Relay-Heck Cross-Coupling Between Alkenyl Halides and Unsaturated Alcohols in the Synthesis of Open-Chain Analogues of Musk Odorant Vulcanolide.

Unactivated alkenyl iodides and bromides underwent an unprecedented palladium-catalyzed relay-Heck cross-coupling with a whole range of alkenols of different chain lengths linking the alkene and the alcohol, affording unsaturated aldehydes and ketones in moderate to good yields. In contrast, alkenyl triflates were not suitable partners for this reaction. This method allowed the preparation of open-chain analogues of the musk odorant Vulcanolide, several of which retained key olfactory properties of the parent molecule.

Effects of a Fish Oil Rich in Docosahexaenoic Acid on Cardiometabolic Risk Factors and Oxidative Stress in Healthy Rats.

Omega-3 polyunsaturated fatty acids are associated with a lower risk of cardiometabolic diseases. However, docosahexaenoic acid (DHA) is easily oxidized, leading to cellular damage. The present study examined the effects of an increased concentration of DHA in fish oil (80% of total fatty acids) on cardiometabolic risk factors and oxidative stress compared to coconut oil, soybean oil, and fish oil containing eicosapentaenoic acid (EPA) and DHA in a balanced ratio. Forty healthy male Sprague-Dawley rats were supplemented with corresponding oil for 10 weeks. Supplementation with the fish oil containing 80% DHA decreased plasma fat, plasma total cholesterol and muscle fat compared to the coconut oil and the soybean oil. Increasing concentrations of DHA induced incorporation of DHA and EPA in cell membranes and tissues along with a decrease in ω-6 arachidonic acid. The increase in DHA promoted lipid peroxidation, protein carbonylation and antioxidant response. Taken together, the increased concentration of DHA in fish oil reduced fat accumulation compared to the coconut oil and the soybean oil. This benefit was accompanied by high lipid peroxidation and subsequent protein carbonylation in plasma and in liver. In our healthy framework, the slightly higher carbonylation found after receiving fish oil containing 80% DHA might be a protecting mechanism, which fit with the general improvement of antioxidant defense observed in those rats.

Polyphenols and Fish Oils for Improving Metabolic Health: A Revision of the Recent Evidence for Their Combined Nutraceutical Effects.

Polyphenols and omega-3 polyunsaturated fatty acids from fish oils, i.e., eicosapentaenoic and docosahexaenoic acids, are well-recognized nutraceuticals, and their single antioxidant and anti-inflammatory properties have been demonstrated in several studies found in the literature. It has been reported that the combination of these nutraceuticals can lead to three-fold increases in glutathione peroxidase activity, two-fold increases in plasma antioxidant capacity, decreases of 50-100% in lipid peroxidation, protein carbonylation, and urinary 8-isoprotanes, as well as 50-200% attenuation of common inflammation biomarkers, among other effects, as compared to their individual capacities. Therefore, the adequate combination of those bioactive food compounds and their single properties should offer a powerful tool for the design of successfully nutritional interventions for the prevention and palliation of a plethora of human metabolic diseases, frequently diet-induced, whose etiology and progression are characterized by redox homeostasis disturbances and a low-grade of chronic inflammation. However, the certain mechanisms behind their biological activities, in vivo interaction (both between them and other food compounds), and their optimal doses and consumption are not well-known yet. Therefore, we review here the recent evidence accumulated during the last decade about the cooperative action between polyphenols and fish oils against diet-related metabolic alterations, focusing on the mechanisms and pathways described and the effects reported. The final objective is to provide useful information for strategies for personalized nutrition based on these nutraceuticals.

Cytochrome c autocatalyzed carbonylation in the presence of hydrogen peroxide and cardiolipins.

Cytochrome c (cyt c) is a small hemoprotein involved in electron shuttling in the mitochondrial respiratory chain and is now also recognized as an important mediator of apoptotic cell death. Its role in inducing programmed cell death is closely associated with the formation of a complex with the mitochondrion-specific phospholipid cardiolipin (CL), leading to a gain of peroxidase activity. However, the molecular mechanisms behind this gain and eventual cyt c autoinactivation via its release from mitochondrial membranes remain largely unknown. Here, we examined the kinetics of the H2O2-mediated peroxidase activity of cyt c both in the presence and absence of tetraoleoyl cardiolipin (TOCL)- and tetralinoleoyl cardiolipin (TLCL)-containing liposomes to evaluate the role of cyt c-CL complex formation in the induction and stimulation of cyt c peroxidase activity. Moreover, we examined peroxide-mediated cyt c heme degradation to gain insights into the mechanisms by which cyt c self-limits its peroxidase activity. Bottom-up proteomics revealed >50 oxidative modifications on cyt c upon peroxide reduction. Of note, one of these by-products was the Tyr-based "cofactor" trihydroxyphenylalanine quinone (TPQ) capable of inducing deamination of Lys ϵ-amino groups and formation of the carbonylated product aminoadipic semialdehyde. In view of these results, we propose that autoinduced carbonylation, and thus removal of a positive charge in Lys, abrogates binding of cyt c to negatively charged CL. The proposed mechanism may be responsible for release of cyt c from mitochondrial membranes and ensuing inactivation of its peroxidase activity.

Establishment of a conditional Nomo1 mouse model by CRISPR/Cas9 technology.

The Nomo1 gene mediates a wide range of biological processes of importance in embryonic development. Accordingly, constitutive perturbation of Nomo1 function may result in myriad developmental defects that trigger embryonic lethality. To extend our understanding of Nomo1 function in postnatal stages and in a tissue-specific manner, we generated a conditional knockout mouse model of Nomo1. To achieve this, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology in C57Bl/6J mouse zygotes to generate a new mouse model in which exon 3 of the Nomo1 gene is specifically flanked (or floxed) by LoxP sites (Nomo1f/f). Nomo1f/f mouse embryonic fibroblasts were transduced with a Cre adenovirus and efficiently recombined between LoxP sites. Genomic and expression studies in Nomo1-transduced MEFs demonstrated that the Nomo1 exon 3 is ablated. Western blot assay showed that no protein or early truncated protein is produced. In vivo assay crossing Nomo1f/f mouse with a Msi1-CRE transgenic mouse corroborated the previous findings and it showed Nomo1 exon 3 deletion at msi1+ cell compartment. This short technical report demonstrates that CRISPR/Cas9 technology is a simple and easy method for creating conditional mouse models. The Nomo1f/f mouse will be useful to researchers who wish to explore the role of Nomo1 in any developmental stage or in a tissue-specific manner.

Effects of Fish Oil and Grape Seed Extract Combination on Hepatic Endogenous Antioxidants and Bioactive Lipids in Diet-Induced Early Stages of Insulin Resistance in Rats.

Diacylglycerols (DAG) and ceramides have been suggested as early predictors of insulin resistance. This study was aimed to examine the combined effects of fish oil (FO) and grape seed extract (GSE) on hepatic endogenous antioxidants, DAG and ceramides in diet-induced early stages of insulin resistance. Thirty-five rats were fed one of the following diets: (1) a standard diet (STD group), (2) a high-fat high-sucrose diet (HFHS group), (3) an HFHS diet enriched with FO (FO group), (4) an HFHS diet enriched with GSE (GSE group) or (5) an HFHS diet enriched with FO and GSE (FO + GSE group). In the liver, endogenous antioxidants were measured using spectrophotometric and fluorometric techniques, and non-targeted lipidomics was conducted for the assessment of DAG and ceramides. After 24 weeks, the FO + GSE group showed increased glutathione peroxidase activity, as well as monounsaturated fatty acid and polyunsaturated fatty acid-containing DAG, and long-chain fatty acid-containing ceramides abundances compared to the STD group. The FO and GSE combination induced similar activation of the antioxidant system and bioactive lipid accumulation in the liver than the HFHS diet without supplementation. In addition, the FO and GSE combination increased the abundances of polyunsaturated fatty acid-containing DAG in the liver.

Similarities and differences in the lexical-grammatical relation of young dual language learners with and without specific language impairment.

This study examines the lexical-grammatical relation within and across in preschool Latino dual language learners (DLLs) with and without specific language impairment (SLI) using language-specific vocabulary and conceptual lexical-semantic skills. The participants were sixty-one typically developing (TD) Spanish-English speaking DLLs and seventy-four DLLs with SLI from low-income households. Standardized and researcher developed assessment tools were used to measure vocabulary, semantics, and grammar in both Spanish and English. Cross-sectional data were analyzed using hierarchical linear regressions to determine the nature of the lexical-grammatical association within and across languages. The study found significant within-language relations between measures of vocabulary and grammar for both groups. Conceptual vocabulary was a significant predictor for English grammar in both groups. For the SLI group only, both English and Spanish vocabulary scores significantly predicted English grammar and bilingual semantics scores predicted Spanish grammar. These findings underscore the role of language-specific vocabulary on grammatical development and suggest the presence of bilingual bootstrapping in DLLs. However, the degree and nature of cross-linguistic associations vary by language ability and language proficiency. The role of age and nonverbal cognition and clinical implications are also discussed.

Bibliometric Analysis of Medication-Related Osteonecrosis of the Jaw: High Citation Rates but Low Evidence.

PURPOSE: Citation analysis is one of the most commonly used bibliometric tools for measuring the academic importance of a report in a specific area of knowledge. The objective of the present study was to identify the 100 most cited reports on medication-related osteonecrosis of the jaw (MRONJ), determine their main bibliometric characteristics, and identify the bibliometric variables that affected the citation rates. MATERIALS AND METHODS: We performed a data search in the Scopus database to determine the number of MRONJ article citations up to September 30, 2018. We next selected the 100 most referenced studies and recorded the following information: ranking according to the number of citations; citation density; number and names of authors; language and year of publication; country and institution of origin; financial support; journal name, impact factor, category, and quartile; type of research; evidence level; and area of study. RESULTS: The 100 most cited reports had a mean citation density of 21.7 ± 20.7 (range, 6.2 to 99.4) and an h-index of 96. The 100 most cited reports on MRONJ had been published in 42 scientific journals, classified into 10 separate categories of the Journal Citation Reports; 56% of the articles were in the first quartile of their category. Most of the studies had been classified with a level of evidence of 4 (n = 45) or 5 (n = 29). In the bivariate analyses, only the conflict of interest (P = .002) was associated with citation density. After adjusting for numerous variables, conflict of interest (r = 0.27; P = .020) and country of the first author (r = 0.23; P = .043) were significantly associated with citation density. CONCLUSIONS: The 100 most cited studies of MRONJ had a large number of citations and had been reported in journals with a high impact factor; however, the studies had a generally low evidence level and randomized clinical trials were lacking.

Modulation of the Liver Protein Carbonylome by the Combined Effect of Marine Omega-3 PUFAs and Grape Polyphenols Supplementation in Rats Fed an Obesogenic High Fat and High Sucrose Diet.

Diet-induced obesity has been linked to metabolic disorders such as cardiovascular diseases andtype 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damagebiomolecules, especially proteins. The present study was designed to investigate the effect of marineomega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid(DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins fromplasma and liver in Wistar Kyoto rats fed an obesogenic diet, namely high-fat and high-sucrose (HFHS)diet. A proteomics approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labelling of proteincarbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification byMS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combinationof both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in bothplasma and liver. The analysis of carbonylated protein targets, also referred to as the 'carbonylome',revealed an individual response of liver proteins to supplements and a modulatory effect on specificmetabolic pathways and processes due to, at least in part, the control exerted by the supplements on theliver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grapeseed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption ofHFHS diets.

Nasometric Comparison Between Spanish-English Bilingual and English Monolingual Children.

OBJECTIVE: It is well established in the literature that English diagnostic tests should not be directly applied to speakers whose primary language is Spanish. Normative nasalance data across word and sentence-level stimuli among Spanish-English bilingual children living in the United States have not been provided. The present study aims to (1) compare differences in nasalance between typically developing Spanish-English bilingual children and English-speaking monolingual children and (2) determine whether within-speaker nasalance differences exist in Spanish-English bilingual children when presented with English and Spanish speech stimuli. DESIGN: Thirty-four typically developing children including 17 monolingual English speakers and 17 Spanish-English bilingual speakers with normal velopharyngeal anatomy between 5 and 7 years of age participated in the study. Speakers were recorded using a nasometer producing sets of stimulus items at the word and sentence level in English (English monolinguals) and in both Spanish and English for bilingual children. RESULTS: Results indicated no statistically significant difference between nasalance values across the different stimuli between monolingual and bilingual participants. However, within-subject effects showed statistical significance between English and Spanish word stimuli among the bilingual group. CONCLUSIONS: These findings emphasize the importance of using language-specific diagnostic materials for nasalance testing, which would be of importance in the treatment of individuals with cleft palate.

A high-fat high-sucrose diet affects the long-term metabolic fate of grape proanthocyanidins in rats.

PURPOSE: Polyphenol metabolites are key mediators of the biological activities of polyphenols. This study aimed to evaluate the long-term effects of a high-fat high-sucrose (HFHS) diet on the metabolism of proanthocyanidins from grape seed extract (GSE). METHODS: Adult female Wistar-Kyoto rats were fed a standard (STD) or HFHS diet supplemented or not with GSE for 16 weeks. PA metabolites were determined by targeted HPLC-MS/MS analysis. RESULTS: A lower concentration of total microbial-derived PA metabolites was present in urine and the aqueous fraction of faeces in the HFHS + GSE group than in the STD + GSE group. In contrast, a tendency towards the formation of conjugated (epi)catechin metabolites in the HFHS + GSE group was observed. CONCLUSIONS: These results show that a HFHS diet significantly modifies PA metabolism, probably via: (1) a shift in microbial communities not counteracted by the polyphenols themselves; and (2) an up-regulation of hepatic enzymes.

Targeting Hepatic Protein Carbonylation and Oxidative Stress Occurring on Diet-Induced Metabolic Diseases through the Supplementation with Fish Oils.

The present study addressed the ability of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFA), i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to ameliorate liver protein damage derived from oxidative stress and induced by consumption of high-caloric diets, typical of Westernized countries. The experimental design included an animal model of Sprague-Dawley rats fed high-fat high-sucrose (HFHS) diet supplemented with ω-3 EPA and DHA for a complete hepatic proteome analysis to map carbonylated proteins involved in specific metabolic pathways. Results showed that the intake of marine ω-3 PUFA through diet significantly decreased liver protein carbonylation caused by long-term HFHS consumption and increased antioxidant system. Fish oil modulated the carbonylation level of more than twenty liver proteins involved in critical metabolic pathways, including lipid metabolism (e.g., albumin), carbohydrate metabolism (e.g., pyruvate carboxylase), detoxification process (e.g., aldehyde dehydrogenase 2), urea cycle (e.g., carbamoyl-phosphate synthase), cytoskeleton dynamics (e.g., actin), or response to oxidative stress (e.g., catalase) among others, which might be under the control of diet marine ω-3 PUFA. In parallel, fish oil significantly changed the liver fatty acid profile given by the HFHS diet, resulting in a more anti-inflammatory phenotype. In conclusion, the present study highlights the significance of marine ω-3 PUFA intake for the health of rats fed a Westernized diet by describing several key metabolic pathways which are protected in liver.

Marine Lipids on Cardiovascular Diseases and Other Chronic Diseases Induced by Diet: An Insight Provided by Proteomics and Lipidomics.

Marine lipids, especially ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have largely been linked to prevention of diet-induced diseases. The anti-inflammatory and hypolipidemic properties of EPA and DHA supplementation have been well-described. However, there is still a significant lack of information about their particular mechanism of action. Furthermore, repeated meta-analyses have not shown conclusive results in support of their beneficial health effects. Modern "omics" approaches, namely proteomics and lipidomics, have made it possible to identify some of the mechanisms behind the benefits of marine lipids in the metabolic syndrome and related diseases, i.e., cardiovascular diseases and type 2 diabetes. Although until now their use has been scarce, these "omics" have brought new insights in this area of nutrition research. The purpose of the present review is to comprehensively show the research articles currently available in the literature which have specifically applied proteomics, lipidomics or both approaches to investigate the role of marine lipids intake in the prevention or palliation of these chronic pathologies related to diet. The methodology adopted, the class of marine lipids examined, the diet-related disease studied, and the main findings obtained in each investigation will be reviewed.

Relations Among the Home Language and Literacy Environment and Children's Language Abilities: A Study of Head Start Dual Language Learners and Their Mothers.

RESEARCH FINDINGS: This study explored the relations between Spanish-English dual language learner (DLL) children's home language and literacy experiences and their expressive vocabulary and oral comprehension abilities in Spanish and in English. Data from Spanish-English mothers of 93 preschool-age Head Start children who resided in central Pennsylvania were analyzed. Children completed the Picture Vocabulary and Oral Comprehension subtests of the Batería III Woodcock-Muñoz and the Woodcock-Johnson III Tests of Achievement. Results revealed that the language spoken by mothers and children and the frequency of mother-child reading at home influenced children's Spanish language abilities. In addition, the frequency with which children told a story was positively related to children's performance on English oral language measures. PRACTICE OR POLICY: The findings suggest that language and literacy experiences at home have a differential impact on DLLs' language abilities in their 2 languages. Specific components of the home environment that benefit and support DLL children's language abilities are discussed.

Effect of n-3 PUFA supplementation at different EPA:DHA ratios on the spontaneously hypertensive obese rat model of the metabolic syndrome.

The increasing incidence of the metabolic syndrome (MetS), a combination of risk factors before the onset of CVD and type 2 diabetes, encourages studies on the role of functional food components such as long-chain n-3 PUFA as preventive agents. In the present study, we explore the effect of EPA and DHA supplementation in different proportions on spontaneously hypertensive obese (SHROB) rats, a model for the MetS in a prediabetic state with mild oxidative stress. SHROB rats were randomised into four groups (n 7), each supplemented with EPA/DHA at ratios of 1:1, 2:1 and 1:2, or soyabean oil as the control for 13 weeks. The results showed that in all the proportions tested, EPA/DHA supplementation significantly lowered total and LDL-cholesterol concentrations, compared with those of the control group. EPA/DHA supplementation at the ratios of 1:1 and 2:1 significantly decreased inflammation (C-reactive protein levels) and lowered oxidative stress (decreased excretion of urinary isoprostanes), mainly at the ratio of 1:2. The activity of antioxidant enzymes increased in erythrocytes, abdominal fat and kidneys, with magnitudes depending on the EPA:DHA ratio. PUFA mixtures from fish affected different MetS markers of CVD risk factors in SHROB rats, depending on the ratios of EPA/DHA supplementation. The activation of endogenous defence systems may be related to the reduction of inflammation and oxidative stress.

Associations between Preschool Teachers' Food-Based Learning Frequency, Level of Personal Priority and Identified Resources and Challenges: A Needs Assessment.

Food-based learning (FBL) is the use of food as a teaching tool in the classroom, which can expose children to healthy foods to improve preference and consumption. However, more research is needed on the use and perception of FBL in the Head Start (HS) preschool classroom. In an online survey, we explored associations between North Carolina HS teachers' (n = 168) experiences (e.g., resources, challenges, needs, and preferences) with FBL, how frequently teachers implemented it, and how much they prioritized it. We used frequencies and chi-square tests of independence to assess associations between study variables. Teachers reported using FBL regularly with access to FBL resources (e.g., books and center play materials) and experiencing challenges (e.g., lack of funding and material resources). Teachers partnered with parents and farmers markets and expressed a need for additional FBL professional development. Our needs assessment findings revealed specific resources, challenges, and perceptions significantly associated with how often teachers used FBL and their priority level. Additional research should investigate how to alleviate FBL challenges and strategies to create policy and environmental changes that facilitate early FBL.

Dietary Marine Oils Selectively Decrease Obesogenic Diet-Derived Carbonylation in Proteins Involved in ATP Homeostasis and Glutamate Metabolism in the Rat Cerebellum.

The regular intake of diets high in saturated fat and sugars increases oxidative stress and has been linked to cognitive decline and premature brain aging. The cerebellum is highly vulnerable to oxidative stress and thus, obesogenic diets might be particularly detrimental to this tissue. However, the precise molecular mechanisms behind obesity-related brain damage are still not clear. Since protein carbonylation, a biomarker of oxidative stress, influences protein functions and is involved in metabolic control, the current investigation addressed the effect of long-term high-fat and high-sucrose diet intake on the cerebellum of Sprague-Dawley rats by deciphering the changes caused in the carbonylated proteome. The antioxidant effects of fish oil supplementation on cerebellar carbonylated proteins were also investigated. Lipid peroxidation products and carbonylated proteins were identified and quantified using immunoassays and 2D-LC-MS/MS in the cerebellum. After 21 weeks of nutritional intervention, the obesogenic diet selectively increased carbonylation of the proteins that participate in ATP homeostasis and glutamate metabolism in the cerebellum. Moreover, the data demonstrated that fish oil supplementation restrained carbonylation of the main protein targets oxidatively damaged by the obesogenic diet, and additionally protected against carbonylation of several other proteins involved in amino acid biosynthesis and neurotransmission. Therefore, dietary interventions with fish oils could help the cerebellum to be more resilient to oxidative damage. The results could shed some light on the effect of high-fat and high-sucrose diets on redox homeostasis in the cerebellum and boost the development of antioxidant-based nutritional interventions to improve cerebellum health.

Discrepancy in medications reported by elderly patients in the dental office and in their electronic medical records: A pilot study.

AIMS: This study's main objective was to analyze the discrepancy between the dental medication record (DMR) and the physician-prescribed active medications recorded in the medical medication record (MMR). METHODS: The study group consisted of 100 adults who attended the University Dental Clinic (Santiago de Compostela, Spain) requesting dental care. A dental history was created for all participants that included the DMR. The MMR were compiled from their electronic medical records. RESULTS: About 80% of the patients consumed at least one drug (94.2% of those >65 years) and 19% took more than five drugs (26.4% of those > 65 years). In total, 54% of the patients had some discrepancy between the medications recorded in the DMR and those in the MMR (48.4% for those ≤65 years and 64.7% for those >65 years). The rate of participants who omitted some drugs was higher for those >65 years. The drugs most omitted from the DMR were analgesics/opioids, antihypertensives and anxiolytics/hypnotics/sedatives. CONCLUSIONS: It is imperative to access the MMR of patients requesting dental care because a significant number of medications are not reflected in their DMR. These discrepancies may be particularly common and relevant in elderly patients, in whom multimorbidity and polypharmacy are more frequent.

OsCYP706C2 diverts rice strigolactone biosynthesis to a noncanonical pathway branch.

Strigolactones exhibit dual functionality as regulators of plant architecture and signaling molecules in the rhizosphere. The important model crop rice exudes a blend of different strigolactones from its roots. Here, we identify the inaugural noncanonical strigolactone, 4-oxo-methyl carlactonoate (4-oxo-MeCLA), in rice root exudate. Comprehensive, cross-species coexpression analysis allowed us to identify a cytochrome P450, OsCYP706C2, and two methyl transferases as candidate enzymes for this noncanonical rice strigolactone biosynthetic pathway. Heterologous expression in yeast and Nicotiana benthamiana indeed demonstrated the role of these enzymes in the biosynthesis of 4-oxo-MeCLA, which, expectedly, is derived from carlactone as substrate. The oscyp706c2 mutants do not exhibit a tillering phenotype but do have delayed mycorrhizal colonization and altered root phenotype. This work sheds light onto the intricate complexity of strigolactone biosynthesis in rice and delineates its role in symbiosis and development.