Temporal speciation pattern in the western Mediterranean genus Tudorella P. Fischer, 1885 (Gastropoda,Pomatiidae) supports the Tyrrhenian vicariance hypothesis

The land snail genus Tudorella shows a peculiar disjunct distribution around the western Mediterranean coasts. Despite high phenotypic plasticity, only two species with a disputed number of subspecific taxa are currently recognised. We delimited the species with mitochondrial (COI & 16S) and nuclear (ITS-1) markers based on the unified species concept and suggested that there are eight species in the genus, two of them currently undescribed. Applying Bayesian phylogenetic model selection, we tested four different biogeographic hypotheses that could be causal for the current distribution pattern of extant Tudorella species. A scenario involving vicariance events resulting from the repeated splits of the Tyrrhenian plate with subsequent dispersal events over land bridges during the Pliocene received greatest support in the data.     

Anaerobic bacteria infection in cystic fibrosis airway disease

Depletion of the periciliary liquid in "Cystic Fibrosis" airway disease results in reduced mucociliary transport, persistent mucus hypersecretion and consequently increased height of the luminal mucus layer, so hypoxic gradients in the mucus plugs are developed. Because of anaerobic lung zones, it is highly probable that anaerobic bacteria not detected by routine bacteriologic culture methods also reside within the mucus. Notwithstanding this evidence, microbiology laboratories working in the cystic fibrosis field do not generally use strict anaerobic bacteriologic cultures to determine the presence of anaerobic bacteria in the Cystic Fibrosis lung. The aim of this review is to focus on the published data regarding the finding of anaerobic bacteria in cystic fibrosis airway disease. Therefore, microbiology, diagnosis, antimicrobial susceptibility and possible impact on clinical management of anaerobic bacteria lung infection in cystic fibrosis are described.     

ATP-mediated cell–cell signaling in the organ of Corti: the role of connexin channels

Connexin 26 (Cx26) and connexin 30 (Cx30) form hemichannels that release ATP from the endolymphatic surface of cochlear supporting and epithelial cells and also form gap junction (GJ) channels that allow the concomitant intercellular diffusion of Ca²⁺ mobilizing second messengers. Released ATP in turn activates G-protein coupled P2Y₂ and P2Y₄ receptors, PLC-dependent generation of IP₃, release of Ca²⁺ from intracellular stores, instigating the regenerative propagation of intercellular Ca²⁺ signals (ICS). The range of ICS propagation is sensitive to the concentration of extracellular divalent cations and activity of ectonucleotidases. Here, the expression patterns of Cx26 and Cx30 were characterized in postnatal cochlear tissues obtained from mice aged between P5 and P6. The expression gradient along the longitudinal axis of the cochlea, decreasing from the basal to the apical cochlear turn (CT), was more pronounced in outer sulcus (OS) cells than in inner sulcus (IS) cells. GJ-mediated dye coupling was maximal in OS cells of the basal CT, inhibited by the nonselective connexin channel blocker carbenoxolone (CBX) and absent in hair cells. Photostimulating OS cells with caged inositol (3,4,5) tri-phosphate (IP₃) resulted in transfer of ICS in the lateral direction, from OS cells to IS cells across the hair cell region (HCR) of medial and basal CTs. ICS transfer in the opposite (medial) direction, from IS cells photostimulated with caged IP₃ to OS cells, occurred mostly in the basal CT. In addition, OS cells displayed impressive rhythmic activity with oscillations of cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) coordinated by the propagation of Ca²⁺ wavefronts sweeping repeatedly through the same tissue area along the coiling axis of the cochlea. Oscillations evoked by uncaging IP₃ or by applying ATP differed greatly, by as much as one order of magnitude, in frequency and waveform rise time. ICS evoked by direct application of ATP propagated along convoluted cellular paths in the OS, which often branched and changed dynamically over time. Potential implications of these findings are discussed in the context of developmental regulation and cochlear pathophysiology.     

Hsp60 Is Actively Secreted by Human Tumor Cells

Background

Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination.

Methodology/Principal Findings

Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts.

Conclusions/Significance

Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likely reflect a general physiological phenomenon, occurring in many tumors.     

Prolonged survival of allografts induced by mycobacterial Hsp70 is dependent on CD4+CD25+ regulatory T cells

Background

Heat shock proteins (Hsps) are stress induced proteins with immunomodulatory properties. The Hsp70 of Mycobacterium tuberculosis (TBHsp70) has been shown to have an anti-inflammatory role on rodent autoimmune arthritis models, and the protective effects were demonstrated to be dependent on interleukin-10 (IL-10). We have previously observed that TBHsp70 inhibited maturation of dendritic cells (DCs) and induced IL-10 production by these cells, as well as in synovial fluid cells.

Methodology/Principal Findings

We investigated if TBHsp70 could inhibit allograft rejection in two murine allograft systems, a transplanted allogeneic melanoma and a regular skin allograft. In both systems, treatment with TBHsp70 significantly inhibited rejection of the graft, and correlated with regulatory T cells (Tregs) recruitment. This effect was not tumor mediated because injection of TBHsp70 in tumor-free mice induced an increase of Tregs in the draining lymph nodes as well as inhibition of proliferation of lymph node T cells and an increase in IL-10 production. Finally, TBHsp70 inhibited skin allograft acute rejection, and depletion of Tregs using a monoclonal antibody completely abolished this effect.

Conclusions/Significance

We present the first evidence for an immunosuppressive role for this protein in a graft rejection system, using an innovative approach – immersion of the graft tissue in TBHsp70 solution instead of protein injection. Also, this is the first study that demonstrates dependence on Treg cells for the immunosuppressive role of TBHsp70. This finding is relevant for the elucidation of the immunomodulatory mechanism of TBHsp70. We propose that this protein can be used not only for chronic inflammatory diseases, but is also useful for organ transplantation management.     

Defecting or not defecting: how to "read" human behavior during cooperative games by EEG measurements

Understanding the neural mechanisms responsible for human social interactions is difficult, since the brain activities of two or more individuals have to be examined simultaneously and correlated with the observed social patterns. We introduce the concept of hyper-brain network, a connectivity pattern representing at once the information flow among the cortical regions of a single brain as well as the relations among the areas of two distinct brains. Graph analysis of hyper-brain networks constructed from the EEG scanning of 26 couples of individuals playing the Iterated Prisoner's Dilemma reveals the possibility to predict non-cooperative interactions during the decision-making phase. The hyper-brain networks of two-defector couples have significantly less inter-brain links and overall higher modularity--i.e., the tendency to form two separate subgraphs--than couples playing cooperative or tit-for-tat strategies. The decision to defect can be "read" in advance by evaluating the changes of connectivity pattern in the hyper-brain network.     

A Common Left Occipito-Temporal Dysfunction in Developmental Dyslexia and Acquired Letter-By-Letter Reading?

Background

We used fMRI to examine functional brain abnormalities of German-speaking dyslexics who suffer from slow effortful reading but not from a reading accuracy problem. Similar to acquired cases of letter-by-letter reading, the developmental cases exhibited an abnormal strong effect of length (i.e., number of letters) on response time for words and pseudowords.

Results

Corresponding to lesions of left occipito-temporal (OT) regions in acquired cases, we found a dysfunction of this region in our developmental cases who failed to exhibit responsiveness of left OT regions to the length of words and pseudowords. This abnormality in the left OT cortex was accompanied by absent responsiveness to increased sublexical reading demands in phonological inferior frontal gyrus (IFG) regions. Interestingly, there was no abnormality in the left superior temporal cortex which—corresponding to the onological deficit explanation—is considered to be the prime locus of the reading difficulties of developmental dyslexia cases.

Conclusions

The present functional imaging results suggest that developmental dyslexia similar to acquired letter-by-letter reading is due to a primary dysfunction of left OT regions.     

Transferrin Receptor 2 Is Frequently and Highly Expressed in Glioblastomas

Under physiological conditions, transferrin receptor 2 (TfR2) is expressed in the liver and its balance is related to the cell cycle rather than to intracellular iron levels. We recently showed that TfR2 is highly expressed in glioblastoma cell lines. Here, we demonstrate that, in these cells, TfR2 appears to localize in lipid rafts, induces extracellular signal-regulated kinase 1/2 phosphorylation after transferrin binding, and contributes to cell proliferation, as shown by RNA silencing experiments. In vitro hypoxic conditions induce a significant TfR2 up-regulation, suggesting a role in tumor angiogenesis. As assessed by immunohistochemistry, the level of TfR2 expression in astrocytic tumors is related to histologic grade, with the highest expression observed in glioblastomas. The level of TfR2 expression represents a favorable prognostic factor, which is associated with the higher sensitivity to temozolomide of TfR2-positive tumor cells in vitro. The endothelial cells of glioblastoma vasculature also stain for TfR2, whereas those of the normal brain vessels do not. Importantly, TfR2 is expressed by the subpopulation of glioblastoma cells with properties of cancer-initiating cells. TfR2-positive glioblastoma cells retain their TfR2 expression on xenografting in immunodeficient mice. In conclusion, our observations demonstrate that TfR2 is a neoantigen for astrocytomas that seems attractive for developing target therapies.