Human DNA topoisomerase I-mediated cleavages stimulated by ultraviolet light-induced DNA damage

DNA topoisomerases have been proposed as the proteins involved in the formation of the DNA-protein cross-links detected after ultraviolet light (UV) irradiation of cellular DNA. This possibility has been investigated by studying the effects of UV-induced DNA damage on human DNA topoisomerase I action. UV lesions impaired the enzyme's ability to relax negatively supercoiled DNA. Decreased relaxation activity correlated with the stimulation of cleavable complexes. Accumulation of cleavable complexes resulted from blockage of the rejoining step of the cleavage-religation reaction. Mapping of cleavage sites on the pAT153 genome indicated UV-induced cleavage at discrete positions corresponding to sites stimulated also by the topoisomerase I inhibitor camptothecin, except for one. Subsequent analysis at nucleotide level within the sequence encompassing the UV-specific cleavage site revealed the precise positions of sites stimulated by camptothecin with respect to those specific for UV irradiation. Interestingly, one of the UV-stimulated cleavage sites was formed within a sequence that did not contain dimerized pyrimidines, suggesting transmission of the distortion, caused by photodamage to DNA, into the neighboring sequences. These results support the proposal that DNA structural alterations induced by UV lesions can be sufficient stimulus to induce cross-linking of topoisomerase I to cellular DNA.     

Assessing the health research’s social impact: a systematic review

Scientometrics - In recent year, a growing attention is dedicated to the assessment of research’s social impact. While prior research has often dealt with results of research, the last decade...     

Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.     

Highly Sensitive Pulsed Digital Holography for Built-in Defect Analysis with a Laser Excitation

A highly sensitive method is presented for noninvasive defect analysis on thin structures with a Q-switched double-pulsed ruby laser with frequency doubling (347 nm). In our research we feature an all-optical arrangement, where a focused laser pulse derived from the same ruby laser (694 nm) acts as a built-in synchronous excitation source for digital holographic interferometry. The recordings are made with a CCD camera for capturing two holograms (two states of the specimen) corresponding to the two UV laser pulses with a short time separation (10-50 mus). Subtraction of the phase distribution in two digital holograms gives a fringe phase map that shows the change in deformation of the specimen between the recordings. The advantage of the proposed method is two fold. First, the use of a shorter wavelength results in a higher sensitivity. Second, owing to the induced synchronous built-in optical excitation, the specimen is not subjected to any external physical excitation devices. Experimental results are presented on identification and evaluation of defects in thin metal sheets.     

Single crystal growth and characterization of LaLuO3

Wide shoulder and fast lateral growth are characteristics of LaLuO₃ during crystallization onto an iridium rod in Czochralski's configuration. Under careful temperature control, necking in and further low-speed pulling provided for single-crystal growth, but spontaneous separation of the growing crystal from the melt is a strongly limiting factor for production of large boules. Ce- and Pr-doped single crystals of up to 0.5 cm³ were obtained and used in measurements of the X-ray data, density, melting point and optical properties and in annealing studies.     

A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy

Recent research on development of the implantable artificial pancreas for treatment of diabetes is reviewed, based on a Medline literature search that focused on glucose sensors, insulin pumps, and pump control systems. To achieve a closed feedback loop, a clinically applicable implantable artificial pancreas requires miniaturization and coordination of three components: an insulin pump, a blood glucose monitor, and a control system. Recent clinical studies have demonstrated that implantable insulin pumps are feasible for satisfactory control of diabetes for over a year, with the major complication being obstruction of the infusion catheter. Research on continuous glucose sensors has predominantly used the glucose-oxidase reaction or near-infrared light spectroscopy. Implantable glucose oxidase sensors have been limited by local factors causing unstable signal output, whereas optical sensors must overcome interference by substances with absorption spectra similar to glucose. Investigators have developed control algorithms in an effort to stabilize operation of the integrated artificial pancreas in the face of variations in sensor output and pump function. The ultimate goals of fully automatic glucose control by an artificial pancreas include prevention or delay of chronic complications of diabetes, lowered risk of hypoglycemia, and less patient inconvenience and discomfort than with multiple daily glucose self-tests and insulin injection. The recent developments of optical glucose sensing, radiotelemetry systems to link pump and sensor, and miniaturization and refinement of insulin pumps are significant steps toward a clinically applicable artificial pancreas.     

In-line digital holographic interferometry

An optical system based on in-line digital holography for the evaluation of deformations is described. In-line holograms are recorded on a CCD chip. The problem of overlapping twin images typical for the in-line arrangement is solved by digital reconstruction and filtering of the unwanted wave fronts. Two separate interferograms of an object under test in its undeformed and deformed states are recorded each on a CCD chip. The phases of the two wave fronts are obtained from the complex amplitudes of the digital reconstructed wave fronts, and the deformation is calculated from the phase differences. Experimental results are presented.     

CANDYBOTS: A New Generation of 3D-Printed Sugar-Based Transient Small-Scale Robots

Sugars are ubiquitous in food, and are among the main sources of energy for almost all forms of life. Sugars can also form structural building blocks such as cellulose in plants. Because of their inherent degradability and biocompatibility characteristics, sugars are compelling materials for transient devices. Here, an additive manufacturing approach for the production of magnetic sugar-based composites is introduced. First, it is shown that sugar-based 3D architectures can be 3D printed by selective laser sintering. This method enables not only the caramelization chemistry but also the mechanical properties of the sugar architectures to be adjusted by varying the laser energy. It is also demonstrated that mixtures of sugar and magnetic particles can be processed as 3D composites. As a proof of concept, a sugar-based millimeter-scale helical swimmer, which is capable of corkscrew motion in a solution with a viscosity comparable to those of biological fluids, is fabricated. The millirobot quickly dissolves in water, while being manipulated through magnetic fields. The present fabrication method can pave the way to a new generation of transient sugar-based small-scale robots for minimally invasive procedures. Due to their rapid dissolution, sugars can be used as an intermediate step for transporting swarms of particles to specific target locations.