Cord blood–derived cytokine-induced killer cells combined with blinatumomab as a therapeutic strategy for CD19+ tumors

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.

Isolation and characterization of eight microsatellite loci in the icefish Chaenocephalus aceratus (Perciformes,Notothenioidei, Channichthyidae)

We characterized eight polymorphic microsatellites in the Scotia icefish Chaenocephalus aceratus (Perciformes, Notothenioidei, Channichthyidae) that is endemic of Southern Ocean waters surrounding the tip of the Antarctic Peninsula. Microsatellites were isolated from a partial genomic library enriched for an AC motif. The number of alleles ranged from two to 19 with a mean observed hererozygosity of 0.71. Loci were in Hardy–Weinberg equilibrium and no evidence for linkage disequilibrium was found. These molecular markers will be useful to investigate Scotia icefish genetic structure, possibly providing insights on its effective population size and demographic history.     

DNA phylogeny supports revised classification of Salmothymus obtusirostris

Salmothymus obtusirostris (soft-muzzled trout) is endemic to the South Adriatic drainage. Owing to its unusual appearance, which resembles both trout and grayling, it has been initially classified as a separate genus. However, this classification is ambiguous and has never been firmly established. We have studied mtDNA (control region and cytochrome b gene) and nuclear DNA (a part of LDH C*1 gene) variation between soft-muzzled trout from the upper part of the River Neretva, Bosnia and Herzegovina, and other salmonid representatives in order to examine how the current classification is congruent with molecular data. On the basis of sequence identity of mtDNA control region among several genera (i.e. Salmo , Oncorhynchus , Salvelinus , Acantholingua , Brachymystax , Thymallus and Coregonus ) a close relationship between Salmothymus , Salmo and Acantholingua was established. Phylogenetic analysis on a combined data set of mitochondrial and nuclear DNA, supported by 100% bootstraping, indicated that S. obtusirostris and A. ohridana are sister taxa which exhibit a closer relationship to S. trutta than to S. salar . This finding refutes the current classification, which recognizes S. obtusirostris as separate genus, and instead suggests its reclassification on the species level as Salmo obtusirostris .  © 2002 The Linnean Society of London, Biological Journal of the Linnean Society , 2002, 77 , 399–411.     

Downy mildew (Plasmopara viticola) epidemics on grapevine under climate change

As climate is a key agro‐ecosystem driving force, climate change could have a severe impact on agriculture. Many assessments have been carried out to date on the possible effects of climate change (temperature, precipitation and carbon dioxide concentration changes) on plant physiology. At present however, likely effects on plant pathogens have not been investigated deeply. The aim of this work was to simulate future scenarios of downy mildew (Plasmopara viticola) epidemics on grape under climate change, by combining a disease model to output from two general circulation models (GCMs). Model runs corresponding to the SRES‐A2 emissions scenario, characterized by high projections of both population and greenhouse gas emissions from present to 2100, were chosen in order to investigate impacts of worst‐case scenarios, among those currently available from IPCC. Three future decades were simulated (2030, 2050, 2080), using as baseline historical series of meteorological data collected from 1955 to 2001 in Acqui Terme, an important grape‐growing area in the north‐west of Italy. Both GCMs predicted increase of temperature and decrease of precipitation in this region. The simulations obtained by combining the disease model to the two GCM outputs predicted an increase of the disease pressure in each decade: more severe epidemics were a direct consequence of more favourable temperature conditions during the months of May and June. These negative effects of increasing temperatures more than counterbalanced the effects of precipitation reductions, which alone would have diminished disease pressure. Results suggested that, as adaptation response to future climate change, more attention would have to be paid in the management of early downy mildew infections; two more fungicide sprays were necessary under the most negative climate scenario, compared with present management regimes. At the same time, increased knowledge on the effects of climate change on host–pathogen interactions will be necessary to improve current predictions.     

Direct and indirect effects of weather variability in a specialist butterfly

1. Climate change poses serious threats to the long‐term persistence of many animal and plant populations. Species having specific niche requirements, or characterised by highly co‐evolved interactions, will face the greatest challenges. An example is represented by Maculinea alcon (Denis & Schiffermüller), a monophagous and univoltine butterfly species, which lays eggs only on larval host plants which occur inparticular phenological conditions. 2. The present 2‐year study focused on two M. alcon populations, both located at the southern boundaries of the species, but facing different climatic conditions (360 m, low altitude versus 860 m, high altitude). Population vulnerability with respect to direct and indirect effects of climate change was analysed, focusing on two important aspects of butterfly biology, i.e. the flight activity of adults and the degree of synchrony in the larval plant–insect interactions. 3. It was observed that, when positive temperature anomalies are reached, the temperature can exert detrimental effects on adults' activity. At a low altitude, in a hotter than usual year, a temperature threshold was recorded (around 32 °C), above which the activity of butterflies is inhibited. In contrast, at a high altitude, temperature increases maintain the opportunity to enhance butterfly activity. Altitudinal differences were also observed in the phenology of the two interacting species, which generate stronger asynchrony at low altitudes. 4. High‐ and low‐altitude populations represent different conservation units: a global increase in temperature would pose a serious threat to the lowland populations, whereas high‐altitude populations would gain a greater role in assuring the persistence of M. alcon at its southern boundaries.     

Ladder webs in orb‐web spiders: ontogenetic and evolutionary patterns in Nephilidae

Spider web research bridges ethology, ecology, functional morphology, material science, development, genetics, and evolution. Recent work proposes the aerial orb web as a one‐time key evolutionary innovation that has freed spider‐web architecture from substrate constraints. However, the orb has repeatedly been modified or lost within araneoid spiders. Modifications include not only sheet‐ and cobwebs, but also ladder webs, which secondarily utilize the substrate. A recent nephilid species level phylogeny suggests that the ancestral nephilid web architecture was an arboricolous ladder and that round aerial webs were derived. Because the web biology of the basalmost Clitaetra and the derived Nephila are well understood, the present study focuses on the webs of the two phylogenetically intervening genera, Herennia and Nephilengys, to establish ontogenetic and macroevolutionary patterns across the nephilid tree. We compared juvenile and adult webs of 95 Herennia multipuncta and 143 Nephilengys malabarensis for two measures of ontogenetic allometric web changes: web asymmetry quantified by the ladder index, and hub asymmetry quantified by the hub displacement index. We define a ‘ladder web’ as a vertically elongated orb exceeding twice the length over width (ladder index ≥ 2) and possessing (sub)parallel rather than round side frames. Webs in both genera allometrically grew from orbs to ladders, more so in Herennia. Such allometric web growth enables the spider to maintain its arboricolous web site. Unexpectedly, hub asymmetry only increased significantly in heavy‐bodied Nephilengys females, and not in Herennia, challenging the commonly invoked gravity hypothesis. The findings obtained in the present study support the intrageneric uniformness of nephilid webs, with Herennia etruscilla webs being identical to H. multipuncta. The nephilid web evolution suggests that the ancestor of Nephila reinvented the aerial orb web because the orb arises at a much more inclusive phylogenetic level, and all intervening nephilids retained the secondarily acquired substrate‐dependent ladder web. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 99 , 849–866.     

Specific and Common Epitopes in Mating Pheromones of Euplotes raikovi Revealed by Monoclonal Antibodies

Polypeptide mating pheromones Er-1 and Er-2, purified from the supernatant of Euplotes raikovi cultures of mating type I and mating type II, respectively, were used to immunize mice and obtain monoclonal antibodies. Five hybridoma clones producing antibodies specific to the mating pheromones were selected. They were analyzed for immunospecificity by immunoperoxidase assay, immunoblotting, and for their efficacy in inhibition of mating pheromone activity. Monoclonal antibodies from two hybridoma clones recognized only the mating pheromone used as antigen; those from the other three clones reacted, to comparable extents, with both mating pheromones. On the basis of these results it was assumed that two immunogenic sites exist in Er-1 and Er-2, one specific and the other common to both mating pheromones.     

Evolutionary distinctness of grayling {Thymallus thymallus) inhabiting the Adriatic river system, as based on mtDNA variation

The northern part of the peri-Adriatic river system is inhabited by a native grayling population. In comparison with the Danubian population most of the Adriatic population is regarded as morphologically distinct and therefore recognized as racially differentiated. DNA sequence analysis of the 394-bp fragment of the mtDNA control region and 363-bp fragment of the cytochrome b gene region from grayling specimens of the Adriatic, Danubian and Atlantic river systems revealed nine composite mtDNA haplotypes. The genetic divergence of the Adriatic and the Danubian-Atlantic haplotypes ranged from 2.52 to 3.10% and from 3.38 to 3.92% in the cytochrome b gene and control region, respectively. On the basis of sequence data an attempt was made to elucidate the phylogeography of the Adriatic population. The molecular data indicate an ancient monophyletic origin and also confirm its distinct position within the Thymallus thymallus species, in spite of the fact that stocking with the Danubian type occurred in the Adriatic river system. Therefore the Adriatic population deserves special attention. As a first step in its preservation, its formal distinction by using the name Adriatic grayling is proposed.     

Arabidopsis lipocalins AtCHL and AtTIL have distinct but overlapping functions essential for lipid protection and seed longevity

Lipocalins are a group of multifunctional proteins, recognized as carriers of small lipophilic molecules, which have been characterized in bacteria and animals. Two true lipocalins have been recently identified in plants, the temperature‐induced lipocalin (TIL) and the chloroplastic lipocalin (CHL), the expression of which is induced by various abiotic stresses. Each lipocalin appeared to be specialized in the responses to specific stress conditions in Arabidopsis thaliana, with AtTIL and AtCHL playing a protective role against heat and high light, respectively. The double mutant AtCHL KO × AtTIL KO deficient in both lipocalins was more sensitive to temperature, drought and light stresses than the single mutants, exhibiting intense lipid peroxidation. AtCHL deficiency dramatically enhanced the photosensitivity of mutants (vte1, npq1) affected in lipid protection mechanisms (tocopherols, zeaxanthin), confirming the role of lipocalins in the prevention of lipid peroxidation. Seeds of the AtCHL KO × AtTIL KO double mutant were very sensitive to natural and artificial ageing, and again this phenomenon was associated with the oxidation of polyunsaturated lipids. The presented results show that the Arabidopsis lipocalins AtTIL and AtCHL have overlapping functions in lipid protection which are essential for stress resistance and survival.