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The Search for Putative Hits in Combating Leishmaniasis:The Contributions of Natural Products Over the Last Decade

Natural Products and Bioprospecting 2021年第5期11卷 489-544页

作者： Patrick O.Sakyi richard k.amewu Robert N.O.A.Devine Emahi Ismaila Whelton A.Miller Samuel k.kwofie Department of Chemistry School of Physical and Mathematical SciencesCollege of Basic and Applied SciencesUniversity of GhanaP.O.BOX LG 56LegonAccraGhana Department of Chemical Sciences School of SciencesUniversity of Energy and Natural ResourcesBox 214SunyaniGhana Department of Medicine Loyola University Medical CenterMaywoodIL 60153USA Department of Molecular Pharmacology and Neuroscience Loyola University Medical CenterMaywoodIL 60153USA Department of Chemical and Biomolecular Engineering School of Engineering and Applied ScienceUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Biomedical Engineering School of Engineering SciencesCollege of Basic&Applied SciencesUniversity of GhanaPMB LG 77LegonAccraGhana Department of Biochemistry Cell and Molecular BiologyWest African Centre for Cell Biology of Infectious PathogensCollege of Basic and Applied SciencesUniversity of GhanaP.O.Box LG 54AccraGhana

Despite advancements in the areas of omics and chemoinformatics,potent novel biotherapeutic molecules with new modes of actions are needed for *** socioeconomic burden of leishmaniasis remains alarming in endemic ***,reports from existing endemic areas such as Nepal,Iran,Brazil,India,Sudan and Afghanistan,as well as newly affected countries such as Peru,Bolivia and Somalia indicate concerns of chemoresistance to the classical antimonial *** a result,effective antileishmanial agents which are safe and affordable are urgently *** products from both flora and fauna have contributed immensely to chemotherapeutics and serve as vital sources of new chemical *** review focuses on a systematic cross-sectional view of all characterized anti-leishmanial compounds from natural sources over the last ***,IC_(50)/EC_(50),cytotoxicity and suggested mechanisms of action of some of these natural products are *** natural product classification includes alkaloids,terpenes,terpenoids,and *** plethora of reported mechanisms involve calcium channel inhibition,immunomodulation and *** avail-able enriched data pertaining to bioactivity and mechanisms of natural products complement current efforts geared towards unraveling potent leishmanicides of therapeutic relevance.

关键词： Chemotherapeutics Chemoinformatics Natural products Cytotoxicity Leishmaniasis Phenotypic screening

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Cell transplantation to replace retinal ganglion cells faces challenges-the Switchboard Dilemma

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Neural Regeneration Research 2021年第6期16卷 1138-1143页

作者： Yuan Liu richard k.Lee Bascom Palmer Eye Institute University of Miami Miller School of MedicineMiamiFLUSA

The mammalian retina displays incomplete intrinsic regenerative capacities;therefore,retina degeneration is a major cause of irreversible blindness such as glaucoma,agerelated macular degeneration and diabetic *** diseases lead to the loss of retinal cells and serious vision loss in the late *** cell transplantation is a great promising novel treatment for these incurable retinal degenerative diseases and represents an exciting area of regenerative *** suitable stem cell sources for transplantation including human embryonic stem cells,induced pluripotent stem cells and adult stem cells have been identified as promising target ***,the retina is an elegant neuronal complex composed of various types of cells with different *** replacement of these different types of cells by transplantation should be addressed *** far,retinal pigment epithelium transplantation has achieved the most advanced stage of clinical trials,while transplantation of retinal neurons such as retinal ganglion cells and photoreceptors has been mostly studied in pre-clinical animal *** this review,we opine on the key problems that need to be addressed before stem cells transplantation,especially for replacing injured retinal ganglion cells,may be used practically for treatment.A key problem we have called the Switchboard Dilemma is a major block to have functional retinal ganglion cell *** use the public switchboard telephone network as an example to illustrate different difficulties for replacing damaged components in the retina that allow for visual *** ganglion cell transplantation is confronted by significant hurdles,because retinal ganglion cells receive signals from different interneurons,integrate and send signals to the correct targets of the visual system,which functions similar to the switchboard in a telephone network-therefore the Switchboard Dilemma.

关键词： cell transplantation optic nerve regeneration photoreceptors retina degeneration retinal ganglion cells stem cells

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The importance of laminin at the blood-brain barrier

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Neural Regeneration Research 2023年第12期18卷 2557-2563页

作者： Sebok k.Halder Arjun Sapkota richard Milner San Diego Biomedical Research Institute San DiegoCAUSA

The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood *** mechanistic basis of this barrier is found at multiple levels,including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes,microglia,and astrocyte *** addition,extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity,not only by providing an adhesive substrate for blood-brain barrier cells to adhere to,but also by providing guidance cues that strongly influence vascular cell *** extracellular matrix protein laminin is one of the most abundant components of the basement membrane,and several lines of evidence suggest that it plays a key role in directing blood-brain barrier *** this review,we describe the basic structure of laminin and its receptors,the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states,and most importantly,how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and ***,we discuss some of the important unanswered questions in the field and provide a“to-do”list of some of the critical outstanding experiments.

关键词： astrocytes basement membrane blood vessels blood-brain barrier integrity dystroglycan endothelial cells inflammation integrins laminin pericytes

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Generalization of predator recognition:Velvet geckos display anti-predator behaviours in response to chemicals from non-dangerous elapid snakes

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Current Zoology 2010年第3期56卷 337-342页

作者： Jonathan k. WEBB Weiguo DU David PIkE richard SHINE School of Biological Sciences University of Sydney NSW 2006 Australia Department of Environmental Sciences School of Life Sciences Hangzhou Normal College 310036 Hangzhou Zhejiang China

Many prey species detect chemical cues from predators and modify their behaviours in ways that reduce their risk ofpredation. Theory predicts that prey should modify their anti-predator responses according to the degree of threat posed by thepredator. That is, prey should show the strongest responses to chemicals of highly dangerous prey, but should ignore or respondweakly to chemicals from non-dangerous predators. However, if anti-predator behaviours are not costly, and predators are rarelyencountered, prey may exhibit generalised antipredator behaviours to dangerous and non-dangerous predators. In Australia, mostelapid snakes eat lizards, and are therefore potentially dangerous to lizard prey. Recently, we found that the nocturnal velvetgecko Oedura lesueurii responds to chemicals from dangerous and non-dangerous elapid snakes, suggesting that it displays generalisedanti-predator behaviours to chemicals from elapid snakes. To explore the generality of this result, we videotaped the behaviourof velvet geckos in the presence of chemical cues from two small elapid snakes that rarely consume geckos: the nocturnalgolden-crowned snake Cacophis squamulosus and the diurnal marsh snake Hemiaspis signata. We also videotaped geckos in trialsinvolving unscented cards (controls) and cologne-scented cards (pungency controls). In trials involving Cacophis and Hemiaspischemicals, 50% and 63% of geckos spent long time periods (> 3 min) freezing whilst pressed flat against the substrate, *** half the geckos tested exhibited anti-predator behaviours (tail waving, tail vibration, running) in response to Cacophis(67%) or Hemiaspis (63%) chemicals. These behaviours were not observed in control or pungency control trials. Our resultssupport the idea that the velvet gecko displays generalised anti-predator responses to chemical cues from elapid *** responses to predator chemicals may be common in prey species that co-occur with multiple, ecologically similar,

关键词： Predation risk Chemical cues Lizard Elapidae Gekkonidae Olfaction Multipredator

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First order dynamics approaching of broiler chicken deep body temperature response to step changes in ambient temperature

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International Journal of Agricultural and Biological Engineering 2017年第4期10卷 13-21页

作者： Takoi k.Hamrita richard H.Conway College of Engineering University of GeorgiaDriftmier Engineering CenterAthensGeorgia 30602USA United Technologies Corporation 700 Olympic Dr.Athens GA 30601USA

Traditional environmental control methods for poultry housing which rely solely on environmental factors fall short in meeting thermal and physiological needs of the *** methods are needed that factor in the physiological needs and responses of the animals in order to maximize well-being of the animals and minimize heat *** body temperature(DBT)has been shown in the literature to be a strong indicator of heat stress,therefore studies are needed that help us gain a deeper understanding of the relationship between this variable and environmental *** aim of this study was to identify the order of the dynamic response of poultry DBT to large step changes in ambient temperature(AT).Temperature steps had to be big enough to take the chickens out of their homeothermic zone.A total of 46 DBT/AT data sets with 23 upward AT steps and 23 downward AT steps were obtained using a biotelemetry system,and involving three *** responses of individual chickens to step changes in AT were found to have a 0.88 average Pearson correlation suggesting consistency in chickens’responses to the same stimuli(pking us one step closer towards making optimal management and risk assessment decisions that are based on physiological needs of the c

关键词： environmental control ambient temperature deep body temperature biotelemetry step response dynamic modeling broiler chicken physiological responses

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Physiological and Growth Responses of C_3 and C_4 Plants to Reduced Temperature When Grown at Low CO_2 of the Last Ice Age

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Journal of Integrative Plant Biology 2008年第11期50卷 1388-1395页

作者： Joy k.Ward David A.Myers richard B.Thomas Department of Ecology and Evolutionary Biology University of Kansas Department of Biology West Virginia University

During the last ice age, CO2 concentration （[CO2]） was 180-200 umol/mol compared with the modern value of 380 umol/mol, and global temperatures were -8 ℃ cooler. Relatively little is known about the responses of C3 and C4 species to longterm exposure to glacial conditions. Here Abutilon theophrasti Medik. （C3） and Amaranthus retroflexus L. （C4） were grown at 200 umol/mol CO2 with current （30/24℃） and glacial （22/16℃） temperatures for 22d. Overall, the C4 species exhibited a large growth advantage over the C3 species at low [CO2]. However, this advantage was reduced at low temperature, where the C4 species produced 5x the total mass of the C3 species versus 14x at the high temperature. This difference was due to a reduction in C4 growth at low temperature, since the C3 species exhibited similar growth between temperatures. Physiological differences between temperatures were not detected for either species, although photorespiration/net photosynthesis was reduced in the C3 species grown at low temperature, suggesting evidence of improved carbon balance at this treatment. This system suggests that C4 species had a growth advantage over C3 species during low [CO2] of the last ice age, although concurrent reductions in temperatures may have reduced this advantage.

关键词： Abutilon theophrasti Amaranthus retroflexus C3 species C4 species climate change low CO2 low temperature photorespiration Pleistocene.

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Friction transitions and connections to third bodies for a Cd coating on steel substrate

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Friction 2020年第4期8卷 784-801页

作者： Priyadarshi BEHERA Lisa LEE Sriraman k.RAJAGOPALAN richard R.CHROMIk Stephen YUE Department of Mining&Materials Engineering McGill UniversityMontrealQC H3A 0C5Canada

Cd coating is used in aerospace industries from last five decades due to its sacrificial protection and lubrication properties. Although Cd coating is primarily used due to its sacrificial corrosion protection when applied on steel substrate, the added benefit of modifying the tribological behavior by acting as a lubricious layer gives it a leading-edge than other coatings. Often the measurement of friction coefficient (CoF) is reported as a value generated after full sliding cycle. This measurement of average CoF generally limits the study of local variation in CoF occurring within one sliding cycle, which can be significantly different with change in spatial position due to change in third body morphology. In this study, a linearly reciprocating sliding test is used to measure the CoF at a sampling rate of 800 Hz along the track length to generate triboscopic image with steel countersphere. The instantaneous CoF obtained with triboscopy is correlated with the wear track morphology using scanning electron microscope (SEM) and optical profilometer for variation in contact conditions. Tribological test performed in dry atmosphere shows an average CoF of 0.4 till the end of the test whereas with increase in relative humidity to 60%, the average CoF changes from 0.4 to 0.8 at the end of the test due to change in contact conditions. Soft Cd coating on low carbon steel substrate is used to study these variations in third body morphology.

关键词： tribology Cd coating triboscopy third body aerospace coating humidity

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Assessment of coastal and mangrove vulnerability in the Andaman Island,Indian Ocean

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Geoscience Frontiers 2024年第5期15卷 47-60页

作者： Biswajit Mondal Rupesh k.Bhomia Ashis kumar Saha richard A.Mackenzie Department of Geography Delhi School of EconomicsUniversity of DelhiDelhi 110007India Centre for International Forestry Research(CIFOR) Jalan CIFORSitu GedeBogor BaratBogor 16115Indonesia Institute of Pacific Islands Forestry Pacific Southwest Research StationUSDA Forest ServiceHiloHI 96720USA

Coastal regions are highly susceptible to the effects of global warming,including rising atmospheric and sea surface temperatures,increased cyclone frequency,and sea level ***,it is imperative to examine coastal vulnerability to minimize the impact of multiple hazards and protect coastal resources,such as *** in India studying the vulnerability of coastal zones of Andaman and Nicobar Islands which fall in seismic zone V is critical for conservation *** conducted a vulnerability analysis of coastal zones impacted by the 2004 earthquake,causing varying degrees of ground upliftment and *** compared coastal vulnerability among sites that experienced uplift,no change,and subsidence(the southern portion).Our analysis utilized the Coastal and Mangrove Vulnerability Index(CVI and MVI)to measure and compare vulnerability in six zones distributed along uplift and subsidence ***-resolution satellite imagery including WorldView-2,3,and GeoEye-1 from year 2022 are utilized on this *** CVI and MVI offers a good way to measure and compare vulnerabilities across sites and offer insights for better *** CVI and MVI results indicate that approximately 34%of coastal grids and over 23%of mangrove grids across all zones are highly to extremely highly *** zones were found to be more vulnerable than uplifted *** findings suggest that large-scale natural disturbances such as tectonic displacement have the potential to impact coastal vegetation and mangrove cover can become even more *** conclusion,our study emphasizes the importance of vulnerability analyses in coastal regions,especially in areas prone to seismic *** findings have direct implications for conservation and restoration efforts and underscore the need for continued monitoring and mitigation efforts to safeguard coastal resources for long-term sustainability.

关键词： Mangroves Coastal vulnerability Mangrove vulnerability 2004 Indian Ocean earthquake Andaman Island

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Combating an invisible enemy: The American military response to global pandemics

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Military Medical Research 2021年第3期8卷 326-335页

作者： Lauren k.Dutton Peter C.Rhee Alexander Y.Shin richard J.Ehrlichman richard J.Shemin Department of Orthopedic Surgery Mayo Clinic2001st Street SWRochesterMN 55905USA Navy Medicine Professional Development Center BethesdaMD 20889USA United States Air Force Reserve the 60th Ops SquadronTravis AFBCA 94535USA Division of Plastic and Reconstructive Surgery Massachusetts General HospitalBostonMA 02114USA Massachusetts National Guard United States ArmyHanscom AFBMA 01731USA Division of Cardiac Surgery Department of SurgeryCardiovascular Center at UCLADavid Geffen School of Medicine at UCLALos AngelesCA 90095USA

The present moment is not the first time that America has found itself at war with a pathogen during a time of international conflict. Between crowded barracks at home and trenches abroad, wartime conditions helped enable the spread of influenza in the fall of 1918 during World War I such that an estimated 20%–40% of U.S. military members were infected. While the coronavirus disease 2019(COVID-19) pandemic is unparalleled for most of today's population, it is essential to not view it as unprecedented lest the lessons of past pandemics and their effect on the American military be forgotten. This article provides a historical perspective on the effect of the most notable antecedent pandemic, the Spanish Influenza epidemic, on American forces with the goal of understanding the interrelationship of global pandemics and the military, highlighting the unique challenges of the current pandemic, and examining how the American military has fought back against pandemics both at home and abroad, both 100 years ago and today.

关键词： Pandemic Spanish influenza COVID-19 Military Influenza

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Analyzing biases of nitrogen contents and δ^(15)N values arising from acidified marine sediments with different CaCO_3 concentrations

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Acta Oceanologica Sinica 2018年第8期37卷 1-5页

作者： PENG Yajun LIU Dongyan WANG Yujue richard Pierre kEESING John k. key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation Yantai Institute of Coastal Zone Research Chinese Academy of Sciences School of Management Science Guizhou University of Finance and Economics State key Laboratory of Estuarine and Coastal Research East China Normal University Littoral Environment et Sociétés UMR 7266 CNRS-Université de La Rochelle CSIRO Oceans and Atmosphere and University of Western Australia Oceans Institute Indian Ocean Marine Research Centre

In some studies, the researchers pretreated and measured organic carbon, nitrogen and their isotopes（δ^（13）C and δ^（15）N） of marine sediment together, to save costs and resources of analysis. However, the procedure of acidification to remove inorganic carbon for analysing δ^（13）C can affect the values of nitrogen and δ^（15）N, and the biases vary a lot depending on the CaCO_3 contents of sediments. In this study, the biases of total nitrogen（TN）and δ^（15）N values arising from acidified sediments were compared between the CaCO_3-poor（1%–16%） and CaCO_3-rich（20%–40%） samples. TN and δ^（15）N values were altered during acid treatment（without centrifugation） that possibly led to N-containing compounds volatilization. For CaCO_3-poor samples, acidification led to a range of 0%–40% TN losses and 0‰–2‰ shift in δ^（15）N values; and 10%–60% TN losses and 1‰–14‰ shift in δ^（15）N values for CaCO_3-rich samples. The biases from most samples exceeded the precision of the instrument（0.002% for TN and 0.08‰ for δ^（15）N）, and high biases could mislead our judgment for the environmental implication of the data. Thus,avoiding co-analysis of organic carbon, nitrogen and their isotopes（δ^（13）C and δ^（15）N） in sediments, even for CaCO_3-poor marine sediments, is necessary.

关键词： stable isotope nitrogen nitrogen CaCO3 acidification marine sediment

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