Metabolic gene function discovery platform GeneMAP identifies SLC25A48 as necessary for mitochondrial choline import.

Organisms maintain metabolic homeostasis through the combined functions of small-molecule transporters and enzymes. While many metabolic components have been well established, a substantial number remains without identified physiological substrates. To bridge this gap, we have leveraged large-scale plasma metabolome genome-wide association studies (GWAS) to develop a multiomic Gene-Metabolite Association Prediction (GeneMAP) discovery platform. GeneMAP can generate accurate predictions and even pinpoint genes that are distant from the variants implicated by GWAS. In particular, our analysis identified solute carrier family 25 member 48 (SLC25A48) as a genetic determinant of plasma choline levels. Mechanistically, SLC25A48 loss strongly impairs mitochondrial choline import and synthesis of its downstream metabolite betaine. Integrative rare variant and polygenic score analyses in UK Biobank provide strong evidence that the SLC25A48 causal effects on human disease may in part be mediated by the effects of choline. Altogether, our study provides a discovery platform for metabolic gene function and proposes SLC25A48 as a mitochondrial choline transporter.

Presence of microplastic in the Patella caerulea from the northeastern Mediterranean Sea.

This study reports first evidence of microplastic detection in the Patella caerulea collected from 5 different stations located in Iskenderun Bay and Mersin Bay. A total of 160 P. caerulea specimens were examined and 40 of them contained MPs in their soft tissues. The number of microplastics extracted per sample varied from 0.20 ± 0.5 items/ind to 0.45 ± 0.7 items/ind depending on station. Fibers were predominant type of MPs and accounted for 75 % to 87.5 % of total extracted MPs, followed by fragments (12.5-25 %). Majority of MPs were 0.5-1 mm size and black in color. Fourier transform infrared spectroscopy (FTIR) showed that the extracted MPs were polypropylene (PP), polyethylene (PE), and polyethylene terephthalate (PET), high density polyethylene (HDPE). This study contributes to the knowledge of the transfer of microplastics to the marine food web and highlights the need for protective measurements.

GeneMAP: A discovery platform for metabolic gene function.

Organisms maintain metabolic homeostasis through the combined functions of small molecule transporters and enzymes. While many of the metabolic components have been well-established, a substantial number remains without identified physiological substrates. To bridge this gap, we have leveraged large-scale plasma metabolome genome-wide association studies (GWAS) to develop a multiomic Gene-Metabolite Associations Prediction (GeneMAP) discovery platform. GeneMAP can generate accurate predictions, even pinpointing genes that are distant from the variants implicated by GWAS. In particular, our work identified SLC25A48 as a genetic determinant of plasma choline levels. Mechanistically, SLC25A48 loss strongly impairs mitochondrial choline import and synthesis of its downstream metabolite, betaine. Rare variant testing and polygenic risk score analyses have elucidated choline-relevant phenomic consequences of SLC25A48 dysfunction. Altogether, our study proposes SLC25A48 as a mitochondrial choline transporter and provides a discovery platform for metabolic gene function.

Microplastic ingestion evidence by economically important farmed fish species from Turkey.

Microplastic pollution and its potential impacts on humans become a global concern. This study is the first study examining the microplastic ingestion in the commercially important species Oncorhynchus mykiss Rainbow trout (Walbaum, 1792), Sparus aurata Gilthead seabream Linnaeus, 1758, and Dicentrarchus labrax European seabass (Linnaeus, 1758) from Turkey. The occurrence frequency of microplastic (MP)in the gastrointestinal tract (GIT) was varied between 50 and 63 %. The highest MP abundance in the GIT was estimated in Rainbow trout (1.2 MPs individual-1) followed by European seabass (0.95 MPs individual-1) and Gilthead seabream (0.8 MPs individual-1). Most of the extracted microplastic particles were black (61 %) and blue (27 %) in color and fiber (80 %) in shape. Major identified polymers were polyethylene (25 %), polyester (20 %), polyamide (10 %). Since fish consumption is an important route for MPs, results light up the danger potential for humans. This study will fill the information gap in Turkey and show the necessity of protection measures in aquaculture industry.

Microplastic occurrence in the gastrointestinal tract and gill of bioindicator fish species in the northeastern Mediterranean.

Microplastic pollution is an extremely emerging problem and its potential threats to the aquatic organisms were investigated worldwide. In this study, four different commercial fish species (Mullus barbatus (Linnaeus, 1758), Mullus surmuletus (Linnaeus, 1758), Mugil cephalus (Linnaeus, 1758), Saurida undosquamis (Richardson, 1848)) were used as a bioindicator to assess the microplastic pollution in the northeastern Mediterranean. The frequency of occurrence in the gastrointestinal tract (GIT) and gill was varied between 66-100% and 68-90%, respectively. The highest microplastic abundance was detected at the GIT of M. cephalus sampled from Asi River estuary. The majority of extracted microplastics were fiber, black in color and less than 1 mm in size. Fourier Transform Infrared Spectroscopy (FTIR) indicated the most common polymer type as polyethylene. This study is the first study examining the microplastic existence in gill and results obtained in this study improve the knowledge about the relationship of microplastic ingestion in fish and environmental conditions in the Northeastern Mediterranean Sea.

First record of microplastic occurence at the commercial fish from Orontes River.

Freshwater environments are more sensitive to anthropogenic influences and usually contain higher concentrations of pollutants than marine environments. Microplastic pollution causes additional stress on freshwater animals; yet, studies evaluating the microplastic occurrence in freshwater biota are still limited. In this study, microplastic occurrence in the gastrointestinal tracts (GIT) and gill of commercial fish species (Prussian carp Carassius gibelio (Bloch, 1782); Abu mullet Planiliza abu (Heckel, 1843); Common carp Cyprinus carpio Linnaeus, 1758; European ell Anguilla Anguilla (Linnaeus, 1758); North African catfish Clarias gariepinus (Burchell, 1822); Goldfish Carassius auratus (Linnaeus, 1758) were reported from Orontes River. MPs abundance in the GIT and gill of six species were found as 5.1 ± 2 MPs fish-1 and 4.4 ± 2 MPs fish-1 with an occurrence of 95% and 74%, respectively. The majority of extracted microplastics were fiber, black and less than 1000 µm in size. FTIR analysis determined the main polymer types as polyester (50%), high-density polyethylene (HDPE) (10%), polypropylene (PP) (8%) and polyethylene terephthalate (PET) (5%). High MPs abundance and frequency of occurence indicate the exposure of microplastic pollution in freshwater biota which could threat the health of both individuals and consumers. Results obtained in this study will increase the acknowledgement of MPs pollution in the Orontes River. Also, this study will provide data to the administrators to set up necessary legislations in freshwater ecosystems.

Physiologic vasomotor symptoms are associated with verbal memory dysfunction in breast cancer survivors.

OBJECTIVE: Vasomotor symptoms (VMS), sleep disturbance, and cognitive complaints are common among women with a history of breast cancer and contribute to decreased quality of life. Studies in healthy women showed an association between verbal memory performance and physiologic VMS measured with ambulatory skin conductance monitors but not with VMS by self-report. We hypothesized that we would find a similar association in women with breast cancer. METHODS: Participants included 30 female breast cancer survivors (mean age 52.7 y; 26.7% African-American) with moderate-to-severe VMS enrolled in a larger clinical trial of a nonhormonal intervention for VMS. At baseline, participants completed assessments of physiologic VMS, actigraphy-based assessments of sleep, questionnaires about mood, and two tests of verbal memory - Logical Memory (LM) and the California Verbal Learning Test (CVLT). Using baseline data, we conducted multivariate regression analyses to examine the association between VMS and memory, controlling for sleep and other factors. RESULTS: On average, women reported 46% of total physiologic VMS. A higher frequency of physiologic VMS - but not reported VMS - was significantly associated with lower scores on the California Verbal Learning Test short-delay free recall (r[28] = -0.41, P = 0.03), long-delay free recall (r[28] = -0.42, P = 0.03), and total clustering, (r[28] = -0.39, P = 0.04). These associations were independent of sleep, mood, and other factors. CONCLUSIONS: Independent of their effect on sleep, VMS may be a modifiable contributor to memory difficulties in women with breast cancer. These findings underscore the importance of objective measurement of VMS in cognitive studies. : Video Summary:http://links.lww.com/MENO/A623.

Video Summary:http://links.lww.com/MENO/A623.

Circulating Levels of Muscle-Related Metabolites Increase in Response to a Daily Moderately High Dose of a Vitamin D3 Supplement in Women with Vitamin D Insufficiency-Secondary Analysis of a Randomized Placebo-Controlled Trial.

Recently, we demonstrated negative effects of vitamin D supplementation on muscle strength and physical performance in women with vitamin D insufficiency. The underlying mechanism behind these findings remains unknown. In a secondary analysis of the randomized placebo-controlled trial designed to investigate cardiovascular and musculoskeletal health, we employed NMR-based metabolomics to assess the effect of a daily supplement of vitamin D3 (70 µg) or an identically administered placebo, during wintertime. We assessed the serum metabolome of 76 postmenopausal, otherwise healthy, women with vitamin D (25(OH)D) insufficiency (25(OH)D < 50 nmol/L), with mean levels of 25(OH)D of 33 ± 9 nmol/L. Compared to the placebo, vitamin D3 treatment significantly increased the levels of 25(OH)D (-5 vs. 59 nmol/L, respectively, p < 0.00001) and 1,25(OH)2D (-10 vs. 59 pmol/L, respectively, p < 0.00001), whereas parathyroid hormone (PTH) levels were reduced (0.3 vs. -0.7 pmol/L, respectively, p < 0.00001). Analysis of the serum metabolome revealed a significant increase of carnitine, choline, and urea and a tendency to increase for trimethylamine-N-oxide (TMAO) and urinary excretion of creatinine, without any effect on renal function. The increase in carnitine, choline, creatinine, and urea negatively correlated with muscle health and physical performance. Combined with previous clinical findings reporting negative effects of vitamin D on muscle strength and physical performance, this secondary analysis suggests a direct detrimental effect on skeletal muscle of moderately high daily doses of vitamin D supplements.

Formulation for Oral Delivery of Lactoferrin Based on Bovine Serum Albumin and Tannic Acid Multilayer Microcapsules.

Lactoferrin (Lf) has considerable potential as a functional ingredient in food, cosmetic and pharmaceutical applications. However, the bioavailability of Lf is limited as it is susceptible to digestive enzymes in gastrointestinal tract. The shells comprising alternate layers of bovine serum albumin (BSA) and tannic acid (TA) were tested as Lf encapsulation system for oral administration. Lf absorption by freshly prepared porous 3 µm CaCO3 particles followed by Layer-by-Layer assembly of the BSA-TA shells and dissolution of the CaCO3 cores was suggested as the most efficient and harmless Lf loading method. The microcapsules showed high stability in gastric conditions and effectively protected encapsulated proteins from digestion. Protective efficiency was found to be 76 ± 6% and 85 ± 2%, for (BSA-TA)4 and (BSA-TA)8 shells, respectively. The transit of Lf along the gastrointestinal tract (GIT) of mice was followed in vivo and ex vivo using NIR luminescence. We have demonstrated that microcapsules released Lf in small intestine allowing 6.5 times higher concentration than in control group dosed with the same amount of free Lf. Significant amounts of Lf released from microcapsules were then absorbed into bloodstream and accumulated in liver. Suggested encapsulation system has a great potential for functional foods providing lactoferrin.