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151.
Marije B Overdijk Sandra Verploegen Marijn B?gels Marjolein van Egmond Jeroen J Lammerts van Bueren Tuna Mutis Richard WJ Groen Esther Breij Anton CM Martens Wim K Bleeker Paul WHI Parren 《MABS-AUSTIN》2015,7(2):311-320
Daratumumab (DARA) is a human CD38-specific IgG1 antibody that is in clinical development for the treatment of multiple myeloma (MM). The potential for IgG1 antibodies to induce macrophage-mediated phagocytosis, in combination with the known presence of macrophages in the tumor microenvironment in MM and other hematological tumors, led us to investigate the contribution of antibody-dependent, macrophage-mediated phagocytosis to DARA''s mechanism of action. Live cell imaging revealed that DARA efficiently induced macrophage-mediated phagocytosis, in which individual macrophages rapidly and sequentially engulfed multiple tumor cells. DARA-dependent phagocytosis by mouse and human macrophages was also observed in an in vitro flow cytometry assay, using a range of MM and Burkitt''s lymphoma cell lines. Phagocytosis contributed to DARA''s anti-tumor activity in vivo, in both a subcutaneous and an intravenous leukemic xenograft mouse model. Finally, DARA was shown to induce macrophage-mediated phagocytosis of MM cells isolated from 11 of 12 MM patients that showed variable levels of CD38 expression. In summary, we demonstrate that phagocytosis is a fast, potent and clinically relevant mechanism of action that may contribute to the therapeutic activity of DARA in multiple myeloma and potentially other hematological tumors. 相似文献
152.
EG Ciolac SS Mantuani CM Neiva CEL Verardi DM Pess?a-Filho L Pimenta 《Biology of sport / Institute of Sport》2015,32(2):103-108
The aim of the present study was to analyse the usefulness of the 6-20 rating of perceived exertion (RPE) scale for prescribing and self-regulating high-intensity interval training (HIT) in young individuals. Eight healthy young subjects (age = 27.5±6.7 years) performed maximal graded exercise testing to determine their maximal and reserve heart rate (HR). Subjects then performed two HIT sessions (20 min on a treadmill) prescribed and regulated by their HR (HR: 1 min at 50% alternated with 1 min at 85% of reserve HR) or RPE (RPE: 1 minute at the 9-11 level [very light-fairly light] alternated with 1 minute at the 15-17 level [hard-very hard]) in random order. HR response and walking/running speed during the 20 min of exercise were compared between sessions. No significant difference between sessions was observed in HR during low- (HR: 135±15 bpm; RPE: 138±20 bpm) and high-intensity intervals (HR: 168±15 bpm; RPE: 170±18 bpm). Walking/running speed during low- (HR: 5.7±1.2 km · h−1; RPE: 5.7±1.3 km · h−1) and high-intensity intervals (HR: 7.8±1.9 km · h−1; RPE: 8.2±1.7 km · h−1) was also not different between sessions. No significant differences were observed in HR response and walking/running speed between HIT sessions prescribed and regulated by HR or RPE. This finding suggests that the 6-20 RPE scale may be a useful tool for prescribing and self-regulating HIT in young subjects. 相似文献
153.
An extract from rat brain has been shown to catalyze the transfer of ganglioside GM1 from sonicated vesicles to erythrocyte ghosts. It also enhanced the transfer of GM1 to a crude neuronal membrane preparation, whereas myelin took up only a very limited amount. The transfer activity was heat-labile. Similar transfer activities were found in extracts from bovine gray and white matter, that of the former being comparable to rat brain whereas the latter was greater per milligram protein. 相似文献
154.
Werner G. Kuhr rew G. Ewing W. Lowry Caudill R. Mark Wightman 《Journal of neurochemistry》1984,43(2):560-569
Microvoltammetric electrodes were employed in the brain of an anesthetized rat to monitor chemical substances in extracellular fluid following electrical stimulation of the medial forebrain bundle. An increase in concentration of an easily oxidized substance is observed in the caudate nucleus and in the nucleus accumbens. A large amount of evidence suggests that the substance that is observed following stimulation is dopamine. (1) The location of the stimulating electrode must be in known dopaminergic tracts to induce release. (2) Release is most easily observed in brain regions that contain significant numbers of dopamine-containing neurons. (3) Two voltammetric electrodes with very different electrochemical responses provide voltammograms of the released species that are unique for catechols in one case and catecholamines in another case. (4) The amount of 3,4-dihydroxyphenylacetic acid found in striatal tissue by postmortem analysis correlates with the calculated amount of dopamine released. (5) Inhibition of tyrosine hydroxylase, and thus dopamine synthesis, decreases the observed release while inhibition of monoamine oxidase, and thus formation of dopamine metabolites, does not. (6) The dependence of release on stimulation parameters agrees with results obtained with perfusion techniques. Thus, a new method has been developed to characterize endogenous dopamine release in the rat brain and can be used on a time scale of seconds. 相似文献
155.
Release of endogenous dopamine (DA) and -aminobutyric acid (GABA) from superfused rat caudate synaptosomes was monitored with liquid chromatography with electrochemical detection. Dopamine was analyzed by oxidative detection following alumina extraction while GABA was analyzed with reductive detection following pre-column derivatization with trinitrobenzenesulfonic acid and extraction. Both spontaneous and K+-stimulated (40 mM) release were examined as well as the effect of several possible neuromodulatory agents (DA, GABA, muscimol, ascorbic acid, acetylcholine). The content of GABA in the sample and the amount released by K+ were approximately fifty times those of DA although the relative amounts released by repetitive K+ stimulations were similar. Muscimol and DA significantly attenuated both the spontaneous and stimulated release of GABA while ascorbate and acetylcholine had no effect. Acetylcholine significantly increased both the stimulated and spontaneous release of DA while the other agents had no effect. Dopamine showed an absolute dependence on calcium for stimulated release while GABA exhibited a significant calcium-independent release. These results indicate that profound differences exist in the factors which modulate the release of endogenous DA and GABA. 相似文献
156.
Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species 总被引:3,自引:0,他引:3
The Mlc1 gene of Drosophila melanogaster encodes two MLC1 isoforms via
developmentally regulated alternative pre-mRNA splicing. In larval muscle
and tubular and abdominal muscles of adults, all of the six exons are
included in the spliced mRNA, whereas, in the fibrillar indirect flight
muscle of adult, exon 5 is excluded from the mRNA. We show that this
tissue-specific pattern of alternative splicing of the Mlc1 pre-mRNA is
conserved in D. simulans, D. pseudoobscura, and D. virilis. Isolation and
sequencing of the Mlc1 genes from these three other Drosophila species have
revealed that the overall organization of the genes is identical and that
the genes have maintained a very high level of sequence identity within the
coding region. Pairwise amino acid identities are 94%-99%, and there are no
charge changes among the proteins. Total nucleotide divergence within the
coding region of the four genes supports the accepted genealogy of these
species, but the data indicate a significantly higher rate of amino acid
replacement in the branch leading to D. pseudoobscura. A comparison of
nucleotide substitutions in the coding portions of exon 5 and exon 6, which
encode the alternative carboxyl termini of the two MLC1 isoforms, suggests
that exon 5 is subject to greater evolutionary constraints than is exon 6.
In addition to the coding sequences, there is significant sequence
conservation within the 5' and 3' noncoding DNA and two of the introns,
including one that flanks exon 5. These regions are candidates for cis-
regulatory elements. Our results suggest that evolutionary constraints are
acting on both the coding and noncoding sequences of the Mlc1 gene to
maintain proper expression and function of the two MLC1 polypeptides.
相似文献
157.
BLA Verçosa CM Lemos IL Mendonça SMMS Silva SM de Carvalho H Goto FAL Costa 《BMC veterinary research》2008,4(1):45
Background
Visceral leishmaniasis in Brazil is caused by the protozoan Leishmania (Leishmania) chagasi and it is transmitted by sandfly of the genus Lutzomyia. Dogs are an important domestic reservoir, and control of the transmission of visceral leishmaniasis (VL) to humans includes the elimination of infected dogs. However, though dogs are considered to be an important element in the transmission cycle of Leishmania, the identification of infected dogs representing an immediate risk for transmission has not been properly evaluated. Since it is not possible to treat infected dogs, they are sacrificed when a diagnosis of VL is established, a measure that is difficult to accomplish in highly endemic areas. In such areas, parameters that allow for easy identification of reservoirs that represents an immediate risk for transmission is of great importance for the control of VL transmission. In this study we aimed to identify clinical parameters, reinforced by pathological parameters that characterize dogs with potential to transmit the parasite to the vector.Results
The major clinical manifestations of visceral leishmaniasis in dogs from an endemic area were onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. The transmission potential of these dogs was assessed by xenodiagnosis using Lutzomyia longipalpis. Six of nine symptomatic dogs were infective to Lutzomyia longipalpis while none of the five asymptomatic dogs were infective to the sandfly. Leishmania amastigotes were present in the skin of all clinically symptomatic dogs, but absent in asymptomatic dogs. Higher parasite loads were observed in the ear and ungueal region, and lower in abdomen. The inflammatory infiltrate was more intense in the ears and ungueal regions of both symptomatic and asymptomatic dogs. In clinically affected dogs in which few or none Leishmania amastigotes were observed, the inflammatory infiltrate was constituted mainly of lymphocytes and macrophages. When many parasites were present, the infiltrate was also comprised of lymphocytes and macrophages, as well as a larger quantity of polymorphonuclear neutrophils (PMNs).Conclusion
Dogs that represent an immediate risk for transmission of Leishmania in endemic areas present clinical manifestations that include onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. Lymphadenopathy in particular was a positive clinical hallmark since it was closely related to the positive xenodiagnosis.158.
Survey of Malassezia sp and dermatophytes in the cutaneous microbiome of free‐ranging golden‐headed lion tamarins (Leontopithecus chrysomelas ‐ Kuhl, 1820) 下载免费PDF全文
159.
Joseph W. Hinton Elizabeth Heppenheimer Kyla M. West Danny Caudill Melissa L. Karlin John C. Kilgo John Joseph Mayer Karl V. Miller Margaret Walch Bridgett vonHoldt Michael J. Chamberlain 《Ecology and evolution》2019,9(6):3389-3404
Prior to 1900, coyotes (Canis latrans) were restricted to the western and central regions of North America, but by the early 2000s, coyotes became ubiquitous throughout the eastern United States. Information regarding morphological and genetic structure of coyote populations in the southeastern United States is limited, and where data exist, they are rarely compared to those from other regions of North America. We assessed geographic patterns in morphology and genetics of coyotes with special consideration of coyotes in the southeastern United States. Mean body mass of coyote populations increased along a west‐to‐east gradient, with southeastern coyotes being intermediate to western and northeastern coyotes. Similarly, principal component analysis of body mass and linear body measurements suggested that southeastern coyotes were intermediate to western and northeastern coyotes in body size but exhibited shorter tails and ears from other populations. Genetic analyses indicated that southeastern coyotes represented a distinct genetic cluster that differentiated strongly from western and northeastern coyotes. We postulate that southeastern coyotes experienced lower immigration from western populations than did northeastern coyotes, and over time, genetically diverged from both western and northeastern populations. Coyotes colonizing eastern North America experienced different selective pressures than did stable populations in the core range, and we offer that the larger body size of eastern coyotes reflects an adaptation that improved dispersal capabilities of individuals in the expanding range. 相似文献
160.
Movement behaviors are central to ecology and conservation. Movement sensing technologies can monitor behaviors that are otherwise difficult to observe under field conditions and may enhance the ability to quantify behaviors at the population scale. We monitored steelhead trout (Oncorhynchus mykiss) spawning behaviors in a seminatural enclosure using accelerometer telemetry tags while simultaneously observing behaviors with underwater cameras. Behavioral assignments from visual observations were compared to acceleration histories to develop assignment criteria for acceleration data, including for a key behavior (oviposition). Behavioral events independently classified using acceleration data prior to reviewing video were compared to video scoring and 97% of holding behaviors, 93% of digging behaviors, and 86% of oviposition/covering behaviors were correctly assigned using acceleration data alone. We applied the method to at‐liberty steelhead in spawning tributaries. Acceleration records revealed putative spawning and oviposition in at‐liberty female steelhead, and time budgets for at‐liberty steelhead were similar to those monitored within enclosures. The use of similar movement sensing tags and classification approaches offers a method for monitoring movement behavior, activity budgets, and habitat use in a broad array of aquatic and terrestrial taxa, and may be especially useful when behaviors are cryptic. 相似文献