A novel aminopeptidase N/CD13 inhibitor selectively targets an endothelial form of CD13 after coupling to proteins.

Aminopeptidase N/CD13, a membrane-bound enzyme upregulated in tumor vasculature and involved in angiogenesis, can be used as a receptor for the targeted delivery of drugs to tumors through ligand-directed targeting approaches. We describe a novel peptide ligand (VGCARRYCS, called "G4") that recognizes CD13 with high affinity and selectivity. Enzymological and computational studies showed that G4 is a competitive inhibitor that binds to the catalytic pocket of CD13 through its N-terminal region. Fusing the peptide C-terminus to tumor necrosis factor-alpha (TNF) or coupling it to a biotin/avidin complex causes loss of binding and inhibitory activity against different forms of CD13, including natural or recombinant ectoenzyme and a membrane form expressed by HL60 promyelocytic leukemia cells (likely due to steric hindrance), but not binding to a membrane form of CD13 expressed by endothelial cells (ECs). Furthermore, G4-TNF systemically administered to tumor-bearing mice exerted anticancer effects through a CD13-targeting mechanism, indicating the presence of a CD13 form in tumor vessels with an accessible binding site. Biochemical studies showed that most CD13 molecules expressed on the surface of ECs are catalytically inactive. Other functional assays showed that these molecules can promote endothelial cell adhesion to plates coated with G4-avidin complexes, suggesting that the endothelial form of CD13 can exert catalytically independent biological functions. In conclusion, ECs express a catalytically inactive form of CD13 characterized by an accessible conformation that can be selectively targeted by G4-protein conjugates. This form of CD13 may represent a specific target receptor for ligand-directed targeted delivery of therapeutics to tumors.

A Tailor-Made, Mirror-Based Infrared Scanner for the Reflectography of Paintings: Development, Features, and Applications.

Since infrared reflectography was first applied in the 1960s to visualize the underdrawings of ancient paintings, several devices and scanning techniques were successfully proposed both as prototypes and commercial instruments. In fact, because of the sensors' small dimension, typically ranging from 0.1 to 0.3 megapixels, scanning is always required. Point, line, and image scanners are all viable options to obtain an infrared image of the painting with adequate spatial resolution. This paper presents a newly developed, tailormade scanning system based on an InGaAs camera equipped with a catadioptric long-focus lens in a fixed position, enabling all movements to occur by means of a rotating mirror and precision step motors. Given the specific design of this system, as the mirror rotates, refocus of the lens is necessary and it is made possible by an autofocus system involving a laser distance meter and a motorized lens. The system proved to be lightweight, low cost, easily portable, and suitable for the examination of large-scale painting surfaces by providing high-resolution reflectograms. Furthermore, high-resolution images at different wavelengths can be obtained using band-pass filters. The in-situ analysis of a 16th-century panel painting is also discussed as a representative case study to demonstrate the effectiveness and reliability of the system described herein.

A pioneer of acrylic painting: new insights into Carmen Herrera's studio practice.

Carmen Herrera, born on May 30th, 1915, is a Cuban American abstract minimalist artist, whose first solo show was held at the Whitney Museum of American Art, New York, in 2016-2017. On this occasion, a scientific study of five paintings from the artist's time in Paris (1948-1953) revealed her pioneering use of solvent-based acrylic paints in post-war Europe. This article presents a second phase of research into Herrera's work aiming to shed light on her studio practice and ascertain the possible presence of other early acrylic paints in her pre-1963 artistic production. A selection of four paintings, namely Iberia #25 (1948), Iberic (1949), Flights of Colors #16 (1949), and Early Dynasty (1953), was subjected to an analytical campaign that relied on both non-invasive and micro-invasive techniques. Results confirmed the use of both oil and solvent-based acrylic paints, supporting our primary research and uncovering the first-known occurrence of acrylic binders in Herrera's Iberia #25. In all cases, the ground layer consists of a mixture of titanium white in its tetragonal form of rutile, anhydrite, and talc, while the color palette was found to be based on both traditional and modern pigments. In most areas, several paint layers appeared to be overlaid on top of one another, revealing a creative process that developed through subsequent compositions. Remnants of earlier paint layers, which appeared to have been scraped off before new ones were applied, were observed directly above the ground in some of the samples examined. In addition, Iberia #25 and Iberic, with analogous geometric and chromatic schemes, underwent technical imaging, which exposed pencil lines and notes underneath the paint layers likely indicative of the intended design and polychromy. Besides corroborating a major alteration in the current scholarship on the availability and use of acrylic-based artists' paints in post-war Europe, this research provides new insights into Herrera's materials, techniques, and studio practice. In addition, the results of this scientific study assisted the development of a suitable treatment plan for Iberic in preparation for its display in The Metropolitan Museum of Art's galleries as part of the museum's 150th anniversary exhibition Making The Met, 1870-2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40494-021-00603-3.

Recent Advances on the Analysis of Polychrome Works of Art: SERS of Synthetic Colorants and Their Mixtures With Natural Dyes.

The development and application of proper sample pretreatments is often a key step toward the successful analysis of dyes used as artists' materials by surface-enhanced Raman spectroscopy (SERS). Complexation of the organic colorants with metal ions to dye fabrics and produce lake pigments, as well as undesired interactions with other matrix components such as substrate, binding media, fillers, and extenders, are just some of the issues that typically complicate dye identification in minute samples from invaluable artworks and museum objects. These concerns may be addressed by using, prior to SERS analysis, ad-hoc sample pretreatments that, in addition to increasing the technique's sensitivity, favorably affect its selectivity toward certain molecules or molecular classes. The present work describes a newly developed sample pretreatment based on the use of nitric acid that has proven crucial for the successful detection of aniline and xanthene dyes-the first synthetic organic colorants to be used in printing and painting, among other art forms-in microscopic samples from works of art such as a 19th-century silk fabric, paper cut-outs by Henri Matisse, Vincent Van Gogh's Irises, and Japanese woodblock prints. This treatment promotes the hydrolysis of the dye-metal bond in mordant dyes or lake pigments, resulting in a more efficient adsorption of the dye molecules on the SERS-active substrate and, hence, enabling the acquisition of high-quality spectra. In the case of synthetic colorants, this method shows advantages over hydrolysis with hydrofluoric acid-a procedure previously established for the analysis of red lakes prepared from natural dyes. The nitric acid treatment presented here may be integrated into a multi-step methodology that, by exploiting differences in solubility of various dyes and lake pigments, has enabled for the first time to successfully characterize intentional mixtures of natural and synthetic colorants of the xanthene and anthraquinone molecular classes, i.e., eosin Y and carmine, in a selection of Japanese prints of the Meiji era. The present study paves the way for the systematic identification of synthetic dyes in objects of artistic and archeological interest, even when they are present in mixtures with natural organic colorants.

Nutritional Characterization and Phenolic Profiling of Moringa oleifera Leaves Grown in Chad, Sahrawi Refugee Camps, and Haiti.

Moringa oleifera is a plant that grows in tropical and subtropical areas of the world. Its leaves are rich of nutrients and bioactive compounds. However, several differences are reported in the literature. In this article we performed a nutritional characterization and a phenolic profiling of M. oleifera leaves grown in Chad, Sahrawi refugee camps, and Haiti. In addition, we investigated the presence of salicylic and ferulic acids, two phenolic acids with pharmacological activity, whose presence in M. oleifera leaves has been scarcely investigated so far. Several differences were observed among the samples. Nevertheless, the leaves were rich in protein, minerals, and ß-carotene. Quercetin and kaempferol glycosides were the main phenolic compounds identified in the methanolic extracts. Finally, salicylic and ferulic acids were found in a concentration range of 0.14-0.33 and 6.61-9.69 mg/100 g, respectively. In conclusion, we observed some differences in terms of nutrients and phenolic compounds in M. oleifera leaves grown in different countries. Nevertheless, these leaves are a good and economical source of nutrients for tropical and sub-tropical countries. Furthermore, M. oleifera leaves are a source of flavonoids and phenolic acids, among which salicylic and ferulic acids, and therefore they could be used as nutraceutical and functional ingredients.

Sample treatment considerations in the analysis of organic colorants by surface-enhanced Raman scattering.

The introduction of surface-enhanced Raman spectroscopy (SERS) in the field of cultural heritage has significantly improved the analysis of the organic dyes and their complexes that have been used as textile dyes and pigments in paintings and other polychrome works of art since antiquity. Over the last five years, a number of different procedures have been developed by various research groups. In this Article, we evaluate the effect of pretreating samples by exposing them to hydrofluoric acid (HF) vapor prior to SERS analysis, a step designed to hydrolyze the dye-metal complexes and increase analyte adsorption on the nanosized metallic support, thus enhancing the SERS signal. Materials studied include pure colorants, commercial lake pigments, and fibers from dyed textiles, as well as actual aged samples, such as microscopic fragments of lakes on paper and ancient pigments and glazes from several works of art, covering a wide range of time, from the second century B.C. to the early 20th century. In each case, SERS spectra obtained with or without HF hydrolysis were critically evaluated. The pretreatment with HF vapor resulted in faster analysis and increased sensitivity in most cases, with the exception of dyed silk fibers, where silk protein hydrolyzates were found to interfere with SERS analysis. As a final point, a two-step procedure including SERS on untreated and treated samples is proposed as a standard approach: by analyzing a sample first without hydrolysis, and then, following removal of the colloid, upon HF treatment, the best and most reliable results for a great number of dyes and substrates are assured.

Identification of natural dyes on laboratory-dyed wool and ancient wool, silk, and cotton fibers using attenuated total reflection (ATR) Fourier transform infrared (FT-IR) spectroscopy and Fourier transform Raman spectroscopy.

Attenuated total reflection (ATR) infrared and Fourier transform (FT) Raman spectra were obtained from wool threads dyed in the laboratory with natural dyes used in antiquity, following a procedure similar to ancient methods for dyeing wool. The ATR spectra were primarily dominated by the signals of the wool, making it difficult to identify the dye on the fibers only by visual inspection of the infrared spectrum. However, the Raman spectra showed more significant characteristics attributable to the dyes as previously studied in the literature on modern synthetic dyes. A library-search method was thus applied to the second derivatives of both the ATR and Raman spectra to verify the possibility of identifying the dye. Two libraries were constructed, one consisting of the ATR spectra of undyed wool (raw, washed, and mordanted) and the transmission spectra of pure dyes and the other consisting of the Raman spectra of undyed wool and of pure dyes. Correlation and first-derivative correlation search algorithms were used. The results presented here suggest that the two types of spectroscopy are complementary in this kind of work, allowing the almost complete identification of historic dyes on wool. In fact, through the combined use of the two searches, most dyes were identified with a good index of similarity and within the first five hits. Only for annatto was identification totally impossible using either technique. Subsequently the same method was applied to wool, silk, and cotton threads taken from ancient Caucasian and Chinese textiles.

A 40-year-old man with ulcerated skin lesions caused by bites of safari ants.

We report a 40-year old man in Uganda with ulcerated skins lesions, hypotension, and anaphylaxis caused by bites of safari ants. Treatment was successful. Physicians should be aware of anaphylaxis caused by ant bites.