Agricultural intensification and climate change are rapidly decreasing insect biodiversity.

Major declines in insect biomass and diversity, reviewed here, have become obvious and well documented since the end of World War II. Here, we conclude that the spread and intensification of agriculture during the past half century is directly related to these losses. In addition, many areas, including tropical mountains, are suffering serious losses because of climate change as well. Crops currently occupy about 11% of the world's land surface, with active grazing taking place over an additional 30%. The industrialization of agriculture during the second half of the 20th century involved farming on greatly expanded scales, monoculturing, the application of increasing amounts of pesticides and fertilizers, and the elimination of interspersed hedgerows and other wildlife habitat fragments, all practices that are destructive to insect and other biodiversity in and near the fields. Some of the insects that we are destroying, including pollinators and predators of crop pests, are directly beneficial to the crops. In the tropics generally, natural vegetation is being destroyed rapidly and often replaced with export crops such as oil palm and soybeans. To mitigate the effects of the Sixth Mass Extinction event that we have caused and are experiencing now, the following will be necessary: a stable (and almost certainly lower) human population, sustainable levels of consumption, and social justice that empowers the less wealthy people and nations of the world, where the vast majority of us live, will be necessary.

Vertebrates on the brink as indicators of biological annihilation and the sixth mass extinction.

The ongoing sixth mass species extinction is the result of the destruction of component populations leading to eventual extirpation of entire species. Populations and species extinctions have severe implications for society through the degradation of ecosystem services. Here we assess the extinction crisis from a different perspective. We examine 29,400 species of terrestrial vertebrates, and determine which are on the brink of extinction because they have fewer than 1,000 individuals. There are 515 species on the brink (1.7% of the evaluated vertebrates). Around 94% of the populations of 77 mammal and bird species on the brink have been lost in the last century. Assuming all species on the brink have similar trends, more than 237,000 populations of those species have vanished since 1900. We conclude the human-caused sixth mass extinction is likely accelerating for several reasons. First, many of the species that have been driven to the brink will likely become extinct soon. Second, the distribution of those species highly coincides with hundreds of other endangered species, surviving in regions with high human impacts, suggesting ongoing regional biodiversity collapses. Third, close ecological interactions of species on the brink tend to move other species toward annihilation when they disappear-extinction breeds extinctions. Finally, human pressures on the biosphere are growing rapidly, and a recent example is the current coronavirus disease 2019 (Covid-19) pandemic, linked to wildlife trade. Our results reemphasize the extreme urgency of taking much-expanded worldwide actions to save wild species and humanity's crucial life-support systems from this existential threat.

Inhibition of GLI2 with antisense-oligonucleotides: A potential therapy for the treatment of bladder cancer.

The sonic hedgehog (SHH) signaling pathway plays an integral role in the maintenance and progression of bladder cancer (BCa) and SHH inhibition may be an efficacious strategy for BCa treatment. We assessed an in-house human BCa tissue microarray and found that the SHH transcription factors, GLI1 and GLI2, were increased in disease progression. A panel of BCa cell lines show that two invasive lines, UM-UC-3 and 253J-BV, both express these transcription factors but UM-UC-3 produces more SHH ligand and is less responsive in viability to pathway stimulation by recombinant human SHH or smoothened agonist, and less responsive to inhibitors including the smoothened inhibitors cyclopamine and SANT-1. In contrast, 253J-BV was highly responsive to these manipulations. We utilized a GLI1 and GLI2 antisense oligonucleotide (ASO) to bypass pathway mechanics and target the transcription factors directly. UM-UC-3 decreased in viability due to both ASOs but 253J-BV was only affected by GLI2 ASO. We utilized the murine intravesical orthotopic human BCa (mio-hBC) model for the establishment of noninvasive BCa and treated tumors with GLI2 ASO. Tumor size, growth rate, and GLI2 messenger RNA and protein expression were decreased. These results suggest that GLI2 ASO may be a promising new targeted therapy for BCa.

Weighing the evidence for using vascular conductance, not resistance, in comparative cardiovascular physiology.

Vascular resistance and conductance are reciprocal indices of vascular tone that are often assumed to be interchangeable. However, in most animals in vivo, blood flow (i.e. cardiac output) typically varies much more than arterial blood pressure. When blood flow changes at a constant pressure, the relationship between conductance and blood flow is linear, whereas the relationship between resistance and blood flow is non-linear. Thus, for a given change in blood flow, the change in resistance depends on the starting point, whereas the attendant change in conductance is proportional to the change in blood flow regardless of the starting conditions. By comparing the effects of physical activity at different temperatures or between species - concepts at the heart of comparative cardiovascular physiology - we demonstrate that the difference between choosing resistance or conductance can be marked. We also explain here how the ratio of conductance in the pulmonary and systemic circulations provides a more intuitive description of cardiac shunt patterns in the reptilian cardiovascular system than the more commonly used ratio of resistance. Finally, we posit that, although the decision to use conductance or resistance should be made on a case-by-case basis, in most circumstances, conductance is a more faithful portrayal of cardiovascular regulation in vertebrates.

Arterial Baroreflex Resetting During Exercise in Humans: Underlying Signaling Mechanisms.

The arterial baroreflex (ABR) resets during exercise in an intensity-dependent manner to operate around a higher blood pressure with maintained sensitivity. This review provides a historical perspective of ABR resetting and the involvement of other neural reflexes in mediating exercise resetting. Furthermore, we discuss potential underlying signaling mechanisms that may contribute to exercise ABR resetting in physiological and pathophysiological conditions.

Effect of centrally acting angiotensin converting enzyme inhibitor on the exercise-induced increases in muscle sympathetic nerve activity.

KEY POINTS: The arterial baroreflex's operating point pressure is reset upwards and rightwards from rest in direct relation to the increases in dynamic exercise intensity. The intraneural pathways and signalling mechanisms that lead to upwards and rightwards resetting of the operating point pressure, and hence the increases in central sympathetic outflow during exercise, remain to be identified. We tested the hypothesis that the central production of angiotensin II during dynamic exercise mediates the increases in sympathetic outflow and, therefore, the arterial baroreflex operating point pressure resetting during acute and prolonged dynamic exercise. The results identify that perindopril, a centrally acting angiotensin converting enzyme inhibitor, markedly attenuates the central sympathetic outflow during acute and prolonged dynamic exercise. ABSTRACT: We tested the hypothesis that the signalling mechanisms associated with the dynamic exercise intensity related increases in muscle sympathetic nerve activity (MSNA) and arterial baroreflex resetting during exercise are located within the central nervous system. Participants performed three randomly ordered trials of 70° upright back-supported dynamic leg cycling after ingestion of placebo and two different lipid soluble angiotensin converting enzyme inhibitors (ACEi): perindopril (high lipid solubility), captopril (low lipid solubility). Repeated measurements of whole venous blood (n = 8), MSNA (n = 7) and arterial blood pressures (n = 14) were obtained at rest and during an acute (SS1) and prolonged (SS2) bout of steady state dynamic exercise. Arterial baroreflex function curves were modelled at rest and during exercise. Peripheral venous superoxide concentrations measured by electron spin resonance spectroscopy were elevated during exercise and were not altered by ACEi at rest (P ≥ 0.4) or during exercise (P ≥ 0.3). Baseline MSNA and mean arterial pressure were unchanged at rest (P ≥ 0.1; P ≥ 0.8, respectively). However, during both SS1 and SS2, the centrally acting ACEi perindopril attenuated MSNA compared to captopril and the placebo (P < 0.05). Arterial pressures at the operating point and threshold pressures were decreased with perindopril from baseline to SS1 with no further changes in the operating point pressure during SS2 under all three conditions. These data suggest that centrally acting ACEi is significantly more effective at attenuating the increase in the acute and prolonged exercise-induced increases in MSNA.

Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia.

BACKGROUND: The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish their relative contribution in vivo, we quantified arterial-venous concentration gradients across the human cerebral and femoral circulation at rest and during exercise, an ideal model system characterized by physiological extremes of O2 tension and blood flow. METHODS: Ten healthy participants (5 men, 5 women) aged 24±4 (mean±SD) years old were randomly assigned to a normoxic (21% O2) and hypoxic (10% O2) trial with measurements performed at rest and after 30 minutes of cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled simultaneously from the brachial artery and internal jugular and femoral veins with plasma and RBC nitric oxide metabolites measured by tri-iodide reductive chemiluminescence. Blood flow was determined by transcranial Doppler ultrasound (cerebral blood flow) and constant infusion thermodilution (femoral blood flow) with net exchange calculated via the Fick principle. RESULTS: Hypoxia was associated with a mild increase in both cerebral blood flow and femoral blood flow (P<0.05 versus normoxia) with further, more pronounced increases observed in femoral blood flow during exercise (P<0.05 versus rest) in proportion to the reduction in RBC oxygenation (r=0.680-0.769, P<0.001). Plasma gradients reflecting consumption (arterial>venous; P<0.05) were accompanied by RBC iron nitrosylhemoglobin formation (venous>arterial; P<0.05) at rest in normoxia, during hypoxia (P<0.05 versus normoxia), and especially during exercise (P<0.05 versus rest), with the most pronounced gradients observed across the bioenergetically more active, hypoxemic, and acidotic femoral circulation (P<0.05 versus cerebral). In contrast, we failed to observe any gradients consistent with RBC SNO-Hb consumption and corresponding delivery of plasma S-nitrosothiols (P>0.05). CONCLUSIONS: These findings suggest that hypoxia and, to a far greater extent, exercise independently promote arterial-venous delivery gradients of intravascular nitric oxide, with deoxyhemoglobin-mediated reduction identified as the dominant mechanism underlying hypoxic vasodilation.

Genome skimming provides new insight into the relationships in Ludwigia section Macrocarpon, a polyploid complex.

PREMISE OF THE STUDY: Interpreting relationships within groups containing polyploids, which are frequent in angiosperms, can be greatly assisted by genomic techniques. In this study, we used a genome-skimming approach to investigate the evolutionary relationships and origins of polyploids in the monophyletic group, Ludwigia section Macrocarpon (Onagraceae), which includes diploid, tetraploid, and hexaploid taxa. METHODS: We sampled all known taxa and ploidy levels in the section and conducted shotgun sequencing. We assembled plastomes, mitochondrial sequences, and completed nuclear ribosomal regions, reconstructed phylogenies, and conducted comparative genomic analyses for plastomes to gain insights into the relationships among studied taxa. KEY RESULTS: Within the section, results showed that the South American diploid taxa L. bonariensis and L. lagunae were closely related. We reported the first chromosome count (2n = 4× = 32) for L. neograndiflora, which is closely related to the two South American diploid taxa, although its exact origin remains unclear. The samples of the widespread, polyploid taxon L. octovalvis do not form a monophyletic group. Both tetraploid and hexaploid L. octovalvis lineages have originated more than once. At least one tetraploid in the L. octovalvis lineage may have been involved in the origins of hexaploids. One or more extinct/unsampled intermediate tetraploids in the L. octovalvis lineages had also likely been involved in the origins of hexaploids. CONCLUSIONS: Genome skimming provided important insights into the complex evolutionary relationships within sect. Macrocarpon, but additional sampling and data from single-copy nuclear regions are necessary to further elucidate the origins of the polyploids in this section.

The influence of the carotid baroreflex on dynamic regulation of cerebral blood flow and cerebral tissue oxygenation in humans at rest and during exercise.

PURPOSE: This preliminary study tested the hypothesis that the carotid baroreflex (CBR) mediated sympathoexcitation regulates cerebral blood flow (CBF) at rest and during dynamic exercise. METHODS: In seven healthy subjects (26 ± 1 years), oscillatory neck pressure (NP) stimuli of + 40 mmHg were applied to the carotid baroreceptors at a pre-determined frequency of 0.1 Hz at rest, low (10 ± 1W), and heavy (30 ± 3W) exercise workloads (WLs) without (control) and with α - 1 adrenoreceptor blockade (prazosin). Spectral power analysis of the mean arterial blood pressure (MAP), mean middle cerebral artery blood velocity (MCAV), and cerebral tissue oxygenation index (ScO2) in the low-frequency range (0.07-0.20 Hz) was estimated to examine NP stimuli responses. RESULTS: From rest to heavy exercise, WLs resulted in a greater than three-fold increase in MCAV power (42 ± 23.8-145.2 ± 78, p < 0.01) and an almost three-fold increase in ScO2 power (0.51 ± 0.3-1.53 ± 0.8, p = 0.01), even though there were no changes in MAP power (from 24.5 ± 21 to 22.9 ± 11.9) with NP stimuli. With prazosin, the overall MAP (p = 0.0017), MCAV (p = 0.019), and ScO2 (p = 0.049) power was blunted regardless of the exercise conditions. Prazosin blockade resulted in increases in the Tf gain index between MAP and MCAV compared to the control (p = 0.03). CONCLUSION: CBR-mediated changes in sympathetic activity contribute to dynamic regulation of the cerebral vasculature and CBF at rest and during dynamic exercise in humans.

Magnetically-actuated drug delivery device (MADDD) for minimally invasive treatment of prostate cancer: An in vivo animal pilot study.

BACKGROUND: The vast majority of prostate cancer presents clinically localized to the prostate without evidence of metastasis. Currently, there are several modalities available to treat this particular disease. Despite radical prostatectomy demonstrating a modest prostate cancer specific mortality benefit in the PIVOT trial, several novel modalities have emerged to treat localized prostate cancer in patients that are either not eligible for surgery or that prefer an alternative approach. METHODS: Athymic nude mice were subcutaneously inoculated with prostate cancer cells. The mice were divided into four cohorts, one cohort untreated, two cohorts received docetaxel (10 mg/kg) either subcutaneously (SC) or intravenously (IV) and the fourth cohort was treated using the magnetically-actuated docetaxel delivery device (MADDD), dispensing 1.5 µg of docetaxel per 30 min treatment session. Treatment in all three therapeutic arms (SC, IV, and MADDD) was administered once weekly for 6 weeks. Treatment efficacy was measured once a week according to tumor volume using ultrasound. In addition, calipers were used to assess tumor volume. RESULTS: Animals implanted with the device demonstrated no signs of distress or discomfort, neither local nor systemic symptoms of inflammation and infection. Using an independent sample t-test, the tumor growth rate of the treated tumors was significant when compared to the control. Post hoc Tukey HSD test results showed that the mean tumor growth rate of our device cohort was significantly lower than SC and control cohorts. Moreover, IV cohort showed slight reduction in mean tumor growth rates than the ones from the device cohort, however, there was no statistical significance in tumor growth rate between these two cohorts. Furthermore, immunohistochemistry demonstrated an increased cellular apoptosis in the MADDD treated tumors and a decreased proliferation when compared to the other cohorts. In addition, IV cohort showed increased treatment side effects (weight loss) when compared to the device cohort. Finally, MADDD showed minimal expression of CD45 comparable to the control cohort, suggesting no signs of chronic inflammation. CONCLUSIONS: In conclusion, this study showed for the first time that MADDD, clearly suppressed tumor growth in local prostate cancer tumors. This could potentially be a novel clinical treatment approach for localized prostate cancer.

N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

NEW FINDINGS: What is the central question of this study? This study evaluated the following central question: does N-acetylcysteine (N-AC), an antioxidant that readily penetrates the blood-brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia? What is the main finding and its importance? We demonstrate that N-AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N-AC, have therapeutic potential in obstructive sleep apnoea. This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg(-1) of N-AC (n = 16) or vehicle placebo (n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity (n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo (P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance (P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea.

Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex.

The last 100 years witnessed a rapid and progressive development of the body of knowledge concerning the neural control of the cardiovascular system in health and disease. The understanding of the complexity and the relevance of the neuroregulatory system continues to evolve and as a result raises new questions. The purpose of this review is to articulate results from studies involving experimental models in animals as well as in humans concerning the interaction between the neural mechanisms mediating the hemodynamic responses during exercise. The review describes the arterial baroreflex, the pivotal mechanism controlling mean arterial blood pressure and its fluctuations along with the two main activation mechanisms to exercise: central command (parallel activation of central somatomotor and autonomic descending pathways) and the muscle metaboreflex, the metabolic component of exercise pressor reflex (feedback from ergoreceptors within contracting skeletal muscles). In addition, the role of the cardiopulmonary baroreceptors in modulating the resetting of arterial baroreflex is identified, and the mechanisms in the central nervous system involved with the resetting of baroreflex function during dynamic exercise are also described. Approaching a very relevant clinical condition, the review also presents the concept that the impaired arterial baroreflex function is an integral component of the metaboreflex-mediated exaggerated sympathetic tone in subjects with heart failure. This increased sympathetic activity has a major role in causing the depressed ventricular function observed during submaximal dynamic exercise in these patients. The potential contribution of a metaboreflex arising from respiratory muscles is also considered.

Effect of an acute increase in central blood volume on cerebral hemodynamics.

Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV.

Autonomic neural control of heart rate during dynamic exercise: revisited.

UNLABELLED: The accepted model of autonomic control of heart rate (HR) during dynamic exercise indicates that the initial increase is entirely attributable to the withdrawal of parasympathetic nervous system (PSNS) activity and that subsequent increases in HR are entirely attributable to increases in cardiac sympathetic activity. In the present review, we sought to re-evaluate the model of autonomic neural control of HR in humans during progressive increases in dynamic exercise workload. We analysed data from both new and previously published studies involving baroreflex stimulation and pharmacological blockade of the autonomic nervous system. Results indicate that the PSNS remains functionally active throughout exercise and that increases in HR from rest to maximal exercise result from an increasing workload-related transition from a 4 : 1 vagal-sympathetic balance to a 4 : 1 sympatho-vagal balance. Furthermore, the beat-to-beat autonomic reflex control of HR was found to be dependent on the ability of the PSNS to modulate the HR as it was progressively restrained by increasing workload-related sympathetic nerve activity. IN CONCLUSION: (i) increases in exercise workload-related HR are not caused by a total withdrawal of the PSNS followed by an increase in sympathetic tone; (ii) reciprocal antagonism is key to the transition from vagal to sympathetic dominance, and (iii) resetting of the arterial baroreflex causes immediate exercise-onset reflexive increases in HR, which are parasympathetically mediated, followed by slower increases in sympathetic tone as workloads are increased.

GM crops, the environment and sustainable food production.

Today, over 7.1 billion people rely on the earth's resources for sustenance, and nearly a billion people are malnourished, their minds and bodies unable to develop properly. Globally, population is expected to rise to more than 9 billion by 2050. Given the combined pressures of human population growth, the rapidly growing desire for increased levels of consumption, and the continued use of inappropriate technologies, it is not surprising that humans are driving organisms to extinction at an unprecedented rate. Many aspects of the sustainable functioning of the natural world are breaking down in the face of human-induced pressures including our individual and collective levels of consumption and our widespread and stubborn use of destructive technologies. Clearly, agriculture must undergo a redesign and be better and more effectively managed so as to contribute as well as possible to feeding people, while at the same time we strive to lessen the tragic loss of biodiversity and damage to all of its productive systems that the world is experiencing. For GM crops to be part of the solution, biosafety assessments should not be overly politically-driven or a burdensome impedance to delivering this technology broadly. Biosafety scientists and policy makers need to recognize the undeniable truth that inappropriate actions resulting in indecision also have negative consequences. It is no longer acceptable to delay the use of any strategy that is safe and will help us achieve the ability to feed the world's people.

Pneumatic antishock garment inflation activates the human sympathetic nervous system by abdominal compression.

Pneumatic antishock garments (PASG) have been proposed to exert their blood pressure-raising effect mechanically, i.e. by increasing venous return and vascular resistance of the lower body. We tested whether, alternatively, PASG inflation activates the sympathetic nervous system. Five men and four women wore PASG while mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), heart rate and stroke volume were measured. One leg bladder (LEG) and the abdominal bladder (ABD) of the trousers were inflated individually and in combination (ABD+LEG), at 60 or 90 mmHg for 3 min. By the end of 3 min of inflation, conditions that included the ABD region caused significant increases in MAP in a dose-dependent fashion (7 ± 2, 8 ± 3, 14 ± 4 and 13 ± 5 mmHg for ABD60, ABD+LEG60, ABD90 and ABD+LEG90, respectively, P < 0.05). Likewise, inflation that included ABD caused significant increases in total MSNA compared with control values [306 ± 70, 426 ± 98 and 247 ± 79 units for ABD60, ABD90 and ABD+LEG90, respectively, P < 0.05 (units = burst frequency × burst amplitude]. There were no changes in MAP or MSNA in the LEG-alone conditions. The ABD inflation also caused a significant decrease in stroke volume (-11 ± 3 and -10 ± 3 ml per beat in ABD90 and ABD+LEG90, respectively, P < 0.05) with no change in cardiac output. Neither cardiopulmonary receptor deactivation nor mechanical effects can account for a slowly developing rise in both sympathetic activity and blood pressure during ABD inflation. Rather, these data provide direct evidence that PASG inflation activates the sympathetic nervous system secondarily to abdominal, but not leg, compression.

Blood pressure regulation XI: overview and future research directions.

While the importance of regulating arterial blood pressure within a 'normal' range is widely appreciated, the definition of 'normal' and the means by which humans and other species regulate blood pressure under various conditions remain hotly debated. The effects of diverse physiological, pathological and environmental challenges on blood pressure and the mechanisms that attempt to maintain it at an optimal level are reviewed and critically analyzed in a series of articles published in this themed issue of the European Journal of Applied Physiology. We summarize here the major points made in these reviews, with emphasis on unifying concepts of regulatory mechanisms and future directions for research.

Mother trees, altruistic fungi, and the perils of plant personification.

There are growing doubts about the true role of the common mycorrhizal networks (CMN or wood wide web) connecting the roots of trees in forests. We question the claims of a substantial carbon transfer from 'mother trees' to their offspring and nearby seedlings through the CMN. Recent reviews show that evidence for the 'mother tree concept' is inconclusive or absent. The origin of this concept seems to stem from a desire to humanize plant life but can lead to misunderstandings and false interpretations and may eventually harm rather than help the commendable cause of preserving forests. Two recent books serve as examples: The Hidden Life of Trees and Finding the Mother Tree.

α1-Adrenergic receptor control of the cerebral vasculature in humans at rest and during exercise.

We tested the hypothesis that pharmacological blockade of α(1)-adrenoreceptors (by prazosin), at rest and during steady-state dynamic exercise, would impair cerebral autoregulation and result in cerebral vasodilatation in healthy humans. In 10 subjects, beat-to-beat mean arterial pressure and mean middle cerebral artery blood velocity were determined at rest and during low (Ex90) and moderate workload (Ex130) on an upright bicycle ergometer without and with prazosin. Plasma noradrenaline concentrations increased significantly from rest to Ex130 during control conditions (from 1.8 ± 0.2 to 3.2 ± 0.3 pmol (ml plasma)(-1)). In the control conditions, the transfer function gain between mean arterial pressure and mean middle cerebral artery blood velocity in the low-frequency range was decreased at Ex90 (P = 0.035) and Ex130 (P = 0.027) from rest. A significant increase in critical closing pressure (CCP) was also observed in the control conditions from rest to Ex90 to Ex130 (from 18 ± 3 to 24 ± 4 to 31 ± 4 mmHg). An average of 74 ± 2% blockade of blood pressure response was achieved with oral prazosin. Following blockade, plasma noradrenaline concentrations further increased at rest and during Ex130 from the control value (from 2.6 ± 0.3 to 4.4 ± 0.5 pmol (ml plasma)(-1)). Prazosin also resulted in an increase in low-frequency gain (P < 0.003) compared with the control conditions. Prazosin blockade abolished the increases in CCP during Ex130 and increased the cerebrovascular conductance index (P = 0.018). These data indicate that in the control conditions a strengthening of cerebral autoregulation occurred with moderate dynamic exercise that is associated with an increase in CCP as a result of the exercise-mediated augmentation of sympathetic activity. Given that α(1)-adrenergic receptor blockade attenuated the increase in dynamic cerebral autoregulation and CCP, we conclude that increases in sympathetic activity have a role in establishing cerebral vascular tone in humans.