Exercise-induced potentiation of the acute hypoxic ventilatory response: Neural mechanisms and implications for cerebral blood flow.

A given dose of hypoxia causes a greater increase in pulmonary ventilation during physical exercise than during rest, representing an exercise-induced potentiation of the acute hypoxic ventilatory response (HVR). This phenomenon occurs independently from hypoxic blood entering the contracting skeletal muscle circulation or metabolic byproducts leaving skeletal muscles, supporting the contention that neural mechanisms per se can mediate the HVR when humoral mechanisms are not at play. However, multiple neural mechanisms might be interacting intricately. First, we discuss the neural mechanisms involved in the ventilatory response to hypoxic exercise and their potential interactions. Current evidence does not support an interaction between the carotid chemoreflex and central command. In contrast, findings from some studies support synergistic interactions between the carotid chemoreflex and the muscle mechano- and metaboreflexes. Second, we propose hypotheses about potential mechanisms underlying neural interactions, including spatial and temporal summation of afferent signals into the medulla, short-term potentiation and sympathetically induced activation of the carotid chemoreceptors. Lastly, we ponder how exercise-induced potentiation of the HVR results in hyperventilation-induced hypocapnia, which influences cerebral blood flow regulation, with multifaceted potential consequences, including deleterious (increased central fatigue and impaired cognitive performance), inert (unchanged exercise) and beneficial effects (protection against excessive cerebral perfusion).

Altered locomotor muscle metaboreflex control of ventilation in patients with COPD.

We investigated the locomotor muscle metaboreflex control of ventilation, circulation, and dyspnea in patients with chronic obstructive pulmonary disease (COPD). Ten patients [forced expiratory volume in 1 second (FEV1; means ± SD) = 43 ± 17% predicted] and nine age- and sex-matched controls underwent 1) cycling exercise followed by postexercise circulatory occlusion (PECO) to activate the metaboreflex or free circulatory flow to inactivate it, 2) cold pressor test to interpret whether any altered reflex response was specific to the metaboreflex arc, and 3) muscle biopsy to explore the metaboreflex arc afferent side. We measured airflow, dyspnea, heart rate, arterial pressure, muscle blood flow, and vascular conductance during reflexes activation. In addition, we measured fiber types, glutathione redox balance, and metaboreceptor-related mRNAs in the vastus lateralis. Metaboreflex activation increased ventilation versus free flow in patients (∼15%, P < 0.020) but not in controls (P > 0.450). In contrast, metaboreflex activation did not change dyspnea in patients (P = 1.000) but increased it in controls (∼100%, P < 0.001). Other metaboreflex-induced responses were similar between groups. Cold receptor activation increased ventilation similarly in both groups (P = 0.46). Patients had greater type II skeletal myocyte percentage (14%, P = 0.010), lower glutathione ratio (-34%, P = 0.015), and lower nerve growth factor (NGF) mRNA expression (-60%, P = 0.031) than controls. Therefore, COPD altered the locomotor muscle metaboreflex control of ventilation. It increased type II myocyte percentage and elicited redox imbalance, potentially producing more muscle metaboreceptor stimuli. Moreover, it decreased NGF expression, suggesting a downregulation of metabolically sensitive muscle afferents.NEW & NOTEWORTHY This study's integrative physiology approach provides evidence for a specific alteration in locomotor muscle metaboreflex control of ventilation in patients with COPD. Furthermore, molecular analyses of a skeletal muscle biopsy suggest that the amount of muscle metaboreceptor stimuli derived from type II skeletal myocytes and redox imbalance overcame a downregulation of metabolically sensitive muscle afferents.

The virome of the invasive Asian bush mosquito Aedes japonicus in Europe.

The Asian bush mosquito Aedes japonicus is rapidly invading North America and Europe. Due to its potential to transmit multiple pathogenic arthropod-borne (arbo)viruses including Zika virus, West Nile virus, and chikungunya virus, it is important to understand the biology of this vector mosquito in more detail. In addition to arboviruses, mosquitoes can also carry insect-specific viruses that are receiving increasing attention due to their potential effects on host physiology and arbovirus transmission. In this study, we characterized the collection of viruses, referred to as the virome, circulating in Ae. japonicus populations in the Netherlands and France. Applying a small RNA-based metagenomic approach to Ae. japonicus, we uncovered a distinct group of viruses present in samples from both the Netherlands and France. These included one known virus, Ae. japonicus narnavirus 1 (AejapNV1), and three new virus species that we named Ae. japonicus totivirus 1 (AejapTV1), Ae. japonicus anphevirus 1 (AejapAV1) and Ae. japonicus bunyavirus 1 (AejapBV1). We also discovered sequences that were presumably derived from two additional novel viruses: Ae. japonicus bunyavirus 2 (AejapBV2) and Ae. japonicus rhabdovirus 1 (AejapRV1). All six viruses induced strong RNA interference responses, including the production of twenty-one nucleotide-sized small interfering RNAs, a signature of active replication in the host. Notably, AejapBV1 and AejapBV2 belong to different viral families; however, no RNA-dependent RNA polymerase sequence has been found for AejapBV2. Intriguingly, our small RNA-based approach identified an ∼1-kb long ambigrammatic RNA that is associated with AejapNV1 as a secondary segment but showed no similarity to any sequence in public databases. We confirmed the presence of AejapNV1 primary and secondary segments, AejapTV1, AejapAV1, and AejapBV1 by reverse transcriptase polymerase chain reaction (PCR) in wild-caught Ae. japonicus mosquitoes. AejapNV1 and AejapTV1 were found at high prevalence (87-100 per cent) in adult females, adult males, and larvae. Using a small RNA-based, sequence-independent metagenomic strategy, we uncovered a conserved and prevalent virome among Ae. japonicus mosquito populations. The high prevalence of AejapNV1 and AejapTV1 across all tested mosquito life stages suggests that these viruses are intimately associated with Ae. japonicus.

Enhanced Respiratory Frequency Response to Lower Limb Mechanoreceptors Activation in Patients with Chronic Obstructive Pulmonary Disease.

PURPOSE: To investigate the mechanoreflex control of respiration and circulation in patients with chronic obstructive pulmonary disease (COPD). METHODS: Twenty-eight patients with moderate-to-severe COPD (mean ± SD: 67.0 ± 7.9 yr, 10 women) and 14 age- and sex-matched controls (67.9 ± 2.6 yr, 7 women) participated in the study. Their dominant knee was passively moved to stimulate mechanoreceptors, whereas vastus lateralis surface electrical activity checked active contractions. A differential pressure flowmeter, an electrocardiogram, and a servo-controlled finger photoplethysmograph acquired cardiorespiratory data. To gain insight into the mechanoreflex arc, we further analyzed reduced/oxidized glutathione ratio and mechanoreceptor-related gene expression in a vastus lateralis biopsy of additional nine patients (63.9 ± 8.1 yr, 33% women) and eight controls (62.9 ± 9.1 yr, 38% women). RESULTS: Patients with COPD had a greater peak respiratory frequency response (COPD: Δ = 3.2 ± 2.3 vs Controls: 1.8 ± 1.2 cycles per minute, P = 0.036) and a smaller peak tidal volume response to passive knee movement than controls. Ventilation, heart rate, stroke volume, and cardiac output peak responses, and total peripheral resistance nadir response, were unaltered by COPD. In addition, patients had a diminished glutathione ratio (COPD: 13.3 ± 3.8 vs controls: 20.0 ± 5.5 a.u., P = 0.015) and an augmented brain-derived neurotrophic factor expression (COPD: 2.0 ± 0.7 vs controls: 1.1 ± 0.4 a.u., P = 0.002) than controls. Prostaglandin E receptor 4, cyclooxygenase 2, and Piezo1 expression were similar between groups. CONCLUSIONS: Respiratory frequency response to mechanoreceptors activation is increased in patients with COPD. This abnormality is possibly linked to glutathione redox imbalance and augmented brain-derived neurotrophic factor expression within locomotor muscles, which could increase mechanically sensitive afferents' stimulation and sensitivity.

Prediction of gas production rate from shale gas reservoirs using a micro-macro analysis.

Shale gas has become one of the important contributors to the global energy supply. The declining pattern of the gas production rate with time from an unconventional gas reservoir is due to the depletion of shale gas stored in the nanovoids of the shale formation. However, there are only limited ways to predict the variation of the gas production rate with time from an unconventional gas reservoir. This is due to the multiple transport mechanisms of gas in nano-scale pores and changes in shale gas permeability with pressures in nano-scale pores, which is impacted by the pore structure of the shale. In this study, the permeability-pressure (K-p) relationship for different shales (Eagle Ford, Haynesville, Longmaxi and Opalinus) were determined using an equivalent anisotropic pore network model (PNM). This PNM has REV-scale shale gas flow in randomly generated nanovoids and their connection in the shale matrix, and the multiphase flow of shale gas including viscous flow, slip flow and Knudsen diffusion. These predicted K-p correlations were then used in a finite element model (FEM) to predict the variation of the gas production rate with time (flux-time curves) at the macroscale. The simulation results show that the flux-time curves can be simplified to two linear segments in logarithmic coordinates, which are influenced by the fracture length and initial gas pressure. The predicted results using the PNM-FEM were validated by comparing them with the reported field test data. The method described in this study can be used to upscale the gas transport process from micro- to macroscale, which can provide a predictive tool for the gas production in shales.

Rad5 HIRAN domain: Structural insights into its interaction with ssDNA through molecular modeling approaches.

The Rad5 protein is an SWI/SNF family ubiquitin ligase that contains an N-terminal HIRAN domain and a RING C3HC4 motif. The HIRAN domain is critical for recognition of the stalled replication fork during the replication process and acts as a sensor to initiate the damaged DNA checkpoint. It is a conserved domain widely distributed in eukaryotic organisms and is present in several DNA-binding proteins from all kingdoms. Here we showed that distant species have important differences in key residues that affect affinity for ssDNA. Based on these findings, we hypothesized that different HIRAN domains might affect fork reversal and translesion synthesis through different metabolic processes. To address this question, we predicted the tertiary structure of both yeast and human HIRAN domains using molecular modeling. Structural dynamics experiments showed that the yeast HIRAN domain exhibited higher structural denaturation than its human homolog, although both domains became stable in the presence of ssDNA. Analysis of atomic contacts revealed that a greater number of interactions between the ssDNA nucleotides and the Rad5 domain are electrostatic. Taken together, these results provide new insights into the molecular mechanism of the HIRAN domain of Rad5 and may guide us to further elucidate differences in the ancient eukaryotes HIRAN sequences and their DNA affinity.Communicated by Ramaswamy H. Sarma.

LMI-based consensus of linear multi-agent systems by reduced-order dynamic output feedback.

This work proposes new conditions for consensus of homogeneous multi-agent systems subjected to exogenous disturbances in directed communication graphs by dynamic output feedback protocols. The agents under investigation are described as linear dynamics, and the communication network is such that each agent receives as information only the output of neighbor agents. The synchronization problem is rewritten as an output feedback stabilization without requiring the Laplacian matrix to be diagonalizable. As the main appeal, we propose new necessary and sufficient conditions for the design of dynamic output feedback controllers of arbitrary order - including static output feedback as a particular case - and sufficient Linear Matrix Inequalities (LMIs) for H∞ consensus. Numerical experiments illustrate the effectiveness of the proposed approach.

Impact of de-ionized water on changes in porosity and permeability of shales mineralogy due to clay-swelling.

Hydraulic fracturing is widely applied for economical gas production from shale reservoirs. Still, the swelling of the clay micro/nano pores due to retained fluid from hydraulic fracturing causes a gradual reduction of gas production. Four different gas-bearing shale samples with different mineralogical characteristics were investigated to study the expected shale swelling and reduction in gas permeability due to hydraulic fracturing. To simulate shale softening, these shale samples were immersed in deionized (DI) water heated to 100 °C temperature and subjected to 8 MPa pressure in a laboratory reactor for 72 hours to simulate shale softening. The low-temperature nitrogen adsorption and density measurements were performed on the original and treated shale to determine the changes in micro and nano pore structure. The micro and nano pore structures changed, and the porosity decreased after shale treatment. The porosity decreased by 4% for clayey shale, while for well-cemented shale the porosity only decreased by 0.52%. The findings showed that the initial mineralogical composition of shale plays a significant role in the change of micro and nano pores and the pore structure alteration due to retained fluid from hydraulic fracturing. A pore network model is used to simulate the permeability of shale used in this study. To define pore structure properties, specific factors such as porosity, pore size, pore throat distribution, and coordination number were used. Furthermore, the anisotropy characteristics of shale were integrated into the model via a coordination number ratio. Finally, the change in permeability due to shale softening was determined and compared with untreated with the progress of shale softening. The simulation showed that the permeability of Longmaxi shale could decrease from 3.82E-16 m2 to 4.71E-17 m2 after treatment.

Cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension at rest and during orthostatic stress: role of the peripheral chemoreflex.

The baroreflex integrity in early-stage pulmonary arterial hypertension (PAH) remains uninvestigated. A potential baroreflex impairment could be functionally relevant and possibly mediated by enhanced peripheral chemoreflex activity. Thus, we investigated 1) the cardiac baroreflex in nonhypoxemic PAH; 2) the association between baroreflex indexes and peak aerobic capacity [i.e., peak oxygen consumption (V̇o2peak)]; and 3) the peripheral chemoreflex contribution to the cardiac baroreflex. Nineteen patients and 13 age- and sex-matched healthy adults (HA) randomly inhaled either 100% O2 (peripheral chemoreceptor inhibition) or 21% O2 (control session) while at rest and during a repeated sit-to-stand maneuver. Beat-by-beat analysis of R-R intervals and systolic blood pressure provided indexes of cardiac baroreflex sensitivity (cBRS) and effectiveness (cBEI). The PAH group had lower cBEI for all sequences (cBEIALL) at rest [means ± SD: PAH = 0.5 ± 0.2 vs. HA = 0.7 ± 0.1 arbitrary units (a.u.), P = 0.02] and lower cBRSALL (PAH = 6.8 ± 7.0 vs. HA = 9.7 ± 5.0 ms·mmHg-1, P < 0.01) and cBEIALL (PAH = 0.4 ± 0.2 vs. HA= 0.6 ± 0.1 a.u., P < 0.01) during the sit-to-stand maneuver versus the HA group. The cBEI during the sit-to-stand maneuver was independently correlated to V̇o2peak (partial r = 0.45, P < 0.01). Hyperoxia increased cBRS and cBEI similarly in both groups at rest and during the sit-to-stand maneuver. Therefore, cardiac baroreflex dysfunction was observed under spontaneous and, most notably, provoked blood pressure fluctuations in nonhypoxemic PAH, was not influenced by the peripheral chemoreflex, and was associated with lower V̇o2peak, suggesting that it could be functionally relevant.NEW & NOTEWORTHY Does the peripheral chemoreflex play a role in cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension (PAH)? Here we provide new evidence of cardiac baroreflex dysfunction under spontaneous and, most notably, provoked blood pressure fluctuations in patients with nonhypoxemic PAH. Importantly, impaired cardiac baroreflex effectiveness during provoked blood pressure fluctuations was independently associated with poorer functional capacity. Finally, our results indicated that the peripheral chemoreflex did not mediate cardiac baroreflex dysfunction among those patients.

Intercostal and vastus lateralis microcirculatory response to a sympathoexcitatory manoeuvre in patients with chronic obstructive pulmonary disease.

Patients with COPD present with systemic vascular malfunctioning and their microcirculation is possibly more fragile to overcome an increase in the sympathetic vasoconstrictor outflow during sympathoexcitatory situations. To test the skeletal muscle microvascular responsiveness to sympathoexcitation, we asked patients with COPD and age- and sex-matched controls to immerse a hand in iced water [Cold Pressor Test (CPT)]. Near-infrared spectroscopy detection of the indocyanine green dye in the intercostal and vastus lateralis microcirculation provided a blood flow index (BFI). BFI divided by mean blood pressure (MBP) provided an index of microvascular conductance (BFI/MBP). The CPT decreased BFI and BFI/MBP in the intercostal (P = 0.01 and < 0.01, respectively) and vastus lateralis (P = 0.08 and 0.03, respectively) only in the COPD group, and the per cent BFI and BFI/MBP decrease was similar between muscles (P = 0.78 and 0.85, respectively). Thus, our findings support that sympathoexcitation similarly impairs intercostal and vastus lateralis microvascular regulation in patients with COPD.

Smart Artificial Markers for Accurate Visual Mapping and Localization.

Artificial marker mapping is a useful tool for fast camera localization estimation with a certain degree of accuracy in large indoor and outdoor environments. Nonetheless, the level of accuracy can still be enhanced to allow the creation of applications such as the new Visual Odometry and SLAM datasets, low-cost systems for robot detection and tracking, and pose estimation. In this work, we propose to improve the accuracy of map construction using artificial markers (mapping method) and camera localization within this map (localization method) by introducing a new type of artificial marker that we call the smart marker. A smart marker consists of a square fiducial planar marker and a pose measurement system (PMS) unit. With a set of smart markers distributed throughout the environment, the proposed mapping method estimates the markers' poses from a set of calibrated images and orientation/distance measurements gathered from the PMS unit. After this, the proposed localization method can localize a monocular camera with the correct scale, directly benefiting from the improved accuracy of the mapping method. We conducted several experiments to evaluate the accuracy of the proposed methods. The results show that our approach decreases the Relative Positioning Error (RPE) by 85% in the mapping stage and Absolute Trajectory Error (ATE) by 50% for the camera localization stage in comparison with the state-of-the-art methods present in the literature.

Towards the Use of Blockchain in Mobile Health Services and Applications.

With the advent of cryptocurrencies and blockchain, the growth and adaptation of cryptographic features and capabilities were quickly extended to new and underexplored areas, such as healthcare. Currently, blockchain is being implemented mainly as a mechanism to secure Electronic Health Records (EHRs). However, new studies have shown that this technology can be a powerful tool in empowering patients to control their own health data, as well for enabling a fool-proof health data history and establishing medical responsibility. Additionally, with the proliferation of mobile health (m-Health) sustained on service-oriented architectures, the adaptation of blockchain mechanisms into m-Health applications creates the possibility for a more decentralized and available healthcare service. Hence, this paper presents a review of the current security best practices for m-Health and the most used and widely known implementations of the blockchain protocol, including blockchain technologies in m-Health. The main goal of this comprehensive review is to further discuss and elaborate on identified open-issues and potential use cases regarding the uses of blockchain in this area. Finally, the paper presents the major findings, challenges and advantages on future blockchain implementations for m-Health services and applications.

The cardiovascular consequences of fatiguing expiratory muscle work in otherwise resting healthy humans.

In 11 healthy adults (25 ± 4 yr; 2 female, 9 male subjects), we investigated the effect of expiratory resistive loaded breathing [65% maximal expiratory mouth pressure (MEP), 15 breaths·min-1, duty cycle 0.5; ERLPm] on mean arterial pressure (MAP), leg vascular resistance (LVR), and leg blood flow ([Formula: see text]). On a separate day, a subset of five male subjects performed ERL targeting 65% of maximal expiratory gastric pressure (ERLPga). ERL-induced expiratory muscle fatigue was confirmed by a 17 ± 5% reduction in MEP (P < 0.05) and a 16 ± 12% reduction in the gastric twitch pressure response to magnetic nerve stimulation (P = 0.09) from before to after ERLPm and ERLPga, respectively. From rest to task failure in ERLPm and ERLPga, MAP increased (ERLPm = 31 ± 10 mmHg, ERLPga = 18 ± 9 mmHg, both P < 0.05), but group mean LVR and [Formula: see text] were unchanged (ERLPm: LVR = 0.78 ± 0.21 vs. 0.97 ± 0.36 mmHg·mL-1·min, [Formula: see text] = 133 ± 34 vs. 152 ± 74 mL·min-1; ERLPga: LVR = 0.70 ± 0.21 vs. 0.84 ± 0.33 mmHg·mL-1·min, [Formula: see text] = 160 ± 48 vs. 179 ± 110 mL·min-1) (all P ≥ 0.05). Interestingly, [Formula: see text] during ERLPga oscillated within each breath, increasing (∼66%) and decreasing (∼50%) relative to resting values during resisted expirations and unresisted inspirations, respectively. In conclusion, fatiguing expiratory muscle work did not affect group mean LVR or [Formula: see text] in otherwise resting humans. We speculate that any sympathetically mediated peripheral vasoconstriction was counteracted by transient mechanical effects of high intra-abdominal pressures during ERL.NEW & NOTEWORTHY Fatiguing expiratory muscle work in otherwise resting humans elicits an increase in sympathetic motor outflow; whether limb blood flow ([Formula: see text]) and leg vascular resistance (LVR) are affected remains unknown. We found that fatiguing expiratory resistive loaded breathing (ERL) did not affect group mean [Formula: see text] or LVR. However, within-breath oscillations in [Formula: see text] may reflect a sympathetically mediated vasoconstriction that was counteracted by transient increases in [Formula: see text] due to the mechanical effects of high intra-abdominal pressure during ERL.

Sex differences in fatigability after ischemic preconditioning of non-exercising limbs.

BACKGROUND: Ischemic preconditioning (IPC) is suggested to decrease fatigability in some individuals but not others. Sex differences in response to IPC may account for this variability and few studies systematically investigated the effects of IPC in men and women. The goal of this study was to determine if time to task failure, perception of pain, and neuromuscular mechanisms of fatigability were altered by IPC in men and women. METHODS: Ten women (29 ± 5 years old) and 10 men (28 ± 6 years old) performed isometric contractions with the plantar flexor muscles of the dominant leg at 20% of maximal voluntary contraction until task failure. We used a repeated measures design where each individual performed 3 randomized and counterbalanced test sessions: (A) IPC session, cuff inflation and deflation (5 min each repeated 3 times) performed before the exercise by inflating cuffs to the non-dominant leg and arm; (B) sham session, cuffs were inflated for a short period (1 min); and (C) control session, no cuffs were involved. RESULTS: Compared with control, IPC increased time to task failure in men (mean difference, 5 min; confidence interval (CI) of mean difference, 2.2; 7.8 min; P = 0.01) but not women (mean difference, - 0.6 min; CI of mean difference, - 3.5; 2.4 min; P = 0.51). In men, but not women, the IPC-induced increase in time to task failure was associated with lower response to pressure pain (r = - 0.79). IPC further exposed sex differences in arterial pressure during fatiguing contractions (session × sex: P < 0.05). Voluntary activation, estimated with the twitch interpolation technique, and presynaptic inhibition of leg Ia afferents were not altered after IPC for men and women. The tested variables were not altered with sham. CONCLUSIONS: The ergogenic effect of IPC on time to task failure was observed only in men and it was associated with reductions in the perception of pain. This pilot data suggest the previously reported inter-individual variability in exercise-induced fatigability after IPC could be a consequence of the sex and individual response to pain.

Modulation of spinal cord excitability following remote limb ischemic preconditioning in healthy young men.

Remote limb ischemic preconditioning (RIPC) has shown to improve dynamic postural control in humans. However, studies on the underlying adaptations of spinal cord networks have never been performed. The present work addresses this issue by investigating parameters from the soleus H-reflex recruitment curve (RC), presynaptic mechanisms of reflex modulation (presynaptic inhibition-PSI, and post activation depression-PAD), and the excursion of the center of pressure (CP) recorded during 1 min in upright stance over a compliant surface. A sham ischemic protocol (partial obstruction of blood flow) was applied to the contralateral thigh along four consecutive days. The same procedure was repeated with full obstruction (RIPC) three days after ending the sham protocol. Data were collected before and after both sham and RIPC protocols. The follow-up data were collected five days after the last ischemic intervention. Significant reduction was detected for both the fast oscillations of the CP (higher frequency components) and the parameter estimated from the RC corresponding to the high amplitude H-reflexes (p < 0.05). Even though the magnitude of effects was similar, it was washed out within three days after sham, but persisted for at least five days after RIPC. No significant differences were found for PSI and PAD levels across conditions. These findings indicate that RIPC leads to enduring changes in spinal cord excitability for the latest reflexively recruited motoneurons, along with improvement in balance control. However, these adaptations were not mediated by the presynaptic mechanisms currently assessed.

Carotid chemoreflex and muscle metaboreflex interact to the regulation of ventilation in patients with heart failure with reduced ejection fraction.

Synergism among reflexes probably contributes to exercise hyperventilation in patients with heart failure with reduced ejection fraction (HFrEF). Thus, we investigated whether the carotid chemoreflex and the muscle metaboreflex interact to the regulation of ventilation ( V˙E ) in HFrEF. Ten patients accomplished 4-min cycling at 60% peak workload and then recovered for 2 min under either: (a) 21% O2 inhalation (tonic carotid chemoreflex activity) with legs' circulation free (inactive muscle metaboreflex); (b) 100% O2 inhalation (suppressed carotid chemoreflex activity) with legs' circulation occluded (muscle metaboreflex activation); (c) 21% O2 inhalation (tonic carotid chemoreflex activity) with legs' circulation occluded (muscle metaboreflex activation); or (d) 100% O2 inhalation (suppressed carotid chemoreflex activity) with legs' circulation free (inactive muscle metaboreflex) as control. V˙E , tidal volume (VT ) and respiratory frequency (fR ) were similar between each separated reflex (protocols a and b) and control (protocol d). Calculated sum of separated reflexes effects was similar to control. Oppositely, V˙E (mean ± SEM: Δ vs. control = 2.46 ± 1.07 L/min, p = .05) and fR (Δ = 2.47 ± 0.77 cycles/min, p = .02) increased versus control when both reflexes were simultaneously active (protocol c). Therefore, the carotid chemoreflex and the muscle metaboreflex interacted to V˙E regulation in a fR -dependent manner in patients with HFrEF. If this interaction operates during exercise, it can have some contribution to the HFrEF exercise hyperventilation.

Verrucoconiothyrium ambiguum sp. nov., a novel species isolated from sea water, and affiliation of the genus Verrucoconiothyrium to the family Didymellaceae.

The genus Verrucoconiothyrium was erected to accommodate Coniothyrium-like species with verruculose conidia. So far, it includes only four species, which have been found in association with plants, and very little is known about their distribution and host preferences. In this study, a Coniothyrium-like fungus isolated from sea water from the north of Portugal was characterised. Phylogenetic analysis, based on sequence data of the internal transcribed spacer and beta-tubulin loci, placed this fungus within the genus Verrucoconiothyrium but clearly distinct from the other known species. A novel species Verrucoconiothyrium ambiguumsp. nov. is described and illustrated. The taxonomic affiliation of the genus Verrucoconiothyrium at the family level was addressed through individual and combined gene genealogies. Our results show that the genus Verrucoconiothyrium is a member of the family Didymellaceae.

Biodiversity of Penicillium species from marine environments in Portugal and description of Penicillium lusitanum sp. nov., a novel species isolated from sea water.

During an extensive survey of marine fungi in coastal marine environments from Portugal, a collection of Penicillium isolates were obtained from sea water, macroalgae and driftwood. Sixteen distinct Penicillium species were identified with Penicillium terrigenum and Penicillium brevicompactum being the most frequent. A Penicillium species isolated from sea water could not be affiliated to any known species. Phylogenetic analyses based on the ITS region of the rDNA and the beta-tubulin (benA) gene placed it into Penicillium section Ramosa, distinct from all currently known species and with Penicillium tunisiense as its closest relative. Although having similar morphological characteristics, these species differ in micromorphological and molecular characters. Thus, Penicillium lusitanum sp. nov. is proposed as a novel species.