The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells.

Thymocytes must bind major histocompatibility complex (MHC) proteins on thymic epithelial cells in order to mature into either CD8+ cytotoxic T cells or CD4+ helper T cells. Thymic precursors express both CD8 and CD4, and it has been suggested that the intracellular signals generated by CD8 or CD4 binding to class I or II MHC, respectively, might influence the fate of uncommitted cells. Here we test the notion that intracellular signaling by CD4 directs the development of thymocytes to a CD4 lineage. A hybrid protein consisting of the CD8 extracellular and transmembrane domains and the cytoplasmic domain of CD4 (CD884) should bind class I MHC but deliver a CD4 intracellular signal. We find that expression of a hybrid CD884 protein in thymocytes of transgenic mice leads to the development of large numbers of class I MHC-specific, CD4 lineage T cells. We discuss these results in terms of current models for CD4 and CD8 lineage commitment

Computing coset leaders and leader codewords of binary codes

In this paper we use the Gr\"obner representation of a binary linear code $\mathcal C$ to give efficient algorithms for computing the whole set of coset leaders, denoted by $\mathrm{CL}(\mathcal C)$ and the set of leader codewords, denoted by $\mathrm L(\mathcal C)$. The first algorithm could be adapted to provide not only the Newton and the covering radius of $\mathcal C$ but also to determine the coset leader weight distribution. Moreover, providing the set of leader codewords we have a test-set for decoding by a gradient-like decoding algorithm. Another contribution of this article is the relation stablished between zero neighbours and leader codewords

Processing and initial comparison of PSR data from CAMEX-3 to SSM/I and TMI data

A multiband Polarimetric Scanning Radiometer (PSR) was integrated on a NASA DC-8 aircraft and flown from August through September of 1998 during the third Convection and Moisture Experiment (CAMEX-3). The PSR is a new conically-scanning imaging radiometer with channels at 10.7, 18.7, 21.5, 37.0 and 89.0 GHz, including both vertical and horizontal polarizations at each of these frequencies. These channels correspond to several key sensing bands of the DMSP (Defense Meteorological Satellite Program) SSM/I (Special Sensor Microwave Imager) and the NASA TRMM (Tropical Rainfall Measuring Mission) TMI (TRMM Microwave Imager). The PSR was developed by Georgia Institute of Technology and the NOAA Environmental Technology Laboratory and is the first airborne imaging radiometer to provide a research quality dataset of high spatial resolution multiband polarimetric microwave imagery within and around a hurricane. The authors describe the processing and calibration of the PSR CAMEX-3 dataset. They also provide a qualitative analysis and comparison of the PSR imagery to the SSM/I and TMI with specific regard to the spatial structure of a hurricane eyewall and surrounding rainbands.Peer ReviewedPostprint (published version

Single amino acid mutation controls hole transfer dynamics in DNAmethyltransferase HhaI complexes

Different mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (socalled holes) on purine nucleobases in the π stack. The interaction of DNA with proteins may protect DNA from the oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acid residues. The HT dynamics is such systems is still poorly understood. Here, we report a computational study of HT in DNA complexes with methyltransferase HhaI and its mutant Q237W, which were experimentally investigated in the Barton group. We employ a combined approach based on molecular dynamics simulations and quantum mechanical calculations to estimate the rate for all individual steps involved in the HT pathways; finally the overall HT kinetics are explored using the Monte-Carlo method. Our results indicate that the HT characteristics are strongly affected by structural deformations of DNA upon its binding to the protein. In the wild-type enzyme complex, a Gln residue inserted in the DNA π-stack is shown to destabilize the radical cation states of neighboring guanines and thereby inhibits the long-range HT in line with experimental findings. In contrast, the HT is estimated to be quite fast in a complex of the Q237W mutant where Trp237 stabilizes hole states on the adjacent G bases and enhances the electronic coupling of these sites. An alternative HT pathway that implies the formation of a Trp+ radical is predicted to be less efficient. Our study provides a consistent molecular picture on how long-range HT in DNA-protein complexes is controlled by amino acids closely interacting with the π stack.Peer Reviewe

Single amino acid mutation controls hole transfer dynamics in DNAmethyltransferase HhaI complexes

Different mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (socalled holes) on purine nucleobases in the π stack. The interaction of DNA with proteins may protect DNA from the oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acid residues. The HT dynamics is such systems is still poorly understood. Here, we report a computational study of HT in DNA complexes with methyltransferase HhaI and its mutant Q237W, which were experimentally investigated in the Barton group. We employ a combined approach based on molecular dynamics simulations and quantum mechanical calculations to estimate the rate for all individual steps involved in the HT pathways; finally the overall HT kinetics are explored using the Monte-Carlo method. Our results indicate that the HT characteristics are strongly affected by structural deformations of DNA upon its binding to the protein. In the wild-type enzyme complex, a Gln residue inserted in the DNA π-stack is shown to destabilize the radical cation states of neighboring guanines and thereby inhibits the long-range HT in line with experimental findings. In contrast, the HT is estimated to be quite fast in a complex of the Q237W mutant where Trp237 stabilizes hole states on the adjacent G bases and enhances the electronic coupling of these sites. An alternative HT pathway that implies the formation of a Trp+ radical is predicted to be less efficient. Our study provides a consistent molecular picture on how long-range HT in DNA-protein complexes is controlled by amino acids closely interacting with the π stack.Peer Reviewe

Reactivity of dolomitizing fluids and Mg source evaluation of fault-controlled dolomitization at the Benicàssim outcrop analogue (Maestrat Basin, E Spain)

Peer reviewedPostprin

Periodontal Regenerative Treatment of Intrabony Defects Associated with Palatal Grooves: A Report of Two Cases

A palatal radicular groove (PRG) is a morphological deformity, occurring during tooth development. It is usually located on the palatal aspect of maxillary incisors and frequently associated with periodontal or endodontic-periodontal lesions. Some treatment options were described for such lesions, including primary endodontic treatment and periodontal surgery and extraction with intentional replantation after removal of a PRG and endodontic treatment. The present paper reported two cases of PRG-associated deep intrabony defects, successfully treated with periodontal surgery with enamel matrix derivative (EMD) application and mechanical removal of PRGs, avoiding endodontic treatment or retreatment. The complexity of the diagnostic process was also discussed

Allanite in Variscan Post-Collisional Lamprophyre Dykes from Les Guilleries (NE Iberia) as a Part of Rare Earth Elements Recycling in Collisional Orogens

Recent studies of Late Permian calc-alkaline lamprophyre dykes located in the Les Guilleries Paleozoic massif of the Catalan Coastal Range have revealed that allanite is present as the main REE-bearing accessory phase, which is the object of this study. The lamprophyre dykes are amphibole-plagioclase-dominated spessartites with a wide variety of accessory phases, including titanite, ilmenite, allanite, fluorapatite, spinel, zircon, and sulfides, and show complex alteration textures related to secondary albite, chlorite, epidote, titanite and calcite. The allanite crystal composition, analyzed by SEM-EPMA and LA-ICP-MS, evidences the solid solution between epidote and allanite with a ferriallanite component, similar to what is found in Variscan post-collisional granitoids from western Europe. However, heterogeneity in crystal shapes, sizes, type of zoning, dissolution embayment textures, growth of epidote coronas, mineral paragenesis, and the unique geochemical characteristics of allanite crystals suggest multiple crystallization events. At least two types of allanite-epidote composite grains have been identified: allanite Type I, with regular allanite-epidote core-to-rim zoning and a secondary allanite rim; and allanite Type II, with anhedral allanite cores surrounded by epidote coronas. Additionally, irregular zoning, complex dissolution textures and REE redistribution suggest the occurrence of deuteric and/or post-magmatic processes, which are also common in Variscan post-collisional plutons from the Catalan Coastal Range and nearby Paleozoic massifs. Multivariate statistical analyses of major elements in allanite-epidote composite grains show a relationship between major textural and geochemical variations for three out of ten principal components, mainly related to cationic substitutions between ferriallanite-(Ce) and epidote, but also involving Mn and Ti(REE + Fe + Ti + Mg + Mn = Al + Ca + Fe). The allanite U-Pb-Th- weighted mean age of 265 ± 15 Ma (MSWD = 0.57) is roughly similar to the age of emplacement of the lamprophyres in the upper crust in the mid-late Permian, and coincides with the period following the main tectonometamorphic and magmatic events of the post-collisional evolution in the Catalan Coastal Range. Th/U and La/Sm ratios suggest a metamorphic origin for most allanite grains, but a combination of metamorphic processes prior to partial melting, early-late magmatic crystallization, and/or post-magmatic hydrothermal processes is the most plausible explanation to account for the diversity of allanite grains in Les Guilleries lamprophyres

Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes

Different mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (so-called holes) on purine nucleobases. The interaction of DNA with proteins may protect DNA from oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acids. However, how protein binding affects HT dynamics in DNA is still poorly understood. Here, we report a computational study of HT in DNA complexes with methyltransferase HhaI with the aim of elucidating the molecular factors that explain why long-range DNA HT is inhibited when the glutamine residue inserted in the double helix is mutated into a tryptophan. We combine molecular dynamics, quantum chemistry, and kinetic Monte Carlo simulations and find that protein binding stabilizes the energies of the guanine radical cation states and significantly impacts the corresponding electronic couplings, thus determining the observed behavior, whereas the formation of a tryptophan radical leads to less efficient HT

Systematic review and meta-analysis on the adjunctive use of host immune modulators in non-surgical periodontal treatment in healthy and systemically compromised patients.

Considering the central role of inflammation in the pathogenesis of periodontitis, the combination of NSPT with different agents that can modulate the host immune-inflammatory response has been proposed to enhance the outcomes of NSPT. The aim of this paper is to systematically review the literature on the efficacy of systemic host modulators (HMs) as adjuncts to non-surgical periodontal therapy (NSPT) in improving pocket depth (PD) reduction and clinical attachment level (CAL) gain in healthy and systemically compromised patients. RCTs with ≥ 3 months follow-up were independently searched by two reviewers. Meta-analysis was performed when ≥ 3 studies on the same HM were identified. The quality of the evidence was rated according to the GRADE approach to rate the certainty of evidence. 38 articles were included in the qualitative assessment and 27 of them were included in the meta-analysis. There is low/very low evidence that the adjunctive use of sub-antimicrobial dose of doxycicline, melatonin and the combination of omega-3 and low dose aspirin (in type 2 diabetic patients) to NSPT would improve PD and/or CAL. Conflicting evidence is available on the efficacy of probiotics. Future studies controlling for confounding factors, using composite outcomes to define the endpoint of therapy and considering not only the patient- but also as the site-specific effect of systemic HMs are warranted. The dosage, posology and long-term effect of HMs still need to be clarified, also in association to the presence of systemic conditions potentially affecting the response to HMs administration