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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2017

The effect of chronic and acute stressors, and their interaction, on gonadal function: an experimental test during gonadal recrudescence

Organisms are expected to invest less in reproduction in response to a stressor, but theory predicts that this effect should depend on the frequency of stressors in the environment. Here we investigated how an acute stressor affected gonadal function in a songbird, and how long-term differences in the stress environment influenced these acute stress responses. We exposed male Dark-eyed Juncos (Junco hyemalis) either to chronic or minimal (control) disturbance during gonadal recrudescence, after which we measured baseline testosterone, testosterone after an acute handling stressor, and the ability to elevate testosterone in response to hormonal stimulation. In a 2x2 design, we then euthanized males from the two chronic treatment groups either immediately or after an acute stressor to investigate the effect of these treatments on the gonadal transcriptome. We found that chronically disturbed birds had marginally lower testosterone. The acute stressor suppressed testosterone in control birds, but not in the chronic disturbance group. The ability to elevate testosterone did not differ between the chronic treatments. Surprisingly, chronic disturbance had a weak effect on the testicular transcriptome, and did not affect transcriptomic response to the acute stressor. The acute stressor, on the other hand, upregulated cellular stress response, and affected expression of genes associated with hormonal stress-response. Overall, we show that both chronic and acute stressors affect reproductive function, and that chronic stress changes how acute stressors affect testosterone physiology. Our findings also suggest that acute and chronic stressors affect testes differently, and that gonadal function is relatively robust to long-term stressors.\n\nSummary statementAn acute stressor downregulated testosterone production, but this effect was absent in chronically disturbed birds. The acute stressor had a strong effect on the gonadal transcriptome, whereas chronic disturbance had a negligible effect.

physiology↗

bioRxiv2017

Versatile open software to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo

Contraction of muscle reflects its physiological state. Methods to quantify contraction are often complex, expensive and tailored to specific models or recording conditions, or require specialist knowledge for data extraction. Here we describe an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes and pharmacological responses. MUSCLEMOTION allowed rapid and easy measurement of contractility in (i) single cardiomyocytes from primary adult heart and human pluripotent stem cells, (ii) multicellular 2D-cardiomyocyte cultures, 3D engineered heart tissues and cardiac organoids/microtissues in vitro and (iii) intact hearts of zebrafish and humans in vivo. Good correlation was found with conventional measures of contraction in each system. Thus, using a single method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell- and animal models and human echocardiograms.

physiology↗

bioRxiv2017

Distress tolerance across self-report, behavioral and psychophysiological domains in women with eating disorders and healthy controls

Background and objectivesThe tendency to engage in impulsive behaviors when distressed is linked to engagement in disordered eating. The current study comprehensively examines emotional responses to a distress tolerance task by utilizing self-report, psychophysiological measures (respiratory sinus arrhythmia [RSA], skin conductance responses [SCRs] and tonic skin conductance levels [SCLs]), and behavioral measures (i.e., termination of task, latency to quit task).\n\nMethods26 healthy controls (HCs) and a sample of treatment-seeking women with Bulimia Nervosa (BN), Binge Eating Disorder (BED) and Anorexia Nervosa (AN) (N=106) completed the Paced Auditory Serial Addition Task-Computerized (PASAT-C). Psychophysiological measurements were collected during baseline, PASAT-C, and recovery, then averaged for each time-period. Self-reported emotions were collected at baseline, post-PASAT-C and post-recovery.\n\nResultsOverall, we found an effect of Time, with all participants reporting greater negative emotions, less happiness, lower RSA, more SCRs and higher tonic SCLs after completion of the PASAT-C relative to baseline. There were no differences in PASAT-C performance between groups. There was an effect of Group for negative emotions, with women with BN, BED and AN reporting overall higher levels of negative emotions relative to HCs. Furthermore, we found an effect of Group for greater urges to binge eat and lower RSA values among BED, relative to individuals with BN, AN and HCs.\n\nLimitationsThis study is cross-sectional and lacked an overweight healthy control group.\n\nConclusionDuring the PASAT-C, individuals with EDs compared to HCs report higher levels of negative emotions, despite similar physiological and behavioral manifestations of distress.

physiology↗

bioRxiv2017

A New Evidence of Lubrication Hypothesis on Nephila pilipes Spider Silk Spinning

In spite of all the efforts on deciphering such spinning process of spiders, the underlying mechanism currently is yet to be fully revealed. In this research, we designed a novel approach to quantitatively estimate the overall concentration change of spider silk along the progression of liquid-to-solid silk transition from the gland silk. As a prior characterization, we first studied the influence of silking-rate, ranged from 1.5 to 8.0 m/min, on spun fiber diameters as well as fiber strengths. Furthermore, the liquid contents of silk in the sac and the silk fibers leaving the spinneret were investigated by thermogravimetric analysis (TGA) and by estimating the ratio of collected dried silk to the weight loss of spider, respectively. The strength of spun silk fiber showed in the range of 7.5 - 8.5 g/denier; while, the fiber diameter of 0.7 - 1.1 deniers for spun silk first increased then decreased with take-up speed of winder. The results showed that the percentage liquid content of silk stored in the major ampullate sac (50.0 wt%) was lower than that of silk leaving the spinnerets (80.9 - 96.1 wt%), indicating a liquid supplying mechanism might be involved during the spinning process. Thus, a hypothesis of liquid coating on the outer surface of the silk thread served as a lubrication layer to reduce the silking resistance in spinning spigot of spider was proposed. In addition, we speculated the spigot serves as a valve-like regulator that controls not only the fiber diameter but also the lubrication layer. These findings provide understanding in physiological function of the spider spinning process and could further shed some light on future biomimetic development of silk material fabrication.

physiology↗

bioRxiv2017

Diminished dynamic cerebral autoregulatory capacity with forced oscillations in mean arterial pressure with elevated cardiorespiratory fitness

The effect that cardiorespiratory fitness has on the dynamic cerebral autoregulatory capacity during changes in mean arterial pressure (MAP) remains equivocal. Using a multiple-metrics approach, challenging MAP across the spectrum of physiological extremes (i.e. spontaneous through forced MAP oscillations), we characterized dynamic cerebral autoregulatory capacity in 19 male endurance athletes and 8 controls via three methods: [1] onset of regulation (i.e., time delay before an increase in middle cerebral artery (MCA) conductance [MCA flow velocity (MCAv)/mean arterial pressure (MAP)] and rate of regulation, after transient hypotension induced by sit-to-stand, and transfer function analysis (TFA) of MAP and MCAv responses during [2] spontaneous and [3] forced oscillations (5-min of squat-stand maneuvers performed at 0.05 and 0.10 Hz). Reductions in MAP and mean MCAv (MCAVmean) during initial orthostatic stress (0-30 s after sit-to-stand) and the prevalence of orthostatic hypotension were also determined. Onset of regulation was delayed after sit-to-stand in athletes (3.1{+/-}1.7 vs. 1.5{+/-}1.0 s; p=0.03), but rate of regulation was not different between groups (0.24{+/-}0.05 vs. 0.21{+/-}0.09 s-1; p=0.82). While both groups had comparable TFA metrics during spontaneous oscillations, athletes had higher TFA gain during 0.10 Hz squat-stand vs. recreational controls (p=0.01). Reductions in MAP (p=0.15) and MCAVmean (p=0.11) during orthostatic stress and the prevalence of initial orthostatic hypotension (p=0.65) were comparable between groups. These results indicate an intact ability of the cerebral vasculature to react to spontaneous oscillations but an attenuated capability to counter rapid and large changes in MAP in individuals with elevated cardiorespiratory fitness.\n\nNew findingsO_ST_ABSWhat is the central question of this study?C_ST_ABSO_LIWhat is the impact of cardiorespiratory fitness on dynamic cerebral autoregulatory capacity?\nC_LI\n\nWhat is the main finding and its importance?O_LIOur results indicate an intact ability of the cerebral vasculature to react to spontaneous oscillations but an attenuated capability to counter rapid and large changes in mean arterial pressure in individuals with elevated cardiorespiratory fitness.\nC_LI

physiology↗

bioRxiv2017

Effects of regional differences on the urinary proteomes of healthy Chinese individuals

Urine is a promising biomarker source for clinical proteomics studies. Although regional physiological differences are common in multi-center clinical studies, the presence of significant differences in the urinary proteomes of individuals from different regions remains unknown. In this study, morning urine samples were collected from healthy urban residents in three regions of China and urinary proteins were preserved using a membrane-based method (Urimem). The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among the three regions. We identified 1,898 proteins from Urimem samples using label-free proteome quantification, of which 62 urine proteins were differentially expressed among the three regions. Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than inter-sex differences. Of the 62 differentially expressed proteins, 10 have been reported to be disease biomarkers in previous clinical studies. Urimem facilitates urinary protein storage for large-scale urine sample collection, and thus accelerates biobank development and urine biomarker studies employing proteomics approaches. Regional differences are a confounding factor influencing the urine proteome and should be considered in future multi-center biomarker studies.

physiology↗

bioRxiv2017

Females recruit faster alpha motor neurons than males during the patellar stretch reflex: evidence for neurophysiological sexual dimorphism

ObjectiveHuman neurophysiology is sexually dimorphic where the pre-motor latency of the patella stretch reflex (PR) in females occurs earlier than males; an effect unaccounted for by stature difference. Using surface electromyography we investigated whether this difference is due to dimorphism in the conduction velocity (MNCV) of the associated alpha-motor neurons.\n\nMethodsExtracellular linear electrode arrays measured vastus lateralis (VL) motor unit action potential activity (MUAP). MNCV was determined from the relationship between the latency of MUAP initiation and VL distance during a PR.\n\nResultsIn females, the PR premotor latency occurred 2.1{+/-}0.3 ms earlier than in males and recruited alpha-motor neurons with a MNCV 5 ms-1 faster (p<0.02) than males: 52.4{+/-}1.5 5 m s-1 (n=40) compared to 47.6{+/-}1.3 5 m s-1 (n=41) respectively.\n\nConclusionsIn males the longer PR premotor latency was accounted for by their slower MNCV. Our finding is contrary to the observations of larger diameter alpha-motor axons and somas seen in males. Since the PR yields MNCVs values at the lower end of published values supports the \"size-principle\" of motor unit recruitment with a physiological stimulus.\n\nSignificanceOur findings evidence gender dimorphism in a routine neurophysiologic test which suggest androgen modulation of skeletal muscle innervation.

physiology↗

bioRxiv2017

Cardio- and neurometabolic effects of lower-body pressure supported exercise in obese non-diabetic women: Resetting autonomic imbalance?

BackgroundOvernutrition and underactivity cause most chronic disease via inflammation and stress. Life-style changes such as diet is largely unsuccessful and exercise is painful, uncomfortable and difficult for people with diabesity, cardiorespiratory and joint diseases and cognitive decline affecting their ability to ambulate and adhere to exercise guidelines. Diets or exercise causing weight loss are stressful and trigger numerous redundant counter regulatory mechanisms defending lean body mass, explaining failures to sustain these behaviors. In this hypothesis-generating pilot study we used a NASA-developed weight supporting lower-body positive pressure (LBPP) treadmill providing comfortable low-amount, low intensity walking, challenging current exercise guidelines.\n\nMethodsSixteen nondiabetic, untrained, Black volunteer women (BMI 28-50), age 18-56 years were studied by anthropometry, analyses of energy expenditure and blood chemistry: oral glucose tolerance tests (OGTT) with insulin, C-peptide, GLP-1 and FFA and fasting lipids, cytokines, adipokines and appetitive peptides, before and after 10 weeks of twice weekly 30-minute weight supported LBPP treadmill sessions.\n\nResultsWe found novel baseline associations between gluco- and neuro-regulatory peptides and plasma lipids, inflammatory cytokines and appetitive hormones related to neurogenesis, mood and energy balance. Post-study, independent of body weight or energy expended there were significant decreases in OGTT plasma insulin (p=0.002) and GLP-1 (p=0.060) and fasting triglycerides (p=0.029), ghrelin (p=0.008) and changes in most molecules including increased leptin and beta-endorphin. Correlations between changes among different classes of peptides were highly significant, notably leptin - adiponectin, and beta-endorphin - oxytocin and orexin A. We propose synergy between low-amount, low-intensity exercise at levels below thresholds of increased sympathetic tone, and baro-physiological effects of LBPP normalizing parasympathetic tone.\n\nConclusionBrief, low-dose, lower-body positive-pressure weight-supported treadmill exercise improved cardiometabolic fitness and exhibited favorable changes in neuro-regulatory peptides without weight loss in inner-city obese Black women.

physiology↗

bioRxiv2017

INSULIN-LIKE PEPTIDES REGULATE FEEDING PREFERENCE AND METABOLISM IN DROSOPHILA

Fruit flies have eight identified Drosophila insulin-like peptides (DILPs) involved in regulation of carbohydrate concentrations in hemolymph as well as accumulation of storage metabolites. In the present study, we investigated diet-dependent roles of DILPs encoded by genes dilp1-5, and dilp7 in regulation of insect appetite, food choice, accumulation of triglycerides, glycogen, glucose, and trehalose in fruit fly body and carbohydrates in hemolymph. We found that dilp2 gene predominantly influences body glycogen level, dilp3 - trehalose level in hemolymph, while dilp5 and dilp7 affect triglyceride level. Fruit fly appetite was found to be regulated by dilp3 and dilp7 genes. Our data contribute to the understanding of Drosophila as a model for further studies of metabolic diseases and may serve as a guide for uncovering the evolution of metabolic regulatory pathways.\n\nHIGHLIGHTSDifferent Drosophila insulin-like peptides play distinctive roles in metabolism, physiology and appetite regulation.\n\nLack of Dilp2 and Dilp5 abrogates glycogen accumulation on high carbohydrate diets\n\nLack of Dilp3 leads to build-up of trehalose in haemolymph on high-carbohydrate-low-protein diets\n\nLack of Dilp3 and Dilp7 leads to increased consumption of protein on low-carbohydrate-high-protein diets\n\nGRAPHICAL ABSTRACT O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

physiology↗

bioRxiv2017

Long-range infra-sound acoustic signaling inhuman in vivo

Acupuncture is widely deployed today, but its basic physiology with Qi and meridian is not understood. This letter postulates that Qi is an infrasound wave packet and meridian is the muscle waveguide. Using video cameras and signal processing in an IRB approved clinical experiment we performed a comparison between control and electro-activated statistical tests on the long range (50-80cm) unidirectional transmission of Qi (p = 0.025). In the reverse direction, there is no transmission even in a distance of less than 10 cm (p = 0.545). The rectification is a surprise but in full agreement with Huang Di Nei Jing.

physiology↗

bioRxiv2018

First evidence that intrinsic fetal heart rate variability exists and is affected by chronic hypoxia

INTRODUCTIONIt is established that normal fetal HRV represents the integration of the autonomic nervous system, components due to fetal body and breathing movements, baroreflex and circadian processes. There is also some evidence of possible intrinsic pacemaker rhythms of the SA node affecting HRV in adult disease.\n\nHowever, whether intrinsic HRV (iHRV) exists in the fetal period and whether this is affected by chronic fetal hypoxia has never been tested. Here, we show iHRV in isolated hearts from fetal sheep in late gestation and significant effects on iHRV of pregnancy complicated by chronic fetal hypoxia.\n\nMETHODSChronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n=6) or hypoxia (10% inspired O2, n=9) for the last third of gestation (105-138 dG; term~145 dG) in bespoke isobaric chambers, as before. At 138dG, isolated hearts were studied under a Langendorff preparation. CIMVA software was used to calculate basal iHRV matrix indices across five signal-analytical domains from the systolic peaks within 15 min segments in each heart, as before. Data presented as Mean+SEM were compared by the Students t test for unpaired data.\n\nRESULTSThis level of maternal H yields fetal PaO2 values of 11.5{+/-}0.6 relative to controls of 20.9{+/-}0.5 mmHg. Hearts isolated from H pregnancy showed approximately 4-fold increases in the Grid transformation feature as well as the AND similarity index (sgridAND, informational domain) and a 4-fold reduction in the Scale dependent Lyapunov exponent slope (SDLEalpha, invariant domain). We also detected a 2-fold reduction in the Recurrence quantification analysis, the percentage of laminarity and recurrences and maximum diagonal line (pL, pR, dlmax, all from geometric domain) and (AsymI, energetic domain). For dlmax and sgridAND measures, this is also correlated to left ventricular end-diastolic pressure (LVEDP) across both groups.\n\nCONCLUSIONSThe isolated fetal hearts from the hypoxic pregnancy group exhibit a lower complexity in iHRV. This is the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it.\n\nSignificance StatementFetal heart rate variability (fHRV) is an important indicator of health and disease, yet its physiological origins are poorly understood. Both, the heart, intrinsically, and extrinsic systems, such as the brain, are hypothesized to contribute to HRV. In a near-term fetal sheep model of human development, we identified fHRV components reflecting intrinsic contributions to fHRV. In addition, we show that these intrinsic fHRV components carry memory of chronic oxygen deprivation the fetus experienced during the last third of gestation.

physiology↗

bioRxiv2018

Structure-guided design of a cell penetrating peptide preventing cAMP modulation of HCN channels

The auxiliary subunit TRIP8b prevents cAMP activation of HCN channels by antagonizing its binding to their cyclic-nucleotide binding domain (CNBD). By determining an NMR-derived structure of the complex formed by the HCN2 channel CNBD and a minimal TRIP8b fragment, TRIPnano, we show here a bipartite interaction between the peptide and CNBD which prevents cAMP binding in two ways: through direct competition for binding at the distal C-helix of the CNBD; and through an allosteric reduction in cAMP affinity induced by TRIP8b binding to the CNBD N-bundle loop. TRIPnano abolishes cAMP binding in all three isoforms, HCN1, HCN2 and HCN4 and can be used to prevent cAMP stimulation in native f-channels. Application of TRIP8bnano, or its delivery via a cell-penetrating sequence, in sinoatrial node myocytes, selectively inhibits beta-adrenergic stimulation of the native If current and mimics the physiological concentrations of acetylcholine leading to a 30% reduction in the spontaneus rate of action potential firing.

physiology↗

bioRxiv2018

A Single Dose Of Ayahuasca Modulates Salivary Cortisol In Treatment-Resistant Depression

Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized placebo-controlled trial supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients and in healthy volunteers. Subjects received a single dose of ayahuasca or placebo, and both plasma and awakening salivary cortisol response were measured at baseline (before dosing) and 48h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients (DM), both with respect to healthy controls group (C). Salivary cortisol also was measured during dosing session and we observed a large increased for both C and DM that ingested ayahuasca, than placebo groups. After 48h of the dosing session (D2) with ayahuasca, awakening salivary cortisol response (for both sexes) of treated patients became similar to levels detected in controls. This was not observed in patients that ingested placebo. No changes in plasma cortisol were observed after 48 hours of ayahuasca or placebo ingestion for both groups and sexes. Therefore, these findings point to new evidence of modulation of ayahuasca on salivary cortisol levels, as cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes related to etiology of depression, this modulation could be an important part of the antidepressant effects observed with ayahuasca. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.

physiology↗

bioRxiv2018

Thermoneutrality induces skeletal muscle myopathy via brown adipose tissue in an IRF4- and myostatin-dependent manner

Skeletal muscle and brown adipose tissue (BAT) share a common lineage and have been functionally linked, as exercise increases browning through the actions of various myokines. It is unknown, however, whether BAT can affect skeletal muscle function. Our prior work has shown that loss of the transcription factor IRF4 in BAT (BATI4KO) reduces adaptive thermogenesis. Here, we note that these mice also have reduced exercise capacity relative to wild-type littermates, associated with diminished mitochondrial function, ribosomal protein synthesis, and mTOR signaling in muscle, in addition to the signature ultrastructural abnormalities of tubular aggregate myopathy. Within brown adipose tissue, loss of IRF4 caused the induction of a myogenic gene expression signature, which includes an increase in the secreted factor myostatin, a known inhibitor of muscle function. Reduction of myostatin activity by the injection of neutralizing antibodies or soluble ActRIIB receptor rescued the exercise capacity of BATI4KO mice. Additionally, overexpression of IRF4 in brown adipocytes reduced serum myostatin and increased mitochondrial function and exercise capacity in muscle. A physiological role for this system is suggested by the observation that mice housed at thermoneutrality show lower exercise capacity with increased serum myostatin; both of these abnormalities are corrected by surgical removal of BAT. Collectively, our data point to an unsuspected level of BAT-muscle cross-talk driven by IRF4 and myostatin.\n\nHighlightsO_LIMice lacking IRF4 in BAT have a decrease in exercise capacity, accompanied by histological, ultrastructural, signaling, gene expression, and bioenergetic evidence of myopathy in white vastus.\nC_LIO_LILoss of IRF4 promotes the expression of a myogenic signature in BAT, including the myokine myostatin.\nC_LIO_LINeutralization of serum myostatin rescues the ability of BATI4KO mice to exercise normally, while overexpression of IRF4 in BAT allows mice to run better than wild-type counterparts.\nC_LIO_LIThermoneutrality reduces the level of IRF4 in BAT of WT mice, resulting in a myopathic phenotype that can be reversed by surgical excision of BAT.\nC_LI

physiology↗

bioRxiv2018

The Stress-Chip: A microfluidic platform for stress analysis in Caenorhabditis elegans

An organisms ability to mount a physiological response to external stressors is fundamental to its interaction with the environment. Experimental exploration of these interactions benefits greatly from the ability to maintain tight control of the environment, even under conditions in which it would be normal for the subject to flee the stressor. ere we present a nematode research platform that pairs automated image acquisition and analysis with a custom microfluidic device. This platform enables tight environmental control in low-density, single-worm arenas, which preclude animal escape while still allowing a broad range of behavioral activities. The platform is easily scalable, with two 50 arena arrays per chip and an imaging capacity of 600 animals per scanning device. Validating the device using dietary, osmotic, and oxidative stress indicates that it should be of broad use as a research platform, including eventual adaptation for additional stressors, anthelmintic-drug screening, and toxicology studies.

physiology↗

bioRxiv2018

Altered Fecal Microbiota and Urine Metabolome as Signatures of Soman Poisoning

The experimental pathophysiology of organophosphorus (OP) chemical exposure has been extensively reported. Here, we describe an altered fecal microbiota and urine metabolome that follows intoxication with soman, a lipophilic G class chemical warfare nerve agent. Non-anaesthetized Sprague-Dawley male rats were subcutaneously administered soman at 0.8 - 1.0 of the median lethal dose (LD50) and evaluated for signs of toxicity. Animals were stratified based on seizing activity to evaluate effects of soman exposure on fecal bacterial biota and urine metabolites. Soman exposure reshaped fecal bacterial biota by preferentially expanding Facklamia, Agrobacterium, Bilophila, Enterobacter, and Morganella genera of the Firmicutes and Proteobacteria phyla, some of which are known to hydrolyze OPs. However, analogous changes were not observed in the bacterial biota of the ileum, which remained the same irrespective of dose or seizing status of animals after exposure. Interestingly, when considering just the seizing status of animals, we found that the urine metabolome was markedly altered. Leukotriene C4, kynurenic acid, 5-hydroxyindoleacetic acid, norepinephrine, and aldosterone were excreted at much higher rates at 72 hrs in seizing animals, consistent with early multi-organ involvement during soman poisoning. However, at 75 days post soman exposure, bacterial biota stabilized and no differences were observed. These findings demonstrate the feasibility of using the dysbiosis of fecal bacterial biota in combination with urine metabolome alterations as forensic evidence for OP exposure temporally.\n\nImportanceThe paucity of assays to determine physiologically relevant OP exposure presents an opportunity to explore the use bacterial sentinels in combination with urine to assess changes in the exposed host. Recent advances in technologies and computational approaches have enabled researches to survey large community level changes of gut bacterial biota and metabolomic changes in various biospecimens. Here, we profile combined changes in bacterial biota and urine metabolome due to chemical warfare OP exposure. The significance of our work is to reveal that monitoring bacterial biota and urine metabolites as surrogates of OP exposure in biospecimens suitable for existing clinical laboratory workflows is plausible without the need for the development of new technology, invasive procedures, or complicated analytical approaches. The larger value of such an approach is that any setting with a moderate clinical chemistry and microbiology capability can determine pre-symptomatic exposure to enhance current triage standards in case of mass exposures, refugee movements, humanitarian missions, and training settings once an algorithm has been validated. In the event of \"potential\" exposures by time or distance, this assay can be further developed to estimate affected radius or time dimension for health monitoring and treatment interventions.

physiology↗

bioRxiv2018

Phloem structure and development in Illicium parviflorum, a basal angiosperm shrub

Recent studies in canopy-dominant trees revealed a structure-function scaling of the phloem. However, whether axial scaling is conserved in woody plants of the understory, the environments of most basal-grade angiosperms, remains mysterious. We used seedlings and adult plants of the shrub Illicium parviflorum to explore the anatomy and physiology of the phloem in their aerial parts, and possible changes through ontogeny. Adult plants maintain a similar proportion of phloem tissue across stem diameters, but scaling of conduit dimensions and number decreases the hydraulic resistance towards the base of the plant. Yet, the small sieve plate pores resulted in an overall higher sieve tube hydraulic resistance than has been reported in other woody angiosperms. Sieve elements scaled from minor to major leaf veins, but were shorter and narrower in petioles. The low carbon assimilation rates of seedlings and mature plants contrasted with a three-fold higher phloem sap velocity in seedlings, suggesting that phloem transport velocity is modulated through ontogeny. While the overall architecture of the phloem tissue in basal-angiosperm understory shrubs scales in a manner consistent with trees, modification of conduit connections may have allowed woody angiosperms to extend beyond their understory origins.

physiology↗

bioRxiv2018

Validation of an automated segmentation algorithm for lower leg MR images, applied to sodium quantification

ObjectiveTo develop and validate an automated segmentation algorithm for the lower leg using a multi-parametric magnetic resonance imaging protocol.\n\nMethodsAn automated algorithm combining active contour and intensity-based thresholding methods was developed to identify skin and muscle regions from proton Dixon MR images of the lower leg. Tissue sodium concentration was then computed using contemporaneously acquired sodium images with calibrated phantoms in the field of view. Resulting sodium concentration measurements were compared to a gold standard manual segmentation in 126 scans.\n\nResultsMost cases had no observable errors in segmentation of muscle and skin. Six cases had minor errors that were not expected to affect quantification; in the worst, 126 mm2 (2%) of a muscle area of 8,042 mm2 was misclassified. In one case the algorithm failed to separate the tibia from the muscle compartment. Correlation between automated and manual measurements of sodium concentration was R2 = 0.84 for skin, R2 = 0.99 for muscle. Additionally, the RMSE was 2.4mM for skin and 0.5mM for muscle; the observed physiological range was 8.5 to 37.4mM.\n\nConclusionFor the purpose of estimating sodium concentrations in muscle and skin compartments, the automated segmentations provided equally accurate results compared to the more time-intensive manual segmentations. Sodium quantification serves as a biomarker for disease progression, which would assist with early diagnostic treatments. The proposed algorithm will improve workflow, reproducibility, and consistency in such studies.

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