionary analysis of gene ages across TADs associates chromatin topology with whole-genome duplications.

Topologically associated domains (TADs) are interaction subnetworks of chromosomal regions in 3D genomes. TAD boundaries frequently coincide with genome breaks while boundary deletion is under negative selection, suggesting that TADs may facilitate genome rearrangements and evolution. We show that genes co-localize by evolutionary age in humans and mice, resulting in TADs having different proportions of younger and older genes. We observe a major transition in the age co-localization patterns between the genes born during vertebrate whole-genome duplications (WGDs) or before and those born afterward. We also find that genes recently duplicated in primates and rodents are more frequently essential when they are located in old-enriched TADs and interact with genes that last duplicated during the WGD. Therefore, the evolutionary relevance of recent genes may increase when located in TADs with established regulatory networks. Our data suggest that TADs could play a role in organizing ancestral functions and evolutionary novelty.

Exploring New Horizons for Wine Grapes: Modulating Functional Effects by Varying Harvest Timing and Solar Exposure.

Grenache (GN) and Cabernet Sauvignon (CS) are two traditional red grape varieties widely cultivated in the Mediterranean area and both late-ripening cultivars, which makes them less sensitive to global warming conditions and more stable to harvest timing. Although different studies have evaluated the final antioxidant properties of grapes and pomaces, few studies have explored the effect of sun exposure and harvest on the nutritional and antioxidant properties of these products. This study investigates the control of sunlight and ripening as tools to tailor nutritional and antioxidant properties of grape juices (GJ) and their byproducts (pomace GP). The compositional analysis showed no significant (p ≥ 0.05) differences associated to either harvesting timing or exposure to sunlight for either of the two studied varieties. However, differences (p ≤ 0.05) were observed between varieties of protein and total dietary fibre (TDF). CS protein content ranged from 0.52 to 3.88 (g 100 g-1) in GJ and from 1.0 to 1.32 (g 100 g-1) in GP; meanwhile, GN had higher protein values in GJ (from 2.11 to 4.77 g 100 g-1) and GP (from 5.11 to 6.75 g 100 g-1). The opposite behaviour was observed in TDF; CS grape had higher values for juice (from 11.43 to 19.53 g 100 g-1) and pomace (from 42.20 to 65.80 g 100 g-1) than GN (from 11.43 to 17.22 g 100 g-1 in juice and from 25.90 to 54.0 g 100 g-1 in pomace). The total phenolic content (TP) in GP was 100 times higher than in the juices and showed a much less pronounced evolution compared to the GJ during the harvesting time. GN TP values ranged from 5835 to 8772 mg GAE 100 g-1; meanwhile, CS values ranged from 7637 to 9040 mg GAE 100 g-1. A significant (p ≤ 0.05) correlation between the TP total antioxidant capacity (TAC) results was observed, regardless of variety, harvesting time, and sunlight exposure. These findings show how the control of different factors can contribute to obtain modified grape-derived products from conventional varieties beyond the wine market.

Combined Strategy Using High Hydrostatic Pressure, Temperature and Enzymatic Hydrolysis for Development of Fibre-Rich Ingredients from Oat and Wheat By-Products.

Wheat bran (WB) and oat hull (OH) are two interesting undervalued cereal processing sources rich in total dietary fibre (TDF) and other associated bioactive compounds, such as ß-glucans and polyphenols. The aim of this study was to optimise a combination chemical (enzymes) and physical (high hydrostatic pressure-temperature) strategies to increase the bioaccessibility of bioactive compounds naturally bound to the bran and hull outer layers. WB and OH were hydrolysed using food-grade enzymes (UltraFloXL and Viscoferm, for WB and OH, respectively) in combination with HPP at different temperatures (40, 50, 60 and 70 °C) and hydrolysis either before or after HPP. Proximal composition, phytic acid, ß-glucans, total phenolics (TPs) and total antioxidant activity (TAC) were evaluated to select the processing conditions for optimal nutritional and bioactive properties of the final ingredients. The application of the hydrolysis step after the HPP treatment resulted in lower phytic acid levels in both matrices (WB and OH). On the other hand, the release of ß-glucan was more effective at the highest temperature (70 °C) used during pressurisation. After the treatment, the TP content ranged from 756.47 to 1395.27 µmol GAE 100 g-1 in WB, and OH showed values from 566.91 to 930.45 µmol GAE 100 g-1. An interaction effect between the temperature and hydrolysis timing (applied before or after HPP) was observed in the case of OH. Hydrolysis applied before HPP was more efficient in releasing OH TPs at lower HPP temperatures (40-50 °C); meanwhile, at higher HPP temperatures (60-70 °C), hydrolysis yielded higher TP values when applied after HPP. This effect was not observed in WB, where the hydrolysis was more effective before HPP. The TP results were significantly correlated with the TAC values. The results showed that the application of optimal process conditions (hydrolysis before HPP at 60 or 70 °C for WB; hydrolysis after HPP at 70 °C for OH) can increase the biological value of the final ingredients obtained.

Effects of Dietary Supplementation with a Ferulic Acid-Rich Bioactive Component of Wheat Bran in a Murine Model of Graft-Versus-Host Disease.

Graft-versus-host disease (GvHD) is a common and severe complication following allogeneic hematopoietic stem cell transplantation (HSCT). Its prevention and treatment is a major challenge. Ferulic acid (FA) has anti-inflammatory and antioxidant properties that could be attractive in this setting. Our aim was to evaluate a bioactive ingredient derived from wheat bran (WB), selected for its high concentration of FA, in a murine model of GvHD. The ingredient was obtained via a bioprocess involving hydrolysis and spray-drying. GvHD was induced via HSCT between MHC-mismatched mouse strains. FA treatment was administered orally. Survival and disease scores (weight loss, hunching, activity, fur texture, and skin integrity, each scored between 0 and 2 depending on disease severity) were recorded daily, histological evaluation was performed at the end of the experiment, and serum inflammatory cytokines were analyzed on days 9 and 28. Treatment with FA did not protect GvHD mice from death, nor did it diminish GvHD scores. However, histological analysis showed that ulcers with large areas of inflammatory cells, vessels, and keratin were less common in skin samples from FA-treated mice. Areas of intense inflammatory response were also seen in fewer small intestine samples from treated mice. In addition, a slight decrease in INF-γ and TNF-α expression was observed in the serum of treated mice on day 28. The results showed some local effect of the ingredient intervention, but that the dose used may not be sufficient to control or reduce the inflammatory response at the systemic level in mice with GvHD. Higher dosages of FA may have an impact when evaluating the immunomodulatory capabilities of the hydrolyzed WB ingredient. Thus, further experiments and the use of technological strategies that enrich the ingredients in soluble ferulic acid to improve its efficacy in this setting are warranted.

Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation.

Histone modifications influence the recruitment of reader proteins to chromosomes to regulate events including transcription and cell division. The idea of a histone code, where combinations of modifications specify unique downstream functions, is widely accepted and can be demonstrated in vitro. For example, on synthetic peptides, phosphorylation of Histone H3 at threonine-3 (H3T3ph) prevents the binding of reader proteins that recognize trimethylation of the adjacent lysine-4 (H3K4me3), including the TAF3 component of TFIID. To study these combinatorial effects in cells, we analyzed the genome-wide distribution of H3T3ph and H3K4me2/3 during mitosis. We find that H3T3ph anti-correlates with adjacent H3K4me2/3 in cells, and that the PHD domain of TAF3 can bind H3K4me2/3 in isolated mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are still displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division.

Repurposing Terfenadine as a Novel Antigiardial Compound.

Giardia lamblia is a highly infectious protozoan that causes giardiasis, a gastrointestinal disease with short-term and long-lasting symptoms. The currently available drugs for giardiasis treatment have limitations such as side effects and drug resistance, requiring the search for new antigiardial compounds. Drug repurposing has emerged as a promising strategy to expedite the drug development process. In this study, we evaluated the cytotoxic effect of terfenadine on Giardia lamblia trophozoites. Our results showed that terfenadine inhibited the growth and cell viability of Giardia trophozoites in a time-dose-dependent manner. In addition, using scanning electron microscopy, we identified morphological damage; interestingly, an increased number of protrusions on membranes and tubulin dysregulation with concomitant dysregulation of Giardia GiK were observed. Importantly, terfenadine showed low toxicity for Caco-2 cells, a human intestinal cell line. These findings highlight the potential of terfenadine as a repurposed drug for the treatment of giardiasis and warrant further investigation to elucidate its precise mechanism of action and evaluate its efficacy in future research.

Study of the Total Antioxidant Capacity (TAC) in Native Cereal-Pulse Flours and the Influence of the Baking Process on TAC Using a Combined Bayesian and Support Vector Machine Modeling Approach.

During the last few years, the increasing evidence of dietary antioxidant compounds and reducing chronic diseases and the relationship between diet and health has promoted an important innovation within the baked product sector, aiming at healthier formulations. This study aims to develop a tool based on mathematical models to predict baked goods' total antioxidant capacity (TAC). The high variability of antioxidant properties of flours based on the aspects related to the type of grain, varieties, proximal composition, and processing, among others, makes it very difficult to innovate on food product development without specific analysis. Total phenol content (TP), oxygen radical absorbance capacity (ORAC), and ferric-reducing antioxidant power assay (FRAP) were used as markers to determine antioxidant capacity. Three Bayesian-type models are proposed based on a double exponential parameterized curve that reflects the initial decrease and subsequent increase as a consequence of the observed processes of degradation and generation, respectively, of the antioxidant compounds. Once the values of the main parameters of each curve were determined, support vector machines (SVM) with an exponential kernel allowed us to predict the values of TAC, based on baking conditions (temperature and time), proteins, and fibers of each native grain.

Valorisation of Buckwheat By-Product as a Health-Promoting Ingredient Rich in Fibre for the Formulation of Gluten-Free Bread.

Bread is a widely consumed food that has often been used as a vehicle for functional ingredients such as dietary fibre. Fibre-rich breads have beneficial physiological effects on health, helping to combat chronic pathologies such as cardiovascular disease, diabetes, and certain types of colon cancer. The aim of this study is to evaluate the technological and nutritional effects of the inclusion of buckwheat hull particles (BH) at two addition levels (3 and 6%) and two particle sizes (fine, D50: 62.7 µm; coarse, D50: 307 µm) in a gluten-free (GF) bread formulation. A significant (p < 0.05) increase in the dough elastic modulus (G') was observed for all doughs containing BH, from 712 Pa for a rice-based dough to 1027-3738 Pa for those containing BH. Compared to rice-based breads, those containing BH showed a significant (p < 0.05) increase in total dietary fibre content (from three to five times) and in antioxidant capacity (from 78 to 290 mg TE/100 g dw. in the ORAC test). Breads containing fine BH at a level of 3% had similar sensory properties to the rice-based bread, demonstrating that it is possible to improve the TDF content while maintaining the sensory quality of the GF bread.

Broad H3K4me3 domains: Maintaining cellular identity and their implication in super-enhancer hijacking.

The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non-coding genome. Recent advances in epigenomic profiling have uncovered non-coding gene proximal promoters and distal enhancers of transcription genome-wide. Extension of promoter-associated H3K4me3 histone mark across the gene body, known as a broad H3K4me3 domain (H3K4me3-BD), is a signature of constitutive expression of cell-type-specific regulation and of tumour suppressor genes in healthy cells. Recently, it has been discovered that the presence of H3K4me3-BDs over oncogenes is a cancer-specific feature associated with their dysregulated gene expression and tumourigenesis. Moreover, it has been shown that the hijacking of clusters of enhancers, known as super-enhancers (SE), by proto-oncogenes results in the presence of H3K4me3-BDs over the gene body. Therefore, H3K4me3-BDs and SE crosstalk in healthy and cancer cells therefore represents an important mechanism to identify future treatments for patients with SE driven cancers.

Effect of postruminal supply of linseed oil in dairy cows: 2. Milk fatty acid profile and oxidative stability.

Our objective was to study the effect of increasing postruminal supply of linseed oil (L-oil), as a source of cis-9, cis-12, cis-15 18:3, on milk fatty acid profile and to assess the resulting impact on the development of volatile degradation products during the storage of homogenized milk. Five Holstein dairy cows fitted with a rumen cannula were randomly distributed in a 5 × 5 Latin square design. Abomasal infusion of L-oil was performed at the rate of 0, 75, 150, 300, and 600 ml/d during periods of 14 d. The concentration of cis-9, cis-12, cis-15 18:3 in milk fat increased linearly with L-oil dose. Concentrations of primary (conjugated diene and triene hydroperoxides) and secondary oxidation products (1-octen-3-one, propanal, hexanal, trans-2 + cis-3-hexenals, cis-4-heptenal, trans-2, cis-6-nonadienal trans-2, trans-4-nonadienal) increased during 11 d of storage at 4°C of homogenized milk under fluorescent light. The magnitude of the increase (difference between final and initial measurements) was linearly greater for all nine lipid oxidation products evaluated in response to increasing level of infusion. Results of the current experiment have shown that milk enriched in cis-9, cis-12, cis-15 18:3 via postruminal supply of L-oil is highly prone to oxidative degradation. This low oxidative stability, exposed under controlled experimental conditions, would represent a major obstacle to those who aim to market milk enriched in polyunsaturated fatty acids.

Effect of postruminal supply of linseed oil in dairy cows: 1. Production performance and fate of postruminally available α-linolenic acid.

Triacylglycerols (TAG) are the primary sources of preformed fatty acids (FA) for lipid synthesis in the mammary gland. However, polyunsaturated FA escaping ruminal biohydrogenation are selectively incorporated into cholesterol esters (CE) and phospholipids (PL). The aim of the current experiment was to study the effects of abomasal infusion of increasing amount of linseed oil (L-oil) on plasma distribution of α-linolenic acid (α-LA) and its transfer efficiency into milk fat. Five rumen-fistulated Holstein cows were randomly distributed in a 5 × 5 Latin square design. Abomasal infusion of L-oil (55.9% α-LA) was performed at the rate of 0, 75, 150, 300, and 600 ml/d. Concentrations of α-LA increased quadratically in TAG, PL, and CE; a less steep slope was observed with an inflexion at an infusion rate of 300 ml L-oil per day. The increase in plasma concentration of α-LA was of a lower magnitude in CE as compared with the other two fractions, resulting in a quadratic decrease in relative proportion of this FA circulating as CE. The transfer efficiency into milk fat increased from 0 to 150 ml L-oil infused, and a plateau was maintained thereafter with greater levels of infusion (quadratic response). This pattern resembles the quadratic response of the relative proportion of α-LA circulating as TAG, and the relative concentration of this FA in TAG. Increasing the postruminal supply of α-LA partly overcame the segregation mechanism of absorbed polyunsaturated FA in different plasma lipid classes. Proportionately more α-LA was then esterified as TAG, at the expense of CE, increasing its efficiency of transfer into milk fat. This mechanism appears to be surpassed in its turn when L-oil infusion was increased over 150 ml/d. Nevertheless, the yield of α-LA in milk fat continued to increase, but at a slower rate at the highest levels of infusion.