Mitochondrial Dysregulation in the Pathogenesis of Diabetes: Potential for Mitochondrial Biogenesis-Mediated Interventions

Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions

High-intensity interval training improves acute plasma volume responses to exercise that is age dependent

Plasma volume (PV) is affected by several factors including age, physical training and, acutely, by exercise intensity. The purpose of this study was to investigate the effects of 6 weeks of high-intensity interval training (HIT) on PV and blood pressure (BP) changes among sedentary individuals. Thirty subjects aged between 18 and 71 years [body mass index=30.1(1.2) kg/m2] completed a 6-weeks HIT program. Anthropometric and fitness variables were obtained at pre- and post- HIT. PV variations during warm-up and after supramaximal cycling test (SCT) were calculated using two methods based on Hematocrit (Ht) and Hemoglobin (Hb) measures. After both the warm-up and SCT, PV decreased significantly among participants at pre- and at post-HIT (P < 0.01). However, PV decreases were significantly greater at pre-HIT compared with post-HIT during warm-up and after SCT (P < 0.01, respectively). In addition, at pre-HIT, a positive relationship was found between age and both PV variations at warm-up and after SCT (r2 = 0.55 and r2 = 0.46; P < 0.01 respectively). However, no relationship was found during the post-HIT period. After SCT and after both visits, only body weight predicted 22% of PV variations. In the current study, a significant relationship was found between systolic and diastolic BP improvements and PV variations in post-HIT (r2 = 0.54 and r2=0.56, P < 0.05, respectively). Our results suggest that HIT may improve PV values and reduce the effects of age on the decrease in PV. These interventions led to improvements in systolic and diastolic BP values among participants. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological SocietyThis work was supported by the Faculty of Superior Studies and Research of the Université de Moncton, New Brunswick, Canada.Scopu

ERPs reveal the temporal dynamics of auditory word recognition in specific language impairment.

We used event-related potentials (ERPs) to compare auditory word recognition in children with specific language impairment (SLI group; N=14) to a group of typically developing children (TD group; N=14). Subjects were presented with pictures of items and heard auditory words that either matched or mismatched the pictures. Mismatches overlapped expected words in word-onset (cohort mismatches; see: DOLL, hear: dog), rhyme (CONE -bone), or were unrelated (SHELL -mug). In match trials, the SLI group showed a different pattern of N100 responses to auditory stimuli compared to the TD group, indicative of early auditory processing differences in SLI. However, the phonological mapping negativity (PMN) response to mismatching items was comparable across groups, suggesting that just like TD children, children with SLI are capable of establishing phonological expectations and detecting violations of these expectations in an online fashion. Perhaps most importantly, we observed a lack of attenuation of the N400 for rhyming words in the SLI group, which suggests that either these children were not as sensitive to rhyme similarity as their typically developing peers, or did not suppress lexical alternatives to the same extent. These findings help shed light on the underlying deficits responsible for SLI

Developmental differences in the influence of phonological similarity on spoken word processing in Mandarin Chinese.

The developmental trajectory of spoken word recognition has been well established in Indo-European languages, but to date remains poorly characterized in Mandarin Chinese. In this study, typically developing children (N=17; mean age 10; 5) and adults (N=17; mean age 24) performed a picture-word matching task in Mandarin while we recorded ERPs. Mismatches diverged from expectations in different components of the Mandarin syllable; namely, word-initial phonemes, word-final phonemes, and tone. By comparing responses to different mismatch types, we uncovered evidence suggesting that both children and adults process words incrementally. However, we also observed key developmental differences in how subjects treated onset and rime mismatches. This was taken as evidence for a stronger influence of top-down processing on spoken word recognition in adults compared to children. This work therefore offers an important developmental component to theories of Mandarin spoken word recognition

Associated reading skills in children with a history of Specific Language Impairment (SLI)

A large cohort of 200 eleven-year-old children with Specific Language Impairment (SLI) were assessed on basic reading accuracy and on reading comprehension as well as language tasks. Reading skills were examined descriptively and in relation to early language and literacy factors. Using stepwise regression analyses in which age and nonverbal IQ were controlled for, it was found that a single word reading measure taken at 7 years was unsurprisingly a strong predictor of the two different types of reading ability. However, even with this measure included, a receptive syntax task (TROG) entered when reading accuracy score was the DV. Furthermore, a test of expressive syntax/narrative and a receptive syntax task completed at 7 years entered into the model for word reading accuracy. When early reading accuracy was excluded from the analyses, early phonological skills also entered as a predictor of both reading accuracy and comprehension at 11 years. The group of children with a history of SLI were then divided into those with no literacy difficulties at 11 and those with some persisting literacy impairment. Using stepwise logistic regression, and again controlling for IQ and age, 7 years receptive syntax score (but not tests of phonology, expressive vocabulary or expressive syntax/narrative) entered as a positive predictor of membership of the ‘no literacy problems’ group regardless of whether early reading accuracy was controlled for in step one. The findings are discussed in relation to the overlap of SLI and dyslexia and the long term sequelae of language impairment

The impact of sound field systems on learning and attention in elementary school classrooms

Purpose: An evaluation of the installation and use of sound field systems (SFS) was carried out to investigate their impact on teaching and learning in elementary school classrooms. Methods: The evaluation included acoustic surveys of classrooms, questionnaire surveys of students and teachers and experimental testing of students with and without the use of SFS. Students ’ perceptions of classroom environments and objective data evaluating change in performance on cognitive and academic assessments with amplification over a six month period are reported. Results: Teachers were positive about the use of SFS in improving children’s listening and attention to verbal instructions. Over time students in amplified classrooms did not differ from those in nonamplified classrooms in their reports of listening conditions, nor did their performance differ in measures of numeracy, reading or spelling. Use of SFS in the classrooms resulted in significantly larger gains in performance in the number of correct items on the nonverbal measure of speed of processing and the measure of listening comprehension. Analysis controlling for classroom acoustics indicated that students ’ listening comprehension score

Altered muscle satellite cell activation following 16 wk of resistance training in young men

Skeletal muscle satellite cells (SC) play an important role in muscle adaptation. In untrained individuals, SC content and activation status have been observed to increase in response to a single bout of exercise. Muscle fiber characteristics change considerably when resistance exercise is performed chronically, but whether training status affects the activity of SC in response to a single bout of exercise remains unknown. We examined the changes in SC content and activation status following a single bout of resistance exercise, before and following a 16-wk progressive resistance training (RT) program in 14 young (25 ± 3 yr) men. Before and after RT, percutaneous biopsies from the vastus lateralis muscle were taken before a single bout of resistance exercise and after 24 and 72 h of postexercise recovery. Muscle fiber size, capillarization, and SC response were determined by immunohistochemistry. Following RT, there was a greater activation of SC after 24 h in response to a single bout of resistance exercise (Pre, 1.4 ± 0.3; 24 h, 3.1 ± 0.3 Pax7+/MyoD+ cells per 100 fibers) compared with before RT (Pre, 1.4 ± 0.3; 24 h, 2.2 ± 0.3 Pax7+/MyoD+ cells per 100 fibers, P &lt; 0.05); no difference was observed 72 h postexercise. Following 16 wk of RT, MyoD mRNA expression increased from basal to 24 h after the single bout of exercise ( P &lt; 0.05); this change was not observed before training. Individual capillary-to-fiber ratio (C/F i) increased in both type I (1.8 ± 0.3 to 2.0 ± 0.3 C/F i, P &lt; 0.05) and type II (1.7 ± 0.3 to 2.2 ± 0.3 C/F i, P &lt; 0.05) fibers in response to RT. After RT, enhanced activation of SC in response to resistance exercise is accompanied by increases in muscle fiber capillarization

Electrical Brain Responses in Language-Impaired Children Reveal Grammar-Specific Deficits

Background: Scientific and public fascination with human language have included intensive scrutiny of language disorders as a new window onto the biological foundations of language and its evolutionary origins. Specific language impairment (SLI), which affects over 7% of children, is one such disorder. SLI has received robust scientific attention, in part because of its recent linkage to a specific gene and loci on chromosomes and in part because of the prevailing question regarding the scope of its language impairment: Does the disorder impact the general ability to segment and process language or a specific ability to compute grammar? Here we provide novel electrophysiological data showing a domain-specific deficit within the grammar of language that has been hitherto undetectable through behavioural data alone. Methods and Findings: We presented participants with Grammatical(G)-SLI, age-matched controls, and younger child and adult controls, with questions containing syntactic violations and sentences containing semantic violations. Electrophysiological brain responses revealed a selective impairment to only neural circuitry that is specific to grammatical processing in G-SLI. Furthermore, the participants with G-SLI appeared to be partially compensating for their syntactic deficit by using neural circuitry associated with semantic processing and all non-grammar-specific and low-level auditory neural responses were normal. Conclusions: The findings indicate that grammatical neural circuitry underlying language is a developmentally unique system in the functional architecture of the brain, and this complex higher cognitive system can be selectively impaired. The findings advance fundamental understanding about how cognitive systems develop and all human language is represented and processed in the brain

Vocal Tract Images Reveal Neural Representations of Sensorimotor Transformation During Speech Imitation

Imitating speech necessitates the transformation from sensory targets to vocal tract motor output, yet little is known about the representational basis of this process in the human brain. Here, we address this question by using real-time MR imaging (rtMRI) of the vocal tract and functional MRI (fMRI) of the brain in a speech imitation paradigm. Participants trained on imitating a native vowel and a similar nonnative vowel that required lip rounding. Later, participants imitated these vowels and an untrained vowel pair during separate fMRI and rtMRI runs. Univariate fMRI analyses revealed that regions including left inferior frontal gyrus were more active during sensorimotor transformation (ST) and production of nonnative vowels, compared with native vowels; further, ST for nonnative vowels activated somatomotor cortex bilaterally, compared with ST of native vowels. Using test representational similarity analysis (RSA) models constructed from participants' vocal tract images and from stimulus formant distances, we found that RSA searchlight analyses of fMRI data showed either type of model could be represented in somatomotor, temporal, cerebellar, and hippocampal neural activation patterns during ST. We thus provide the first evidence of widespread and robust cortical and subcortical neural representation of vocal tract and/or formant parameters, during prearticulatory ST

Second-Generation Sequencing Supply an Effective Way to Screen RNAi Targets in Large Scale for Potential Application in Pest Insect Control

The key of RNAi approach success for potential insect pest control is mainly dependent on careful target selection and a convenient delivery system. We adopted second-generation sequencing technology to screen RNAi targets. Illumina's RNA-seq and digital gene expression tag profile (DGE-tag) technologies were used to screen optimal RNAi targets from Ostrinia furnalalis. Total 14690 stage specific genes were obtained which can be considered as potential targets, and 47 were confirmed by qRT-PCR. Ten larval stage specific expression genes were selected for RNAi test. When 50 ng/µl dsRNAs of the genes DS10 and DS28 were directly sprayed on the newly hatched larvae which placed on the filter paper, the larval mortalities were around 40∼50%, while the dsRNAs of ten genes were sprayed on the larvae along with artificial diet, the mortalities reached 73% to 100% at 5 d after treatment. The qRT-PCR analysis verified the correlation between larval mortality and the down-regulation of the target gene expression. Topically applied fluorescent dsRNA confirmed that dsRNA did penetrate the body wall and circulate in the body cavity. It seems likely that the combination of DGE-tag with RNA-seq is a rapid, high-throughput, cost less and an easy way to select the candidate target genes for RNAi. More importantly, it demonstrated that dsRNAs are able to penetrate the integument and cause larval developmental stunt and/or death in a lepidopteron insect. This finding largely broadens the target selection for RNAi from just gut-specific genes to the targets in whole insects and may lead to new strategies for designing RNAi-based technology against insect damage