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151.
Thein M Cheng A Khanna P Zhang C Park EJ Ahmed D Goodrich CJ Asphahani F Wu F Smith NB Dong C Jiang X Zhang M Xu J 《Biosensors & bioelectronics》2011,27(1):25-33
We developed a new instrumental method by which human melanoma cells (LU1205) are sonoporated via radiation pressures exerted by highly-confined ultrasonic waves produced by high lateral-resolution ultrasonic micro-transducer arrays (UMTAs). The method enables cellular-level site-specific sonoporation within the cell monolayer due to UMTAs and can be applicable in the delivery of drugs and gene products in cellular assays. In this method, cells are seeded on the biochip that employs UMTAs for high spatial resolution and specificity. UMTAs are driven by 30-MHz sinusoidal signals and the resulting radiation pressures induce sonoporation in the targeted cells. The sonoporation degree and the effective lateral resolution of UMTAs are determined by performing fluorescent microscopy and analysis of carboxylic-acid-derivatized CdSe/ZnS quantum dots passively transported into the cells. Models representing the transducer-generated ultrasound radiation pressure, the ultrasound-inflicted cell membrane wound, and the transmembrane transport through the wound are developed to determine the ultrasound-pressure-dependent wound size and enhanced cellular uptake of nanoparticles. Model-based calculations show that the effective wound size and cellular uptake of nanoparticles increase linearly with increasing ultrasound pressure (i.e., at applied radiation pressures of 0.21, 0.29, and 0.40 MPa, the ultrasound-induced initial effective wound radii are 150, 460, and 650 nm, respectively, and the post-sonoporation intracellular quantum-dot concentrations are 7.8, 22.8, and 29.9 nM, respectively) and the threshold pressure required to induce sonoporation in LU1205 cells is ~0.12 MPa. 相似文献
152.
Fatimazohra Lenda Nadine Crouzin M��lanie Cavalier Janique Guiramand Fabien Lant�� G��rard Barbanel Catherine Cohen-Solal Jean Martinez Farhate Guenoun Fr��d��ric Lamaty Michel Vignes 《Amino acids》2011,40(3):913-922
Five derivatives of 2-amino-adipic acid bearing a tetrazole-substituted in C5 position were synthesized. These compounds displayed selective antagonism towards N-methyl-d-aspartate (NMDA) receptors compared with AMPA receptors, and they were devoid of any neurotoxicity. Among these five analogues, one exhibited a higher affinity for synaptic NMDA responses than the other four. Therefore, C5 tetrazole-substituted of 2-amino-adipic acid represent an interesting series of new NMDA receptor antagonists. This approach may be considered as a new strategy to develop ligands specifically targeted to synaptic or extra-synaptic NMDA receptors. 相似文献
153.
Cavallari N Frigato E Vallone D Fröhlich N Lopez-Olmeda JF Foà A Berti R Sánchez-Vázquez FJ Bertolucci C Foulkes NS 《PLoS biology》2011,9(9):e1001142
The circadian clock is synchronized with the day-night cycle primarily by light. Fish represent fascinating models for deciphering the light input pathway to the vertebrate clock since fish cell clocks are regulated by direct light exposure. Here we have performed a comparative, functional analysis of the circadian clock involving the zebrafish that is normally exposed to the day-night cycle and a cavefish species that has evolved in perpetual darkness. Our results reveal that the cavefish retains a food-entrainable clock that oscillates with an infradian period. Importantly, however, this clock is not regulated by light. This comparative study pinpoints the two extra-retinal photoreceptors Melanopsin (Opn4m2) and TMT-opsin as essential upstream elements of the peripheral clock light input pathway. 相似文献
154.
Isolated juvenile golden hamsters produce ultrasonic and audible vocalizations, so-called isolation calls, as a reaction to being separated from their mother and nest and their cooling down. Their aim is to stimulate mothers to search and retrieve the pups. In this work, the vocalization of juvenile laboratory (Zoh:GOHA; Institute of Zoology, Martin-Luther-University Halle-Wittenberg) and juvenile wild-derived golden hamsters (captured in northern Syria and southern Turkey) from birth up to the age of 18 days were digitally recorded, analyzed and compared using an ultrasonic microphone and the software Avisoft. Furthermore, the retrieving behavior of the mothers was observed and compared. The results showed that the number of isolation calls was age-specific and the structure of the calls was influenced by body temperature, body mass and sex of the pups. The age of the pups determined retrieval by the maternal golden hamsters; however these did not discriminate between their own pups or foreign pups. In spite of enormous genetic differences between wild-derived and laboratory golden hamsters, only minor differences between the strains were found. 相似文献
155.
Alessandra Villa Valeria Lovato Emil Bujak Sarah Wulhfard Nadine Pasche Dario Neri 《MABS-AUSTIN》2011,3(3):264-272
Human monoclonal antibodies (mAbs) can routinely be isolated from phage display libraries against virtually any protein available in sufficient purity and quantity, but library design can influence epitope coverage on the target antigen. Here we describe the construction of a novel synthetic human antibody phage display library that incorporates hydrophilic or charged residues at position 52 of the CDR2 loop of the variable heavy chain domain, instead of the serine residue found in the corresponding germline gene. The novel library was used to isolate human mAbs to various antigens, including the alternatively-spliced EDA domain of fibronectin, a marker of tumor angiogenesis. In particular, the mAb 2H7 was proven to bind to a novel epitope on EDA, which does not overlap with the one recognized by the clinical-stage F8 antibody. F8 and 2H7 were used for the construction of chelating recombinant antibodies (CRAbs), whose tumor-targeting properties were assessed in vivo in biodistribution studies in mice bearing F9 teratocarcinoma, revealing a preferential accumulation at the tumor site.Key words: human antibody library, phage display, oncofetal fibronectin, vascular tumor targeting, scFv antibody fragments, chelating recombinant antibody (CRAb) 相似文献
156.
Howard MA Krause K Khawaja N Massat N Zelaya F Schumann G Huggins JP Vennart W Williams SC Renton TF 《PloS one》2011,6(2):e17096
Development of treatments for acute and chronic pain conditions remains a challenge, with an unmet need for improved sensitivity and reproducibility in measuring pain in patients. Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain. We demonstrate repeatable, reproducible assessment of ongoing pain that is independent of patient self-report. In a cross-over trial design, 16 participants requiring bilateral removal of lower-jaw third molars underwent pain-free pre-surgical pCASL scans. Following extraction of either left or right tooth, repeat scans were acquired during post-operative ongoing pain. When pain-free following surgical recovery, the pre/post-surgical scanning procedure was repeated for the remaining tooth. Voxelwise statistical comparison of pre and post-surgical scans was performed to reveal rCBF changes representing ongoing pain. In addition, rCBF values in predefined pain and control brain regions were obtained. rCBF increases (5-10%) representing post-surgical ongoing pain were identified bilaterally in a network including primary and secondary somatosensory, insula and cingulate cortices, thalamus, amygdala, hippocampus, midbrain and brainstem (including trigeminal ganglion and principal-sensory nucleus), but not in a control region in visual cortex. rCBF changes were reproducible, with no rCBF differences identified across scans within-session or between post-surgical pain sessions. This is the first report of the cerebral representation of ongoing post-surgical pain without the need for exogenous tracers. Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report. Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments. 相似文献
157.
Mutapi F Imai N Nausch N Bourke CD Rujeni N Mitchell KM Midzi N Woolhouse ME Maizels RM Mduluza T 《PloS one》2011,6(5):e19149
In animal experimental models, parasitic helminth infections can protect the host from auto-immune diseases. We conducted a population-scale human study investigating the relationship between helminth parasitism and auto-reactive antibodies and the subsequent effect of anti-helminthic treatment on this relationship. Levels of antinuclear antibodies (ANA) and plasma IL-10 were measured by enzyme linked immunosorbent assay in 613 Zimbabweans (aged 2-86 years) naturally exposed to the blood fluke Schistosoma haematobium. ANA levels were related to schistosome infection intensity and systemic IL-10 levels. All participants were offered treatment with the anti-helminthic drug praziquantel and 102 treated schoolchildren (5-16 years) were followed up 6 months post-antihelminthic treatment. ANA levels were inversely associated with current infection intensity but were independent of host age, sex and HIV status. Furthermore, after allowing for the confounding effects of schistosome infection intensity, ANA levels were inversely associated with systemic levels of IL-10. ANA levels increased significantly 6 months after anti-helminthic treatment. Our study shows that ANA levels are attenuated in helminth-infected humans and that anti-helminthic treatment of helminth-infected people can significantly increase ANA levels. The implications of these findings are relevant for understanding both the aetiology of immune disorders mediated by auto-reactive antibodies and in predicting the long-term consequences of large-scale schistosomiasis control programs. 相似文献
158.
Thirant C Bessette B Varlet P Puget S Cadusseau J Tavares Sdos R Studler JM Silvestre DC Susini A Villa C Miquel C Bogeas A Surena AL Dias-Morais A Léonard N Pflumio F Bièche I Boussin FD Sainte-Rose C Grill J Daumas-Duport C Chneiweiss H Junier MP 《PloS one》2011,6(1):e16375
Background
Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined.Methodology/Principal Findings
Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting.Conclusions/Significance
In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors. 相似文献159.
160.
Juan F Masello Petra Quillfeldt Gopi K Munimanda Nadine Klauke Gernot Segelbacher H Martin Schaefer Mauricio Failla Maritza Cortés Yoshan Moodley 《Frontiers in zoology》2011,8(1):1-17