Structure of a lectin with antitumoral properties in king bolete (Boletus edulis) mushrooms.

A novel lectin has been isolated from the fruiting bodies of the common edible mushroom Boletus edulis (king bolete, penny bun, porcino or cep) by affinity chromatography on a chitin column. We propose for the lectin the name BEL (B. edulis lectin). BEL inhibits selectively the proliferation of several malignant cell lines and binds the neoplastic cell-specific T-antigen disaccharide, Galβ1-3GalNAc. The lectin was structurally characterized: the molecule is a homotetramer and the 142-amino acid sequence of the chains was determined. The protein belongs to the saline-soluble family of mushroom fruiting body-specific lectins. BEL was also crystallized and its three-dimensional structure was determined by X-ray diffraction to 1.15 Å resolution. The structure is similar to that of Agaricus bisporus lectin. Using the appropriate co-crystals, the interactions of BEL with specific mono- and disaccharides were also studied by X-ray diffraction. The six structures of carbohydrate complexes reported here provide details of the interactions of the ligands with the lectin and shed light on the selectivity of the two distinct binding sites present in each protomer

Ortho-para transition in molecular hydrogen

The radiative ortho-para transition in the molecular hydrogen is studied. This highly forbidden transition is very sensitive to relativistic and subtle nonadiabatic effects. Our result for the transition rate in the ground vibrational level \Gamma(J=1\to J=0) = 6.20(62)\cdot 10^{-14} \iyr is significantly lower in comparison to all the previous approximate calculations. Experimental detection of such a weak line by observation of, for example, the cold interstellar molecular hydrogen is at present unlikely.Comment: 4 pages, submitted to Phys. Rev.

Growth and dislocation studies of β-HMX

Background: The defect structure of organic materials is important as it plays a major role in their crystal growth properties. It also can play a subcritical role in “hot-spot” detonation processes of energetics and one such energetic is cyclotetramethylene-tetranitramine, in the commonly used beta form (β-HMX). Results: The as-grown crystals grown by evaporation from acetone show prismatic, tabular and columnar habits, all with {011}, {110}, (010) and (101) faces. Etching on (010) surfaces revealed three different types of etch pits, two of which could be identified with either pure screw or pure edge dislocations, the third is shown to be an artifact of the twinning process that this material undergoes. Examination of the {011} and {110} surfaces show only one type of etch pit on each surface; however their natural asymmetry precludes the easy identification of their Burgers vector or dislocation type. Etching of cleaved {011} surfaces demonstrates that the etch pits can be associated with line dislocations. All dislocations appear randomly on the crystal surfaces and do not form alignments characteristic of mechanical deformation by dislocation slip. Conclusions: Crystals of β-HMX grown from acetone show good morphological agreement with that predicted by modelling, with three distinct crystal habits observed depending upon the supersaturation of the growth solution. Prismatic habit was favoured at low supersaturation, while tabular and columnar crystals were predominant at higher super saturations. The twin plane in β-HMX was identified as a (101) reflection plane. The low plasticity of β-HMX is shown by the lack of etch pit alignments corresponding to mechanically induced dislocation arrays. On untwinned {010} faces, two types of dislocations exist, pure edge dislocations with b = [010] and pure screw dislocations with b = [010]. On twinned (010) faces, a third dislocation type exists and it is proposed that these pits are associated with pure screw dislocations with b = [010]

An Alternative Yukawa Unified SUSY Scenario

Supersymmetric SO(10) Grand Unified Theories with Yukawa unification represent an appealing possibility for physics beyond the Standard Model. However Yukawa unification is made difficult by large threshold corrections to the bottom mass. Generally one is led to consider models where the sfermion masses are large in order to suppress these corrections. Here we present another possibility, in which the top and bottom GUT scale Yukawa couplings are equal to a component of the charged lepton Yukawa matrix at the GUT scale in a basis where this matrix is not diagonal. Physically, this weak eigenstate Yukawa unification scenario corresponds to the case where the charged leptons that are in the 16 of SO(10) containing the top and bottom quarks mix with their counterparts in another SO(10) multiplet. Diagonalizing the resulting Yukawa matrix introduces mixings in the neutrino sector. Specifically we find that for a large region of parameter space with relatively light sparticles, and which has not been ruled out by current LHC or other data, the mixing induced in the neutrino sector is such that $sin^2 2\Theta_{23} \approx 1$, in agreement with data. The phenomenological implications are analyzed in some detail.Comment: 32 pages, 22 Figure

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Thoracoscopic resection of a paraaortic bronchogenic cyst

Bronchogenic mediastinal cysts (BMC) represent 18% of primitive mediastinal tumors and the most frequent cystic lesions in this area. Nowadays, BMC are usually treated by VATS. However, the presence of major adhesions to vital structures is often considered as an unfavourable condition for thoracoscopic treatment. The authors report the thoracoscopic treatment of a BMC having dense adhesions to the aortic arch. Diagnosis and surgical treatment is described. Review of the literature and surgical options on this topic are discussed

FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

BACKGROUND: Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. METHODS: We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. RESULTS: FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples. CONCLUSION: The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis

The research leading to these results has received funding from the British Heart Foundation Center of Research Excellence, Imperial College London, the European Commission under the Seventh Framework Program (FP7/2007–2013; contract no. 201668; AtheroRemo and HEALTH.2012-1.2-1; contract no. 305739 RiskyCAD), The Kennedy Trustees, The Swedish Heart and Lung foundation (20150277), The Swedish Research Council (2015-00582), the Swedish Society of Medicine (SLS-500141), Skåne University Hospital funds, Region Skåne Research funds, and the Novo Nordisk Foundation (grant no. NNF15CC0018346)

Minimal Yukawa-Gauge Mediation

We consider a scenario in which Supersymmetry breaking is communicated to the MSSM fields through the interplay of yukawa and gauge interactions. The MSSM spectrum resembles that of split SUSY scenarios, but on top of that it develops some peculiar features like heavy higgsinos and an inverted hierarchy of sfermion masses. The predictions obtained are consistent with the most recent LHC SUSY and Higgs boson searches.Comment: 33 pages, 3 figures, 2 table