Separating vascular and neuronal effects of age on fMRI BOLD signals.

Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.This work is supported by the British Academy (PF160048), the Guarantors of Brain (G101149), the Wellcome Trust (103838), the Medical Research Council (SUAG/051 G101400; and SUAG/046 G101400), European Union’s Horizon 2020 (732592) and the Cambridge NIHR Biomedical Research Centre

Ground-based optical transmission spectrum of the hot Jupiter HAT-P-1b

Time-series spectrophotometric studies of exoplanets during transit using ground-based facilities are a promising approach to characterize their atmospheric compositions. We aim to investigate the transit spectrum of the hot Jupiter HAT-P-1b. We compare our results to those obtained at similar wavelengths by previous space-based observations. We observed two transits of HAT-P-1b with the Gemini Multi-Object Spectrograph (GMOS) instrument on the Gemini North telescope using two instrument modes covering the 320 - 800 nm and 520 - 950 nm wavelength ranges. We used time-series spectrophotometry to construct transit light curves in individual wavelength bins and measure the transit depths in each bin. We accounted for systematic effects. We addressed potential photometric variability due to magnetic spots in the planet's host star with long-term photometric monitoring. We find that the resulting transit spectrum is consistent with previous Hubble Space Telescope (HST) observations. We compare our observations to transit spectroscopy models that marginally favor a clear atmosphere. However, the observations are also consistent with a flat spectrum, indicating high-altitude clouds. We do not detect the Na resonance absorption line (589 nm), and our observations do not have sufficient precision to study the resonance line of K at 770 nm. We show that even a single Gemini/GMOS transit can provide constraining power on the properties of the atmosphere of HAT-P-1b to a level comparable to that of HST transit studies in the optical when the observing conditions and target and reference star combination are suitable. Our 520 - 950 nm observations reach a precision comparable to that of HST transit spectra in a similar wavelength range of the same hot Jupiter, HAT-P-1b. However, our GMOS transit between 320 - 800 nm suffers from strong systematic effects and yields larger uncertainties.Comment: A&A, accepted, 16 pages, 8 figures, 5 table

Leydig cell-immune cell interaction: an example of neuroendocrine-immune communication in testis

In her paper "Tilings will never be the same again" Dr Kathleen L. Wishner quoted Alvin Toffler's book Future Shock written in 1970. Toffler defined "future shock" as a time phenomenon, a product of the greatly accelerated change in society. The scientific research itself is a demonstration of this accelerated change. In particular, data systematized by Davidoff et al in this volume of Biomedical Reviews indicate the change in the understanding of the nature and origin of Leydig cells of the human testis.Biomedical Reviews 1996; 6: 1-4

Phase curves of WASP-33b and HD 149026b and a New Correlation Between Phase Curve Offset and Irradiation Temperature

We present new 3.6 and 4.5 $\mu m$ Spitzer phase curves for the highly irradiated hot Jupiter WASP-33b and the unusually dense Saturn-mass planet HD 149026b. As part of this analysis, we develop a new variant of pixel level decorrelation that is effective at removing intrapixel sensitivity variations for long observations (>10 hours) where the position of the star can vary by a significant fraction of a pixel. Using this algorithm, we measure eclipse depths, phase amplitudes, and phase offsets for both planets at 3.6 $\mu m$ and 4.5 $\mu m$. We use a simple toy model to show that WASP-33b's phase offset, albedo, and heat recirculation efficiency are largely similar to those of other hot Jupiters despite its very high irradiation. On the other hand, our fits for HD 149026b prefer a very high albedo and an unusually high recirculation efficiency. We also compare our results to predictions from general circulation models, and find that while neither are a good match to the data, the discrepancies for HD 149026b are especially large. We speculate that this may be related to its high bulk metallicity, which could lead to enhanced atmospheric opacities and the formation of reflective cloud layers in localized regions of the atmosphere. We then place these two planets in a broader context by exploring relationships between the temperatures, albedos, heat transport efficiencies, and phase offsets of all planets with published thermal phase curves. We find a striking relationship between phase offset and irradiation temperature--the former drops with increasing temperature until around 3400 K, and rises thereafter. Although some aspects of this trend are mirrored in the circulation models, there are notable differences that provide important clues for future modeling efforts

Nerve-mast cell-nerve growth factor link: the mast cell as yin-yang modulator in inflammation and fibrosis

Inflammation and fibroproliferation are biological responses aiming at recovering from injury. Wound healing is considered a paradigm of such a homeostatic phenomenon. However, what begins as a protective response, in excess becomes a damaging process we call chronic inflammatory-fibroproliferative disease.Biomedical Reviews 1995; 4: 1-6

Neural-immune-effector (NIE) cross-talk in vascular trophobiology: proposal for new and not yet exploited purinergic regulatory mechanisms

In a state-of-the-art approach, Dr. Hasséssian presents purinoceptor-mediated vasoconstriction/vasodilation mechanisms of the pulmonary circulation. He focuses on P2 purinoceptors of smooth muscle cells, endothelial cells, platelets and mast cells, without addressing P1 (adenosine) purinoceptors. Recently, the Burnstock's purinoceptorology is "arborizing" into a variety of members of P1 and P2 purinoceptor families classified by the International Union of Pharmacology. Here we would like to add some possible, new and not yet exploited, purinergic regulatory mechanisms to the Hasséssian's work. Accordingly, we shall briefly focus on the involvement of connective tissue (adventitial) mast cells and their interactions with perivascular nerves and medial smooth muscle cells.Biomedical Reviews 1994; 3: 81-86

A suggestive neurotrophic potential of mast cells in heart and submandibular glands of the rat

According to the neurotrophic theory, the nerve growth factor (NGF) is widely distributed in the effector tissues of peripheral sympathetic and sensory neurons, suggesting that the density of innervation is controlled by effector derived NGF. Sympathetic neurons require access to NGF for survival throughout life, whereas sensory neurons are dependent on NGF only during restricted period of embryonic development. This development-related feature of sympathetic neurons suggests that they crucially depend on plasticity of NGF biology, including secretion, availability, and utilization, to maintain appropriate neuronal function in adult life, and even in old age. While most previous studies on the cellular source of NGF have focused on neuronal and nonneuronal effector cells, it was recently demonstrated that NGF secretion is not only restricted to cells receiving a direct innervation. Immune cells, including mast cells (MC), lymphocytes and macrophages, for example, produce and release NGF as well as NGF secretion-inducing cytokines. Likewise, since the first evidence that NGF treatment causes a significant increase in the number and size of MC has been published by Aloe and Levi-Montalcini in 1977, it has been repeatedly shown that these cells are also NGF-responsive cells, thus providing further evidence for a widely investigated MC-nerve interaction. Further on this trophobiological line, a positive correlation of the amount of NGF and expression of NGF mRNA with the density of sympathetic innervation was demonstrated in a variety of organs. In the rat heart, one such example, the atrium contains a higher amount of NGF corresponding to a denser sympathetic nerve supply compared to the ventricle. Such a correlation was also revealed in the submandibular glands (SMG) and iris. Likewise, the density of MC in the ankle joint capsule, which is heavily innervated, is greater than in the capsule of the knee, which is less densely innervated, and the MC number in the synovial joint of spontaneously hypertensive rats, which have increased sympathetic nerve supply, is significantly greater than in normotensive rats. A summing-up of the above mentioned data shows that (i) MC are NGF secreting/responsive cells and frequently colocalized with nerves, and (ii) a higher NGF amount correlates with a denser sympathetic innervation of a tissue . This, in our eyes, brings into question the sole contribution of the "classical" effector cells to neurotrophic support of sympathetic nerve-innervated tissues. Consequently, we suggest that MC, through their own and/or cytokine-induced NGF secretion, may also be implicated in the neurotrophic potential in these tissues.Biomedical Reviews 1998; 9: 143-145