Predicting potentially pathogenic effects of hRPE65 missense mutations: a computational strategy based on molecular dynamics simulations

The human retinal pigment epithelium-specific 65-kDa protein (hRPE65) plays a crucial role within the retinoid visual cycle and several mutations affecting either its expression level or its enzymatic function are associated with inherited retinal diseases such as Retinitis Pigmentosa. The gene therapy product voretigene neparvovec (Luxturna) has been recently approved for treating hereditary retinal dystrophies; however, the treatment is currently accessible only to patients presenting confirmed biallelic mutations that severely impair hRPE65 function, and many reported hRPE65 missense mutations lack sufficient evidences for proving their pathogenicity. In this context, we developed a computational approach aimed at evaluating the potential pathogenic effect of hRPE65 missense variants located on the dimerisation domain of the protein. The protocol evaluates how mutations may affect folding and conformation stability of this protein region, potentially helping clinicians to evaluate the eligibility for gene therapy of patients diagnosed with this type of hRPE65 variant of uncertain significance.     

Colonisation patterns and vertical movements of stream invertebrates in the interstitial zone: a case study in the Apennines, NW Italy

We examined vertical migration and colonisation patterns of stream macroinvertebrates within the substratum of an Apennine creek in NW Italy. Macrobenthos was sampled at three depths in the streambed (0–5, 5–10, 10–15 cm) by means of artificial baskets filled with natural substratum. We placed 42 traps (5×5×15 cm), i.e. 21 top-opened (T-traps) and 21 bottom-opened (B-traps), each composed of three overlapping baskets (high-H, medium-M and low-L), to evaluate differences in the vertical movements. We also collected Surber samples to compare interstitial assemblages with streambed communities. The multilevel traps yielded 42 taxa, compared with 60 taxa in the natural riverbed. Interstitial traps were rapidly colonised; both taxa richness and organism number increased during the 42-day study period. We found active migration in both vertical directions, but there were more invertebrates in the top-opened traps than in the bottom-opened traps. In the T-traps the most colonised baskets were those placed at the H level, while in the B-traps the L level baskets were more rapidly colonised. The interstitial assemblages differed markedly from the streambed communities in both composition and functional organisation, with more collector-gatherers and predators in the interstitial zone and more filterers and scrapers in the natural riverbed. In Apennine lotic systems, the interstitial zone is an important habitat for stream macrobenthos, although it may not be used by all species.     

Salicylaldoxime derivatives as new leads for the development of carbonic anhydrase inhibitors

New compounds containing a novel zinc binding group (salicylaldoxime system) were identified as effective inhibitors of carbonic anhydrases (CAs). This structural motif seems to bind the catalytic zinc ion of CAs, revealing itself as a new valid alternative to the sulfonamide group. Computational procedures were used to investigate the binding mode of this class of compounds, within the active site of CAII. This study suggests that the salicylaldoxime moiety binds the zinc ion through the oxime oxygen atom that also forms an H-bond with T199. The results herein obtained will allow the development of new CA-inhibitors bearing the salicylaldoxime moiety.     

Microhabitat preference of sympatric Hydraena Kugelann, 1794 species (Coleoptera: Hydraenidae) in a low-order forest stream

Aim of this study was to investigate the presence and distribution of Hydraenidae in relation to selected abiotic parameters in a single, uniform riffle of the Caramagna Stream (northwestern Italy). Six species belonging to the genus of Hydraena Kugelann, 1794 were found (H. andreinii D'Orchymont, 1934, H. subimpressa Rey, 1885, H. assimilis Rey, 1885, H. heterogyna Bedel, 1898, H. truncata Rey, 1884 and H. devillei Ganglbauer, 1901), with evident niche preferences. Our study provided interesting information about ecological requirements of minute moss beetles at small-scale and evidenced that maintaining elevate habitat diversity is essential to preserve high species abundance at local scale.     

MicroRNAs expression profiles as diagnostic biomarkers of gastric cancer: a systematic literature review

Objective: The early identification of gastric cancer (GC) represents a major clinical challenge. We conducted a systematic review of studies evaluating the miRNA expression profiling as a diagnostic tool in GC.

Methods: We performed a search of PubMed, ISI Web of Science and SCOPUS databases for studies on diagnostic miRNAs and GC, published in English up to October 2017. Eligibility criteria included case-control studies evaluating blood or tissue-based miRNA expression profiles, and incorporating at least two detection phases (screening and validation).

Results: We included 27 eligible studies, that reported on 97 deregulated miRNAs either in blood or tissue, out of which 30 were reported in at least two studies. Among 22 studies on tissue-diagnostic miRNAs, 13 consistently upregulated miRNAs (miR-214, miR-21, miR-103, miR-107, miR-196a, miR-196b, miR-7, miR-135b, miR-222, miR-23b, miR-25, miR-92 and miR-93), and six consistently downregulated miRNAs (miR-148a, miR-375, miR-133b, miR-30a, miR-193a and miR-204) were reported. Ten miRNAs with inconsistent direction of expression in tissues were identified. Among the five studies performed on blood samples, only one miRNA was consistently upregulated (miR-20a).

Conclusions: This review shows that some tissue or blood miRNAs may be considered as potential biomarkers for GC diagnosis, that urgently needs to be confirmed from large prospective studies.     

Rational design and characterization of bioplastics from Hermetia illucens prepupae proteins

In this study proteins extracted from prepupae of Hermetia illucens, also known as black soldier fly, are investigated as promising base for a new type of bioplastics for agricultural purposes. Design of experiments techniques are employed to perform a rational study on the effects of different combination of glycerol as plasticizer, citric acid as cross-linking agent and distilled water as solvent on the capability of proteins to form a free-standing film through casting technique, keeping as fixed the quantity of proteins. Glycerol shows interesting properties as plasticizer contributing to the formation of homogenous and free-standing film. Moreover, mechanical and thermal characterizations are performed to estimate the effect of increasing amounts of proteins on the final properties and thickness of the specimens. Proteins derived from H. illucens can be successfully employed as base for bioplastics to be employed for agricultural purposes.