84 research outputs found
Rethinking feasibility analysis for urban development: a multidimensional decision support tool
Large-scale urban development projects featured over the past thirty years have shown some critical issues related to the implementation phase. Con-sequently, the current practice seems oriented toward minimal and wide-spread interventions meant as urban catalyst. This planning practice might solve the problem of limited reliability of large developments’ feasibility studies, but it rises an evaluation demand related to the selection of coali-tion of projects within a multidimensional and multi-stakeholders deci-sion-making context. This study aims to propose a framework for the generation of coalitions of elementary actions in the context of urban regeneration processes and for their evaluation using a Multi Criteria Decision Analysis approach. The proposed evaluation framework supports decision makers in exploring dif-ferent combinations of actions in the context of urban interventions taking into account synergies, i.e. positive or negative effects on the overall per-formance of an alternative linked to the joint realization of specific pairs of actions. The proposed evaluation framework has been tested on a pilot case study dealing with urban regeneration processes in the city of Milan (Italy)
Past, present, and future strategies for enhanced assessment of embryo's genome and reproductive competence in women of advanced reproductive age
Recent advancements in genomic analysis allow testing of an increasing number of genetic features in human preimplantation embryos. Typical single gene mutation and whole chromosomes testing can now be integrated with assessment of mitochondrial DNA and polygenic conditions. Diagnostic expansion into epigenetic and transcriptomic assessment in the near future are potential technological targets which may improve the prognostic outlook of patients of advanced reproductive age and overall in vitro fertilization (IVF) treatment outcomes. In this review, we discuss the technological progress of recent years and their future applications in preimplantation genetic testing in IVF
Cerebral deficiency of vitamin B5 (D-pantothenic acid; pantothenate) as a potentially-reversible cause of neurodegeneration and dementia in sporadic Alzheimer's disease
Alzheimer's disease (AD) is the most common cause of age-related neurodegeneration and dementia, and there are no available treatments with proven disease-modifying actions. It is therefore appropriate to study hitherto-unknown aspects of brain structure/function in AD to seek alternative disease-related mechanisms that might be targeted by new therapeutic interventions with disease-modifying actions. During hypothesis-generating metabolomic studies of brain, we identified apparent differences in levels of vitamin B5 between AD cases and controls. We therefore developed a method based on gas chromatography-mass spectrometry by which we quantitated vitamin B5 concentrations in seven brain regions from nine AD cases and nine controls. We found that widespread, severe cerebral deficiency of vitamin B5 occurs in AD. This deficiency was worse in those regions known to undergo severe damage, including the hippocampus, entorhinal cortex, and middle temporal gyrus. Vitamin B5 is the obligate precursor of CoA/acetyl-CoA (acetyl-coenzyme A), which plays myriad key roles in the metabolism of all organs, including the brain. In brain, acetyl-CoA is the obligate precursor of the neurotransmitter acetylcholine, and the complex fatty-acyl groups that mediate the essential insulator role of myelin, both processes being defective in AD; moreover, the large cerebral vitamin B5 concentrations co-localize almost entirely to white matter. Vitamin B5 is well tolerated when administered orally to humans and other mammals. We conclude that cerebral vitamin B5 deficiency may well cause neurodegeneration and dementia in AD, which might be preventable or even reversible in its early stages, by treatment with suitable oral doses of vitamin B5
Substantively Lowered Levels of Pantothenic Acid (Vitamin B5) in Several Regions of the Human Brain in Parkinson’s Disease Dementia
From MDPI via Jisc Publications RouterHistory: accepted 2021-08-23, pub-electronic 2021-08-25Publication status: PublishedFunder: Endocore Research Associates, NZ; Grant(s): 60147, 3626585; 3702766, JXU058, UOAX0815Funder: Maurice and Phyllis Paykel Trust; Grant(s): 3627036Funder: Maurice Wilkins Centre for Molecular Biodiscovery; Grant(s): 9341-3622506Funder: Oakley Mental Health Research Foundation; Grant(s): 3456030; 3627092; 3701339; 3703253; 3702870Funder: Neurological Foundation of New Zealand; Grant(s): N/AFunder: Medical Research Council; Grant(s): MR/L010445/1 and MR/L011093/1Funder: Alzheimer’s Research UK; Grant(s): ARUK-PPG2014B-7Pantothenic acid (vitamin B5) is an essential trace nutrient required for the synthesis of coenzyme A (CoA). It has previously been shown that pantothenic acid is significantly decreased in multiple brain regions in both Alzheimer’s disease (ADD) and Huntington’s disease (HD). The current investigation aimed to determine whether similar changes are also present in cases of Parkinson’s disease dementia (PDD), another age-related neurodegenerative condition, and whether such perturbations might occur in similar regions in these apparently different diseases. Brain tissue was obtained from nine confirmed cases of PDD and nine controls with a post-mortem delay of 26 h or less. Tissues were acquired from nine regions that show high, moderate, or low levels of neurodegeneration in PDD: the cerebellum, motor cortex, primary visual cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons. A targeted ultra–high performance liquid chromatography—tandem mass spectrometry (UHPLC-MS/MS) approach was used to quantify pantothenic acid in these tissues. Pantothenic acid was significantly decreased in the cerebellum (p = 0.008), substantia nigra (p = 0.02), and medulla (p = 0.008) of PDD cases. These findings mirror the significant decreases in the cerebellum of both ADD and HD cases, as well as the substantia nigra, putamen, middle frontal gyrus, and entorhinal cortex of HD cases, and motor cortex, primary visual cortex, hippocampus, middle temporal gyrus, cingulate gyrus, and entorhinal cortex of ADD cases. Taken together, these observations indicate a common but regionally selective disruption of pantothenic acid levels across PDD, ADD, and HD
Mechanism of Human Papillomavirus Binding to Human Spermatozoa and Fertilizing Ability of Infected Spermatozoa
Human papillomaviruses (HPVs) are agents of the most common sexually transmitted diseases in females and males. Precise data about the presence, mechanism of infection and clinical significance of HPV in the male reproductive tract and especially in sperm are not available. Here we show that HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm exposed to HPV L1 capsid protein are capable to penetrate the oocyte and transfer the virus into oocytes, in which viral genes are then activated and transcribed. These data show that sperm might function as vectors for HPV transfer into the oocytes, and open new perspectives on the role of HPV infection in males and are particularly intriguing in relation to assisted reproduction techniques
Mitigazione e adattamento ai cambiamenticlimatici: valutazioni di efficacia di piani epolitiche in Usa, in Europa e in Italia
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