A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells

<p>Abstract</p> <p>Background</p> <p>Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca²⁺signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO₂NPs), a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain.</p> <p>Results</p> <p>TiO₂NP exposure increased both histamine secretion and cytosolic Ca²⁺concentration ([Ca²⁺]_C) in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca²⁺levels resulted primarily from an extracellular Ca²⁺influx via membrane L-type Ca²⁺channels. Unspecific Ca²⁺entry via TiO₂NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO₂NPs also contributed to cytosolic Ca²⁺signaling. The PLC-IP₃-IP₃receptor pathways and endoplasmic reticulum (ER) were responsible for the sustained elevation of [Ca²⁺]_Cand histamine secretion.</p> <p>Conclusion</p> <p>Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO₂NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.</p

Pancreas and islet cell transplantation

Currently, for the patient with type 1 diabetes, a definitive treatment without resorting to the use of exogenous insulin can be achieved only with pancreas or islet cell transplantation. These means of restoring β-cell mass can completely maintain essentially normal long-term glucose homeostasis, although the need for powerful immunosuppressive regimens limits their application to only a subgroup of adult patients. Apart from the shortage of donors that has limited all kinds of transplantation, however, the widespread use of β-cell replacement has been precluded until recently by the drawbacks associated with both organ and islet cell transplantation. Although the study of recurrence of diabetes has generated attention, the fundamental obstacle to pancreas and islet transplantation has been, and remains, the alloimmune response. With a better elucidation of the mechanisms of alloengraftment achieved during the last 3 years, the stage has been set for further advances

The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability

Aim: Symptoms of autonomic failure are frequently the presentation of advanced age and neurodegenerative diseases that impair adaptation to common physiologic stressors. The aim of this work was to examine the interaction between the sympathetic and motor nervous system, the involvement of the sympathetic nervous system (SNS) in neuromuscular junction (NMJ) presynaptic motor function, the stability of postsynaptic molecular organization, and the skeletal muscle composition and function. Methods: Since muscle weakness is a symptom of diseases characterized by autonomic dysfunction, we studied the impact of regional sympathetic ablation on muscle motor innervation by using transcriptome analysis, retrograde tracing of the sympathetic outflow to the skeletal muscle, confocal and electron microscopy, NMJ transmission by electrophysiological methods, protein analysis, and state of the art microsurgical techniques, in C57BL6, MuRF1KO and Thy-1 mice. Results: We found that the SNS regulates motor nerve synaptic vesicle release, skeletal muscle transcriptome, muscle force generated by motor nerve activity, axonal neurofilament phosphorylation, myelin thickness, and myofibre subtype composition and CSA. The SNS also modulates the levels of postsynaptic membrane acetylcholine receptor by regulating the Gα i2 -Hdac4-Myogenin-MuRF1pathway, which is prevented by the overexpression of the guanine nucleotide-binding protein Gα i2 (Q205L), a constitutively active mutant G protein subunit. Conclusion: The SNS regulates NMJ transmission, maintains optimal Gα i2 expression, and prevents any increase in Hdac4, myogenin, MuRF1, and miR-206. SNS ablation leads to upregulation of MuRF1, muscle atrophy, and downregulation of postsynaptic AChR. Our findings are relevant to clinical conditions characterized by progressive decline of sympathetic innervation, such as neurodegenerative diseases and aging.Fil: Rodrigues, Anna C. Zaia. Wake Forest School of Medicine; Estados UnidosFil: Messi, Maria Laura. Wake Forest School of Medicine; Estados UnidosFil: Wang, Zhong Min. Wake Forest School of Medicine; Estados UnidosFil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Pereyra, Andrea Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Wake Forest School of Medicine; Estados UnidosFil: Birbrair, Alexander. Wake Forest School of Medicine; Estados UnidosFil: Zhang, Tan. Wake Forest School of Medicine; Estados UnidosFil: O´Meara, Meaghan. Wake Forest School of Medicine; Estados UnidosFil: Kwan, Ping. Wake Forest School of Medicine; Estados UnidosFil: Lopez, Elsa I. S.. Wake Forest School of Medicine; Estados UnidosFil: Willis, Monte S.. University of North Carolina; Estados UnidosFil: Mintz, Akiva. Wake Forest School of Medicine; Estados UnidosFil: Files, D. Clark. University of North Carolina; Estados UnidosFil: Furdui, Cristina. Wake Forest School of Medicine; Estados UnidosFil: Oppenheim, Ronald W.. Wake Forest School of Medicine; Estados UnidosFil: Delbono, Osvaldo. Wake Forest School of Medicine; Estados Unido

What is the biological basis of pattern formation of skin lesions?

Pattern recognition is at the heart of clinical dermatology and dermatopathology. Yet, while every practitioner of the art of dermatological diagnosis recognizes the supreme value of diagnostic cues provided by defined patterns of 'efflorescences', few contemplate on the biological basis of pattern formation in and of skin lesions. Vice versa, developmental and theoretical biologists, who would be best prepared to study skin lesion patterns, are lamentably slow to discover this field as a uniquely instructive testing ground for probing theoretical concepts on pattern generation in the human system. As a result, we have at best scraped the surface of understanding the biological basis of pattern formation of skin lesions, and widely open questions dominate over definitive answer. As a symmetry-breaking force, pattern formation represents one of the most fundamental principles that nature enlists for system organization. Thus, the peculiar and often characteristic arrangements that skin lesions display provide a unique opportunity to reflect upon – and to experimentally dissect – the powerful organizing principles at the crossroads of developmental, skin and theoretical biology, genetics, and clinical dermatology that underlie these – increasingly less enigmatic – phenomena. The current 'Controversies' feature offers a range of different perspectives on how pattern formation of skin lesions can be approached. With this, we hope to encourage more systematic interdisciplinary research efforts geared at unraveling the many unsolved, yet utterly fascinating mysteries of dermatological pattern formation. In short: never a dull pattern

Imagining technology-enhanced learning with heritage artefacts: teacher-perceived potential of 2D and 3D heritage site visualisations

Background: There is much to be realised in the educational potential of national and world heritage sites. Such sites need to be supported in sharing their resources with a wide and international public, especially within formal education. Two-dimensional (2D) and three-dimensional (3D) heritage site visualisations could serve this need. Our study focuses on the teacher-perceived possibilities and benefits for education around such visualisations. Purpose: We describe how a group of UK teachers perceive the potential of cross-curricular learning that could arise from an Italian world heritage site. The teachers commented on 2D visualisations of artefacts from this site, as well as the design of a 3D immersive environment to serve educational purposes. We consider as follows: (1) how the cross-curricular teaching potential of such resources is perceived, and (2) what design features of a 3D immersive environment teachers suggest are needed for educational explorations. Sample: We recruited 10 teachers from the Midlands region of the UK and carried out semi-structured interviews. Methods: Interviews were transcribed and a thematic analysis applied to the conversations. Questioning was grounded in the examination of 2D and 3D visual resources. This provoked cross-curricular and educational design thinking. Results: Teacher responses highlighted a wide range of cross-curricular possibilities. However, they expressed a more ‘assimilative’ than ‘accommodative’ approach when relating resources to the curriculum. Such ‘assimilation’ involved seeing the site artefacts as raw material for more instrumental ‘curriculum activities’ (e.g. within art and design, geography, maths or literacy) rather than a more accommodative approach whereby curricular disciplines were exercised to make new meaning from the artefacts. In relation to 3D technology design, most teachers highlighted three technology features that would render it well matched to educational practice and three educational benefits over non-3D immersive environments. Conclusions: Teachers can easily imagine a rich range of opportunities to utilise 2D and 3D heritage site artefacts within the curriculum. However, the largely assimilative nature of this cross-curricular appropriation suggests the value of providing more guidance and support to teachers in the interpretation and application of artefacts. Their design suggestions can usefully inform construction of educational features within 3D immersive technologies that support heritage site experiences

Tendencies, variability and persistence of sea surface temperature anomalies

Quantifying global trends and variability in sea surface temperature (SST) is of fundamental importance to understanding changes in the Earth’s climate. One approach to observing SST is via remote sensing. Here we use a 37-year gap-filled, daily-mean analysis of satellite SSTs to quantify SST trends, variability and persistence between 1981-2018. The global mean warming trend is 0.08 K per decade globally, with 95 % of local trends being between -0.1 K and +0.35 K. Excluding perennial sea-ice regions, the mean warming trend is 0.11 K per decade. After removing the long-term trend we calculate the SST power spectra over different time periods. The maximum variance in the SST power spectra in the equatorial Pacific is 1.9 K2 on 1-5 year timescales, dominated by ENSO processes. In western boundary currents characterised by an intense mesoscale activity, SST power on sub-annual timescales dominates, with a maximum variance of 4.9 K2. Persistence timescales tend to be shorter in the summer hemisphere due to the shallower mixed layer. The median short-term persistence length is 11-14 days, found over 71-79 % of the global ocean area, with seasonal variations. The mean global correlation between monthly SST anomalies with a three-month time-lag is 0.35, with statistically significant correlations over 54.0 % of the global oceans, and notably in the northern and equatorial Pacific, and the sub-polar gyre south of Greenland. At six months, the mean global SST anomaly correlation falls to 0.18. The satellite data record enables the detailed characterisation of temporal changes in SST over almost four decades