Modulation of the Cell Membrane Potential and Intracellular Protein Transport by High Magnetic Fields

To explore cellular responses to high magnetic fields (HMF), we present a model of the interactions of cells with a homogeneous HMF that accounts for the magnetic force exerted on paramagnetic/diamagnetic species. There are various chemical species inside a living cell, many of which may have large concentration gradients. Thus, when an HMF is applied to a cell, the concentration‐gradient magnetic forces act on paramagnetic or diamagnetic species and can either assist or oppose large particle movement through the cytoplasm. We demonstrate possibilities for changing the machinery in living cells with HMFs and predict two new mechanisms for modulating cellular functions with HMFs via (i) changes in the membrane potential and (ii) magnetically assisted intracellular diffusiophoresis of large proteins. By deriving a generalized form for the Nernst equation, we find that an HMF can change the membrane potential of the cell and thus have a significant impact on the properties and biological functionality of cells. The elaborated model provides a universal framework encompassing current studies on controlling cell functions by high static magnetic fields. Bioelectromagnetics. 2021;42:27–36. © 2020 Bioelectromagnetics Society.     

The chemical form of mitochondrial iron in Friedreich's ataxia

Friedreich's ataxia (FRDA) results from cellular damage caused by a deficiency in the mitochondrial matrix protein frataxin. To address the effect of frataxin deficiency on mitochondrial iron chemistry, the heavy mitochondrial fraction (HMF) was isolated from primary fibroblasts from FRDA affected and unaffected individuals. X-ray absorption spectroscopy was used to characterize the chemical form of iron. Near K-edge spectra were fitted with a series of model iron compounds to determine the proportion of each iron species. Most of the iron in both affected and unaffected fibroblasts was ferrihydrite. The iron K-edge from unaffected HMFs were best fitted with poorly organized ferrihydrite modeled by frataxin whereas HMFs from affected cells were best fitted with highly organized ferrihydrite modeled by ferritin. Both had several minor iron species but these did not differ consistently with disease. Since the iron K-edge spectra of ferritin and frataxin are very similar, we present additional evidence for the presence of ferritin-bound iron in HMF. The predominant ferritin subunit in HMFs from affected cells resembled mitochondrial ferritin (MtFt) in size and antigenicity. Western blotting of native gels showed that HMF from affected cells had 3-fold more holoferritin containing stainable iron. We conclude that most of the iron in fibroblast HMF from both affected and unaffected cells is ferrihydrite but only FRDA affected cells mineralize significant iron in mitochondrial ferritin.     

Effects of intradistrict school mobility and high student turnover rates on early reading achievement

The primary aim of this study was to assess the relations between concurrent, cumulative, and contextual intradistrict school mobility and early reading achievement. Longitudinal administrative school records were used for an entire cohort of students in a large urban district from first through third grade. Findings indicated that students with a concurrent intradistrict school move had lower reading achievement scores at the end of each grade compared to children who did not change schools. Cumulative intradistrict school mobility was also associated with poor reading achievement by the end of third grade. Students enrolled in schools with high turnover rates demonstrated worse reading achievement after accounting for individual school mobility experiences, and this effect worsened as children reached third grade.     

Reactive Oxygen Species: Potential Regulatory Molecules in Response to Hypomagnetic Field Exposure

Organisms, including humans, could be exposed to hypomagnetic fields (HMFs, intensity <5 μT), e.g. in some artificially shielded magnetic environments and during deep-space flights. Previous studies have demonstrated that HMF exposure could have negative effects on the central nervous system and embryonic development in many animals. However, the underlying mechanisms remain unknown. Studies have revealed that HMFs affect cellular reactive oxygen species (ROS) levels and thereby alter physiological and biological processes in organisms. ROS, the major component of highly active free radicals, which are ubiquitous in biological systems, were hypothesized to be the candidate signaling molecules that regulate diverse physiological processes in response to changes in magnetic fields. Here, we summarize the recent advances in the study of HMF-induced negative effects on the central nervous system and early embryonic development in animals, focusing on cellular ROS and their role in response to HMFs. Furthermore, we discuss the potential mechanism through which HMFs regulate ROS levels in cells. © 2020 Bioelectromagnetics Society     

A clinical and neuropsychological analysis of mental functions in 6- to 7-year-old children

The neuropsychological analysis of the state of higher mental functions (HMF) in children aged 6-7-years entering the first class of the school providing general education showed that the HMF of 52-73% of the future schoolchildren are underdeveloped with respect to their age. The underdevelopment of the emotional-volitional sphere, of the dynamic organization of object activity, audio-speech memory, sphere of images-representations, visually-image and verbally-logical forms of thinking has been revealed. The experimental data suggest the absence of the primary (structural) derangements of the studied HMF in the examined children and dependence of the extent of their formation on the extent of readiness of the voluntary organization of activity. Insufficient formation of the HMF with respect to age is manifested in the lag of the formation of the internal structure of the psychic process, i.e., the absence of interiorization of the psychic processes and formation of the internal mental act. The neuropsychological assessment of underdevelopment of the HMF in reference to age suggests an insufficient age-related maturity of subcortical structures and subcortical corticopetal pathways as well as a dysfunction of the frontal neocortex and a secondary dysfunction of the posterofrontal and TPO areas, non-auditory cortical temporal regions of the left hemisphere due to underdevelopment of connections of these areas with the frontal structures.     

p38 MAP kinase mediates platelet-derived growth factor-stimulated migration of hepatic myofibroblasts

Although the migration of hepatic myofibroblasts (HMFs) contributes to the development of fibrosis, the signals regulating migration of these cells are poorly understood. In this study, we tested the hypothesis that HMF migration is stimulated by platelet-derived growth factor-BB (PDGF-BB) through p38 mitogen-activated protein (MAP) kinase and extracellular signal-regulated kinase (ERK) signaling pathways. This hypothesis was addressed by directly visualizing the migration of cultured human HMFs into a wound. PDGF-BB stimulated membrane ruffling, migration, and proliferation. PDGF-BB also induced activation of p38 MAP kinase, its downstream effector, heat shock protein (HSP) 27, ERK 1 and ERK 2, and p125 focal adhesion kinase (FAK). Selective antagonism of p38 MAP kinase blocked PDGF-BB-stimulated HSP 27 phosphorylation, membrane ruffling, and migration, but did not alter PDGF-BB-induced proliferation. Selective antagonism of ERK kinase inhibited PDGF-BB-induced ERK phosphorylation and proliferation, but did not affect PDGF-BB-stimulated migration. Concentrations of PDGF-BB that stimulated migration and proliferation did not influence myosin-dependent contractility. Neither selective inhibition of p38 MAP kinase nor ERKs altered PDGF-BB-induced activation of FAK. In conclusion, these results provide novel evidence indicating that (1) HMF migration is stimulated by PDGF-BB through the regulation of membrane ruffling by a p38 MAP kinase signaling pathway, (2) whereas p38 MAP kinase mediates PDGF-BB-stimulated migration, but not proliferation, ERKs mediate PDGF-induced proliferation, but not migration, and (3) increases in myosin-dependent contractility are not required for PDGF-BB-stimulated migration.     

Platelet-derived growth factor-BB and lysophosphatidic acid distinctly regulate hepatic myofibroblast migration through focal adhesion kinase

Although hepatic myofibroblast (HMF) migration contributes to the development of fibrosis, the mechanisms coordinating this movement are uncertain. We determined the effects of lysophosphatidic acid (LPA) and platelet-derived growth factor-BB (PDGF) on actin polymerization, FAK tyrosine phosphorylation, and migration of cultured human HMFs. LPA (0.4-100 microM) stimulated migration, FAK tyrosine phosphorylation, and stress fiber assembly with a sigmoidal dose response. PDGF (1-250 ng/ml) stimulated migration, FAK tyrosine phosphorylation, and actin polymerization with a bell-shape dose-response characterized by a maximum at 10-25 ng/ml. Concentrations of cytochalasin D, which abolished FAK tyrosine phosphorylation, also blocked LPA- and PDGF-induced migration. A dose of 1-10 ng/ml PDGF acted synergistically with LPA (10 microM) to stimulate FAK tyrosine phosphorylation and migration, whereas higher concentrations of PDGF (100-250 ng/ml) inhibited FAK tyrosine phosphorylation and migration in response to LPA (10 microM). These data indicate that PDGF and LPA coordinately govern the migration of HMFs by differentially regulating FAK and suggest a novel model in which PDGF, acting as an amplifier/attenuator of LPA-induced signaling, facilitates HMF accumulation within injured areas of the liver.     

Grades of undernutrition and socioeconomic status influence cognitive development in school children of Kolkata

Cognitive development of children is influenced by different environmental factors like nutritional and socio‐economic status. The objectives of the present study were to determine the influence of grades of undernutrition and socio‐economic status (SES) on the cognitive development of school children of Kolkata. Five hundred sixty six (566) school children having 5–12 years of age were selected from different schools of Kolkata. The cognitive development was measured by the scores of Raven's colored progressive matrices (RCPM). The chronic and acute nutritional statuses were measured from height‐for‐age (HAZ) and weight‐for‐age (WAZ) Z scores respectively with reference to the values of WHO. SES was determined by updated Kuppuswamy scale. The prevalences of undernutrition in the observed children were 57.95% (according to HAZ) and 52.82% (according to WAZ). The age dependent growth curve of RCPM scores of the observed children remains in between the 10th and 25th centile of British children. The children belonging to superior and intellectual deficit IQ classes were 21.55 and 36.40%, respectively of the total subjects. Most of the subjects belong to lower middle (39.93%) and upper middle (36.40%) class of SES. RCPM scores of school children were gradually decreased with the grades of undernutrition and SES. RCPM scores were significantly correlated with HAZ, WAZ, SES, age, and sex (P < 0.001) and strongly associated with HAZ, SES, age, and sex (P < 0.001, P < 0.05). Present study indicates that cognitive development of school children of Kolkata is influenced by the grade of undernutrition and SES. Am J Phys Anthropol 156:274–285, 2015. © 2014 Wiley Periodicals, Inc.     

Neurophysiologic mechanisms of attention disorder in children with learning difficulties

In order to study neurophysiological mechanisms of the disturbance of voluntary attention in children of 6.5-9 years old, which had difficulties in learning caused by a delay of psychic development (DPD), characteristics were studied of electrocortical and vegetative components of orienting reaction (OR) to indifferent and relevant stimuli and also of background EEG. A decrease of OR components revealed in situation of involuntary attention against the background of insufficiently formed cortical rhythm of alpha-range, as compared with the norm, is compensated at the increase of stimuli significance by verbal instruction. These facts confirm the supposition about deficit of regulating influences of the frontal cortical areas on the ascending activating system in children with difficulties in learning. Deficiency of the involvement of the central cortical areas in OR realization, typical of the children with DPD in a situation of voluntary directed attention, can be considered as reflection of disturbances of integrative brain activity.     

Brain Mechanisms of Voluntary Regulation of Activity during Acquisition of the Skill of Writing in Seven- to Eight-Year-Old Children

With the aim of studying the formation of brain mechanisms of voluntary activity regulation in junior schoolchildren and the role of these mechanisms in the acquisition of the skill of writing, a complex neuropsychological investigation was carried out. In the EEG of children with learning problems and a deficit of voluntary activity regulation (VAR), signs of the functional immaturity of the fronto–thalamic regulatory system (FTS) were found. Comparative neuropsychological analysis revealed a specific impairment of the VAR in these children in the form of pronounced impulsiveness, instability of a program, problems in switching over from one program to another, and self-control difficulties. It is concluded that the functional maturation of the FTS is a mechanism of VAR development. It is shown that the VAR deficiency in children with FTS immaturity is combined with a delay in the development of semantic and mediating speech functions. It was found that the features of the development of the higher mental functions in seven- to eight-year-old children with FTS immaturity specifically affect both the semantic and graphic aspects of writing acquisition.     

Peculiarities of formation of the cognitive functions in junior school children with different maturity of regulatory brain systems

To reveal the specific role of maturation of modulating, regulatory brain systems in formation of cognitive processes at the junior school age, was performed a complex electroencephalographic and neuropsychological examination of the 7–8-year-old children with different degrees of functional maturity of the regulatory systems. It has been shown that an essential factor determining formation of the higher psychic functions (HPF) at the junior school age is maturation of the fronto-thalamic system. Immaturity of this system in the 7–8-year-old children leads to a deficiency of functions of programming, regulation, and control of the activity. The most substantial changes were revealed for the components of the voluntary organization of the activity, which are connected with its selectivity both in realization of current tasks and in creation of the activity strategy. The deficiency of processes of voluntary regulation in the 7–8-year-old children with immaturity of the fronto-thalamic system is combined with a delay of development of the meaning-forming speech function. Comparison of data of the neuropsychological and electroencephalographic examination has permitted suggesting that the basis of the revealed changes in the HPF formation in the 7–8-year-old children is immaturity of the main neurophysiological mechanisms that provide a selective involvement of different cortical regions in providing their activity both in the course of its realization and during preparation to it as well as an under-development of differentiated intracortical connections in the left hemisphere.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 40, No. 5, 2004, pp. 427–435.Original Russian Text Copyright © 2004 by Machinskaya, Semenova.To the 100-Anniversary of N. N. Traugott     

Circadian variations in self-monitoring,a component of executive functions

The objective of this study was to identify circadian rhythms in self-monitoring, a component of executive functions. Participants were 10 undergraduate students, age: 18.5 ± 2.68 years, two male and eight female. They were recorded on a 30-h constant routine protocol; rectal temperature was recorded every minute and performance on a tracking task was assessed every 100 min. Self-monitoring indicators were adjustments of responses to random changes of speed and trajectory of a circle moving on the computer screen. Participants showed better accuracy during the afternoon, with decreases in the morning (06:20 and 08:00 h). These variations showed a phase delay of 2:29 ± 2:19 h with respect to the circadian rhythm of body temperature. In conclusion, there are circadian variations in self-monitoring. The decline in this component of executive functions could cause serious accidents among people working or studying during a morning shift, as well as commuting to and from work or school.     

Evening chronotype and sleepiness predict impairment in executive abilities and academic performance of adolescents

The study aim was to better understand sleep and sleep-related factors affecting everyday executive capacities and academic performance among healthy adolescents. A cross-sectional survey on sleep, phase preference, academic performance and executive functions of high-school students was conducted. Female gender, grade status, sleepiness and evening chronotype accounted for approximately 25–30% of the variance in daily executive ability. Sleep duration was a weak predictor of executive skills. Lower school grades were associated with increased sleepiness, evening preference and poorer executive skills. These findings support the need for health education on ways to attenuate sleepiness and delayed phase in this population.     

Eating the right amount of fish: inverted U-shape association between fish consumption and cognitive performance and academic achievement in Dutch adolescents

Fish consumption has shown its benefits for cognitive functioning in the elderly or children with disorders (e.g., autism, ADHD), but has rarely been investigated in relation to cognitive performance and school performance of healthy adolescents. We executed an observational study in 700 Dutch high school students aged 12-18 years. Fish consumption data, end term grades, scores on the Amsterdam Vocabulary Test, and scores on the Youth Self-Report were collected. Results revealed that 13.6% of the Dutch adolescents never ate fish, 6.4% met national guidelines, 16.9% reached half of the norm, and 63.1% did eat fish but too little to meet at least half of the norm. Analysis of variance, controlled for relevant covariates, showed significant differences between the four fish consumption groups in vocabulary (p=.05). A trend for significance was found for end term grades (p=.07). Contrast analyses demonstrated significant quadratic associations between fish consumption and vocabulary (p=.01) and end term grades (p=.01). Thus higher fish intake was associated with more advanced vocabulary and higher end term grades. However, eating more fish than the described norm seemed no longer beneficial.     

Malaria education from school to community in Oudomxay province, Lao PDR

School-based malaria education has been shown to be effective for improving the knowledge, attitudes, and practices of school children toward malaria control. However, little has been reported about the effect of such education on communities in developing countries. To evaluate the influence of school-based malaria education on the knowledge, attitudes, and practices of people in the community toward malaria, we conducted a school-based intervention in Oudomxay province, Lao PDR, and compared scores obtained before and after the intervention. Participants were 130 school children in grades 3-5 at two primary schools, 103 guardians of these children, and 130 married women who did not have children in the target grades. The intervention included presentation of a flipchart at home and a 1-day campaign conducted by the school children and aimed at the community. The flipchart presentation was conducted at villages where school children of both primary schools resided. The 1-day campaign was, however, conducted only at one village. Before and after the intervention, we conducted a questionnaire-based survey of community women that pertained to malaria. Our main finding was that, in married women without children in the target grades, particularly those who were presented with the flipchart and participated in the campaign, the scores of the mean knowledge, attitudes and practices were significantly increased 1 month after the intervention. In conclusion, our results suggest that school children can act as health information messengers from schools to communities for malaria control in Lao PDR.     

Mechanically tuned 3 dimensional hydrogels support human mammary fibroblast growth and viability

Background

Carcinoma associated fibroblasts (CAFs or myofibroblasts) are activated fibroblasts which participate in breast tumor growth, angiogenesis, invasion, metastasis and therapy resistance. As such, recent efforts have been directed toward understanding the factors responsible for activation of the phenotype. In this study, we have investigated how changes in the mechanical stiffness of a 3D hydrogel alter the behavior and myofibroblast-like properties of human mammary fibroblasts (HMFs).

Results

Here, we utilized microbial transglutaminase (mTG) to mechanically tune the stiffness of gelatin hydrogels and used rheology to show that increasing concentrations mTG resulted in hydrogels with greater elastic moduli (G’). Upon encapsulation of HMFs in 200 (compliant), 300 (moderate) and 1100 Pa (stiff) mTG hydrogels, it was found that the HMFs remained viable and proliferated over the 7 day culture period. Specifically, rates of proliferation were greatest for HMFs in moderate hydrogels. Regarding morphology, HMFs in compliant and moderate hydrogels exhibited a spindle-like morphology while HMFs in stiff hydrogels exhibited a rounded morphology with several large cellular protrusions. Quantification of cell morphology revealed that HMFs cultured in all mTG hydrogels overall assumed a more elongated phenotype over time in culture; however, few significant differences in morphology were observed between HMFs in each of the hydrogel conditions. To determine whether matrix stiffness upregulated expression of ECM and myofibroblast markers, western blot was performed on HMFs in compliant, moderate and stiff hydrogels. It was found that ECM and myofibroblast proteins varied in expression during both the culture period and according to matrix stiffness with no clear correlation between matrix stiffness and a myofibroblast phenotype. Finally, TGF-β levels were quantified in the conditioned media from HMFs in compliant, moderate and stiff hydrogels. TGF-β was significantly greater for HMFs encapsulated in stiff hydrogels.

Conclusions

Overall, these results show that while HMFs are viable and proliferate in mTG hydrogels, increasing matrix stiffness of mTG gelatin hydrogels doesn’t support a robust myofibroblast phenotype from HMFs. These results have important implications for further understanding how modulating 3D matrix stiffness affects fibroblast morphology and activation into a myofibroblast phenotype.

     

Diurnal changes in psychophysiological variables of school girls: comparison with regard to age and teacher's appreciation of learning.

Ninety-five nonresident girls of a private school volunteered for the study with the teachers' help as well as parental consent. Ages were approximately 8, 9, and 10 years. They were synchronized with diurnal activity from 0730 to 2100 h and nocturnal rest. Fatigue, drowsiness, and attention were self-rated using visual analogue scales; oral temperature was self-measured and a letter cancellation test was performed. Each of these variables was measured at school at 0900, 1100, 1400, and 1600 h on Mondays, Thursdays, Fridays, and Saturdays for two consecutive weeks in 1987 (March 30-April 11) and again in 1989 (March 13-25) when the youngest group had become 10 years old. According to conventional teacher evaluation of learning (learning performance) within each group, three subgroups were formed: top third, middle third, and bottom third. Time series (more than 50,000 data) were analyzed according to several statistical methods, but mainly chronograms with ANOVA. Similar diurnal changes in oral temperature were validated for each group and subgroups. The occurrence of a diurnal change in self-rated variables (fatigue and drowsiness) and score in letter cancellation was age related: no detection in the 8-year-old group (and subgroups) and validation (p less than 0.002) in 9- and 10-year-old groups (and respective subgroups). A good learning performance was associated with a reduced drowsiness in school girls of 9 and 10 years. Age-related, time-of-day differences in drowsiness (when detected) as well as learning performance effect were not associated with observed duration of sleep. Validated changes in self-rated fatigue were close to that of drowsiness. At 0900 h, girls of 9 and 10 years were more tired when belonging to the bottom third than top third subgroup. Whatever the time of day, self-rated attention was greater in the top than in the bottom third for these girls. Differences related to learning performance were validated in each grade. However, best scores were recorded for the bottom third in the 8-year-old group, while best scores were provided by top third subgroups in 10-year-old girls. It seems that in girls around 8 years of age, critical changes can be detected with regard to the (ontogenic?) occurrence of time-of-day differences in a set of psychophysiologic variables as well as influential effects of learning performance on the same variables. Reported finding are compatible with the hypothesis of circadian oscillators working at the level of the cortex of the human brain.     

Numerical Capacities as Domain-Specific Predictors beyond Early Mathematics Learning: A Longitudinal Study

The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3^rd and 4^th grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively “start-up” tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school.     

Assessing Parent Perceptions of School Fit: The Development and Measurement Qualities of a Survey Scale

Students whose school environment fits their developmental needs also typically experience academic success and increased motivation. Most investigations of school fit, which focus on teachers’ and students’ perceptions, have found a general decline in fit across the transition from elementary to middle school. However, little research has examined the school-child fit from the parent perspective. In this article, we first detail the development process behind a new survey measure of parent perceptions of school fit. Second, using three online panel-based samples of parents from across the country (n₁ = 323, n₂ = 188, n₃ = 1,033), we evaluate the scale's measurement properties and conduct exploratory analyses examining grade-level and income-based differences on reported school fit. Finally, in line with previous research, we find that parents of middle school children perceived statistically significantly worse fit than parents of elementary school children. Among parents of high school students, we found that, on average, high-income parents perceive statistically significantly better fit than low-income parents.