1,721,002 research outputs found
La contrattazione di secondo livello nel settore dei pubblici esercizi: vecchi e nuovi modelli
Full text linkThe author reviews evidence that the bargaining structure is becoming more decentralized in the hospitality industry for bars, cafés and restaurants, although in somewhat different degrees and ways for small, medium and large companies. He then examines the various hypotheses that have been offered from the last century untill now.
Despite undeniable trends towards the decentralisation of collective bargaining structures in Italy, the hospitality industry sector very centralised. Collective bargaining takes place predominantly at a national or regional level. The importance of sectoral collective agreements – and, thus, multi-employer collective bargaining – is indicated by the fact that these agreements are used for a large share of employees as well as companies.
At the same time, the tendency towards a company-based approach to collective bargaining cannot be ignored. Indeed, the author also talks about the obstacles of the decentralisation of collective bargaining and explores, at the same time, new possibilities for company-level deviations (from norms set under national-sectoral agreements). He emphasises the need for more decentralisation, especially for wage setting, in order to satisfy companies’ competitive needs, or to allow companies to overcome temporary economic difficulties, thus permitting companies to cope better with global competition and unstable markets
Mitoepigenetics investigations in neurodegenerative diseases
No full textNeurodegenerative diseases (NDs) represent a group of disorders characterized by the
progressive neuronal loss in specific areas of the central nervous system. NDs are incurable
and often fatal shortly after diagnosis. The global prevalence of these disorders is
dramatically increasing worldwide as populations age and life expectancies increase. The
identification of valuable biomarkers for an early diagnosis is of outmost importance as it
would promote early interventions able to prevent or delay as much as possible the onset of
the disease. Despite their high heterogeneity and the differences in their primary etiologies,
NDs share many common aspects in relation to their clinical, biochemical, and
pathological features and multiple lines of evidence suggest that mitochondrial dysfunction
is involved in the pathogenesis of many NDs, especially Alzheimer ́s disease (AD),
Parkinson ́s disease (PD) and amyotrophic lateral sclerosis (ALS). To date, several papers
showed that aberrant epigenetic mechanisms in the nuclear DNA may be involved in the
onset and development of NDs, and several studies have found altered gene methylation
levels in both post-mortem brain specimens and peripheral tissues from patients with these
diseases. In recent years growing evidence for a potential role of altered mitochondrial
DNA (mtDNA) methylation and hydroxymethylation in several diseases has emerged.
Although mitochondrial impairment is a classical feature of neurodegeneration, little
attention has been given until now to the role of the mitochondrial epigenome itself in
NDs. Particularly, studies performed so far have investigated mtDNA methylation in
animal models of ALS, and in brain tissue of patients with AD, PD and ALS. However,
potential mtDNA methylation alterations in peripheral tissues of NDs patients have not
been investigated in those studies.
The main aim of the work presented in the current thesis was to investigate the
presence of mitoepigenetic signatures in peripheral blood of patients with AD (Study 1),
ALS (Study 2) and PD (Study 3). DNA methylation analysis of the mitochondrial D-loop
region, which regulates mitochondrial transcription and replication, was performed by
means of Methylation Sensitive-High Resolution Melting and Pyrosequencing techniques.
In study 1 D-loop methylation levels were analyzed in people affected by AD with
different clinical dementia impairment degrees and results suggest that mtDNA
methylation could vary with the stage of the disease. In study 2 D-loop methylation levels
were analyzed in ALS patients with mutations in SOD1, TARDBP, FUS or C9ORF72
genes, and in their relatives, and results showed that mtDNA methylation levels were
decreased in ALS tissues, partcularly in carriers of SOD1 mutations. In study 3 higher Dloop
methylation levels, although not statistically significant, were detected in peripheral
blood from PD patients.
Results presented in the current thesis indicate a potential involvement for impaired
mtDNA methylation in NDs, which is detectable in peripheral blood suggesting that this
field of research deserves to be further studied. Moreover, current results suggest that
mtDNA methylation could be sensitive to different disease stages and dementia levels, thus
adding a new layer of interest in the search for peripheral mitoepigenetic biomarkers for
neurodegeneration. Given the pivotal role of mitochondrial dysfunction and of epigenetic
mechanisms in neurodegeneration, the field of mitoepigenetics in neurodegenerative
diseases is a timely and attractive recent area of investigation, where preliminary results
really seem encouraging, but more research is warranted to clarify the connections between
epigenetic changes occurring in the mitochondrial genome, mitochondrial DNA dynamics,
and the neurodegenerative process
Epigenetic Peripheral Biomarkers for Early Diagnosis of Alzheimer’s Disease
No full textAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and represents the leading cause of cognitive impairment and dementia in older individuals throughout the world. The main hallmarks of AD include brain atrophy, extracellular deposition of insoluble amyloid-β (Aβ) plaques, and the intracellular aggregation of protein tau in neurofibrillary tangles. These pathological modifications start many years prior to clinical manifestations of disease and the spectrum of AD progresses along a continuum from preclinical to clinical phases. Therefore, identifying specific biomarkers for detecting AD at early stages greatly improves clinical management. However, stable and non-invasive biomarkers are not currently available for the early detection of the disease. In the search for more reliable biomarkers, epigenetic mechanisms, able to mediate the interaction between the genome and the environment, are emerging as important players in AD pathogenesis. Herein, we discuss altered epigenetic signatures in blood as potential peripheral biomarkers for the early detection of AD in order to help diagnosis and improve therapy
Role of epigenetics in Alzheimer's disease pathogenesis
No full textAdvances in molecular biology technologies have allowed uncovering the role of epigenetic regulation in several complex diseases, such as cancer and neurodegenerative disorders. Although the role of epigenetic mechanisms in Alzheimer's disease is still little understood, recent findings clearly show that such mechanisms are dysregulated during disease progression, already in its early stages. However, it is not clear if the observed epigenetic changes represent a cause or a consequence of the disease. Promising results are emerging from studies performed in peripheral blood DNA that could provide early biomarkers of the pathology. Moreover, given the dynamic nature of the epigenetic marks, intense research is carried out to investigate the therapeutic efficacy of compounds exerting epigenetic properties
Mitochondrial DNA Methylation and Human Diseases
Full text linkEpigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases
Exposure to Metals, Pesticides, and Air Pollutants: Focus on Resulting DNA Methylation Changes in Neurodegenerative Diseases
Full text linkIndividuals affected by neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are dramatically increasing worldwide. Thus, several efforts are being made to develop strategies for stopping or slowing the spread of these illnesses. Although causative genetic variants linked to the onset of these diseases are known, they can explain only a small portion of cases. The etiopathology underlying the neurodegenerative process in most of the patients is likely due to the interplay between predisposing genetic variants and environmental factors. Epigenetic mechanisms, including DNA methylation, are central candidates in translating the effects of environmental factors in genome modulation, and they play a critical role in the etiology of AD, PD, and ALS. Among the main environmental exposures that have been linked to an increased risk for these diseases, accumulating evidence points to the role of heavy metals, pesticides, and air pollutants. These compounds could trigger neurodegeneration through different mechanisms, mainly neuroinflammation and the induction of oxidative stress. However, increasing evidence suggests that they are also capable of inducing epigenetic alterations in neurons. In this article, we review the available literature linking exposure to metals, pesticides, and air pollutants to DNA methylation changes relevant to neurodegeneration
Epigenetic biomarkers in personalized medicine
No full textIncreasing evidence reveals that epigenetic biomarkers, mainly markers of DNA methylation or noncoding RNA molecules, can become valuable tools as minimally invasive diagnostic biomarkers in cancerous conditions as well as monitoring disease status over time and predicting favorable or worse outcome. In addition, drugs acting on writer and eraser proteins of the epigenetic marks, such as DNA methyltransferases and histone deacetylases, are among the most promising novel therapeutic approaches in either cancerous or noncancerous conditions. In parallel, there are indications, mainly from studies in cancer cell lines, that most chemotherapeutic and immune resistance is mediated by epigenetic changes, paving the way for epigenetic markers of response to treatment. The role of epigenetics is not confined to cancer onset and progression, but is becoming increasingly recognized in most noncancerous human complex diseases, indicating that the analysis of the epigenome could represent one of the most promising approaches to refining diagnosis, predicting prognosis, and choosing the most personalized therapeutic approach in human disease
Investigation of GHSR and GHRL methylation in colorectal cancer
No full textAIM:
To investigate GHSR and GHRL methylation in 73 pairs of colorectal cancer (CRC) tissues and healthy adjacent mucosa.
METHODS:
Methylation was assessed with methylation-sensitive high-resolution melting.
RESULTS:
GHSR was significantly hypermethylated in CRC tissues than in healthy mucosa (p < 1 × 10-5), but no significant changes of GHRL methylation were observed. GHSR hypermethylation was already detectable at the adenoma stage and maintained in later stages independently of age, gender, anatomical location, histological grading, MLH1 deficiency, as well as of major polymorphisms in folate-pathway genes, yielding an area under the curve of 0.824 for discriminating cancers from respective non-neoplastic mucosa specimens.
CONCLUSION:
GHSR hypermethylation occurs early in CRC, but is not paralleled by significant changes of GHRL methylation
Editorial: Epigenetics of Neurodevelopmental, Neuromuscular and Neurodegenerative Disorders
Full text linkArtificial Neural Networks Link One-Carbon Metabolism to Gene-Promoter Methylation in Alzheimer's Disease
Full text linkBackground: There is increasing interest in DNA methylation studies in Alzheimer's disease (AD), but little is still known concerning the relationship between gene-promoter methylation and circulating biomarkers of one-carbon metabolism in patients. Objective: To detect the connections among circulating folate, homocysteine (hcy) and vitamin B12 levels and promoter methylation levels of PSEN1, BACE1, DNMT1, DNMT3A, DNMT3B, and MTHFR genes in blood DNA. Methods: We applied a data mining system called Auto Contractive Map to an existing database of 100 AD and 100 control individuals. Results: Low vitamin B12 was linked to the AD condition, to low folates, and to high hcy. Low PSEN1 methylation was linked to low folate levels as well as to low promoter methylation of BACE1 and DNMTs genes. Low hcy was linked to controls, to high folates and vitamin B12, as well as to high methylation levels of most of the studied genes. Conclusions: The present pilot study suggests that promoter methylation levels of the studied genes are linked to circulating levels of folates, hcy, and vitamin B12
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