Biological clock function is linked to proactive and reactive personality types

Background

Many physiological processes in our body are controlled by the biological clock and show circadian rhythmicity. It is generally accepted that a robust rhythm is a prerequisite for optimal functioning and that a lack of rhythmicity can contribute to the pathogenesis of various diseases. Here, we tested in a heterogeneous laboratory zebrafish population whether and how variation in the rhythmicity of the biological clock is associated with the coping styles of individual animals, as assessed in a behavioural assay to reliably measure this along a continuum between proactive and reactive extremes.

Results

Using RNA sequencing on brain samples, we demonstrated a prominent difference in the expression level of genes involved in the biological clock between proactive and reactive individuals. Subsequently, we tested whether this correlation between gene expression and coping style was due to a consistent change in the level of clock gene expression or to a phase shift or to altered amplitude of the circadian rhythm of gene expression. Our data show a remarkable individual variation in amplitude of the clock gene expression rhythms, which was also reflected in the fluctuating concentrations of melatonin and cortisol, and locomotor activity. This variation in rhythmicity showed a strong correlation with the coping style of the individual, ranging from robust rhythms with large amplitudes in proactive fish to a complete absence of rhythmicity in reactive fish. The rhythmicity of the proactive fish decreased when challenged with constant light conditions whereas the rhythmicity of reactive individuals was not altered.

Conclusion

These results shed new light on the role of the biological clock by demonstrating that large variation in circadian rhythmicity of individuals may occur within populations. The observed correlation between coping style and circadian rhythmicity suggests that the level of rhythmicity forms an integral part of proactive or reactive coping styles.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Urine metabolic fingerprinting can be used to predict the risk of metritis and highlight the pathobiology of the disease in dairy cows

Introduction

Metritis is an uterine pathology that causes economic losses for the dairy industry. It is associated with lower reproductive efficiency, increased culling rates, decreased milk production and increased veterinary costs.

Objectives

To gain a more detailed view of the urine metabolome and to detect metabolite signature in cows with metritis. In addition, we aimed to identify early metabolites which can help to detect cows at risk to develop metritis in the future.

Methods

We used nuclear magnetic resonance spectroscopy starting at 8 and 4 weeks prior to the expected day of parturition, during the week of diagnosis of metritis, and at 4 and 8 weeks after diagnosis of metritis in Holstein dairy cows.

Results

At 8 weeks before parturition, pre-metritic cows had a total of 30 altered metabolites. Interestingly, 28 of them increased in urine when compared with control cows (P?<?0.05). At 4 weeks before parturition, 34 metabolites were altered. At the week of diagnosis of metritis a total of 20 metabolites were altered (P?<?0.05). The alteration continued at 4 and 8 weeks after diagnosis.

Conclusions

The metabolic fingerprints in the urine of pre-metritic and metritic cows point toward excretion of multiple amino acids, tricarboxylic acid cycle metabolites and monosaccharides. Combination of galactose, leucine, lysine and panthotenate at 8 weeks before parturition might serve as predictive biomarkers for metritis.

     

Retrieving hidden atrial repolarization waves from standard surface ECGs

Background

This study estimates atrial repolarization activities (Ta waves), which are typically hidden most of the time from body surface electrocardiography when diagnosing cardiovascular diseases. The morphology of Ta waves has been proven to be an important marker for the early sign of inferior injury, such as acute atrial infarction, or arrhythmia, such as atrial fibrillation. However, Ta waves are usually unseen except during conduction system malfunction, such as long QT interval or atrioventricular block. Therefore, justifying heart diseases based on atrial repolarization becomes impossible in sinus rhythm.

Methods

We obtain TMPs in the atrial part of the myocardium which reflects the correct excitation sequence starting from the atrium to the end of the apex.

Results

The resulting TMP shows the hidden atrial part of ECG waves.

Conclusions

This extraction makes many diseases, such as acute atrial infarction or arrhythmia, become easily diagnosed.

     

Cinnamon: does it hold its promises in cows? Using non-targeted blood serum metabolomics profiling to test the effects of feeding cinnamon to dairy cows undergoing lactation-induced insulin resistance

Introduction

Cinnamon exerts insulin-enhancing activity in vitro and was demonstrated to improve blood glucose and lipid profiles in several human studies. Such effects may have an impact on metabolically stressed cows.

Objective

To study the effects of cinnamon supplementation during the transition from late pregnancy to early lactation on the metabolism in dairy cows.

Methods

Twenty-four Holstein cows (n?=?8/group) were assigned to either the control group (CTR; without supplementation) or the supplementation groups [supplemental cinnamon at 20 (LCIN) or 40 (HCIN) g/cow per day (d)] from 28 d before calving until 21 d thereafter. Blood samples were assayed for glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and insulin; an index estimating insulin sensitivity (RQUICKI) was calculated. The serum metabolome was characterized in the samples collected from d 14 using a non-targeted approach.

Results

The serum concentrations of glucose and insulin did not differ among groups and followed a similar pattern over time. The serum NEFA concentrations were greater in LCIN (d 2, 7, and 14) and HCIN (d 14) than in CTR. On d 14 and 21, LCIN and HCIN had greater serum BHBA concentrations than CTR cows. The top 10 metabolites identified with significantly higher levels in the supplemented than the CTR cows were related to fatty acid metabolism.

Conclusion

The data suggest lipolytic and ketogenic effects of cinnamon supplementation in dairy cows during the transition from late gestation to early lactation. The fatty acid metabolites found elevated in the supplemented cows point towards impaired mitochondrial fatty acid β-oxidation.

     

Prepartal overfeeding alters the lipidomic profiles in the liver and the adipose tissue of transition dairy cows

Introduction

Physiological adaptations in the energy metabolism of dairy cows during the periparturient period are partly mediated by insulin resistance (IR), which may subsequently induce metabolic disorders postpartum. The molecular mechanisms underlying IR in dairy cows are largely unknown.

Objective

This study aimed to find a novel insight into the molecular mechanisms underlying IR in dairy cows during the periparturient period by analyzing the effects of prepartal overfeeding on the lipidomic profiles in the liver and adipose tissue (AT).

Methods

Sixteen cows were allocated to controlled-energy and high-energy feeding groups. Lipidomic profiling was conducted on liver and adipose tissue samples collected at 8 days prior to the predicted parturition, and 1 day (only AT) and 9 days after the actual parturition.

Results

Five ceramides (Cers) were identified to be significantly increased by prepartal overfeeding in AT in the analysis of the variance between groups within time points. Principal component-linear discriminant analysis showed that lipidomic profiles between the feeding groups were mainly characterized by phosphatidylcholines (PC), phosphatidylethanolamines (PE), lysophophosphatidylcholines (LysoPC), and lysophosphatidylethanolamines (LysoPE) in the liver, and by Cer, PE, and phosphatidylinositols (PI) in AT. Lipid class levels indicated that prepartal overfeeding elevated the concentration of PE, PI, LysoPC, LysoPE, and sphingomyelin in the liver, and increased the concentration of Cer in AT during the periparturient period.

Conclusion

Prepartal overfeeding significantly altered the concentrations of various sphingolipids, phospholipids, and lysophospholipids in the liver and AT of dairy cows during the periparturient period.

     

Metallotyping of ketotic dairy cows reveals major alterations preceding,associating, and following the disease occurrence

Introduction

Ketosis is a common metabolic disorder, which is characterized by elevated concentrations of ketone bodies or ketoacids in three body fluids including blood, urine, and milk. Two of the ketones including β-hydroxybutyric acid and acetoacetic acid are strong acids which at high concentrations trigger ketoacidosis influencing physiological functions of various tissues and organs.

Objectives

The objectives of this study were to: (1) investigate mineral alterations in both serum and urine of preketotic, ketotic, and postketotic cows, (2) identify potential predictive and diagnostic mineral biomarkers for ketosis in serum and urine, and (3) better understand the role of minerals in the pathobiology of the disease.

Methods

Inductively coupled plasma mass spectrometry metallotyping was performed in the serum and urine of six cases of ketosis and 20 healthy controls cows at ?8 and ?4 weeks prepartum, at disease diagnosis week, and at +4 and +8 weeks postpartum.

Results

Data showed that concentrations of aluminum (Al), iron (Fe), manganese (Mn), and arsenic (As) were greater (P?<?0.001) in the serum of preketotic, ketotic and postketotic cows at most of the tested time points. Moreover, boron (B) and Al as well as calcium (Ca), phosphorus (P), potassium (K), and magnesium (Mg) were found to be elevated in the urine of preketotic and postketotic cows (P?<?0.001).

Conclusions

It is concluded that alterations of mineral elements observed in the serum and urine of preketotic, ketotic, and postketotic cows might be related to the state of chronic acidosis in those cows. The mineral elements identified in both serum and urine can be used as biomarkers to early diagnose ketosis at its pre-subclinical state and develop preventive interventions in the future.

     

Metabotyping reveals distinct metabolic alterations in ketotic cows and identifies early predictive serum biomarkers for the risk of disease

Introduction

Ketosis is a prevalent metabolic disease of transition dairy cows that affects milk yield and the development of other periparturient diseases.

Objectives

The objective of this study was to retrospectively metabotype the serum of dairy cows affected by ketosis before clinical signs of disease, during the diagnosis of ketosis, and after the diagnosis of disease and identify potential predictive and diagnostic serum metabolite biomarkers for the risk of ketosis.

Methods

Targeted metabolomics was used to identify and quantify 128 serum metabolites in healthy (CON, n?=?20) and ketotic (n?=?6) cows by DI/LC-MS/MS at ?8 and ?4 weeks prepartum, during the disease week, and at +4 and +8 weeks after parturition.

Results

Significant changes were detected in the levels of several metabolite groups including amino acids, glycerophospholipids, sphingolipids, acylcarnitines, and biogenic amines in the serum of ketotic cows during all time points studied.

Conclusions

Results of this study support the idea that ketosis is preceded and associated and followed by alterations in multiple metabolite groups. Moreover, two sets of predictive biomarker models and one set of diagnostic biomarker model with very high sensitivity and specificity were identified. Overall, these findings throw light on the pathobiology of ketosis and some of the metabolites identified might serve as predictive biomarkers for the risk of ketosis. The data must be considered as preliminary given the lower number of ketotic cows in this study and more research with a larger cohort of cows is warranted to validate the results.

     

Numerical study of entrainment of the human circadian system and recovery by light treatment

Background

While the effects of light as a zeitgeber are well known, the way the effects are modulated by features of the sleep-wake system still remains to be studied in detail.

Methods

A mathematical model for disturbance and recovery of the human circadian system is presented. The model combines a circadian oscillator and a sleep-wake switch that includes the effects of orexin. By means of simulations, we characterize the period-locking zone of the model, where a stable 24-hour circadian rhythm exists, and the occurrence of circadian disruption due to both insufficient light and imbalance in orexin. We also investigate how daily bright light treatments of short duration can recover the normal circadian rhythm.

Results

It is found that the system exhibits continuous phase advance/delay at lower/higher orexin levels. Bright light treatment simulations disclose two optimal time windows, corresponding to morning and evening light treatments. Among the two, the morning light treatment is found effective in a wider range of parameter values, with shorter recovery time.

Conclusions

This approach offers a systematic way to determine the conditions under which circadian disruption occurs, and to evaluate the effects of light treatment. In particular, it could potentially offer a way to optimize light treatments for patients with circadian disruption, e.g., sleep and mood disorders, in clinical settings.

     

Predictors of post-stroke body temperature elevation

Background

Growing evidence indicates that elevated body temperature after stroke is associated with unfavorable outcome. The aim of the current study was to investigate which factors predict temperature elevation within 48 h of stroke onset. Specifically, we hypothesized that temperature elevation would be associated with stroke symptom severity and that hemorrhagic stroke would cause a more pronounced temperature increase compared to ischemic stroke.

Methods

The medical records of 400 stroke patients were retrospectively reviewed. Multiple linear regression analysis was used to determine which factors were associated with elevated body temperature.

Results

Several factors were significantly associated with peak body temperature (the highest recorded body temperature) within 48 h of stroke onset: stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) (regression coefficient; (RC) 0.022), female gender (RC 0.157), tympanic/non-rectal temperature reading (RC ?0.265), swallowing difficulties (RC 0.335), intubation (RC 0.470), antipyretic treatment (RC 0.563), and C-reactive protein?>?50 or signs of infection at admission (RC 0.298). Contrary to our expectations, patients with intracerebral hemorrhage did not have higher peak body temperatures than patients with ischemic stroke.

Conclusions

In conclusion, temperature elevation within the first 48 h of stroke onset is common, can be partially predicted using information at admission and is strongly associated with stroke severity. The strong association with stroke severity may, at least partly, explain the previously described association between post-stroke temperature elevation and unfavorable outcome.

     

Accumulation of Fascin<Superscript>+</Superscript> cells during experimental autoimmune neuritis

Background

Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Fascin is an evolutionarily highly conserved cytoskeletal protein of 55 kDa containing two actin binding domains that cross-link filamentous actin to hexagonal bundles.

Methods

Here we have studied by immunohistochemistry the spatiotemporal accumulation of Fascin?+?cells in sciatic nerves of EAN rats.

Results

A robust accumulation of Fascin?+?cell was observed in the peripheral nervous system of EAN which was correlated with the severity of neurological signs in EAN.

Conclusion

Our results suggest a pathological role of Fascin in EAN.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticphatology.diagnomx.eu/vs/6734593451114811

     

A metabolomics approach to characterize phenotypes of metabolic transition from late pregnancy to early lactation in dairy cows

Introduction

Dairy cows experience metabolic stress during the transition from late pregnancy to early lactation, due to the complex adaptation processes affecting energy homeostasis in support of milk production, collectively referred to as homeorhesis. According to the individual efficiency of this adaptation, some cows develop severe metabolic diseases while others are able to maintain metabolic health.

Objectives

This study aimed to characterize patterns and changes of metabolic phenotype during the transition period, and to identify how far different metabolic pathways are affected by or contributing to the complex system of homeorhesis.

Methods

Blood samples were collected from 26 German Holstein cows, repeatedly during the transition period: 42 and 10 days before calving and 3, 21 and 100 days after calving. Blood serum samples were subjected to a liquid chromatography–mass spectrometry based targeted metabolomics analysis using the AbsoluteIDQ p180 Kit of Biocrates Life Science AG (Innsbruck, Austria). Processed metabolomics data were evaluated by multivariate data analysis techniques such as principal component analysis (PCA) and partial least squares-discriminant analysis and by heatmap visualization.

Results

The PCA revealed a clear separation according to sampling days, indicating a notable shift of the metabolic phenotype during the transition period. The heatmap showed that acylcarnitines provided a consistent clustering within sampling days, while the concentration of glycerophospholipids and sphingolipids were remarkably decreased 10 days before and 3 days after calving than earlier and later in the transition period.

Conclusion

Analyzing longitudinal changes of the blood metabolome and identifying new biomarkers by this approach can help understanding the multifaceted metabolic adaptation of transition dairy cows.

     

An oncoplastic technique to reduce the formation of lateral 'dog-ears' after mastectomy

Background

Lateral skin folds or 'dog-ears' are frequent following mastectomy, particularly in patients with large body habitus.

Methods

We describe a method of modifying the mastectomy incision and suturing to eliminate these lateral 'dog-ears'.

Conclusion

This surgical technique, as compared to others described in the literature, is simple, does not require additional incisions and is cosmetically acceptable to the patient.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Serum metabolomics using ultra performance liquid chromatography coupled to mass spectrometry in lactating dairy cows following a single dose of sporidesmin

Introduction

Photosensitization is a common clinical sign in cows suffering from liver damage caused by the mycotoxin sporidesmin. This disease, called facial eczema (FE), is of major importance in New Zealand. Current techniques for diagnosing animals with subclinical sporidesmin-induced liver damage (i.e. without photosensitization) are nonspecific. In addition, little is known of the mechanisms involved in sporidesmin resistance, nor the early effects seen following low-dose sporidesmin intoxication.

Objective

The objective of this study was to identify individual metabolites or metabolic profiles that could be used as serum markers for early stage FE in lactating cows.

Methods

Results are presented from a 59-day sporidesmin challenge in Friesian-cross dairy cows. Serum metabolite profiles were obtained using reversed phase ultra-performance liquid chromatography (UPLC) electrospray ionization mass spectrometry (MS) and UPLC tandem MS. Multivariate and time series analyses were used to assess the data.

Results

Statistical analysis, both with and without the temporal component, could distinguish the profiles of animals with clinical signs from the others, but not those affected subclinically. An increase in the concentrations of a combination of taurine- and glycine-conjugated secondary bile acids (BAs) was the most likely cause of the separation. This is the first time that MS methods have been applied to FE and that bile acids changes have been detected in cattle exposed to sporidesmin.

Conclusions

It is well known that BA concentrations increase during cholestasis due to damage to bile ducts and leakage of the bile. This is the first study to investigate metabolomic changes in serum following a sporidesmin challenge. Further work to establish the significance of the elevation of individual BAs concentrations in the serum of early-stage sporidesmin-poisoned cows is necessary.

     

Portable wireless neurofeedback system of EEG alpha rhythm enhances memory

Background

Effect of neurofeedback training (NFT) on enhancement of cognitive function or amelioration of clinical symptoms is inconclusive. The trainability of brain rhythm using a neurofeedback system is uncertainty because various experimental designs are used in previous studies. The current study aimed to develop a portable wireless NFT system for alpha rhythm and to validate effect of the NFT system on memory with a sham-controlled group.

Methods

The proposed system contained an EEG signal analysis device and a smartphone with wireless Bluetooth low-energy technology. Instantaneous 1-s EEG power and contiguous 5-min EEG power throughout the training were developed as feedback information. The training performance and its progression were kept to boost usability of our device. Participants were blinded and randomly assigned into either the control group receiving random 4-Hz power or Alpha group receiving 8–12-Hz power. Working memory and episodic memory were assessed by the backward digital span task and word-pair task, respectively.

Results

The portable neurofeedback system had advantages of a tiny size and long-term recording and demonstrated trainability of alpha rhythm in terms of significant increase of power and duration of 8–12 Hz. Moreover, accuracies of the backward digital span task and word-pair task showed significant enhancement in the Alpha group after training compared to the control group.

Conclusions

Our tiny portable device demonstrated success trainability of alpha rhythm and enhanced two kinds of memories. The present study suggest that the portable neurofeedback system provides an alternative intervention for memory enhancement.

     

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.

     

Daily variation and effect of dietary folate on urinary pteridines

Introduction

Urinary pteridines are putative molecular biomarkers for noninvasive cancer screening and prognostication. Central to their translational biomarker development is the need to understand the sources and extent of their non-epidemiological variation.

Objectives

This study was designed to characterize the two primary sources of urinary pteridine variance: daily variation and the effect of dietary folate.

Methods

Daily variation was studied by collecting urine specimens (n = 81) three times daily for 3 days. The effect of dietary folate was investigated in a treatment study in which urine specimens (n = 168) were collected daily during a control week and a treatment week during which participants received dietary folate supplements. Measurements of six urinary pteridines were made using high-performance liquid chromatography–tandem mass spectrometry. Coefficients of variation were calculated to characterize daily variance between and within subjects, while nearest neighbor non-parametric analyses were used to identify diurnal patterns and measure dietary folate effects.

Results

Daily variance was approximately 35 % RSD for both within-day and between-day periods for most pteridines. Diurnal patterns in response to circadian rhythms were similarly observed for urinary pteridines. Folate supplementation was shown to alter urinary pteridine profiles in a pathway dependent manner, suggesting that dietary folate may regulate endogenous neopterin and biopterin biosynthesis.

Conclusions

Urinary pteridine levels were found to be responsive to both daily variation and folate supplementation. These findings provide new insights into pteridine biosynthesis and regulation as well as useful information for the design of future clinical translational research.

     

A review on melatonin action as therapeutic agent in cancer

Background

Melatonin is a hormone which is produced from pineal gland in human and is said to have various impacts in human body like controlling sleep wake cycle, regulating the immune and cardiovascular system and regulating the peripheral organ functioning to name a few. Researchers have reported that the melatonin levels correlates with cancer risks.

Objective

In this review article, focus has been given to the therapeutic applications and impact of melatonin hormone in human behavior and physiologic activities. Through this article we aim in compiling the scattered information regarding melatonin and its various aspects of importance in human system.

Methods

We made an analysis of existing hypothesis and studies published on melatonin and circadian rhythm, factors effecting Melatonin secretions in body, sleep disturbances and cancer risks and melatonin therapy in cancer patients.

Results

Melatonin’s role as an endogenous synchronizer, growing evidence suggests its anti-oxidative activity as well as its having a role in modulating immune responses. Fluctuating melatonin levels can be boosted by ingesting products containing melatonin. A large portion of the examinations detailed by the researchers clearly conclude that keeping up an impeccable sleep-wake cycle and having a healthy diet is extremely important to keep up the regular melatonin levels and in order to stay fit.

Conclusions

Melatonin is considered as a critical hormone that controls and regulates many functions in our body. Melatonin production is emphatically related to the night time duration. Its most absolute biological role is to convey information to the body about day length for a variety of physiologic functions. In addition to melatonin’s role as an endogenous synchronizer, growing evidence suggests its anti-oxidative activity as well as its having a role in modulating immune responses. At present, a growing interest is focused on the validity of the anti-tumor mechanisms of melatonin.