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Dysregulated Choline, Methionine, and Aromatic Amino Acid Metabolism in Patients with Wilson Disease: Exploratory Metabolomic Profiling and Implications for Hepatic and Neurologic Phenotypes.
Wilson disease (WD) is a genetic copper overload condition characterized by hepatic and neuropsychiatric symptoms with a not well-understood pathogenesis. Dysregulated methionine cycle is reported in animal models of WD, though not verified in humans. Choline is essential for lipid and methionine metabolism. Defects in neurotransmitters as acetylcholine, and biogenic amines are reported in WD; however, less is known about their circulating precursors. We aimed to study choline, methionine, aromatic amino acids, and phospholipids in serum of WD subjects. Hydrophilic interaction chromatography-quadrupole time-of-flight mass spectrometry was employed to profile serum of WD subjects categorized as hepatic, neurologic, and pre-clinical. Hepatic transcript levels of genes related to choline and methionine metabolism were verified in the Jackson Laboratory toxic milk mouse model of WD (tx-j). Compared to healthy subjects, choline, methionine, ornithine, proline, phenylalanine, tyrosine, and histidine were significantly elevated in WD, with marked alterations in phosphatidylcholines and reductions in sphingosine-1-phosphate, sphingomyelins, and acylcarnitines. In tx-j mice, choline, methionine, and phosphatidylcholine were similarly dysregulated. Elevated choline is a hallmark dysregulation in WD interconnected with alterations in methionine and phospholipid metabolism, which are relevant to hepatic steatosis. The elevated phenylalanine, tyrosine, and histidine carry implications for neurologic manifestations and are worth further investigation
Shallow landslides and rockfalls velocity assessment at regional scale: a methodology based on a morphometric approach
Velocity is one of the most important parameters to evaluate the damaging potential of a mass movement, but its assessment, especially for extremely rapid landslides, is a complex task. In the literature, several models to assess mass movement velocity exist, but they usually require many detailed parameters, and therefore, they are applicable only to a single slope and not usable for regional-scale analyses. This study aims to propose a simple morphometric methodology, based on the spatialisation of the Energy Line method, to determine the velocity of shallow landslides and rockfalls at a regional scale. The proposed method requires a limited amount of input data (landslide perimeters and a digital elevation model), and its application can be carried out using GIS software and a Matlab code. The test area of this work is the Valle d’Aosta Region (Northern Italy), selected due to its peculiar geological and geomorphological setting that makes this region susceptible to the occurrence of both shallow landslides and rockfalls. Since measured velocity values for rockfalls and shallow landslides were not available, the results obtained with the proposed method have been validated through the implementation of a model in the literature, namely the Gravitational Process Path (GPP) model, for some selected landslides
Sorveglianza delle gastroenteriti da Norovirus in Italia: comparsa e diffusione della nuova variante GII.4 Sydney 2012
In the 2012-2013 winter season, global surveillance for norovirus circulation evidenced the onset of a new norovirus GII.4 variant, termed Sydney 2012. In Italy, ISGEV hospital-based surveillance revealed that this variant already circulated at low frequency in the winter season 2011-2012 and emerged definitively only in the late 2012. This lag-time pattern mirrors the findings reported elsewhere and suggests that the novel variant circulated at low prevalence before spreading globally
TIBIO-FIBULAR BONE TRANSPOSITION FOR THE TREATMENT OF ONCOLOGICAL PERIPROSTHETIC INFECTION OF THE KNEE WITH MASSIVE BONE LOSS
Chronic periprosthetic joint infection (PJI) is one of the most relevant complications in orthopaedic
surgery, especially in the case of limb reconstruction with megaprostheses after malignant tumoral
resection. This is the report of a case of a 35-year-old patient, affected by a chronic PJI around a
knee megaprosthesis implanted after the resection of an osteosarcoma of the distal femur. “En bloc”
resection and limb reconstruction with an expandable megaprothesis of the knee were performed at
the age of 5 years old (1989). PJI occurred after the definitive megaprosthesis implantation (2002),
and became chronic over the years.
In 2019, due to a massive recrudescence of the infection and the severe femoral bone loss, the
patient underwent a wide intercalary resection and a thigh stump reconstruction by transposition of
the fibula and the distal third of the tibia in order to avoid a hip disarticulation.
Although complex, the proposed treatment allowed improved outcomes in a young patient with
high function requests, justifying the global surgical invasiveness
Genetic heterogeneity and recombination in human type 2 astroviruses
Novel lineages of human astrovirus (HAstV) types 2, 2c, and 2d have been identified. Upon sequencing of the 3= end of the genome, the type 2c and 2d HAstVs were found to be open reading frame 1b (ORF1b)-ORF2 recombinant, with ORF1b being derived from type 3 and type 1 HAstVs, respectively. An ORF2 interlineage recombinant strain, 2c/2b, was also identified
Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis.
AIM: To evaluate whether combination therapy with anti-tumour necrosis factor α
(TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS)
colitis.
METHODS: Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d. The
experimental mice were then randomised into the following subgroups: standard
diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25
μg anti-TNFα treated group; Zn acetate treated group + DSS + subcutaneous 25 μg
anti-TNFα; standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and
Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα. Each group of
mice was matched with a similar group of sham control animals. Macroscopic and
histological features were scored blindly. Homogenates of the colonic mucosa were
assessed for myeloperoxidase activity as a biochemical marker of inflammation and
DNA adducts (8OH-dG) as a measure of oxidative damage.
RESULTS: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration
and cryptic abscesses which were reduced in both groups of mice receiving either
anti-TNFα alone or combined with zinc. The effect was more pronounced in the
latter group (vs Zn diet, P < 0.02). Myeloperoxidase activity (vs controls, P <
0.02) and DNA adducts, greatly elevated in the DSS fed colitis group (vs
controls, P < 0.05), were significantly reduced in the treated groups, with a
more remarkable effect in the group receiving combined therapy (vs standard diet,
P < 0.04).
CONCLUSION: DSS induces colonic inflammation which is modulated by the
administration of anti-TNFα. Combining anti-TNFα with Zn acetate offers marginal
benefit in colitis severity
High pressure deformation mechanism of Li-ABW: synchrotron XRPD study and ab-initio molecular dynamic simulations
A family of kojic acid derivatives aimed to remediation of Pb2+ and Cd2+
The present work analyzes the complex formation ability towards Pb2+ and Cd2+ of a series of kojic acid derivatives that join the chelating properties of the pyrone molecules and those of polyamines, with the aim of evaluating how the different effects of oxygen and nitrogen coordinating groups act on the stability of metal complexes. Experimental research is carried out using potentiometric and spectrophotometric techniques supported by 1H and 13C NMR spectroscopy and DFT calculations. Actually, a different coordination mechanism toward Pb2+ and Cd2+ was proved: in the case of Pb2+, coordination takes place exclusively via the oxygen atoms, while the contribute of the nitrogen atoms appears relevant in the case of Cd2+. Lead complexes of all the studied ligands are characterized by significantly stronger stability than those of cadmium. Finally, on the basis of the measured complex formation stabilities, some of the proposed molecules seems promising effective ligands for lead and cadmium ion decorporation from polluted soils or waste waters
Orbitally resolved lifetimes in Ba(Fe0.92Co0.08)2As2 measured by ARPES
Despite many ARPES investigations of iron pnictides, the structure of the
electron pockets is still poorly understood. By combining ARPES measurements in
different experimental configurations, we clearly resolve their elliptic shape.
Comparison with band calculation identify a deep electron band with the dxy
orbital and a shallow electron band along the perpendicular ellipse axis with
the dxz/dyz orbitals. We find that, for both electron and hole bands, the
lifetimes associated with dxy are longer than for dxz/dyz. This suggests that
the two types of orbitals play different roles in the electronic properties and
that their relative weight is a key parameter to determine the ground state
Highlighting chromosome loops in DNA-picked chromatin (DPC).
"Growing evidence supports the concept that dynamic intra-and inter-chromosomal links between specific loci contribute to the creation of cell type-specific gene expression profiles. Therefore, analysis of the establishment of peculiar functional correlations between sites, also distant on linear DNA, that govern the transcriptional process appears to be of fundamental relevance. We propose here an experimental approach showing that 17 beta-estradiol-induced transcription associates to formation of loops between the promoter and termination regions of hormone-responsive genes. This strategy reveals as a tool to be also suitably used, in conjunction with automated techniques, for an extensive analysis of sites shared by multiple genes for induced expression.
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