150 research outputs found
The role of collective motion in examples of coarsening and self-assembly
No full textThe simplest prescription for building a patterned structure from its constituents is to add particles, one at a time, to an appropriate template. However, self-organizing molecular and colloidal systems in nature can evolve in much more hierarchical ways. Specifically, constituents (or clusters of constituents) may aggregate to form clusters (or clusters of clusters) that serve as building blocks for later stages of assembly. Here we evaluate the character and consequences of such collective motion in a set of prototypical assembly processes. We do so using computer simulations in which a system's capacity for hierarchical dynamics can be controlled systematically. By explicitly allowing or suppressing collective motion, we quantify its effects. We find that coarsening within a two dimensional attractive lattice gas (and an analogous off-lattice model in three dimensions) is naturally dominated by collective motion over a broad range of temperatures and densities. Under such circumstances, cluster mobility inhibits the development of uniform coexisting phases, especially when macroscopic segregation is strongly favored by thermodynamics. By contrast, the assembly of model viral capsids is not frustrated but is instead facilitated by collective moves, which promote the orderly binding of intermediates consisting of several monomers
Targeting microRNAs as a therapeutic strategy to reduce oxidative stress in diabetes
No full textDiabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia as a consequence of pancreatic β cell loss and/or dysfunction, also caused by oxidative stress. The molecular mechanisms involved inβ cell dysfunction and in response to oxidative stress are also regulated by microRNAs (miRNAs). miRNAs are a class of negative gene regulators, which modulate pathologic mechanisms occurring in diabetes and its complications. Although several pharmacological therapies specifically targeting miRNAs have already been developed and brought to the clinic, most previous miRNA-based drug delivery methods were unable to target a specific miRNA in a single cell type or tissue, leading to important off-target effects. In order to overcome these issues, aptamers and nanoparticles have been described as non-cytotoxic vehicles for miRNA-based drug delivery. These approaches could represent an innovative way to specifically target and modulate miRNAs involved in oxidative stress in diabetes and its complications. Therefore, the aims of this review are: (i) to report the role of miRNAs involved in oxidative stress in diabetes as promising therapeutic targets; (ii) to shed light onto the new delivery strategies developed to modulate the expression of miRNAs in diseases
Non-coding RNAs: novel players in insulin resistance and related diseases
No full textThe rising prevalence of metabolic diseases related to insulin resistance (IR) have stressed the urgent need of accurate and applicable tools for early diagnosis and treatment. In the last decade, non-coding RNAs (ncRNAs) have gained growing interest because of their potential role in IR modulation. NcRNAs are variable-length transcripts which are not translated into proteins but are involved in gene expression regulation. Thanks to their stability and easy detection in biological fluids, ncRNAs have been investigated as promising diagnostic and therapeutic markers in metabolic diseases, such as type 2 diabetes mellitus (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). Here we review the emerging role of ncRNAs in the development of IR and related diseases such as obesity, T2D and NAFLD, and summarize current evidence concerning their potential clinical application
The Landscape of microRNAs in βCell: between phenotype maintenance and protection
No full textDiabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules
Cranial trepanation. An ancient neurosurgical therapy? Thoughts of a follower of positivist medicine and anthropology
No full textThe authors' aim is to define a framework around the history of studies and analyses on cranial trepanation. In addition, based on the analytical approach of Abele de Blasio, the authors would like to reach an understanding of the various different interpretations of the origin and aetiology of the art of cranial trepanation, starting in the prehistoric era. In this brief study, historical discussions are intertwined with ethnoiatric and anthropometric techniques of the author, leading the reader into a fascinating discussion on the practice of trepanation in ancient populations
Double, Ghost and Mother: Communicating Vessels in Valeria Luiselli's Los ingrávidos
No full textpeer reviewedEn este ensayo analizamos conjuntamente los temas del Doble, del fantasma y de la maternidad en Los ingrávidos (2011), de Valeria Luiselli, porque tal como leemos la novela estos funcionan como vasos comunicantes recorridos por los mismos motivos: un trastorno del cuerpo y una dispersión de la personalidad. Después de examinar la forma en que la autora se apropia de las figuras literarias del Doble y del fantasma nos centramos en sus enlaces e intersecciones con la experiencia materna de la narradora-protagonista, cuyas fronteras corporales se fluidifican y que aparece simbólicamente dividida entre pasado y presente, trabajo y cuidado de los hijos, vida personal y responsabilidades maternas.In this essay we analyse together the themes of the Double, the ghost and motherhood in Valeria Luiselli’s Los ingrávidos (2011) [Faces in the Crowd (2014)], because according to our reading of the novel they function as communicating vessels traversed by the same motifs: a disturbance of the body and a dispersion of the personality. After examining the way the author appropriates the literary figures of the Double and the ghost, we focus on their junctions and intersections with the maternal experience of the narrator-protagonist, whose bodily borders become fluid and who symbolically appears scattered between past and present, work and child care, personal life and maternal responsibilities
Un anello ebraico in bronzo da Porto Torres (sec. IV-V e.v.), e l'epigrafe di Anabatia rinvenuta a Gerace (sec. XIV), con una nota su una lucerna funeraria ebraica da Licata (secc. IV-V e.v.)
No full textThe study presents a number of new archaeological discoveries of Jewish artifacts and proposes a new reading of an already known inscription. Perani, author of Part I, describes a recently discovered Jewish bronze ring from Porto Torres, Sardinia, dating to late antiquity (4th-5th centuries e.v.), relating to similar Jewish rings, discovered in Sicily and Sardinia in the past. Colafemmina, author of Part II, presents his reading of the inscription of Anabatyya found in 1990 in Gerace, province of Reggio Calabria. Finally, M.S. Rizzo and A. Toscano Raffa describe a recently discovered Jewish funerary lamp with menorah from late Roman period (4th-5th centuries), just found in Licata (Sicily)
Five brains of alienated criminals. Neurological investigations of early twentieth century criminal anthropology
No full textBackground: For the followers of criminal anthropology, during the second half of the 19th and the beginning of the 20th century, the association “anatomical anomaly – psyche anomaly” represented an immediate diagnostic tool to identify mental illness and consequently the tendency to become a criminal. In this article, we analyse a clinical report published in 1900 in which the author, Dr. Saporito, described five brains of alienated criminals from the Aversa asylum. Methods: Through the observations of Dr. Saporito's autoptic evaluations and the literature of the times, the beliefs of the positivist science of that time are highlighted. Results: The identification of multiple physical anomalies focused on the brains, with particular attention to the alteration at the level of some fissures, could lead to identify psychiatric disorders and criminal tendency. Conclusions: From the observations presented here, the author reiterated that several anomalies recorded in these five brains reproduced atavistic characteristics, which disappeared in the ontogenetic and phylogenetic evolution of the human brain
Efficacy of 8 weeks elbasvir/grazoprevir regimen for naïve-genotype 1b, HCV infected patients with or without glucose abnormalities: Results of the EGG18 study
No full textBackground and aim: Direct Acting Antivirals(DAAs) achieve the highest rate of sustained viral re- sponse(SVR) in patients with genotype-1b(G1b) Hepatitis C virus(HCV) infection. Reducing treatment du- ration can simplify the management and improve adherence of therapy. Patients and methods: The study evaluates the efficacy of 8 weeks of elbasvir/grazoprevir regimen in 75 treatment-naïve(TN), G1b patients with mild-moderate fibrosis(Liver Stiffness by Fibroscan®< 9.0 kPa). Viral load(VL) has been evaluated by Roche TaqMan RT-PCR(LLOQ < 15 IU/ml). Results: Mean age was 61.0 ±14.2 years, 44% were male, mean LS by Fibroscan®was 6.1 ±1.8 kPa. Twenty-eight patients(37.3%) had an HOMA > 2.5. Two patients were excluded from analysis(one dropped out and the other one had diagnosed genotype 2c at genotyping by sequencing performed after relapse). At 8 weeks(EOT), 71 out of 73 patients(97.3%) had undetectable HCV-RNA, while in two cases HCV- RNA was detectable but with VL < 15 IU/ml. Both of them achieved SVR. Two G1b patients relapsed at 12 weeks of follow-up, both with baseline VL > 80 0,0 0 0 IU/ml and HOMA score 1.3 and 3.8 respectively. Both had undetectable HCV VL at 4th week and at the EOT. Modified intention-to-treat SVR12 for G1b patients was 71/73(97.3%). Conclusion: In naïve, genotype-1b HCV-infected patients with mild/moderate liver fibrosis, short course of 8 weeks of EBR/GZR appears to achieve high efficacy regardless of features of insulin resistance
Increased Expression of Viral Sensor MDA5 in Pancreatic Islets and in Hormone-Negative Endocrine Cells in Recent Onset Type 1 Diabetic Donors
No full textThe interaction between genetic and environmental factors determines the development of type 1 diabetes (T1D). Some viruses are capable of infecting and damaging pancreatic β-cells, whose antiviral response could be modulated by specific viral RNA receptors and sensors such as melanoma differentiation associated gene 5 (MDA5), encoded by the IFIH1 gene. MDA5 has been shown to be involved in pro-inflammatory and immunoregulatory outcomes, thus determining the response of pancreatic islets to viral infections. Although the function of MDA5 has been previously well explored, a detailed immunohistochemical characterization of MDA5 in pancreatic tissues of nondiabetic and T1D donors is still missing. In the present study, we used multiplex immunofluorescence imaging analysis to characterize MDA5 expression and distribution in pancreatic tissues obtained from 22 organ donors (10 nondiabetic autoantibody-negative, 2 nondiabetic autoantibody-positive, 8 recent-onset, and 2 long-standing T1D). In nondiabetic control donors, MDA5 was expressed both in α- and β-cells. The colocalization rate imaging analysis showed that MDA5 was preferentially expressed in α-cells. In T1D donors, we observed an increased colocalization rate of MDA5-glucagon with respect to MDA5-insulin in comparison to nondiabetic controls; such increase was more pronounced in recent-onset with respect to long-standing T1D donors. Of note, an increased colocalization rate of MDA5-glucagon was found in insulin-deficient-islets (IDIs) with respect to insulin-containing-islets (ICIs). Strikingly, we detected the presence of MDA5-positive/hormone-negative endocrine islet-like clusters in T1D donors, presumably due to dedifferentiation or neogenesis phenomena. These clusters were identified exclusively in donors with recent disease onset and not in autoantibody-positive nondiabetic donors or donors with long-standing T1D. In conclusion, we showed that MDA5 is preferentially expressed in α-cells, and its expression is increased in recent-onset T1D donors. Finally, we observed that MDA5 may also characterize the phenotype of dedifferentiated or newly forming islet cells, thus opening to novel roles for MDA5 in pancreatic endocrine cells
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