Functional Connectivity During Handgrip Motor Fatigue in Older Adults Is Obesity and Sex-Specific

The prevalence of obesity in older adults, particularly in females, is increasing rapidly and is associated with declines in both the brain and physical health. Both the obese and the female populations have shown greater motor fatigue than their counterparts, however, the central neural mechanisms for fatigue are unclear. The present study measured fatigue-related functional connectivity across frontal and sensorimotor areas using functional near-infrared spectroscopy (fNIRS). Fifty-nine older adults (30 non-obese and 29 obese) performed submaximal handgrip motor fatigue until voluntary exhaustion. Functional connectivity and cerebral hemodynamics were compared across eight cortical areas during motor fatigue and across obesity and sex groups along with neuromuscular fatigue outcomes (i.e., endurance time, strength loss, and force steadiness). Both obesity- and sex-specific functional architecture and mean activation differences during motor fatigue in older adults were observed, which were accompanied by fatigue-related changes in variability of force steadiness that differed between groups. While primary indicators of fatigue, i.e., endurance and strength loss, did not differ between groups, the motor steadiness changes indicated different neural adaptation strategies between the groups. These findings indicate that obesity and sex differences exist in brain function in older adults, which may affect performance during motor fatigue

Fatigue monitoring in offshore energy operations: Research to Practice gaps

PresentationThe oil and gas extraction (OGE) industry continues to experience an elevated fatality rate; from 2010-2014 fatality the rate in this industry was nearly seven times higher than that for all U.S. workers. OGE workers are exposed to intensive shift patterns and long work durations inherent in the OGE environment, which can lead to fatigue, thereby increasing risks of accidents and injuries. Fatigue, often defined as a physiological state of reduced mental or physical performance capability resulting from sleep loss, circadian phase, and workload, has been implicated as a critical risk in both offshore and onshore OGE operations. The aims of this study were to explore the effect of offshore shiftwork on physiological and subjective fatigue outcomes. 10 male workers (age: 31.3 (6.1) years; stature: 1.72 (0.1) m; weight: 85.24 (9.8) kg) were monitored throughout their daily shifts for six days using intrinsically safer physiological sensors (EQ02 LifeMonitor, EquivitalTM, Cambridge, UK) that recorded various physiological parameters at 250Hz and subjective fatigue scales were employed to obtain perceptions of fatigue. Results indicate that overall average ambulatory heart rate (an indicator of fatigue) were elevated for all participants and was highest and raised the most for those who started and ended their hitch on the day shift. The same measure was lowest and did not change for those who started on the day shift and swung to the night shift. The ambulation rates (a measure of movement) were higher later in the participants’ hitch and this effect was seen primarily for those who started their hitch in the day shift. Participants’ reports of fatigue were relatively high for acute fatigue and intershift recovery as well as for lack of effort and sleepiness; however, the physiological measures were not consistently or predictably correlated with the self-report measures of fatigue or activity. The study outcomes identified a critical gap in fatigue assessment in OGE operations; existing fatigue surveys for the general (or other) working populations are not comprehensive of OGE operations and are thus not applicable for OGE workers, nor are they validated against physiological fatigue outcomes in OGE workers

Neuromuscular Control and Performance Differences Associated With Gender and Obesity in Fatiguing Tasks Performed by Older Adults

Obesity rates in the geriatric population have emerged as a serious health concern in recent decades. Yet, obesity-related differences in neuromuscular performance and motor control during fatiguing tasks, and how they are modified by gender, specifically among older adults, are still largely unexplored. The first aim of this study was to understand obesity and gender-related differences in endurance time among older adults. Motor variability has been linked with inter-individual differences in the rate of fatigue development, and as potentially revealing underlying mechanisms of neuromuscular control. Hence, the second and third aims of this study were to investigate to what extent motor variability at baseline could predict inter-individual differences in endurance time, and whether systematic obesity and gender differences exist in motor variability among older adults. Fifty-nine older adults (65 years or older) were recruited into four groups: obese male, obese female, non-obese male, and non-obese female. Participants performed submaximal intermittent isometric knee extensions until exhaustion. Knee extension force and muscle activation signals (surface electromyography) of a primary agonist muscle, the Vastus Lateralis (VL), were collected. Endurance time and metrics quantifying both the size and structure of variability were computed for the force and EMG signals, using coefficient of variation (within cycles and between cycles) and sample entropy measures. While group differences in endurance time were primarily associated with gender, adding individual motor variability measures as predictor variables explained significantly more variance in endurance time, thus highlighting the relevance of motor variability in understanding neuromotor control strategies. Males exhibited longer endurance times, higher EMG CV, lower EMG SaEn, lower force CV, and higher force SaEn than females. These findings are interpreted to indicate males as using a motor strategy involving better “distribution” of the neural efforts across synergists and antagonists to achieve better performance during the knee extension task. No obesity-related changes in endurance time were found. However, obese individuals exhibited a greater cycle-to-cycle variability in muscle activation, indicating a larger alteration in the recruitment of motor units across successive contractions and potentially increased neural costs, which may have contributed to comparable endurance time and performance as non-obese older adults

Proteomic analysis of pregnancy-related proteins from pig uterus endometrium during pregnancy

Many important molecular events associated with implantation and development occur within the female reproductive tract, especially within the uterus endometrium, during pregnancy periods. The endometrium includes the mucosal lining of the uterus, which provides a suitable site for implantation and development of a fertilized egg and fetus. To date, the molecular cascades in the uterus endometrium during pregnancy periods in pigs have not been elucidated fully. In this study, we compared the functional regulated proteins in the endometrium during pregnancy periods with those in non-pregnant conditions and investigated changes in expression patterns during pregnancy (days 40, 70, and 93) using two-dimensional gel electrophoresis (2-DE) and western blotting. The functional regulated proteins were identified and discovered from differentially expressed proteins in the uterus endometrium during pregnancy. We discovered 820 protein spots in a proteomic analysis of uterus endometrium tissues with 2-DE gels. We identified 63 of the 98 proteins regulated differentially among non-pregnant and pregnant tissues (matched and unmatched spots). Interestingly, 10 of these 63 proteins are development-, cytoskeleton- and chaperon-related proteins such as transferrin, protein DJ-1, transgelin, galectin-1, septin 2, stathmin 1, cofilin 1, fascin 1, heat shock protein (HSP) 90β and HSP 27. The specific expression patterns of these proteins in the endometrium during pregnancy were confirmed by western blotting. Our results suggest that the expressions of these genes involved in endometrium function and endometrium development from early to late gestation are associated with the regulation of endometrium development for maintaining pregnancy

Variation in Molybdenum Content Across Broadly Distributed Populations of Arabidopsis thaliana Is Controlled by a Mitochondrial Molybdenum Transporter (MOT1)

Molybdenum (Mo) is an essential micronutrient for plants, serving as a cofactor for enzymes involved in nitrate assimilation, sulfite detoxification, abscisic acid biosynthesis, and purine degradation. Here we show that natural variation in shoot Mo content across 92 Arabidopsis thaliana accessions is controlled by variation in a mitochondrially localized transporter (Molybdenum Transporter 1 - MOT1) that belongs to the sulfate transporter superfamily. A deletion in the MOT1 promoter is strongly associated with low shoot Mo, occurring in seven of the accessions with the lowest shoot content of Mo. Consistent with the low Mo phenotype, MOT1 expression in low Mo accessions is reduced. Reciprocal grafting experiments demonstrate that the roots of Ler-0 are responsible for the low Mo accumulation in shoot, and GUS localization demonstrates that MOT1 is expressed strongly in the roots. MOT1 contains an N-terminal mitochondrial targeting sequence and expression of MOT1 tagged with GFP in protoplasts and transgenic plants, establishing the mitochondrial localization of this protein. Furthermore, expression of MOT1 specifically enhances Mo accumulation in yeast by 5-fold, consistent with MOT1 functioning as a molybdate transporter. This work provides the first molecular insight into the processes that regulate Mo accumulation in plants and shows that novel loci can be detected by association mapping

Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1

Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life. Previously, we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo. However, the contribution of individual Notch receptors and the downstream signaling mechanism have not been elucidated. Here we report that removal of Notch2, but not Notch1, from the embryonic limb mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion of the transcription factor RBPjk, a mediator of all canonical Notch signaling, in the mesenchymal progenitors but not the more mature osteoblast-lineage cells, caused a dramatic high-bone-mass phenotype characterized by increased osteoblast numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age-dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1 expression in bone. Finally, pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo

Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Background: Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood. Methods: This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies. Results: We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation. Conclusions: This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation

Redundant roles of four ZIP family members in zinc homeostasis and seed development in Arabidopsis thaliana

© 2021 Society for Experimental Biology and John Wiley & Sons LtdZinc (Zn) is essential for normal plant growth and development. The Zn-regulated transporter, iron-regulated transporter (IRT)-like protein (ZIP) family members are involved in Zn transport and cellular Zn homeostasis throughout the domains of life. In this study, we have characterized four ZIP transporters from Arabidopsis thaliana (IRT3, ZIP4, ZIP6, and ZIP9) to better understand their functional roles. The four ZIP proteins can restore the growth defect of a yeast Zn uptake mutant and are upregulated under Zn deficiency. Single and double mutants show no phenotypes under Zn-sufficient or Zn-limited growth conditions. In contrast, triple and quadruple mutants show impaired growth irrespective of external Zn supply due to reduced Zn translocation from root to shoot. All four ZIP genes are highly expressed during seed development, and siliques from all single and higher-order mutants exhibited an increased number of abnormal seeds and decreased Zn levels in mature seeds relative to wild type. The seed phenotypes could be reversed by supplementing the soil with Zn. Our data demonstrate that IRT3, ZIP4, ZIP6, and ZIP9 function redundantly in maintaining Zn homeostasis and seed development in A. thaliana.11Nsciescopu