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11.
Heather A Huet Joseph D Growney Jennifer A Johnson Jing Li Sanela Bilic Lance Ostrom Mohammad Zafari Colleen Kowal Guizhi Yang Axelle Royo Michael Jensen Bruno Dombrecht Kris RA Meerschaert Joost A Kolkman Karen D Cromie Rebecca Mosher Hui Gao Alwin Schuller Randi Isaacs William R Sellers Seth A Ettenberg 《MABS-AUSTIN》2014,6(6):1560-1570
Multiple therapeutic agonists of death receptor 5 (DR5) have been developed and are under clinical evaluation. Although these agonists demonstrate significant anti-tumor activity in preclinical models, the clinical efficacy in human cancer patients has been notably disappointing. One possible explanation might be that the current classes of therapeutic molecules are not sufficiently potent to elicit significant response in patients, particularly for dimeric antibody agonists that require secondary cross-linking via Fcγ receptors expressed on immune cells to achieve optimal clustering of DR5. To overcome this limitation, a novel multivalent Nanobody approach was taken with the goal of generating a significantly more potent DR5 agonist. In the present study, we show that trivalent DR5 targeting Nanobodies mimic the activity of natural ligand, and furthermore, increasing the valency of domains to tetramer and pentamer markedly increased potency of cell killing on tumor cells, with pentamers being more potent than tetramers in vitro. Increased potency was attributed to faster kinetics of death-inducing signaling complex assembly and caspase-8 and caspase-3 activation. In vivo, multivalent Nanobody molecules elicited superior anti-tumor activity compared to a conventional DR5 agonist antibody, including the ability to induce tumor regression in an insensitive patient-derived primary pancreatic tumor model. Furthermore, complete responses to Nanobody treatment were obtained in up to 50% of patient-derived primary pancreatic and colon tumor models, suggesting that multivalent DR5 Nanobodies may represent a significant new therapeutic modality for targeting death receptor signaling. 相似文献
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13.
Charlene Cavalheiro de Menezes Aracélli Gnatta Dorneles Rita Leal Sperotto Marta Medeiros Frescura Duarte Maria Rosa Chitolina Schetinger Vania Lúcia Loro 《Neurochemical research》2009,34(7):1255-1260
This study aimed to determine whether patients with aseptic and bacterial meningitis presented alterations in oxidative stress
parameters of cerebrospinal fluid (CSF). A total of 30 patients were used in the research. The CSF oxidative stress status
has been evaluated through many parameters, such as lipid peroxidation through thiobarbituric acid reactive substances (TBARS)
and antioxidant defense systems such as superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and ascorbic acid. TBARS levels, SOD and GST activity increase in aseptic meningitis
and in bacterial meningitis. The ascorbic acid concentration increased significantly in patients with both meningitis types.
The reduced glutathione levels were reduced in CSF of patients with aseptic and bacterial meningitis. In present study we
may conclude that oxidative stress contributes at least in part to the severe neurological dysfunction found in meningitis. 相似文献
14.
MARIA C. BLASSIOLI‐MORAES DIEGO M. MAGALHÃES ANDREJ ČOKL RAÚL A. LAUMANN JOSEANE P. DA SILVA CLEONOR C. A. SILVA MIGUEL BORGES 《Physiological Entomology》2014,39(1):1-11
Vibrational communication is important for successful mating in various stink bugs species. The vibrational signals from males and females of Dichelops melacanthus Dallas (Hemiptera: Pentatomidae) are recorded from a nonresonant substrate (i.e. a loudspeaker membrane) to characterize the temporal and spectral properties of these vibrational signals, as well as on a resonant substrate (i.e. bean plants) to obtain information about how these signals are altered when they are transmitted through the plants. On the loudspeaker membrane, D. melacanthus males and females emit only one male or one female song, respectively. However, when the insects are placed on bean leaves, a more complex repertoire is recorded, with three different songs for each sex. The first female and male songs appear to have calling functions and the third male and female songs are emitted during courtship. The second female and male songs are emitted after the first song, although their functions in mating behaviour are not clear. The identified repertoire is similar to those of other Neotropical stink bugs, starting with songs 1 and 2 and developing into song 3. Frequency modulation is observed in the female songs recorded from the loudspeaker membrane and the plants. The signals recorded from plants present higher harmonic peaks compared with the signals recorded from the loudspeaker membrane. The presence of species and sex‐specific songs during mating confirms the important role of vibrational communication in mate location and recognition. The temporal and spectral characteristic signals are influenced by the substrate used to record the songs emitted by D. melacanthus. 相似文献
15.
We have isolated the delta-globin gene of the New-World spider monkey,
Ateles geoffroyi, and compared its nucleotide sequence with those of other
primate delta- and beta-globin genes. Among primate delta-globin genes, the
rate of nonsynonymous substitutions is much less than the rate of
synonymous substitutions. This suggests that primate delta- globin genes
may remain under evolutionary conservation, perhaps because hemoglobin A2
has an as yet unknown physiological importance.
相似文献
16.
Phylogenetic utility of the nuclear gene arginine decarboxylase: an example from Brassicaceae 总被引:8,自引:2,他引:8
Arginine decarboxylase (ADC) is an important enzyme in the production of
putrescine and polyamines in plants. It is encoded by a single or low-copy
nuclear gene that lacks introns in sequences studied to date. The rate of
Adc amino acid sequence evolution is similar to that of ndhF for the
angiosperm family studied. Highly conserved regions provide several target
sites for PCR priming and sequencing and aid in nucleotide and amino acid
sequence alignment across a range of taxonomic levels, while a variable
region provides an increased number of potentially informative characters
relative to ndhF for the taxa surveyed. The utility of the Adc gene in
plant molecular systematic studies is demonstrated by analysis of its
partial nucleotide sequences obtained from 13 representatives of
Brassicaceae and 3 outgroup taxa, 2 from the mustard oil clade (order
Capparales) and 1 from the related order Malvales. Two copies of the Adc
gene, Adc1 and Adc2, are found in all members of the Brassicaceae studied
to data except the basal genus Aethionema. The resulting Adc gene tree
provides robust phylogenetic data regarding relationships within the
complex mustard family, as well as independent support for proposed tribal
realignments based on other molecular data sets such as those from
chloroplast DNA.
相似文献
17.
LORENA GÓMEZ‐APARICIO RAÚL GARCÍA‐VALDÉS PALOMA RUÍZ‐BENITO MIGUEL A. ZAVALA 《Global Change Biology》2011,17(7):2400-2414
Most large‐scale multispecies studies of tree growth have been conducted in tropical and cool temperate forests, whereas Mediterranean water‐limited ecosystems have received much less attention. This limits our understanding of how growth of coexisting tree species varies along environmental gradients in these forests, and the implications for species interactions and community assembly under current and future climatic conditions. Here, we quantify the absolute effect and relative importance of climate, tree size and competition as determinants of tree growth patterns in Iberian forests, and explore interspecific differences in the two components of competitive ability (competitive response and effect) along climatic and size gradients. Spatially explicit neighborhood models were developed to predict tree growth for the 15 most abundant Iberian tree species using permanent‐plot data from the Spanish Second and Third National Forest Inventory (IFN). Our neighborhood analyses showed a climatic and size effect on tree growth, but also revealed that competition from neighbors has a comparatively much larger impact on growth in Iberian forests. Moreover, the sensitivity to competition (i.e. competitive response) of target trees varied markedly along climatic gradients causing significant rank reversals in species performance, particularly under xeric conditions. We also found compelling evidence for strong species‐specific competitive effects in these forests. Altogether, these results constitute critical new information which not only furthers our understanding of important theoretical questions about the assembly of Mediterranean forests, but will also be of help in developing new guidelines for adapting forests in this climatic boundary to global change. If we consider the climatic gradients of this study as a surrogate for future climatic conditions, then we should expect absolute growth rates to decrease and sensitivity to competition to increase in most forests of the Iberian Peninsula (in all but the northern Atlantic forests), making these management considerations even more important in the future. 相似文献
18.
Lucas R Lopes Vitor AR Miranda Rodrigo A Goes Gabriel GA Souza Giuliana R Souza Jessica CS Rocha Victor RA Cossich Jamila A Perini 《Biology of sport / Institute of Sport》2021,38(4):703
The COVID-19 pandemic has presented significant challenges and implications for the sports community. Thus, this study aimed to describe the prevalence of COVID-19 in Brazilian athletes and identify the epidemiological, clinical, athletic, life and health factors associated with the disease in these individuals. A cross-sectional study was performed involving 414 athletes from 22 different sports using an online questionnaire from August to November 2020. The association between the athletes’ characteristics and COVID-19 was evaluated using a logistic regression model. The prevalence of COVID-19 was 8.5%, although only 40% of athletes reported having been tested. Being under 27 years of age (3-fold), having children (~5-fold), having a teammate test positive for COVID-19 (2.5-fold), and smoking (14-fold) were associated with a possible higher risk of disease. Almost 20% of athletes self-reported musculoskeletal injuries during the period of the pandemic that was studied. Athletes with a university education (P = 0.02), a profession other than sports (P < 0.001), those from a low-income family (P = 0.01), and public health system users (P = 0.04) were significantly less frequently tested for COVID-19, whereas international competitors, athletes who received a wage, and athletes who had a teammate who tested positive for COVID-19 were 2-, 3-, and 15-fold more likely to be tested for COVID-19, respectively. Approximately 26% of the athletes who tested negative or were untested reported more than three characteristic COVID-19 symptoms, and 11% of athletes who tested positive for COVID-19 were asymptomatic. The identification of modifiable (have children, smoking, and teammates positively tested) and non-modifiable (age under 27 years) factors related to COVID-19 in athletes can contribute to implementing surveillance programmes to decrease the incidence of COVID-19 in athletes and its negative impacts in sports. 相似文献
19.
In Drosophila pseudoobscura, the amylase (Amy) multigene family is
contained within a series of inversions, or gene arrangements, on the third
chromosome. The Standard (ST), Santa Cruz (SC), and Tree Line (TL)
inversions are central to the phylogeny of arrangements, and have clusters
of other arrangements derived from them. The gene arrangements belonging to
each of these three clusters have a characteristic number of Amy genes,
ranging from three in ST to two in SC to one in TL. This distribution
pattern can reflect a history of either duplications or deletions, although
the data available in the past did not permit a decision between these
alternatives. We provide unambiguous evidence that three Amy genes were
present before the divergence of the ST, SC, and TL arrangements. Thus, the
current status of the Amy multigene family is the result of deletions in
the TL and SC arrangements, which created three new pseudogenes: TL
Amy2-psi, TL Amy3-psi, and SC Amy3- psi. Analysis of pseudogene sequences
revealed that, in the SC and ST arrangements, pseudogene evolution has been
retarded, most likely due to the homogenization effect of gene conversion.
Finally, by determining the original copy number, we have reconstructed the
evolutionary history of the Amy multigene family and linked it with the
evolution of the central gene arrangements.
相似文献
20.
JINDŘIŠKA BOJKOVÁ KLÁRA KOMPRDOVÁ TOMÁŠ SOLDÁN SVĚTLANA ZAHRÁDKOVÁ 《Freshwater Biology》2012,57(12):2550-2567
1. Rapid expansion and intensification of anthropogenic activities in the 20th century has caused profound changes in freshwater assemblages. Unfortunately, knowledge of the extent and causes of species loss (SL) is limited due to the lack of reliable historical data. An unusual data set allows us to compare changes in the most sensitive of aquatic insect orders, the Plecoptera, at some 170 locations in the Czech Republic between two time periods, 1955–1960 and 2006–2010. Historical data (1890–1911) on assemblages of six lowland rivers allow us to infer even earlier changes. 2. Regional stonefly diversity decreased in the first half of the 20th century. Streams at lower altitudes lost a substantial number of species, which were never recovered. In the second half of the century, large‐scale anthropogenic pressure caused SL in all habitats, leading to a dissimilarity of contemporary and previous assemblages. The greatest changes were found at sites affected by organic pollution and a mixture of organic pollution and channelisation or impoundment. Colonisation of new habitats was observed in only three of the 80 species evaluated. 3. Species of moderate habitat specialisation and tolerance to organic pollution were most likely to be lost. Those with narrow specialisations in protected habitats were present in both historical and contemporary collections. 4. Contemporary assemblages are the consequence of more than a 100 years of anthropogenic impacts. In particular, streams at lower altitude and draining intensively exploited landscapes host a mere fragment of the original species complement. Most stonefly species are less frequently present than before, although their assemblages remain almost intact in near‐natural mountain streams. Our analyses demonstrate dramatic restriction of species ranges and, in some cases, apparent changes in altitudinal preference throughout the area. 相似文献