58 research outputs found

    Herpes simplex virus-type1 (HSV-1) impairs DNA repair in cortical neurons

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    Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer's disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions

    Synthesis and Characterization of a Colloidal Novel Folic Acid–β-cyclodextrin Conjugate for Targeted Drug Delivery

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    A novel folic acid–b-cyclodextrin (b-CD) conjugate was synthesized and preliminarily characterized by 1H NMR, ESI-MS, and MALDI-MS. 1H NMR shows the presence of a- and c-conjugates which are generated by b-CD linkage in turn with both carboxylic functions of folic acid. Moreover ROESY evidences supramolecular interactions between the benzene ring of the folic acid and the b-CD cavity. DOSY suggests that ethylenediamine derived b-CD–folic acid forms a colloidal dispersion difficult to purify from free folic acid. An analysis of self-diffusion coefficient (Ds) of the three species (a-, c-conjugates, and free folic acid) and relaxation times (T1 and T2) is reported to tentatively explain the colloidal behaviour of the new species in an aqueous solution

    Influence of Hashimoto thyroiditis on the development of thyroid nodules and cancer in children and adolescents

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    It is unclear whether patients with Hashimoto thyroiditis (HT) are predisposed to develop thyroid nodules and/or thyroid cancer. The objective of our study was therefore to assess the prevalence of thyroid nodules and/or cancer in patients with HT and to look for possible prognostic factors. A retrospective survey of 904 children/adolescents with HT (709 females, 195 males) regularly followed in nine Italian centers of pediatric endocrinology was performed. Median period of follow-up was 4.5 years (1.2 to 12.8 years). We evaluated free T4, TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies, and thyroid ultrasound yearly. One hundred seventy-four nodules were detected, with an annual incidence rate of 3.5%. Ten nodules were malignant (8 papillary and 2 papillary follicular variant), giving a 5.7% prevalence of cancer among patients with nodules. The severity of hypo-echogenity at ultrasound, TPOAb, and free T4 serum concentrations were predictive for the appearance of new nodules. Furthermore, a positive correlation was observed between TPOAb titer and the development of thyroid cancer. In conclusion, HT seems to influence the development of thyroid nodules, but not cancer in children and adolescents

    Reconnaissance of 2016 Central Italy Earthquake Sequence

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    The Central Italy earthquake sequence nominally began on 24 August 2016 with a M6.1 event on a normal fault that produced devastating effects in the town of Amatrice and several nearby villages and hamlets. A major international response was undertaken to record the effects of this disaster, including surface faulting, ground motions, landslides, and damage patterns to structures. This work targeted the development of high-value case histories useful to future research. Subsequent events in October 2016 exacerbated the damage in previously affected areas and caused damage to new areas in the north, particularly the relatively large town of Norcia. Additional reconnaissance after a M6.5 event on 30 October 2016 documented and mapped several large landslide features and increased damage states for structures in villages and hamlets throughout the region. This paper provides an overview of the reconnaissance activities undertaken to document and map these and other effects, and highlights valuable lessons learned regarding faulting and ground motions, engineering effects, and emergency response to this disaster

    PS-02-011 Sexism and sexual dysfunctional beliefs: exploring the association with sexual and relational satisfaction

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    The objective of the present study is to explore the correlation between these attitudes and levels of sexism, social homophobia and internalized sexual stigma. Methods: The participants were 826 (534 F, 292 M), aged between 17 and 70. 59,8% defined him/her-self as “exclusively heterosexual”, 29,2% as “exclusively homosexual” and 11% as “bisexual”. The following tests have been administered: Questionnaire on socio-demographic Information, Ambivalent Sexism Inventory; Measure of Internalized Sexual Stigma for Lesbians and Gays; Modern Homophobia Scale, The Katuzny Same-sex Marriage Scale; D’Amore and Green Same-sex Parenting Scale. Results: Positive correlations have been found between: sexism and homophobia (r ¼ .378; p < .01) and sexism and internalized sexual stigma (r ¼ .320; p < .01). Male subjects obtained higher scores in sexism (F(1,559) ¼ 15,555; p < .01) and homophobia (F(1,559) ¼ 44,977; p < .01). Heterosexuals were significantly less favorable regarding gay and lesbian marriage (F(1,821) ¼ 96,936; p < .05) and parenthood (F(1,821) ¼ 84,260; p < .05) compared to the non-heterosexuals. Heterosexual males were the most unfavorable towards parenting (F(1,821) ¼ 4,786; p < .05). Conclusion: The results offer a contribute to scientific research which still has significant gaps regarding the attitude-associated variables towards marriage and parenting between people of the same gender. Sexual education at schools and clinic supervision interventions should take these evidences into account. Policy of full disclosure: None

    Transient Sulfenic Acids in the Synthesis of Biologically Relevant Products

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    Sulfenic acids as small molecules are too unstable to be isolated and their transient nature offers the possibility to involve them in concerted processes that lead to the obtainment of functional groups such as sulfoxides, sulfones, and disulfides. All these functions are present in a number of natural and synthetic drugs and can represent structural motives inducing biologically relevant properties. In this small review the generation and reactions of sulfenic acid bearing naturally occurring residues are described. Carbohydrate and aminoacid-derived sulfenic acids have been used in concerted addition with triple bonds to obtain alliin derivatives and thiosugars in enantiomerically pure form. Glycoconjugates with sulfinyl, sulfonyl, and disulfane functional groups and pyridine-derived disulfides have been obtained from bis- and tris-sulfinyl precursors of sulfenic acids. Small families of such compounds have been subjected to preliminary biological tests. Starting from the evidence that the control of molecular architecture and the presence of suitable functional groups can play a significant role on the exhibition of biological properties, apoptotic effects on malignant cells by glycoconjugates and inhibitory activity against the important human pathogen S. aureus by pyrimidine-derived disulfides have been found
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