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Bone Research 2016年第2期4卷 91-100页

作者： Atum M Buo Mark S Williams Jaclyn p Kerr joseph p stains Department of Orthopaedics University of Maryland School of Medicine Department of Microbiology and Immunology University of Maryland School of Medicine

We report here a method for the use of poly-L-lysine （pLL） to markedly improve the adenoviral transduction efficiency of primary murine osteoblasts and bone marrow stromal cells （BMSCs） in culture and in situ, which are typically difficult to transduce. We show by fluorescence microscopy and flow cytometry that the addition of pLL to the viral-containing medium significantly increases the number of green fluorescence protein （GFp）-positive osteoblasts and BMSCs transduced with an enhanced GFp-expressing adenovirus. We also demonstrate that pLL can greatly enhance the adenoviral transduction of osteoblasts and osteocytes in situ in ex vivo tibia and calvaria, as well as in long bone fragments. In addition, we validate that pLL can improve routine adenoviral transduction studies by permitting the use of low multiplicities of infection to obtain the desired biologic effect. Ultimately, the use of pLL to facilitate adenoviral gene transfer in osteogenic cells can provide a cost-effective means of performing efficient gene transfer studies in the context of bone research.

关键词： A cost-effective method to enhance adenoviral transduction of primary murine osteoblasts and bone marrow stromal cells pLL bone

peptidomimetic inhibitor of L-plastin reduces osteoclastic bone resorption in aging female mice

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Bone Research 2021年第2期9卷 213-222页

作者： Hanan Aljohani joseph p.stains Sunipa Majumdar Deepa Srinivasan Linda Senbanjo Meenakshi A.Chellaiah Department of Oncology and Diagnostic Sciences School of DentistryUniversity of MarylandBaltimoreMDUSA Department of Oral Medicine and Diagnostics Sciences King Saud UniversitySchool of DentistryRiyadhKingdom of Saudi Arabia Department of Orthopedics University of Maryland School of MedicineBaltimoreMDUSA

L-plastin(LpL)was identified as a potential regulator of the actin-bundling process involved in forming nascent sealing zones(NSZs),which are precursor zones for mature sealing ***-fused cell-penetrating small molecular weight LpL peptide(TATMARGSVSDEE,denoted as an inhibitory LpL peptide)attenuated the formation of NSZs and impaired bone resorption in vitro in ***,the genetic deletion of LpL in mice demonstrated decreased eroded perimeters and increased trabecular bone *** the present study,we hypothesized that targeting LpL with the inhibitory LpL peptide in vivo could reduce osteoclast function and increase bone density in a mice model of low bone *** injected aging C57BL/6 female mice(36 weeks old)subcutaneously with the inhibitory and scrambled peptides of LpL for 14 ***-CT and histomorphometry analyses demonstrated an increase in trabecular bone density of femoral and tibial bones with no change in cortical thickness in mice injected with the inhibitory LpL peptide.A reduction in the serum levels of CTX-1 peptide suggests that the increase in bone density is associated with a decrease in osteoclast *** changes in bone formation rate and mineral apposition rate,and the serum levels of p1Np indicate that the inhibitory LpL peptide does not affect osteoblast *** study shows that the inhibitory LpL peptide can block osteoclast function without impairing the function of *** peptide could be developed as a prospective therapeutic agent to treat osteoporosis.

关键词： function. sealing impaired

Axial strain enhances osteotomy repair with a concomitant increase in connexin43 expression

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Bone Research 2015年第2期3卷 83-91页

作者： Rishi R Gupta Hyunchul Kim Yu-Kwan Chan Carla Hebert Leah Gitajn David J Yoo Robert V O’Toole Adam H Hsieh joseph p stains Department of Orthopaedics University of Maryland Fischell Department of Bioengineering University of MarylandCollege Park

The mechanical environment is known to influence fracture healing. We speculated that connexin43 （Cx43） gap junctions, which impact skeletal homeostasis, fracture healing and the osteogenic response to mechanical load, may play a role in mediating the response of the healing bone to mechanical strain. Here, we used an established rat fracture model, which uses a 2 mm osteotomy gap stabilized by an external fixator, to examine the impact of various cyclical axial loading protocols （2%, 10%, and 30% strain） on osteotomy healing. We examined the presence of Cx43 in the osteotomy-healing environment and assessed how mechanical strain modulates Cx43 expression patterns in the callus. We demonstrated that increased cyclical axial strain results in increased radiographic and histologic bone formation. In addition, we show by immunohistochemistry that Cx43 is abundantly expressed in the healing callus, with the expression most robust in samples exposed to increased cyclical axial strain. These data are consistent with the concept that an increase in Cx43 expression by mechanical load may be part of the mechanisms by which mechanical forces enhances fracture healing.

关键词： fracture healing mechanical strain external fixator environment and fracture model

L-plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction

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Bone Research 2020年第1期8卷 53-62页

作者： Meenakshi AChellaiah Megan CMoorer Sunipa Majumdar Hanan Aljohani Sharon CMorley Vanessa Yingling joseph pstains Department of Oncology and Diagnostic Sciences School of DentistryUniversity of MarylandBaltimoreMDUSA Department of Orthopedics University of Maryland School of MedicineBaltimoreMDUSA Department of pediatrics Division of Infectious Diseasesand Department of Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA Department of Kinesiology California State UniversityEast BayHaywardCAUSA

Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones(NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro. Transduction of TAT-fused full-length L-plastin peptide into osteoclasts from L-plastin knockout mice rescued the formation of nascent sealing zones and sealing rings in a time-dependent manner. This response was not observed with mutated full-length L-plastin(Ser-5 and-7 to Ala-5 and-7) peptide. In contrast to the observed defect in the NSZ, L-plastin deficiency did not affect podosome formation or adhesion of osteoclasts in vitro or in vivo. Histomorphometry analyses in 8-and 12-week-old female L-plastin knockout mice demonstrated a decrease in eroded perimeters and an increase in trabecular bone density, without a change in bone formation by osteoblasts. This decrease in eroded perimeters supports that osteoclast function is attenuated in L-plastin knockouts. Micro-CT analyses confirmed a marked increase in trabecular bone mass. In conclusion, female L-plastin knockout mice had increased trabecular bone density due to impaired bone resorption by osteoclasts. L-plastin could be a potential target for therapeutic interventions to treat trabecular bone loss.

关键词： sealing impaired fused

Calculation of First Sound Speed in Liquid Helium

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Chinese physics Letters 1999年第4期16卷 276-278页

作者： pAO Lu joseph p.Foy Department of physics and Astronomy Arizona State UniversityTempeArizona 85287USA

The speed of first sound in liquid helium II is calculated quantum *** calculation is made by using a modified version of Brueckner and Sawada’s method[***.106(1959)1128]and is based on the postulate that the hard co... 详细信息

关键词： quantum Sound sound

Strategies to enhance monoclonal antibody uptake and distribution in solid tumors

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Cancer Biology & Medicine 2021年第3期18卷 649-664页

作者： Brandon M.Bordeau joseph p.Balthasar Department of pharmaceutical Science University at BuffaloBuffaloNY 14214USA

Despite the significant resources dedicated to the development of monoclonal antibody(m Ab)therapies for solid tumors,the clinical success,thus far,has been *** efficacy of m Ab in solid tumors likely relates to unique aspects of tumor *** tumors have an aberrant vasculature and a dense extracellular matrix that slow both the convective and diffusive transport of m Abs into and within *** m Abs that are directed against cellular antigens,high antigen expression and rapid antigen turnover can result in perivascular cells binding to and eliminating a significant amount of extravasated m Ab,limiting m Ab distribution to portions of the tumor that are distant from functional *** preclinical investigations have reported strategies to improve m Ab uptake and distribution;however,to our knowledge,none have translated into the ***,we provide an overview of several barriers in solid tumors that limit m Ab uptake and distribution and discuss approaches that have been utilized to overcome these barriers in preclinical studies.

关键词： Solid tumors antibody uptake and distribution monoclonal antibody antibody-drug conjugate

Comparative study of mechanical, corrosion and erosion-corrosion properties of cast hyper-duplex and super-duplex stainless steels

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International Journal of Minerals,Metallurgy and Materials 2020年第7期27卷 954-961页

作者： p.Nithin Raj p.K.Navaneethkrishnan K.Sekar M.A.joseph Department of Mechanical Engineering National Institute of TechnologyCalicutIndia

Duplex stainless steels(DSSs)used in subsea structures and desalination industries require high corrosion and erosion resistance as well as excellent mechanical *** newly introduced cast duplex grade ASTM A8907 A has a unique composition and is expected to have a much better resistance to corrosion and erosion compared with the super-duplex grades 5 A and 6 *** work is a comparative study of the mechanical properties,corrosion,and erosion-corrosion resistance of super-duplex grades 5 A and 6 A and the hyper-duplex grade 7 *** three DSSs exhibited equiaxial austenite islands in the ferrite matrix and balanced phase *** hardness of the grade 7 A was nearly 15%higher than those of the super-duplex grades,which is attributed to the effect of the higher contents of W and Mn in 7 *** impact toughness of grade 7 A was found to be lower than those of the super-duplex grades due to the carbide precipitation resulting from the partial substitution of Mo with *** oxide layer strengthening effect of rare earth elements and the higher pitting resistance equivalent number(pREN)of grade7 A resulted in higher corrosion *** harder and more passive grade 7 A showed a 35%lower material loss during erosion-corrosion.

关键词： hyper-duplex stainless steels erosion−corrosion electrochemical corrosion marine environment super-duplex stainless steels

Morphometric aspects of a small tropical mountain river system,the southern Western Ghats,India

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International Journal of Digital Earth 2010年第2期3卷 135-156页

作者： Jobin Thomas Sabu joseph K.p.Thrivikramaji Department of Environmental Sciences University of KeralaThiruvananthapuram 695581KeralaIndia Department of Geology University of KeralaThiruvananthapuram 695581KeralaIndia

The Muthirapuzha watershed(MW)is one among the major tributaries of periyarthe longest west flowing river in Kerala,India.A morphometric analysis was carried out to determine the spatial variations in the drainage characteristics of MW and its 14 fourth order sub-watersheds(SW1SW14)using Survey of India topographic maps and Landsat ETM*** study revealed that the watershed includes a sixth order stream and lower order streams dominate the *** did indicate that rainfall has a significant role in the drainage development whereas structure and relief of rocks dictate the drainage *** asymmetry in the drainage distribution is correlated with the tectonic history of the Munnar plateau in the late paleocene *** watershed is moderate to well-drained and exhibited a geomorphic maturity in its physiographic *** shape parameters revealed the elongated nature of MW and drainage network development in the ***,the analysis provided significant insight into the terrain *** study strongly brings to light,(a)the tendency of the watershed to soil loss and(b)the hydrological makeup of the subwatersheds,which combined helped to formulate a comprehensive watershed management plan.

关键词： morphometry digital earth Muthirapuzha watershed Western Ghats India

Assessment of soil erosion in a tropical mountain river basin of the southern Western Ghats,India using RUSLE and GIS

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Geoscience Frontiers 2018年第3期9卷 893-906页

作者： Jobin Thomas Sabu joseph K.p.Thrivikramji EWRE Department of Civil EngineeringIndian Institute of Technology MadrasChennai600036Tamil NaduIndia Department of Environmental Sciences University of KeralaThiruvananthapuram695581KeralaIndia Center for Environment and Development Thiruvananthapuram695013KeralaIndia

Revised Universal Soil Loss Equation(RUSLE) model coupled with transport limited sediment delivery(TLSD) function was used to predict the longtime average annual soil loss, and to identify the critical erosion-/deposition-prone areas in a tropical mountain river basin, viz., Muthirapuzha River Basin(MRB; area=271.75 km^2), in the southern Western Ghats, India. Mean gross soil erosion in MRB is 14.36 t ha^(-1) yr^(-1), whereas mean net soil erosion(i.e., gross erosion-deposition) is only 3.60 t ha^(-1) yr^(-1)(i.e., roughly 25% of the gross erosion). Majority of the basin area(~86%) experiences only slight erosion(positional environment for the eroded sediments(e.g., the terraces of stream reaches, the gentle plains as well as the foot slopes of the plateau scarps and the terrain with concordant summits). Although mean gross soil erosion rates in the natural vegetation belts are relatively higher, compared to agriculture, settlement/built-up areas and tea plantation, the sediment transport efficiency in agricultural areas and tea plantation is significantly high,reflecting the role of human activities on accelerated soil erosion. In MRB, on a mean basis, 0.42 t of soil organic carbon(SOC) content is being eroded per hectare annually, and SOC loss from the 4th order subbasins shows considerable differences, mainly due to the spatial variability in the gross soil erosion rates among the sub-basins. The quantitative results, on soil erosion and deposition, modelled using RUSLE and TLSD, are expected to be beneficial while formulating comprehensive land management strategies for reducing the extent of soil degradation in tropical mountain river basins.

关键词： Soil erosion RUSLE Transport limited sediment delivery Muthirapuzha river basin Western Ghats Kerala

Calreticulin surface presentation: a signal for natural killer cells to attack

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3883-3884页

作者： Jasmine p.Castellanos joseph C.Genereux Microbiology Graduate program University of CaliforniaRiversideCA 92521USA Department of Chemistry University of CaliforniaRiversideCA 92521USA

In a recent article published in Nature,Sen Santara et *** a general mechanism that allows endoplasmic reticulum(ER)stress,a common response to many cellular dysfunctions,to signal to natural killer(NK)cells to destroy the stressed cell(Fig.1).1 This mechanism suggests that targeting this signaling pathway might serve as a common therapeutic approach to treat disparate diseases,including cancers and *** innate immune system recognizes molecular signa-tures that indicate threats to the organism,and transduces these signatures into an immune response to counter these *** part of the innate immune system,NK cells constitute a lymphoid immune cell type that kills infected or cancerous cells on the basis of their presentation of specific ligands or markers on the surface of abnormal cells.

关键词： killer surface