A fast and straightforward procedure for vault nanoparticle purification and the characterization of its endocytic uptake

Background

Vaults are eukaryotic ribonucleoprotein particles composed of up 78 copies of the 97?kDa major vault protein that assembles into a barrel-like, “nanocapsule” enclosing poly(ADP-ribose) polymerase, telomerase-associated protein-1 and small untranslated RNAs. Overall, the molecular mass of vault particles amounts to about 13?MDa. Although it has been implicated in several cellular functions, its physiological roles remain poorly understood. Also, the possibility to exploit it as a nanovector for drug delivery is currently being explored in several laboratories.

Conformational properties of intrinsically disordered proteins bound to the surface of silica nanoparticles

Background

Protein-nanoparticle (NP) interactions dictate properties of nanoconjugates relevant to bionanotechnology. Non-covalent adsorption generates a protein corona (PC) formed by an inner and an outer layer, the hard and soft corona (HC, SC). Intrinsically disordered proteins (IDPs) exist in solution as conformational ensembles, whose response to the presence of NPs is not known.

Clinical expression of cystic fibrosis in a large cohort of Italian siblings

Background

A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF.

Methods

We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis.

Results

Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV₁% at 12?years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15?years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5?years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance >?50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the “whole” CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency.

Conclusions

Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain.

     

Abundance,density and activity of Salvator merianae (Reptilia: Teiidae) and the effect of poaching on the site occupancy by the lizard in an Atlantic Forest Reserve,Brazil

We aimed to estimate the density, occupancy and detectability of Salvator merianae (Tegu) in one of the largest Atlantic rainforest remnants in Espírito Santo, Brazil, the VNR. Species patch occupancy was modelled and used to predict the response direction of six covariates based on prior knowledge of the Tegu's ecology. A priori, we expected that the covariates measured should represent key habitat features for the species (i.e. temperature, forest edge, open habitats) or elements possibly avoided by the species, based on the hypothesis that poaching would have a negative effect on patch occupancy. We used line‐transect surveys to estimate density and abundance. Camera‐traps were used to estimate patch occupancy by the Tegu. Estimated density for S. merianae was 0.21 ± 0.02 Tegus/ha and estimated population size was 4990 ± 521 individuals. Patch occupancy was best described by two covariates: poaching intensity and distance to the forest edge. Detectability was affected by three covariates: poaching intensity, tree density and temperature. Our study presents robust information on abundance and density, habitat use, and activity of S. merianae in the VNR and is the first study providing data on the effects that poaching has on patch occupancy of this lizard. The data indicated that the occupancy and detectability of this species were influenced by a set of factors, providing information that can be useful in management plans in areas where this species can potentially decline and in areas where it may be introduced.     

Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 ± 6.6 for Sham, 7.8 ± 4.1 for Beam only, 4.4 ± 5.6 for BPA-BNCT I and 0.45 ± 0.20 for BPA-BNCT II; tumor nodule weight was 750 ± 480 mg for Sham, 960 ± 620 mg for Beam only, 380 ± 720 mg for BPA-BNCT I and 7.3 ± 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.     

Osservazioni sulla polistelia in Primula glaucescens Moretti e Primula longobarda Porta

Abstract

Notes on the polystelic structure in Primula glaucescens Moretti and Primula longobarda Porta. — The rhizome anatomy of Primula glaucescens Moretti and Primula longobarda Porta (two species endemic to Lombardy) have been studied. It has been found that the polystelic structure is present in the rhizome of both species, but with some differences. The taxa show a difference in the number and size of steles and amount of sclerenchymatic tissue within the single stele.

Our investigations confirm the necessity to separate in a specific rank Primula glaucescens Moretti from Primula longobarda Porta, as already proposed by Arietti and Crescini (1976).