Metal–Organic Framework Nanoparticles Induce Pyroptosis in Cells Controlled by the Extracellular pH

Ion homeostasis is essential for cellular survival, and elevated concentrations of specific ions are used to start distinct forms of programmed cell death. However, investigating the influence of certain ions on cells in a controlled way has been hampered due to the tight regulation of ion import by cells. Here, it is shown that lipid-coated iron-based metal–organic framework nanoparticles are able to deliver and release high amounts of iron ions into cells. While high concentrations of iron often trigger ferroptosis, here, the released iron induces pyroptosis, a form of cell death involving the immune system. The iron release occurs only in slightly acidic extracellular environments restricting cell death to cells in acidic microenvironments and allowing for external control. The release mechanism is based on endocytosis facilitated by the lipid-coating followed by degradation of the nanoparticle in the lysosome via cysteine-mediated reduction, which is enhanced in slightly acidic extracellular environment. Thus, a new functionality of hybrid nanoparticles is demonstrated, which uses their nanoarchitecture to facilitate controlled ion delivery into cells. Based on the selectivity for acidic microenvironments, the described nanoparticles may also be used for immunotherapy: the nanoparticles may directly affect the primary tumor and the induced pyroptosis activates the immune system.     

An Object-oriented Interpretation of the EAT System

In a previous paper we characterized, in the Category Theory setting, a class of implementations of Abstract Data Types, which has been suggested by the way of programming in the EAT system. (EAT, Effective Algebraic Topology, is one of Sergeraerts systems for effective homology and homotopy computation.) This characterization was established using classical tools, in an unrelated way to the current mainstream topics in the field of Algebraic Specifications. Looking for a connection with these topics, we have found, rather unexpectedly, that our approach is related to some object-oriented formalisms, namely hidden specifications and the coalgebraic view. In this paper, we explore these relations making explicit the implicit object-oriented features of the EAT system and generalizing the data structure analysis we had previously done.     

Expression, purification, reconstitution and inhibition of Ustilago maydis sterol 14 alpha-demethylase (CYP51; P450(14DM))

PURPOSE: To assess the efficacy of percutaneous embolization with an alcoholic solution of zein in the treatment of aneurysmal bone cysts. MATERIALS AND METHODS: Eighteen patients with aneurysmal bone cysts were treated percutaneously with alcoholic zein. The cysts were in the lower limb (n = 7), upper limb (n = 5), pelvis (n = 3), cervical spine (n = 2), and mandible (n = 1). All patients were symptomatic, three had previously undergone surgery. Percutaneous embolization was performed with fluoroscopic or computed tomographic guidance with the patient under general anesthesia. Clinical and imaging follow-up lasted 18 months to 4 years. RESULTS: Percutaneous embolization was performed in 16 cases. In two cases, cystograms showed marked venous drainage and thus embolization was not attempted. Six patients underwent repeat embolization. Complications consisted of a local transitory inflammatory reaction (n = 5), aseptic osteitis (n = 1), and a small pulmonary infarct without sequelae (n = 1). Relief of symptoms was achieved in all patients except one, who underwent surgery. At imaging, improvement was total in 13 cases (87%) and partial in two cases (13%). No recurrence was noted during follow-up. CONCLUSION: Percutaneous embolization of aneurysmal bone cysts with alcoholic zein should be considered a reliable alternative to surgery, especially in cases with a difficult surgical approach or cases of postsurgical recurrence.     

Examining functional content in widely used Health-Related Quality of Life scales.

Purpose: Assess extent to which generic Quality of Life (QOL) and Health-Related Quality of Life (HRQOL) scales include function in assessment of health, and identify health assessment items that are free of functional content. Methods: An expert panel on measurement of health and disability reached consensus on definitions of health, disability, and function. They assessed all items of all generic (non-condition-specific) scales in the 2006 ProQolid database for being important to measuring health as distinct from function. Ratings were summarized as content validity ratios. Retained items were written into standard format and reviewed again by the expert panel and a validity panel with expertise in specific disabilities. Results: Of 85 scales, 21 were retained as containing items important for assessing health. Scales ranged from 100% (BRFSS HRQOL, WHO-5) to only 4% of items rated as important. In further review of “important” items, functional content was identified in many of the items, particularly with regard to mental functioning. Conclusions: Popular generic scales of QOL and HRQOL vary greatly in the degree to which they include content on function. A pool of items can be identified that are relatively free of function. Distinguishing measurement of function and health is particularly important for people with long-standing functional limitations and for assessing the relationship of health with function. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A time-frame model of termination in psychotherapy.

Presents a 7-session time-frame model for the termination of individual psychotherapy. Issues appropriate for discussion during those sessions are identified—review of therapy, content, the therapy relationship, and separation and loss. Suggested modifications of the model, depending on such factors as presenting client concerns, duration of treatment, and emphasis that the therapist places on the therapeutic relationship as a vehicle for change, are described. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

p70s6k function is essential for G1 progression

An essential step in the pathway by which growth factors trigger cellular proliferation is the induction of high levels of protein synthesis. This appears in part to be controlled by multiple phosphorylation of the ribosomal protein S6 (refs 4, 5). The main kinase responsible, p70s6k (refs 6-8), is activated through the phosphorylation of four sites clustered in a putative autoinhibitory domain, which is mediated by a signalling pathway distinct from those used by other well characterized mitogen-activated serine/threonine kinases (such as p42/p44mapk or p90rsk; refs 10, 11). Here we investigate the role of p70s6k in the mitogenic response. Microinjection of quiescent rat embryo fibroblasts with any of three distinct polyclonal antibodies to p70s6k abolishes serum-induced entry into S phase of the cell cycle. This effect is preceded by almost complete abrogation of the activation of protein synthesis and the expression of an essential immediate early gene product, c-fos. The inhibitory effect on DNA synthesis is also elicited by microinjection of the antibodies late in G1 phase, consistent with the finding that p70s6k activity remains high throughout G1.     

The relationship between in-treatment abstinence and post-treatment abstinence in a smoking cessation treatment.

Previous research has indicated that abstinence early in a smoking cessation program is predictive of successful posttreatment abstinence. However, it has not been established whether or not this effect is independent of other in-treatment abstinence patterns. In this paper the relationship between three potentially important aspects of in-treatment smoking abstinence and posttreatment smoking abstinence are examined: early abstinence, extended abstinence, and end-of-treatment abstinence. We examined the relationship between smoking behavior measured each weekday over 70 visits (approximately 14 weeks) of a contingency management smoking cessation program and at a follow-up visit 6 months after study entry (3 months after the scheduled end of treatment). Ninety-five of 102 participants were successfully followed-up. Seven of these 95 participants were confirmed abstinent. Early abstinence, defined as abstinence during the first 10 treatment visits, was significantly and independently related to follow-up abstinence (OR = 56.67 [7.29–440.63]). Extended abstinence and end-of-treatment abstinence were related to follow-up abstinence, but not independent of early abstinence based on multiple regression models. Inclusion of a variety of demographic and environmental characteristics did not significantly alter this relationship. Thus, consistent with the previous literature, the establishment of early abstinence appears to be crucial to establishing longer-term abstinence, independent of other in-treatment abstinence patterns. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perspectives on an internship: The passages of training directors during the internship year.

Proposes a model to explain the transitions experienced by training directors during an internship year. Six transitions are identified, including courting, bonding, rapprochement, mentoring, launching, and reunion, and the particular behaviors and events that signal each passage are described. These transitions are contrasted with those often experienced by interns. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)