Higgs pair production at the LHC in models with universal extra dimensions

In this Letter we study the process of gluon fusion into a pair of Higgs bosons in a model with one universal extra dimension. We find that the contributions from the extra top quark Kaluza-Klem excitations lead to a Higgs pair production cross section at the LHC that can be significantly altered compared to the Standard Model value for small values of the compactification scale. (C) 2007 Elsevier B.V. All rights reserved.

Right adolescent idiopathic thoracic curve (Lenke 1 A and B): does cost of instrumentation and implant density improve radiographic and cosmetic parameters?

In adolescent idiopathic scoliosis (AIS) there has been a shift towards increasing the number of implants and pedicle screws, which has not been proven to improve cosmetic correction. To evaluate if increasing cost of instrumentation correlates with cosmetic correction using clinical photographs. 58 Lenke 1A and B cases from a multicenter AIS database with at least 3 months follow-up of clinical photographs were used for analysis. Cosmetic parameters on PA and forward bending photographs included angular measurements of trunk shift, shoulder balance, rib hump, and ratio measurements of waist line asymmetry. Pre-op and follow-up X-rays were measured for coronal and sagittal deformity parameters. Cost density was calculated by dividing the total cost of instrumentation by the number of vertebrae being fused. Linear regression and spearman`s correlation were used to correlate cost density to X-ray and photo outcomes. Three independent observers verified radiographic and cosmetic parameters for inter/interobserver variability analysis. Average pre-op Cobb angle and instrumented correction were 54A degrees (SD 12.5) and 59% (SD 25) respectively. The average number of vertebrae fused was 10 (SD 1.9). The total cost of spinal instrumentation ranged from $6,769 to $21,274 (Mean $12,662, SD $3,858). There was a weak positive and statistically significant correlation between Cobb angle correction and cost density (r = 0.33, p = 0.01), and no correlation between Cobb angle correction of the uninstrumented lumbar spine and cost density (r = 0.15, p = 0.26). There was no significant correlation between all sagittal X-ray measurements or any of the photo parameters and cost density. There was good to excellent inter/intraobserver variability of all photographic parameters based on the intraclass correlation coefficient (ICC 0.74-0.98). Our method used to measure cosmesis had good to excellent inter/intraobserver variability, and may be an effective tool to objectively assess cosmesis from photographs. Since increasing cost density only improves mildly the Cobb angle correction of the main thoracic curve and not the correction of the uninstrumented spine or any of the cosmetic parameters, one should consider the cost of increasing implant density in Lenke 1A and B curves. In the area of rationalization of health care expenses, this study demonstrates that increasing the number of implants does not improve any relevant cosmetic or radiographic outcomes.

New transposons to generate GFP protein fusions in Candida albicans

Transposon elements are important tools for gene function analysis, for example they can be used to easily create genome-wide collections of insertion mutants. Transposons may also carry sequences coding for an epitope or fluorescent marker useful for protein expression and localization analysis. We have developed three new Tn5-based transposons that incorporate a GFP (green fluorescent protein) coding sequence to generate fusion proteins in the important fungal pathogen Candida albicans. Each transposon also contains the URA3 and Kan(R) genes for yeast and bacterial selection, respectively. After in vitro transposition, the insertional allele is transferred to the chromosomal locus by homologous recombination. Transposons Tn5-CaGFP and Tn5-CaGFP-URA3:FLIP can generate C-terminal truncated GFP fusions. A URA3 flipper recycling cassette was incorporated into the transposon Th5-CaGFP-UFRA3:FLIP. After the induction of Flip recombinase to excise the marker, the heterozygous strain is transformed again in order to obtain a GFP-tagged homozygous strains. In the Tn5-CaGFP-FL transposon the markers are flanked by a rare-cutting enzyme. After in vitro transposition into a plasmid-borne target gene, the markers are eliminated by restriction digestion and religation, resulting in a construct coding for full-length GFP-fusion proteins. This transposon can generate plasmid libraries of GFP insertions in proteins where N- or C-terminal tagging may alter localization. We tested our transposon system by mutagenizing the essential septin CDC3 gene. The results indicate that the Cdc3 C-terminal extension is important for correct septin filament assembly. The transposons described here provide a new system to obtain global gene expression and protein localization data in C. albicans. (c) 2008 Elsevier B.V. All rights reserved.

GD1b-Derived Gangliosides Modulate Fc epsilon RI Endocytosis in Mast Cells

The role of the mast cell-specific gangliosides in the modulation of the endocytic pathway of Fc epsilon RI was investigated in RBL-2H3 cells and in the ganglioside-deficient cell lines, E5 and D1. MAb BC4, which binds to the alpha subunit of Fc epsilon RI, was used in the analysis of receptor internalization. After incubation with BC4-FITC for 30 min, endocytic vesicles in RBL-2H3 and E5 cells were dispersed in the cytoplasm. After 1 hr, the endocytic vesicles of the RBL-2H3 cells had fused and formed clusters, whereas in the E5 cells, the fusion was slower. In contrast, in D1 cells, the endocytic vesicles were smaller and remained close to the plasma membrane even after 3 hr of incubation. When incubated with BC4-FITC and subsequently imunolabeled for markers of various endocytic compartments, a defect in the endocytic pathway in the E5 and D1 cells became evident. In the D1 cells, this defect was observed at the initial steps of endocytosis. Therefore, the ganglioside derivatives from GD1b are important in the endocytosis of Fc epsilon RI in mast cells. Because gangliosides may play a role in mast cell-related disease processes, they provide an attractive target for drug therapy and diagnosis. (J Histochem Cytochem 59:428-440, 2011)

Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is characterized by a block in differentiation and accumulation of promyelocytes in the bone marrow and blood. The majority of APL patients harbor the t(15: 17) translocation leading to expression of the fusion protein promyelocytic-retinoic acid receptor alpha. Treatment with retinoic acid leads to degradation of promyelocytic-retinoic acid receptor alpha protein and disappearance of leukemic cells; however, 30% of APL patients relapse after treatment. One potential mechanism for relapse is the persistence of cancer ""stem"" cells in hematopoietic organs after treatment. Using a novel sorting strategy we developed to isolate murine myeloid cells at distinct stages of differentiation, we identified a population of committed myeloid cells (CD34(+), c-kit(+), Fc gamma RIII/II(+), Gr1(int)) that accumulates in the spleen and bone marrow in a murine model of APL. We observed that these cells are capable of efficiently generating leukemia in recipient mice, demonstrating that this population represents the APL cancer-initiating cell. These cells down-regulate the transcription factor CCAAT/enhancer binding protein alpha (C/EBP alpha) possibly through a methylation-dependent mechanism, indicating that C/EBP alpha deregulation contributes to transformation of APL cancer-initiating cells. Our findings provide further understanding of the biology of APL by demonstrating that a committed transformed progenitor can initiate and propagate the disease. (Blood. 2009; 114: 5415-5425)

Supporting content-based image retrieval and computer-aided diagnosis systems with association rule-based techniques

In this work, we take advantage of association rule mining to support two types of medical systems: the Content-based Image Retrieval (CBIR) systems and the Computer-Aided Diagnosis (CAD) systems. For content-based retrieval, association rules are employed to reduce the dimensionality of the feature vectors that represent the images and to improve the precision of the similarity queries. We refer to the association rule-based method to improve CBIR systems proposed here as Feature selection through Association Rules (FAR). To improve CAD systems, we propose the Image Diagnosis Enhancement through Association rules (IDEA) method. Association rules are employed to suggest a second opinion to the radiologist or a preliminary diagnosis of a new image. A second opinion automatically obtained can either accelerate the process of diagnosing or to strengthen a hypothesis, increasing the probability of a prescribed treatment be successful. Two new algorithms are proposed to support the IDEA method: to pre-process low-level features and to propose a preliminary diagnosis based on association rules. We performed several experiments to validate the proposed methods. The results indicate that association rules can be successfully applied to improve CBIR and CAD systems, empowering the arsenal of techniques to support medical image analysis in medical systems. (C) 2009 Elsevier B.V. All rights reserved.

Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia

Loss-of-function mutations in telomerase complex genes can cause bone marrow failure, dyskeratosis congenita, and acquired aplastic anemia, both diseases that predispose to acute myeloid leukemia. Loss of telomerase function produces short telomeres, potentially resulting in chromosome recombination, end-to-end fusion, and recognition as damaged DNA. We investigated whether mutations in telomerase genes also occur in acute myeloid leukemia. We screened bone marrow samples from 133 consecutive patients with acute myeloid leukemia and 198 controls for variations in TERT and TERC genes. An additional 89 patients from a second cohort, selected based on cytogenetic status, and 528 controls were further examined for mutations. A third cohort of 372 patients and 384 controls were specifically tested for one TERT gene variant. In the first cohort, 11 patients carried missense TERT gene variants that were not present in controls (P<0.0001); in the second cohort, TERT mutations were associated with trisomy 8 and inversion 16. Mutation germ-line origin was demonstrated in 5 patients from whom other tissues were available. Analysis of all 3 cohorts (n = 594) for the most common gene variant (A1062T) indicated a prevalence 3 times higher in patients than in controls (n = 1,110; P = 0.0009). Introduction of TERT mutants into telomerase-deficient cells resulted in loss of enzymatic activity by haploinsufficiency. Inherited mutations in TERT that reduce telomerase activity are risk factors for acute myeloid leukemia. We propose that short and dysfunctional telomeres limit normal stem cell proliferation and predispose for leukemia by selection of stem cells with defective DNA damage responses that are prone to genome instability.

Inhibition of Expression of HTLV-1 Structural Genes Mediated by Short Hairpin RNA In Vitro

Background: Human T-lymphotropic virus 1 (HTLV-1) is associated with the T-cell malignancy known as adult T-cell leukemia! lymphoma (ATLL) and with a disorder called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Currently, the treatment of these diseases is based on symptom relief. RNA interference (RNAi) technology has been described as an efficient mechanism for development of new therapeutic methods. Thus, the aim of this study was to evaluate the inhibition of HTLV-1 structural proteins using short hairpin RNAs (shRNAs) expressed by non-viral vectors. Materials and Methods: Reporter plasmids that express enhanced green fluorescent protein-Gag (EGFP-Gag) and EGFP-Env fusion proteins and vectors that express shRNAs corresponding to the HTLV-1 gag and env genes were constructed. shRNA vectors and reporter plasmids were simultaneously transfected into HEK 293 cells. Results: Fluorescence microscopy, flow cytometry and real-time PCR showed that shRNAs were effective in inhibiting the fusion proteins. Conclusion: These shRNAs are effective against the expression of structural genes and may provide an approach to the development of new therapeutic agents.

An association rule-based method to support medical image diagnosis with efficiency

In this paper, we propose a method based on association rule-mining to enhance the diagnosis of medical images (mammograms). It combines low-level features automatically extracted from images and high-level knowledge from specialists to search for patterns. Our method analyzes medical images and automatically generates suggestions of diagnoses employing mining of association rules. The suggestions of diagnosis are used to accelerate the image analysis performed by specialists as well as to provide them an alternative to work on. The proposed method uses two new algorithms, PreSAGe and HiCARe. The PreSAGe algorithm combines, in a single step, feature selection and discretization, and reduces the mining complexity. Experiments performed on PreSAGe show that this algorithm is highly suitable to perform feature selection and discretization in medical images. HiCARe is a new associative classifier. The HiCARe algorithm has an important property that makes it unique: it assigns multiple keywords per image to suggest a diagnosis with high values of accuracy. Our method was applied to real datasets, and the results show high sensitivity (up to 95%) and accuracy (up to 92%), allowing us to claim that the use of association rules is a powerful means to assist in the diagnosing task.

Mucoepidermoid Carcinoma of the Lung Arising at the Primary Site of A Bronchogenic Cyst: Clinical, Cytogenetic, and Molecular Findings

Primary lung tumors are rare in children, and mucoepidermoid carcinoma (MEC) represents less than 10% of them. Additionally, MEC arising from bronchogenic cysts (BC) is particularly unusual. We describe the clinical and genetic findings on a MEC occurring within a previous location of a BC in an adolescent. This particular association has not been previously reported. The lesion revealed normal karyotype without the typical t(11;19)(q21;p13) translocation. Cyclin D1 overexpression (165-fold increase) was demonstrated by real-time PCR although FISH assessment showed normal hybridization at 11q13. Information on these unusual clinical presentations may present relevant insight on tumorigenesis of infrequent pediatric pulmonary tumors. Pediatr Blood Cancer 2011;56:311-313. (C) 2010 Wiley-Liss, Inc.

Secondary PSF/TFE3-associated renal cell carcinoma in a child treated for genitourinary rhabdomyosarcoma

Xp11.2 translocation-associated renal cell carcinoma (RCC) is a rare tumor that accounts for at least one-third of childhood RCC. Different reports have emphasized that previous radio/chemotherapy might be involved in its pathogenesis. We describe a child who developed a t(X;1) (p11.2;p34) associated RCC after previous treatment for genitourinary rhabdomyosarcoma in infancy. The presence of the PSF-TFE3 fusion has only been described in a very limited number of cases. Our report expands the spectrum of tumors in which RCC can arise in the pediatric age group after chemotherapy.

Degeneration of dystrophic or injured skeletal muscles induces high expression of Galectin-1

Muscle degenerative diseases such as Duchenne Muscular Dystrophy are incurable and treatment options are still restrained. Understanding the mechanisms and factors responsible for muscle degeneration and regeneration will facilitate the development of novel therapeutics. Several recent studies have demonstrated that Galectin-1 (Gal-1), a carbohydrate-binding protein, induces myoblast differentiation and fusion in vitro, suggesting a potential role for this mammalian lectin in muscle regenerative processes in vivo. However, the expression and localization of Gal-1 in vivo during muscle injury and repair are unclear. We report the expression and localization of Gal-1 during degenerative-regenerative processes in vivo using two models of muscular dystrophy and muscle injury. Gal-1 expression increased significantly during muscle degeneration in the murine mdx and in the canine Golden Retriever Muscular Dystrophy animal models. Compulsory exercise of mdx mouse, which intensifies degeneration, also resulted in sustained Gal-1 levels. Furthermore, muscle injury of wild-type C57BL/6 mice, induced by BaCl(2) treatment, also resulted in a marked increase in Gal-1 levels. Increased Gal-1 levels appeared to localize both inside and outside the muscle fibers with significant extracellular Gal-1 colocalized with infiltrating CD45(+) leukocytes. By contrast, regenerating muscle tissue showed a marked decrease in Gal-1 to baseline levels. These results demonstrate significant regulation of Gal-1 expression in vivo and suggest a potential role for Gal-1 in muscle homeostasis and repair.

Healing of skin wounds in the African catfish Clarias gariepinus

The African catfish Clarias gariepinus was used as a model for wound healing and tissue regeneration in a scale-less fish. A temporal framework of histological and cell proliferation markers was established after wound induction in the dorsolateral cranial region, by removing the epidermal and dermal layers, including stratum adiposum (SA). Wound closure and epidermis formation was initiated within 3 h post-procedure (hpp) with migration and concomitant proliferation of epidermal cells from the wound borders. The wound was covered by this primary epidermal front 12 hpp and fusion of the opposing epidermal fronts occurred within 24 hpp. Attachment of the newly formed epidermal layer to the underlying dermis was observed 48 hpp concomitant with a second wave of cell proliferation at the wound edge. Normal epidermal thickness within the wound was achieved 72 hpp. Formation of a basement membrane occurred by 120 hpp with concomitant emergence of the SA from the wound borders. Wound healing in C. gariepinus skin involved closure of the wound and re-epithelization through cell migration with a single wave of early cell proliferation not documented in other species. Furthermore, covering of the wound by epithelium as well as the reappearance of the basement membrane and SA occurred sooner than in other fish species. (C) 2008 The Authors Journal compilation (C) 2008 The Fisheries Society of the British Isles.

Evaluation of Leptospiral Recombinant Antigens MPL17 and MPL21 for Serological Diagnosis of Leptospirosis by Enzyme-Linked Immunosorbent Assays

Leptospirosis is a zoonosis of multisystem involvement caused by pathogenic strains of the genus Leptospira. In the last few years, intensive studies aimed at the development of a vaccine have provided important knowledge about the nature of the immunological mechanisms of the host. The purpose of this study was to analyze the immune responses to two recombinant proteins, MPL17 and MPL21 (encoded by the genes LIC10765 and LIC13131, respectively) of Leptospira interrogans serovar Copenhageni in individuals during infection. The recombinant proteins were expressed in Escherichia coli as six-His tag fusion proteins and were purified from the soluble bacterial fraction by affinity chromatography with Ni2+ -charged resin. The recombinant proteins were used to evaluate their ability to bind to immunoglobulin G (IgG) (and IgG subclass) or IgM antibodies in serum samples from patients in the early and convalescent phases of leptospirosis (n = 52) by enzyme-linked immunosorbent assays. The prevalences of total IgG antibodies against MPL17 and MPL21 were 38.5% and 21.2%, respectively. The titers achieved with MPL17 were statistically significantly higher than those obtained by the reference microscopic agglutination test. The specificity of the assay was estimated to be 95.5% for MPL17 and 80.6% for MPL21 when serum samples from individuals with unrelated febrile diseases and control healthy donors were tested. The proteins are conserved among Leptospira strains that cause human and animal diseases. MPL17 and MPL21 are most likely new surface proteins of leptospires, as revealed by liquid-phase immunofluorescence assays with living organisms. Our results demonstrate that these recombinant proteins are highly immunogenic and, when they are used together, might be useful as a means of diagnosing leptospirosis.

Morphological assessment of dentine and cementum following apicectomy with Zekrya burs and Er:YAG laser associated with direct and indirect Nd:YAG laser irradiation

Objectives. This study aimed to assess the apical surface morphology of maxillary central incisors resected 3.0 mm from the tooth apex using Zekrya burs or Er:YAG laser, with or without subsequent direct Nd:YAG laser irradiation (apical and buccal surfaces) and indirect irradiation (palatal surface). Study design. Forty maxillary central incisors were instrumented and obturated. The roots were divided into 4 groups according to the root resection method (Zekrya bur or Er: YAG laser -1.8 W, 450 mJ, 4 Hz, 113 J/cm(2)) and further surface treatment (none or Nd: YAG laser -2.0 W, 100 mJ, 20 Hz, 124 J/cm(2)). The teeth were prepared for SEM analysis. Scores ranging from 1 to 4 were attributed to cut quality and morphological changes. The data were analyzed by the Kruskal-Wallis test and by Dunn`s test. Results. SEM images showed irregular surfaces on the apical portions resected with Zekrya burs, with smear layer and grooves in the resected dentine and slight gutta-percha displacement and plasticization. On the other hand, apicectomies carried out with Er: YAG laser showed morphological changes compatible with ablated dentine, with rough surfaces and craters. In spite of the presence of plasticized gutta-percha, with the presence of bubbles, an irregular adaptation of the filling material to the root walls was also observed. Direct Nd: YAG laser irradiation of the apical and buccal surfaces of the resected roots resulted in areas of resolidification and fusion in the dentine and cementum, with a vitrified aspect; indirect Nd: YAG laser irradiation of the palatal surfaces yielded a lower number of changes in the cementum, with irregular resolidification areas. Conclusions. There were no differences in terms of cut quality between the use of burs and Er: YAG laser or between the 2 surfaces (apical and buccal) treated with Nd: YAG laser with direct irradiation. However, morphological changes were significantly less frequent on surfaces submitted to indirect irradiation (palatal) when compared with those directly irradiated. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: e77-e82)