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Exploiting fly models to investigate rare human neurological disorders

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Neural Regeneration Research 2025年第1期20卷 21-28页

作者： Tomomi Tanaka Hyung-Lok Chung Department of Neurology Houston Methodist Research InstituteHoustonTXUSA Department of Neurology Weill Cornell Medical CollegeNew YorkNYUSA

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological *** attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted *** investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as dr.sophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary *** tools available in dr.sophila,including CRISPR-cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological *** boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential dr.g *** can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical *** this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic *** discuss rare diseases associated with both neuron-expressed and glial-expressed *** cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal *** we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell ***-of-fun

关键词： ACOX1 dr.sophila melanogaster glia lipid metabolism model organisms neuroinflammation neurologic disorders neuron rare disease VLCFA

A Nutrient Mixture Inhibits MMP Secretion, Invasion, Growth, and Induction of Apoptosis in Human Tongue cancer Cell Line SC-255

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Open Journal of Apoptosis 2013年第4期2卷 37-44页

作者： M. Waheed Roomi Nusrath W. Roomi Bilwa Bhanap Aleksandr. Niedzwiecki Matthias Rath dr. Rath Research Institute Oncology Division Santa Clara USA

A majority of oral cancers is squamous cell carcinoma and tongue carcinomas comprise 30% of all oral cancers. However, Phytochemicals, herbal and dietary antioxidants have been reported to prevent cancers. A nutrient mixture containing, ascorbic acid, lysine, proline and green tea extract, among other nutrients, has previously been shown to exhibit a broad spectrum chemo preventative and therapeutic anti-cancer properties in a number of cell lines. In a recent study, we found that the nutrient mixture significantly inhibited acetaminophen induced hepatic and renal toxicity, and it suppressed carbon tetrachloride induced hepatic toxicity in ICR mice as well. This study was undertaken to determine if the nutrient mixture is useful in inhibiting various parameters of cancer progression on human tongue cancer cell line SC-255. SC-255 cells were grown in a Dulbecco’s Eagle medium and treated with the nutrient mixture at 0, 10, 50, 100, 500 and 1000 μg/ml, in triplicate. The nutrient mixture exhibited 20% and 30% toxicity at 500 and 1000 μg/ml, respectively. Zymography demonstrated the expression of MMP-2 and MMP-9;and PMA treatment further enhanced MMP-9 activity. The nutrient mixture inhibited the secretion of MMP-2 and MMP-9 in a dose-dependent fashion with a total inhibition at 500 μg/ml. Matrigel invasion was significantly reduced by 40%, 80% and 100% at 100, 500 and 1000 μg/ml, respectively. The nutrient mixture also inhibited cell migration and induced apoptosis in a dose response fashion. Thus, the nutrient mixture may have a potential in the tongue cancer treatment.

关键词： Oral cancer Nutrient Mixture MMP Apoptosis

Abiotic Stress Tolerance： From Gene Discovery in Model Organisms to Crop Improvement

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Molecular Plant 2009年第1期2卷 1-2页

作者： Ray Bressan Hans Bohnert Jian-Kang Zhu Purdue University Department of Horticulture and Landscape Architecture 625 Agriculture Mall Drive West Lafayette IN 47907-2010 USA University of Illinois Department of Plant Biology ERML 196 1201 W. Gregory Dr. Urbana IL 61801 USA University of california Botany and Plant Sciences 2150 Batchelor Hall Institute for Integrative Genome Biology Riverside CA 92521 USA

Productive and sustainable agriculture necessitates growing plants in sub-optimal environments with less input of precious resources such as fresh water. For a better understanding and rapid improvement of abiotic stress tolerance, it is important to link physiological and biochemical work to molecular studies in genetically tractable model organisms. With the use of several technologies for the discovery of stress tolerance genes and their appropriate alleles, transgenic approaches to improving stress tolerance in crops remarkably parallels breeding principles with a greatly expanded germplasm base and will succeed eventually.

关键词： Abiotic Stress Tolerance From Gene Discovery

Early Mesoproterozoic evolution of midcontinental Laurentia: Defining the geon 14 Baraboo orogeny

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Geoscience Frontiers 2021年第5期12卷 37-53页

作者： L.Gordon Medaris Jr Brad S.Singer Brian R.Jicha David H.Malone Joshua J.Schwartz Esther K.Stewart Amanda Van Lankvelt Michael L.Williams Peter W.Reiners Department of Geoscience University of Wisconsin-MadisonMadisonWI 53706USA Department of Geography Geology&EnvironmentIllinois State UniversityNormalIL 61790USA Department of Geological Sciences California State University-NorthridgeNorthridgeCA 91330USA Wisconsin Geological&Natural History Survey MadisonWI 53705USA cameca Instruments 5470 Nobel Dr.MadisonWI 54711USA Department of Geosciences University of Massachusetts-AmherstAmherstMA 01003USA Department of Geosciences University of ArizonaTucsonAZ 85721USA

New geochronologic data from midcontinental Laurentia demonstrate that emplacement of the 1476-1470 Ma Wolf River granitic batholith was not an isolated igneous event,but was accompanied by regional metamorphism,deformation,and *** for such metamorphism and deformation is best seen in siliciclastic sedimentary rocks of the Baraboo Interval,which were deposited closely following the 1.65-1.63 Ga Mazatzal *** Baraboo Interval strata,muscovite parallel to slatey cleavage,in hydr.thermal veins,in quartzite breccia,and in metamorphosed paleosol yielded ^(40)Ar/^(39)Ar plateau ages of 1493-1465 *** addition,U-Th-total Pb dating of neoblastic overgrowths on detrital monazite gave an age of 1488±20 Ma,and recrystallized hematite in folded metapelite gave a mean U/Th-He age of 1411±39 ***-Baraboo,arkosic polymictic conglomerate,which contains detrital zircon with a minimum peak age of 1493 Ma,was intruded by a 1470 Ma granite porphyry at the northeastern margin of the Wolf River *** episode of magmatism,regional deformation and metamorphism,and sedimentation,which is designated herein as the Baraboo orogeny,provides a midcontinental link between the Picuris orogeny to the southwest and the Pinware orogeny to the northeast,completing the extent of early Mesoproterozoic(calymmian)orogenesis for 5000 km along the southern margin of *** transcontinental orogen is unique among Precambrian orogenies for its great width(-1600 km),the predominance of ferroan granites derived from partial melting of lower continental crust,and the prevalence of regional high T-P metamorphism related to advective heating by granitic magmas emplaced in the middle to upper crust.

关键词： Mesoproterozoic orogeny Ferroan granite Detrital zircon ^(40)Ar/^(39)Ar geochronology U-Th-total Pb geochronology U/Th-He geochronology

Advanced interatrial block as a key marker for atrial fibrillation recurrence： Bayes＇ syndr.me

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Journal of Geriatric cardiology 2017年第3期14卷 169-173页

作者： Adr.an Baranchuk Andr.s Enriquez Pavel Antiperovitch Bryce Alexander Goksel Cinier Department of Medicine Kingston General Hospital Queen's University Kingston Ontario Canada Section of cardiac Electrophysiology Hospital of the University of Pennsylvania Philadelphia Pennsylvania USA dr. Siyami Ersek Thoracic and cardiovascular Surgery Center Istanbul Turkey

It was not until 1979 that Bayes de Ltma described atrial conduction blocks and classified them as interatrial and intra- *** blocks refer to conduction disorders lo- cated between the atria, while intraalxial blocks occur within the same atrium. This work motivated several authors, in- cluding Bayes himself, to further investigate atrial conduc- tion and interatrial block （IAB）.

关键词： Atrial fibrillation Bayes syndr.me Bachmann's bundle Interatrial block

Low Thrust Minimum Time Orbit Transfer Nonlinear Optimization Using Impulse Discretization via the Modified Picard–Chebyshev Method

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Computer Modeling in Engineering & Sciences 2016年第1期111卷 1-27页

作者： Darin Koblick Shujing Xu Joshua Fogel Praveen Shankar california State University-Long Beach CAUSA. Millennium Space Systems Inc. El SegundoCAUSA. Claremont Graduate University CAUSA. University of california-San Diego CAUSA. University of Southern california Los AngelesCAUSA.

The Modified Picard-Chebyshev Method(MPCM)is implemented as an orbit propagation solver for a numerical optimization method that determines minimum time orbit transfer trajectory of a satellite using a series of multiple impulses at intermediate *** waypoints correspond to instantaneous impulses that are determined using a nonlinear constrained optimization routine,SNOPT with numerical force models for both Two-Body and J2 *** is found that using the MPCM increases run-time performance of the discretized lowthrust optimization method when compared to other sequential numerical solvers,such as Adams-Bashforth-Moulton and Gauss-Jackson 8th order methods.

关键词： Low Thrust Picard–Chebyshev Optimization Multi-Impulse Boundary Value Problem.

Advances in nanomaterials for brain microscopy

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Nano Research 2018年第10期11卷 5144-5172页

作者： Jackson T. Del Bonis-O'Donnell Linda Chio Gabriel F. Dorlhiac lan R. McFarlane Markita P. Landr. Department of Chemical and Biomolecular Engineering University of California Berkeley CA 94720 USA Biophysics Graduate Group University of California Berkeley CA 94720 USA Innovative Genomics Institute (IGI) Berkeley CA 94720 USA california Institute for Quantitative Biosciences QB3 University of California Berkeley CA 94720 USA Chan-Zuckerberg Biohub San Francisco CA 94158 USA

Microscopic imaging of the brain continues to reveal details of its structure, connectivity, and function. To further improve our understanding of the emergent properties and functions of neural circuits, we need to directly visualize the relationship between brain structure, neuron activity, and neurochemistry. Advances in the chemical and optical properties of nanomaterials, and developments in deep-tissue microscopy, may help to overcome the current challenges of in-vivo brain imaging, particularly when imaging the brain through optically-dense brain tissue, skull, and scalp. Developments in nanomaterials may enable the implementation of tunable chemical functionality for neurochemical targeting and sensing, and fluorescence stability for long-term imaging. In this review, we summarize the current methods used for brain microscopy and describe the diverse classes of nanomaterials recently offered as contrast agents and functional probes for microscopic optical imaging of the brain.

关键词： nanomaterials neuroscience imaging microscopy

Biopsy-free in vivo virtual histology of skin using deep learning

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Light(Science & Applications) 2021年第12期10卷 2421-2442页

作者： Jingxi Li Jason Garfinkel Xiaoran Zhang Di Wu Yijie Zhang Kevin de Haan Hongda Wang Tairan Liu Bijie Bai Yair Rivenson Gennady Rubinstein Philip O.Scumpia Aydogan Ozcan Electrical and Computer Engineering Department University of CaliforniaLos AngelesCA 90095USA Bioengineering Department University of CaliforniaLos AngelesCA 90095USA california NanoSystems Institute(CNSI) University of CaliforniaLos AngelesCA 90095USA Dermatology and Laser Centre Studio CityCA 91604USA Computer Science Department University of CaliforniaLos AngelesCA 90095USA Division of Dermatology University of CaliforniaLos AngelesCA 90095USA Department of Dermatology Veterans Affairs Greater Los Angeles Healthcare SystemLos AngelesCA 90073USA Department of Surgery University of CaliforniaLos AngelesCA 90095USA

An invasive biopsy followed by histological staining is the benchmark for pathological diagnosis of skin *** process is cumbersome and time-consuming,often leading to unnecessary biopsies and *** noninvasive optical technologies such as reflectance confocal microscopy(RCM)can provide label-free,cellular-level resolution,in vivo images of skin without performing a *** RCM is a useful diagnostic tool,it requires specialized training because the acquired images are grayscale,lack nuclear features,and are difficult to correlate with tissue ***,we present a deep learning-based framework that uses a convolutional neural network to rapidly transform in vivo RCM images of unstained skin into virtually-stained hematoxylin and eosin-like images with microscopic resolution,enabling visualization of the epidermis,dermal-epidermal junction,and superficial dermis *** network was trained under an adversarial learning scheme,which takes ex vivo RCM images of excised unstained/label-free tissue as inputs and uses the microscopic images of the same tissue labeled with acetic acid nuclear contrast staining as the ground *** show that this trained neural network can be used to rapidly perform virtual histology of in vivo,label-free RCM images of normal skin structure,basal cell carcinoma,and melanocytic nevi with pigmented melanocytes,demonstrating similar histological features to traditional histology from the same excised *** application of deep learning-based virtual staining to noninvasive imaging technologies may permit more rapid diagnoses of malignant skin neoplasms and reduce invasive skin biopsies.

关键词： network vivo virtual

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

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Neural Regeneration Research 2025年第11期20卷 3063-3075页

作者： Stephen Vidman Yee Hang Ethan Ma Nolan Fullenkamp Giles W.Plant Department of Neuroscience Ohio State UniversityColumbusOHUSA

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative *** the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained *** work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as *** embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns *** barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem *** advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal *** precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed *** the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma *** of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of *** the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor ***,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support ***,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for *** to a clinical setting wi

关键词： axon regeneration central nervous system regeneration induced pluripotent stem cells neurotrauma regenerative medicine spinal cord injury stem cell therapy