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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 433 records · Page 24Linked to original sources

Mountain stoneflies may tolerate warming streams: evidence from organismal physiology and gene expression

Rapid glacier recession is altering the physical conditions of headwater streams. Stream temperatures are predicted to rise and become increasingly variable, putting entire meltwater-associated biological communities at risk of extinction. Thus, there is a pressing need to understand how thermal stress affects mountain stream insects, particularly where glaciers are likely to vanish on contemporary timescales. In this study, we tested the critical thermal maximum (CTMAX) of stonefly nymphs representing multiple species and a range of thermal regimes in the high Rocky Mountains, USA. We then collected RNA-sequencing data to assess how organismal thermal stress translated to the cellular level. Our focal species included the meltwater stonefly, Lednia tumana, which was recently listed under the U.S. Endangered Species Act due to climate-induced habitat loss. For all study species, critical thermal maxima (CTMAX > 20{degrees}C) far exceeded the stream temperatures mountain stoneflies experience (< 10{degrees}C). Moreover, while evidence for a cellular stress response was present, we also observed constitutive expression of genes encoding proteins known to underlie thermal stress (i.e., heat shock proteins) even at low temperatures that reflected natural conditions. We show that high-elevation aquatic insects may not be physiologically threatened by short-term exposure to warm temperatures and that longer term physiological responses or biotic factors (e.g., competition) may better explain their extreme distributions.

physiology↗

Discriminant Analysis of Principle Component analyses of Physiological Data.

There are many situations in physiological and pharmacological analyses where multivariate data is collected. Frequently these are analysed with t-tests and multiple (Bonferroni) comparisons or ANOVA with post-hoc test. Increasingly, even with more powerful computers many variables and it seems that feature reduction would be a useful approach. The most commonly used method is principle component analyses, but in this report we compare this to a technique developed for genetic analyses, discriminant analysis of principle component (DAPC) analyses. A simple to use and well-maintained library exists for DAPC analyses, Adegenet2, and using this we find that DAPC detects differences between synthetic physiological datasets with significantly greater accuracy than traditional PCA.

physiology↗

Physiological and Metabolic Features of Mice with CRISPR/Cas9-Mediated Loss-of-Function in Growth Hormone-Releasing Hormone

Our previous study demonstrated that the loss of growth hormone releasing hormone (GHRH) results in increased lifespan and improved metabolic homeostasis in the mouse model generated by classical embryonic stem cell based gene-targeting method. In this study, we targeted the GHRH gene using the CRISPR/Cas9 technology to avoid passenger alleles/mutations and performed in-depth physiological and metabolic characterization. In agreement with our previous observation, male and female GHRH-/- mice have significantly reduced body weight and enhanced insulin sensitivity when compared to wild type littermates. Dual-energy X-ray absorptiometry showed that there were significant decreases in lean mass, bone mineral content and density, and a dramatic increase in fat mass of GHRH-/- mice when compared to wild type littermates. Indirect calorimetry measurements including oxygen consumption, carbon dioxide production and energy expenditure were dramatically reduced in GHRH-/- mice compared to wild type mice. Respiratory exchange ratio was significantly lower in GHRH-/- mice during the light cycle, but not during the dark cycle, indicating a circadian related metabolic shift towards fat utilization in the growth hormone deficient mice. The novel CRISPR/Cas9 GHRH-/- mice are exhibiting the consistent and unique physiological and metabolic characteristics, which might mediate the longevity effects of growth hormone deficiency in mice.

physiology↗

Physiological and cognitive consequences of a daily 26h photoperiod in a primate (M. murinus)

Daily resetting of the circadian clock to the 24h natural photoperiod might induce marginal costs that would accumulate over time and forward affect fitness. It was proposed as the circadian resonance theory by Pittendrigh in 1972. For the first time, we aimed to evaluate these physiological and cognitive costs that would partially explain the mechanisms of the circadian resonance hypothesis. We evaluated the potential costs of imposing a 26h photoperiodic regimen compared to the classical 24h entrainment measuring several physiological and cognitive parameters (body temperature, energetic expenditure, oxidative stress, cognitive performances). We found significant higher resting body temperature and energy expenditure and lower cognitive performances when the photoperiodic cycle length was 26h. Together these results suggest that a great deviation of external cycles from 24h leads to daily greater synchronization costs, and lower cognitive capacities. To our knowledge, this study is the first to highlight potential mechanisms of circadian resonance theory.

physiology↗

Rapid toxin sequestration impacts poison frog physiology

Poison frogs sequester chemical defenses from their diet of leaf litter arthropods for defense against predation. Little is known about the physiological adaptations that confer this unusual bioaccumulation ability. We conducted an alkaloid-feeding experiment with the Diablito poison frog (Oophaga sylvatica) to determine how quickly alkaloids are accumulated and how toxins modify frog physiology using quantitative proteomics. Diablito frogs rapidly accumulated the alkaloid decahydroquinoline within four days, and dietary alkaloid exposure altered protein abundance in the intestines, liver, and skin. Many proteins that increased in abundance with decahydroquinoline accumulation are plasma glycoproteins, including the complement system and the toxin-binding protein saxiphilin. Other protein classes that change in abundance with decahydroquinoline accumulation are membrane proteins involved in small molecule transport and metabolism. Overall, this work shows poison frogs can rapidly accumulate alkaloids, which alter carrier protein abundance, initiate an immune response, and alter small molecule transport and metabolism dynamics across tissues. Summary StatementPoison frogs rapidly accumulate toxins, which changes abundance of proteins involved in the immune system and small molecule binding and metabolism across tissues.

physiology↗

The Vagus Nerve Mediates the Physiological but not Pharmacological Effects of PYY3-36 on Food Intake

Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity mediated by the neuropeptide Y (NPY) Y2 receptor (Y2R). However, the neuronal pathways by which PYY3-36 acts to supress appetite are unclear. Determining how the PYY3-36 system physiologically regulates food intake may help exploit its therapeutic potential. Here we demonstrate that germline and post-natal targeted knockdown of the Y2R in the afferent vagus nerve inhibits the anorectic effects of physiologically-released PYY3-36, but not peripherally-administered higher doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is compensated for in the germline model. Loss of vagal Y2R signalling also alters meal patterning and accelerates gastric emptying. These results may facilitate the design of PYY-based anti-obesity agents. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/241851v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@bef424org.highwire.dtl.DTLVardef@8e7d68org.highwire.dtl.DTLVardef@cb6757org.highwire.dtl.DTLVardef@1edb059_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

Quantifying Physiological Synchrony through Windowed Cross-Correlation Analysis: Statistical and Theoretical Considerations

Interpersonal synchrony is a widely studied phenomenon. A great challenge is to statistically capture the dynamics of social interactions with fluctuating levels of synchrony and varying delays between responses of individuals. Windowed Cross-Correlation analysis accounts for both characteristics by segmenting the time series into smaller windows and shifting the segments of two interacting individuals away from each other up to a maximum lag. Despite evidence showing that these parameters affect the estimated synchrony level, there is a lack of guidelines on which parameter configurations to use. The current study aimed to close this knowledge gap by comparing the effect of different parameter configurations on two outcome criteria: i) the ability to distinguish synchrony from pseudosynchrony by means of surrogate data analyses and ii) the sensitivity to detect change in synchrony as measured by the difference between two within-subject conditions. Focusing on physiological synchrony, we performed these analyses on heartrate, skin conductance level, pupil size, and facial expressions data. Results revealed that a range of parameters were able to discriminate synchrony from pseudosynchrony. Window size was more influential than the maximum lag with smaller window sizes showing better discrimination. No clear patterns emerged for the second criterion. Integrating the statistical findings and theoretical considerations regarding the physiological characteristics and biological boundaries of the signals, we provide recommendations for optimizing the parameter settings to the signal of interest.

physiology↗

Effects of age and hearing loss on perceptual and physiological measures of temporal envelope processing and spatial release from speech-on-speech masking

Older adults often experience difficulties understanding speech in adverse listening conditions. These difficulties are partially attributed to auditory temporal-processing deficits associated with aging even in the absence of hearing loss. The aim of this study was to assess effects of age and hearing loss on temporal envelope processing and speech-on-speech masking. Listeners with normal and near-normal hearing across a wide age range (20 to 66 years) were tested using a series of psychophysical (amplitude-modulation detection, gap detection, and interaural-envelope-phase discrimination), physiological (electroencephalographic envelope-following responses), speech perception (spatial release from masking), and cognitive (processing speed) measures. Results showed that: (i) psychophysical measures of monaural and binaural envelope processing and neural measures of envelope processing are not affected by aging after accounting for audiometric hearing loss, (ii) behavioral gap-detection thresholds decline with age, (iii) aging results in a reduction of spatial release from masking, even as speech intensity is amplified in the region of hearing loss, (iv) aging is associated with poorer measures of cognitive function. Although age significantly contributed to a decline in spatial release from speech-on-speech masking, individual differences in envelope processing and in scores from nonauditory cognitive tests used in this study were not significant predictors of speech performance. HighlightsO_LIAge per se does not affect psychophysical and physiological measures of monaural amplitude-modulation processing. C_LIO_LIAge does not affect the ability to detect interaural disparities in envelope timing between the ears. C_LIO_LIGap detection thresholds degrades with age even after hearing thresholds are statistically accounted for. C_LIO_LIAge, independent of hearing thresholds, can substantially reduce spatial release from masking. C_LIO_LICognitive ability declines with age. However, such declines do not necessarily cause deficits in spatial release from masking. C_LI

physiology↗

Pumiliotoxin metabolism and molecular physiology in a poison frog

Poison frogs bioaccumulate alkaloids for chemical defense from their arthropod diet. Although many alkaloids are accumulated without modification, some poison frog species can metabolize pumiliotoxin (PTX 251D) into the more potent allopumiliotoxin (aPTX 267A). Despite extensive research characterizing the chemical arsenal of poison frogs, the physiological mechanisms involved in the sequestration and metabolism of individual alkaloids remain unclear. We first performed a feeding experiment with the Dyeing poison frog (Dendrobates tinctorius) to ask if this species can metabolize PTX 251D into aPTX 267A and what gene expression changes are associated with PTX 251D exposure in the intestines, liver, and skin. We found that D. tinctorius can metabolize PTX 251D into aPTX 267A, and that PTX 251D exposure changed the expression level of genes involved in immune system function and small molecule metabolism and transport. To better understand the functional significance of these changes in gene expression, we then conducted a series of high-throughput screens to determine the molecular targets of PTX 251D and identify potential proteins responsible for metabolism of PTX 251D into aPTX 267A. Although screens of PTX 251D binding human voltage-gated ion channels and G-protein coupled receptors were inconclusive, we identified human CYP2D6 as a rapid metabolizer of PTX 251D in a cytochrome P450 screen. Furthermore, a CYP2D6-like gene had increased expression in the intestines of animals fed PTX, suggesting this protein may be involved in PTX metabolism. These results show that individual alkaloids can modify gene expression across tissues, including genes involved in alkaloid metabolism. More broadly, this work suggests that specific alkaloid classes in wild diets may induce physiological changes for targeted accumulation and metabolism.

physiology↗

Stimulated oxygen transport in tissue by magnetic needles - Physiology of acupuncture

AimTo understand physiology of magnetic needle acupuncture by investigating O2 transport in tissue during needle intervention. MethodsO2 transport in tissue is modeled by utilizing COMSOL with magnetic needle inserted into muscle tissue in a 2D porous media. The damaged tissue has been mimicked by an extracted tissue block with 1st order O2 consumption rate. The convection-diffusion O2 transport in the damaged tissue has been further evaluated by varying magnetic flux density B0 of the needle (0-1 T), myoglobin concentration (0-1 mM), O2 tension (5-100 Torr), O2 consumption rates, tissue permeability (10-12-10-6 m2) and porosity (0.1-0.9). Results1) Active O2 transport carried by interstitial flow is enhanced with the intervention of a magnetic needle by generating a high gradient magnetic field around the tip, which exerts a strong force (104 N/m3) on the diamagnetic interstitial fluid to accelerate the flow. 2) This interstitial flow can reach 30 m/s at B0 = 1T and strongly correlates to the needle B0 and tissue permeability. 3) The needle stirs the interstitial flow can pump O2 flux by 1-2 orders of magnitude compared to that without magnetic field. 4) The enhancement of active O2 transport by magnetic needle is site-specific to the tissue in the vicinity of the tip. This enhancement is more effective in edema condition with a high tissue permeability (>10-9 m2). ConclusionsThe dramatic enhancement of O2 transport to restore the O2 mitochondria metabolism for dysfunctional muscle tissues is the fundamental physiological mechanism of magnetic needle acupuncture.

physiology↗

Denoising physiological data collected during multi-band, multi-echo EPI sequences

Collecting physiological data during fMRI experiments can improve fMRI data cleaning and contribute to our understanding of psychophysiological processes; however, these recordings are frequently fraught with artifacts from the MRI pulse sequence. Here, we assess data from BIOPAC Systems, Inc., one of the more widely-used manufacturers of physiological monitoring equipment, and evaluate their recommendations for filtering such artifacts from electrocardiogram and electrodermal activity data collected during single-band, single-echo fMRI sequences and extend these recommendations to address artifacts associated with multiband, multi-echo fMRI sequences. While the magnitude and frequencies of artifacts differ with these aspects of pulse sequences, their effects can be mitigated via application of digital filters incorporating slice collection, multiband factor, and repetition time. The implementation of these filters is provided both in interactive online notebooks and an open source denoising tool.

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Ciliary IFT88 safeguards coordinated epiphyseal vascularisation, resorption and ossification from disruptive physiological mechanical forces

In the musculoskeletal system, appropriate cell and tissue responses to mechanical force delineate morphogenesis and ensure lifelong health. Despite this, how mechanical cues are integrated into biological programmes remains unclear. Primary cilia are microtubule-based organelles that tune a range of cell activities, including signalling cascades activated or modulated, by extracellular biophysical cues. Here, we demonstrate that the inducible, cartilage-specific deletion of Intraflagellar transport protein 88 (IFT88), which reduces ciliation in the adolescent mouse growth plate (GP), uncouples chondrocyte differentiation from cartilage resorption and mineralisation in a mechano-dependent manner. Targeting IFT88, inhibits hypertrophic chondrocyte VEGF expression, vascular recruitment, osteoclastic activity and the replacement of cartilage with bone. These effects are largely restricted to peripheral tibial regions beneath the load-bearing compartments of the knee. Increases in physiological loading, in control mice, also impairs ossification in the peripheral GP, mimicking the effects of IFT88 deletion. Strikingly, limb immobilisation rescues disrupted VEGF and restores epiphyseal dynamics in Ift88cKO mice. These data indicate, that during this pivotal phase in adolescent skeletal maturation that defines the cessation of growth, ciliary IFT88 protects the coordinated ossification of the growth plate from an otherwise disruptive heterogeneity of physiological mechanical forces.

physiology↗

Physiological activation of the nephron central command drives endogenous kidney tissue regeneration

Tissue regeneration is limited in several organs including the kidney, contributing to the high prevalence of kidney disease globally. However, evolutionary and physiological adaptive responses and the presence of renal progenitor cells suggest existing remodeling capacity. This study uncovered a novel endogenous tissue remodeling mechanism in the kidney that is activated by the loss of body fluid and salt and involves a unique niche of chief cells called macula densa (MD) that control resident progenitor cells via secreted angiogenic, growth and extracellular matrix remodeling factors, cytokines and chemokines. Serial intravital imaging, MD Wnt mouse models and transcriptome analysis provide functional and molecular characterization of this newly identified MD program for kidney regeneration complemented with human and therapeutic translation. The concept that chief cells responding to organ-specific physiological inputs control local progenitors and direct them to remodel or repair tissues may be applicable to other organs and diverse tissue regenerative therapeutic strategies.

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Physiological and molecular mechanisms regulated mesophyll conductance under severe drought in water-saving drought-resistant rice

Water-saving and drought-resistant rice (WDR) is a new type of rice varieties. It plays an important role in responding to drought with high yield and has been widely planted in central China at present. High photosynthetic production potential caused by high mesophyll conductance (gm) is the main factor promoted high yield formation in drought for WDR. But little is known about physiological and molecular mechanisms regulated gm in drought for WDR. Therefore, WDR cultivar HY73 and drought-sensitive cultivar HLY898 were used for comparative studies with three irrigation regimes before applying severe drought treatment at heading to create different differential individuals of photosynthetic potential and gm. The results showed that cultivar HY73 had lower up-regulation different expression genes (DEGs) than cultivar HLY898 in drought at transcriptional level. Conversely, DEGs of down-regulation was higher in cultivar HY73 than cultivar HLY898. In addition, 3071 DEGs were clustered in 3 modules named Midnightblue (734 DEGs), Blue (921 DEGs), and Turquoise (1416 DEGs) in severe drought merged three irrigation regimes and both cultivars, which the modules had significant correlational relationship with gm based on weighted gene co-expression network analysis (P<0.05). Only DEGs in midnightblue module were enriched in photosynthesis process and positively regulated gm (P<0.05). The main biological process were photosynthesis (GO:0015979), light harvesting in photosystem I (GO:0009768), reductive pentose-phosphate cycle (GO:0019253), protein-chromophore linkage (GO:0018298), photosynthetic electron transport in photosystem I (GO:0009773), and photosystem II repair (GO:0010206). These results indicate that gm and energy distribution in PSI and PSII systems could synergistic effect photosynthetic production potential in severe drought for rice plants. In the modules, the 18 most highly connected hub genes were screened using co-expression networks method. RT-PCR analysis indicated that CSP41B, PGLP1A, LHCA5, and GSTU6 genes had a similar variation trend with gm among treatments for both cultivar. LHCA5 and CSP41B genes were significantly up-regulated in HY73 compared with HLY898 in drought (P<0.05). And the both genes locates in thylakoid membrane in photosystems. Therefore, LHCA5 and CSP41B genes could be key genes to synergistically manage gm and energy distribution in photosystems. Our results provide some new physiological and molecular mechanisms regulated gm in severe drought for WDR.

physiology↗

Fic-mediated AMPylation tempers the Unfolded Protein Response during physiological stress

The proper balance of synthesis, folding, modification and degradation of proteins, also known as protein homeostasis, is vital to cellular health and function. The unfolded protein response (UPR) is activated when the mechanisms maintaining protein homeostasis in the endoplasmic reticulum (ER) become overwhelmed. However, prolonged or strong UPR responses can result in elevated inflammation and cellular damage. Previously, we discovered that the bifunctional enzyme Fic can modulate the UPR response via post-translational modification of BiP by AMPylation and deAMPylation. Loss of fic in Drosophila leads to vision defects and altered UPR activation in the fly eye. To investigate the importance of Fic-mediated AMPylation in a mammalian system, we generated a conditional null allele of Fic in mice and characterized the effect of Fic loss on the exocrine pancreas. Compared to controls, Fic-/- mice exhibit elevated serum markers for pancreatic dysfunction and display enhanced UPR signaling in the exocrine pancreas in response to physiologic and pharmacological stress. In addition, both fic-/- flies and Fic-/- mice show reduced capacity to recover from damage by stress that triggers the UPR. These findings show that Fic- mediated AMPylation acts as a molecular rheostat that is required to temper the UPR response in the mammalian pancreas during physiological stress.

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Physiological Changes Associated with Copper Sulfate-Induced Emesis in Felines

Nausea is a common disease symptom, yet there is no consensus regarding its physiological markers. In contrast, the process of vomiting is well documented as sequential muscular contractions of the diaphragm and abdominal muscles and esophageal shortening. Nausea, like other self-reported perceptions, is difficult to distinguish in preclinical models, but based on human experience emesis is usually preceded by nausea. Here we focused on measuring gastrointestinal and cardiorespiratory changes prior to emesis to provide additional insights into markers for nausea. Felines were instrumented to chronically record heart rate, respiration, and electromyographic (EMG) activity from the stomach and duodenum before and after intragastric delivery of saline or copper sulfate (CuSO4, from 83 to 322 mg). CuSO4 is a prototypical emetic test agent that triggers vomiting primarily by action on GI vagal afferent fibers when administered intragastrically. CuSO4 infusion elicited a significant increase in heart rate, decrease in respiratory rate, and a disruption of gastric and intestinal EMG activity several minutes prior to emesis. The change in EMG activity was most consistent in the duodenum. Administration of saline did not induce these effects. Increasing the dose of CuSO4 did not alter the physiologic changes induced by the treatment. It is postulated that the intestinal EMG activity was related to a retrograde movement of chyme from the intestine to the stomach. These findings suggest that monitoring of intestinal EMG activity, perhaps in combination with heart rate, may provide the best indicator of the onset of nausea following treatments and in disease conditions, including GI disease, associated with emesis.

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Joint effects of social interactions and environmental challenges on physiology, internal microbiome, and reproductive performance in tree swallows (Tachycineta bicolor).

The social environment that individuals experience appears to be a particularly salient mediator of stress resilience, as the nature and valence of social interactions are often related to subsequent health, physiology, microbiota, and overall stress resilience. Relatively few studies have simultaneously manipulated the social environment and ecological challenges under natural conditions. Here, we report the results of experiments in wild tree swallows (Tachycineta bicolor) in which we manipulated both ecological challenges (predator encounters and flight efficiency reduction) and social interactions (by experimental dulling of a social signal). In two experiments conducted in separate years, we reversed the order of these treatments so that females experienced either an altered social environment followed by a challenge or vice-versa. Before, during, and after treatments were applied, we tracked breeding success, morphology and physiology (mass, corticosterone, and glucose), social interactions via an RFID sensor network, cloacal microbiome diversity, and fledging success. Overall, we found that predator exposure during the nestling period reduced the likelihood of fledging and that signal manipulation sometimes altered social interactions, but little evidence that the two categories of treatment interacted with each other. We discuss the implications of our results for understanding what types of challenges and what conditions are most likely to result in interactions between the social environment and ecological challenges.

physiology↗

Motor unit tracking using blind source separation filters and waveform cross-correlations: reliability under physiological and pharmacological conditions

Recent advancements in the analysis of high-density surface electromyography (HDsEMG) have enabled the identification, and tracking, of motor units (MUs) to study muscle activation. This study aimed to evaluate the reliability of MU tracking using two common methods: blind source separation filters and two-dimensional waveform cross-correlation. An experiment design was developed to assess physiological reliability, and reliability for a drug intervention known to reduce the firing rate of motoneurones (cyproheptadine). HDsEMG signals were recorded from tibialis anterior during isometric dorsiflexions to 10%, 30%, 50% and 70% of maximal voluntary contraction. MUs were matched within session (2 hr) using the filter method, and between sessions (7 days) via the waveform method. Both tracking methods demonstrated similar reliability during physiological conditions (e.g., MU discharge: filter ICC 10% of MVC = 0.76, to 70% of MVC = 0.86; waveform ICC: 10% of MVC = 0.78, to 70% of MVC = 0.91). Although reliability slightly reduced after the pharmacological intervention, there were no discernible differences in tracking performance (e.g., MU disc filter ICC: 10% of MVC = 0.73, to 70% of MVC = 0.75; DR waveform ICC: 10% of MVC = 0.84, to 70% of MVC = 0.85). The poorest reliability typically occurred at higher contraction intensities, which aligned with the greatest variability in MU characteristics. This study confirms that tracking method may not impact the interpretation of MU data, provided that an appropriate experiment design is employed. However, caution should be used when tracking MUs during higher intensity isometric contractions. NEW AND NOTEWORTHYThe most direct way to validate longitudinal tracking of motor unit data extracted from high-density surface electromyography is to contrast findings with intramuscular electromyography. We use pharmacology to changes motor unit discharge properties as a non-invasive alternative to validate the reliability tracking motor units. This study confirmed that the specific tracking method may not impact interpretation of motor unit data at lower contraction intensities, however caution should be used when tracking units during higher intensities.

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