Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis.

To define specific pathways important in the multistep transformation process of normal plasma cells (PCs) to monoclonal gammopathy of uncertain significance (MGUS) and multiple myeloma (MM), we have applied microarray analysis to PCs from 5 healthy donors (N), 7 patients with MGUS, and 24 patients with newly diagnosed MM. Unsupervised hierarchical clustering using 125 genes with a large variation across all samples defined 2 groups: N and MGUS/MM. Supervised analysis identified 263 genes differentially expressed between N and MGUS and 380 genes differentially expressed between N and MM, 197 of which were also differentially regulated between N and MGUS. Only 74 genes were differentially expressed between MGUS and MM samples, indicating that the differences between MGUS and MM are smaller than those between N and MM or N and MGUS. Differentially expressed genes included oncogenes/tumor-suppressor genes (LAF4, RB1, and disabled homolog 2), cell-signaling genes (RAS family members, B-cell signaling and NF-kappaB genes), DNA-binding and transcription-factor genes (XBP1, zinc finger proteins, forkhead box, and ring finger proteins), and developmental genes (WNT and SHH pathways). Understanding the molecular pathogenesis of MM by gene expression profiling has demonstrated sequential genetic changes from N to malignant PCs and highlighted important pathways involved in the transformation of MGUS to MM.

Expression of high amounts of the CD117 molecule in a case of B-cell non-Hodgkin's lymphoma carrying the t(14:18) translocation.

The c-kit proto-oncogen (CD117) has been described to be present in normal and neoplastic hemopoietic cells including both myeloid and lymphoid lineages. Among the normal lymphoid cells CD117 expression would be restricted to a small subset of NK-cells, and to early T-cell precursors and it is not expressed by normal B-cells. Regarding chronic lymphoproliferative disorders the only data provided up to now suggests that CD117 expression is restricted to cases of Hodgkin's disease and anaplastic large-cell lymphoma. In the present paper we describe a case of a B-cell chronic lymphoproliferative disorder carrying the t(14:18) translocation as demonstrated by molecular studies, in which the flow cytometric immunophenotypic analysis of both peripheral blood and bone marrow samples revealed the expression of high amounts of the CD117 antigen in the surface of the clonal B-cell population. Further studies are necessary to explore both the functional role of c-kit expression in the neoplastic B-cells from this patient and its potential utility for the diagnosis and follow-up of patients with B-cell non-Hodgkin's lymphoma.

Role of NleH, a type III secreted effector from attaching and effacing pathogens, in colonization of the bovine, ovine, and murine gut

The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 colonizes human and animal gut via formation of attaching and effacing lesions. EHEC strains use a type III secretion system to translocate a battery of effector proteins into the mammalian host cell, which subvert diverse signal transduction pathways implicated in actin dynamics, phagocytosis, and innate immunity. The genomes of sequenced EHEC O157:H7 strains contain two copies of the effector protein gene nleH, which share 49% sequence similarity with the gene for the Shigella effector OspG, recently implicated in inhibition of migration of the transcriptional regulator NF-kappaB to the nucleus. In this study we investigated the role of NleH during EHEC O157:H7 infection of calves and lambs. We found that while EHEC DeltanleH colonized the bovine gut more efficiently than the wild-type strain, in lambs the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. Using the mouse pathogen Citrobacter rodentium, which shares many virulence factors with EHEC O157:H7, including NleH, we observed that the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. We found no measurable differences in T-cell infiltration or hyperplasia in colons of mice inoculated with the wild-type or the nleH mutant strain. Using NF-kappaB reporter mice carrying a transgene containing a luciferase reporter driven by three NF-kappaB response elements, we found that NleH causes an increase in NF-kappaB activity in the colonic mucosa. Consistent with this, we found that the nleH mutant triggered a significantly lower tumor necrosis factor alpha response than the wild-type strain.

Contact dermatitis from shoes: an update

Contact dermatitis is a common inflammatory skin condition characterized by erythematous and pruritic skin lesions that occur after contact with a foreign substance. There are two forms of contact dermatitis: irritant and allergic. Irritant contact dermatitis is caused by the non–immune-modulated irritation of the skin by a substance, leading to skin changes. Allergic contact dermatitis is a delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin; skin changes occur after reexposure to the substance. A medical condition referred to as “shoe dermatitis” is a form of contact dermatitis caused by the contact of the foot with parts of the shoe due to these materials. Shoe dermatitis is a diagnostic and therapeutic challenge and is a common type of contact dermatitis. It is imperative the foot and ankle physician become familiar with recognizing signs and symptoms of shoe dermatitis so that their patients can be accurately diagnosis and appropriately treated to avoid secondary infections and disability. This review will first present causative factors for the etiology of shoe contact dermatitis supported by clinical-based evidence as found in the medical literature. Secondly, a description of the signs and symptoms of shoe contact dermatitis will be presented in a narrative fashion. Finally, both treatment options and preventative measures to avoid shoe.

Unfolding the Archive (Group Exhibition)

Unfolding the Archive, an exhibition of new work by the international artists’ group Floating World, is the result of a collaboration between the National Irish Visual Arts Library (NIVAL) and the F.E. McWilliam Gallery & Studio in partnership with the NCAD Gallery at the National College of Art & Design. The exhibition takes its title from the tangible starting point for engagement with an archive – the simple act of unfolding – and the practice of appraisal, valuation and interpretation that is inherent in this process.

The Ballets Russes connection with fashion.

This paper examines the influence that the costume designers of the Ballets Russes, many of whom were important artists from significant art movements of the day, had on contemporaneous fashion. It looks at why in particular the 'Ballets Russes' artists Leon Bakst and Natalia Goncharova went on to involve themselves in actual fashion production and the similarities between their work and the fashion designers producing work at the same time, principally Paul Poiret, Mariano Fortuny and Coco Chanel. Overall, this paper investigates the significance of the cultural times and of the distinct characteristics of the separate art forms, that may have encouraged avant-garde art and fashion to crossover and collaborate so unreservedly.

Evaluating the conservation of graffiti based on cultural significance.

Purpose – Graffiti, both ancient and contemporary, could be argued to be significant and therefore worthy of protection. Attaching value is, however, subjective with no specific method being solely utilised for evaluating these items. The purpose of this paper to help those who are attempting to evaluate the merit of graffiti to do so, by determining “cultural significance”, which is a widely adopted concept for attaching value to the historic built environment. The current Scottish system utilised to assess “cultural significance” is the Scottish Historic Environment Policy (SHEP) which shares many common features with other determinants of cultural significance in different countries. The SHEP document, as with other systems, could however be criticised for being insufficiently sensitive to enable the evaluation of historic graffiti due, in part, to the subjective nature of determination of aesthetic value. Design/methodology/approach – A review of literature is followed by consideration of case studies taken from a variety of historical and geographical contexts. The majority of examples of graffiti included in this paper have been selected for their relative high profile, previous academic study, and breadth of geographic spread. This selection will hopefully enable a relatively comprehensive, rational assessment to be undertaken. That being said, one example has been integrated to reflect commonly occurring graffiti that is typical to all of the built environment. Findings – The determination of aesthetic value is particularly problematic for the evaluator and the use of additional art‐based mechanisms such as “significant form”, “self expression” and “meaning” may aid this process. Regrettably, these determinants are also in themselves subjective, enhancing complexity of evaluation. Almost all graffiti could be said to have artistic merit, using the aforementioned determinants. However, whether it is “good” art is an all together different question. The evaluation of “good” art and graffiti would have traditionally been evaluated by experts. Today, determination of graffiti should be evaluated and value attached by broader society, community groups, and experts alike. Originality/value – This research will assist those responsible for historic building conservation with the evaluation of whether graffiti is worthy of conservation.

Thermochromic dyes and sunlight activating systems - An alternative means to induce colour change.

The general purpose of this work is to investigate the potential of a mobile phone to capture soil colour images and process them, returning the corresponding Munsell colour coordi- nates from the digital RGB captured images, and also estimate the tristimulus values from the same images. A mobile phone HTC Desire HD, which runs Android 2.2, has been used to take and process images of a Munsell Soil Colour Chart under fixed illumination conditions. To obtain tristimulus values of each sample a Konica Minolta CS2000d spectroradiometer has been used under the same conditions. Penrose’s pseudoinverse method has been used to compute relationship between RGB coordinates from digital images and tristimulus values. Once the model has been computed it was implemented in the mobile phone. Results of this calibration show that more than 90% of the samples used in the calibration (238 chips) were measured by our mobile phone application with accuracy below 2.03 CIELAB units and a mean correlation coefficient equal to 0.9972. In case of Munsell models mean correlation coefficient is equal to 0.9407. This points to the idea that a conventional mobile device can be used to determine the colour of a soil under controlled illumination conditions.

Desempenho de sementes de soja revestidas com biopolímeros

The use of biopolymers that help to fix pesticides efficiently and degrade easily without harming the environment, and still improve the physiological performance of field soybean seed may bring contributions to the soybean yield. This study aimed to evaluate the effect of cassava starch polymers (AM), sodium alginate (ALG) and polyvinyl alcohol (PVOH), in the concentrations 2, 4 and 6 g / 100 ml of solution, in the physiological attributes of seeds soy, seed speed soaking and performance of soybean seeds after three months of storage. The soybean variety used was the NK 7059 RR. The experimental design used for the three studies was a factorial with 48 experimental units: 3 polymers (AM, ALG and PVOH), 4 different concentrations (0%, 2%, 4% and 6%), with four replications, in a completely randomized design. It was observed the level of significance of the factors and their interactions, applying the test F. The polymers were evaluated by the Tukey test at 5% probability, and the concentrations were evaluated by polynomial regression. The witness obtained better results for most variables studied. Among the polymers, the best coating was observed PVOH because it was the less viscous polymer and visually not served as a substrate for microorganisms. However, also, satisfactory results were obtained for the AM and ALG polymers at a concentration of 2%. There was not interference of the polymers studied with regard to reduction of imbibition rate of soybean seeds. The hydrophilicity of polymers, mainly the AM and ALG accelerated soaking seeds harming germination at concentrations 4% and 6%. In general, the higher the concentration of polymers tended to worse results.

Diagnostico precoz de la inmunodeficiencia severa combinada: es un candidato a incluir en los programas de cribado neonatal?

Inmunodeficiencia Combinada Severa (SCID): Se caracteriza por una ausencia o muy baja concentración de células T funcionales, en muchos casos combinada con una deficiencia cuantitativa de células B y/o NK.

Separating deviant and non-deviant sexual preferences with a dual-target rapid serial visual presentation task

Forskning visar att avvikande sexuell preferens (ASP) är en av de mest centrala prediktorerna för återfall i sexualbrott. Eftersom det är viktigt att det i juridiskt beslutsfattande och behandling av sexualförbrytare finns valida och standardiserade verktyg att tillgå för bedömning av ASP, har forskningen under de senaste åren fokuserats på uppmärksamhetsbaserade metoder. Syftet med avhandlingen var att förbättra uppmärksamhetsbaserade metoder genom utvecklingen av en s.k. Rapid Serial Visual Presentation (dtRSVP) metod för att identifiera ASP. Innan vi testade sampel med sexualbrottslingar så genomförde vi tre studier för att kalibrera förfarandena. I dessa studier undersökte vi möjligheten att differentiera mellan homosexuella och heterosexuella män och hur enkelt deltagarna kunde fuska. Dessutom skapade vi en ny uppsättning standardiserade stimuli för bedömningen av pedofilt sexuellt intresse (Virtual People Set, VPS). I skapandet av stimuli togs de etiska och juridiska problemen i beaktande så långt som möjligt. När vi använde dtRSVP som mätningsförfarande för att skilja åt sexuellläggning i ett sampel av homosexuella och heterosexuella män fann vi att sexuellt relevanta stimuli påverkade informationsbehandlingen på ett förutsägbart sätt. Förfarandet hade en god förmåga att skilja sexuella preferenser mellan grupperna och förfarandet var svårt att påverka genom att fuska. När vi använde dtRSVP som mätningsförfarande för att identifiera avvikande sexuell läggning bland dömda sexbrottslingar fann vi att de visade en annorlunda bearbetning av sexuella stimuli jämfört med andra deltagare och att dessa skillnader var i de förväntade riktningarna. Det var däremot svårt att dra några slutsatser angående denna mätmetods förmåga att skilja mellan grupperna pedofiler och icke-pedofiler. Slutligen fann vi att VPS verkar vara ett användbart stimuluspaket för experimentell forskning om pedofilt sexuellt intresse. ---------------------------------------------------- Tutkimuksien mukaan poikkeava seksuaalinen mieltymys (PSM) on yksi seksuaalirikoksen uusimisen keskeisimmistä ennustajista. Oikeudellisessa päätöksenteossa ja seksuaalirikollisten hoidossa on tärkeää, että on käytettävissä kelvollisia ja standardisoituja välineitä PSM:n arvioinnissa. Sen vuoksi on tutkimuksissa viime vuosina keskitytty huomaavaisuuteen perustuviin menetelmiin. Tämän tutkielman tarkoitus oli parantaa huomaavaisuuteen perustuvia menetelmiä kehittämällä nk. Rapid Serial Visual Presentation (dtRSVP) menetelmän. Kalibroidakseen menettelytapoja suoritettiin kolme tutkimusta ennen kuin tutkittiin koeryhmää, johon kuuluvat seksuaalirikollisia. Näissä tutkimuksissa tutkittiin mahdollisuutta erotella homoseksuaalisia ja heteroseksuaalisia miehiä ja tutkittiin missä määrin osallistujien oli helppo huiputtaa. Sen lisäksi, pedofiilisen seksuaalisen mieltymyksen arviointia varten kehitettiin uutta sarjaa standardisoituja virikkeitä (Virtual People Set, VPS). Kehitettäessä virikkeitä otettiin mahdollisimman pitkälti huomioon eettisiä ja oikeudellisia ongelmia. Käytettäessä dtRSVP mittausmenetelmää erotellakseen homo- ja heteroseksuaalista suuntautumista havaitsimme, että seksuaaliset virikkeet vaikuttivat tietojenkäsittelyyn ennustettavalla tavalla. Menettelytavan avulla pystyttiin erotella koeryhmässä olevia seksuaalisia mieltymyksiä ja menettelytapaan oli vaikeaa vaikuttaa huijaamalla. Käytettäessä dtRSVP mittausmenetelmää tunnistaakseen poikkeavaa seksuaalista mieltymystä tuomittujen seksuaalirikollisten keskenään havaitsimme, että he osoittivat erilaista käsittelyä seksuaalisista virikkeistä toisiin osallistujiin verrattuna ja tulokset olivat ennustettavia. Silti oli vaikeaa tehdä johtopäätöksiä mittausmenetelmän kyvystä erotella ryhmiä pedofiilisiä ja ei-pedofiilisiä miehiä. Lopuksi havaitsimme, että VPS näyttää olevan käyttökelpoinen stimulussarja pedofiilisen seksuaalisen mieltymyksen kokeellisissa tutkimuksissa.

Climbing Combinatorial Fitness Landscapes

International audience

Design and validation of a novel generic platform for the production of tetravalent IgG1-like bispecific antibodies

International audience