Plasticity in visual cortex is disrupted in a mouse model of tauopathy

Alzheimer’s disease and other dementias are thought to underlie a progressive impairment of neural plasticity. Previous work in mouse models of Alzheimer’s disease shows pronounced changes in artificially-induced plasticity in hippocampus, perirhinal and prefrontal cortex. However, it is not known how degeneration disrupts intrinsic forms of brain plasticity. Here we characterised the impact of tauopathy on a simple form of intrinsic plasticity in the visual system, which allowed us to track plasticity at both long (days) and short (minutes) timescales. We studied rTg4510 transgenic mice at early stages of tauopathy (5 months) and a more advanced stage (8 months). We recorded local field potentials in the primary visual cortex while animals were repeatedly exposed to a stimulus over 9 days. We found that both short- and long-term visual plasticity were already disrupted at early stages of tauopathy, and further reduced in older animals, such that it was abolished in mice expressing mutant tau. Additionally, visually evoked behaviours were disrupted in both younger and older mice expressing mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy. This simple measure of plasticity may help understand how tauopathy disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease

Altered low-frequency brain rhythms precede changes in gamma power during tauopathy

Neurodegenerative disorders are associated with widespread disruption to brain activity and brain rhythms. Some disorders are linked to dysfunction of the membrane-associated protein Tau. Here, we ask how brain rhythms are affected in rTg4510 mouse model of tauopathy, at an early stage of tauopathy (5 months), and at a more advanced stage (8 months). We measured brain rhythms in primary visual cortex in presence or absence of visual stimulation, while monitoring pupil diameter and locomotion to establish behavioral state. At 5 months, we found increased low-frequency rhythms during resting state in tauopathic animals, associated with periods of abnormally increased neural synchronization. At 8 months, this increase in low-frequency rhythms was accompanied by a reduction of power in the gamma range. Our results therefore show that slower rhythms are impaired earlier than gamma rhythms in this model of tauopathy, and suggest that electrophysiological measurements can track the progression of tauopathic neurodegeneration

The orthogonality of the fractional circle polynomials and its application in modeling of ophthalmic surfaces

In this paper we establish some new fractional differential properties for a class of fractional circle polynomials. We apply the Zernike polynomials and a new class of fractional circle polynomials in modeling ophthalmic surfaces in visual optics and we compare the obtained results. The total RMS error is presented when addressing capability of these functions in fitting with surfaces, and it is showed that the new fractional circle polynomials can be used as an alternative to the Zernike Polynomials to represent the complete anterior corneal surface.publishe

Establishing a link between endothelial cell metabolism and vascular behaviour in a type 1 diabetes mouse model

Background/Aims: Vascular complications contribute significantly to the extensive morbidity and mortality rates observed in people with diabetes. Despite well known that the diabetic kidney and heart exhibit imbalanced angiogenesis, the mechanisms implicated in this angiogenic paradox remain unknown. In this study, we examined the angiogenic and metabolic gene expression profile (GEP) of endothelial cells (ECs) isolated from a mouse model with type1 diabetes mellitus (T1DM). Methods: ECs were isolated from kidneys and hearts of healthy and streptozocin (STZ)-treated mice. RNA was then extracted for molecular studies. GEP of 84 angiogenic and 84 AMP-activated Protein Kinase (AMPK)-dependent genes were examined by microarrays. Real time PCR confirmed the changes observed in significantly altered genes. Microvessel density (MVD) was analysed by immunohistochemistry, fibrosis was assessed by the Sirius red histological staining and connective tissue growth factor (CTGF) was quantified by ELISA. Results: The relative percentage of ECs and MVD were increased in the kidneys of T1DM animals whereas the opposite trend was observed in the hearts of diabetic mice. Accordingly, the majority of AMPK-associated genes were upregulated in kidneys and downregulated in hearts of these animals. Angiogenic GEP revealed significant differences in Tgfß, Notch signaling and Timp2 in both diabetic organs. These findings were in agreement with the angiogenesis histological assays. Fibrosis was augmented in both organs in diabetic as compared to healthy animals. Conclusion: Altogether, our findings indicate, for the first time, that T1DM heart and kidney ECs present opposite metabolic cues, which are accompanied by distinct angiogenic patterns. These findings enable the development of innovative organ-specific therapeutic strategies targeting diabetic-associated vascular disorders.This work was supported by CAPES (Sciences without Borders - Full Doctorate Fellowship – Process 10010-13-0); FEDER funds by COMPETE: [POCI-01-0145-FEDER-007440, POCI-01-0145-FEDER-016385]; NORTE2020 [NORTE-01-0145FEDER-000012]; HealthyAging2020 [CENTRO-01-0145-FEDER-000012-N2323]; FCT - Fundação para a Ciência e a Tecnologia [UID/BIM/04293/2013, EXPL/BIM-MED/0492/2012, SFRH/BPD/88745/2012, SFRH/BD/111799/2015]; Claude Pepper Older Americans Independence Center; grant: P30 AG028718, NIGMS Award P20GM109096; European Structural and Investment Funds (ESIF). AUTHOR CONTRIBUTION: CS and RS participated in the design and conception of the study; CS performed the whole laboratory and statistical analyses and drafted the manuscript; VSP, PPO, DSN carried out the FACS assay design and data acquisition, as well as the interpretation of FACS data; SA advised and performed microarray and RT-PCR assays; IR headed the parafin embedded tissue and histologial staining; SG, EC were responsible for the animal studies and immunohistochemistry analyses; RC advised the methodological laboratorial analysis and animal studies; RS and EC critically revised the manuscript for important intellectual content. All authors were involved in drafting and revising the article. All authors read and approved the final version of the manuscript

Creating and controlling visual environments using BonVision.

Real-time rendering of closed-loop visual environments is important for next-generation understanding of brain function and behaviour, but is often prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. BonVision has been tested on humans and mice, and is capable of supporting new experimental designs in other animal models of vision. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks, and communication with behavioural and physiological measurement and manipulation devices

Biogeographical ancestry is associated with socioenvironmental conditions and infections in a Latin American urban population.

Racial inequalities are observed for different diseases and are mainly caused by differences in socioeconomic status between ethnoracial groups. Genetic factors have also been implicated, and recently, several studies have investigated the association between biogeographical ancestry (BGA) and complex diseases. However, the role of BGA as a proxy for non-genetic health determinants has been little investigated. Similarly, studies comparing the association of BGA and self-reported skin colour with these determinants are scarce. Here, we report the association of BGA and self-reported skin colour with socioenvironmental conditions and infections. We studied 1246 children living in a Brazilian urban poor area. The BGA was estimated using 370,539 genome-wide autosomal markers. Standardised questionnaires were administered to the children's guardians to evaluate socioenvironmental conditions. Infection (or pathogen exposure) was defined by the presence of positive serologic test results for IgG to seven pathogens (Toxocara spp, Toxoplasma gondii, Helicobacter pylori, and hepatitis A, herpes simplex, herpes zoster and Epstein-Barr viruses) and the presence of intestinal helminth eggs in stool samples (Ascaris lumbricoides and Trichiuris trichiura). African ancestry was negatively associated with maternal education and household income and positively associated with infections and variables, indicating poorer housing and living conditions. The self-reported skin colour was associated with infections only. In stratified analyses, the proportion of African ancestry was associated with most of the outcomes investigated, particularly among admixed individuals. In conclusion, BGA was associated with socioenvironmental conditions and infections even in a low-income and highly admixed population, capturing differences that self-reported skin colour miss. Importantly, our findings suggest caution in interpreting significant associations between BGA and diseases as indicative of the genetic factors involved

Valorizing the 'Irulas' traditional knowledge of medicinal plants in the Kodiakkarai Reserve Forest, India

A mounting body of critical research is raising the credibility of Traditional Knowledge (TK) in scientific studies. These studies have gained credibility because their claims are supported by methods that are repeatable and provide data for quantitative analyses that can be used to assess confidence in the results. The theoretical importance of our study is to test consensus (reliability/replicable) of TK within one ancient culture; the Irulas of the Kodiakkarai Reserve Forest (KRF), India. We calculated relative frequency (RF) and consensus factor (Fic) of TK from 120 Irulas informants knowledgeable of medicinal plants. Our research indicates a high consensus of the Irulas TK concerning medicinal plants. The Irulas revealed a diversity of plants that have medicinal and nutritional utility in their culture and specific ethnotaxa used to treat a variety of illnesses and promote general good health in their communities. Throughout history aboriginal people have been the custodians of bio-diversity and have sustained healthy life-styles in an environmentally sustainable manner. However this knowledge has not been transferred to modern society. We suggest this may be due to the asymmetry between scientific and TK, which demands a new approach that considers the assemblage of TK and scientific knowledge. A greater understanding of TK is beginning to emerge based on our research with both the Irulas and Malasars; they believe that a healthy lifestyle is founded on a healthy environment. These aboriginal groups chose to share this knowledge with society-at-large in order to promote a global lifestyle of health and environmental sustainability

A time-fractional Borel-Pompeiu formula and a related hypercomplex operator calculus

In this paper we develop a time-fractional operator calculus in fractional Clifford analysis. Initially we study the $L_p$-integrability of the fundamental solutions of the multi-dimensional time-fractional diffusion operator and the associated time-fractional parabolic Dirac operator. Then we introduce the time-fractional analogues of the Teodorescu and Cauchy-Bitsadze operators in a cylindrical domain, and we investigate their main mapping properties. As a main result, we prove a time-fractional version of the Borel-Pompeiu formula based on a time-fractional Stokes' formula. This tool in hand allows us to present a Hodge-type decomposition for the forward time-fractional parabolic Dirac operator with left Caputo fractional derivative in the time coordinate. The obtained results exhibit an interesting duality relation between forward and backward parabolic Dirac operators and Caputo and Riemann-Liouville time-fractional derivatives. We round off this paper by giving a direct application of the obtained results for solving time-fractional boundary value problems.The work of M. Ferreira, M.M. Rodrigues and N. Vieira was supported by Portuguese funds through CIDMA-Center for Research and Development in Mathematics and Applications, and FCT–Fundação para a Ciência e a Tecnologia, within project UID/MAT/04106/2019. The work of the authors was supported by the project New Function Theoretical Methods in Computational Electrodynamics / Neue funktionentheoretische Methoden für instationäre PDE, funded by Programme for Cooperation in Science between Portugal and Germany (“Programa de Ações Integradas Luso-Alemãs 2017” - DAAD-CRUP - Acção No. A-15/17 / DAAD-PPP Deutschland-Portugal, Ref: 57340281). N. Vieira was also supported by FCT via the FCT Researcher Program 2014 (Ref: IF/00271/2014).publishe