HLA Class I or Class II and Disease Association: Catch the Difference if You Can

The association of autoimmune diseases with HLA has been known for many decades. To date, however, the underlying mechanisms have not been fully understood. The recently introduced genome-wide association studies (GWAS) have suggested that several genes converging in common pathways contribute to the genetic susceptibility in such disorders. Nevertheless, for most autoimmune/autoinflammatory diseases, the HLA genes are by far the strongest risk factors. The basis of some associations has now been elucidated, particularly in those cases in which exogenous factors are involved

Ankylosing Spondylitis: a trade Off of HLA-B27, ERAP, and pathogen interconnections? Focus on Sardinia

The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to be associated with AS. The highly homogenous genetic structure of the Sardinian population has favored the search of relevant variants for disease-association studies. Moreover, malaria, once endemic in the island, has been shown to have contributed to shape the native population genome affecting the relative allele frequency of relevant genes. In Sardinia, the prevalence of HLA-B*2709, which differs from the strongly AS-associated B*2705 prototype for one amino acid (His/Asp116) in the F pocket of the peptide binding groove, is around 20% of all HLA-B27 alleles. We have previously hypothesized that malaria could have contributed to the establishment of this allele in Sardinia. Based on our recent findings, in this perspective article we speculate that the Endoplasmic Reticulum Amino Peptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria. These genes, besides shaping the immunopeptidome of HLA-class I molecules, have other biological functions that could also be involved in the immunosurveillance against malaria

Synchronization of dynamical hypernetworks: dimensionality reduction through simultaneous block-diagonalization of matrices

We present a general framework to study stability of the synchronous solution for a hypernetwork of coupled dynamical systems. We are able to reduce the dimensionality of the problem by using simultaneous block-diagonalization of matrices. We obtain necessary and sufficient conditions for stability of the synchronous solution in terms of a set of lower-dimensional problems and test the predictions of our low-dimensional analysis through numerical simulations. Under certain conditions, this technique may yield a substantial reduction of the dimensionality of the problem. For example, for a class of dynamical hypernetworks analyzed in the paper, we discover that arbitrarily large networks can be reduced to a collection of subsystems of dimensionality no more than 2. We apply our reduction techique to a number of different examples, including a class of undirected unweighted hypermotifs of three nodes.Comment: 9 pages, 6 figures, accepted for publication in Phys. Rev.

Experimental Observations of Group Synchrony in a System of Chaotic Optoelectronic Oscillators

We experimentally demonstrate group synchrony in a network of four nonlinear optoelectronic oscillators with time-delayed coupling. We divide the nodes into two groups of two each, by giving each group different parameters and by enabling only inter-group coupling. When coupled in this fashion, the two groups display different dynamics, with no isochronal synchrony between them, but the nodes in a single group are isochronally synchronized, even though there is no intra-group coupling. We compare experimental behavior with theoretical and numerical results

CAD/CAM Diagnostic Esthetic Functional Splint (DEFS) as a removable prototype to evaluate the final prosthetic rehabilitation: a narrative review.

The main objective of this narrative review was to provide an overview of DEFS (Diagnostic Esthetic Functional Splint), namely CAD/CAM manufactured, “snap-retained”, tooth-colored splints available by materials exhibiting a certain degree of elasticity (like polycarbonates or acetal resins) for restoring function, esthetics and occlusion in several clinical situations, before or as an intermediate alternative to undergoing the final treatment. The search strategy included all papers dealing with snap-retained prosthetic systems and was based on a literature review of papers available in electronic databases (Pubmed/Medline, Evidence-Based Dentistry, BMJ Evidence-Based Medicine, Dynamed, Embase, BMJ Clinical Evidence, Web of Science, Scientific reports); eligible papers were researched on Opengreyand a manual search was performed, as well. From the electronic databases emerged 13,199 records, many of which were duplicates. The grey literature and the manual research did not produce any eligible article. After duplicates removal, 7690 records were obtained. Titles, abstracts and keywords were analyzed. The studies concerning the topic of interest were examined by the reviewers and discussed. Although no evidence-based data were found in the literature, according to the authors’ clinical experience, the DEFS (Diagnostic Esthetic Functional Splint) is a very promising solution in multiple clinical situations, due to its diagnostic, therapeutical, functional and esthetic versatility

Cooling of Sr to high phase-space density by laser and sympathetic cooling in isotopic mixtures

Based on an experimental study of two-body and three-body collisions in ultracold strontium samples, a novel optical-sympathetic cooling method in isotopic mixtures is demonstrated. Without evaporative cooling, a phase-space density of $6\times10^{-2}$ is obtained with a high spatial density that should allow to overcome the difficulties encountered so far to reach quantum degeneracy for Sr atoms.Comment: 5 pages, 4 figure

Treatment of Vascular Dementia: The Route of Prevention

Vascular dementia (VaD), rather than being considered as a univocal nosological entity, should be regarded as a heterogeneous clinical entity which differs in clinical-pathological phenotype as well as in pathophysiological mechanisms, but shares cerebrovascular disease (CVD), resulting from vascular or circulatory pathology, as the cause of dementia. The aim of this review is to discuss VaD treatment focusing particularly on more prevalent ischemic forms. Due to the fact that there are presently no treatments capable of obtaining considerable results once VaD is clinically established, specific emphasis will be given to the therapeutic strategies aimed at the prevention of CVD risk factors. The therapeutic strategies aimed at slowing the progression of the disease will also be discussed

Interdisciplinary full digital restorative treatment of a young patient with severe open bite and amelogenesis imperfecta: a case report.

Background Amelogenesis Imperfecta (AI) is a syndromic entity comprising several clinical conditions, mostly genetic- based, affecting quality and quantity of enamel. The use of digital tools can be advantageous to enhance communication between the dental team and patients. Moreover, a full digital approach would allow to check each single clinical step according to the treatment plan with a backward approach. The aim of this case report is to describe a multidisciplinary treatment program of a young patient with severe open bite and amelogenesis imperfecta, whose restorative rehabilitation was planned in a full-digital workflow, from the initial communication phase up to the final prosthodontic rehabilitation. Case report An 8-year old female patient was diagnosed with a Class II division 1 malocclusion, severe open bite and AI. The treatment plan included 3 phases: the elimination of the tongue interposition habit and the anterior open bite, the orthodontic correction of dental deviation and leveling of both dental arches and a prosthetic rehabilitation. The extraction of the four first molars corrected the canine and molar Angle Class II relationships, deviation of the midline and repositioning of the maxillary incisors on the sagittal plane. Feldspathic ceramics was used in anterior sites to enhance the esthetic outcome. CAD/CAM hybrid ceramo-polymeric restorative material (PICN) was chosen for posterior regions. Conclusion The outcomes of the present case report proved that the planned objectives were satisfactorily obtained thanks to proper treatment planning, full digital workflow and the patient’s optimal compliance with the extraoral device

An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes

The Endoplasmatic Reticulum Aminopeptidases ERAP1 and ERAP2 are implicated in a variety of immune and non-immune functions. Most studies however have focused on their role in shaping the HLA class I peptidome by trimming peptides to the optimal size. Genome Wide Association Studies highlighted non-synonymous polymorphisms in their coding regions as associated with several immune mediated diseases. The two genes lie contiguous and oppositely oriented on the 5q15 chromosomal region. Very little is known about the transcriptional regulation and the quantitative variations of these enzymes. Here, we correlated the level of transcripts and proteins of the two aminopeptidases in B-lymphoblastoid cell lines from 44 donors harbouring allelic variants in the intergenic region between ERAP1 and ERAP2. We found that the presence of a G instead of an A at SNP rs75862629 in the ERAP2 gene promoter strongly influences the expression of the two ERAPs with a down-modulation of ERAP2 coupled with a significant higher expression of ERAP1. We therefore show here for the first time a coordinated quantitative regulation of the two ERAP genes, which can be relevant for the setting of specific therapeutic approaches