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Constitutive phosphatidylinositide 3-kinase ( PI3K) signalling has been implicated in multiple myeloma ( MM) pathophysiology and is regarded as an actionable target for pharmacological intervention. Isoform-specific PI3K inhibition may offer the most focused treatment approach and could result in greater clinical efficacy and reduced side effects. We therefore performed isoform-specific knockdown of PIK3 CA, PIK3 CB, PIK3 CD, and PIK3 CG to analyse their individual contributions to MM cell survival and downstream signalling. In addition, we tested the effectivity of the novel PI3K isoform-specific inhibitors BYL-719 ( PIK3 CA), TGX-221 ( PIK3 CB), CAL-101 ( PIK3 CD), and CAY10505 ( PIK3 CG). We found the PIK3 CA isoform to be of paramount importance for constitutive Akt activity in MM cells, and - in contrast to inhibition of other class I isoforms - only the blockade of PIK3 CA was sufficient to induce cell death in a sizeable subgroup of MM samples. Furthermore, pharmacological PIK3 CA inhibition in combination treatments of BYL-719 and established anti-myeloma agents resulted in strongly enhanced MM cell death. Our data thus clearly indicate therapeutic potential of PIK3 CA inhibitors and support their clinical evaluation in multiple myeloma. [ABSTRACT FROM AUTHOR]

Simple Summary: Most animals blend well into their natural environment, which protects them from predators. However, in captive environments, animals are often exposed, which can lead to stress. Research suggests that animals are more difficult to detect in complex environments. We tested background preferences in the Gouldian finch, which occurs in two main head color morphs in the wild. Birds were tested in groups of four in either the same head color (black or red) or mixed head color (two black and two red) pairings. One half of the cage had a simple background pattern, the other a complex background pattern. We measured the time spent in front of each background after 10 days in the cage (phase 1), after which backgrounds were swapped (left to right), and assessed preferences again on day 17 (phase 2). Birds preferred the simple background, particularly in phase 1. However, females initially chose the simple background but used both backgrounds in phase 2, whereas changes in males were not significant. Both color morphs preferred the simple background in phase 1, with the black-headed birds moving to the complex background in phase 2. Results indicate that background preferences differ among individuals, which should be considered when designing enclosures. Most wild animals camouflage well into their environment, providing protection from predators, whereas captive animals often contrast with their background. This can cause stress for the animal, which may perceive it as being exposed. Theory suggests that prey is more difficult to detect in front of complex backgrounds; hence, animals should prefer complex over simple backgrounds. We tested this in the polymorphic Gouldian finch by providing a complex background pattern in one half of the flight cage and a simple background pattern in the other half for 10 days (phase 1). Patterns were then swapped and presented for another week (phase 2). Groups of four birds consisting of either pure black-headed or red-headed or mixed head color (two black-headed and two red-headed) pairings were tested. Gouldian finches spent significantly more time in front of the simple background in phase 1 but not in phase 2. Specifically, females preferred the simple background in phase 1 significantly more than males. Moreover, red-headed birds consistently perched in front of the simple background, whereas black-headed birds used both backgrounds, particularly in phase 2. Results indicate that background preferences differ between sexes and morphs, which should be considered when designing backgrounds. Moreover, natural habitat preferences need consideration. [ABSTRACT FROM AUTHOR]

Resident and nomadic species differ substantially in their mobility, with the former spending most of their lives in a restricted area and the latter encountering many areas while tracking spatiotemporal unpredictable resources. Earlier studies have shown that information gathering differs alongside this mobility axis—resident species pay more attention to changes in their familiar environment than nomadic ones. However, little is known about spatial exploration in resident and nomadic species. We investigated spatial exploration in 10 closely related parrot species that differed in their mobility by giving them access to two unfamiliar aviaries left and right of the familiar aviary. For analyses, mobility and some diet and habitat variables were related to spatial exploration. Nomadic species spent less time exploring the novel aviaries and also started tactile exploration later than resident/nomadic and pure resident species. Furthermore, diet specialists visited more new locations in relation to their overall movements than diet generalists. The variables were not correlated with the molecular phylogeny (mitochondrial cytochrome b) of the species. The results indicate that nomads invest less in spatial exploration than residents possibly because they stay only for limited periods of time in one particular area or use easier-to-assess cues. Residents, in contrast, assess a novel environment in detail as they may collect information about future breeding sites for which they need short- and long-term information. Finally, diet specialists may pay attention to fewer environmental cues than generalists, which allows them to move faster through a novel environment. [ABSTRACT FROM PUBLISHER]

Disturbance in vitamin A metabolism seems to be an important attribute of cancer cells. Retinoids, particularly retinoic acid, have critical regulatory functions and appear to modulate tumor development and progression. The key step of vitamin A metabolism is the esterification of all- trans retinol, catalyzed by lecithin/retinol acyltransferase (LRAT). In this work, we show that malignant melanoma cells are able to esterify all- trans retinol and subsequently isomerize all-trans retinyl esters (RE) into 11- cis retinol, whereas their benign counterparts-melanocytes are not able to catalyze these reactions. Besides, melanoma cell lines express lecithin/retinol acyltranseferase both at the mRNA and protein levels. In contrast, melanocytes do not express this enzyme at the protein level, but mRNA of lecithin/retinol acyltransefrase could still be present at mRNA level. RPE65 is expressed in both melanocytic counterparts, and could be involved in the subsequent isomerization of RE produced by lecithin/retinol acyltransefrase to 11- cis retinol. Cellular retinol-binding protein 2 does not appear to be involved in the regulation of all- trans retinol esterification in these cells. Expression of LRAT and RPE65 can be modulated by retinoids. We propose that the post-transcriptional regulation of lecithin/retinol acyltransefrase could be involved in the differential expression of this enzyme. Besides, activities of LRAT and RPE65 may be important for removal of all- trans retinal which is the substrate for retinoic acid production in skin cells. Consequently, the decreasing cellular amount of retinoic acid and its precursor molecules could result in a change of gene regulation. J. Cell. Physiol. 227: 718-728, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Armed groups pose a severe challenge to current peace- and state-building processes. Their degree of dispersion, influence, and effect on local and international politics make it necessary to consider ways and strategies for coping and interacting with them. The article assesses and reviews the contribution of specific options, their suitability, and their applicability regarding particular types of actors. First, it delineates options for dealing with armed groups based on three perspectives: realist, institutionalist and constructivist. Second, the article matches these perspectives with the capabilities of international third parties. Finally, the paper reflects on the difficulties that arise from the plurality of different types of armed groups as well as external actors. [ABSTRACT FROM AUTHOR]

Sociality exists in an extraordinary range of ecological settings. For individuals to accrue the benefits associated with social interactions, they are required to maintain a degree of spatial and temporal coordination in their activities, and make collective decisions. Such coordination and decision-making has been the focus of much recent research. However, efforts largely have been directed toward understanding patterns of collective behaviour in relatively stable and cohesive groups. Less well understood is how fission-fusion dynamics mediate the process and outcome of collective decisions making. Here, we aim to apply established concepts and knowledge to highlight the implications of fission-fusion dynamics for collective decisions, presenting a conceptual framework based on the outcome of a small-group discussion INCORE meeting (funded by the European Community's Sixth Framework Programme). First, we discuss how the degree of uncertainty in the environment shapes social flexibility and therefore the types of decisions individuals make in different social settings. Second, we propose that the quality of social relationships and the energetic needs of each individual influence fission decisions. Third, we explore how these factors affect the probability of individuals to fuse. Fourth, we discuss how group size and fission-fusion dynamics may affect communication processes between individuals at a local or global scale to reach a consensus or to fission. Finally, we offer a number of suggestions for future research, capturing emerging ideas and concepts on the interaction between collective decisions and fission-fusion dynamics. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the implications on aging rusty blackbirds of the prebasic and previously undescribed prealternate molt at Whitehorse, Yukon Territory. It says that a Friedman test was used in the study to compare molt intensity in feather and a Kruskal-Wallis test to test the molt intensity variation of the aging rusty blackbirds. The result of the study shows that presence of the pale-eye ring can be used to identify the age of aging birds along with the chin.

The article presents a study which investigates regarding the incidence of hematozoa infections in wintering and breeding Rusty Blackbirds (Euphagus carolinus) in different times of the year. It states that the differences of prevalence and the comparison of prevalence of hematozoa between Alaska and Maine was analyzed using the chi-squared test. The result of the study shows that a nonseasonal relapse was suggested in overwintering Rusty Blackbirds for the high prevalence of hematozoans.

The article offers a study on the geographical and seasonal differences in the levels of mercury concentrations in the blood and feathers of rusty blackbirds (Euphagus carolinus) in several North American regions. It says that mercury concentrations in bloods and feathers of birds in Acadian forests were higher than those of the western boreal forests of Alaska and wintering areas in the U.S. Moreover, it states that wintering birds have lower blood mercury levels than those of breeding birds.

The article offers a study on stable hydrogen isotopes in feathers of rusty blackbirds (Euphagus carolinus) in Mississippi Alluvial Valley and coastal South Carolina and Virginia, and in museum specimens from 1879 to 1990 to determine a migratory connectivity. It says that modern and historical isotopic analyses show a difference in the breeding origins of birds wintering in those regions. Moreover, it suggests that wildlife management should be tailored on both breeding and wintering grounds.

Background Oligodeoxynucleotides (ODNs) containing unmethylated cytosine--eguanosine (CpG) sequence motifs constitute the immunostimulatory components of bacterial DNA which potently activate innate immunity. Administration of CpG-ODNs before the onset of experimental colitis prevents intestinal inflammation by induction of colitis-suppressing T cells. Aims To identify the interplay between innate and adaptive immune cells finally leading to protective CpG-ODN effects in intestinal inflammation. Methods Total splenic cells or purified selected cell types (CD4+CD62L+ T cells alone or with B cells or dendritic cells (DCs)) from BALB/c mice were (co)-incubated in vitro with CpG-ODN for 5 days and CD4+CD62L+ cells were injected intraperitoneally into C. B.-17 SCID (severe combined immunodeficiency) mice. Splenic CD4+CD62L+ T cells were isolated from transgenic donor mice in which CD11c+ DCs were depleted by diphtheria toxin administration during CpG-ODN treatment and injected into C57BL/6 Rag2-/- recipients. Intestinal inflammation was evaluated by histological scoring and cytokine secretion of mesenteric lymph node cells. Results CpG-ODN treatment of total splenic cells but not of purified CD4+CD62L+ cells reduced the colitogenic potential of transferred T cells. While CpGODN stimulation of co-cultured CD4+CD62L+ and B-cells did not alter the colitogenic potential of T cells, co-incubation of CpG-ODN-stimulated DCs and CD4+CD62L+ cells reduced the colitogenic potential of the T cell population. Depletion of CD11c+ DCs during CpG-ODN administration in vivo abolished the protective CpG-ODN effects. Conclusions CpG-ODN-dependent protective effects in experimental colitis act indirectly on CD4+CD62L+ T cells. While the involvement of B cells could be excluded, CD11c+ DCs were identified as key mediators of CpG-ODN-induced protection in experimental colitis. [ABSTRACT FROM AUTHOR]

Abstract: The chromosome of Bacillus subtilis codes for seven extracytoplasmic function sigma factors the activity of which is modulated normally by a cognate anti-sigma factor. While inducing factors and genes for four of them (σM, σW, σX, and σY) have been identified, those of the remaining three sigma factors including σV remain elusive. The objective of the present study was the unequivocal identification of its anti-sigma factor and of genes controlled by σV. In many cases reported so far the gene coding for the anti-sigma factor is located immediately downstream of the gene coding for the sigma factor, and both form a bicistronic operon. We could show by two different experimental approaches that this is also the case for sigV and rsiV. Under conditions of overproduction of σV, 13 genes could be identified being induced several-fold by the DNA macroarray technique. Induction of three of them was confirmed by Northern blots, and the potential promoter of sigV was identified by primer extension. This led to the deduction of a consensus sequence recognized by σV. [Copyright &y& Elsevier]

Migratory birds stay in a particular area for only short periods and must rapidly acquire appropriate information about stopover sites. In contrast, resident birds can update their knowledge whenever necessary. In a novel environment migrants are thus predicted to assess relevant information faster than nonmigrants. We tested this prediction with two closely related species, the migratory garden warbler, Sylvia borin, and the resident Sardinian warbler, S. melanocephala momus. Each bird was allowed to explore two unfamiliar boxes, one of which contained food. Garden warblers found food significantly faster than Sardinian warblers. Garden warblers may have a wide-area exploration strategy to assess a novel room and Sardinian warblers may have a local-area exploration strategy. We conclude that a wide-area exploration strategy might be required for migrants to assess environmental information as rapidly as possible. [Copyright &y& Elsevier]