High Ca<Superscript>2+</Superscript> Influx During Traumatic Brain Injury Leads to Caspase-1-Dependent Neuroinflammation and Cell Death

We investigated the hypothesis that high Ca²⁺ influx during traumatic brain injury induces the activation of the caspase-1 enzyme, which triggers neuroinflammation and cell apoptosis in a cell culture model of neuronal stretch injury and an in vivo model of fluid percussion injury (FPI). We first established that stretch injury causes a rapid increase in the intracellular Ca²⁺ level, which activates interleukin-converting enzyme caspase-1. The increase in the intracellular Ca²⁺ level and subsequent caspase-1 activation culminates into neuroinflammation via the maturation of IL-1β. Further, we analyzed caspase-1-mediated apoptosis by TUNEL staining and PARP western blotting. The voltage-gated sodium channel blocker, tetrodotoxin, mitigated the stretch injury-induced neuroinflammation and subsequent apoptosis by blocking Ca²⁺ influx during the injury. The effect of tetrodotoxin was similar to the caspase-1 inhibitor, zYVAD-fmk, in neuronal culture. To validate the in vitro results, we demonstrated an increase in caspase-1 activity, neuroinflammation and neurodegeneration in fluid percussion-injured animals. Our data suggest that neuronal injury/traumatic brain injury (TBI) can induce a high influx of Ca²⁺ to the cells that cause neuroinflammation and cell death by activating caspase-1, IL-1β, and intrinsic apoptotic pathways. We conclude that excess IL-1β production and cell death may contribute to neuronal dysfunction and cognitive impairment associated with TBI.     

Emerging Heterogeneities in Italian Customs and Comparison with Nearby Countries

In this work we apply techniques and modus operandi typical of Statistical Mechanics to a large dataset about key social quantifiers and compare the resulting behaviors of five European nations, namely France, Germany, Italy, Spain and Switzerland. The social quantifiers considered are i. the evolution of the number of autochthonous marriages (i.e., between two natives) within a given territorial district and ii. the evolution of the number of mixed marriages (i.e., between a native and an immigrant) within a given territorial district. Our investigations are twofold. From a theoretical perspective, we develop novel techniques, complementary to classical methods (e.g., historical series and logistic regression), in order to detect possible collective features underlying the empirical behaviors; from an experimental perspective, we evidence a clear outline for the evolution of the social quantifiers considered. The comparison between experimental results and theoretical predictions is excellent and allows speculating that France, Italy and Spain display a certain degree of internal heterogeneity, that is not found in Germany and Switzerland; such heterogeneity, quite mild in France and in Spain, is not negligible in Italy and highlights quantitative differences in the habits of Northern and Southern regions. These findings may suggest the persistence of two culturally distinct communities, long-term lasting heritages of different and well-established customs. Also, we find qualitative differences between the evolution of autochthonous and of mixed marriages: for the former imitation in decisional mechanisms seems to play a key role (and this results in a square root relation between the number of autochthonous marriages versus the percentage of possible couples inside that country), while for the latter the emerging behavior can be recovered (in most cases) with elementary models with no interactions, suggesting weak imitation patterns between natives and migrants (and this translates in a linear growth for the number of mixed marriages versus the percentage of possible mixed couples in the country). However, the case of mixed marriages displays a more complex phenomenology, where further details (e.g., the provenance and the status of migrants, linguistic barriers, etc.) should also be accounted for.     

Fluorescent-fipronil: Design and synthesis of a stable conjugate

Fipronil is a phenyl pyrazole molecule widely used across the world as both insecticide and veterinary drug. The main goal of this work was to synthesize a fluorescently labeled fipronil derivative for cellular imaging without affecting its intrinsic properties. We selected fluorescein as fluorescent probe and we investigated different strategies for stable chemical ligation between both entities, such as thiourea and direct peptide bond. While thiourea bond displayed low stability, direct peptide bond was difficult to achieve due to problems of steric hindrance. The best result was obtained by conjugation using click chemistry, which allowed to obtain fipronil stably labeled with the fluorescent probe.     

Species composition, comparative size and abundance of the genus Littoraria (Gastropoda: Littorinidae) from different mangrove strata along the East African coast

Variation in the abundance, distribution and size of four species of mangrove littorinid gastropods (genus Littoraria) was investigated using a nested sampling design at different spatial scales along the East African coast, from Tanzania to South Africa. Littorinid abundance and diversity decreased abruptly south of Inhaca Island at the southern end of the study area. All species presented a large-scale spatial variation in abundance, with L. subvittata showing the greatest abundance while L. intermedia was rare. Littoraria scabra and L. intermedia were found mainly at the seaward edge of the forests. Littoraria subvittata increased in abundance in the middle of the forest and towards the landward side. Littoraria pallescens occurred mainly at the seaward edge and in the middle areas in the Rhizophora zone. These small-scale variations show contrasting specific distribution patterns within the mangrove, likely reflecting different tolerances to physical factors and biological interactions. All species appeared decreased in shell height from north to south. Littoraria scabra was always significantly larger than other species at all mangrove study sites. Handling editor: P. Viaroli     

Transition of the prion protein from a structured cellular form (PrPC) to the infectious scrapie agent (PrPSc)

Prion diseases in mammals are caused by a conformational transition of the cellular prion protein from its native conformation (PrP^C) to a pathological isoform called “prion protein scrapie” (PrP^Sc). A molecular level of understanding of this conformational transition will be helpful in unveiling the disease etiology. Experimental structural biological techniques (NMR and X‐ray crystallography) have been used to unravel the atomic level structural information for the prion and its binding partners. More than one hundred three‐dimensional structures of the mammalian prions have been deposited in the protein databank. Structural studies on the prion protein and its structural transitions will deepen our understanding of the molecular basis of prion pathogenesis and will provide valuable guidance for future structure‐based drug discovery endeavors.     

Combining vegetable oil and sub-lethal concentrations of Imidacloprid with Beauveria bassiana and Metarhizium anisopliae against adult guava weevil Conotrachelus psidii (Coleoptera: Curculionidae)

Of the insect pests that attack guava fruits, the guava weevil, Conotrachelus psidii Marshall, 1922 (Coleoptera: Curculionidae), is one of the most important in Brazil. In search of alternatives to chemical pesticides, this study was performed to select fungal isolates of Beauveria bassiana and Metarhizium anisopliae as potential candidates for the control of adult C. psidii. Tests were carried out using three products applied with the entomopathogenic fungi: Tween 80, sunflower oil and Imidacloprid (IMI). A sub-lethal concentration of IMI was determined (100 ppm). The results demonstrated that LPP 19 and LPP 114 were the most effective isolates when used in combination with all of the products. The least virulent isolate, ESALQ 818, when applied in Tween 80 caused only 26.6% mortality, however, this isolate showed significantly improved efficiency when applied together with either sunflower oil or IMI, causing 57.3 and 88.6% mortality, respectively. The efficiency of all the isolates tested here improved when applied together with IMI, with LT₅₀ values of 5.3–10.3 days when compared to LT₅₀ values in Tween alone of 9.5–17 days. The isolate that produced the highest number of conidia on the cadavers of adult C. psidii was LPP138, independent of the product used; however, conidial production was slightly reduced when fungi were applied together with IMI. These results are promising for developing new formulations of the isolates to be tested in the field.