Neuronal activity controls the development of interneurons in the somatosensory cortex

BACKGROUND

Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions.

OBJECTIVE

In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on interneuron maturation and integration. We include studies on the effect of various neurotransmitters and on the influence of thalamocortical afferent activity on circuit development. We additionally reviewed studies describing network activity patterns.

METHODS

We conducted an extensive literature search using both the PubMed and Google Scholar search engines. The following keywords were used in various iterations: “interneuron”, “somatosensory”, “development”, “activity”, “network patterns”, “thalamocortical”, “NMDA receptor”, “plasticity”. We additionally selected papers known to us from past reading, and those recommended to us by reviewers and members of our lab.

RESULTS

We reviewed a total of 132 articles that focused on the role of activity in interneuronal migration, maturation, and circuit development, as well as the source of electrical inputs and patterns of cortical activity in the somatosensory cortex. 79 of these papers included in this timely review were written between 2007 and 2016.

CONCLUSION

Neuronal activity shapes the developmental assembly of functional circuitry in the somatosensory cortical interneurons. This activity impacts nearly every aspect of development and acquisition of mature neuronal characteristics, and may contribute to changing phenotypes, altered transmitter expression, and plasticity in the adult. Progressively changing oscillatory network patterns contribute to this activity in the early postnatal period, although a direct requirement for specific patterns and origins of activity remains to be demonstrated.

     

Metabolic heterogeneity of the normal human brain: multivariate analysis of <Superscript>1</Superscript>H MRS in vivo spectra acquired at 3T

Introduction

In recent years multivariate projection techniques of data analysis (PCA, PLS-DA) have been increasingly used for detection of complex ¹H MRS derived metabolic signatures in pathologic conditions. However, these techniques have not been applied in the studies of metabolic heterogeneity of the normal human brain.

Objective

In this work we extended current knowledge about regional distribution of metabolites by multivariate analysis of metabolite levels obtained from various cortical and subcortical regions.

Methods

The studied group consisted of 71 volunteers with no neurological disorders. The metabolite levels obtained from short echo time ¹H MRS in vivo spectra were subjected to univariate and multivariate analysis.

Results

The major variance direction in the dataset was dominated by glutamine?+?glutamate, creatine, myo-inositol and was successful in differentiation of the cortical grey matter and cerebellar vermis from the cortical white matter, pons, basal ganglia, hippocampus and thalamus. The projection plane formed by the second and third variance directions was dominated by N-acetylaspartate?+?N-acetylaspartylglutamate, choline and glutamine?+?glutamate variation not explained by the first direction. This plane revealed a huge metabolic contrast between the pons and basal ganglia, differentiation between the cortical grey matter regions and cerebellar vermis as well as biochemical heterogeneity between the regions such as: thalamus, basal ganglia and hippocampus.

Conclusion

Multivariate approach to ¹H MRS data analysis provides an insight into the normal brain biochemistry and is helpful in understanding the regional heterogeneity of the normal brain. Such knowledge is crucial for a proper interpretation of altered metabolic pathways in diseases.

     

Monitoring spatial and temporal metabolic dynamics of woody poplar root under mechanical stress conditions by NMR-based metabolomics

Introduction

Molecular factors are differentially observed in various bent sectors of poplar (Populus nigra) woody taproots. Responses to stress are modulated by a complex interplay among different hormones and signal transduction pathways. In recent years, metabolomics has been recognized as a powerful tool to characterize metabolic network regulation, and it has been widely applied to investigate plant responses to biotic and abiotic stresses.

Objectives

In this paper we used metabolomics to understand if long term-bending stress induces a “spatial” and a “temporal” metabolic reprogramming in woody poplar roots.

Methods

By NMR spectroscopy and statistical analysis we investigated the unstressed and three portions of stressed root (above-bent, bent, and below-bent) sectors collected at 12 (T₀), 13 (T₁) and 14 (T₂) months after stress induction.

Results

The data indicate a clear between-class separation of control and stressed regions, based on the metabolites regulation, during both spatial and temporal changes. We found that taproots, as a consequence of the stress, try to restore homeostasis and normal metabolic fluxes thorough the synthesis and/or accumulation of specific compounds related to mechanical forces distribution along the bent taproot.

Conclusion

The data demonstrate that the impact of mechanical stress on plant biology can efficiently be studied by NMR-based metabolomics.

     

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.

     

<Emphasis Type="Italic">massPix</Emphasis>: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics

Introduction

Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.

Objectives

We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.

Methods

massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.

Results

Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.

Conclusion

massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.

     

Metabolic response of porcine colon explants to in vitro infection by <Emphasis Type="Italic">Brachyspira hyodysenteriae</Emphasis>: a leap into disease pathophysiology

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.

     

Identifying functional relationships within sets of co-expressed genes by combining upstream regulatory motif analysis and gene expression information

Background

Existing clustering approaches for microarray data do not adequately differentiate between subsets of co-expressed genes. We devised a novel approach that integrates expression and sequence data in order to generate functionally coherent and biologically meaningful subclusters of genes. Specifically, the approach clusters co-expressed genes on the basis of similar content and distributions of predicted statistically significant sequence motifs in their upstream regions.

Results

We applied our method to several sets of co-expressed genes and were able to define subsets with enrichment in particular biological processes and specific upstream regulatory motifs.

Conclusions

These results show the potential of our technique for functional prediction and regulatory motif identification from microarray data.

     

Statistical analysis of fractionation resistance by functional category and expression

Background

The current literature establishes the importance of gene functional category and expression in promoting or suppressing duplicate gene loss after whole genome doubling in plants, a process known as fractionation. Inspired by studies that have reported gene expression to be the dominating factor in preventing duplicate gene loss, we analyzed the relative effect of functional category and expression.

Methods

We use multivariate methods to study data sets on gene retention, function and expression in rosids and asterids to estimate effects and assess their interaction.

Results

Our results suggest that the effect on duplicate gene retention fractionation by functional category and expression are independent and have no statistical interaction.

Conclusion

In plants, functional category is the more dominant factor in explaining duplicate gene loss.

     

Invulnerability of bromelain against oxidative degeneration and cholinergic deficits imposed by dichlorvos in mice brains

Background

The present study elucidates the protective potential of bromelain against dichlorvos intoxication in mice brains. Dichlorvos induces the oxidative stress by disproportionating the balance between free radicals generation and their scavenging in neurons which leads to neuronal degeneration.

Methods

In this study, mice were divided into four groups-group I (control), group II (dichlorvos treated), group III (bromelain treated) and group IV (exposed to both bromelain and dichlorvos both).

Results

Dichlorvos treatment increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) which indicate the increased oxidative stress. Meanwhile, brain endogenous antioxidants and cholinesterases level was decreased after dichlorvos exposure. Levels of TBARS and PCC decreased whereas cholinesterases level was recorded to be elevated after bromelain exposure.

Conclusion

Bromelain offered neuroprotection by decreasing oxidative stress and augmenting cholinesterases in mice brains. This study highlights the invulnerability of bromelain against oxidative and cholinergic deficits in mice brains.

     

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.

     

Microcystin-LR regulates circadian clock and antioxidant gene expression in cultured rat cardiomyocytes

Background

Microcystins are waterborne environmental toxins that induce oxidative stress and cause injuries in the heart. On the other hand, many physiological processes, including antioxidant defense, are under precise control by the mammalian circadian clock.

Results

In the present study, we evaluated the effect of microcystin-LR (MC-LR) on the rhythmic expression patterns of circadian and antioxidant genes in rat cardiomyocytes using the serum shock technique. We found that a non-toxic dose (10 μm) of MC-LR decreased the amplitudes of rhythmic patterns of clock genes, while it increased the expression levels of antioxidant genes.

Conclusions

Our results indicate an influence of MC-LR on the circadian clock system and clock-controlled antioxidant genes, which will shed some light on the explanation of heart toxicity induced by MC-LR from the viewpoint of chronobiology.

     

Non-invasive nuclear magnetic resonance analysis of male and female embryo metabolites during in vitro embryo culture

Introduction

In the past 20+ years, several studies of bovine embryo production showed how the ratio of male to female embryos changes if embryos are made in vivo or in vitro. It is known that in in vitro systems, the sex ratio is in favor of males when there are high levels of glucose, and favors females when the principal energetic substrate is one other than glucose, like citrate.

Objectives

The aim of this study was to evaluate the embryo metabolism during three important periods of in vitro development: the early development (from day 1 until day 3), the middle of culture (day 3 until day 5), and later development (day 5 until day 7).

Methods

To obtain this information we evaluated the spent medium from each time period by ¹H NMR.

Results

Our results confirm that embryo metabolism is different between sexes. The new information obtained by identifies markers that we can use to predict the embryo sex.

Conclusion

These results open a new, non-invasive method to evaluate sex of the embryos before the transfer. In the first period of embryo culture, valine concentration is good indicator (66.7% accurate), while in the last phase of culture, pyruvate depletion is the best marker (64% accurate) to evaluate the sex of the embryo.

     

Sex differences in hepatic one-carbon metabolism

Background

There are large differences between men and women of child-bearing age in the expression level of 5 key enzymes in one-carbon metabolism almost certainly caused by the sex hormones. These male-female differences in one-carbon metabolism are greatly accentuated during pregnancy. Thus, understanding the origin and consequences of sex differences in one-carbon metabolism is important for precision medicine.

Results

We have created a mathematical model of hepatic one-carbon metabolism based on the underlying physiology and biochemistry. We use the model to investigate the consequences of sex differences in gene expression. We give a mechanistic understanding of observed concentration differences in one-carbon metabolism and explain why women have lower S-andenosylmethionine, lower homocysteine, and higher choline and betaine. We give a new explanation of the well known phenomenon that folate supplementation lowers homocysteine and we show how to use the model to investigate the effects of vitamin deficiencies, gene polymorphisms, and nutrient input changes.

Conclusions

Our model of hepatic one-carbon metabolism is a useful platform for investigating the mechanistic reasons that underlie known associations between metabolites. In particular, we explain how gene expression differences lead to metabolic differences between males and females.

     

Analysis of influencing factor of coexisting prediabetes and prehypertension in adult residents of Jilin Province

Background

To explore the risk factors of coexisting prediabetes and prehypertension, to provide theoretical basis for early intervention.

Methods

A multi-stage stratified random cluster sampling method was used to randomly select adult residents from Jilin Province in 2013 for questionnaire surveys, physical examinations, and laboratory tests.

Results

The prevalence of coexisting prediabetes and prehypertension in Jilin Province was 11.3%. The binary Logistic regression results showed that age, sex, education, triglyceride (TG), BMI, waist circumference and alcohol consumption were the effects of factor coexisting prediabetes and prehypertension.

Conclusion

It is important to pay attention to the early stage of hypertension and diabetes, control the transition from prehypertension and prediabetes to hypertension and diabetes, and improve the health of residents.

     

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.

     

Plant growth-promoting bacterium <Emphasis Type="Italic">Pseudomonas fluorescens</Emphasis> FR1 secrets a novel type of extracellular polyhydroxybutyrate polymerase involved in abiotic stress response in plants

Objectives

Identification of novel microbial factors contributing to plant protection against abiotic stress.

Results

The genome of plant growth-promoting bacterium Pseudomonas fluorescens FR1 contains a short mobile element encoding a novel type of extracellular polyhydroxybutyrate (PHB) polymerase (PhbC) associated with a type I secretion system. Genetic analysis using a phbC mutant strain and plants showed that this novel extracellular enzyme is related to the PHB production in planta and suggests that PHB could be a beneficial microbial compound synthesized during plant adaptation to cold stress.

Conclusion

Extracellular PhbC can be used as a new tool for improve crop production under abiotic stress.

     

Determinants of fatigue and stress

Background

Fatigue can be triggered by previous perceived stress which may lead to impairment of performance and function. The purpose of the study was to investigate the relationship between fatigue and perceived stress.

Method

Health determinants including sociodemographic factors for associations between fatigue and perceived stress in the general population (N = 2,483) are outlined. Fatigue and stress were assessed with the Chalder Fatigue Scale (CFS) and the Perceived Stress Questionnaire (PSQ).

Results

Within the general population, 25.9% of male and 34.5% of female respondents reported moderate fatigue during the last six months; 9.7% of subjects reported substantial fatigue lasting six months or longer. An adjusted regression analysis (R²corr = .28, p < .001) showed that fatigue is highest associated with perceived stress and self-perceived health status. The following factors were correlated with increased rates of fatigue and perceived stress: female gender, divorce/separation, low social class and poor health status.

Conclusion

We conclude that the two conditions overlap most in terms of socio-economic status and self-perceived health status.

     

Is HPA axis reactivity in childhood gender-specific? A systematic review

Background

In adults, hypothalamus–pituitary–adrenal (HPA) axis activity shows sexual dimorphism, and this is thought to be a mechanism underlying sex-specific disease incidence. Evidence is scarce on whether these sex differences are also present in childhood. In a meta-analysis, we recently found that basal (non-stimulated) cortisol in saliva and free cortisol in 24-h urine follow sex-specific patterns. We explored whether these findings could be extended with sex differences in HPA axis reactivity.

Methods

From inception to January 2016, PubMed and EMBASE.com were searched for studies that assessed HPA axis reactivity in healthy girls and boys aged ≤18 years. Articles were systematically assessed and reported in the categories: (1) diurnal rhythm, (2) cortisol awakening response (CAR), (3) protocolled social stress tests similar or equal to the Trier Social Stress Test for children (TSST-C), (4) pharmacological (ACTH and CRH) stress tests, and (5) miscellaneous stress tests.

Results

Two independent assessors selected 109 out of 6158 records for full-text screening, of which 81 studies (with a total of 14,591 subjects) were included. Studies showed that girls had a tendency towards a more variable diurnal rhythm (12 out of 29 studies), a higher CAR (8 out of 18 studies), and a stronger cortisol response to social stress tests (9 out of 21 studies). We found no evidence for sex differences in cortisol response after a pharmacological challenge or to miscellaneous stress tests.

Discussion

Sex differences in HPA axis reactivity appear to be present in childhood, although evidence is not unequivocal. For a better evaluation of sex differences in HPA axis reactivity, standardization of protocols and reports of stress tests is warranted.

     

Nitric oxide-mediated cytosolic glucose-6-phosphate dehydrogenase is involved in aluminum toxicity of soybean under high aluminum concentration

Aims

Glucose-6-phosphate dehydrogenase (G6PDH) has been reported to be involved in resistance to various environmental stresses. However, the role of G6PDH in aluminum (Al) toxicity remains unclear.

Methods

Physiological and biochemical methods together with histochemical analysis were used to investigate the participation of G6PDH in Al-induced inhibition of root growth.

Results

Exposure to high Al concentration caused a significant increase in the activities of total and cytosolic G6PDH in roots of soybean. Al-induced inhibition of root growth and oxidative stress were alleviated by a G6PDH inhibitor. Reactive oxygen species (ROS) accumulation in Al-treated root apexes could be abolished by a NADPH oxidase inhibitor. Furthermore, treatment with a G6PDH inhibitor reduced NADPH content and NADPH oxidase activity in Al-treated root apexes. Further investigation demonstrates that nitric oxide (NO) mediates Al-induced increase in cytosolic G6PDH activity by modulating the expression of genes encoding cytosolic G6PDH. In addition, nitrate reductase pathway is mainly responsible for Al-induced NO production in root apexes.

Conclusions

These results indicate that NADPH produced by NO-modulated cytosolic G6PDH in root apexes is responsible for ROS accumulation mediated by NADPH oxidase under Al stress, subsequently suffering from oxidative stress and thus causing the inhibition of root elongation.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.