Immunological profiles of patients from endemic areas infected with Schistosoma mansoni

Crude extracts of eggs (SEA) adult worms (SWAP) or cercariae (Cerc) have been used to stimulate Peripheral Blood Mononuclear cells (PBMC) and have provided rather distinct profiles of responses in different types of patients. In genenral it is clear that patients with early infections respond strongly to SEA while response to SWAP are developed more slowly. As infection progresses into the more chronic phases, a general pattern is seen whic leads to lower anti-SEA proliferative responses in the face of higher responses to SWAP and variable anti-cerc responsiveness. Cured not re-exposed patients express very high levels of anti-SEA proliferation. It has recently been seen that those individuals who live in endemic areas and have continued water contact, but are reapeatedly stool-negative (who are presumed to have self-cured or be putatively resistant; endemic normals) are strongly responsive to antigenic extracts, particularly to SEA. Furthermore, our results show that endemic normal individuals have significantly higher IFN gamma production upon PBMC stimulation with schistosome antigens than infected individuals. With the emergence of more studies it is becoming apparent that both the intensity and the prevalence of a given area may influence or shape the general responsiveness of the population under study.

The normative dimension of social life from a second-person perspective

This thesis argues that insofar as we want to account for the normative dimension of social life, we must be careful to avoid construing that normative dimension in such a way as to exclude that which the second-person perspective reveals is important to social life and our ability to participate in it.¦The second-person perspective reveals that social life ought to be understood as a mix or balance of the regular and the irregular, where, in addition, those one interacts with are always to some extent experienced as other in a way that is neither immediately, nor perhaps ultimately, understandable. For persons to be able to participate in social life, conceived of in this way, they must have abilities that allow them to be, to some extent, hesitant and tentative in their relations with others, and thus tolerant of ambiguity, uncertainty and unpredictability, and responsive to and capable of learning from the otherness of others in the course of interacting with them.¦Incorporating the second-person perspective means we have to make some changes to the way we think about the normative in general, and the normative dimension of social life in particular. It does not mean giving up on the distinction between the normative and the regular - that continues to be fundamentally important but it does mean not excluding, as part of social life and as worthy of explanation, all that which is irregular. A radical way of putting it would be to say that there must be a sense in which the irregular is part of the normative. A less radical way, and the way adopted by this thesis, is to say that any account of the normative dimension of social life must not be such as to exclude the importance of irregularity from social life. This will mean 1) not characterising conventions, norms and rules as determinants of appropriateness and inappropriateness; 2) not thinking of them as necessary; 3) not thinking of them as necessarily governing minds; and 4) not thinking of them as necessarily shared.¦-¦L'argument principal de la thèse est que, pour rendre compte de la dimension normative de la vie sociale, il faut veiller à ne pas exclure la perspective de la deuxième personne - une perspective importante pour comprendre la vie sociale et la capacité requise pour y participer.¦Cette perspective nous permet d'imaginer la vie sociale comme un mélange ou un équilibre entre le régulier et l'irrégulier, l'interaction entre des individus pouvant être appréhendée comme l'expérience de chaque personne avec «l'autre» d'une manière qui n'est pas immédiatement compréhensible, et qui ne peut pas, peut-être, être ultimement comprise. Pour participer à la vie sociale, l'on doit avoir la capacité de rester hésitant et «réactif» dans ses relations avec les autres, de rester ouvert à leur altérité et de tolérer l'ambiguïté, l'incertitude et l'imprévisibilité des interactions sociales.¦Adopter une perspective «à la deuxième personne» conduit à une autre manière de penser la normativité en général, et la dimension normative de la vie sociale en particulier. Cela ne veut pas dire qu'il faut abandonner la distinction entre le normatif et le régulier - une distinction qui garde une importance fondamentale - mais qu'il faut reconnaître l'irrégulier comme faisant partie de la vie sociale et comme étant digne, en tant que tel, d'être expliqué. Une conception radicale pourrait même concevoir l'irrégulier comme faisant partie intégrante de la normativité. Une approche moins radicale, qui est celle adoptée dans cette thèse, est de dire que tout compte-rendu de la dimension normative de la vie sociale doit prendre en considération l'importance de l'irrégularité dans la vie sociale. Une telle approche implique que les conventions, normes et règles (1) ne déterminent pas ce qui est approprié ou inapproprié; (2) ne sont pas toujours nécessaires ; (3) ne gouvernent pas le fonctionnement de l'esprit ; et (4) ne sont pas nécessairement partagées.

Materials porosos per liofilització: els liogels

En aquest treball sobre materials porosos obtinguts per liofilització, s’ha demostrat que es poden produir materials anàlegs als aerogels de sílice mitjançant un procés de congelació i posterior sublimació. Malgrat les dificultats que es presenten en el procés de congelació, s’ha aconseguit un nou producte que hem denominat LIOGELS (per diferenciar-los dels aerogels) amb més o menys graus de monoliticitat segons la composició i el procés realitzat. S’han estudiat diversos sistemes de congelació, principalment amb nitrogen líquid i en la cambra del liofilitzador a -80ºC, però també s’han comparat els resultats de congelacions de gels amb tert-butanol a 12ºC (el tert-butanol fon a 25,69ºC). S’han sintetitzat diferents tipus de gels, de cara a la seva liofilització posterior. Alguns dels gels s’han deixat assecar amb molta cura i molt lentament per produir xerogels monolítics, amb l’objectiu de comparar les estructures dels aerogels, els xerogels i els nous liogels produïts en aquest treball. Per tal d’aconseguir líquids de rentat que al congelar no trenquessin l’estructura, s’han buscat les mescles idònies de dissolvents (que no canviessin de volum al congelar). S’ha instal·lat un equip de liofilització a l’Icmab, que s’ha utilitzat per elaborar les mostres estudiades. L’equip de liofilització té fonamentalment dos modes de funcionament: sublimació a través d’un "manifold" i dins d’una cambra amb safates. Per a la caracterització de les mostres dels nous materials obtinguts, s’ha utilitzat l’equip BET, i els equips de microscòpia electrònica SEM i TEM de l’ICMAB. S’han avaluat els resultats obtinguts amb l’equip de porosimetria (BET) i s’han analitzat les fotografies del SEM i del TEM, fent les oportunes comparacions entre aerogels i liogels, i entre aquests i els xerogels.

MSight: an image analysis software for liquid chromatography-mass spectrometry.

Images obtained from high-throughput mass spectrometry (MS) contain information that remains hidden when looking at a single spectrum at a time. Image processing of liquid chromatography-MS datasets can be extremely useful for quality control, experimental monitoring and knowledge extraction. The importance of imaging in differential analysis of proteomic experiments has already been established through two-dimensional gels and can now be foreseen with MS images. We present MSight, a new software designed to construct and manipulate MS images, as well as to facilitate their analysis and comparison.

Mobile termination, network externalities, and consumer expectations

We re-examine the literature on mobile termination in the presence of network externalities. Externalities arise when firms discriminate between on- and off-net calls or when subscription demand is elastic. This literature predicts that profit decreases and consumer surplus increases in termination charge in a neighborhood of termination cost. This creates a puzzle since in reality we see regulators worldwide pushing termination rates down while being opposed by network operators. We show that this puzzle is resolved when consumers' expectations are assumed passive but required to be fulfilled in equilibrium (as defined by Katz and Shapiro, AER 1985), instead of being rationally responsive to non-equilibrium prices, as assumed until now.

Eosinophilic esophagitis: Updated consensus recommendations for children and adults.

Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. In 2007, a consensus recommendation provided clinical and histopathologic guidance for the diagnosis and treatment of EoE; however, only a minority of physicians use the 2007 guidelines, which require fulfillment of both histologic and clinical features. Since 2007, the number of EoE publications has doubled, providing new disease insight. Accordingly, a panel of 33 physicians with expertise in pediatric and adult allergy/immunology, gastroenterology, and pathology conducted a systematic review of the EoE literature (since September 2006) using electronic databases. Based on the literature review and expertise of the panel, information and recommendations were provided in each of the following areas of EoE: diagnostics, genetics, allergy testing, therapeutics, and disease complications. Because accumulating animal and human data have provided evidence that EoE appears to be an antigen-driven immunologic process that involves multiple pathogenic pathways, a new conceptual definition is proposed highlighting that EoE represents a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. The diagnostic guidelines continue to define EoE as an isolated chronic disorder of the esophagus diagnosed by the need of both clinical and pathologic features. Patients commonly have high rates of concurrent allergic diatheses, especially food sensitization, compared with the general population. Proved therapeutic options include chronic dietary elimination, topical corticosteroids, and esophageal dilation. Important additions since 2007 include genetic underpinnings that implicate EoE susceptibility caused by polymorphisms in the thymic stromal lymphopoietin protein gene and the description of a new potential disease phenotype, proton pump inhibitor-responsive esophageal eosinophila. Further advances and controversies regarding diagnostic methods, surrogate disease markers, allergy testing, and treatment approaches are discussed.

A modified assay for measuring thymocyte co-stimulatory activity

The observation that murine thymocytes increase their proliferation to interleukin 1 (IL-1) in the presence of phytohemagglutinin (PHA) when pre-incubated with interleukin 2 (IL-2) allowed the introduction of a modified assay for the measurement of IL-1 or the search of thymocyte-inducing proliferative activities in biological samples. Pre-incubation of thymocytes for 24 hr with 50 u/ml IL-2, followed by washings, elicited their maximal response to IL-1 in the usual lymphocyte activating factor (LAF) assay. This suggests that sequential events lead to thymocyte activation. The responsiveness is three to five fold greater than, and the total time of assay is the same as that of the LAF assay. Interestingly, pre-incubation with IL-2 renders thymocytes more sensitive than responsive to crude monocyte conditioned media. The use of the MTT colorimetric method for the assessment of thymocyte proliferation, and of the lectin jacalin as a co-mitogen are suggested as alternatives to be used in co-stimulatory assays.

Expression of human estrogen receptor mutants in Xenopus oocytes: correlation between transcriptional activity and ability to form protein-DNA complexes.

The human estrogen receptor (hER) is a trans-acting regulatory protein composed of a series of discrete functional domains. We have microinjected an hER expression vector (HEO) into Xenopus oocyte nuclei and demonstrate, using Western blot assay, that the hER is synthesized. When nuclear extracts from oocytes were prepared and incubated in the presence of a 2.7 kb DNA fragment comprising the 5' end of the vitellogenin gene B2, formation of estrogen-dependent complexes could be visualized by electron microscopy over the estrogen responsive element (ERE). Of crucial importance is the observation that the complex formation is inhibited by the estrogen antagonist tamoxifen, is restored by the addition of the hormone and does not take place with extracts from control oocytes injected with the expression vector lacking the sequences encoding the receptor. The presence of the biologically active hER is confirmed in co-injection experiments, in which HEO is co-introduced with a CAT reporter gene under the control of a vitellogenin promoter containing or lacking the ERE. CAT assays and primer extensions analyses reveal that both the receptor and the ERE are essential for estrogen induced stimulation of transcription. The same approach was used to analyze selective hER mutants. We find that the DNA binding domain (region C) is essential for protein--DNA complex formation at the ERE but is not sufficient by itself to activate transcription from the reporter gene. In addition to region C, both the hormone binding (region E) and amino terminal (region A/B) domains are needed for an efficient transcription activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Novel testis germ cell-specific transcript of the CREB gene contains an alternatively spliced exon with multiple in-frame stop codons.

The gene encoding the cAMP-responsive transcription factor CREB consists of multiple small exons some of which undergo alternative RNA splicing. We describe the finding of a novel transcript of the CREB gene expressed at high levels in the germ cells of the rat testis. The transcript contains an alternatively spliced exon inserted within the sequence encoding the transcriptional transactivation domain of CREB and this exon contains multiple in-frame stop codons. Furthermore, the exon is conserved in both rat and human genes (75% nucleotide identity). Although the function(s) of this RNA or the truncated CREB protein predicted to result from the translation of this unusual transcript is unknown, the high level of expression in the testicular germ cells and remarkable conservation of sequences in rat and human suggests that it may have a unique biological function in these cells.

The Impact of democratization: a preliminary investigation on social policies and political violence in Latin America

The recent strides of democracy in Latin America have been associated to conflicting outcomes. The expectation that democracy would bring about peace and prosperity have been only partly satisfied. While political violence has been by and large eradicated from the sub-continent, poverty and social injustice still prevail and hold sway. Our study argues that democracy matters for inequality through the growing strength of center left and left parties and by making political leaders in general more responsive to the underprivileged. Furthermore, although the pension reforms recently enacted in the region generated overall regressive outcomes on income distribution, democratic countries still benefit from their political past: where democratic tradition was stronger, such outcomes have been milder. Democratic tradition and the specific ideological connotations of the parties in power, on the other hand, did not play an equally crucial role in securing lower levels of political violence: during the last wave of democratizations in Latin America, domestic peace was rather an outcome of political and social concessions to those in distress. In sum, together with other factors and especially economic ones, the reason why recent democratizations have provided domestic peace in most cases, but have been unable so far to solve the problem of poverty and inequality, is that democratic traditions in the subcontinent have been relatively weak and, more specifically, that this weakness has undermined the growth of left and progressive parties, acting as an obstacle to redistribution. Such weakness, on the other hand, has not prevented the drastic reduction of domestic political violence, since what mattered in this case was a combination of symbolic or material concessions and political agreements among powerful élites and counter-élites.

A comparison of input-output models: ghosh reduces to leontief (but "closing" ghosh makes it more plausible)

Ghosh's model is discussed in this paper under two alternative scenarios. In an open version we compare it with Leontief's model and prove that they reduce to each other under some specific productive conditions. We then move onto reconsidering Ghosh's model alleged implausibility and we do so reformulating the model to incorporate a closure rule. The closure solves, to some extent, the implausibility problem very clearly put out by Oosterhaven for then value-added is correctly computed and responsive to allocation changes resulting from supply shocks.

Constitutive expression of a chimeric receptor that delivers IL-2/IL-15 signals allows antigen-independent proliferation of CD8+CD44high but not other T cells.

We have prepared transgenic mice whose T cells constitutively express a chimeric receptor combining extracellular human IL-4R and intracellular IL-2Rbeta segments. This receptor can transmit IL-2/IL-15-like signals in response to human, but not mouse, IL-4. We used these animals to explore to what extent functional IL-2R/IL-15R expression controls the capacity of T cells to proliferate in response to IL-2/IL-15-like signals. After activation with Con A, naive transgenic CD8+ and CD4+ T cells respond to human IL-4 as well as to IL-2. Without prior activation, they failed to proliferate in response to human IL-4, although human IL-4 did prolong their survival. Thus, IL-2-induced proliferation of activated T cells requires at least one other Ag-induced change apart from the induction of a functional IL-2R. However, a fraction of CD8+CD44high T cells proliferate in human IL-4 without antigenic stimulation or syngeneic feeder cells. In contrast, CD4+CD44high T cells are not constitutively responsive to human IL-4. We conclude that although all transgenic T cells express a functional chimeric receptor, only some CD8+CD44high T cells contain all molecules required for entry into the cell cycle in response to human IL-4 or IL-15.

BRX promotes Arabidopsis shoot growth.

? BREVIS RADIX (BRX) has been identified through a loss-of-function allele in the Umkirch-1 accession in a natural variation screen for Arabidopsis root growth vigor. Physiological and gene expression analyses have suggested that BRX is rate limiting for auxin-responsive gene expression by mediating cross-talk with the brassinosteroid pathway, as impaired root growth and reduced auxin perception of brx can be (partially) rescued by external brassinosteroid application. ? Using genetic tools, we show that brx mutants also display significantly reduced cotyledon and leaf growth. ? Similar to the root, the amplitude and penetrance of this phenotype depends on genetic background and shares the physiological features, reduced auxin perception and brassinosteroid rescue. Furthermore, reciprocal grafting experiments between mutant and complemented brx shoot scions and root stocks suggest that the shoot phenotypes are not an indirect consequence of the root phenotype. Finally, BRX gain-of-function lines display epinastic leaf growth and, in the case of dominant negative interference, increased epidermal cell size. Consistent with an impact of BRX on brassinosteroid biosynthesis, this phenotype is accompanied by increased brassinosteroid levels. ? In summary, our results demonstrate a ubiquitous, although quantitatively variable role of BRX in modulating the growth rate in both the root and shoot.

Research needs in allergy: an EAACI position paper, in collaboration with EFA.

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

Compressed collagen gel: a novel scaffold for human bladder cells.

Collagen is highly conserved across species and has been used extensively for tissue regeneration; however, its mechanical properties are limited. A recent advance using plastic compression of collagen gels to achieve much higher concentrations significantly increases its mechanical properties at the neo-tissue level. This controlled, cell-independent process allows the engineering of biomimetic scaffolds. We have evaluated plastic compressed collagen scaffolds seeded with human bladder smooth muscle cells inside and urothelial cells on the gel surface for potential urological applications. Bladder smooth muscle and urothelial cells were visualized using scanning electron microscopy, conventional histology and immunohistochemistry; cell viability and proliferation were also quantified for 14 days in vitro. Both cell types tested proliferated on the construct surface, forming dense cell layers after 2 weeks. However, smooth muscle cells seeded within the construct, assessed with the Alamar blue assay, showed lower proliferation. Cellular distribution within the construct was also evaluated, using confocal microscopy. After 14 days of in vitro culture, 30% of the smooth muscle cells were found on the construct surface compared to 0% at day 1. Our results provide some evidence that cell-seeded plastic compressed collagen has significant potential for bladder tissue regeneration, as these materials allow efficient cell seeding inside the construct as well as cell proliferation.