Replication protein A and proliferating cell nuclear antigen coordinate DNA polymerase selection in 8-oxo-guanine repair

The adenine misincorporated by replicative DNA polymerases (pols) opposite 7,8-dihydro-8-oxoguanine (8-oxo-G) is removed by a specific glycosylase, leaving the lesion on the DNA. Subsequent incorporation of C opposite 8-oxo-G on the resulting 1-nt gapped DNA is essential for the removal of the 8-oxo-G to prevent G–C to T–A transversion mutations. By using model DNA templates, purified DNA pols β and λ and knockout cell extracts, we show here that the auxiliary proteins replication protein A and proliferating cell nuclear antigen act as molecular switches to activate the DNA pol λ- dependent highly efficient and faithful repair of A:8-oxo-G mismatches in human cells and to repress DNA pol β activity. By using an immortalized human fibroblast cell line that has the potential to induce cancer in mice, we show that the development of a tumoral phenotype in these cells correlated with a differential expression of DNA pols λ and β.     

New generation biologics for the treatment of psoriasis and psoriatic arthritis. State of the art and considerations about the risk of infection

Psoriasis is a chronic immune‐mediated disease characterized by inflammation of skin (psoriasis) or joints (psoriatic arthritis) or both, resulting from a dysregulation in particular of the T helper (Th)17 functions. There is no available cure for psoriasis, and a life‐long treatment is needed to control signs and symptoms. Research interest is high around the newest biological drugs approved for the treatment of moderate to severe psoriasis and psoriatic arthritis, and especially drugs blocking the IL‐23/IL‐17 axis. Our aim is to review the new biological drugs for the treatment of psoriasis and their adverse effects, focusing on the risk of infections.     

Leber hereditary optic neuropathy plus dystonia,and transverse myelitis due to double mutations in MT-ND4 and MT-ND6

Journal of Neurology - Leber hereditary optic neuropathy (LHON) typically presents as painless central or centrocecal scotoma and is due to maternally inherited mitochondrial DNA (mtDNA) mutations....     

The C(-260)>T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction

Abstract. CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide.Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients with and acute myocardial infarction 213 healthy controls were included in the study. Genotype frequencies of the C(-260)T polymorphism in the CD14 promoter were determined by polimerase chain reaction and the amplified product was cleaved with HaeIII. The frequency of the T allele was not significantly different in patients compared with controls. In this study we were not able to detect differences of frequency of the allele T (-260) in the promoter of the CD14 receptor gene in survivors of myocardial infarction and controls.     

HIV‐associated psoriasis: Epidemiology,pathogenesis, and management

People living with HIV (PLWH) are affected by a higher incidence skin disorders, which are often associated with high morbidity and mortality. In particular, psoriasis affects PLWH severely and for a longer time than the general population. Human immunodeficiency virus (HIV) infection is characterized by a progressive decrease in CD4⁺ T‐cell count, and it could seem paradoxical that psoriasis exacerbations are more frequent in this subset of patients than the general population, even though it is commonly observed at any stage of infection. For a long time, there have been limited therapeutic choices for PLWH affected by psoriasis. The introduction of the combined antiretroviral therapy dramatically changed the natural course of both HIV and psoriasis in PLWH, leading to an improvement of quality and duration of life. However, the clinical severity of psoriasis in PLWH often requires the use of immunosuppressant drugs. Knowledge about their safety and efficacy are limited to case‐reports, small case‐series and studies, therefore their use has not yet entered the routine. Further studies are needed to determine if immunosuppressive drugs can be safely and effectively used in PLWH affected by psoriasis and other autoimmune disorders.     

Treatment of sexual dysfunctions secondary to male infertility with sildenafil citrate

With the assumption that infertility and related diagnostic and therapeutic processes are stressful, an uncontrolled pilot study was designed to evaluate the effect of sildenafil citrate on sexual compliance and reproductive outcome. A group of sexually healthy men were studied after the administration of 50 mg sildenafil before semen collection for intrauterine artificial insemination (n = 25) or planned intercourse for a postcoital test (n = 12). We demonstrated that sexual dysfunction is highly prevalent in patients undergoing diagnostic procedures for infertility, and that sildenafil is effective in reversing stress-induced transitory impotence. Furthermore, sildenafil improved some seminal parameters, such as the percentage of spermatozoa with linear progressive motility, as well as the number of spermatozoa penetrating the cervical mucus. Two pregnancies were obtained after sildenafil administration.     

Exposure to mother's pregnancy and lactation in infancy is associated with sexual attraction to pregnancy and lactation in adulthood

IntroductionSeveral theories, including psychodynamic theories, sexual imprinting and early conditioning have been formulated to explain sexual development. Empirical data, however, remain insufficient for a thorough evaluation of these theories.AimIn this study, we test the hypothesis that a critical period exists for the acquisition of sexual preferences, as suggested by empirical findings in birds and mammals (sexual imprinting).MethodsAn Internet questionnaire was used.Main Outcome MeasuresWe gather data from individuals with a sexual preference for pregnant and/or lactating women, under the hypothesis that pregnancy or lactation may become sexually attractive in adulthood following an exposure to pregnant or lactating women in infancy.ResultsWe find that these preferences are more common in older siblings, i.e., in individuals who have been exposed to more maternal pregnancy and lactation. This result is independent of respondent and sibling sex. In addition, only maternal pregnancies and lactations experienced between 1.5 and 5 years of age are associated with the preferences.ConclusionsWe discuss our findings in relation to theories of sexual development and to earlier reports of birth order effects on sexual behavior. We suggest that this age range may constitute a sensitive period for the acquisition of sexual preferences. Enquist M, Aronsson H, Ghirlanda S, Jansson L, and Jannini EA. Exposure to mother's pregnancy and lactation in infancy is associated with sexual attraction to pregnancy and lactation in adulthood.