Polymerase alpha components associate with telomeres to mediate overhang processing

Telomeres consist of TTAGGG repeats, which end with a 3\u27 G-overhang and are bound by a six-protein complex, known as Shelterin. In humans, telomeres shorten at each cell division, unless telomerase is expressed and able to add telomeric repeats to the 3\u27 G-overhang. However, for effective telomere maintenance, the DNA strand complementary to that made by telomerase must be synthesized. In this study, I focused on the Polα/primase complex, in particular the subunits p68 (POLA2, the regulatory subunit) and p180 (Polα, the catalytic subunit), and their potential roles at telomeres. I was able to detect p180, p68 and OBFC1, a subunit in the CST complex, at telomeres in S phase using chromatin immunoprecipitations. I could also show that OBFC1, Shelterin and Polα/primase interact, revealing contacts occurring at telomeres. Finally, depletion of p68 by shRNA and p68 and p180 by siRNA, led to increased overhang amounts at telomeres. I propose a model in which Polα-primase is important for proper telomeric overhang processing, perhaps through fill-in synthesis. These results shed light on important events necessary for efficient telomere maintenance and protection

Histórias de vida : (des) proteções sociais vivenciadas pelos familiares de crianças e adolescentes em acolhimento institucional

O presente estudo tem como temática central as proteções e desproteções sociais vivenciadas pelas famílias de crianças e adolescentes em medida de proteção de acolhimento. Foi desenvolvido um estudo de nível exploratório e natureza qualitativa, guiado pelo método Materialista Histórico Dialético, que buscou conhecer qual a percepção que as famílias de crianças e adolescentes em acolhimento institucional, no município de Gravataí/ RS, no ano de 2017, possuem sobre a situação de acolhimento e de (des) Proteção Social vivenciada pelas famílias. Tomaram-se como sujeitos do estudo seis familiares de crianças e adolescentes em acolhimento no município, no ano de 2017. A pesquisa utilizou a metodologia de História de Vida para possibilitar escuta e visibilidade às narrativas dos sujeitos. A proteção social é destacada neste estudo, como fundamental, em meio à perversidade e violência do modelo de acumulação capitalista – sendo um instrumento que serve à reprodução do capital, mas que, em um processo dialético, é também uma conquista da classe trabalhadora. As perspectivas preponderantes, em um cenário neoliberal, sobre a função/participação das famílias na execução do sistema de proteção no Brasil, mostram-se com viés Familista e de Pluralismo de Bem-Estar, os quais caminham de encontro aos processos de responsabilização dos indivíduos e famílias por sua proteção. Esses primas e configuração da proteção social, trazem implicações sobre a aplicação da medida de acolhimento de crianças e adolescentes e proteção das famílias. Dessa forma, emergem nesse estudo, trajetórias de vida permeadas por processos de violações de direitos e desproteções sociais, nos quais, muitas vezes, o acolhimento de crianças e adolescentes é resultado desse processo. Ainda, a medida de acolhimento é percebida de forma ambígua pelos familiares: insurge como uma proteção, que garante acesso aos serviços e bens que as famílias não possuem condições de prover; como algo que “não traz coisas boas”; e, também, como uma punição pelo comportamento. Por fim, aponta-se para a necessidade de se direcionar um olhar atento para as famílias das crianças e adolescentes em acolhimento, para compreender quais são trajetórias de vida dessas pessoas, quais as violações de direitos foram e são vivenciadas por elas e como a proteção social, enquanto um sistema, atende suas necessidades e garante as condições para que as crinças e adolescentes tenham o direito à permanência na família. A partir disso, é possível que se construam estratégias, de forma conjunta com os sujeitos, visando superar possíveis vulnerabilidades e riscos sociais e fortalecimento de suas capacidades protetivas.The present study has as its central theme the protection and the lack of social protection experienced by families with children and teenagers in protective measures. A study of exploratory level and qualitative nature was developed guided by the Materialistic Dialectical method, which sought to know what these families’ perception of the program of social care and protection is (in the city of Gravataí in 2017). Six family members of these children and teenagers in social care (in town in 2017) were taken as subjects of the study. The research used the Life History methodology to enable listening and visibility to these relatives’ narratives. Social protection is highlighted, as fundamental, amid the perversity and violence of the capitalist accumulation model - being an instrument that serves the reproduction of capital, but which, in a dialectical process, is also a working-class achievement. The prevailing perspectives, in a neoliberal scenario, on the role/participation of families in the implementation of the protection system in Brazil, present themselves with Familial and Welfare Pluralism bias, which match the processes of accountability of individuals and families for their protection. These prisms and configurations of social protection, have implications over the application of the fostering measures in relation to children and adolescents and the protection of families. Therefore, this study brings out life trajectories permeated by processes of rights violations and social deprotection, where, often, the reception of children and adolescents is the result of this process. Moreover, the measure of institutional home is perceived ambiguously by family members: it emerges as a protection, which guarantees access to services and goods that families cannot afford; As well as something that "doesn’t bring good things"; and is given as a punishment for behavior. Finally, it is pointed out the need to take a close look at the families of these children and teenagers in the institutional home, to understand their life trajectories, which rights violations have been and are experienced by them and how the social protection, while a system, meets their needs and guarantees the conditions for the children and adolescents to have the right to stay in the family. With that in mind, it is possible to build strategies, together with the relatives in order to overcome possible vulnerabilities and social risks and therefore strengthen their protective capacities

Sustainable Recycling of Electric Arc Furnace Steel Slag as Aggregate in Concrete: Effects on the Environmental and Technical Performance

The aim of this research work was the evaluation of the feasibility to utilize industrial by-products, such as electric arc furnace steel slags, for sustainable concrete production. The paper evaluated the environmental and mechanical properties of steel slags and concrete, respectively. Specifically, the release of contaminants from steel slags was investigated by leaching test and the properties of fresh and hardened concrete were evaluated for a concrete mixture designed with a partial substitution (30%) of natural coarse aggregates with electric arc furnace steel slags. The results show that the concentrations of pollutants were lower than the legal limits imposed by the Ministerial Decree 186/2006 and the addition of steel slag can enhance the mechanical performance of concrete. The compressive strength of cubic specimens was also measured after different cycles of alternate wetting–drying. The steel slag incorporation results in a stiffness comparable to that of a traditional concrete. Overall, the mechanical and leaching characterization has shown that the reuse of electric arc furnace steel slags for sustainable concrete production is feasible and reliable

HCV Proteins and Immunoglobulin Variable Gene (IgV) Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved

Hepatitis C virus (HCV) infection may elicit neutralizing antibodies targeting epitopes conserved in all viral genotypes

Anti-hepatitis C virus (HCV) cross-neutralizing human monoclonal antibodies, directed against conserved epitopes on surface E2 glycoprotein, are central tools for understanding virus-host interplay, and for planning strategies for prevention and treatment of this infection. Recently, we developed a research aimed at identifying these antibody specificities. The characteristics of one of these antibodies (Fab e20) were addressed in this study. Firstly, using immunofluorescence and FACS analysis of cells expressing envelope HCV glycoproteins, Fab e20 was able to recognize all HCV genotypes. Secondly, competition assays with a panel of mouse and rat monoclonals, and alanine scanning mutagenesis analyses located the e20 epitope within the CD81 binding site, documenting that three highly conserved HCV/E2 residues (W529, G530 and D535) are critical for e20 binding. Finally, a strong neutralizing activity against HCV pseudoparticles (HCVpp) incorporating envelope glycoproteins of genotypes 1a, 1b, 2a, 2b and 4, and against the cell culture-grown (HCVcc) JFH1 strain, was observed. The data highlight that neutralizing antibodies against HCV epitopes present in all HCV genotypes are elicited during natural infection. Their availability may open new avenues to the understanding of HCV persistence and to the development of strategies for the immune control of this infection

The role of physical activity against chemotherapy-induced peripheral neuropathy: a narrative review

Several studies investigated the side effect of adjuvant cancer treatments, and different types of preventive techniques or treatments have been assessed. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological side effect. Exercise training has been widely studied as an adjuvant therapy to prevent CIPN and improve post-chemotherapy functional outcome and quality of life (QoL). This narrative review aims to summarize the data obtained from the latest studies about physical activity (PA) for the prevention and treatment of CIPN and associated QoL measures. Literature research was conducted to obtain studies including PA interventions for patients with CIPN. Ten studies met inclusion criteria and were therefore summarized and discussed, focusing on exercise type and functional outcome. It seems clear that, regardless of the type of exercise, PA plays a positive role in the treatment of CIPN, providing a significant symptom improvement. There has been no standardization of type, quantity, and intensity of PA administered to the subjects in the various studies probably due to a physiological difference between samples, grade of neuropathy, and difference among therapies

Telomeric and Sub-Telomeric Structure and Implications in Fungal Opportunistic Pathogens

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity levels. In this review, telomere structure, as well as functional implications, will be examined in opportunistic fungal pathogens, including Aspergillus fumigatus, Candida albicans, Candida glabrata, and Pneumocystis jirovecii

JC polyomavirus (JCV) and monoclonal antibodies: friends or potential foes?

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS), observed in immunodeficient patients and caused by JC virus ((JCV), also called JC polyomavirus (JCPyV)). After the HIV pandemic and the introduction of immunomodulatory therapy, the PML incidence significantly increased. The correlation between the use of natalizumab, a drug used in multiple sclerosis (MS), and the PML development of particular relevance. The high incidence of PML in natalizumab-treated patients has highlighted the importance of two factors: the need of PML risk stratification among natalizumab-treated patients and the need of effective therapeutic options. In this review, we discuss these two needs under the light of the major viral models of PML etiopathogenesis

Fast inactivation of SARS-CoV-2 by UV-C and ozone exposure on different materials

The extremely rapid spread of the SARS-CoV-2 has already resulted in more than 1 million reported deaths of coronavirus disease 2019 (COVID-19). The ability of infectious particles to persist on environmental surfaces is potentially considered a factor for viral spreading. Therefore, limiting viral diffusion in public environments should be achieved with correct disinfection of objects, tissues, and clothes. This study proves how two widespread disinfection systems, short-wavelength ultraviolet light (UV-C) and ozone (O3), are active in vitro on different commonly used materials. The development of devices equipped with UV-C, or ozone generators, may prevent the virus from spreading in public places

Pulmonary metastasectomy : an overview

Metastasectomy is the most frequent surgical resection undertaken by thoracic surgeons, being the lung the second common site of metastases. The present oncological criteria for pulmonary metastasectomy are: (I) the primary cancer need to be controlled or controllable; (II) no extrathoracic metastasis-that is not controlled or controllable-exists; (III) all of the tumor must be resectable, with adequate pulmonary reserve; (IV) there are no alternative medical treatment options with lower morbidity. General favourable prognostic features in patients with pulmonary metastases are: (I) one or few metastases; (II) long disease free interval; (III) normal CEA levels in colorectal cancers. Negative predictive features in patients candidate to pulmonary metastasectomies are: (I) active primary cancer; (II) extrathoracic metastases; (III) inability to obtain surgical radicality; (IV) mediastinal lymphatic spread. The lack of controlled trials and studies limited by short follow-up and small cohorts did not allow to overcome some skepticism; moreover, the heterogeneity of these patients in terms of demographic, biologic and histologic characteristics represents a clear limit even in the largest series. On the basis of present knowledge, without results coming from on-going randomized trials, radical resection, histology, and disease free interval seem to be independent prognostic factors identifying a cohort of patients maximally benefitting from lung metastasectomy