Ultra-low carbon dioxide partial pressure improves the galactosylation of a monoclonal antibody produced in Chinese hamster ovary cells in a bioreactor

Objective

To explore the influence of ultra-low carbon dioxide partial pressure (pCO₂) on the monoclonal antibody (mAb) N-glycosylation profile in Chinese hamster ovary (CHO) cell culture.

Results

In fed-batch bioreactor cultures, lowering the pCO₂ in the medium (<?25 mmHg) via increasing headspace aeration decreased the cell viability and mAb production in CHO cells. Additionally, mAb galactosylation under low pCO₂ was approximately 27.45?±?2.13%, noticeably higher than that observed under normal pCO₂ (21.36?±?1.66%) at harvest. However, all of the relevant intracellular nucleotide sugar concentrations were dramatically decreased to approximately 50% of the levels found under normal pCO₂ on day 7. Real-time PCR revealed that the upregulation of galactosylation-related glycosyltransferase genes and substrate transporter genes played a critical role in the improved galactosylation under the ultra-low pCO₂ condition.

Conclusions

In the bioreactor culture processes, ultra-low pCO₂ demonstrated a positive effect on mAb galactosylation.

     

The association of fecal microbiota and fecal,blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome

Introduction

The human gut microbiota has the ability to modulate host metabolism. Metabolic profiling of the microbiota and the host biofluids may determine associations significant of a host–microbe relationship. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disorder of fatigue that is poorly understood, but has been linked to gut problems and altered microbiota.

Objectives

Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites.

Methods

A workflow was developed that correlates microbial counts with fecal, blood serum and urine metabolites quantitated by high-throughput ¹H NMR spectroscopy. The study consists of thirty-four females with ME/CFS (34.9?±?1.8 SE years old) and twenty-five non-ME/CFS female (33.0?±?1.6 SE years old).

Results

The workflow was validated using the non-ME/CFS cohort where fecal short chain fatty acids (SCFA) were associated with serum and urine metabolites indicative of host metabolism changes enacted by SCFA. In the ME/CFS cohort a decrease in fecal lactate and an increase in fecal butyrate, isovalerate and valerate were observed along with an increase in Clostridium spp. and a decrease in Bacteroides spp. These differences were consistent with an increase in microbial fermentation of fiber and amino acids to produce SCFA in the gut of ME/CFS patients. Decreased fecal amino acids positively correlated with substrates of gluconeogenesis and purine synthesis in the serum of ME/CFS patients.

Conclusion

Increased production of SCFA by microbial fermentation in the gut of ME/CFS patients may be associated with deleterious effects on the host energy metabolism.

     

Monitoring of pre-frontal oxygen status in helicopter pilots using near-infrared spectrophotometers

Background

There are few in-flight studies of cognition-related cerebral oxygen status in helicopter pilots.

Methods

Four male helicopter pilots volunteered for nine sorties during visual flight in a BK117 and UH-60J. The pilots' pre-frontal oxy-hemoglobin (O₂Hb) and deoxy-hemoglobin (HHb) concentration were continuously monitored from the right/left sections of the forehead using near-infrared spectrophotometers with a consideration of motion artifacts.

Results

The concentration of O₂Hb progressively increased (13.98 μmol?L^-1 as a maximum increased concentration) in both the right/left sections of the forehead from the basal level during the heightened cognitive demand of helicopter flight. There was comparatively little change (4.32 μmol?L^-1 as a maximum increased concentration) in HHb concentration during measurement of helicopter flight. HHb changes were apparently not affected by a heightened cognitive demand of helicopter pilots.

Conclusion

These results demonstrate that near-infrared spectroscopy, especially O₂Hb measurements, provides a sensitive method for the monitoring of cognitive demand (maneuvers) in helicopter pilots.

     

Responses of switchgrass soil respiration and its components to precipitation gradient in a mesocosm study

Aims

The objective of this study was to investigate the effects of the precipitation changes on soil, microbial and root respirations of switchgrass soils, and the relationships between soil respiration and plant growth, soil moisture and temperature.

Methods

A mesocosm experiment was conducted with five precipitation treatments over two years in a greenhouse in Nashville, Tennessee. The treatments included ambient precipitation, ?50%, ?33%, +33% and +50% of ambient precipitation. Soil, microbial, and root respirations were quantified during the growing seasons.

Results

Mean soil and root respirations in the +50% treatment were the highest (2.48 and 0.93 μmol CO₂ m^?2 s^?1, respectively) among all treatments. Soil microbial respiration contributed more to soil respiration, and had higher precipitation sensitivity mostly than root respiration. Increases in precipitation mostly enhanced microbial respiration while decreases in precipitation reduced both microbial and root respirations. Across precipitation treatments, soil respiration was significantly influenced by soil moisture, soil temperature, and aboveground biomass.

Conclusions

Our results showed that microbial respiration was more sensitive to precipitation changes, and precipitation regulated the response of soil respiration to soil temperature. The information generated in this study will be useful for model simulation of soil respiration in switchgrass fields under precipitation changes.

     

Over-expression of miR-146b and its regulatory role in intestinal epithelial cell viability,proliferation, and apoptosis in piglets

Background

Weaning stress affects the small intestine of piglets. MiR-146b is differentially expressed in suckling and weaned piglets. In this study, we evaluated the effects of miR-146b on cell viability, proliferation, and apoptosis in IPEC-J2 cells.

Results

Transfection with miR-146b mimics successfully increased miR-146b levels by 1000× (P?<?0.001). The over-expression of miR-146b significantly promoted the apoptosis (P?<?0.01) of IPEC-J2 cells, with no significant effects on cell viability or proliferation. MiR-146b suppressed the luciferase activity of the miR-TLR4-wt by 57% compared with the negative control, while mutation of the miR-146b binding site significantly blocked the suppressive effect (P?<?0.05). Western blot results showed that TLR4 levels decreased in IPEC-J2 cells transfected with miR-146b mimics (P?<?0.05).

Conclusions

The over-expression of miR-146b promotes IPEC-J2 cell apoptosis. TLR4 is a direct target of miR-146b in IPEC-J2 cells.

Reviewers

This article was reviewed by Eugene Berezikov and Jan B Hoek.

     

Quantitative metabolomics comparison of traditional blood draws and TAP capillary blood collection

Introduction

Mass spectrometry and computational biology have advanced significantly in the past ten years, bringing the field of metabolomics a step closer to personalized medicine applications. Despite these analytical advancements, collection of blood samples for routine clinical analysis is still performed through traditional blood draws.

Objective

TAP capillary blood collection has been recently introduced for the rapid, painless draw of small volumes of blood (~?100 μL), though little is known about the comparability of metabolic phenotypes of blood drawn via traditional venipuncture and TAP devices.

Methods

UHPLC-MS-targeted metabolomics analyses were performed on blood drawn traditionally or through TAP devices from 5 healthy volunteers. Absolute quantitation of 45 clinically-relevant metabolites was calculated against stable heavy isotope-labeled internal standards.

Results

Ranges for 39 out of 45 quantified metabolites overlapped between drawing methods. Pyruvate and succinate were over threefold higher in the TAP samples than in traditional blood draws. No significant changes were observed for other carboxylates, glucose or lactate. TAP samples were characterized by increases in reduced glutathione and decreases in urate and cystine, markers of oxidation of purines and cysteine—overall suggesting decreased oxidation during draws. The absolute levels of bile acids and acyl-carnitines, as well as almost all amino acids, perfectly correlated among groups (Spearman r?≥?0.95).

Conclusion

Though further more extensive studies will be mandatory, this pilot suggests that TAP-derived blood may be a logistically-friendly source of blood for large scale metabolomics studies—especially those addressing amino acids, glycemia and lactatemia as well as bile acids, acyl-carnitine levels.

     

Sex difference in thermal preference of adult mice does not depend on presence of the gonads

Background

The thermoneutral zone (TNZ) is a species-specific range of ambient temperature (T _a), at which mammals can maintain a constant body temperature with the lowest metabolic rate. The TNZ for an adult mouse is between 26 and 34 °C. Interestingly, female mice prefer a higher T _a than male mice although the underlying mechanism for this sex difference is unknown. Here, we tested whether gonadal hormones are dominant factors controlling temperature preference in male and female mice.

Methods

We performed a temperature preference test in which 10-week-old gonadectomized and sham-operated male and female C57BL/6J mice were allowed to choose to reside at the thermoneutral cage of 29 °C or an experimental cage of 26, 29, or 32 °C.

Results

All mice preferred a T _a higher than 26 °C, especially in the inactive phase. Choosing between 29 and 32 °C, female mice resided more at 32 °C while male mice had no preference between the temperatures. Hence, the preferred T _a for female mice was significantly higher (0.9?±?0.2 °C) than that for male mice. However, gonadectomy did not influence the T _a preference.

Conclusions

Female mice prefer a warmer environment than male mice, a difference not affected by gonadectomy. This suggests that thermal-sensing mechanisms may be influenced by sex-specific pathways other than gonadal factors or that the thermoregulatory set point has already been determined prior to puberty.

     

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis,tricarboxylic acid and urea metabolism

Background

Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet.

Objectives

We aimed to study the effects of interventional LAAC on systemic metabolism.

Methods

Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ? p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1).

Results

During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta ?0.19, p?<?0.01) and the increase of sarcosine (beta 0.16, p?<?0.01).

Conclusions

Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.

     

Effect of food intake on myocardial performance index

Background

Myocardial performance index (MPI) has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether myocardial performance index is affected by food intake in healthy subjects.

Methods

Twenty-three healthy subjects aged 25.6?±?4.5 years were investigated. MPI was measured before, 30 min after, and 110 min after a standardized meal.

Results

MPI decreased significantly (P?<?0.05) from fasting values 30 min after the meal, and had almost returned to baseline after 110 min. MPI decreased from 0.28?±?0.06 (fasting) to 0.20?±?0.07 30 min after eating. At 110 min after eating the index value was almost back to the baseline value 0.26?±?0.06. (P?=?0.15).

Conclusions

This study shows that myocardial performance index is affected by food intake in healthy subjects.

     

The reliability and validity for Japanese type 2 diabetes patients of the Japanese version of the acceptance and action diabetes questionnaire

Background

The purpose of this study was to determing which psychological traits of Japanese type 2 diabetes patients would provide reliability and validity to the Japanese version of the Acceptance and Action Diabetes Questionnaire (AADQ-J).

Methods

Various questionnaires were administered to type 2 diabetes patients who were registered on the database of the research service provider; data from a total of 600 patients (mean?±?SD age was 57.50?±?9.87 years, female 21.83%) were analyzed.

Results

Three items were excluded because of psychometric concerns related to the original 11-item AADQ. Confirmation factor analyses revealed that the eight-item version demonstrated the best indicators of a goodness of fit. The questionnaire showed adequate internal consistency. The questionnaire demonstrated high measurement accuracy in broad trait values by the test information function of Item Response Theory. The questionnaire showed stronger positive correlations with self-care activities and HbA1c than with diabetes distress and depressive mood.

Conclusions

The eight-item Japanese version of AADQ has reliability and validity for type 2 diabetes patients.

     

Carbon dioxide pneumothorax following retroperitoneal laparoscopic partial nephrectomy: a case report and literature review

Background

Laparoscopy has many advantages when used to assist surgery. However, pneumothorax, as a rare but potentially life-threatening complication, it requires rapid recognition and treatment. CO₂ pneumothorax may be distinct from air pneumothorax. Here we present a case with unexpected large and symptomatic CO₂ pneumothorax and treated successfully in a conservative way.

Case presentation

A 27-year-old woman who was scheduled a laparoscopic partial nephrectomy received general anesthesia. At the end of surgery, she waked up and got spontaneous breathing. However, she developed a sudden fall in SpO₂ (approximately 30%) and blood pressure with subsequent unconsciousness after switching mechanical ventilation to spontaneous mode. With immediate manual ventilation, SpO₂ and blood pressure recovered simultaneously and the patient regained consciousness. Point-of-care chest X-ray revealed a large, right pneumothorax occupying 70% of the hemi-thorax. Without chest drainage, she was extubated in the operating room and treated with supplemental facial mask oxygen therapy in PACU. On the postoperative 5th day, she was discharged without any further complication.

Conclusion

Retroperitoneal laparoscopic surgeries are likely to bring about severe capno-thorax, which could be absorbed rapidly. Chest X-ray could be used to assist diagnosis but point-of-care transthoracic ultrasound is recommended. Even severe capno-thorax could be treated conservatively. This case highlights the awareness and therapeutic choice of noninvasive management for capno-thorax.

     

A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil

Background

Emergence agitation (EA) is a common phenomenon in preschool children during emergence from general anesthesia. This study evaluated the safety and efficacy of dezocine for emergence agitation in preschool children anesthetized with sevoflurane-remifentanil.

Methods

A total of 100 preschool children, scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into two groups: Group C (n?=?50) received Ringer’s lactate 10 mL and Group D received Ringer’s lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively.

Results

Incidence of EA, defined as a score?≥?3 on Aono’s four point scale or Pediatric Anesthesia Emergence Delirium (PAED) score?≥?10 in the PACU (10% vs. 76%) and the percentage of patients with severe EA (PAED score?≥?13) (12% vs. 76%) were significantly lower in Group D compared to Group C (P?<?0.05). Mean Children and Infants Postoperative Pain Scale (CHIPPS) score was significantly lower in Group D compared to Group C (1.2?±?0.5 vs. 5.2?±?0.6; P?<?0.05). Patients need for fentanyl (18% vs. 4%) or propofol rescue (20% vs. 0) was significantly greater in Group C compared to Group D. No significant differences in other relative aspects after surgery between groups.

Conclusion

Administration of dezocine 0.1 mg/kg decreased the incidence and severity of EA in preschool children that had undergone laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia.

Trial registration

A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil effectively: A double-blind, prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID: ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.

     

Salivary metabolic profile of children and adolescents after hemodialysis

Introduction

The application of metabolomic analysis in the pediatric nephrology field may offer an innovative approach to profile analysis of renal diseases.

Objective

We aimed to analyze the salivary the major metabolites in the saliva of children and adolescents with chronic kidney disease (CKD) before and after hemodialysis.

Method

Thirty-six children diagnosed with CKD and forty healthy children were recruited for the study. ¹H-NMR spectra were analyzed using multivariate and univariate approaches.

Results

The CKD and the healthy control groups presented with similar numbers of dental caries (p?>?0.05) as determined by the number of decayed, missing, or filled deciduous teeth (0.87?±?2.2 and 0.67?±?2.1, respectively) or permanent teeth (0.79?±?1.30 and 0.90?±?1.7, respectively). The amount of dental calculus was significantly higher in the CKD group than in the healthy control group (p?<?0.001). Multivariate analyses using PLS-DA and O-PLS-DA demonstrated differences in the salivary metabolome of CKD patients before and after hemodialysis, as well as between post-dialysis CKD patients and healthy controls, suggesting that HD was not able to recover oral homeostasis. PLS-DA and OPLS-DA models showed satisfactory accuracy (ACC?=?0.72) and prediction (0.64). On multivariate and univariate analyses, urea, acetate, ethanol, and fatty acid were significantly decreased in CKD saliva after hemodialysis. By contrast, saliva from the healthy controls had significantly higher levels of acetate and propionate and lower levels of ethanol, lactate, butyrate, phenylalanine, and creatinine than saliva from post-dialysis CKD patients.

Conclusion

Our results demonstrate that hemodialysis alters the expression of salivary metabolites; however, this alteration does not reestablish the healthy salivary metabolome, as the salivary metabolomic profile of healthy children is significantly different from that of children and adolescents with CKD, both before and after hemodialysis. The unique salivary characteristics of children with CKD may influence their oral health status.

     

GC–MS analysis of the ruminal metabolome response to thiamine supplementation during high grain feeding in dairy cows

Introduction

Thiamine is known to attenuate high-concentrate diet induced subacute ruminal acidosis (SARA) in dairy cows, however, the underlying mechanisms remain unclear.

Objectives

The major objective of this study was to investigate the metabolic mechanisms of thiamine supplementation on high-concentrate diet induced SARA.

Methods

Six multiparous, rumen-fistulated Holstein cows were used in a replicated 3?×?3 Latin square design. The treatments included a control diet (CON; 20% starch, dry matter basis), a SARA-inducing diet (SAID; 33.2% starch, dry matter basis) and SARA-inducing diet supplemented with 180 mg of thiamine/kg of dry matter intake (SAID?+?T). On d21 of each period, ruminal fluid samples were collected at 3 h post feeding, and GC/MS was used to analyze rumen fluid samples.

Results

PCA and OPLS-DA analysis demonstrated that the ruminal metabolite profile were different in three treatments. Compared with CON treatment, SAID feeding significantly decreased rumen pH, acetate, succinic acid, increased propionate, pyruvate, lactate, glycine and biogenic amines including spermidine and putrescine. Thiamine supplementation significantly decreased rumen content of propionate, pyruvate, lactate, glycine and spermidine; increase rumen pH, acetate and some medium-chain fatty acids. The enrichment analysis of different metabolites indicated that thiamine supplementation mainly affected carbohydrates, amino acids, pyruvate and thiamine metabolism compared with SAID treatment.

Conclusions

These findings revealed that thiamine supplementation could attenuate high-concentrate diet induced SARA by increasing pyruvate formate-lyase activity to promote pyruvate to generate acetyl-CoA and inhibit lactate generation. Besides, thiamine reduced biogenic amines to alleviate ruminal epithelial inflammatory response.

     

Elevated CO<Subscript>2</Subscript> and virus infection impacts wheat and aphid metabolism

Introduction

The aphid Rhopalosiphum padi L. is a vector of Barley yellow dwarf virus (BYDV) in wheat and other economically important cereal crops. Increased atmospheric CO₂ has been shown to alter plant growth and metabolism, enhancing BYDV disease in wheat. However, the biochemical influences on aphid metabolism are not known.

Objectives

This work aims to determine whether altered host-plant quality, influenced by virus infection and elevated CO₂, impacts aphid weight and metabolism.

Methods

Untargeted ¹H NMR metabolomics coupled with multivariate statistics were employed to profile the metabolism of R. padi reared on virus-infected and non-infected (sham-inoculated) wheat grown under ambient CO₂ (aCO₂, 400 µmol mol^?1) and future, predicted elevated CO₂ (eCO₂, 650 µmol mol^?1) concentrations. Un-colonised wheat was also profiled to observe changes to host-plant quality (i.e., amino acids and sugars).

Results

The direct impacts of virus or eCO₂ were compared. Virus presence increased aphid weight under aCO₂ but decreased weight under eCO₂; whilst eCO₂ increased non-viruliferous (sham) aphid weight but decreased viruliferous aphid weight. Discriminatory metabolites due to eCO₂ were succinate and sucrose (in sham wheat), glucose, choline and betaine (in infected wheat), and threonine, lactate, alanine, GABA, glutamine, glutamate and asparagine (in aphids), irrespective of virus presence. Discriminatory metabolites due to virus presence were alanine, GABA, succinate and betaine (in wheat) and threonine and lactate (in aphids), irrespective of CO₂ treatment.

Conclusion

This study confirms that virus and eCO₂ alter host-plant quality, and these differences are reflected by aphid weight and metabolism.

     

Consideration of carbon dioxide release during shell production in LCA of bivalves

Purpose

Life cycle assessment (LCA) can be used to understand the environmental impacts of the shellfish aquaculture and wild harvest industries. To date, LCA of shellfish exclude carbon dioxide (CO₂) release from bivalve shell production when quantifying global warming potential per functional unit. In this study, we explain the rationale for including CO₂ released during shell production in LCA of bivalves, demonstrate a method for estimating this CO₂ release, and apply the method to previous studies to demonstrate the importance of including CO₂ from shell production in LCA.

Methods

A simple approach for calculating CO₂ from bivalve shell production was developed utilizing the seacarb package in R statistical software. The approach developed allows for inclusion of site-specific environmental parameters such as water temperature, salinity, pH, and pCO₂ when calculating CO₂ release from shell production. We applied the method to previously published LCA of bivalve production systems to assess the impact of including this CO₂ source in the LCA. The past studies include aquaculture and wild harvest production strategies and multiple bivalve species.

Results and discussion

When we recalculated the total kg CO₂ released in past studies including CO₂ release from shell production, the additional CO₂ release increased the total global warming impact category (CO₂ equivalents) in cradle-to-gate studies by approximately 250% of the original reported value. Discussion of our results focuses on the importance of different components of our calculations and site-specific environmental parameters. We make predictions on how the magnitude and importance of CO₂ released during shell production could change due to climate change and ocean acidification, and provide suggestions on how CO₂ release from shell production can be reduced through careful selection of aquaculture facility location and aquaculture practices.

Conclusions

We provide a method for including CO₂ from shell release in LCA of bivalves and recommend that future LCA of bivalves include this CO₂ as part of the global warming impact category.

     

Rapid and efficient degradation of bisphenol A by chloroperoxidase from <Emphasis Type="Italic">Caldariomyces fumago</Emphasis>: product analysis and ecotoxicity evaluation of the degraded solution

Objectives

To degrade enzymatically bisphenol A (BPA) that causes serious environmental concerns and is difficult to be degraded by chemical or physical methods.

Results

BPA (150 mg l^?1) was completely degraded by chloroperoxidase (CPO)/H₂O₂ within 7 min at room temperature, atmospheric pressure with the enzyme at 6 μg CPO ml^?1. The degradation products were identified by HPLC–MS, which suggested involvement of multiple steps. Enzymatic treatment followed by existing bioremediation technologies (activated sludge) enhanced removal of COD from 9 to 54 %. Using an ecotoxicity evaluation with Chlorella pyrenoidosa, the degradation products had a lower toxicity than BPA.

Conclusion

BPA can be degraded rapidly and efficiently under mild conditions with chloroperoxidase at 6 μg ml^?1. The degradation products had a lower toxicity than BPA.

     

NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations

Introduction

Elucidating molecular alterations due to mitochondrial Complex I (CI) mutations may help to understand CI deficiency (CID), not only in mitochondriopathies but also as it is caused by drugs or associated to many diseases.

Objectives

CID metabolic expression was investigated in Leber’s hereditary optic neuropathy (LHON) caused by an inherited mutation of CI.

Methods

NMR-based metabolomics analysis was performed in intact skin fibroblasts from LHON patients. It used several datasets: one-dimensional ¹H-NMR spectra, two-dimensional ¹H-NMR spectra and quantified metabolites. Spectra were analysed using orthogonal partial least squares-discriminant analysis (OPLS-DA), and quantified metabolites using univariate statistics. The response to idebenone (IDE) and resveratrol (RSV), two agents improving CI activity and mitochondrial functions was evaluated.

Results

LHON fibroblasts had decreased CI activity (??43%, p?<?0.01). Metabolomics revealed prominent alterations in LHON including the increase of fatty acids (FA), polyunsaturated FA and phosphatidylcholine with a variable importance in the prediction (VIP)?>?1 in OPLS-DA, p?<?0.01 in univariate statistics, and the decrease of amino acids (AA), predominantly glycine, glutamate, glutamine (VIP?>?1) and alanine (VIP?>?1, p?<?0.05). In LHON, treatment with IDE and RSV increased CI activity (+?40 and +?44%, p?<?0.05). IDE decreased FA, polyunsaturated FA and phosphatidylcholine (p?<?0.05), but did not modified AA levels. RSV decreased polyunsaturated FA, and increased several AA (VIP?>?1 and/or p?<?0.05).

Conclusion

LHON fibroblasts display lipid and amino acid metabolism alterations that are reversed by mitochondria-targeted treatments, and can be related to adaptive changes. Findings bring insights into molecular changes induced by CI mutation and, beyond, CID of other origins.

     

Metabolomic biomarkers and novel dietary factors associated with gestational diabetes in China

Introduction

Gestational diabetes mellitus (GDM) is impaired glucose tolerance first recognised during pregnancy; its development is associated with many adverse outcomes. Mechanisms of GDM development are not fully elucidated and few studies have used Chinese participants.

Objectives

The aim of this study was to investigate the maternal metabolome associated with GDM in a Chinese population, and explore the relationship with maternal diet.

Methods

Ninety-three participants were recruited at 26–28 weeks’ gestation from Chongqing, China. Maternal urine, serum, and hair metabolomes were analysed using gas and liquid chromatography–mass spectrometry. Dietary intake was assessed using a 96-item food frequency questionnaire.

Results

Of the 1064 metabolites identified, 73 were significantly different between cases and controls (P?<?0.05), but only 2-aminobutyric acid had both a p- and q-value?<?0.05. A “snack-based-dietary-pattern” was associated with an increased likelihood of GDM (odds ratio 2·1; 95% confidence interval 1.1–3.9). The association remained significant after adjustment for calorie intake but not food volume.

Conclusion

This study provides a comprehensive characterization of the maternal metabolome. The snack-based dietary pattern associated with GDM suggests that timing and frequency of consumption are important factors in the relationship between maternal diet and GDM.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.