Key points
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The partial pressures of arterial carbon dioxide () and oxygen () has a marked influence on brain blood flow.
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It is unclear if the larger brain arteries are also sensitive to ...changing and and if different areas of the brain possess different sensitivities.
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We separately altered and and measured the diameter and blood flow in the main arteries delivering blood to the cortex and brainstem.
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During alterations in and , the large arteries changed diameter and blood flow to the brainstem changed more than that to the cortex.
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These findings change the basis of our understanding of brain blood flow control in humans.
Despite the importance of blood flow on brainstem control of respiratory and autonomic function, little is known about regional cerebral blood flow (CBF) during changes in arterial blood gases. We quantified: (1) anterior and posterior CBF and reactivity through a wide range of steady‐state changes in the partial pressures of CO2 () and O2 () in arterial blood, and (2) determined if the internal carotid artery (ICA) and vertebral artery (VA) change diameter through the same range. We used near‐concurrent vascular ultrasound measures of flow through the ICA and VA, and blood velocity in their downstream arteries (the middle (MCA) and posterior (PCA) cerebral arteries). Part A (n= 16) examined iso‐oxic changes in , consisting of three hypocapnic stages (=∼15, ∼20 and ∼30 mmHg) and four hypercapnic stages (=∼50, ∼55, ∼60 and ∼65 mmHg). In Part B (n= 10), during isocapnia, was decreased to ∼60, ∼44, and ∼35 mmHg and increased to ∼320 mmHg and ∼430 mmHg. Stages lasted ∼15 min. Intra‐arterial pressure was measured continuously; arterial blood gases were sampled at the end of each stage. There were three principal findings. (1) Regional reactivity: the VA reactivity to hypocapnia was larger than the ICA, MCA and PCA; hypercapnic reactivity was similar. With profound hypoxia (35 mmHg) the relative increase in VA flow was 50% greater than the other vessels. (2) Neck vessel diameters: changes in diameter (∼25%) of the ICA was positively related to changes in (R2, 0.63 ± 0.26; P < 0.05); VA diameter was unaltered in response to changed but yielded a diameter increase of +9% with severe hypoxia. (3) Intra‐ vs. extra‐cerebral measures: MCA and PCA blood velocities yielded smaller reactivities and estimates of flow than VA and ICA flow. The findings respectively indicate: (1) disparate blood flow regulation to the brainstem and cortex; (2) cerebrovascular resistance is not solely modulated at the level of the arteriolar pial vessels; and (3) transcranial Doppler ultrasound may underestimate measurements of CBF during extreme hypoxia and/or hypercapnia.
Fibrillin-1 is a pivotal structural component of the kidney's glomerulus and peritubular tissue. Mutations in the fibrillin-1 gene result in Marfan syndrome (MFS), an autosomal dominant disease of ...the connective tissue. Although the kidney is not considered a classically affected organ in MFS, several case reports describe glomerular disease in patients. Therefore, this study aimed to characterize the kidney in the mgΔlpn-mouse model of MFS. Affected animals presented a significant reduction of glomerulus, glomerulus-capillary, and urinary space, and a significant reduction of fibrillin-1 and fibronectin in the glomerulus. Transmission electron microscopy and 3D-ultrastructure analysis revealed decreased amounts of microfibrils which also appeared fragmented in the MFS mice. Increased collagen fibers types I and III, MMP-9, and α-actin were also observed in affected animals, suggesting a tissue-remodeling process in the kidney. Video microscopy analysis showed an increase of microvessel distribution coupled with reduction of blood-flow velocity, while ultrasound flow analysis revealed significantly lower blood flow in the kidney artery and vein of the MFS mice. The structural and hemodynamic changes of the kidney indicate the presence of kidney remodeling and vascular resistance in this MFS model. Both processes are associated with hypertension which is expected to worsen the cardiovascular phenotype in MFS.
Abstract
The microplastic body burden of marine animals is often assumed to reflect levels of environmental contamination, yet variations in feeding ecology and regional trait expression could also ...affect a species’ risk of contaminant uptake. Here, we explore the global inventory of individual microplastic body burden for invertebrate species inhabiting marine sediments across 16 biogeographic provinces. We show that individual microplastic body burden in benthic invertebrates cannot be fully explained by absolute levels of microplastic contamination in the environment, because interspecific differences in behaviour and feeding ecology strongly determine microplastic uptake. Our analyses also indicate a degree of species-specific particle selectivity; likely associated with feeding biology. Highest microplastic burden occurs in the Yellow and Mediterranean Seas and, contrary to expectation, amongst omnivores, predators, and deposit feeders rather than suspension feeding species. Our findings highlight the inadequacy of microplastic uptake risk assessments based on inventories of environmental contamination alone, and the need to understand how species behaviour and trait expression covary with microplastic contamination.
We report on the first successful proof-of-principle experiment to manipulate laser-matter interactions on microscales using highly ordered Si microwire arrays. The interaction of a high-contrast ...short-pulse laser with a flat target via periodic Si microwires yields a substantial enhancement in both the total and cutoff energies of the produced electron beam. The self-generated electric and magnetic fields behave as an electromagnetic lens that confines and guides electrons between the microwires as they acquire relativistic energies via direct laser acceleration.
Miniaturized gas chromatography (GC) systems can provide fast, quantitative analysis of chemical vapors in an ultrasmall package. We describe a chemical sensor technology based on resonant ...nanoelectromechanical systems (NEMS) mass detectors that provides the speed, sensitivity, specificity, and size required by the microscale GC paradigm. Such NEMS sensors have demonstrated detection of subparts per billion (ppb) concentrations of a phosphonate analyte. By combining two channels of NEMS detection with an ultrafast GC front-end, chromatographic analysis of 13 chemicals was performed within a 5 s time window.
Failures in mitophagy, a process by which damaged mitochondria are cleared, results in neurodegeneration, while enhancing mitophagy promotes the survival of dopaminergic neurons. Using an artificial ...intelligence platform, we employed a natural language processing approach to evaluate the semantic similarity of candidate molecules to a set of well-established mitophagy enhancers. Top candidates were screened in a cell-based mitochondrial clearance assay. Probucol, a lipid-lowering drug, was validated across several orthogonal mitophagy assays. In vivo, probucol improved survival, locomotor function, and dopaminergic neuron loss in zebrafish and fly models of mitochondrial damage. Probucol functioned independently of PINK1/Parkin, but its effects on mitophagy and in vivo depended on ABCA1, which negatively regulated mitophagy following mitochondrial damage. Autophagosome and lysosomal markers were elevated by probucol treatment in addition to increased contact between lipid droplets (LDs) and mitochondria. Conversely, LD expansion, which occurs following mitochondrial damage, was suppressed by probucol and probucol-mediated mitophagy enhancement required LDs. Probucol-mediated LD dynamics changes may prime the cell for a more efficient mitophagic response to mitochondrial damage.
Summary
Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen were first published by the British Committee for Standards in Haematology (BCSH) ...in 1996 and formally reviewed in 2002. Although the guidelines originated from discussion within the BCSH, the intended readership is wide given the multidisciplinary nature of the management of hyposplenism.
Of the over 800 exoplanets detected to date, over half are on non-circular orbits, with eccentricities as high as 0.93. Such orbits lead to time-variable stellar heating, which has major implications ...for the planet's atmospheric dynamical regime. In our study, we vary the eccentricity and orbit-average stellar flux over a wide range. We demonstrate that the eccentric hot Jupiter regime is qualitatively similar to that of planets on circular orbits; the planets possess a super-rotating equatorial jet and exhibit large day-night temperature variations. For those planets that have large temperature differences from day-side to night-side and rapid rotation rates, we find that the light curves can exhibit "ringing" as the planet's hottest region rotates in and out of view from Earth. The results can be used to explain future observations of eccentric transiting exoplanets.
The Arctic Ocean already experiences areas of low pH and high CO ₂, and it is expected to be most rapidly affected by future ocean acidification (OA). Copepods comprise the dominant Arctic ...zooplankton; hence, their responses to OA have important implications for Arctic ecosystems, yet there is little data on their current under-ice winter ecology on which to base future monitoring or make predictions about climate-induced change. Here, we report results from Arctic under-ice investigations of copepod natural distributions associated with late-winter carbonate chemistry environmental data and their response to manipulated pCO ₂ conditions (OA exposures). Our data reveal that species and life stage sensitivities to manipulated OA conditions were correlated with their vertical migration behavior and with their natural exposures to different pCO ₂ ranges. Vertically migrating adult Calanus spp. crossed a pCO ₂ range of >140 μatm daily and showed only minor responses to manipulated high CO ₂. Oithona similis , which remained in the surface waters and experienced a pCO ₂ range of <75 μatm, showed significantly reduced adult and nauplii survival in high CO ₂ experiments. These results support the relatively untested hypothesis that the natural range of pCO ₂ experienced by an organism determines its sensitivity to future OA and highlight that the globally important copepod species, Oithona spp., may be more sensitive to future high pCO ₂ conditions compared with the more widely studied larger copepods.
To investigate the initial events in the development of the human cornea, focusing on cell migration, and extracellular matrix synthesis and organization. To determine whether elastic fibers are ...present in the extracellular matrix during early human corneal development.
Human corneas were collected from week 7 to week 17 of development. An elastic fiber-enhancing stain, tannic acid-uranyl acetate, was applied to all tissue. Three-dimensional serial block-face scanning electron microscopy combined with conventional transmission electron microscopy was used to analyze the corneal stroma.
An acellular collagenous primary stroma with an orthogonal arrangement of fibrils was identified in the central cornea from week 7 of corneal development. At week 7.5, mesenchymal cells migrated toward the central cornea and associated with the acellular collagenous matrix. Novel cell extensions from the endothelium were identified. Elastic fibers were found concentrated in the posterior peripheral corneal stroma from week 12 of corneal development.
This study provides novel evidence of an acellular primary stroma in the early development of the embryonic human cornea. Cell extensions exist as part of a communication system and are hypothesized to assist in the migration of the mesenchymal cells and the development of the mature cornea. Elastic fibers identified in early corneal development may play an important role in establishing corneal shape.
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