Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying a TINF2 Variant

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αβ+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment.     

Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!

Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a Drosophila Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.     

Microstructure of Reaction Zone Formed During Diffusion Bonding of TiAl with Ni/Al Multilayer

In this article, the characterization of the interfacial structure of diffusion bonding a TiAl alloy is presented. The joining surfaces were modified by Ni/Al reactive multilayer deposition as an alternative approach to conventional diffusion bonding. TiAl substrates were coated with alternated Ni and Al nanolayers. The nanolayers were deposited by dc magnetron sputtering with 14 nm of period (bilayer thickness). Joining experiments were performed at 900 °C for 30 and 60 min with a pressure of 5 MPa. Cross sections of the joints were prepared for characterization of their interfaces by scanning electron microscopy (SEM), transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), high resolution TEM (HRTEM), energy dispersive x-ray spectroscopy (EDS), and electron backscatter diffraction (EBSD). Several intermetallic compounds form at the interface, assuring the bonding of the TiAl. The interface can be divided into three distinct zones: zone 1 exhibits elongated nanograins, very small equiaxed grains are observed in zone 2, while zone 3 has larger equiaxed grains. EBSD analysis reveals that zone 1 corresponds to the intermetallic Al₂NiTi and AlNiTi, and zones 2 and 3 to NiAl.     

Ultrastructural and developmental toxicity of potato and tomato leaf extracts to beet armyworm,Spodoptera exigua (lepidoptera: noctuidae)

Beet Armyworm, Spodoptera exigua is a herbivorous moth and a serious pest of many economically important plants, which are used as food sources. Because of rigorous standards of food quality, usage of synthetic insecticides in crop protection, against pests, is limited. Solanaceae plant extracts may be a relatively cheap source of efficient natural insecticides that can limit usage of synthetic substances. Their biological activity is not fully known. In particular, ultrastructural studies, using transmission electron microscopy, are not usual. In the present article we describe the effects of sublethal concentrations of tomato and potato leaf extracts against S. exigua. Acute lethal effects were not observed. Both extracts exerted similar effects within midgut and fat body cells. Midgut cells were not significantly altered while fat body cells showed prominent swelling of nuclear envelope and endoplasmic reticulum, vacuolization of mitochondria and fusion of fat droplets. These changes were much more intensive within groups exposed to potato than tomato extracts at highest concentration at least. Light microscopy was used to observe and document developmental alterations of S. exigua exposed to potato and tomato leaf extracts. Potato leaf extracts significantly decreased hatching success and caused morphological malformations of imagoes. Among them, malformations of wings were the most prominent. Interestingly, these effects were not observed within populations exposed to tomato extracts at highest concentration at least.     

The connection between Bell's inequalities based on probabilities and those based on correlations

Abstract

Violation of Bell inequalities is widely regarded as a definitive test for non-locality. However, Bell correlational inequalities must always be satisfied by all jointly present, cross-correlated data. The correlations of variable pairs obtained in repeated runs are not cross-correlated in this way and are not required to satisfy the Bell inequality. In addition, by using information regarded as non-local, proper joint correlations may be computed among counterfactual and measured variables. These correlations satisfy the Bell inequality, but are spatially non-stationary in angle. By using a simple symmetry condition, such considerations may be extended to inequalities in probabilities. The latter may be derived directly from correlational inequalities developed by Clauser, Horne, Shimony and Holt (CHSH). Violation of either correlational or probabilistic Bell inequalities then implies that the Bell correlation cannot be accounted for by a stochastic process that is spatially stationary in angle coordinates. However, other processes may still be allowed.     

Antioxidant activity of phenolic and phenylethanoid glycosides from Teucrium polium L

In the present study, the chemical composition and antioxidant activities of Teucrium polium L. (Lamiaceae) were assessed. Fractionation of methanol extract obtained from the aerial parts of T. polium yielded one new phenylethanoid glycoside, named poliumoside B, together with four known flavonoids, two iridoid glycosides and a known poliumoside. The structures of all of these compounds were elucidated on the basis of spectroscopic data from 1D and 2D NMR experiments and MS spectral analyses. The antioxidant activities of the crude extracts and of the isolated compounds were evaluated through tests such as DPPH radical-scavenging capability, reducing power, xanthine oxidase inhibitory effect and inhibition of linoleic acid peroxidation. The highest antioxidant activity was found in the n-butanol extract, which also contained active polyphenols, thus suggesting that this plant could be used as a source of natural molecules, to provide safe antioxidant additives and nutraceuticals. The structure–activity relationships of the isolated compounds are also discussed.     

Reactive Commercial Ni/Al Nanolayers for Joining Lightweight Alloys

Reactive nanoscale multilayer foils for use in joining techniques have attracted a great deal of attention. A common feature of these nanolayers is the large amount of heat released during the reaction between the layers to form a new phase. In this study, films of alternated Ni and Al nanolayers (NanoFoil^® made by the Indium Corporation) with period (bilayer thickness) close to 54 nm and with a thickness of 60 μm were used as local heat sources to bond lightweight alloys. The as-deposited Ni and Al alternated nanolayers evolve into NiAl nanometric grains when the multilayer, ignited by an electrical discharge, reacts. Joining of lightweight alloys was performed at room temperature under pressures of 10-80 MPa. The ability of the nanolayers to join these alloys by high temperature diffusion bonding was also investigated. The microstructural and chemical characterizations of the interfaces were performed on cross-sections of the joints by scanning electron microscopy and energy dispersive x-ray spectroscopy. Ni/Al nanolayers are an effective means of joining titanium alloys at room temperature. A sound interface, mainly composed by NiAl grains, is obtained in joints of TiAl/TiAl and TiAl/Inconel, produced with NanoFoil^® by annealing at 700 ºC, during 60 min under a pressure of 10 MPa. The low shear strength revealed a weak adhesion of the nanofoil to the base materials.     

Effect of self-etching dual-curing universal adhesive system application on bond strength of dentin resinous liners dentin

Purpose: The aim of this study was to evaluate the influence of previous application of an adhesive system on bond strength of resinous liner materials to dentin. Methods: Ninety bovine incisors crowns had a 6 × 6 mm area of dentin exposed, with minimum of 2 mm thickness. They were embedded in acrylic resin, and the dentin was polished with P600 SiC sandpaper for 30 s to standardize the smear layer. The specimens were divided into 6 groups (n = 15) according to the application or not of a self-etching system (Futurabond U – Voco) and the type of resinous liner used: A+Ionoseal (adhesive and Ionoseal – Voco); Ionoseal (Ionoseal only); A+Vitrebond (adhesive and Vitrebond – 3M/ESPE); Vitrebond (Vitrebond only); A+Ionosit (adhesive and Ionosit – DMG) and Ionosit (Ionosit only). Adhesives were used following manufacturer’s instructions, and the liner materials were applied inside a 2-mm-depth matrix and light-cured for 20 s. The bond strength was measured by microtensile test, using a universal testing machine with a cross-speed of 1 mm/min. Data were analyzed using one-way ANOVA and Tukey’s test (p < 0.05). Results: The adhesive system application increased bond strength of all liners tested. Ionoseal presented the highest bond strength when the adhesive system was used and exhibited similar performance to Vitrebond without adhesive. Ionosit without adhesive showed the smallest bond strength compared with the other liners tested. Conclusion: The application of an adhesive system prior to the use of the resinous liners improved the bond strength to dentin and should be preconized.     

Cold Atmospheric Plasma Apoptotic and Oxidative Effects on MCF7 and HCC1806 Human Breast Cancer Cells

Breast cancer (BC) is a malignant neoplasia with the highest incidence and mortality rates in women worldwide. Currently, therapies include surgery, radiotherapy, and chemotherapy, including targeted therapies in some cases. However, treatments are often associated with serious adverse effects. Looking for new options in BC treatment, we evaluated the therapeutic potential of cold atmospheric plasma (CAP) in two cell lines (MCF7 and HCC1806) with distinct histological features. Apoptosis seemed to be the most prevalent type of death, as corroborated by several biochemical features, including phosphatidylserine exposure, the disruption of mitochondrial membrane potential, an increase in BAX/BCL2 ratio and procaspase 3 loss. Moreover, the accumulation of cells in the G2/M phase of the cell cycle points to the loss of replication ability and decreased survival. Despite reported toxic concentrations of peroxides in culture media exposed to plasma, intracellular peroxide concentration was overall decreased accompanying a reduction in GSH levels shortly after plasma exposure in both cell lines. In HCC1806, elevated nitric oxide (NO) concentration accompanied by reduced superoxide levels suggests that these cells are capable of converting plasma-derived nitrites into NO that competes with superoxide dismutase (SOD) for superoxide to form peroxinitrite. The concomitant inhibition of the antioxidative activity of cells during CAP treatment, particularly the inhibition of cytochrome c oxidase with sodium azide, synergistically increased plasma toxicity. Thus, this in vitro research enlightens the therapeutic potential of CAP in the treatment of breast cancer, elucidating its possible mechanisms of action.