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Animal models of neurodegenerative diseases
Animal models of adult-onset neurodegenerative diseases have enhanced the understanding of the molecular pathogenesis of Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Nevertheless, our understanding of these disorders and the development of mechanistically designed therapeutics can still benefit from more rigorous use of the models and from generation of animals that more faithfully recapitulate human disease. Here we review the current state of rodent models for Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. We discuss the limitations and utility of current models, issues regarding translatability, and future directions for developing animal models of these human disorders.
Journal Article
Too much fun : the five lives of the Commodore 64 computer
\"A platform studies approach to the Commodore 64, considered by Guinness World records as the highest-selling single computer model of all time\"-- Provided by publisher.
BOOK
Pesticide exposure and the microbiota-gut-brain axis
The gut microbiota exist within a dynamic ecosystem shaped by various factors that includes exposure to xenobiotics such as pesticides. It is widely regarded that the gut microbiota plays an essential role in maintaining host health, including a major influence on the brain and behaviour. Given the widespread use of pesticides in modern agriculture practices, it is important to assess the long-term collateral effects these xenobiotic exposures have on gut microbiota composition and function. Indeed, exposure studies using animal models have shown that pesticides can induce negative impacts on the host gut microbiota, physiology and health. In tandem, there is a growing body of literature showing that the effects of pesticide exposure can be extended to the manifestation of behavioural impairments in the host. With the increasing appreciation of the microbiota-gut-brain axis, in this review we assess whether pesticide-induced changes in gut microbiota composition profiles and functions could be driving these behavioural alterations. Currently, the diversity of pesticide type, exposure dose and variation in experimental designs hinders direct comparisons of studies presented. Although many insights presented, the mechanistic connection between the gut microbiota and behavioural changes remains insufficiently explored. Future experiments should therefore focus on causal mechanisms to examine the gut microbiota as the mediator of the behavioural impairments observed in the host following pesticide exposure.
Journal Article
Optical imaging of metabolic dynamics in animals
Direct visualization of metabolic dynamics in living animals with high spatial and temporal resolution is essential to understanding many biological processes. Here we introduce a platform that combines deuterium oxide (D
2
O) probing with stimulated Raman scattering (DO-SRS) microscopy to image in situ metabolic activities. Enzymatic incorporation of D
2
O-derived deuterium into macromolecules generates carbon–deuterium (C–D) bonds, which track biosynthesis in tissues and can be imaged by SRS in situ. Within the broad vibrational spectra of C–D bonds, we discover lipid-, protein-, and DNA-specific Raman shifts and develop spectral unmixing methods to obtain C–D signals with macromolecular selectivity. DO-SRS microscopy enables us to probe de novo lipogenesis in animals, image protein biosynthesis without tissue bias, and simultaneously visualize lipid and protein metabolism and reveal their different dynamics. DO-SRS microscopy, being noninvasive, universally applicable, and cost-effective, can be adapted to a broad range of biological systems to study development, tissue homeostasis, aging, and tumor heterogeneity.
Non-destructive methods to image metabolism in situ in living tissues are limited. Here the authors combine deuterium oxide probing and stimulated Raman scattering microscopy to image lipid metabolic dynamics and protein synthesis in cells and in vivo in mice,
C. elegans
, and zebrafish.
Journal Article
إمارة حمص خلال العصر الروماني : دراسة تاريخية (64 ق. م.-273 م)
يسلط الكتاب الضوء على التحولات السياسية والاجتماعية التي شهدتها مدينة حمص خلال الحقبة الرومانية. يدرس العلاقة بين حمص والإمبراطورية الرومانية، سواء من حيث الإدارة أو الاقتصاد أو الدين. يناقش الكيفية التي حافظت بها حمص على هويتها المحلية الكنعانية-الآرامية، بالرغم من التأثير الروماني الثقافي والسياسي. كما يتناول الأوضاع السياسية لحمص في نهاية العصر السلجوقي، توسع إمارة حمص والمتغيرات المحلية.
Book
Maintenance of postmitotic neuronal cell identity
This Review discusses the molecular mechanisms by which neuronal identity is maintained throughout animals' development and lives. Drawing from the invertebrate and vertebrate literature, Deneris and Hobert also describe common themes, where the initial specification of neurons and subsequent maintenance of cell identity may share transcriptional programming and transcription factors. The piece also discusses such mechanism's implications for neurological diseases.
The identity of specific cell types in the nervous system is defined by the expression of neuron type–specific gene batteries. How the expression of such batteries is initiated during nervous system development has been under intensive study over the past few decades. However, comparatively little is known about how gene batteries that define the terminally differentiated state of a neuron type are maintained throughout the life of an animal. Here we provide an overview of studies in invertebrate and vertebrate model systems that have carved out the general and not commonly appreciated principle that neuronal identity is maintained in postmitotic neurons by the sustained, and often autoregulated, expression of the same transcription factors that initiate terminal differentiation in a developing organism. Disruption of postmitotic maintenance mechanisms may result in neuropsychiatric and neurodegenerative conditions.
Journal Article
BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons
Optogenetic manipulation of neuronal activity through excitatory and inhibitory opsins has become an indispensable experimental strategy in neuroscience research. For many applications bidirectional control of neuronal activity allowing both excitation and inhibition of the same neurons in a single experiment is desired. This requires low spectral overlap between the excitatory and inhibitory opsin, matched photocurrent amplitudes and a fixed expression ratio. Moreover, independent activation of two distinct neuronal populations with different optogenetic actuators is still challenging due to blue-light sensitivity of all opsins. Here we report BiPOLES, an optogenetic tool for potent neuronal excitation and inhibition with light of two different wavelengths. BiPOLES enables sensitive, reliable dual-color neuronal spiking and silencing with single- or two-photon excitation, optical tuning of the membrane voltage, and independent optogenetic control of two neuronal populations using a second, blue-light sensitive opsin. The utility of BiPOLES is demonstrated in worms, flies, mice and ferrets.
Currently, bidirectional control of activity in the same neurons in the same experiment is difficult. Here the authors report a Bidirectional Pair of Opsins for Light-induced Excitation and Silencing, BiPOLES, which they use in a range of organisms including worms, fruit flies, mice and ferrets.
Journal Article