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Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5

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骨研究:英文版 2023年第3期11卷 595-606页

作者： Cassandra R.Diegel Ina Kramer Charles Moes Gabrielle E.Foxa Mitchell J.McDonald zachary b.madaj Sabine Guth Jun Liu Jennifer L.Harris Michaela Kneissel bart O.Williams Department of Cell biology Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Diseases of Aging and Regenerative Medicine Novartis Institutes for Biomedical ResearchCH-4002 BaselSwitzerland bioinformatics and biostatistics Core Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Oncology Novartis Institutes for Biomedical ResearchSan DiegoCA 92121USA

Proper regulation of Wnt signaling is critical for normal bone development and *** in several Wnt signaling components,which increase the activity of the pathway in the skeleton,cause high bone mass in human subjects and mouse *** bone mass is often accompanied by severe headaches from increased intracranial pressure,which can lead to fatality and loss of vision or hearing due to the entrapment of cranial *** addition,progressive forehead bossing and mandibular overgrowth occur in almost all *** that would provide symptomatic relief in these subjects are ***-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled *** inhibition of porcupine is a highly selective method of Wnt signaling *** treated three different mouse models of high bone mass caused by aberrant Wnt signaling,including homozygosity for loss-of-function in Sost,which models sclerosteosis,and two strains of mice carrying different point mutations in Lrp5(equivalent to human G171V and A214V),at 3 months of age with porcupine inhibitors for 5–6 *** significantly reduced both trabecular and cortical bone mass in all three *** demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.

关键词： homeostasis function mass

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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk brendan boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-b ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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Dynamic nitrogen vacancy magnetometry by single-shot optical streaking microscopy

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Photonics Research 2022年第9期10卷 2147-2156页

作者： MARK A.KEPPLER zachary A.STEELMAN zachary N.COKER MILOŠNESLÁDEK PHILIP R.HEMMER VLADISLAV V.YAKOVLEV JOEL N.bIXLER Department of biomedical Engineering Texas A&M UniversityCollege StationTexas 77843USA SAIC JBSA Fort Sam HoustonTexas 78234USA National Research Council Research Associateship Program WashingtonDC 20001USA IMOMEC Division IMECB-3590 DiepenbeekBelgium Institute for Materials Research(IMO) Hasselt UniversityB-3590 DiepenbeekBelgium Czech Technical University in Prague 27201 KladnoCzech Republic Department of Electrical and Computer Engineering Texas A&M UniversityCollege StationTexas 77843USA bioeffects Division Airman System DirectorateAir Force Research LaboratoryJBSA Fort Sam HoustonTexas 78234USA

Nitrogen vacancy diamonds have emerged as sensitive solid-state magnetic field sensors capable of producing diffraction limited and sub-diffraction field ***,for the first time,to our knowledge,we extend those measurements to high-speed imaging,which can be readily applied to analyze currents and magnetic field dynamics in circuits on a microscopic *** overcome detector acquisition rate limitations,we designed an optical streaking nitrogen vacancy microscope to acquire two-dimensional spatiotemporal *** demonstrate magnetic field wave imaging with micro-scale spatial extent and~400μs temporal *** validating this system,we detected magnetic fields down to 10μT for 40 Hz magnetic fields using single-shot imaging and captured the spatial transit of an electromagnetic needle at streak rates as high as 110μm/*** design has the capability to be readily extended to full 3D video acquisition by utilizing compressed sensing techniques and a potential for further improvement of spatial resolution,acquisition speed,and *** device opens opportunities to many potential applications where transient magnetic events can be isolated to a single spatial axis,such as acquiring spatially propagating action potentials for brain imaging and remotely interrogating integrated circuits.

关键词： vacancy utilizing overcome

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Recent advancements in noninvasive brain modulation for individuals with autism spectrum disorder

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Neural Regeneration Research 2023年第6期18卷 1191-1195页

作者： Jessica R.Griff Jake Langlie Nathalie b.bencie zachary J.Cromar Jeenu Mittal Idil Memis Steven Wallace Alexander E.Marcillo Rahul Mittal Adrien A.Eshraghi Hearing Research and Communication Disorders Laboratory Department of OtolaryngologyNeurotology DivisionUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Neurological Surgery University of Miami Miller School of MedicineMiamiFLUSA Department of biomedical Engineering University of MiamiCoral GablesFLUSA Department of Pediatrics University of Miami Miller School of MedicineMiamiFLUSA

Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive *** with autism spectrum disorder show deficits in a variety of areas including cognition,memory,attention,emotion recognition,and social *** no definitive treatment or cure,the main interventions for individuals with autism spectrum disorder are based on behavioral ***,noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity,particularly in individuals with autism spectrum *** evidence from small cohort studies,pilot studies,and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum ***,little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial *** objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.

关键词： autism spectrum disorder behavior cognition neurostimulation interventions noninvasive brain modulation theta burst stimulation transcranial direct current stimulation transcranial magnetic stimulation

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A Multi-Point Distance-bounding Protocol for Securing Automatic Dependent Surveillance-broadcast in Unmanned Aerial Vehicle Applications

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Journal of Computer Science & Technology 2020年第4期35卷 825-842页

作者： zachary P.Languell Qijun Gu Department of Computer Science Texas State UniversitySan MarcosTX 78666USA

The Automatic Dependent Surveillance-broadcast(ADS-b)protocol is being adopted for use in unmanned aerial vehicles(UAVs)as the primary source of information for emerging multi-UAV collision avoidance *** lack of security features in ADS-b leaves any processes dependent upon the information vulnerable to a variety of threats from compromised and dishonest *** could result in substantial losses or damage to *** research proposes a new distance-bounding scheme for verifying the distance and flight trajectory in the ADS-b broadcast data from surrounding *** proposed scheme enables UAVs or ground stations to identify fraudulent UAVs and avoid *** scheme was implemented and tested in the ArduPilot SITL(Software In The Loop)simulator to verify its ability to detect fraudulent *** experiments showed that the scheme achieved the desired accuracy in both flight trajectory measurement and attack detection.

关键词： automatic dependent surveillance-broadcast (ADS-b) unmanned aerial vehicle (UAV) distance bounding collision airspace safety

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First integrals of the axisymmetric shape equation of lipid membranes

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Chinese Physics b 2018年第3期27卷 551-559页

作者： Yi-Heng Zhang zachary McDargh Zhan-Chun Tu Department of Physics Beijing Normal University Beijing 100875 China Department of Physics Carnegie Mellon University 5000 Forbes Avenue Pittsburgh PA 15213 USA

The shape equation of lipid membranes is a fourth-order partial differential equation. Under the axisymmetric condi- tion, this equation was transformed into a second-order ordinary differential equation （ODE） by Zheng and Liu （Phys. Rev. E 48 2856 （1993））. Here we try to further reduce this second-order ODE to a first-order ODE. First, we invert the usual process of variational calculus, that is, we construct a Lagrangian for which the ODE is the corresponding Euler-Lagrange equation. Then, we seek symmetries of this Lagrangian according to the Noether theorem. Under a certain restriction on Lie groups of the shape equation, we find that the first integral only exists when the shape equation is identical to the Will- more equation, in which case the symmetry leading to the first integral is scale invariance. We also obtain the mechanical interpretation of the first integral by using the membrane stress tensor.

关键词： lipid membrane shape equation first integral Noether theorem

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From landrace to modern hybrid broccoli:the genomic and morphological domestication syndrome within a diverse *** collection

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Horticulture Research 2020年第1期7卷 574-590页

作者： zachary Stansell Thomas björkman Cornell University School of Integrative Plant ScienceCornell UniversityIthacaNY 14850USA Cornell AgriTech Cornell UniversityGenevaNY 14456USA

Worldwide,broccoli(brassica oleracea ***)is among the most economically important,nutritionally rich,and widely-grown vegetable *** explore the genomic basis of the dramatic changes in broccoli morphology in the last century,we evaluated 109 broccoli or broccoli/cauliflower intermediates for 24 horticultural ***-bysequencing markers were used to determine four subpopulations within italica:Calabrese broccoli landraces and hybrids,sprouting broccoli,and violet cauliflower,and to evaluate between and within group relatedness and *** overall horticultural quality and harvest index of improved hybrid broccoli germplasm has increased by year of cultivar release,this improvement has been accompanied by a considerable reduction in allelic diversity when compared to the larger pool of *** landraces are the most likely founding source of modern broccoli hybrids,and within these modern hybrids,we identified 13 reduction-in-diversity genomic regions,53 selective sweeps,and 30(>1 Mbp)runs of *** accessions collected in southern Italy contained 4.8-fold greater unique alleles per accessions compared to modern hybrids and provide a valuable resource in subsequent improvement *** work broadens the understanding of broccoli germplasm,informs conservation efforts,and enables breeding for complex quality traits and regionally adapted cultivars.

关键词： cultivar germplasm breeding

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boldness and predator evasion in naturally hybridizing swordtails （Teleostei： Xiphophorus）

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Current Zoology 2015年第4期61卷 596-603页

作者： James b. JOHNSON zachary W. CULUMbER Ryan EASTERLING Gil G. R.OSENTHAL Department of biology Texas A&M University College Station Texas TX 77843 USA Centro de lnvestigaciones Cientificas de las Huastecas "Aguazarca" Calnali Hidalgo Mexico

Correlations among behavioral traits can generate trade-offs and constrain phenotypic evolution. Interspecific hybridization has the potential to alter behavioral trait correlations, but the effect of hybridization on suites of behavioral traits has received relatively little attention. We evaluated how natural hybridization changes the relationship between boldness （time of emergence and proportion of time out of shelter） and response to a simulated predator threat in swordtails （Teleostei： Xiphophorus）. In poeciliid fishes, bold individuals have increased survival in the presence of predators. This non-intuitive observation may arise as a result of bold individuals being more likely to engage in anti-predator behaviors. Contrary to our prediction, bold indi- viduals were less likely to perform a fast-start response to a predator threat. This correlation was consistent among populations and species but was only significant in hybrids. The observed correlation between boldness and anti-predator behavior could im- pact hybrid fitness and the evolvability of hybrid lineages. More generally, our findings suggest that hybridization could influence the integration of behavioral phenotypes, as has been amply documented for morphology. Animal personality and behavioral syndromes could therefore play an important role in the evolutionary fate of natural hybrids [Current Zoology 61 （4）： 596-603, 2015].

关键词： Trait compensation Fast-Start Anti-predator behavior hybridization behavioral syndrome Animal personality

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Altered serotonin metabolism in Takeda G protein-coupled receptor 5 knockout mice protects against diet-induced hepatic fibrosis

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Liver Research 2022年第4期6卷 214-226页

作者： Jessica M.Ferrell Matthew Dilts zachary Stahl Shannon boehme Sabita Pokhrel Xinwen Wang John Y.L.Chiang Department of Integrative Medical Sciences Northeast Ohio Medical UniversityRootstownOHUSA Department of Pharmaceutical Sciences Northeast Ohio Medical UniversityRootstownOHUSA

background and aims:Diet-induced obesity and metabolic syndrome can trigger the progression of fatty liver disease to non-alcoholic steatohepatitis and fibrosis,which is a major public health *** acids regulate metabolic homeostasis and inflammation in the liver and gut via the activation of nuclear farnesoid X receptor(Fxr)and the membrane receptor Takeda G protein-coupled receptor 5(Tgr5).Tgr5 is highly expressed in the gut and skeletal muscle,and in cholangiocytes and Kupffer cells of the ***5 is implicated in the mediation of liver and gut inflammation,as well as the maintenance of energy ***,we used a high fat,high fructose,and high sucrose(HFS)diet to determine how bile acid signaling through Tgr5 may regulate metabolism during the progression from fatty liver to non-alcoholic steatohepatitis and *** and methods:Female C57bL/6J control wild type(WT)and Tgr5 knockout(Tgr5^(-/-))mice were fed HFS(high fat(40%kcal),high fructose,and 20%sucrose water)diet for 20 *** phe-notypes were characterized through examination of bile acid synthesis pathways,lipid and cholesterol metabolism pathways,and fibrosis and inflammation ***:Tgr5^(-/-)mice were more glucose intolerant when fed HFS diet,despite gaining the same amount of weight as WT ***5^(-/-)mice accumulated significantly more hepatic cholesterol and triglycerides on HFS diet compared to WT mice,and gene expression of lipogenic genes was significantly *** cholesterol 7alpha-hydroxylase(Cyp7a1)gene expression was consistently elevated in Tgr5^(-/-)mice,while oxysterol 7alpha-hydroxylase(Cyp7b1),sterol 27-hydroxylase(Cyp27a1),Fxr,and small heterodimer partner(Shp)were downregulated by HFS ***,hepatic inflammation and fibrosis were also significantly reduced in Tgr5^(-/-)mice fed HFS diet,which may be due to altered se-rotonin signaling in the ***:Tgr5^(-/-)mice may be protected from high fat,high sugar-

关键词： Non-alcoholic fatty liver disease(NAFLD) Liver fibrosis Takeda G protein-coupled receptor 5(TGR5) Serotonin(5-HT) High fat,high fructose,and high sucrose (HFS)

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Long-Term Cropping System, Tillage, and Poultry Litter Application Affect the Chemical Properties of an Alabama Ultisol

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Pedosphere 2019年第2期29卷 180-194页

作者： Zhongqi HE Irenus A.TAZISONG Xinhua YIN Dexter b.WATTS zachary N.SENWO Henry Allen TORbERT United States Department of Agriculture-Agricultural Research Service(USDA-ARS) Southern Regional Research Center Department of biological and Environmental Sciences Alabama A&M University Department of Plant Sciences University of Tennessee United States Department of Agriculture-Agricultural Research Service(USDA-ARS) National Soil Dynamics Laboratory

Sustainable agricultural practices have been steadily increasing in the last couple of decades. These management practices frequently involve cover crops, less or no-tillage, and organic fertilization. In this study, we evaluated the effects of cropping systems,tillage and no-tillage, and the application of poultry litter(PL) on selected soil physicochemical properties and soil test nutrients. Soil samples were collected from the topmost surface(0–5 cm) and subsurface(5–10 cm) layers. The general effect trend was PL application > no-tillage > cover crop > cropping type. There were more statistically significant(P ≤ 0.05) correlations between the 18 soil attributes at the topmost surface than at the subsurface. This could be due to the accumulation of external C inputs and nutrients by crop residues and PL application as well as the retaining effects of no-tillage on less mobile nutrient components. because of their high mobility and volatile nature, total nitrogen(N), ammonia-N(NH_4^+-N), and nitrate-N(NO_3^--N) levels varied greatly(high standard deviations), showing no consistent patterns among the treatments. Compared to the soybean cropping system, corn, especially with the wheat cover crop, contributed more to the total carbon(C) and sulfur(S) in the topmost surface soils(0–5 cm). Poultry litter application greatly increased pH, cation exchange capacity(CEC), base saturation, magnesium(Mg), phosphorus(P), calcium(Ca),sodium(Na), potassium(K), manganese(Mn), copper(Cu), and zinc(Zn) in both soil layers. Contrast comparisons revealed that PL application had more of an effect on these soil chemical properties than no-tillage and cropping systems. These results will shed light on developing better nutrient management practices while reducing their runoff potentials.

关键词： conventional tillage cover crop Mehlich-3 extraction no-tillage nutrient management practice organic fertilization soil attributes soil test nutrients

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