Running as fast as it can: How spiking dynamics form object groupings in the laminar circuits of visual cortex

How spiking neurons cooperate to control behavioral processes is a fundamental problem in computational neuroscience. Such cooperative dynamics are required during visual perception when spatially distributed image fragments are grouped into emergent boundary contours. Perceptual grouping is a challenge for spiking cells because its properties of collinear facilitation and analog sensitivity occur in response to binary spikes with irregular timing across many interacting cells. Some models have demonstrated spiking dynamics in recurrent laminar neocortical circuits, but not how perceptual grouping occurs. Other models have analyzed the fast speed of certain percepts in terms of a single feedforward sweep of activity, but cannot explain other percepts, such as illusory contours, wherein perceptual ambiguity can take hundreds of milliseconds to resolve by integrating multiple spikes over time. The current model reconciles fast feedforward with slower feedback processing, and binary spikes with analog network-level properties, in a laminar cortical network of spiking cells whose emergent properties quantitatively simulate parametric data from neurophysiological experiments, including the formation of illusory contours; the structure of non-classical visual receptive fields; and self-synchronizing gamma oscillations. These laminar dynamics shed new light on how the brain resolves local informational ambiguities through the use of properly designed nonlinear feedback spiking networks which run as fast as they can, given the amount of uncertainty in the data that they process.     

Zucchini Yellow Fleck Virus is an Emergent Virus on Melon in Sicily (Italy)

Since 2006, winter melon plants (Cucumis melo L. var inodorus) showing symptoms of pin‐point yellow spots were noticed in Sicily (Italy). Leaf samples were tested by enzyme‐linked immunosorbent assay to the most important viruses‐infecting cucurbits. Zucchini yellow fleck virus (ZYFV, genus Potyvirus) was the only virus detected. Surveys in 2007 and 2008 revealed an increasing number of sites in Sicily with ZYFV‐infected winter melon plants. To confirm the identity of the virus as ZYFV, two isolates from different locations were sequenced and shown to be approximately 85% identical to the published sequences of isolates previously identified in Italy and France. This is the first report of ZYFV occurring on melon in Italy.     

Bacterial and Protozoal Communities and Fatty Acid Profile in the Rumen of Sheep Fed a Diet Containing Added Tannins

This study evaluated the effects of tannins on ruminal biohydrogenation (BH) due to shifts in the ruminal microbial environment in sheep. Thirteen lambs (45 days of age) were assigned to two dietary treatments: seven lambs were fed a barley-based concentrate (control group) while the other six lambs received the same concentrate with supplemental quebracho tannins (9.57% of dry matter). At 122 days of age, the lambs were slaughtered, and the ruminal contents were subjected to fatty acid analysis and sampled to quantify populations of Butyrivibrio fibrisolvens, which converts C_18:2 c9-c12 (linoleic acid [LA]) to C_18:2 c9-t11 (rumenic acid [RA]) and then RA to C_18:1 t11 (vaccenic acid [VA]); we also sampled for Butyrivibrio proteoclasticus, which converts VA to C_18:0 (stearic acid [SA]). Tannins increased (P < 0.005) VA in the rumen compared to the tannin-free diet. The concentration of SA was not affected by tannins. The SA/VA ratio was lower (P < 0.005) for the tannin-fed lambs than for the controls, suggesting that the last step of the BH process was inhibited by tannins. The B. proteoclasticus population was lower (−30.6%; P < 0.1), and B. fibrisolvens and protozoan populations were higher (+107% and +56.1%, respectively; P < 0.05) in the rumen of lambs fed the tannin-supplemented diet than in controls. These results suggest that quebracho tannins altered BH by changing ruminal microbial populations.The fatty acid profile of the meat and milk of ruminants is strongly affected by diet (2, 15). When ingested, the dietary polyunsaturated fatty acids (PUFA) undergo a process known as biohydrogenation (BH) carried out by ruminal microorganisms (20). During the BH of C_18:2(n-6) (linoleic acid [LA]) and C_18:3(n-3) (linolenic acid [LNA]) a number of C_18:1 and C_18:2 isomers are formed (6). The last step in the BH process leads to the formation of C_18:0 (stearic acid [SA]). Among the intermediate products formed during this process, the isomer C_18:2 c9t11 (rumenic acid [RA]) is active in preventing cancer in mammals (17). Only a small amount of the RA found in meat and milk originates during BH. It is produced to a larger extent in muscle and mammary glands from the desaturation of C_18:1 t11 (vaccenic acid [VA], another intermediate of ruminal BH) by the action of Δ⁹-desaturase enzyme (41, 43).Ruminal BH is carried out mostly by bacteria belonging to the Butyrivibrio genus (38). Butyrivibrio fibrisolvens has the capacity to convert LA to RA and RA to VA, while Butyrivibrio proteoclasticus (previously classified as Clostridium proteoclasticum [35]) hydrogenates VA to SA (38, 39). According to Or-Rashid et al. (37), ruminal protozoa also play a role in BH by converting LA to RA. However, this issue is still controversial, as Devillard et al. (11) have reported that protozoa do not have the capability of hydrogenating LA. The proportion of BH intermediates in the rumen can vary depending on changes in ruminal microbial populations (7, 51). Changes in ruminal fatty acid profiles are also reflected in intramuscular fatty acid composition (48, 52).Tannins are phenolic compounds that are widespread in plants. When ingested by ruminants in large amounts, tannins can reduce the activity and the proliferation of ruminal microorganisms (34). Tannins from Lotus corniculatus (33) or from Acacia spp. (12) reduce the proliferation of B. proteoclasticus B316^T and B. proteoclasticus P18, respectively. Durmic et al. (12) reported that VA increased and SA decreased when extracts from Acacia iteaphylla, which contains condensed tannins (1), were incubated in vitro with sheep ruminal fluid inoculated with B. fibrisolvens JW11 and B. proteoclasticus P18 strains. In two recent in vitro studies, the inclusion of tannins in fermentor systems containing bovine ruminal fluid inhibited the conversion of VA to SA, while no effect was detected on RA production (21, 47). These results have been also confirmed in vivo in the rumen of sheep fed a diet with 4.0% dry matter (DM) quebracho tannin (48). However, to date there is no in vivo study focusing on the effects of dietary tannins on the proliferation of the microorganisms involved in ruminal BH.We assessed whether dietary tannins may affect the BH pathway via changes in bacterial and protozoal ruminal populations. We gave particular emphasis to B. fibrisolvens and B. proteoclasticus. We also assayed the production of conjugated linoleic acids (CLAs) by linoleic acid isomerase (LA-I) enzyme.     

Linking Well-Tempered Metadynamics Simulations with Experiments

Linking experiments with the atomistic resolution provided by molecular dynamics simulations can shed light on the structure and dynamics of protein-disordered states. The sampling limitations of classical molecular dynamics can be overcome using metadynamics, which is based on the introduction of a history-dependent bias on a small number of suitably chosen collective variables. Even if such bias distorts the probability distribution of the other degrees of freedom, the equilibrium Boltzmann distribution can be reconstructed using a recently developed reweighting algorithm. Quantitative comparison with experimental data is thus possible. Here we show the potential of this combined approach by characterizing the conformational ensemble explored by a 13-residue helix-forming peptide by means of a well-tempered metadynamics/parallel tempering approach and comparing the reconstructed nuclear magnetic resonance scalar couplings with experimental data.     

Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels

Novel antiangiogenic strategies with complementary mechanisms are needed to maximize efficacy and minimize resistance to current angiogenesis inhibitors. We explored the therapeutic potential and mechanisms of alphaPlGF, an antibody against placental growth factor (PlGF), a VEGF homolog, which regulates the angiogenic switch in disease, but not in health. alphaPlGF inhibited growth and metastasis of various tumors, including those resistant to VEGF(R) inhibitors (VEGF(R)Is), and enhanced the efficacy of chemotherapy and VEGF(R)Is. alphaPlGF inhibited angiogenesis, lymphangiogenesis, and tumor cell motility. Distinct from VEGF(R)Is, alphaPlGF prevented infiltration of angiogenic macrophages and severe tumor hypoxia, and thus, did not switch on the angiogenic rescue program responsible for resistance to VEGF(R)Is. Moreover, it did not cause or enhance VEGF(R)I-related side effects. The efficacy and safety of alphaPlGF, its pleiotropic and complementary mechanism to VEGF(R)Is, and the negligible induction of an angiogenic rescue program suggest that alphaPlGF may constitute a novel approach for cancer treatment.     

Aluminium and iron air pollution near an iron casting and aluminium foundry in Turin district (Italy)

This work reports the results of an environmental survey carried out in an industrial area in the Province of Turin: its main aim is to assess the levels of iron and aluminium in the outside air during the period from July to September to assess the influence of industrial activity (a cast-iron and aluminium foundry) which is interrupted during the month of August, on the level of metals present in the air. Conducting the analysis during this period of time made it possible to avoid the confounding effect of pollution due to domestic central heating. The measurements were taken from nine areas at different distances from the foundry in the area and according to the direction of the prevailing winds, as deduced from the historical data. The results of this survey show a statistically significant difference in iron and aluminium levels in the outside air in the geographic areas between the two main periods examined: during August (no foundry activity) v/s July-September (foundry activity). The values recorded are: Aluminium 0.4+/-0.45 microg/m(3) v/s 1.12+/-1.29 microg/m(3) (p<0.0001); Iron 0.95+/-0.56 microg/m(3) v/s 1.6+/-1.0 microg/m(3) (p<0.0001). There were no statistically significant differences between the nine sampling points from the point of view of the sampling sites, climate conditions and wind directions. We found no correlation with car traffic, in terms of the number of vehicles, and metals. The values of iron tended to be higher in the areas farther away from the foundry site in the areas located along the path of the prevailing winds.     

Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water

Epidemiological evidence suggests a link between consumption of chlorinated drinking water and various cancers. Chlorination of water rich in organic chemicals produces carcinogenic organochlorine by-products (OBPs) such as trihalomethanes and haloacetic acids. Since the discovery of the first OBP in the 1970s, there have been several investigations designed to determine the biological effects of single chemicals or small artificial OBP combinations. However, there is still insufficient information regarding the general biological response to these compounds, and further studies are still needed to evaluate their potential genotoxic effects. In the current study, we evaluated the effect of three drinking water disinfectants on the activity of cytochrome P450 (CYP)-linked metabolizing enzymes and on the generation of oxidative stress in the livers of male and female Cyprinus carpio fish (carp). The fish were exposed in situ for up 20 days to surface water obtained from the Trasmene lake in Italy. The water was treated with 1-2 mg/L of either sodium hypochlorite (NaClO) or chlorine dioxide (ClO2) as traditional disinfectants or with a relatively new disinfectant product, peracetic acid (PAA). Micronucleus (MN) frequencies in circulating erythrocytes from the fish were also analysed as a biomarker of genotoxic effect. In the CYP-linked enzyme assays, a significant induction (up to a 57-fold increase in the deethylation of ethoxyresorufin with PAA treatment) and a notable inactivation (up to almost a 90% loss in hydroxylation of p-nitrophenol with all disinfectants, and of testosterone 2beta-hydroxylation with NaClO) was observed in subcellular liver preparations from exposed fish. Using the electron paramagnetic resonance (EPR) spectroscopy radical-probe technique, we also observed that CYP-modulation was associated with the production of reactive oxygen species (ROS). In addition, we found a significant increase in MN frequency in circulating erythrocytes after 10 days of exposure of fish to water treated with ClO2, while a non-significant six-fold increase in MN frequency was observed with NaClO, but not with PAA. Our data suggest that the use of ClO2 and NaClO to disinfect drinking water could generate harmful OBP mixtures that are able to perturb CYP-mediated reactions, generate oxidative stress and induce genetic damage. These data may provide a mechanistic explanation for epidemiological studies linking consumption of chlorinated drinking water to increased risk of urinary, gastrointestinal and bladder cancers.     

Mechanical testing of cancellous bone from the femoral head: experimental errors due to off-axis measurements

The aim of this study was to verify whether a misalignment between the testing direction and the trabecular main direction has a significant effect on the compressive behaviour of cancellous bone. Ten cylindrical specimens were extracted from femoral heads with a misalignment to the trabecular main direction of approximately 20 degrees. Each specimen was paired with a specimen extracted aligned with the main direction of the trabeculae on the basis of the closest bone volume fraction, obtaining two groups, one 'aligned' and one 'misaligned'. The average off-axis angle was 6.1 degrees and 21.6 degrees for the 'aligned' and 'misaligned' group, respectively. The specimens underwent micro-tomographic analysis, compressive testing, micro-indentation testing and ashing. No significant differences were found in histomorphometric parameters, hardness and ash density between the two groups, whereas significant differences were found in Young's modulus and ultimate stress: both parameters, measured for the 'misaligned' group, were about 40% lower than those measured for the 'aligned' group. These results demonstrate a great effect of the angle between the testing direction and the main direction of the trabecular structure on the compressive behaviour of cancellous bone. This angle should be reduced as much as possible (in the present work the average value was 6.6+/-3.3 degrees), in any case measured, and always reported together with the mechanical parameters of cancellous bone.     

Phylogenetic relationships among the Lorisoidea as indicated by craniodental morphology and mitochondrial sequence data

The phylogeny of the Afro-Asian Lorisoidea is controversial. While postcranial data attest strongly to the monophyly of the Lorisidae, most molecular analyses portray them as paraphyletic and group the Galagidae alternately with the Asian or African lorisids. One of the problems that has bedevilled phylogenetic analysis of the group in the past is the limited number of taxa sampled for both ingroup families. We present the results of a series of phylogenetic analyses based on 635 base pairs (bp) from two mitochondrial genes (12S and 16S rRNA) with and without 36 craniodental characters, for 11 galagid and five lorisid taxa. The outgroup was the gray mouse lemur (Microcebus murinus). Analyses of the molecular data included maximum parsimony (MP), neighbor joining (NJ), maximum likelihood (ML), and Bayesian methods. The model-based analyses and the combined "molecules+morphology" analyses supported monophyly of the Lorisidae and Galagidae. The lorisids form two geographically defined clades. We find no support for the taxonomy of Galagidae as proposed recently by Groves [Primate Taxonomy, Washington, DC: Smithsonian Institution Press. 350 p, 2001]. The taxonomy of Nash et al. [International Journal of Primatology 10:57-80, 1989] is supported by the combined "molecules+morphology" analysis; however, the model-based analyses suggest that Galagoides may be an assemblage of species united by plesiomorphic craniodental characters.