Human motor cortex excitability during the perception of others' action

Neuroscience research during the past ten years has fundamentally changed the traditional view of the motor system. In monkeys, the finding that premotor neurons also discharge during visual stimulation (visuomotor neurons) raises new hypotheses about the putative role played by motor representations in perceptual functions. Among visuomotor neurons, mirror neurons might be involved in understanding the actions of others and might, therefore, be crucial in interindividual communication. Functional brain imaging studies enabled us to localize the human mirror system, but the demonstration that the motor cortex dynamically replicates the observed actions, as if they were executed by the observer, can only be given by fast and focal measurements of cortical activity. Transcranial magnetic stimulation enables us to instantaneously estimate corticospinal excitability, and has been used to study the human mirror system at work during the perception of actions performed by other individuals. In the past ten years several TMS experiments have been performed investigating the involvement of motor system during others' action observation. Results suggest that when we observe another individual acting we strongly 'resonate' with his or her action. In other words, our motor system simulates underthreshold the observed action in a strictly congruent fashion. The involved muscles are the same as those used in the observed action and their activation is temporally strictly coupled with the dynamics of the observed action.     

When Bergmann's rule fails: evidences of environmental selection pressures shaping phenotypic diversification in a widespread seabird

Organisms tend to exhibit phenotypes that can be shaped by climate, commonly demonstrating clinal variations along latitudinal gradients. In vertebrates, air temperature plays a major role in shaping body size in both ectothermic and endothermic animals. However, additional small‐scale environmental factors can also act as selection pressures in the marine ecosystem (e.g. primary productivity), evidencing multi‐scale processes acting on marine organisms. In this study, we tested Bergmann's rule in a widely distributed seabird, the brown booby Sula leucogaster, in addition to evaluating the relationship of sea surface temperature and chlorophyll α with phenotypes. We used traits from a morphometric dataset (culmen, wing chord, and tarsus length) and body mass of 276 brown boobies distributed on six breeding sites along a latitudinal gradient in the South Atlantic Ocean (0–27°S). We found significant differentiation among colonies, but phenotypic similarities were observed between colonies located at the extremes of the latitudinal gradient. As the colony nearest to the Equator, Saint Peter and Saint Paul archipelago, had the largest and heaviest individuals, the model containing only air temperature explained < 5% of the allometric variation, providing no substantial support for Bergmann's rule. However, when we added the interaction of chlorophyll α and sea surface temperature the deviance explained rose to over 80%. Primary productivity and sea surface temperature do not follow a latitudinal gradient in the ocean and, therefore, the role of small‐scale oceanographic processes in shaping body size and the importance of considering additional environmental variables when testing Bergmann's rule in marine organisms are evident.     

Genetic Diversity of Isolates of Glomus mosseae from Different Geographic Areas Detected by Vegetative Compatibility Testing and Biochemical and Molecular Analysis

We detected, for the first time, the occurrence of vegetative incompatibility between different isolates of the arbuscular mycorrhizal fungal species Glomus mosseae. Vegetative compatibility tests performed on germlings belonging to the same isolate showed that six geographically different isolates were capable of self-anastomosing, and that the percentage of hyphal contacts leading to fusions ranged from 60 to 85%. Successful anastomoses were characterized by complete fusion of hyphal walls, protoplasm continuity and occurrence of nuclei in the middle of hyphal bridges. No anastomoses could be detected between hyphae belonging to different isolates, which intersected without any reaction in 49 to 68% of contacts. Microscopic examinations detected hyphal incompatibility responses in diverse pairings, consisting of protoplasm retraction from the tips and septum formation in the approaching hyphae, even before physical contact with neighboring hyphae. Interestingly, many hyphal tips showed precontact tropism, suggesting that specific recognition signals may be involved during this stage. The intraspecific genetic diversity of G. mosseae revealed by vegetative compatibility tests was confirmed by total protein profiles and internal transcribed spacer-restriction fragment length polymorphism profiles, which evidenced a higher level of molecular diversity between the two European isolates IMA1 and BEG25 than between IMA1 and the two American isolates. Since arbuscular mycorrhizal fungi lack a tractable genetic system, vegetative compatibility tests may represent an easy assay for the detection of genetically different mycelia and an additional powerful tool for investigating the population structure and genetics of these obligate symbionts.     

Quaternary narcotic antagonists' relative ability to prevent antinociception and gastrointestinal transit inhibition in morphine-treated rats as an index of peripheral selectivity

Single doses of naloxone (0.025 to 0.5 mg/kg) or of one of four quaternary narcotic antagonists (i.e. nalorphine allobromide, nalorphine methobromide, naloxone methobromide or naltrexone methobromide, 1 to 60 mg/kg) were given s.c. to rats before morphine, 5 mg/kg i.v. In the absence of antagonists morphine reduced G.I. transit of a charcoal meal to about 15% of drug-free controls and consistently delayed nociceptive reactions (55°C hot plate) in all animals. Doses of antagonists slightly reducing morphine antinociception (centrally effective = A) and restoring G.I. transit to about 50% of drug-free rats (peripherally effective = B) were estimated. The A:B ratio, indicating peripheral selectivity, was at least 8 for any of the quaternary antagonists given 10 min before morphine, but prolonging this interval may have resulted in a lower figure (i.e. less peripheral selectivity) because of reduced A and increased B. This was definitely so for naltrexone methobromide (A:B, > 60 at 10 min, about 1 at 80 min) and was not apparent for nalorphine methobromide according to available data, which for nalorphine allobromide and to a lesser extent for naloxone methobromide showed only an increase in B at intervals longer than 10 min. Both morphine-induced antinociception and inhibition of G.I. transit were reduced by naloxone at the lower doses tested and were fully prevented at the higher. These findings indicate that, unlike naloxone, the investigated quaternary narcotic antagonists are interesting prototype drugs for selective blockade of opiate receptors outside the CNS, although certain critical aspects, possibly biological N-dealkylation to the corresponding tertiary antagonists, condition peripheral selectivity.     

PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.     

Effect of various drugs producing convulsive seizures on rat brain glycerolipid metabolism

Convulsive seizures were elicited in the rat by the injection of several different drugs (pyridoxal phosphate, bicuculline, penicillin and ouabain). Glycerolipid metabolism was studied after the intraventricular injection of [2-³H]glycerol, which was incorporated into rat brain glycerides. The percentage of total lipid label found in each lipid class (phosphatidylethanolamine, PE; phosphatidylcholine, PC; phosphatidylserine, PS; phosphatidic acid, PA; phosphatidylinositol, PI; diacylglycerol (+ monoacylglycerol), DG and triacylglycerol, TG) depended on the time elapsed from the injection of the labeled precursor. The percent of total lipid radioactivity as PE and PC increased with time (3–60 min), whereas the opposite was true for the radioactivity of DG and PA. The radioactivity of other lipid classes did not appreciabily vary between 3 and 60 min from the injection of the labeled glycerol. The intraventricular administration of pyridoxal phosphate together with labeled glycerol decreased the percent of lipid radioactivity as PE and increased that as DG. This lipid effect was detected also after the administration of other convulsants, such as ouabain and penicillin. The intraperitoneal administration of bicuculline affected lipid metabolism in cerebellum.     

Meta‐replication,sampling bias,and multi‐scale model selection: A case study on snow leopard (Panthera uncia) in western China

Replicated multiple scale species distribution models (SDMs) have become increasingly important to identify the correct variables determining species distribution and their influences on ecological responses. This study explores multi‐scale habitat relationships of the snow leopard (Panthera uncia) in two study areas on the Qinghai–Tibetan Plateau of western China. Our primary objectives were to evaluate the degree to which snow leopard habitat relationships, expressed by predictors, scales of response, and magnitude of effects, were consistent across study areas or locally landcape‐specific. We coupled univariate scale optimization and the maximum entropy algorithm to produce multivariate SDMs, inferring the relative suitability for the species by ensembling top performing models. We optimized the SDMs based on average omission rate across the top models and ensembles’ overlap with a simulated reference model. Comparison of SDMs in the two study areas highlighted landscape‐specific responses to limiting factors. These were dependent on the effects of the hydrological network, anthropogenic features, topographic complexity, and the heterogeneity of the landcover patch mosaic. Overall, even accounting for specific local differences, we found general landscape attributes associated with snow leopard ecological requirements, consisting of a positive association with uplands and ridges, aggregated low‐contrast landscapes, and large extents of grassy and herbaceous vegetation. As a means to evaluate the performance of two bias correction methods, we explored their effects on three datasets showing a range of bias intensities. The performance of corrections depends on the bias intensity; however, density kernels offered a reliable correction strategy under all circumstances. This study reveals the multi‐scale response of snow leopards to environmental attributes and confirms the role of meta‐replicated study designs for the identification of spatially varying limiting factors. Furthermore, this study makes important contributions to the ongoing discussion about the best approaches for sampling bias correction.     

Waist Circumference and Cardiovascular Risk Factors in Prepubertal Children

Objective: Intra‐abdominal fat has been identified as being the most clinically relevant type of fat in humans. Therefore, an assessment of body‐fat distribution could possibly identify subjects with the highest risk of adverse lipid profile and hypertension. Few data on the relationship between body‐fat distribution and cardiovascular risk factors are available in children, especially before puberty. Research Methods and Procedures: This cross‐sectional study was undertaken to explore the relationship between anthropometric variables, lipid concentrations, and blood pressure (BP) in a sample of 818 prepubertal children (ages 3 to 11 years) and to assess the clinical relevance of waist circumference in identifying prepubertal children with higher cardiovascular risk. Height, weight, triceps and subscapular skinfolds, waist circumference, and BP were measured. Plasma levels for triacylglycerol, total cholesterol, high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein cholesterol, apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) were determined. Results: Females were fatter than males (5.8 [3.5] vs. 4.8 [3.3] kg of fat mass; p < 0.01). Males had higher HDL cholesterol and ApoA1/ApoB plasma concentrations than females (p < 0.001 and p < 0.01, respectively). Waist circumference had a higher correlation with systolic and diastolic BP (r = 0.40 and 0.29, respectively; p < 0.001) than triceps (r = 0.35 and 0.21, respectively; p < 0.001) and subscapular (r = 0.28 and 0.16, respectively; p < 0.001) skinfolds and relative body weight (0.33 and 0.23, respectively; p < 0.001). Multivariate linear model analysis showed that ApoA1/ApoB, HDL cholesterol, total cholesterol/HDL cholesterol, and systolic as well as diastolic BP were significantly associated with waist circumference and triceps and subscapular skinfolds, independently of age, gender, and body mass index. Discussion: Waist circumference as well as subscapular and triceps skinfolds may be helpful parameters in identifying prepubertal children with an adverse blood‐lipids profile and hypertension. However, waist circumference, which is easy to measure and more easily reproducible than skinfolds, may be considered in clinical practice. Children with a waist circumference greater than the 90th percentile are more likely to have multiple risk factors than children with a waist circumference that is less than or equal to the 90th percentile.