Preparation of biomolecule gel matrices for electron microscopy

We report a new sample preparation method that allows the direct transmission electron microscopy evaluation of the architectural characteristics of biomolecules entrapped in gel matrices. We demonstrate that this sample preparation technique can be used for the identification and ultrastructural characterization of liposomes, collagen I and collagen III embedded in gel matrices, and has the potential to be useful for transmission electron microscopy (TEM) characterization of other biomolecule-gel matrix systems.     

A Step Forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach

Breast cancer is one of the most frequently diagnosed malignancies and common causes of cancer death in women. Recent studies suggest that environmental exposures to certain chemicals, such as 7,12-Dimethylbenzanthracene (DMBA), a chemical present in tobacco, may increase the risk of developing breast cancer later in life. The first-line treatments for breast cancer (surgery, chemotherapy or a combination of both) are generally invasive and frequently associated with severe side effects and high comorbidity. Consequently, novel approaches are strongly required to find more natural-like experimental models that better reflect the tumors’ etiology, physiopathology and response to treatments, as well as to find more targeted, efficient and minimally invasive treatments. This study proposes the development and an in deep biological characterization of an experimental model using DMBA-tumor-induction in Sprague-Dawley female rats. Moreover, a photothermal therapy approach using a near-infrared laser coupled with gold nanoparticles was preliminarily assessed. The gold nanoparticles were functionalized with Epidermal Growth Factor, and their physicochemical properties and in vitro effects were characterized. DMBA proved to be a very good and selective inductor of breast cancer, with 100% incidence and inducing an average of 4.7 tumors per animal. Epigenetic analysis showed that tumors classified with worst prognosis were hypomethylated. The tumor-induced rats were then subjected to a preliminary treatment using functionalized gold nanoparticles and its activation by laser (650–900 nm). The treatment outcomes presented very promising alterations in terms of tumor histology, confirming the presence of necrosis in most of the cases. Although this study revealed encouraging results as a breast cancer therapy, it is important to define tumor eligibility and specific efficiency criteria to further assess its application in breast cancer treatment on other species.     

Inhibition of para‐Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels,the Causative Agent of Alkaptonuria

Alkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2‐dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone ( 1 ), an inhibitor of p‐hydroxyphenylpyruvate dioxygenase (4‐HPPD). 1 has been used as a life‐saving drug in infants with type I tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1 , providing the first report of LD₅₀ values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4‐HPPD inhibitors with a more favorable profile than that of 1 in terms of IC₅₀, LD₅₀, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU.     

Synthesis and Structure–Activity Relationship Studies of Benzo[b][1,4]oxazin-3(4H)-one Analogues as Inhibitors of Mycobacterial Thymidylate Synthase X

Since the discovery of a flavin-dependent thymidylate synthase (ThyX or FDTS) that is absent in humans but crucial for DNA biosynthesis in a diverse group of pathogens, the enzyme has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous screening efforts and report herein an optimization campaign of a novel series of inhibitors with a unique inhibition profile. The inhibitors display competitive inhibition toward the methylene tetrahydrofolate cofactor of ThyX, enabling us to generate a model of the compounds bound to their target, thus offering insight into their structure–activity relationships.     

Skateboarders exploring urban public space: Ollies, obstacles and conflicts

This paper reports on an explorative study about skateboarding practices in Amsterdam. One indoor spot and nine street locations for skateboarding were observed and over thirty skaters were interviewed. The research questions concern the identity of the people involved, the group interactions, and the use of urban space and routes. The majority of the observed skateboarders are male middle-class youngsters. In this respect, the skateboarding scene is not very different from other forms of urban public play where men predominate. At the same time, however, skateboarding can be seen as a way of experimenting with new forms of masculinity. Since hanging about by adolescents is mainly a lower-class phenomenon, the middle-class status of the skateboarding youth is surprising. Notwithstanding their individual skateboarding acts, youngsters involved in skateboarding negotiate their claim on specific spaces in groups. The colonizing of public spaces for skateboarding does not remain free of conflict. Groups of skaters are continuously putting public spaces into and out of use. In a sense, skateboarders can be considered the nomads of the city. Their `traveling in packs' results in a map of skate locations which is constantly changing. To understand the phenomenon of skateboarding, further research is needed, not only in Amsterdam but also in other cities and the suburbs.     

Space art: aesthetics design as psychological support

The purpose of this article is to explore the possibilities of art and design in the context of space development. The focus is the effects of arts on feelings, how to enjoy arts as a creator (Ono expressed together with “Art for psychological support”, the paper presented at European Space Agency (ESA), Tools for psychological support during exploration missions to Mars and Moon, Noordwijk, The Netherlands, 2007), supporting the idea of Joseph Beuys that “every human being is an artist” (Art into society, society into art. First published in English in Caroline Tisdall, ICA, London, p 48, 1973). Expression with arts is helpful to find our real selves. When humans create arts, their inner feelings will appear. Art therapy works in this way (Ono in Expressive arts therapy—drawing, clay, music, drama, and dance, Seishinshobo, Japan, 2005). Artistic expressions effect positively the human well-being. This work hypotheses that also in outer space artistic expression will be able to improve astronauts’ quality of life. The topics approached in this article are: (1) Space Art; (2) Psychology and Space Art; (3) Lunar Zen Garden Habitat; (4) Astronaut′s Art.     

Method for quantifying the sample collected by an Andersen Cascade Impactor using total organic carbon analysis

A sensitive and precise method is proposed in which total organic carbon (TOC) analysis is used to quantify aerosol powder samples collected on the stages of an Andersen Cascade Impactor (ACI). In order to demonstrate the versatility of the method, size distributions of powders of varying composition and dose are presented. The results of ACI collections analyzed by both the TOC method and gravimetry are also compared, and particle size distributions created by TOC analysis of ACI collections are compared to aerodynamic size distributions (mass-weighted) acquired with an Aerodynamic Particle Sizer (APS). A TOC analysis of the effects of particle bounce during ACI runs with and without plate surface coatings is also presented. ACI results analyzed by the TOC method and gravimetry were found to be comparable; APS-generated particle size distributions were also found to be similar to those created by TOC analysis of an 8-stage ACI run.     

ADR Briefs

On July 2, 2014, the Fifth Circuit Court of Appeals considered the creation and potential waiver of an arbitration provision in Al Rushaid (ARPD) v. Nat'l Oilwell Varco, Inc., ( 1.usa.gov/1tXonKF ). Plaintiff ARPD had entered into a series of contracts with Aramco to supply certain drilling services. ARPD then entered into contracts with individual defendants, including NOV Norway, to purchase equipment for these oil rigs. The contracts were formed when ARPD accepted the quotations submitted by the defendants. The quotations included certain terms and conditions applicable to the transactions.     

Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bone marrow. In patients affected by multiple myeloma, vitamin D deficiency is commonly correlated with an advanced stage of the disease, greater risk of progression, the development of pathological fractures, and a worse prognosis. Changes in the vitamin D receptor often contribute to the occurrence and progress of deficiencies, which can be overcome by supplementation with vitamin D or analogues. However, in spite of the findings available in the literature, there is no clear standard of care and clinical practice varies. Further research is needed to better understand how vitamin D influences outcomes in patients with monoclonal gammopathies.