Brain-derived neurotrophic factor (BDNF): an effect biomarker of neurodevelopment in human biomonitoring programs

The present narrative review summarizes recent findings focusing on the role of brain-derived neurotrophic factor (BDNF) as a biomarker of effect for neurodevelopmental alterations during adolescence, based on health effects of exposure to environmental chemical pollutants. To this end, information was gathered from the PubMed database and the results obtained in the European project Human Biomonitoring for Europe (HBM4EU), in which BDNF was measured at two levels of biological organization: total BDNF protein (serum) and BDNF gene DNA methylation (whole blood) levels. The obtained information is organized as follows. First, human biomonitoring, biomarkers of effect and the current state of the art on neurodevelopmental alterations in the population are presented. Second, BDNF secretion and mechanisms of action are briefly explained. Third, previous studies using BDNF as an effect biomarker were consulted in PubMed database and summarized. Finally, the impact of bisphenol A (BPA), metals, and nonpersistent pesticide metabolites on BDNF secretion patterns and its mediation role with behavioral outcomes are addressed and discussed. These findingswere obtained from three pilot studies conducted in HBM4EU project. Published findings suggested that exposure to some chemical pollutants such as fine particle matter (PM), PFAS, heavy metals, bisphenols, and non-persistent pesticides may alter circulating BDNF levels in healthy population. Therefore, BDNF could be used as a valuable effect biomarker to investigate developmental neurotoxicity of some chemical pollutants.European Human Biomonitoring Initiative (HMB4EU) project supported financially by the European Union’s Horizon 2020 research and innovation program under grant agreements No’s 733032Partnership for the Assessment of Risks from Chemicals (PARC), supported financially by the European Union’s Horizon 2020 research and innovation program under grant agreements No’s 101057014Postdoctoral fellowship granted by the Fundación Ramón Areces (BEVP34P01A6845), Spai

Isokinetic Fatigue Characteristics for the Leg Extensors versus Flexors

Maximal isokinetic muscle actions are often used in research studies to examine fatigability and even estimate muscle fiber-type. However, the majority of previous investigations have examined these topics for the leg extensors (i.e., quadriceps), and we are unaware of investigations that have specifically assessed the fatigue characteristics for the flexors (i.e., hamstrings). The purpose of this study was to compare the percent decline values for the leg extensors versus flexors for 50 and 100 repeated, maximal concentric isokinetic muscle actions. Fifteen healthy men (mean ± SD age = 23 ± 3 years; body mass = 94.1 ± 11.9 kg) with previous lower-body strength training experience volunteered to participate in this study. All of the subjects were familiarized with the testing procedures prior to data collection. For data collection, each subject performed 100 repeated, maximal concentric isokinetic muscle actions of the left leg extensors and flexors in a reciprocal manner. Each muscle action was performed at 180 degrees/second through a full 90 degree range of motion. Strong verbal encouragement was provided throughout testing. Percent decline was determined using the mean peak torque values of the initial and final three muscle actions for each muscle group (i.e., extensors versus flexors) and condition (i.e., 50 versus 100 repetitions). A two-way repeated measure analysis of variance was used to examine the data. The mean ± SD percent decline for the leg extensors was 61.8 ± 7.8 and 71.2 ± 6.5% for the 50 and 100 conditions, respectively (Cohen’s d = 1.31). For the leg flexors, these corresponding values were 48.0 ± 12.2 and 54.3 ± 11.7 % (Cohen’s d = 0.53). There was no significant muscle group × condition interaction (p= .114; partial eta squared = .169) There were, however, main effects for both factors. The bonferroni marginal mean pairwise comparisons indicated that when collapsed across condition, the leg extensors fatigued more so than the flexors (66.5 vs. 51.2%). Similarly, when collapsed across muscle group, the percent decline values were greater following 100 (62.8%) versus 50 (54.9%) repetitions. These finding demonstrated greater isokinetic fatigue characteristics for the leg extensors versus flexors. Furthermore, the additional decline in peak torque from repetitions 50-100 was more pronounced for the extensors. We speculate that these findings could be related to differences in muscle fiber-type, lower absolute strength and mass for the posterior aspect of the thigh, and/or unfamiliarity with single-joint testing of the leg flexors

Functional Profiling of Transcription Factor Genes in Neurospora crassa.

Regulation of gene expression by DNA-binding transcription factors is essential for proper control of growth and development in all organisms. In this study, we annotate and characterize growth and developmental phenotypes for transcription factor genes in the model filamentous fungus Neurospora crassa We identified 312 transcription factor genes, corresponding to 3.2% of the protein coding genes in the genome. The largest class was the fungal-specific Zn2Cys6 (C6) binuclear cluster, with 135 members, followed by the highly conserved C2H2 zinc finger group, with 61 genes. Viable knockout mutants were produced for 273 genes, and complete growth and developmental phenotypic data are available for 242 strains, with 64% possessing at least one defect. The most prominent defect observed was in growth of basal hyphae (43% of mutants analyzed), followed by asexual sporulation (38%), and the various stages of sexual development (19%). Two growth or developmental defects were observed for 21% of the mutants, while 8% were defective in all three major phenotypes tested. Analysis of available mRNA expression data for a time course of sexual development revealed mutants with sexual phenotypes that correlate with transcription factor transcript abundance in wild type. Inspection of this data also implicated cryptic roles in sexual development for several cotranscribed transcription factor genes that do not produce a phenotype when mutated

Relationships Between Anthropometric and Performance Variables in Youth: Predictors of Lower-Body Vertical Jump Peak Power

ABSTRACT Anthropometric and physical performance measurements are commonly used for identifying specific physical traits in youth. Laboratory-based tests (e.g., linear velocity transducers), while accurate, provide practical limitations due to high costs and technical necessities. Thus, commonly used field tests may be useful alternatives for assessing fitness/performance characteristics of youth. The purpose of this study was to examine the relationships between anthropometric measures and lower-and upper-body power and strength measures; and to assess the predictive ability of these measures for lower-body vertical jump peak power (PP) output in youth. Thirty-nine pre-adolescent (mean±SD, range: age=7.8±1.7, 5-12 years) children volunteered to participate in this investigation. Subjects were measured for body mass and stature on a calibrated physicians scale. Lower-body PP was assessed using a linear velocity transducer, which was attached to the posterior side of a belt that was securely fastened to the subjects’ waistline. Subjects performed countermovement jumps, starting in a standing position, with hands placed on hips and feet firmly on the ground. Following the descent to the midpoint position and without pause, the subjects exploded upward as hard and fast as possible. Broad jump testing involved subjects performing a countermovement jump in the horizontal direction, on a scaled mat. Maximum isometric hand grip strength of the dominant hand was assessed using a dynamometer. For all testing, 1-2 practice trials were performed, followed by testing consisting of 2-3 trials. The highest trial was used for analyses. Peak power values were normalized to body mass using allometric scaling procedures (PP· body mass-0.67). Pearson correlation (r) and stepwise linear regression analyses were performed to examine the relationships. Results indicated all variables (age, stature, body mass, broad jump and grip strength) were significantly correlated (r=0.38-0.64) to PP. Age was correlated to all variables (r=0.39-0.82) and stature and body mass were correlated to all variables (r=0.37-0.77) except broad jump. Broad jump was correlated only to age (r=0.39) and PP (r=0.38). Linear regression for all variables revealed that stature was the only variable entered into the model (R=0.64; R2=0.41). With the anthropometric variables removed, grip strength was the only variable entered into the model (R=0.57; R2=0.32). These findings suggest that while all the anthropometric and performance variables may be correlated to PP, only stature and grip strength were effective, and thus, necessary to predict PP abilities. Interestingly, broad jump performance was not a good predictor of lower body vertical PP

Tuning the pseudospin polarization of graphene by a pseudo-magnetic field

One of the intriguing characteristics of honeycomb lattices is the appearance of a pseudo-magnetic field as a result of mechanical deformation. In the case of graphene, the Landau quantization resulting from this pseudo-magnetic field has been measured using scanning tunneling microscopy. Here we show that a signature of the pseudo-magnetic field is a local sublattice symmetry breaking observable as a redistribution of the local density of states. This can be interpreted as a polarization of graphene's pseudospin due to a strain induced pseudo-magnetic field, in analogy to the alignment of a real spin in a magnetic field. We reveal this sublattice symmetry breaking by tunably straining graphene using the tip of a scanning tunneling microscope. The tip locally lifts the graphene membrane from a SiO$_2$ support, as visible by an increased slope of the $I(z)$ curves. The amount of lifting is consistent with molecular dynamics calculations, which reveal a deformed graphene area under the tip in the shape of a Gaussian. The pseudo-magnetic field induced by the deformation becomes visible as a sublattice symmetry breaking which scales with the lifting height of the strained deformation and therefore with the pseudo-magnetic field strength. Its magnitude is quantitatively reproduced by analytic and tight-binding models, revealing fields of 1000 T. These results might be the starting point for an effective THz valley filter, as a basic element of valleytronics.Comment: Revised manuscript: streamlined the abstract and introduction, added methods to supplement, Nano Letters, 201

Canonical Particle Acceleration in FRI Radio Galaxies

Matched resolution multi-frequency VLA observations of four radio galaxies are used to derive the asymptotic low energy slope of the relativistic electron distribution. Where available, low energy slopes are also determined for other sources in the literature. They provide information on the acceleration physics independent of radiative and other losses, which confuse measurements of the synchrotron spectra in most radio, optical and X-ray studies. We find a narrow range of inferred low energy electron energy slopes, n(E)=const*E^-2.1 for the currently small sample of lower luminosity sources classified as FRI (not classical doubles). This distribution is close to, but apparently inconsistent with, the test particle limit of n(E)=const*E^-2.0 expected from strong diffusive shock acceleration in the non-relativistic limit. Relativistic shocks or those modified by the back-pressure of efficiently accelerated cosmic rays are two alternatives to produce somewhat steeper spectra. We note for further study the possiblity of acceleration through shocks, turbulence or shear in the flaring/brightening regions in FRI jets as they move away from the nucleus. Jets on pc scales and the collimated jets and hot spots of FRII (classical double) sources would be governed by different acceleration sites and mechanisms; they appear to show a much wider range of spectra than for FRI sources.Comment: 16 figures, including 5 color. Accepted to Astrophysical Journa

Global Analysis of Predicted G Protein-Coupled Receptor Genes in the Filamentous Fungus, Neurospora crassa.

G protein-coupled receptors (GPCRs) regulate facets of growth, development, and environmental sensing in eukaryotes, including filamentous fungi. The largest predicted GPCR class in these organisms is the Pth11-related, with members similar to a protein required for disease in the plant pathogen Magnaporthe oryzae. However, the Pth11-related class has not been functionally studied in any filamentous fungal species. Here, we analyze phenotypes in available mutants for 36 GPCR genes, including 20 Pth11-related, in the model filamentous fungus Neurospora crassa. We also investigate patterns of gene expression for all 43 predicted GPCR genes in available datasets. A total of 17 mutants (47%) possessed at least one growth or developmental phenotype. We identified 18 mutants (56%) with chemical sensitivity or nutritional phenotypes (11 uniquely), bringing the total number of mutants with at least one defect to 28 (78%), including 15 mutants (75%) in the Pth11-related class. Gene expression trends for GPCR genes correlated with the phenotypes observed for many mutants and also suggested overlapping functions for several groups of co-transcribed genes. Several members of the Pth11-related class have phenotypes and/or are differentially expressed on cellulose, suggesting a possible role for this gene family in plant cell wall sensing or utilization

Passing to the Limit in a Wasserstein Gradient Flow: From Diffusion to Reaction

We study a singular-limit problem arising in the modelling of chemical reactions. At finite {\epsilon} > 0, the system is described by a Fokker-Planck convection-diffusion equation with a double-well convection potential. This potential is scaled by 1/{\epsilon}, and in the limit {\epsilon} -> 0, the solution concentrates onto the two wells, resulting into a limiting system that is a pair of ordinary differential equations for the density at the two wells. This convergence has been proved in Peletier, Savar\'e, and Veneroni, SIAM Journal on Mathematical Analysis, 42(4):1805-1825, 2010, using the linear structure of the equation. In this paper we re-prove the result by using solely the Wasserstein gradient-flow structure of the system. In particular we make no use of the linearity, nor of the fact that it is a second-order system. The first key step in this approach is a reformulation of the equation as the minimization of an action functional that captures the property of being a curve of maximal slope in an integrated form. The second important step is a rescaling of space. Using only the Wasserstein gradient-flow structure, we prove that the sequence of rescaled solutions is pre-compact in an appropriate topology. We then prove a Gamma-convergence result for the functional in this topology, and we identify the limiting functional and the differential equation that it represents. A consequence of these results is that solutions of the {\epsilon}-problem converge to a solution of the limiting problem.Comment: Added two sections, corrected minor typos, updated reference

A splicing-dependent transcriptional checkpoint associated with prespliceosome formation

There is good evidence for functional interactions between splicing and transcription in eukaryotes, but how and why these processes are coupled remain unknown. Prp5 protein (Prp5p) is an RNA-stimulated adenosine triphosphatase (ATPase) required for prespliceosome formation in yeast. We demonstrate through in vivo RNA labeling that, in addition to a splicing defect, the prp5-1 mutation causes a defect in the transcription of intron-containing genes. We present chromatin immunoprecipitation evidence for a transcriptional elongation defect in which RNA polymerase that is phosphorylated at Ser5 of the largest subunit’s heptad repeat accumulates over introns and that this defect requires Cus2 protein. A similar accumulation of polymerase was observed when prespliceosome formation was blocked by a mutation in U2 snRNA. These results indicate the existence of a transcriptional elongation checkpoint that is associated with prespliceosome formation during cotranscriptional spliceosome assembly. We propose a role for Cus2p as a potential checkpoint factor in transcription

Shotgun metagenomic analysis of microbial communities from the Loxahatchee nature preserve in the Florida Everglades.

BackgroundCurrently, much is unknown about the taxonomic diversity and the mechanisms of methane metabolism in the Florida Everglades ecosystem. The Loxahatchee National Wildlife Refuge is a section of the Florida Everglades that is almost entirely unstudied in regard to taxonomic profiling. This short report analyzes the metagenome of soil samples from this Refuge to investigate the predominant taxa, as well as the abundance of genes involved in environmentally significant metabolic pathways related to methane production (nitrogen fixation and dissimilatory sulfite reduction).MethodsShotgun metagenomic sequencing using the Illumina platform was performed on 17 soil samples from four different sites within the Loxahatchee National Wildlife Refuge, and underwent quality control, assembly, and annotation. The soil from each sample was tested for water content and concentrations of organic carbon and nitrogen.ResultsThe three most common phyla of bacteria for every site were Actinobacteria, Acidobacteria, and Proteobacteria; however, there was variation in relative phylum composition. The most common phylum of Archaea was Euryarchaeota for all sites. Alpha and beta diversity analyses indicated significant congruity in taxonomic diversity in most samples from Sites 1, 3, and 4 and negligible congruity between Site 2 and the other sites. Shotgun metagenomic sequencing revealed the presence of biogeochemical biomarkers of particular interest (e.g., mrcA, nifH, and dsrB) within the samples. The normalized abundances of mcrA, nifH, and dsrB exhibited a positive correlation with nitrogen concentration and water content, and a negative correlation with organic carbon concentration.ConclusionThis Everglades soil metagenomic study allowed examination of wetlands biological processes and showed expected correlations between measured organic constituents and prokaryotic gene frequency. Additionally, the taxonomic profile generated gives a basis for the diversity of prokaryotic microbial life throughout the Everglades