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31.
32.

Background

Cytokine-induced killer cells (CIKs) are an advanced therapeutic medicinal product (ATMP) that has shown therapeutic activity in clinical trials but needs optimization. We developed a novel strategy using CIKs from banked cryopreserved cord blood units (CBUs) combined with bispecific antibody (BsAb) blinatumomab to treat CD19+ malignancies.

Methods

CB-CIKs were expanded in vitro and fully characterized in comparison with peripheral blood (PB)–derived CIKs.

Results

CB-CIKs, like PB-CIKs, were mostly CD3+ T cells with mean 45% CD3+CD56+ and expressing mostly TCR(T cell receptor)αβ with a TH1 phenotype. CB-CIK cultures had, however, a larger proportion of CD4+ cells, mostly CD56?, as well as a greater proportion of naïve CCR7+CD45RA+ and a lower percentage of effector memory cells, compared with PB-CIKs. CB-CIKs were very similar to PB-CIKs in their expression of a large panel of co-stimulatory and inhibitory/exhaustion markers, except for higher CD28 expression among CD8+ cells. Like PB-CIKs, CB-CIKs were highly cytotoxic in vitro against natural killer (NK) cell targets and efficiently lysed CD19+ tumor cells in the presence of blinatumomab, with 30–60% lysis of target cells at very low effector:target ratios. Finally, both CB-CIKs and PB-CIKs, combined with blinatumomab, showed significant therapeutic activity in an aggressive PDX Ph+ CD19+ acute lymphoblastic leukemia model in NOD-SCID mice, without sign of toxicity or graft-versus-host disease. The improved expansion protocol was finally validated in good manufacturing practice conditions, showing reproducible expansion of CIKs from cryopreserved cord blood units with a median of 28.8?×?106 CIK/kg.

Discussion

We conclude that CB-CIKs, combined with bispecific T-cell–engaging antibodies, offer a novel, effective treatment strategy for leukemia.  相似文献   
33.
The present study quantifies changes in soil organic carbon (SOC) stocks in Belgium between 1960, 1990 and 2000 for 289 spatially explicit land units with unique soil association and land‐use type, termed landscape units (LSU). The SOC stocks are derived from multiple nonstandardized sets of field measurements up to a depth of 30 cm. Approximately half of the LSU show an increase in SOC between 1960 and 2000. The significant increases occur mainly in soils of grassland LSU in northern Belgium. Significant decreases are observed on loamy cropland soils. Although the largest SOC gains are observed for LSU under forest (22 t C ha?1 for coniferous and 29 t C ha?1 for broadleaf and mixed forest in the upper 30 cm of soil), significant changes are rare because of large variability. Because the number of available measurements is very high for agricultural land, most significant changes occur under cropland and grassland, but the corresponding average SOC change is smaller than for forests (9 t C ha?1 increase for grassland and 1 t C ha?1 decrease for cropland). The 1990 data for agricultural LSU show that the SOC changes between 1960 and 2000 are not linear. Most agricultural LSU show a higher SOC stock in 1990 than in 2000, especially in northern Belgium. The observed temporal and spatial patterns can be explained by a change in manure application intensity. SOC stock changes caused by land‐use change are estimated. The SOC change over time is derived from observed differences between SOC stocks in space. Because SOC stocks are continuously influenced by a number of external factors, mainly land‐use history and current land management and climate, this approach gives only an approximate estimate whose validity is limited to these conditions.  相似文献   
34.
Occasional observations of Black‐shouldered Kites Elanus caeruleus in Europe date back to the mid‐19th century, but it was only recorded as a breeding species in the early 1960s in Portugal and a few years later in neighbouring Spain. This recent colonization, possibly from Africa where the species is abundant, may be due to climate change, land‐use changes in southern Europe, or both. As a first step to understanding this range expansion process we have developed a habitat selection model using data from the current strongholds of its European distribution. Comparing the proportion of different habitat types around 46 breeding sites and 45 randomly chosen plots, we have found that the area of cultivated parklands known as dehesas in Spain is a strong predictor of the current distribution range of breeding pairs of Black‐shouldered Kites. Specifically, the percentage of dehesas with planted cereal and a low density of trees (i.e. < 7 trees/ha and thus a savannah‐like habitat) within the study plots explained 44.6% of the residual deviance in our model. The minimal adequate model classified 81.3% of breeding sites and random plots correctly. Our results suggest that Black‐shouldered Kites may have taken advantage of the gradual increase of cultivated dehesas in the second half of the 20th century to expand its range in Europe. This particular type of dehesa is structurally similar to the African savannahs where the species thrives and may offer a higher density of rodents than traditional dehesas, which primarily contain pastureland for livestock ranching.  相似文献   
35.
We describe three new species of the genus Gromia from bathyal and abyssal depths in the Weddell Sea. The new species are characterized by a combination of morphological and molecular criteria. All three species possess a distinct oral capsule and a layer of ‘honeycomb membranes’, which form the inner part of the organic test wall. Both these features are typical of gromiids. Their identification as gromiids is confirmed by analyses of partial small subunit ribosomal DNA (SSU rDNA) gene sequences. Gromia marmorea sp. nov. is a rounded species with a prominent oral capsule and a characteristically mottled appearance. In Gromia melinus sp. nov. , the test surface exhibits a polygonal pattern of ridges, with a layer of clay particles coating the surface between the ridges. Gromia winnetoui sp. nov. represents an elongate morphotype in which the organic test is enclosed within an agglutinated case, a feature previously unknown in gromiids. Phylogenetic analysis using the maximum‐likelihood method revealed that all three species form distinct clades, reflecting the morphological differences among Weddell Sea species, as well as between deep‐water Southern Ocean Gromia and previously described gromiids. © 2009 The Linnean Society of London, Zoological Journal of the Linnean Society, 2009, 157 , 451–469.  相似文献   
36.
In colonial species, first‐time breeders may use the number of settled conspecifics in colony selection, but such a relationship is confused by the correlation between colony size and nest‐site availability. To distinguish conspecific attraction from neutral colony selection, we experimentally increased nest availability for first‐year Lesser Kestrels Falco naumanni, allowing us to dissociate the number of vacant nest‐sites from colony size at the arrival time of first‐year birds. Under natural conditions, the number of first‐year birds settling was positively correlated with both the number of philopatric and the total number of breeding pairs (colony size) already settled. However, the probability of occupation of experimentally manipulated nests by first‐year birds was independent of colony size. In experimental colonies, the number of first‐year birds settling was positively correlated with the number of manipulated nest‐sites but not with the number of conspecifics. Overall, these results support a neutral colony selection by first‐year Lesser Kestrels based on nest‐site availability.  相似文献   
37.
Abstract: A specimen of Curculionidae (Curculioninae) is described as Arariperhinus monnei gen. et sp. nov. The specimen is preserved on a laminated limestone sample of the Crato Formation (Santana Group), Lower Cretaceous (Aptian–Albian), and was collected from a quarry near Nova Olinda, Chapada do Araripe, State of Ceará, Brazil. The genus is placed in the subfamily Curculioninae because of its strongly convex body and relatively slender rostrum, but mainly by its rounded eyes and lack of a prosternal sulcus and tibial spurs. The very prominent eyes in lateral view, a cylindrical rostrum and a straight posterior margin of ventrite II are strong indications that this fossil belongs to the tribe Anthonomini. However, the claws, which would resolve the exact placement of this fossil, are poorly preserved. Arariperhinus monnei gen. et sp. nov. is distinguishable by the combination of several characters and the first record of the family Curculionidae in the Santana Group; it is the oldest record of a member of the subfamily Curculioninae.  相似文献   
38.
Summary 1. The relationship between altitudinal gradients on small spatial scales and latitudinal gradients on broader scales has been repeatedly recognised in the biogeography of animals and plants. However, little is known about this topic in the ecology and biogeography of ostracod communities in Mediterranean flowing waters or the factors underlying these spatial patterns. 2. We analysed the ostracod assemblages of near‐natural headwater streams in the Betic and Pre‐Betic Mountains in the southern Iberian Peninsula to decipher the most important environmental gradients structuring ostracod communities on a local scale. In addition, the European altitudinal and latitudinal distributions of the most commonly found species were analysed with GIS and regression models to compare geographical effects from local to continental scales. 3. Forty sampling sites, distributed among six catchments and ranging in altitude between 150 and 1940 m a.s.l., were sampled seasonally. Limnological and geographical information was also recorded for each sample. Seventeen ostracod species were found, two of which were new findings for the Iberian Peninsula: Potamocypris fulva and Cypria reptans. The most common species were Potamocypris zschokkei, Candona neglecta, Herpetocypris brevicaudata, Cyclocypris ovum, Potamocypris villosa and Pseudocandona albicans. The distribution of these species in 918 European locations was analysed to test the hypothesised change in altitudinal distribution with varying latitude. 4. The best subset of logistic and linear regression models, selected by means of the information‐theoretic approach, found that oxygen content and the variables related with substratum and discharge were the most important variables with a negative influence on ostracod presence, abundance and species richness on a local scale. These findings suggest that the negative effect on benthic invertebrates of physical disturbances relates to high flow velocity and turbulences. 5. Multivariate ordination methods show how altitude and water chemistry are the most important variables to explain the distribution of ostracod assemblages on the small spatial scale. On a larger scale, differences in latitudinal distribution throughout Europe were significant for the six most common species found in Granada. In addition, four of these showed significant negative linear relationships between latitude and altitude in Europe, supporting the important effect of climate on local and continental scale distributions. While ostracod biogeographies are still poorly known, our results indicate the influence of Quaternary climate variability on ostracod dynamic colonisation and extinction in Europe in accordance with species‐specific temperature and water chemistry preferences.  相似文献   
39.
Intraspecific variation in morphology has often been related to fitness differences through its effects on performance. In lizards, variation in hind limb length can be shaped by natural selection for increased locomotor performance, sexual selection on the number or size of femoral pores involved in chemical signalling, or both. Here, we analyse the selective forces involved in sexual dimorphism and differences in hind limb length between two populations of Psammodromus algirus living at different elevation. Males were more robust and had longer hind limbs and limb segments than females, and low‐elevation lizards had longer limbs than high‐elevation lizards. However, differences in locomotor performance were small and non‐significant, making natural selection for faster runs an unlikely explanation for the observed pattern. On the other hand, males had more femoral pores than females, and lizards had more pores at lower elevation, although the difference was significant only for males (which invest more in chemical signalling). In males, the number of pores, which remains constant along a lizard's life, was not correlated with hind limb length. However, femur length was positively correlated with mean pore size, allowing low‐elevation males to have larger than expected pores, which could increase the effectiveness with which they spread their signals in a dry and warm habitat where chemicals become volatile rapidly. Also, saturation of the sexual coloration of the head was higher for low‐elevation males, suggesting that sexual selection pressures may be more intense. Overall, our results indicate that sexual selection plays a significant role in shaping intraspecific variation in hind limb length. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104 , 318–329.  相似文献   
40.
The Maldanidae annelid worms are reviewed and the phylogenetic relationships of their subgroups provided, based on Hennigian principles and maximum parsimony. Characters were coded as binary and multistate (transformation series). We used 33 terminal taxa (species), and 50 characters. Characters were treated as unordered and of equal weight, and analysis was run in TNT. Three equally most-parsimonious trees were obtained with heuristic searches, with lengths of 64 steps; CI = 0.95, and RI = 0.98. The monophyly of Maldanidae was supported with 100% of bootstrap and jackknife values. As a result of our analysis, Arenicolidae remains the sister-group of Maldanidae, and both should be referred to Maldanomorpha. Maldanidae was supported by the following synapomorphies: dorsal prostomium; prostomium keel-shaped and fused to peristomium; torus globose behind median chaetigers; median chaetigers greatly elongated; number of pre-anal segments reduced. The subfamily Bogueinae was not monophyletic; Boguea and Boguella were included within Rhodininae. Clymenura, previously included in the Clymenurinae, was included within Euclymeninae. The taxa Notoproctinae, Maldaninae, Nicomachinae and Euclymeninae were grouped in the Maldanoplaca, a new taxon. Eight further new clades have been found, but were not named.  相似文献   
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