Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells.

IL-2 immunotherapy is an attractive treatment option for certain metastatic cancers. However, administration of IL-2 to patients can lead, by ill-defined mechanisms, to toxic adverse effects including severe pulmonary edema. Here, we show that IL-2-induced pulmonary edema is caused by direct interaction of IL-2 with functional IL-2 receptors (IL-2R) on lung endothelial cells in vivo. Treatment of mice with high-dose IL-2 led to efficient expansion of effector immune cells expressing high levels of IL-2Rbetagamma, including CD8(+) T cells and natural killer cells, which resulted in a considerable antitumor response against s.c. and pulmonary B16 melanoma nodules. However, high-dose IL-2 treatment also affected immune cell lineage marker-negative CD31(+) pulmonary endothelial cells via binding to functional alphabetagamma IL-2Rs, expressed at low to intermediate levels on these cells, thus causing pulmonary edema. Notably, IL-2-mediated pulmonary edema was abrogated by a blocking antibody to IL-2Ralpha (CD25), genetic disruption of CD25, or the use of IL-2Rbetagamma-directed IL-2/anti-IL-2 antibody complexes, thereby interfering with IL-2 binding to IL-2Ralphabetagamma(+) pulmonary endothelial cells. Moreover, IL-2/anti-IL-2 antibody complexes led to vigorous activation of IL-2Rbetagamma(+) effector immune cells, which generated a dramatic antitumor response. Thus, IL-2/anti-IL-2 antibody complexes might improve current strategies of IL-2-based tumor immunotherapy.

RF pulse concatenation for spatially selective inversion

It is shown that spatially selective inversion and saturation can be achieved by concatenation of RF pulses with lower flip angles. A concatenation rule which enables global doubling of the flip angle of any given excitation pulse applied to initial z magnetization is proposed. In this fashion, the selectivity of the single pulse is preserved, making the high selectivity achievable in the low flip-angle regime available for inversion and large flip-angle saturation purposes. The profile quality achievable with exemplary concatenated pulses is investigated in comparison with adiabatic inversion. It is verified that by using concatenated inversion in the transfer insensitive labeling technique (TILT), the MT artifact is suppressed. Copyright 2000 Academic Press.

A selective nociceptive block is not sufficient to prevent central changes after peripheral nerve injury

Background: Providing analgesia without suppressing motor or sensory function is a challenge for regional anesthesia and postoperative pain management. Resiniferatoxin (RTX), an ultrapotent agonist for transient receptor potential subtype-1 (TRPV1) can produce this selective blockade, as TRPV1 is selectively expressed on nociceptors. Futhermore, after peripheral nerve injury, spontaneous ectopic activity arises from all types of nerve fibers that can affect spinal neurons and glial cells. The goal of the present experiment is to determine whether spontaneous activity generated in C-fibers or in both A&C-fibers is required for microglia activation. Method: We applied RTX (0.01%) or bupivacaine microspheres to the sciatic nerve of rats to block the conduction of C-fibers or A&C-fibers, respectively, before spared nerve injury (SNI). Behavior was tested and all the rats were sacrificed 2 days later; immunohistochemistry was performed on their spinal cord for mitogen-activated protein kinase (MAPK) p38, bromodeoxyuridine (BrdU, marker of proliferation) and Iba1 (microglial marker). Result: At day 2 after SNI robust mechanical allodynia and p38 activation in spinal microglia were documented. There was also a substantial cell proliferation in the spinal cord, all proliferating cells (BrdU+) being microglia (Iba1+). RTX blocked heat sensitivity and produced heat hypoalgesia without affecting mechanical allodynia and motor function. Microglial proliferation and p38 activation in the spinal cord were not affected by RTX (p >0.05). In contrast, a complete sensory and motor blockade was seen with bupivacaine which also significantly inhibited p38 activation and microglial proliferation in the spinal cord (p <0.05). Conclusion: We conclude that (1) RTX can provide a selective nociceptive blockade but that (2) blocking only nociceptive fibers does not impair the development of mechanical allodynia and microglia activation. Therefore (3) if microglia activation is important for chronic pain development then specific nociceptive blockade won't be sufficient to prevent it.

Selective expression of a dominant-negative form of peroxisome proliferator-activated receptor in keratinocytes leads to impaired epidermal healing.

Many nuclear hormone receptors are involved in the regulation of skin homeostasis. However, their role in the epithelial compartment of the skin in stress situations, such as skin healing, has not been addressed yet. The healing of a skin wound after an injury involves three major cell types: immune cells, which are recruited to the wound bed; dermal fibroblasts; and epidermal and hair follicle keratinocytes. Our previous studies have revealed important but nonredundant roles of PPARalpha and beta/delta in the reparation of the skin after a mechanical injury in the adult mouse. However, the mesenchymal or epithelial cellular compartment in which PPARalpha and beta/delta play a role could not be determined in the null mice used, which have a germ line PPAR gene invalidation. In the present work, the role of PPARalpha was studied in keratinocytes, using transgenic mice that express a PPARalpha mutant with dominant-negative (dn) activity specifically in keratinocytes. This dn PPARalpha lacks the last 13 C terminus amino acids, binds to a PPARalpha agonist, but is unable to release the nuclear receptor corepressor and to recruit the coactivator p300. When selectively expressed in keratinocytes of transgenic mice, dn PPARalphaDelta13 causes a delay in the healing of skin wounds, accompanied by an exacerbated inflammation. This phenotype, which is similar to that observed in PPARalpha null mice, strongly suggests that during skin healing, PPARalpha is required in keratinocytes rather than in other cell types.

Finnish embryo transfer breeding program "ASMO" : description of the goals and a summary of the results of initial selection

Selostus: Alkionsiirtojalostusohjelma "ASMO", sen tavoitteet ja yhteenveto alkuvalinnan tuloksista

Effect of feeding level during autumn and winter on breeding weight and result in single and pair-housed minks

Selostus: Syys- ja talviruokinnan vaikutus yksin ja pareittain kasvatettujen minkkien lisääntymistulokseen

Differences in diet between the two largest breeding colonies of Audouin's gulls: the effects of fishery activities

We analysed and compared the diet of Audouin´s gulls Larus audouinii between their two largest breeding sites in the world: the Ebro Delta and the Chafarinas Islands (western Mediterranean). These two localities showed marked differences in the features of the commercial fishing fleet: in the Ebro Delta area a large fishing fleet produced large amounts of discards, while in the Chafarinas the fleet discarded smaller amounts of fish and marine invertebrates, due to the smaller number of vessels. It is also likely that the percentage of discards from total catches is also lower around the Chafarinas than at the Ebro Delta. We distinguished two types of fishing to compare diet compositions: diurnal (only trawling activity) and diurnal and nocturnal (trawling and purse-seine activity, respectively). We also differentiated regurgitates from young nestlings (up to 20 days old) and from older nestlings or adult birds. At the two localities, fish was the main food of Audouin´s gulls, with epipelagic prey (mainly clupeoids) being more important when both diurnal and nocturnal fisheries were operating. This confirms that epipelagic prey either caught actively by the gulls or linked to fisheries was particularly important in the feeding habits of Audouin´s gulls. Nevertheless, differences between the two colonies appear mainly when only trawlers operated: while at the Ebro Delta gulls showed higher consumption of benthic-mesopelagic prey (probably linked to a higher trawler discard availability), gulls from the Chafarinas Islands consumed higher biomass of epipelagic prey probably caught actively at night. When both fleets operated around the two colonies, the average biomass of prey in a regurgitate of younger chicks was significantly higher at the Ebro Delta than at Chafarinas, and the opposite trend was recorded for older nestlings and adults. Niche width was broader in Chafarinas than in the Ebro Delta for both age classes and for any fishing fleet schedule, suggesting again that the exploitation of discards was higher at the Ebro Delta than at the Chafarinas, where gulls showed a more varied diet. Despite the fact that availability of discards was probably higher at the Ebro Delta than at Chafarinas, the per capita availability was not so different at both localities due to the increasing seabird community population at the Ebro Delta, which ca. doubled that at Chafarinas in the last decade.

Impact of fisheries on activity, diet and predatory interactions between yellow-legged and Audouin's gulls breeding at the Chafarinas Is.

Interactions between yellow-legged Larus cachinnans and Audouin´s Larus audouinii gulls and fisheries operating around the Chafarinas Islands, located 4.5 km off the Moroccan Mediterranean coast, are reviewed. At the Chafarinas archipelago two distinct types of fisheries operate: trawlers and purse seines. Gulls take advantage of both fisheries. They scavenge trawler discards and congregate around shoals of fish attracted to the surface by the purse-seine lamps. When both trawlers and purse-seine boats are in operation, the diet of both gull species is similar, with epipelagic fish accounting for over 60% of the biomass, partially collected in association with the purse-seine fishery. When only trawlers operated yellow-legged gulls, but not Audouin´s gulls, augmented their diet mainly with human waste from refuse dumps, suggesting that competition for food between the two species is mainly limited to the periods when resources made available by fishery activities are abundant. Likewise, when only trawlers operated, there was an increase in the predation pressure on eggs and chicks of Audouin´s gulls. In particular, during the week of celebrations for the holy lamb festival when neither fishery operated, egg losses of Audouin´s gull increased dramatically, suggesting that severe food shortage caused by the cessation of fishing can result in an increased predation pressure by yellow-legged gulls, affecting Audouin´s gull productivity. These results suggest a novel socio-ecological link between gulls, fisheries and local feasts.

Sustainability - a challenge to animal production and breeding

Selostus: Kestävän kehityksen vaatimukset kotieläintuotannossa ja -jalostuksessa

Maturation of the lymphoid system. III. Induction of selective unresponsiveness by injection of a haptenated carbohydrate into neonatal mice.

Neonatal treatment of A/J mice with DNP-Ficoll reduced or eliminated indirect anti-DNP PFC normally produced in response to adult challenge with DNP-keyhole limpet hemocyanin. The remaining direct anti-DNP PFC response was of low avidity. Spleen cells from neonatal A/J mice inhibited the in vitro but not the in vivo response of adult spleen cells to DNP-Ficoll.

Cognition and brain function in schizotypy : a selective review

Schizotypy refers to a set of personality traits thought to reflect the subclinical expression of the signs and symptoms of schizophrenia. Here, we review the cognitive and brain functional profile associated with high questionnaire scores in schizotypy. We discuss empirical evidence from the domains of perception, attention, memory, imagery and representation, language, and motor control. Perceptual deficits occur early and across various modalities. Whilst the neural mechanisms underlying visual impairments may be linked to magnocellular dysfunction, further effects may be seen downstream in higher cognitive functions. Cognitive deficits are observed in inhibitory control, selective and sustained attention, incidental learning and memory. In concordance with the cognitive nature of many of the aberrations of schizotypy, higher levels of schizotypy are associated with enhanced vividness and better performance on tasks of mental rotation. Language deficits seem most pronounced in higher-level processes. Finally, higher levels of schizotypy are associated with reduced performance on oculomotor tasks, resembling the impairments seen in schizophrenia. Some of these deficits are accompanied by reduced brain activation, akin to the pattern of hypoactivations in schizophrenia spectrum individuals. We conclude that schizotypy is a construct with apparent phenomenological overlap with schizophrenia and stable inter-individual differences that covary with performance on a wide range of perceptual, cognitive and motor tasks known to be impaired in schizophrenia. The importance of these findings lies not only in providing a fine-grained neurocognitive characterisation of a personality constellation known to be associated with real-life impairments, but also in generating hypotheses concerning the aetiology of schizophrenia.

Estimating sex-specific dispersal rates with autosomal markers in hierarchically structured populations.

A recent study suggests that sex-specific dispersal rates can be quantitatively estimated on the basis of sex- and state-specific (pre- vs. postdispersal) F-statistics. In the present paper, we extend this approach to account for the hierarchical structure of natural populations, and we validate it through individual-based simulations. The model is applied to an empirical data set consisting of 536 individuals (males, females, and predispersal juveniles) of greater white-toothed shrews (Crocidura russula), sampled according to a hierarchical design and typed for seven autosomal microsatellite loci. From this dataset, dispersal is significantly female biased at the local scale (breeding-group level), but not at the larger scale (among local populations). We argue that selective pressures on dispersal are likely to depend on the spatial scale considered, and that short-distance dispersal should mainly respond to kin interactions (inbreeding or kin competition avoidance), which exert differential pressure on males and females.

Optimizing anther culture for barley breeding

Selostus: Ponsiviljelymenetelmän optimointi ohranjalostuksen käyttöön

Ecology and evolution of social-organization: insights from fire ants and other highly eusocial insects

Social organisms exhibit conspicuous intraspecific variation in all facets of their social organization. A prominent example of such variation in the highly eusocial Hymenoptera is differences in the number of reproductive queens per colony, Differences in queen number in ants are associated with differences in a host of reproductive and social traits, including queen phenotype and breeding strategy, mode of colony reproduction, and pattern of sex allocation. We examine the causes and consequences of changes in colony queen number and associated traits using the fire ant Solenopsis invicta as a principal model. Ecological constraints on mode of colony founding may act as important selective forces causing the evolution of queen number in this and many other ants, with social organization generally perpetuated across generations by means of the social environment molding appropriate queen phenotypes and reproductive strategies. Shifts in colony queen number have profound effects on genetic structure within nests and may also influence genetic structure at higher levels (aggregations of nests or local demes) because of the association of queen number with particular mating and dispersal habits. Divergence of breeding habits between populations with different social organizations has the potential to promote genetic differentiation between these social variants. Thus, evolution of social organization can be important in generating intrinsic selective regimes that channel subsequent social evolution and in initiating the development of significant population genetic structure, including barriers to gene flow important in cladogenesis.