Capillary interactions drive the self-organization of bacterial colonies.

Many bacteria inhabit thin layers of water on solid surfaces both naturally in soils or on hosts or textiles and in the lab on agar hydrogels. In these environments, cells experience capillary forces, yet an understanding of how these forces shape bacterial collective behaviors remains elusive. Here, we show that the water menisci formed around bacteria lead to capillary attraction between cells while still allowing them to slide past one another. We develop an experimental apparatus that allows us to control bacterial collective behaviors by varying the strength and range of capillary forces. Combining 3D imaging and cell tracking with agent-based modeling, we demonstrate that capillary attraction organizes rod-shaped bacteria into densely packed, nematic groups, and profoundly influences their collective dynamics and morphologies. Our results suggest that capillary forces may be a ubiquitous physical ingredient in shaping microbial communities in partially hydrated environments.

Relationships between nitric oxide biomarkers and physiological outcomes following dietary nitrate supplementation.

Dietary nitrate (NO3-) supplementation can increase nitric oxide (NO) bioavailability, reduce blood pressure (BP) and improve muscle contractile function in humans. Plasma nitrite concentration (plasma [NO2-]) is the most oft-used biomarker of NO bioavailability. However, it is unclear which of several NO biomarkers (NO3-, NO2-, S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle correlate with the physiological effects of acute and chronic dietary NO3- supplementation. Using a randomized, double-blind, crossover design, 12 participants (9 males) consumed NO3--rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3--depleted placebo beetroot juice (PL) acutely and then chronically (for two weeks). Biological samples were collected, resting BP was assessed, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5-3.5 h following supplement ingestion on day 1 and day 14. Diastolic BP was significantly lower in BR (-2 ± 3 mmHg, P = 0.03) compared to PL following acute supplementation, while the absolute rate of torque development (RTD) was significantly greater in BR at 0-30 ms (39 ± 57 N m s-1, P = 0.03) and 0-50 ms (79 ± 99 N m s-1, P = 0.02) compared to PL following two weeks supplementation. Greater WB [RSNOs] rather than plasma [NO2-] was correlated with lower diastolic BP (r = -0.68, P = 0.02) in BR compared to PL following acute supplementation, while greater skeletal muscle [NO3-] was correlated with greater RTD at 0-30 ms (r = 0.64, P=0.03) in BR compared to PL following chronic supplementation. We conclude that [RSNOs] in blood, and [NO3-] in skeletal muscle, are relevant biomarkers of NO bioavailability which are related to the reduction of BP and the enhanced muscle contractile function following dietary NO3- ingestion in humans.

Rheological Dynamics of Active Myxococcus xanthus Populations during Development.

The bacterium Myxococcus xanthus produces multicellular droplets called fruiting bodies when starved. These structures form initially through the active dewetting of a vegetative biofilm into surface-associated droplets. This motility-driven aggregation is succeeded by a primitive developmental process in which cells in the droplets mature into nonmotile spores. Here, we use atomic force microscopy to probe the mechanics of these droplets throughout their formation. Using a combination of time- and frequency-domain rheological experiments, we characterize and develop a simple model of the linear viscoelasticity of these aggregates. We then use this model to quantify how cellular behaviors predominant at different developmental times-motility during the dewetting phase and cellular sporulation during later development-manifest as decreased droplet viscosity and increased elasticity, respectively.

Reduction in blood pressure following acute dietary nitrate ingestion is correlated with increased red blood cell S-nitrosothiol concentrations.

Dietary nitrate (NO3-) supplementation can enhance nitric oxide (NO) bioavailability and lower blood pressure (BP) in humans. The nitrite concentration ([NO2-]) in the plasma is the most commonly used biomarker of increased NO availability. However, it is unknown to what extent changes in other NO congeners, such as S-nitrosothiols (RSNOs), and in other blood components, such as red blood cells (RBC), also contribute to the BP lowering effects of dietary NO3-. We investigated the correlations between changes in NO biomarkers in different blood compartments and changes in BP variables following acute NO3- ingestion. Resting BP was measured and blood samples were collected at baseline, and at 1, 2, 3, 4 and 24 h following acute beetroot juice (∼12.8 mmol NO3-, ∼11 mg NO3-/kg) ingestion in 20 healthy volunteers. Spearman rank correlation coefficients were determined between the peak individual increases in NO biomarkers (NO3-, NO2-, RSNOs) in plasma, RBC and whole blood, and corresponding decreases in resting BP variables. No significant correlation was observed between increased plasma [NO2-] and reduced BP, but increased RBC [NO2-] was correlated with decreased systolic BP (rs = -0.50, P = 0.03). Notably, increased RBC [RSNOs] was significantly correlated with decreases in systolic (rs = -0.68, P = 0.001), diastolic (rs = -0.59, P = 0.008) and mean arterial pressure (rs = -0.64, P = 0.003). Fisher's z transformation indicated no difference in the strength of the correlations between increases in RBC [NO2-] or [RSNOs] and decreased systolic blood pressure. In conclusion, increased RBC [RSNOs] may be an important mediator of the reduction in resting BP observed following dietary NO3- supplementation.

15 N-labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production.

AIM: Dietary nitrate (NO3 - ) supplementation increases nitric oxide bioavailability and can enhance exercise performance. We investigated the distribution and metabolic fate of ingested NO3 - at rest and during exercise with a focus on skeletal muscle. METHODS: In a randomized, crossover study, 10 healthy volunteers consumed 12.8 mmol 15 N-labeled potassium nitrate (K15 NO3 ; NIT) or potassium chloride placebo (PLA). Muscle biopsies were taken at baseline, at 1- and 3-h post-supplement ingestion, and immediately following the completion of 60 maximal intermittent contractions of the knee extensors. Muscle, plasma, saliva, and urine samples were analyzed using chemiluminescence to determine absolute [NO3 - ] and [NO2 - ], and by mass spectrometry to determine the proportion of NO3 - and NO2 - that was 15 N-labeled. RESULTS: Neither muscle [NO3 - ] nor [NO2 - ] were altered by PLA. Following NIT, muscle [NO3 - ] (but not [NO2 - ]) was elevated at 1-h (from ~35 to 147 nmol/g, p < 0.001) and 3-h, with almost all of the increase being 15 N-labeled. There was a significant reduction in 15 N-labeled muscle [NO3 - ] from pre- to post-exercise. Relative to PLA, mean muscle torque production was ~7% greater during the first 18 contractions following NIT. This improvement in torque was correlated with the pre-exercise 15 N-labeled muscle [NO3 - ] and the magnitude of decline in 15 N-labeled muscle [NO3 - ] during exercise (r = 0.66 and r = 0.62, respectively; p < 0.01). CONCLUSION: This study shows, for the first time, that skeletal muscle rapidly takes up dietary NO3 - , the elevated muscle [NO3 - ] following NO3 - ingestion declines during exercise, and muscle NO3 - dynamics are associated with enhanced torque production during maximal intermittent muscle contractions.

Accounting for Dynamic Changes in the Power-Duration Relationship Improves the Accuracy of W' Balance Modeling.

PURPOSE: This study aimed 1) to examine the accuracy with which W' reconstitution (W' REC ) is estimated by the W' balance (W' BAL ) models after a 3-min all-out cycling test (3MT), 2) to determine the effects of a 3MT on the power-duration relationship, and 3) to assess whether accounting for changes in the power-duration relationship during exercise improved estimates of W' REC . METHODS: The power-duration relationship and the actual and estimated W' REC were determined for 12 data sets extracted from our laboratory database where participants had completed two 3MT separated by 1-min recovery (i.e., control [C-3MT] and fatigued [F-3MT]). RESULTS: Actual W' REC (6.3 ± 1.4 kJ) was significantly overestimated by the W' BAL·ODE (9.8 ± 1.3 kJ; P < 0.001) and the W' BAL·MORTON (16.9 ± 2.6 kJ; P < 0.001) models but was not significantly different to the estimate provided by the W' BAL·INT (7.5 ± 1.5 kJ; P > 0.05) model. End power (EP) was 7% lower in the F-3MT (263 ± 40 W) compared with the C-3MT (282 ± 44 W; P < 0.001), and work done above EP (WEP) was 61% lower in the F-3MT (6.3 ± 1.4 kJ) compared with the C-3MT (16.9 ± 3.2 kJ). The size of the error in the estimated W' REC was correlated with the reduction in WEP for the W' BAL·INT and W' BAL·ODE models (both r > -0.74, P < 0.01) but not the W' BAL·MORTON model ( r = -0.18, P > 0.05). Accounting for the changes in the power-duration relationship improved the accuracy of the W' BAL·ODE and W' BAL·MORTON , but they remained significantly different to actual W' REC . CONCLUSIONS: These findings demonstrate that the power-duration relationship is altered after a 3MT, and accounting for these changes improves the accuracy of the W' BAL·ODE and the W' BAL·MORTON , but not W' BAL·INT models. These results have important implications for the design and use of mathematical models describing the energetics of exercise performance.

Attitudes and awareness of Australian women regarding peripartum antibiotic use: A multicentre survey.

BACKGROUND: Peripartum antibiotics are commonly administered. Little is known of the attitudes of pregnant women toward peripartum antibiotics. AIM: We aimed to assess the awareness of and attitudes toward peripartum antibiotic use in Australian women. MATERIALS AND METHODS: We surveyed post-partum women at three hospitals over six months. Women reported if they received antibiotics 48 h either side of delivery and responded to statements assessing attitudes to peripartum antibiotic use. Administered antibiotics were recorded. We reported the proportion receiving antibiotics and the proportion aware of receiving them. Participants responded on five-point Likert scales and selected side effects of concern. RESULTS: Participants responding were 248 of 299 (83%, Royal Brisbane and Women's Hospital), 56 of 106 (53%, Caboolture Hospital) and 17 (Redcliffe Hospital, denominator not recorded). Of 183 (57%) receiving antibiotics, 134 (73%) received them pre-delivery only, 18 (10%) post-delivery only and 31 (17%) pre- and post-delivery. Pre-delivery, the most common indication was pre-incisional prophylaxis for caesarean delivery (93 of 160 responses, 58%). Seventy-nine (51%, 156 responses) of those receiving pre-delivery antibiotics were aware. Of 49 women receiving post-delivery antibiotics, 36 (73%) were aware. Most agreed they were worried that pre-delivery antibiotics would affect their baby (198, 62%) and 160 (50%) were concerned about effects on their own microbiome. Most (204, 65%) agreed they would rather not take antibiotics while breastfeeding. CONCLUSION: Many women were unaware of receiving pre-delivery antibiotics. Most had concerns about side effects. Improved communication regarding peripartum antibiotic use would improve patient-centred care.

Living donor liver transplantation versus donation after brain death and donation after circulatory death liver transplantation in the US.

While previous research has compared outcomes between living donor liver transplantation (LDLT) and deceased donor liver transplantation, evidence is lacking regarding how donation after circulatory death (DCD) vs donation after brain death (DBD) affects this comparison. Using data from the Scientific Registry of Transplant Recipients for adults listed for liver transplant from 2012 to 2018, we compared 5-year patient and graft survival, readmissions, posttransplant chronic kidney disease (CKD), and return to work for 25,151 patients who underwent LDLT (1223 [4.9%]), DCD-LT (1431 [6.4%]), and DBD-LT (22,497 [89.4%]). LDLT recipients were significantly more likely to have a Model for End-Stage Liver Disease (MELD) score < 15 and to be working prior to transplant (P < 0.001 for both). At 5 years posttransplant, LDLT recipients had significantly more readmissions, but significantly less CKD and better survival than DBD-LT and DCD-LT recipients, as well as significantly better graft survival than DCD-LT recipients (P ≤ 0.01 for all). Significantly more LDLT recipients also returned to work for income (P < 0.01). This study shows a clear advantage of LDLT vs DCD-LT. This information should be weighed in transplantation decisions for patients such as those with low MELD scores who will realistically only be considered for DCD-LT.

Pseudomonas aeruginosa distinguishes surfaces by stiffness using retraction of type IV pili.

The ability of eukaryotic cells to differentiate surface stiffness is fundamental for many processes like stem cell development. Bacteria were previously known to sense the presence of surfaces, but the extent to which they could differentiate stiffnesses remained unclear. Here we establish that the human pathogen Pseudomonas aeruginosa actively measures surface stiffness using type IV pili (TFP). Stiffness sensing is nonlinear, as induction of the virulence factor regulator is peaked with stiffness in a physiologically important range between 0.1 kPa (similar to mucus) and 1,000 kPa (similar to cartilage). Experiments on surfaces with distinct material properties establish that stiffness is the specific biophysical parameter important for this sensing. Traction force measurements reveal that the retraction of TFP is capable of deforming even stiff substrates. We show how slow diffusion of the pilin PilA in the inner membrane yields local concentration changes at the base of TFP during extension and retraction that change with substrate stiffness. We develop a quantitative biomechanical model that explains the transcriptional response to stiffness. A competition between PilA diffusion in the inner membrane and a loss/gain of monomers during TFP extension/retraction produces substrate stiffness-dependent dynamics of the local PilA concentration. We validated this model by manipulating the ATPase activity of the TFP motors to change TFP extension and retraction velocities and PilA concentration dynamics, altering the stiffness response in a predictable manner. Our results highlight stiffness sensing as a shared behavior across biological kingdoms, revealing generalizable principles of environmental sensing across small and large cells.

Time course of human skeletal muscle nitrate and nitrite concentration changes following dietary nitrate ingestion.

Dietary nitrate (NO3-) ingestion can be beneficial for health and exercise performance. Recently, based on animal and limited human studies, a skeletal muscle NO3- reservoir has been suggested to be important in whole body nitric oxide (NO) homeostasis. The purpose of this study was to determine the time course of changes in human skeletal muscle NO3- concentration ([NO3-]) following the ingestion of dietary NO3-. Sixteen participants were allocated to either an experimental group (NIT: n = 11) which consumed a bolus of ∼1300 mg (12.8 mmol) potassium nitrate (KNO3), or a placebo group (PLA: n = 5) which consumed a bolus of potassium chloride (KCl). Biological samples (muscle (vastus lateralis), blood, saliva and urine) were collected shortly before NIT or PLA ingestion and at intervals over the course of the subsequent 24 h. At baseline, no differences were observed for muscle [NO3-] and [NO2-] between NIT and PLA (P > 0.05). In PLA, there were no changes in muscle [NO3-] or [NO2-] over time. In NIT, muscle [NO3-] was significantly elevated above baseline (54 ± 29 nmol/g) at 0.5 h, reached a peak at 3 h (181 ± 128 nmol/g), and was not different to baseline from 9 h onwards (P > 0.05). Muscle [NO2-] did not change significantly over time. Following ingestion of a bolus of dietary NO3-, skeletal muscle [NO3-] increases rapidly, reaches a peak at ∼3 h and subsequently declines towards baseline values. Following dietary NO3- ingestion, human m. vastus lateralis [NO3-] expressed a slightly delayed pharmacokinetic profile compared to plasma [NO3-].

Highly Cushioned Shoes Improve Running Performance in Both the Absence and Presence of Muscle Damage.

PURPOSE: We tested the hypotheses that a highly cushioned running shoe (HCS) would 1) improve incremental exercise performance and reduce the oxygen cost (Oc) of submaximal running, and 2) attenuate the deterioration in Oc elicited by muscle damage consequent to a downhill run. METHODS: Thirty-two recreationally active participants completed an incremental treadmill test in an HCS and a control running shoe (CON) for the determination of Oc and maximal performance. Subsequently, participants were pair matched and randomly assigned to one of the two footwear conditions to perform a moderate-intensity running bout before and 48 h after a 30-min downhill run designed to elicit muscle damage. RESULTS: Incremental treadmill test performance was improved (+5.7%; +1:16 min:ss; P < 0.01) in the HCS when assessed in the nondamaged state, relative to CON. This coincided with a significantly lower Oc (-3.2%; -6 mL·kg-1·km-1; P < 0.001) at a range of running speeds and an increase in the speed corresponding to 3 mM blood lactate (+3.2%; +0.4 km·h-1; P < 0.05). As anticipated, the downhill run resulted in significant changes in biochemical, histological, and perceptual markers of muscle damage, and a significant increase in Oc (+5.2%; 10.1 mL·kg-1·km-1) was observed 48 h post. In the presence of muscle damage, Oc was significantly lower in HCS (-4.6%; -10 mL·kg-1·km-1) compared with CON. CONCLUSIONS: These results indicate that HCS improved incremental exercise performance and Oc in the absence of muscle damage and show, for the first time, that despite worsening of Oc consequent to muscle damage, improved Oc in HCS is maintained.

Physiological and performance effects of dietary nitrate and N-acetylcysteine supplementation during prolonged heavy-intensity cycling.

The purpose of this study was to investigate effects of concurrent and independent administration of dietary nitrate (NO3-), administered as NO3--rich beetroot juice (BR; ~12.4 mmol of NO3-), and N-acetylcysteine (NAC; 70 mg·kg-1) on physiological responses during prolonged exercise and subsequent high-intensity exercise tolerance. Sixteen recreationally active males supplemented with NO3--depleted beetroot juice (PL) or BR for 6 days and ingested an acute dose of NAC or maltodextrin (MAL) 1 h prior to performing 1 h of heavy-intensity cycling exercise immediately followed by a severe-intensity time-to-exhaustion (TTE) test in four conditions: 1) PL+MAL, 2) PL+NAC, 3) BR+MAL and 4) BR+NAC. Pre-exercise plasma [NO3-] and nitrite ([NO2-]) were elevated following BR+NAC  and BR+MAL (both P < 0.01) compared with PL+NAC and PL+MAL; plasma [cysteine] was increased in PL+NAC  and BR+NAC (both P < 0.01) compared to PL+MAL. Muscle excitability declined over time during the prolonged cycling bout in all conditions  but was better preserved in PL+NAC  compared to BR+NAC (P < 0.01) and PL+MAL (P < 0.05). There was no effect of supplementation on subsequent TTE . These findings indicate that co-ingestion of BR and NAC does not appreciably alter physiological responses during prolonged heavy-intensity cycling or enhance subsequent exercise tolerance.

Development and Evaluation of a Point-of-Care Test in a Low-Resource Setting with High Rates of Chlamydia trachomatis Urogenital Infections in Fiji.

Rapid and precise detection of Chlamydia trachomatis, the leading global cause of sexually transmitted infections (STI), at the point of care (POC) is required for treatment decisions to prevent transmission and sequelae, including pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and preterm birth. We developed a rapid POC test (POCT), termed LH-POCT, which uses loop-mediated amplification (LAMP) of nucleic acids. We performed a head-to-head comparison with the Cepheid Xpert CT/NG assay using clinician-collected, deidentified paired vaginal samples from a parent study that consecutively enrolled symptomatic and asymptomatic females over 18 years of age from the Ministry of Health and Medical Services Health Centers in Fiji. Samples were processed by the Xpert CT/NG assay and LH-POCT, blinded to the comparator. Discrepant samples were resolved by quantitative PCR. Deidentified clinical data and tests for Trichomonas vaginalis, Candida, and bacterial vaginosis (BV) were provided. There were a total of 353 samples from 327 females. C. trachomatis positivity was 16.7% (59/353), while the prevalence was 16.82% (55/327) after discrepant resolution. Seven discrepant samples resolved to four false negatives, two false positives, and one true positive for the LH-POCT. The sensitivity of the LH-POCT was 93.65% (95% confidence interval [CI], 84.53% to 98.24%), and specificity was 99.31% (95% CI, 97.53% to 99.92%). Discrepant samples clustered among women with vaginal discharge and/or BV. The prototype LH-POCT workflow has excellent performance, meeting many World Health Organization ASSURED criteria for POC tests, including a sample-to-result time of 35 min. Our LH-POCT holds promise for improving clinical practice to prevent and control C. trachomatis STIs in diverse health care settings globally.

Is internal mammary artery graft beneficial in emergent coronary artery bypass surgery? A Society of Thoracic Surgeons national database analysis.

BACKGROUND: Often, only saphenous vein grafts (SVGs) are used in emergent coronary artery bypass graft (CABG) procedures to provide quicker myocardial revascularization despite its lower long-term patency relative to the internal mammary artery (IMA) grafts. We examined differences between IMA and non-IMA graft recipients in emergent CABGs and its impact on in-hospital outcomes. METHODS: Retrospective review of Society of Thoracic Surgeon National Database was done to identify patients age ≥18 years undergoing primary emergent isolated CABG between 2013 and 2016. Emergent salvage, non-LAD disease, subclavian stenosis and revascularization with other arterial grafts were excluded. The study population was divided in two groups: IMA and non-IMA groups. Demographics, preoperative, intraoperative factors and postoperative outcomes were analyzed between the groups. RESULTS: Of 18,280 emergent CABGs during the study period, 16281 had IMA used and 1999 had only vein grafts. The IMA group was younger, more likely to be male, had lower creatinine and higher ejection fraction. The non-IMA and IMA groups were then propensity risk matched with ratio of 1:2 which showed significantly higher in-hospital mortality in the non-IMA group (15% vs. 7%, P<0.0001). The non-IMA groups also had higher rates bleeding (5% vs. 3%, P<0.01), renal failure (10% vs.6%, P<0.0001) and prolonged vent (44% vs. 30%, P<0.0001). CONCLUSIONS: IMA grafts in primary isolated emergent CABGs are associated with significantly lower rates of in-hospital mortality. Even for emergent CABG there may be a clinical benefit in using IMA grafts rather than SVGs only.

The Anthropometry of Economical Running.

The influence of anthropometry and body composition on running economy is unclear, with previous investigations involving small relatively homogeneous groups of runners and limited anthropometric/composition measurements. PURPOSE: To comprehensively investigate the relationships of anthropometry and body composition with running economy within a large heterogeneous sample of runners. METHODS: Eighty-five runners (males [M], n = 45; females [F], n = 40), of diverse competitive standard, performed a discontinuous protocol of incremental treadmill running (4-min stages, 1 km·h increments) to establish locomotory energy cost (LEc) of running at submaximal speeds (averaged across 10-12 km·h; the highest common speed < lactate turnpoint). Measurements of anthropometry, including segment lengths, perimeters, masses and moments of inertia, and body composition were obtained using tape-based measurements and dual-energy x-ray absorptiometry. RESULTS: Absolute LEc (ABSLEc, kcal·km) was positively correlated with 21 (of 27) absolute anthropometric variables in both male and female cohorts. Multiple-regression analyses revealed that one variable (mean perimeter z score) explained 49.4% (M) and 68.9% (F) of the variance in ABSLEc. Relative LEc (RELLEc, kcal·kg·km) was also correlated with five (M) and seven (F) normalized anthropometric variables, and regression analyses explained 31.6% (M; percentage bone mass and normalized hip perimeter) and 33.3% (F, normalized forearm perimeter) of the variance in RELLEc. CONCLUSIONS: These findings provide novel and robust evidence that anthropometry and body composition variables, predominantly indicative of relative slenderness, explain a considerable proportion of the variance in running economy (i.e., more slender, lower energy cost). We, therefore, recommend that runners and coaches are attentive to relative slenderness in selecting and training athletes with the aim of enhancing running economy, and improving distance running performance.

Diaphragmatic fenestrations seen after peritoneal dialysis catheter placement: A rare cause of hydrothorax.

This case report summarizes the clinical course of a patient who developed diaphragmatic fenestrations leading to hydrothorax after the initiation of peritoneal dialysis. We will discuss the interesting disease process in the setting of patient presentation, diagnosis, treatment, and outcome.

Response to considerations regarding Maximal Lactate Steady State determination before redefining the gold-standard.

We reinforce the key messages in our earlier review paper that critical power, rather than maximal lactate steady state, provides the better index for defining steady-state vs non-steady state physiological behaviour during exercise.

Human skeletal muscle nitrate store: influence of dietary nitrate supplementation and exercise.

KEY POINTS: Nitric oxide (NO), a potent vasodilator and a regulator of many physiological processes, is produced in mammals both enzymatically and by reduction of nitrite and nitrate ions. We have previously reported that, in rodents, skeletal muscle serves as a nitrate reservoir, with nitrate levels greatly exceeding those in blood or other internal organs, and with nitrate being reduced to NO during exercise. In the current study, we show that nitrate concentration is substantially greater in skeletal muscle than in blood and is elevated further by dietary nitrate ingestion in human volunteers. We also show that high-intensity exercise results in a reduction in the skeletal muscle nitrate store following supplementation, likely as a consequence of its reduction to nitrite and NO. We also report the presence of sialin, a nitrate transporter, and xanthine oxidoreductase in human skeletal muscle, indicating that muscle has the necessary apparatus for nitrate transport, storage and metabolism. ABSTRACT: Rodent skeletal muscle contains a large store of nitrate that can be augmented by the consumption of dietary nitrate. This muscle nitrate reservoir has been found to be an important source of nitrite and nitric oxide (NO) via its reduction by tissue xanthine oxidoreductase. To explore if this pathway is also active in human skeletal muscle during exercise, and if it is sensitive to local nitrate availability, we assessed exercise-induced changes in muscle nitrate and nitrite concentrations in young healthy humans, under baseline conditions and following dietary nitrate consumption. We found that baseline nitrate and nitrite concentrations were far higher in muscle than in plasma (∼4-fold and ∼29-fold, respectively), and that the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (∼19-fold) and muscle (∼5-fold). Consistent with these observations, and with previous suggestions of active muscle nitrate transport, we present western blot data to show significant expression of the active nitrate/nitrite transporter sialin in human skeletal muscle. Furthermore, we report an exercise-induced reduction in human muscle nitrate concentration (by ∼39%), but only in the presence of an increased muscle nitrate store. Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise. Together, these findings suggest that skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans.