Current and emerging intralesional immunotherapies in cutaneous oncology.

Immunotherapies have revolutionized the management of advanced cutaneous malignancies. However, some patients fail to respond to these therapies, others are ineligible because of comorbidities, and a minority of patients experience treatment-limiting systemic immune-related adverse events. To address these issues and expand treatment options for patients with early-stage disease, a variety of immunotherapies are being developed for direct intratumoral administration.

Range-wide persistence of the endangered arroyo toad () for 20+ years following a prolonged drought.

Prolonged drought due to climate change has negatively impacted amphibians in southern California, U.S.A.

A case of vancomycin-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome with failure to respond to cyclosporine treatment.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare delayed drug reaction that often occurs 2-6 weeks after initiation of therapy and may develop into a life-threatening systemic reaction. Besides immediate discontinuation of the suspected inciting drug, initiation of high dose systemic corticosteroids has long been the mainstay of treatment for severe cases. Nevertheless, significant drawbacks associated with systemic corticosteroid therapy, such as the requirement of a long tapering period post resolution and extensive adverse side effects profile, have motivated clinicians to seek alternative treatment options.

Improvement in exercise duration, lung function and well-being in G551D-cystic fibrosis patients: a double-blind, placebo-controlled, randomized, cross-over study with ivacaftor treatment.

Unlabelled: G551D, a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in CF is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor.

Partial Functional Diversification of Drosophila melanogaster Septin Genes Sep2 and Sep5.

The septin family of hetero-oligomeric complex-forming proteins can be divided into subgroups, and subgroup members are interchangeable at specific positions in the septin complex. Drosophila melanogaster has five septin genes, including the two SEPT6 subgroup members Sep2 and Sep5 We previously found that Sep2 has a unique function in oogenesis, which is not performed by Sep5 Here, we find that Sep2 is uniquely required for follicle cell encapsulation of female germline cysts, and that Sep2 and Sep5 are redundant for follicle cell proliferation. The five D.

Pulmonary and systemic pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients: targeting advantage of inhalational administration.

The purpose of this study was to define the pulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following intravenous (i.v.) and inhaled administration in cystic fibrosis (CF) patients.

The Drosophila melanogaster septin gene Sep2 has a redundant function with the retrogene Sep5 in imaginal cell proliferation but is essential for oogenesis.

Septins are cytoskeletal proteins that form hetero-oligomeric complexes and function in many biological processes, including cytokinesis. Drosophila melanogaster has five septin genes. Sep5, which is the most recently evolved septin gene in Drosophila, is a retrogene copy of Sep2.

Evolution of three parent genes and their retrogene copies in Drosophila species.

Retrogenes form a class of gene duplicate lacking the regulatory sequences found outside of the mRNA-coding regions of the parent gene. It is not clear how a retrogene's lack of parental regulatory sequences affects the evolution of the gene pair. To explore the evolution of parent genes and retrogenes, we investigated three such gene pairs in the family Drosophilidae; in Drosophila melanogaster, these gene pairs are CG8331 and CG4960, CG17734 and CG11825, and Sep2 and Sep5.

Transcriptional regulation of the purine de novo synthesis gene Prat in Drosophila melanogaster.

The first step of the purine de novo synthesis pathway is catalyzed by amidophosphoribosyltransferase (E.C.2.

A link between impaired purine nucleotide synthesis and apoptosis in Drosophila melanogaster.

The biosynthetic pathways and multiple functions of purine nucleotides are well known. However, the pathways that respond to alterations in purine nucleotide synthesis in vivo in an animal model organism have not been identified. We examined the effects of inhibiting purine de novo synthesis in vivo and in cultured cells of Drosophila melanogaster.

Modifiers of Prat, a de novo purine synthesis gene, in Drosophila melanogaster.

Drosophila melanogaster was used to identify genes with a potential role in genetic regulation of purine biosynthesis. In this study we examine two dominant genetic modifiers of the essential gene Prat, which encodes amidophosphoribosyltransferase (EC 2.4.

Protection of Salmonella by ampicillin-resistant Escherichia coli in the presence of otherwise lethal drug concentrations.

Microbial systems have become the preferred testing grounds for experimental work on the evolution of traits that benefit other group members. This work, based on conceptual and theoretical models of frequency-dependent selection within populations, has proven fruitful in terms of understanding the dynamics of group beneficial or 'public goods' traits within species. Here, we expand the scope of microbial work on the evolution of group-beneficial traits to the case of multi-species communities, particularly those that affect human health.

Evolution of altruists and cheaters in near-isogenic populations of Escherichia coli.

Emergence of antibiotic-resistant bacteria threatens the continued efficacy of many critical drugs used to treat serious infections. What if such resistant organisms could also act as altruists and "share" their resistance with sensitive cohorts without any actual genetic exchange? We competed resistant strains that differ solely in their ability to secrete a plasmid-encoded beta-lactamase. Sensitive strains were otherwise isogenic with their resistant counterparts and were either plasmid-free or contained a "Dummy" plasmid of roughly the same size as that of the resistance plasmids.

Expression pattern diversity and functional conservation between retroposed PRAT genes from Drosophila melanogaster and Drosophila virilis.

Gene duplication by retrotransposition duplicates only the coding and untranslated regions of a gene and, thus, biases retroduplicated genes toward having different expression patterns from their parental genes. As such, genes duplicated by retrotransposition are more likely to develop novel expression domains. To explore this idea further, we used the Prat/Prat2 gene duplication in Drosophila as a case study to examine the aftermath of a retrotransposition event that resulted in both the parent and the child gene becoming essential for survival.

The benign course of liver disease in adults with cystic fibrosis and the effect of ursodeoxycholic acid.

Background And Aims: The life expectancy of patients with cystic fibrosis (CF) has been increasing and the associated liver disease has emerged as a significant medical issue. Our aim was to describe the clinical features, course and effect of ursodeoxycholic acid (UDCA) on liver disease in an adult CF population.

Study: From 1983 to 2005, 278 patients with CF were followed up at the Alfred Hospital, an adult tertiary referral centre.

An artificial mitochondrial tail signal/anchor sequence confirms a requirement for moderate hydrophobicity for targeting.

Tail-anchored proteins are a group of membrane proteins oriented with their amino terminus in the cytoplasm and their carboxy terminus embedded in intracellular membranes. This group includes the apoptosis-mediating proteins of the Bcl-2 family as well as the vesicle targeting proteins of the SNARE group, among others. A stretch of hydrophobic amino acids at the extreme carboxy terminus of these proteins serves both as a membrane anchor and as a targeting signal.

Parent genes of retrotransposition-generated gene duplicates in Drosophila melanogaster have distinct expression profiles.

Genes arising by retrotransposition are always different from their parent genes from the outset. In addition, the cDNA must insert into a region that allows expression or it will become a processed pseudogene. We sought to determine whether this class of gene duplication differs from other gene duplications based on functional criteria.

Interleukin-10 production after pro-inflammatory stimulation of neutrophils and monocytic cells of the newborn. Comparison to exogenous interleukin-10 and dexamethasone levels needed to inhibit chemokine release.

Background: Neutrophils followed by monocytic cells are recruited into the lung during the early development of bronchopulmonary dysplasia (BPD).

Objectives: We determined: (1) the capacity of polymorphonuclear leukocytes (PMNs) and peripheral blood monocytic cells (PBMCs) of the newborn to produce and release the anti-inflammatory cytokine, interleukin (IL)-10, after stimulation by lipopolysaccharide (LPS) or tumor necrosis factor (TNF), and (2) the levels of exogenous IL-10 and/or dexamethasone (DEX) needed to inhibit the release of the pro-inflammatory chemokine IL-8 from stimulated cells.

Methods: PMNs and PBMCs were isolated from cord blood of healthy term infants.

Cytotoxic and mutagenic effects of tobacco-borne free fatty acids.

Tobacco smoke contains substances capable of binding iron in an aqueous medium and transferring the metal into both organic solvents and intact mammalian red cells. This iron-binding activity is due to free fatty acids which are abundant in tobacco smoke and form 2:1 (free fatty acid:iron) chelates with ferrous iron. These earlier observations suggested that smoke-borne free fatty acids and the associated delocalization of iron within the lung might contribute to both the chronic pulmonary inflammation and the carcinogenesis associated with smoking.

The purine synthesis gene Prat2 is required for Drosophila metamorphosis, as revealed by inverted-repeat-mediated RNA interference.

PRAT (phosphoribosylamidotransferase; E.C. 2.

Telomerase-immortalized human fibroblasts retain UV-induced mutagenesis and p53-mediated DNA damage responses.

Immortalized cells frequently have disruptions of p53 activity and lack p53-dependent nucleotide excision repair (NER). We hypothesized that telomerase immortalization would not alter p53-mediated ultraviolet light (UV)-induced DNA damage responses. DNA repair proficient primary diploid human fibroblasts (GM00024) were immortalized by transduction with a telomerase expressing retrovirus.

Drosophila melanogaster Prat, a purine de novo synthesis gene, has a pleiotropic maternal-effect phenotype.

In Drosophila melanogaster, two genes, Prat and Prat2, encode the enzyme, amidophosphoribosyltransferase, that performs the first and limiting step in purine de novo synthesis. Only Prat mRNA is present in the female germline and 0- to 2-hr embryos prior to the onset of zygotic transcription. We studied the maternal-effect phenotype caused by Prat loss-of-function mutations, allowing us to examine the effects of decreased purine de novo synthesis during oogenesis and the early stages of embryonic development.