Successful rechallenge with azacytidine and venetoclax after sustained treatment-free remission in a relapsed acute myeloid leukemia patient: a case report.

Combined therapy with venetoclax and hypomethylating agents has significantly improved the outcome of unfit patients ineligible for intensive chemotherapy. A recently published exploratory analysis of the VIALE-A trial reported that up to 51% of patients achieving remission survived more than 2 years. These data along with those from reallife settings, lead to questioning how long it is appropriate to continue treatment in long-term survivors.

Site-specific incorporation of a fluorescent nucleobase analog enhances i-motif stability and allows monitoring of i-motif folding inside cells.

The i-motif is an intriguing non-canonical DNA structure, whose role in the cell is still controversial. Development of methods to study i-motif formation under physiological conditions in living cells is necessary to study its potential biological functions. The cytosine analog 1,3-diaza-2-oxophenoxazine (tCO) is a fluorescent nucleobase able to form either hemiprotonated base pairs with cytosine residues, or neutral base pairs with guanines.

High-density SNP markers elucidate the genetic divergence and population structure of Noticiana sheep breed in the Mediterranean context.

Among livestock species, sheep have played an early major role in the Mediterranean area. Italy has a long history of sheep breeding and, despite a dramatic contraction in numbers, still raise several local populations that may represent a unique source of genetic diversity. The Noticiana is a breed of the south-eastern part of Sicily appreciated both for its dairy products and for its resistance to harsh environment.

High-density single nucleotide polymorphism markers reveal the population structure of 2 local chicken genetic resources.

Italy counts a large number of local chicken populations, some without a recognized genetic structure, such as Val Platani (VPL) and Cornuta (COS), which represent noteworthy local genetic resources. In this study, the genotype data of 34 COS and 42 VPL, obtained with the Affymetrix Axiom600KChicken Genotyping Array, were used with the aim to investigate the genetic diversity, the runs of homozygosity (ROH) pattern, as well as the population structure and relationship within the framework of other local Italian and commercial chickens. The genetic diversity indices, estimated using different approaches, displayed moderate levels of genetic diversity in both populations.

Stronger than Ever: Multifilament Fiberglass Posts Boost Maxillary Premolar Fracture Resistance.

This paper investigates the influence of cavity configuration and post-endodontic restoration on the fracture resistance, failure mode and stress distribution of premolars by using a method of fracture failure test and finite elements analysis (FEA) coupled to Weibull analysis (WA). One hundred premolars were divided into one control group (G) ( = 10) and three experimental groups, according to the post-endodontic restoration ( = 30), G, restored using composite, G, restored using single fiber post and G, restored using multifilament fiberglass posts (m-FGP) without post-space preparation. Each experimental group was divided into three subgroups according to the type of coronal cavity configuration ( = 10): G, G and G with occlusal (O) cavity configuration; G, G, and G with mesio-occlusal (MO); and G, G, and G with mesio-occluso-distal (MOD).

The Effectiveness of Different Irrigation Techniques on Debris and Smear Layer Removal in Primary Mandibular Second Molars: An Study.

Aims: The aim of the present study was to compare the effectiveness of passive ultrasonic irrigation (PUI), sonic irrigation, and mechanic dynamic activation on the removal of debris and smear layer from primary mandibular second molars during pulpectomy.

Materials And Methods: Mesial roots of 48 primary mandibular second molars were prepared with an R-motion 21 mm file (30/0.04) (FKG Dentaire SA, La Chaux-de-Fonds, Switzerland), irrigated with 1% sodium hypochlorite (NaOCl) and 17% ethylenediaminetetraacetic acid (EDTA), and divided into four groups ( = 24 canals) according to the final irrigation activation technique: control group without activation, PUI with Ultra-X (Eighteeth, Changzhou, China), mechanical activation with XP-endo Finisher (FKG), and sonic irrigation with EQ-S (Meta Biomed, Chungcheongbuk-do, Korea).

Effectiveness of Two Endodontic Instruments in Calcium Silicate-Based Sealer Retreatment.

The objective of the present in vitro work was to investigate the effectiveness and time required for the removal of calcium silicate-based sealer using two rotary retreatment systems. Sixty extracted, single-canal, lower premolars were used. After obturation using the single-cone technique with calcium silicate-based sealer, samples were divided into four groups according to the technique of desobturation: Group 1 (G1): D-Race; Group 2 (G2): D-Race followed by the use of XP-Endo Finisher R; Group 3 (G3): Protaper Universal Retreatment; and Group 4 (G4): Protaper Universal Retreatment followed by the use of XP-Endo Finisher R.

i-Motif folding intermediates with zero-nucleotide loops are trapped by 2'-fluoroarabinocytidine via F···H and O···H hydrogen bonds.

G-quadruplex and i-motif nucleic acid structures are believed to fold through kinetic partitioning mechanisms. Such mechanisms explain the structural heterogeneity of G-quadruplex metastable intermediates which have been extensively reported. On the other hand, i-motif folding is regarded as predictable, and research on alternative i-motif folds is limited.

Physicochemical and Mechanical Properties of Premixed Calcium Silicate and Resin Sealers.

The aim of the present in vitro study was to evaluate specific mechanical and physicochemical properties of two calcium silicate based sealers, (AH Plus Bioceramic “AHPB”; Well-Root ST “WRST”), and a conventional resin sealer (AH Plus “AHP”). These aims were accomplished by assessing the porosity, pH, compression strength, roughness, wettability and cell attachment of the tested materials. The results were compared statistically using the one-way ANOVA test.

Toxic metals in Loggerhead sea turtles () stranded freshly dead along Sicilian coasts.

Background: The Loggerhead sea turtle () is a marine reptile belonging to a monophyletic group of chelonians. As these animals are long-lived, they have the ability to accumulate pollutants.

Aim: To collect epidemiological data on toxic metals in marine Loggerhead sea turtles.

Compressive Strength and Porosity Evaluation of Innovative Bidirectional Spiral Winding Fiber Reinforced Composites.

The aim of this in vitro study was to investigate the compressive strength and the bulk porosity of a bidirectional (bFRC) and an experimental bidirectional spiral winding reinforced fiber composite (bswFRC). Cylindrical-shape specimens were prepared for each material group and processed for the evaluation of compressive strength after different storage conditions (dry, 1 and 3 months) in distilled water at 37 °C. The specimens were also assessed for the degree of bulk porosity through X-ray tomography.

Protein control of photochemistry and transient intermediates in phytochromes.

Phytochromes are ubiquitous photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of the embedded chromophore, triggering large conformational changes in the protein. Despite numerous experimental and computational studies, the role of chromophore-protein interactions in controlling the mechanism and timescale of the process remains elusive.

Physicochemical and Antibacterial Properties of Bioactive Retrograde Filling Materials.

The purpose of the present study was to evaluate the physicochemical properties and antibacterial activity of three calcium silicate cements. Mineral trioxide aggregate (MTA Biorep “BR”), Biodentine (BD) and Well-Root PT (WR) materials were investigated using scanning electron microscopy (SEM) at 24, 72 and 168 h of immersion in phosphate buffered saline (PBS). The antibacterial activity against Enterococcus faecalis (E.

A novel endocast technique providing a 3D quantitative analysis of the gastrovascular system in Rhizostoma pulmo: An unexpected through-gut in cnidaria.

The investigation of jellyfish gastrovascular systems mainly focused on stain injections and dissections, negatively affected by thickness and opacity of the mesoglea. Therefore, descriptions are incomplete and data about tridimensional structures are scarce. In this work, morphological and functional anatomy of the gastrovascular system of Rhizostoma pulmo (Macri 1778) was investigated in detail with innovative techniques: resin endocasts and 3D X-ray computed microtomography.

From crystallographic data to the solution structure of photoreceptors: the case of the AppA BLUF domain.

Photoreceptor proteins bind a chromophore, which, upon light absorption, modifies its geometry or its interactions with the protein, finally inducing the structural change needed to switch the protein from an inactive to an active or signaling state. In the Blue Light-Using Flavin (BLUF) family of photoreceptors, the chromophore is a flavin and the changes have been connected with a rearrangement of the hydrogen bond network around it on the basis of spectroscopic changes measured for the dark-to-light conversion. However, the exact conformational change triggered by the photoexcitation is still elusive mainly because a clear consensus on the identity not only of the light activated state but also of the dark one has not been achieved.

Ultrafast Transient Infrared Spectroscopy of Photoreceptors with Polarizable QM/MM Dynamics.

Ultrafast transient infrared (TRIR) spectroscopy is widely used to measure the excitation-induced structural changes of protein-bound chromophores. Here, we design a novel and general strategy to compute TRIR spectra of photoreceptors by combining μs-long MM molecular dynamics with ps-long QM/AMOEBA Born-Oppenheimer molecular dynamics (BOMD) trajectories for both ground and excited electronic states. As a proof of concept, the strategy is here applied to AppA, a blue-light-utilizing flavin (BLUF) protein, found in bacteria.

The structural changes in the signaling mechanism of bacteriophytochromes in solution revealed by a multiscale computational investigation.

Phytochromes are red-light sensing proteins, with important light-regulatory roles in different organisms, which are capturing an increasing interest in bioimaging and optogenetics. Upon absorption of light by the embedded bilin chromophore, they undergo structural changes that extend from the chromophore to the protein and finally drive the biological function. Up to now, the underlying mechanism still has to be characterized fully.

Role of Chemical Dynamics Simulations in Mass Spectrometry Studies of Collision-Induced Dissociation and Collisions of Biological Ions with Organic Surfaces.

In this article, a perspective is given of chemical dynamics simulations of collisions of biological ions with surfaces and of collision-induced dissociation (CID) of ions. The simulations provide an atomic-level understanding of the collisions and, overall, are in quite good agreement with experiment. An integral component of ion/surface collisions is energy transfer to the internal degrees of freedom of both the ion and the surface.

Elucidating the role of structural fluctuations, and intermolecular and vibronic interactions in the spectroscopic response of a bacteriophytochrome.

We present the first comprehensive multiscale computational investigation of Resonance Raman, absorption and Circular Dichroism spectra of the resting state of the Deinococcus radiodurans phytochrome. The spectra are simulated in all their components, namely the energy position and the lineshapes of both the far-red and the blue bands. To achieve such a goal, we have combined a 4.

Fragmentation Spectra Prediction and DNA Adducts Structural Determination.

In this work, chemical dynamics simulations were optimized and used to predict fragmentation mass spectra for DNA adduct structural determination. O-methylguanine (O-Me-G) was used as a simple model adduct to calculate theoretical spectra for comparison with measured high-resolution fragmentation data. An automatic protocol was established to consider the different tautomers accessible at a given energy and obtain final theoretical spectra by insertion of an initial tautomer.

l-Cysteine Modified by S-Sulfation: Consequence on Fragmentation Processes Elucidated by Tandem Mass Spectrometry and Chemical Dynamics Simulations.

Low-energy collision-induced dissociation (CID) of deprotonated l-cysteine S-sulfate, [cysS-SO], delivered in the gas phase by electrospray ionization, has been found to provide a means to form deprotonated l-cysteine sulfenic acid, which is a fleeting intermediate in biological media. The reaction mechanism underlying this process is the focus of the present contribution. At the same time, other novel species are formed, which were not observed in previous experiments.

Threshold for shattering fragmentation in collision-induced dissociation of the doubly protonated tripeptide TIK(H).

In a recent direct dynamics simulations of the collision induced dissociation (CID) of the doubly protonated tripeptide threonine-isoleucine-lysine and threonine-leucine-lysine ions, TIK(H+)2 and TLK(H+)2, a shattering fragmentation mechanism was found, in which the ion fragmented upon impact with N2 (Z. Homayoon et al., Phys.

Chemical dynamics simulations of CID of peptide ions: comparisons between TIK(H) and TLK(H) fragmentation dynamics, and with thermal simulations.

Gas phase unimolecular fragmentation of the two model doubly protonated tripeptides threonine-isoleucine-lysine (TIK) and threonine-leucine-lysine (TLK) is studied using chemical dynamics simulations. Attention is focused on different aspects of collision induced dissociation (CID): fragmentation pathways, energy transfer, theoretical mass spectra, fragmentation mechanisms, and the possibility of distinguishing isoleucine (I) and leucine (L). Furthermore, discussion is given regarding the differences between single collision CID activation, which results from a localized impact between the ions and a colliding molecule N, and previous thermal activation simulation results; Z.

Unimolecular dissociation of peptides: statistical vs. non-statistical fragmentation mechanisms and time scales.

In the present work we have investigated mechanisms of gas phase unimolecular dissociation of a relatively simple dipeptide, the di-proline anion, by means of chemical dynamics simulations, using the PM3 semi-empirical Hamiltonian. In particular, we have considered two activation processes that are representative limits of what occurs in collision induced dissociation experiments: (i) thermal activation, corresponding to several low energy collisions, in which the system is prepared with a microcanonical distribution of energy; (ii) collisional activation where a single shock of hundreds of kcal mol (300 kcal mol in the present case) can transfer sufficient energy to allow dissociation. From these two activation processes we obtained different product abundances, and for one particular fragmentation pathway a clear mechanistic difference for the two activation processes.

Model Simulations of the Thermal Dissociation of the TIK(H) Tripeptide: Mechanisms and Kinetic Parameters.

Direct dynamics simulations, utilizing the RM1 semiempirical electronic structure theory, were performed to study the thermal dissociation of the doubly protonated tripeptide threonine-isoleucine-lysine ion, TIK(H), for temperatures of 1250-2500 K, corresponding to classical energies of 1778-3556 kJ/mol. The number of different fragmentation pathways increases with increase in temperature. At 1250 K there are only three fragmentation pathways, with one contributing 85% of the fragmentation.