Choosing in Freedom or Forced to Choose? Introspective Blindness to Psychological Forcing in Stage-Magic

We investigated an individual ability to identify whether choices were made freely or forced by external parameters. We capitalized on magical setups where the notion of psychological forcing constitutes a well trodden path. In live stage magic, a magician guessed cards from spectators while inquiring how freely they thought they had made the choice. Our data showed a marked blindness in the introspection of free choice. Spectators assigned comparable ratings when choosing the card that the magician deliberately forced them compared to any other card, even in classical forcing, where the magician literally handles a card to the participant This observation was paralleled by a laboratory experiment where we observed modest changes in subjective reports by factors with drastic effect in choice. Pupil dilatation, which is known to tag slow cognitive events related to memory and attention, constitutes an efficient fingerprint to index subjective and objective aspects of choice.     

Ecological correlates between cladocerans and their endoparasites from permanent and rain pools: patterns in community composition and diversity

Water fleas (Cladocera) constitute a major component in freshwater food webs, with important ecosystem-level consequences. Their abundance and richness are strongly influenced by their ecology and coevolution with numerous endoparasites. We investigated how parasitism shapes cladoceran community structure and diversity. We surveyed 204 freshwater permanent and rain pools in Israel, identified all cladoceran specimens and screened them for infection. Daphniid species richness in this survey was lower than in previous surveys and the distribution pattern of the species was different, most likely due to local extinction and habitat loss. We recorded a total of 21 taxa of endoparasites, of which 13 are most likely species not yet described. Variation in parasite richness among hosts and sites could not be attributed to differences in host body size and behavioral feeding strategies. We extend the known host range and geographic distribution of eight parasites from Europe and North America (between latitudes 40° and 70°) to much southern areas (latitudes 31° and 32°) and to different climate zones (arid and semi-arid areas). In many infected populations we found co-occurrence of at least two endoparasites, and in most of these cases Daphnia individuals were found to be infected by several endoparasite species simultaneously. Such multiple infections may have important consequences for community structure as well as host?Cparasite coevolution.     

Integrin regulation by vascular endothelial growth factor in human brain microvascular endothelial cells: role of alpha6beta1 integrin in angiogenesis

The precise role of vascular endothelial growth factor (VEGF) in regulating integrins in brain microvascular endothelial cells is unknown. Here, we analyzed VEGF effects on integrin expression and activation in human brain microvascular endothelial cells (HBMECs). Using human cDNA arrays and ribonuclease (RNase) protection assays, we observed that VEGF up-regulated the mRNA expression of alpha(6) integrin in HBMECs. VEGF significantly increased alpha(6)beta(1) integrin expression, but not alpha(6)beta(4) integrin expression in these cells. Specific down-regulation of alpha(6) integrin expression by small interfering RNA (siRNA) oligonucleotides inhibited both the capillary morphogenesis of HBMECs and their adhesion and migration. Additionally, VEGF treatment resulted in activation of alpha(6)beta(1) integrins in HBMECs. Functional blocking of alpha(6) integrin with its specific antibody inhibited the VEGF-induced adhesion and migration as well as in vivo angiogenesis, and markedly suppressed tumor angiogenesis and breast carcinoma growth in vivo. Thus, VEGF can modulate angiogenesis via increased expression and activation of alpha(6)beta(1) integrins, which may promote VEGF-driven tumor angiogenesis in vivo.     

Ovarian hormones modulate 'compulsive' lever-pressing in female rats

Life events related to the female hormonal cycle may trigger the onset of obsessive-compulsive disorder (OCD) or exacerbate symptoms in women already suffering from it. These observations suggest a possible role for ovarian hormones in the course of this disorder. Yet, the mechanisms that may subserve the modulatory effect of ovarian hormones are currently unknown. The aim of the present study was therefore to test the role of ovarian hormones in the signal attenuation rat model of OCD. Experiment 1 compared the behavior of pre-pubertal and adult male and female rats in the model, and found no age and sex differences in compulsive responding. Experiment 2 found that compulsive responding fluctuates along the estrous cycle, being highest during late diestrous and lowest during estrous. Acute administration of estradiol to pre-pubertal female rats was found to attenuate compulsive behavior (Experiment 3), and withdrawal from chronic administration of estradiol was shown to increase this behavior (Experiment 4). These findings extend the use of the signal attenuation model of OCD to female rats, and by demonstrating that the model is sensitive to the levels of ovarian hormones, provide the basis for using the model to study the role of ovarian hormones in OCD. In addition, the present findings support the hypothesis that the increased risk of onset and exacerbation of OCD in women post-partum may be a result of the decrease in the level of estradiol, which was elevated during pregnancy.     

Autosomal-Recessive Early-Onset Retinitis Pigmentosa Caused by a Mutation in PDE6G, the Gene Encoding the Gamma Subunit of Rod cGMP Phosphodiesterase

Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration, with a worldwide prevalence of 1 in 4000. Over 30 genes and loci have been implicated in nonsyndromic autosomal-recessive (ar) RP. Genome-wide homozygosity mapping was conducted in two sibships from an extended consanguineous Muslim Arab Israeli family segregating ar severe early-onset RP. A shared homozygous region on chromosome 17q25.3 was identified in both sibships, with an overlap of 4.7 Mb. One of the genes located in this interval is PDE6G, encoding for the inhibitory γ subunit of rod photoreceptor cyclic GMP-phosphodiesterase. Mutations in the genes encoding for the catalytic subunits of this holoenzyme, PDE6A and PDE6B, cause arRP. Sequencing of all coding exons, including exon-intron boundaries, revealed a homozygous single base change (c.187+1G>T) located in the conserved intron 3 donor splice site of PDE6G. This mutation cosegregated with the disease in the extended family. We used an in vitro splicing assay to demonstrate that this mutation leads to incorrect splicing. Affected individuals had markedly constricted visual fields. Both scotopic and photopic electroretinograms were severely reduced or completely extinct. Funduscopy showed typical bone spicule-type pigment deposits spread mainly at the midperiphery, as well as pallor of the optic disk. Macular involvement was indicated by the lack of foveal reflex and typical cystoid macular edema, proved by optical coherence tomography. These findings demonstrate the positive role of the γ subunit in maintaining phosphodiesterase activity and confirm the contribution of PDE6G to the etiology of RP in humans.     

Protective Effect of Human Amniotic Fluid Stem Cells in an Immunodeficient Mouse Model of Acute Tubular Necrosis

Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit^pos stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN.     

PAK1 and aPKCzeta regulate myosin II-B phosphorylation: a novel signaling pathway regulating filament assembly

Many signaling pathways regulate the function of the cellular cytoskeleton. Yet we know very little about the proteins involved in the cross-talk between the signaling and the cytoskeletal systems. Here we show that myosin II-B, an important cytoskeletal protein, resides in a complex with p21-activated kinase 1 (PAK1) and atypical protein kinase C (PKC) zeta (aPKCzeta) and that the interaction between these proteins is EGF-dependent. We further show that PAK1 is involved in aPKCzeta phosphorylation and that aPKCzeta phosphorylates myosin II-B directly on a specific serine residue in an EGF-dependent manner. This latter phosphorylation is specific to isoform B of myosin II, and it leads to slower filament assembly of myosin II-B. Furthermore, a decrease in aPKCzeta expression in the cells alters myosin II-B cellular organization. Our finding of a new signaling pathway involving PAK1, aPKCzeta, and myosin II-B, which is implicated in myosin II-B filament assembly and cellular organization, provides an important link between the signaling system and cytoskeletal dynamics.