The Role of Y-PARK9 protein in preventing manganese-induced Parkinson's disease

A variety of metals are essential trace elements but can reach localized toxic concentrations through various disease processes or environmental exposures and have been implicated as having a role in neurodegeneration. In particular, chronic inorganic manganese exposure causes selective toxicity to the nigrostriatal dopaminergic system, resulting in a Parkinsonian-like neurological condition known as Manganism. YPK9 gene (Yeast PARK9; also known as YOR291W) encodes a transmembrane P-type transport ATPase presumably involved in metal coordination and transportation, though its substrate specificity still remains unknown. Mutations in the human homolog of YPK9, PARK9 (ATP13A2), have been linked to genetic forms of early onset parkinsonism. Recently a strong genetic interaction between YPK9 and another Parkinson's disease protein, α-synuclein, has been evidenced in multiple model systems, indicating a crucial role for YPK9 in manganese detoxification in yeast and a specific protecting effect against manganese poisoning [1,3]. With the purpose to shed light on the protective property of YPK9 in Manganese-induced Parkinsonism, we tested the binding ability of Mn(II) and other divalent cations (Cu(II), Zn(II)) towards several peptide sequences from YPK9, with a particular focus on highly conserved sequences from yeast to human. The work was carried out at different pH values and ligand/metal molar ratios by means of potentiometric and spectroscopic techniques (multidimensional and heteronuclear NMR and UV-visible), in order to evaluate and compare the coordination propensity of such fragments with Mn(II) and the other metal probes selected [4,5]

UCLID-Net: Single View Reconstruction in Object Space

Most state-of-the-art deep geometric learning single-view reconstruction approaches rely on encoder-decoder architectures that output either shape parametrizations or implicit representations. However, these representations rarely preserve the Euclidean structure of the 3D space objects exist in. In this paper, we show that building a geometry preserving 3-dimensional latent space helps the network concurrently learn global shape regularities and local reasoning in the object coordinate space and, as a result, boosts performance. We demonstrate both on ShapeNet synthetic images, which are often used for benchmarking purposes, and on real-world images that our approach outperforms state-of-the-art ones. Furthermore, the single-view pipeline naturally extends to multi-view reconstruction, which we also show.Comment: Added supplementary materia

Interaction of divalent cations with protein PARK9

Metals have been shown to play a role in the genesis and development of many neurodegenerative diseases. Park9 encoded protein can protect cells from manganese poisoning, an environmental risk factor for a Parkinson’s disease- like syndrome. Park9 belongs to a family of ATP-ases involved in metal coordination and transportation; familial mutations of this gene may result in early development of PD. We tested two peptide sequences from Park9, -P1D2E3K4H5E6L7- (1) and -F1C2G3D4G5A6N7D8C9G10- (2), for Mn(II), Zn(II) and Cu(II) binding. These fragments are located from 1165 to 1171 and from 1184 to 1193 residues in Park9 sequence, and are highly conserved in a number of organisms, from yeasts to humans. Experiments have been carried out at different pH values and ligand/metal molar ratios with both potentiometric and spectroscopic (NMR, UV-vis) techniques, showing that the three metals are able to effectively bind the examined peptides. Mn(II) and Zn(II) coordination with peptide (1) involves imidazol of His5 and carboxyl γ-O of Asp2, Glu3 and Glu6 residues, in a distorted octahedral geometry, possibly involving bidentate interaction of carboxyl groups; four donor atoms participate in Zn(II) binding, resulting in a tetracoordinated geometry. Mn(II) and Zn(II) coordination involves the two cysteines in peptide (2); Mn(II) accepts additional ligand bonds from D4 and D8 to complete the coordination sphere, together with some water molecules. Details of Cu(II) coordination are under study

Clinical Features of SARS-CoV-2 Infection in Older Adults

The COVID-19 clinical presentation is extremely heterogenous and, in older people, it is influenced not simply by chronologic age but also by common geriatric syndromes, such as multimorbidity, motor disability, and frailty. Consequently, although typical respiratory symptoms remain the most frequent clinical presentation of COVID-19 in all age classes, in older patients, atypical symptoms (including but not limited to delirium and hyporexia) are more common than in middle-aged adults and have been associated with adverse outcomes. Moreover, some studies described the tendency of COVID-19 presenting symptoms to aggregate in clusters, and this approach seems to better capture the complexity of COVID-19 disease. The prognostic value of COVID-19 symptom clusters, however, is currently poorly investigated, especially in the older population

The Ecotoxicity Approach as a Tool for Assessing Vermiremediation Effectiveness in Polychlorobiphenyls, Polychlorodibenzo-p-Dioxins and Furans Contaminated Soils

Chemical analyses are inadequate for assessing soil biological quality. Instead, the soil living community can be used both for monitoring and restoring soil health. The aim of this research was to verify vermiremediation efficiency in PCDD/F and PCB contaminated soils from Brescia-Caffaro (Italy), using an ecotoxicity approach. To gauge whether Caffaro soil could sustain a living community, a characterization of the arthropod community was conducted. Earthworms’ suitability for soil bioremediation was assessed applying ecotoxicity tests. Five treatments were set up: 1) contaminated soil; 2) contaminated soil + Eisenia fetida; 3) contaminated soil + Lepidium sativum; 4) contaminated soil + E. fetida + L. sativum, 5) uncontaminated soil + E. fetida. The ecotoxicity tests were: L. sativum germination index and root elongation inhibition, and Folsomia candida survival and reproduction, applied on soil and elutriate on: starter soil (T0), after 56 and 112 days (T56 and T112), the last after water percolation. Soil arthropod community was dominated by Hypogastruridae, Oribatida and, to a lesser degree, Formicidae and Coleoptera larvae. Ecotoxicity tests showed that F. candida reproduction and L. sativum root elongation were more adversely affected by pollutants than survival and germination. The higher soil ecotoxicity at T112 than at T56, suggested higher contaminant bioavailability after water addition. F. candida showed more variability between soil and elutriate than L. sativum. Both bioassays suggested earthworm treatment as the most promising. The importance of selecting different organisms in soil ecotoxicity monitoring, and the role of elutriate like a solid phase complement, was highlighted

Natural surface hydrocarbons and soil faunal biodiversity: A bioremediation perspective

Hydrocarbon pollution threatens aquatic and terrestrial ecosystems globally, but soil fauna in oil-polluted soils has been insufficiently studied. In this research, soil hydrocarbon toxicity was investigated in two natural oil seepage soils in Val D'Agri (Italy) using two different approaches: (i) toxicological tests with Folsomia candida (Collembola) and Eisenia fetida (Oligochaeta) and (ii) analysis of abundance and composition of micro- and meso-fauna. Soil sampling was done along 20 m-transepts starting from the natural oil seepages. Toxicological testing revealed that no exemplars of F. candida survived, whereas specimens of E. fetida not only survived but also increased in weight in soils with higher PAH concentrations, although no reproduction was observed. Analysis on microfauna showed that Nematoda was the most abundant group, with distance from seepages not affecting its abundance. Arthropoda results showed that Acarina, Collembola and Diptera larvae represented the most abundant taxa. The highest divergence in community composition was found between soils situated near seepages and at 5 m and 10 m distance. Arthropoda taxa numbers, total abundance and Acarina were lower in soils with high PAH concentration, while Diptera larvae were not significantly affected. Earthworms, together with Nematoda and Diptera larvae, could therefore represent ideal candidates in PAH degradation studies

Geodesic Convolutional Shape Optimization

Aerodynamic shape optimization has many industrial applications. Existing methods, however, are so computationally demanding that typical engineering practices are to either simply try a limited number of hand-designed shapes or restrict oneself to shapes that can be parameterized using only few degrees of freedom. In this work, we introduce a new way to optimize complex shapes fast and accurately. To this end, we train Geodesic Convolutional Neural Networks to emulate a fluidynamics simulator. The key to making this approach practical is remeshing the original shape using a polycube map, which makes it possible to perform the computations on GPUs instead of CPUs. The neural net is then used to formulate an objective function that is differentiable with respect to the shape parameters, which can then be optimized using a gradient-based technique. This outperforms state- of-the-art methods by 5 to 20% for standard problems and, even more importantly, our approach applies to cases that previous methods cannot handle

Prevalence and impact of polypharmacy in older patients with type 2 diabetes

Background: Polypharmacy is a prevalent condition in older adults, especially those with multiple chronic diseases, and has been largely associated with adverse outcomes, including disability, hospitalizations, and death. Aims: This systematic review focused on diabetes and aimed to investigate the prevalence and impact of polypharmacy in older adults affected by such disease. Methods: Observational (either cross-sectional or longitudinal) or experimental studies investigating the frequency and impact of polypharmacy in older adults with diabetes were identified from scientific databases and grey literature until August 2021. The prevalence and the 95% Confidence Interval (95% CI) of polypharmacy in older people with diabetes were summarized by a random-effects meta-analysis. Results: From a total of 1465 records, 9 were selected for the qualitative synthesis, and 8 for the quantitative synthesis. Most studies defined polypharmacy using a cut-off for the minimum number of medications ranging from 4 to 6 drugs/day. The pooled prevalence of polypharmacy in older people with diabetes was 64% (95% CI 45–80%). Considering studies that used the same definition of polypharmacy (i.e. ≥ 5 drugs/day), the pooled prevalence was 50% (95% CI 37–63%). The between-studies heterogeneity was high. Across the selected studies, polypharmacy seemed to negatively influence both diabetes-specific (poor glycemic control and risk of hypoglycemia) and health-related (risk of incident falls, syncope, hospitalization, and death) outcomes. Conclusion: This systematic review confirms the high prevalence of polypharmacy in older people with diabetes and its strong impact on several health-related outcomes, including mortality. These results strengthen the need to improve care strategies for management of these patients

Delirium in hip fractured patients

The current clinical case concerns the mixed delirium in a 70-year-old man with hip fracture, following a fall at home. In his medical history, the patient reported several comorbidities, among which also sarcopenia. Delirium was already diagnosed by the geriatrician on hospital admission. The patient underwent hip endoprosthesis surgery after 24 hours without any intra-operative complications. However, in the post-operative period delirium persisted, causing a prolonged hospital stay, a delayed physio-therapy rehabilitation with poor functional recovery, and subsequent insti-tutionalization. The prevalence of delirium in older people with hip fracture is extremely high and it is associated with several negative outcomes. Delirium is considered a multifactorial disorder, and, in particular, sarcopenia appears directly linked to the development of delirium. The systematic assessment of sarcopenia should be performed in hospitalized older patients with hip fracture, together with the other predisposing risk factors for delirium, to timely identify people at higher risk for both delirium and disability