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Turning the corner from observation to intervention in human genetics

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Journal of Genetics and Genomics 2018年第2期45卷 57-59页

作者： david l.nelson Department of Molecular and Human Genetics Baylor College of Medicine Jan and Dan Duncan Neurological Research Institute

In the early 1990s,shortly after we identified the genetic defect in FMR1 that results in fragile X syndrome（Verkerk et al.,1991）,I attended a conference sponsored by the US National Fragile X Foundation.This biannu... 详细信息

关键词： Turning the corner from observation to intervention in human genetics

Discharge-Stage Relationship on Urban Streams Evaluated at USGS Gauging Stations,St.louis,Missouri

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Journal of Earth Science 2020年第6期31卷 1133-1141页

作者： Robert E.Criss david l.nelson Department of Earth and Planetary Sciences Washington UniversitySt.Louis MO 63130USA Columbia Cir Pasadena CA 91105USA

Extensive USGS data tables and detailed,1 m2 li DAR surveys are used to determine the optimal power n that relates discharge(Q)to stage(h*)above channel bottom(ho)at 39 gauging stations on small streams in the St.louis,Missouri area,all of which have catchments of 0.6 to 220 km2.Four different methodologies are employed to determine both n and ho:(1)optimizing linearity in a plot of Q1/n vs.local stage(hl)using USGS field measurements at each site;(2)optimizing linearity in a plot of Q1/n vs.hl using USGS rating tables at each site;(3)a mathematical inverse method applied to the same USGS rating tables;(4)use of li DAR data on channel geometry to determine the power dependences of channel area A and hydraulic radius H on h*,combined with the Manning and rational equations to predict n.Of these methods,only methods 2 and 3 compare favorably,and these values compare poorly with Method 1 based on field data,and with method 4 based on theoretical and empirical relationships.Because Method 4 is predictive,it provides a useful alternative to methods 1–3 that are based on USGS field measurements,which are heavily weighted toward low discharges.We conclude that the apparent values of n in the USGS rating tables are systematically too low for small streams.

关键词： stream gauging li DAR topography urban flooding discharge hydrology

The Cloud Model for Climate Change

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International Journal of Geosciences 2024年第5期15卷 366-395页

作者： Michael.nelson david B. nelson Retired Pleasanton CA USA

In 1995, the Intergovernmental Panel on Climate Change (IPCC) released a thermodynamic model based on the Greenhouse Effect, aiming to forecast global temperatures. This study delves into the intricacies of that model. Some interesting observations are revealed. The IPCC model equated average temperatures with average energy fluxes, which can cause significant errors. The model assumed that all energy fluxes remained constant, and the Earth emitted infrared radiation as if it were a blackbody. Neither of those conditions exists. The IPCC’s definition of Climate Change only includes events caused by human actions, excluding most causes. Satellite data aimed at the tops of clouds may have inferred a high Greenhouse Gas absorption flux. The model showed more energy coming from the atmosphere than absorbed from the sun, which may have caused a violation of the First and Second laws of Thermodynamics. There were unexpectedly large gaps in the satellite data that aligned with various absorption bands of Greenhouse Gases, possibly caused by photon scattering associated with re-emissions. Based on science, we developed a cloud-based climate model that complied with the Radiation laws and the First and Second laws of Thermodynamics. The Cloud Model showed that 81.3% of the outgoing reflected and infrared radiation was applicable to the clouds and water vapor. In comparison, the involvement of CO2 was only 0.04%, making it too minuscule to measure reliably.

关键词： Climate Change Greenhouse Gas CO2 Clouds Model Thermodynamics

Decoupling CO₂ from Climate Change

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International Journal of Geosciences 2024年第3期15卷 246-269页

作者： Michael.nelson david B. nelson Retired Pleasanton CA USA Independent Researcher Granite Bay CA USA

This study determines if there is a correlation between rising carbon dioxide levels and global warming. Historical data were reviewed from three different time periods spanning 500 million years. It showed that the curves and trends were too dissimilar to establish a connection. Observations from CO2/temp ratios showed that the CO2 and the temperature moved in opposite directions 42% of the time. Many ratios displayed zero or near zero values, reflecting a lack of response. As much as 87% of the ratios revealed negative or near zero values, which strongly negate a correlation. The infrared spectra showed the Greenhouse Gases had an exceptionally low absorption band between 11.67 μm to 9.1 μm, which is a zone called the infrared atmospheric window. Most of the Greenhouse Gases absorb little infrared inside that zone. And that zone is where the Earth’s surface emits almost all infrared radiation. Even with minimal absorbance, water vapor captures the most infrared radiation. It absorbs 84 times more than CO2, 407 thousand times more than methane, 452 thousand times more than ozone and 2.3 million times more than nitrous oxide. The Intergovernmental Panel on Climate Change (IPCC) and the United States EPA excluded water vapor because it was not associated with man-made activities. They reported that water vapor and clouds were simply feedback mechanisms from CO2. Clouds reflect radiation from the sun. The Northern Hemisphere is 2.7°F warmer than the Southern Hemisphere because of clouds. The world cloud cover has gone down 4.1% from 1982 to 2018. Calculations show that this could be responsible for 2.4°F of the 2.7°F. The research shows that most of the recent increase in temperature (89.9%) is because of fewer clouds.

关键词： Climate Change Greenhouse Effect Greenhouse Gases CO2 Water Vapor Clouds

SMXl5 attenuates strigolactone signaling in Arabidopsis thaliana by inhibiting SMXl7 degradation

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Molecular Plant 2024年第4期17卷 631-647页

作者： Qingtian li Haiyang Yu Wenwen Chang Sunhyun Chang Michael Guzman lionel Faure Eva-Sophie Wallner Heqin Yan Thomas Greb lei Wang Ruifeng Yao david C.nelson Department of Botany and Plant Sciences University of CaliforniaRiversideRiversideCA 2521USA Yazhouwan National laboratory Sanya 572025China Hainan Seed Industry laboratory Sanya 57205China State Key laboratory of Chemo/Biosensing and Chemometrics Hunan Provincial Key Laboratory of Plant Functional Genomics and Developmental RegulationCollege of BiologyHunan UniversityChangsha 410082China Key laboratory of Seed Innovation Center for Agricultural Resources ResearchInstitute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuangHebei 050021China University of Chinese Academy of Sciences Beijing 10004China School of the Sciences Biology DivisionTexas Woman’s UniversityDentonTX 76204USA Centre for Organismal Studies(COS) Heidelberg University6120 HeidelbergGermany

Hormone-activated proteolysis is a recurring theme of plant hormone signaling mechanisms.In strigolactone signaling,the enzyme receptor DWARF14(D14)and an F-box protein,MORE AXIllARY GROWTH2(MAX2),mark SUPPRESSOR OF MAX21-lIKE(SMXl)family proteins SMXl6,SMXl7,and SMXl8 for rapid degradation.Removal of these transcriptional corepressors initiates downstream growth responses.The homologous proteins SMXl3,SMXl4,and SMXl5,however,are resistant to MAX2-mediated degradation.We discovered that the smxl4 smxl5 mutant has enhanced responses to strigolactone.SMXl5 attenuates strigolactone signaling by interfering with AtD14-SMXl7 interactions.SMXl5 interacts with AtD14 and SMXl7,providing two possible ways to inhibit SMXl7 degradation.SMXl5 function is partially dependent on an ethylene-responsive-element binding-factor-associated amphiphilic repression(EAR)motif,which typically mediates interactions with the TOPlESS family of transcriptional corepressors.However,we found that loss of the EAR motif reduces SMXl5-SMXl7 interactions and the attenuation of strigolactone signaling by SMXl5.We hypothesize that integration of SMXl5 into heteromeric SMXl complexes reduces the susceptibility of SMXl6/7/8 proteins to strigolactone-activated degradation and that the EAR motif promotes the formation or stability of these complexes.This mechanism may provide a way to spatially or temporally fine-tune strigolactone signaling through the regulation of SMXl5 expression or translation.

关键词： Arabidopsis typically inhibiting

Macroalgal deep genomics illuminate multiple paths to aquatic,photosynthetic multicellularity

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Molecular Plant 2024年第5期17卷 747-771页

作者： david R.nelson Alexandra Mystikou Ashish Jaiswal Cecilia Rad-Menendez Michael J.Preston Frederik De Boever Diana C.El Assal Sarah Daakour Michael W.lomas Jean-Claude Twizere david H.Green William C.Ratcliff Kourosh Salehi-Ashtiani Division of Science and Math New York University Abu DhabiAbu DhabiUAE Center for Genomics and Systems Biology(CGSB) New York University Abu DhabiAbu DhabiUAE Biotechnology Research Center Technology Innovation InstitutePO Box 9639Masdar CityAbu DhabiUAE Culture Collection of Algae and Protozoa Scottish Association for Marine ScienceObanScotlandUK National Center for Marine Algae and Microbiota Bigelow Laboratory for Ocean SciencesEast BoothbayMEUSA laboratory of Viral Interactomes GIGA InstituteUniversity of LiegeLiegeBelgium School of Biological Sciences Georgia Institute of TechnologyAtlantaGAUSA

Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity phenotypes.However,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized.In this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal relatives.Genes for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular processes.Adhesome genes show phylum-and climate-specific expansions that may facilitate niche adaptation.Collectively,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.

关键词： macroalgae multicellularity comparative genomics evolution adhesome endogenous viral elements

Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease

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Journal of Sport and Health Science 2024年第3期13卷 398-408页

作者： Pedro l.Valenzuela Alfredo Santalla lidia B.Alejo Andrea Merlo Asuncion Bustos laura Castellote-Belles Roser Ferrer-Costa Nicola A.Maffiuletti david Barranco-Gil Tomas Pinos Alejandro lucia Physical Activity and Health Research Group(“PaHerg”) Research Institute of Hospital“12 de Octubre”(“imas12”)Madrid 28041Spain Department of Systems Biology University of AlcalaMadrid 28871Spain Department of Sport and Computer Science Section of Physical Education and SportsFaculty of SportUniversidad Pablo de OlavideSevilla 41013Spain EVOPRED Research Group Universidad Europea de CanariasTenerife 38300Spain Faculty of Sport Sciences Universidad Europea de MadridMadrid 28670Spain Gait&Motion Analysis laboratory Sol et Salus HospitalTorre Pedrera di Rimini(RN)47922Italy Department of Clinical Biochemistry Laboratoris ClınicsHospital Universitari Vall d’HebronBarcelona 08035Spain Human Performance lab Schulthess ClinicZurich 8008Switzerland Biomedical Research Networking Center on Rare Disorders(CIBERER) Barcelona 08035Spain Mitochondrial and Neuromuscular Disorders Unit Vall d’Hebron Institut de RecercaUniversitat Autonoma de BarcelonaBarcelona 08035Spain

Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/l).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all platory threshold and55%peak power output,both pless of the CHO dose(placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.

关键词： Endurance Glycogen storage disease Glycogenosis Nutrition Supplement

Cognitive function among military veterans with STEM occupations

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Military Medical Research 2024年第2期11卷 308-310页

作者： Justin T.McDaniel Kevin N.Hascup Erin R.Hascup Ugochukwu G.Ezigbo Amanda M.Weidhuner Harvey Henson david l.Albright Dale and Deborah Smith Center for Alzheimer's Research and trEatment(CARE) Southern Illinois University School of MedicineSpringfieldIL 62794USA STEM Education Research Center Southern Illinois UniversityCarbondaleIL 62901USA Department of Political Science The University of AlabamaTuscaloosaAL 35487USA

Dear Editor,There is limited research on the relationship between science,technology,engineering,and mathematics(STEM)occupational history and cognitive function in later life,especially among military veterans,who may be at greater risk for later-life cognitive decline.This study examines a nationally representative sample of military veterans to address this gap in knowledge.

关键词： Alzheimer's disease Veterans Science technology engineering and mathematics(STEM) Animal fluency test Dementia

Harnessing the power of complex light propagation in multimode fibers for spatially resolved sensing

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Photonics Research 2024年第3期12卷 411-422页

作者： DARCY l.SMITH lINH V.NGUYEN MOHAMMAD I.REJA ERIK P.SCHARTNER HEIKE EBENDORFF-HEIDEPRIEM david J.OTTAWAY STEPHEN C.WARREN-SMITH Institute for Photonics and Advanced Sensing and School of Physics Chemistry and Earth SciencesThe University of AdelaideAdelaideSA 5005Australia Australian Research Council Centre of Excellence for Gravitational Wave Discovery(OzGrav) AdelaideSAAustralia Future Industries Institute University of South AustraliaMawson LakesSA 5095Australia laser Physics and Photonics Devices laboratory University of South AustraliaMawson LakesSA 5095Australia

The propagation of coherent light in multimode optical fibers results in a speckled output that is both complex and sensitive to environmental effects.These properties can be a powerful tool for sensing,as small perturbations lead to significant changes in the output of the fiber.However,the mechanism to encode spatially resolved sensing information into the speckle pattern and the ability to extract this information are thus far unclear.In this paper,we demonstrate that spatially dependent mode coupling is crucial to achieving spatially resolved measurements.We leverage machine learning to quantitatively extract the spatially resolved sensing information from three fiber types with dramatically different characteristics and demonstrate that the fiber with the highest degree of spatially dependent mode coupling provides the greatest accuracy.

关键词： fiber spatially resolved