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Paterson, D. J.

Publications and source records attributed to Paterson, D. J..

5 recordsLinked to original sources

Multimodal imaging reveals no evidence for magnetite-based magnetoreceptors in the mole-rat eye

Magnetoreception, the ability to perceive the geomagnetic field, is widespread across animals. The underlying sensory mechanism remains elusive, but a long-standing hypothesis proposes single-domain magnetite linked to mechanosensitive ion channels. The Ansells mole-rat (Fukomys anselli) is a subterranean rodent with a magnetic sense, and published behavioral and histological data are consistent with magnetite-based magnetoreceptors in the cornea or retina. Here, we systematically screened for magnetite in the mole-rat eye, combining iron detection via enhanced Prussian blue staining and synchrotron X-ray fluorescence microscopy (XFM) with magnetic detection via MRI quantitative susceptibility mapping (MRI-QSM) and quantum-diamond microscopy (QDM). This revealed only a few iron particles in the retina and cornea, which predominantly overlapped with titanium or chromium, indicating a non-biogenic origin. XFM showed iron-enriched lines in the cornea, but these did not show ferrimagnetic signals. Focusing on other ocular tissues, MRI-QSM revealed the highest susceptibility in the ciliary body, where iron-rich pigmented cells were identified. A TEM-screen, however, failed to detect single-domain magnetite particles in these cells. We conclude that our high-sensitivity multimodal screen provides no evidence for magnetite-based magnetoreceptors in the mole-rat eye, suggesting that mole-rat magnetoreceptors either do not reside in the eye or are based on different physical principles.

neuroscience↗

β2AR Agonists Sustain Thermogenesis and Leanness via Sympathofacilitation

Human thermogenesis depends on {beta}2-adrenoceptors ({beta}2AR) expressed in thermogenic adipocytes, which are activated by norepinephrine released from sympathetic neurons. Whether {beta}2AR also modulates thermogenesis via direct presynaptic action within sympathetic neurons has remained unclear. Here, we identify Adrb2 expression in human and rodent cervical sympathetic neurons. {beta}2AR agonism exerts neurotrophic effects and facilitates cholinergic responsiveness in mouse sympathetic neurons, indicating a sympathofacilitatory role. Selective deletion of {beta}2AR in sympathetic neurons leads to impaired nerve activity in brown adipose tissue, sympathetic neuropathy, worsened fasting-induced hypothermia, and progressive obesity in chow-fed mice--without changes in food intake. These findings uncover a presynaptic role for {beta}2AR in sustaining thermogenesis and regulating adiposity, suggesting sympathofacilitation as a therapeutic avenue for obesity. HighlightsO_LIHuman and mouse cervical sympathetic neurons express adrenoceptor beta 2 (Adrb2) C_LIO_LI{beta}2-adrenoceptor ({beta}2AR) activation is neurotrophic and facilitates sympathetic neuronal excitability C_LIO_LILoss of {beta}2AR in sympathetic neurons leads to neuropathy in brown adipose tissue and reduced sympathetic activity C_LIO_LIDeletion of {beta}2AR in sympathetic neurons exacerbates fasting-induced hypothermia and promotes obesity independently of food intake C_LI

physiology↗

Microbial activated mineral weathering and cementation as precursors to hardpan formation and heavy metal encapsulation in sulfidic tailings

Extensive mineral weathering and formation of large amounts of Fe-rich secondary mineral gels have been identified as precursors critical to forming massive hardpan caps in the surface layers of sulfidic tailings. However, how to initiate and accelerate these precursor processes remains to be established before developing this hardpan-based novel method to rehabilitate sulfidic tailings landscapes. In a 5-month microcosm experiment, the present study has demonstrated the concept of bio-engineering sulfidic tailings by inoculating Fe/S-oxidizing bacterial consortium to accelerate the weathering of sulfides and other Si-rich minerals for mineral gels formation. Synchrotron-based X-ray absorption fine structure spectroscopy (XAFS) demonstrated that the weathering of pyrite and biotite-like minerals was rapidly accelerated by the presence of Fe/S-oxidizing bacterial consortium. The microbial process and associated mineral transformation led to the formation of critical precursor mineral gels, i.e., jarosite-like minerals, as indicators of the onset of hardpan formation. In the meantime, the labile Zn liberated in the weathering was encapsulated in the jarosite-like minerals as revealed by X-ray fluorescence microscopy (XFM). This concept-proven bio-engineering process is ready to be scaled up in further studies under field conditions to develop an alternative hardpan-based method to cover and rehabilitate sulfidic tailing landscapes. TOC Art O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/285858v1_ufig1.gif" ALT="Figure 1"> View larger version (83K): org.highwire.dtl.DTLVardef@fc0292org.highwire.dtl.DTLVardef@10ce8c7org.highwire.dtl.DTLVardef@868a63org.highwire.dtl.DTLVardef@e77d57_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

M-current downregulation leads to stellate ganglia sympathetic hyperactivity associated with hypertension

The activity of cardiac sympathetic nerves from the stellate ganglia is increased in many cardiovascular diseases contributing to the pathophysiology, however the mechanisms underlying this are unknown. Moreover, clinical studies show their surgical removal is an effective treatment, despite the biophysical properties of these neurons being largely unstudied. Here we demonstrate that stellate ganglia neurons from prehypertensive spontaneously hypertensive rats are hyperactive and describe in detail their electrophysiological phenotype guided by single cell RNA-sequencing, molecular biology and perforated patch-clamp to uncover the underlying mechanism. The expression of key transcripts was confirmed in human stellate ganglia. We further demonstrate the contribution of a plethora of ion channels to stellate ganglia neuronal firing, and show that hyperexcitability was curbed by M-current activators, non-selective sodium current blockers or inhibition of Nav1.1-1.3, Nav1.6 or INaP. These findings have implications for target discovery to reduce cardiac sympathetic activity without resorting to surgery.

neuroscience↗

Optical interrogation of sympathetic neuronal effects on macroscopic cardiac monolayer dynamics

Alterations in autonomic function are known to occur in cardiac conditions including sudden cardiac death. Cardiac stimulation via sympathetic neurons can potentially trigger arrhythmias. Dissecting direct neural-cardiac interactions at the cellular level is technically challenging and understudied due to the lack of experimental model systems and methodologies. Here we demonstrate the utility of optical interrogation of sympathetic neurons and their effects on macroscopic cardiac monolayer dynamics to address research targets such as the effects of adrenergic stimulation via the release of neurotransmitters, the effect of neuronal numbers on cardiac wave behaviour and the applicability of optogenetics in mechanistic in vitro studies. We combine photo-uncaging or optogenetic neural stimulation with imaging of cardiac monolayers to measure electrical activity in an automated fashion, illustrating the power and high throughput capability of such interrogations. The methods described highlight the challenges and benefits of co-cultures as experimental model systems.

biophysics↗