Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

Background.Xenon is a noble gas with neuroprotective properties. We previously showed that xenon improves short and long-term outcomes in young adult mice after controlled cortical impact (CCI). This is a follow-up study investigating xenon’s effect on very long-term outcome and survival. Methods.C57BL/6N (n=72) young adult male mice received single CCI or sham surgery and were treated with either xenon (75%Xe:25%O2) or control gas (75% N2:25%O2). The outcomes used were: 1) 24-hour lesion volume and neurological outcome score; 2)contextual fear-conditioning at 2 weeks and 20 months; 3) corpus callosum white matter quantification; 4) immunohistological assessment of neuroinflammation and neuronal loss; 5) long-term survival. Results.Xenon treatment significantly reduced secondary injury development (p<0.05), improved short-term vestibulomotor function (p<0.01),and prevented development of very late-onset traumatic brain injury (TBI)-related memory deficits. Xenon treatment reducedwhite matter loss in the contralateral corpus callosum and neuronal loss in the contralateral hippocampal CA1 andDG areas at 20 months. Xenon’s long-term neuroprotective effects were associated with a significant (p<0.05) reduction in neuroinflammation in multiple brain areas involved in associative memory, including reduction in reactive astrogliosis and microglial cell proliferation. Survival was improved significantly (p<0.05) in xenon-treated animals, compared to untreated animals up to 12 months after injury.Conclusions.These results show that xenon treatment after TBI results in very long-term improvements in clinically relevant outcomes and survival. Our findings support the idea that xenon treatment shortly after TBI may have long-term benefits in the treatment of brain trauma patients

The Barretos Cancer Hospital Animal Facility: implementation and results of a dedicated platform for preclinical oncology models

The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy.This study was funded by the Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer) and by Pio XII Foundation, Barretos Cancer Hospital internal funds, Grant Number: 13/2021

Brain angioarchitecture and intussusceptive microvascular growth in a murine model of Krabbe disease

Abstract Defects of the angiogenic process occur in the brain of twitcher mouse, an authentic model of human Krabbe disease caused by genetic deficiency of lysosomal b-galactosylceramidase (GALC), leading to lethal neurological dysfunctions and accumulation of neurotoxic psychosine in the central nervous system. Here, quantitative computational analysis was used to explore the alterations of brain angioarchitecture in twitcher mice. To this aim, customized ImageJ routines were used to assess calibers, amounts, lengths and spatial dispersion of CD31? vessels in 3D volumes from the postnatal frontal cortex of twitcher animals. The results showed a decrease in CD31 immunoreactivity in twitcher brain with a marked reduction in total vessel lengths coupled with increased vessel fragmentation. No significant changes were instead observed for the spatial dispersion of brain vessels throughout volumes or in vascular calibers. Notably, no CD31? vessel changes were detected in twitcher kidneys in which psychosine accumulates at very low levels, thus confirming the specificity of the effect. Microvascular corrosion casting followed by scanning electron microscopy morphometry confirmed the presence of significant alterations of the functional angioarchitecture of the brain cortex of twitcher mice with reduction in microvascular density, vascular branch remodeling and intussusceptive angiogenesis. Intussusceptive microvascular growth, con- firmed by histological analysis, was paralleled by alterations of the expression of intussusception-related genes in twitcher brain. Our data support the hypothesis that a marked decrease in vascular development concurs to the onset of neuropathological lesions in twitcher brain and suggest that neuroinflammation-driven intussusceptive responses may represent an attempt to compensate impaired sprouting angiogenesis

Hilltown Able: a unit memoir of Battery A--744th Field Artillery Battalion to V-E day

The American Third Army is the cockiest of all the armies and the fastest-moving. Long on armor, it is led by Lieut. General George S. Patton Jr. and, like him, it is colorful, proud and bold. Its motto is speed and more speed. Its record is the best possible evidence that Marshall and Eisenhower were right when they refused to fire Patton after the face-slapping incident in Sicily.https://digicom.bpl.lib.me.us/ww_reg_his/1010/thumbnail.jp

Apocalypse - 2002

Contributers include: Danny Byzantine, Corey Emory, Stone Abang, James Nguyen, John Desjarlais, Michael L. Johnson, John Grey, Eric Shapiro, Melissa K. Simmons, Dennis Van Wey, Daniel Green, Jenene O. Ravesloot, Jane McClellan, Diana Smith, Corey Emory, Chris-Marie Ware, Mike Catalano, B.Z. Niditchhttps://neiudc.neiu.edu/apocalypse/1005/thumbnail.jp

Washington University Record, October 1, 1998

https://digitalcommons.wustl.edu/record/1804/thumbnail.jp

Bird song as a basis for new techniques and improvisational practice with the baroque flute

Merged with duplicate record 10026.1/2753 on 03.04.2017 by CS (TIS)Subsequent to a period of training as a flautist, I ultimately specialised professionally on the baroque flute. Consequently, a significant part of my research for a PhD was practice-led. My later career; concerned with dance and choreography, represented a widening and diversification of my interest in music in particular, and the allied arts in general. This was (and continues to be) paralleled, however, with a substantial research-interest in aspects of the performance of music and its potential interconnection(s) with modalities of speech. However, my own research commenced with a strong desire to discover new performance techniques on the baroque flute. Earlier performer/composers on the instrument explored, documented and analysed new ways of performing on the instrument. This research continues that form of practice-led investigation. This investigation has been centred on performance-experiments of an often improvisatory kind, but by the time of its completion, I too became a performer/composer on the instrument. The research became focussed on a critical and analytical study of birdsong. Birdsong offers a degree of pitch and timbral variation of phenomenal power. My research questioned and interrogated the structure; modes of delivery and sonorities in birdsong because I wanted to devise a new method of playing that might approach these avian sonic possibilities and by absorbance, produce a new musical language on the baroque flute. Previous ornithological writings (Thorpe; Armstrong, Hartshorne, et at) have frequently considered birdsong as a form of music. Thus, my research examined documentary outcomes from research into birdsong in the form of analysis of recordings, and critical scrutiny of sonographs. Birds `perform' in varying degrees of tonal, atonal and microtonal systems. The research paralleled these treatments of pitch and harmony. It also addressed issues of structure, dynamics, timbre, rhythm and the physical aspects of delivery with the intention of devising a new `method' for the generation of a new music for the instrument. The research has of course been polymodal and interdisciplinary. It consisted of the following methodological, practical and theoretical domains, namely: • critical and analytical readings in the science of ornithology; especially birdsong • critical and analytical readings in historical models for performance on the baroque flute; • field-studies in the form of recordings and notational transcriptions (via Messiaen and Cowie, et al) of birdsong; • practical experiments as a soloist (improviser) together with collaborative, experimental and practical research with an ensemble and/or another baroque flautist. The purpose of this research was to find new techniques for contemporary musicians, accompanied by a body of writing that embodies a kind of treatise on the instrument with potential for use by other contemporary musicians. Thus, the written thesis, together with recordings of experiments, improvisations and concert-performance should be considered as a collective body of new knowledge in relation to performance on the baroque flute in particular, but with potential for use by other (or all) musical instruments. My findings are that: • a new performance technique is required as a result of a study of birdsong and with the effect of producing a vastly extended repertoire of effects and pitch frequencies on the instrument; • this new technique generates a new musical language particularly in respect of treatments of microtonality; new breathing and fingering techniques; • the technique is transferable by teaching and demonstration to other performers and of potential use for contemporary composers writing for the instrument; • these new techniques were enhanced (if not made entirely possible) by field-studies and cross-disciplinary (arts/sciences) and illustrate the potency of cross-field research in the generation of new music. The principal outcome of my research was the development of a system of playing that has now been named by me as ecosonic performance. It is so-named, because the performance-techniques developed are based on a phenomenological study of the ecology of sound in birds; themselves already ecosonic performers. This written thesis is a documentation of my modalities of research, experimentation and practice. It is designed in the form of a commentary/treatise, and should be considered as a form of `primer', not only for the baroque flute, but also for the further investigation of the performance-capabilities of any musical instrument

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

Background: Limited knowledge of stem cell therapies‘ mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods: We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo. Findings: PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. Interpretation: Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. Funding: Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Healt

Embodied prediction

Versions of the “predictive brain” hypothesis rank among the most promising and the most conceptually challenging visions ever to emerge from computational and cognitive neuroscience. In this paper, I briefly introduce (section 1) the most radical and comprehensive of these visions —the account of “active inference”, or “action-oriented predictive processing” (Clark 2013a), developed by Karl Friston and colleagues. In section 2, I isolate and discuss four of the framework’s most provocative claims: (i) that the core flow of information is top-down, not bottom-up, with the forward flow of sensory information replaced by the forward flow of prediction error; (ii) that motor control is just more top-down sensory prediction; (iii) that efference copies, and distinct “controllers”, can be replaced by top-down predictions; and (iv) that cost functions can fruitfully be replaced by predictions. Working together, these four claims offer a tantalizing glimpse of a new, integrated framework for understanding perception, action, embodiment, and the nature of human experience. I end (section 3) by sketching what may be the most important aspect of the emerging view: its ability to embed the use of fast and frugal solutions (as highlighted by much work in robotics and embodied cognition) within an over-arching scheme that includes more structured, knowledge-intensive strategies, combining these fluently and continuously as task and context dictate