Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells.

CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T cell-mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigen-specific Treg from antigenically naive precursors in vitro using allogeneic nontransformed B cells as stimulators. By this approach naive CD4(+)CD25(-) T cells could be expanded 8-fold into alloantigen-specific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO(+)CCR7(-) memory cells, and had a CD4(high), CD25(+), Foxp3(+), and CD62L (L-selectin)(+) phenotype. Although these CD4(high)CD25(+)Foxp3(+) alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on cytotoxic T lymphocyte antigen-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases.

Database resources for the tuberculosis community.

Access to online repositories for genomic and associated "-omics" datasets is now an essential part of everyday research activity. It is important therefore that the Tuberculosis community is aware of the databases and tools available to them online, as well as for the database hosts to know what the needs of the research community are. One of the goals of the Tuberculosis Annotation Jamboree, held in Washington DC on March 7th-8th 2012, was therefore to provide an overview of the current status of three key Tuberculosis resources, TubercuList (tuberculist.epfl.ch), TB Database (www.tbdb.org), and Pathosystems Resource Integration Center (PATRIC, www.patricbrc.org). Here we summarize some key updates and upcoming features in TubercuList, and provide an overview of the PATRIC site and its online tools for pathogen RNA-Seq analysis.

Moderate-Vigorous Physical Activity across Body Mass Index in Females: Moderating Effect of Endocannabinoids and Temperament.

BACKGROUND Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI. METHODS Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA. RESULTS Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039) and high MVPA levels were associated with elevated anandamide (AEA) levels (b = 0.16, p = .049) and N-oleylethanolamide (OEA) levels (b = 0.22, p = .004), as well as high Novelty seeking (b = 0.18, p<.001) and low Harm avoidance (b = -0.16, p<.001). CONCLUSIONS Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.

Olfaction in eating disorders and abnormal eating behavior: a systematic review.

The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

Changes in Body Composition in Anorexia Nervosa: Predictors of Recovery and Treatment Outcome.

The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome.

In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations

This study was conducted to identify enzyme systems eventually catalysing a local cerebral metabolism of citalopram, a widely used antidepressant of the selective serotonin reuptake inhibitor type. The metabolism of citalopram, of its enantiomers and demethylated metabolites was investigated in rat brain microsomes and in rat and human brain mitochondria. No cytochrome P-450 mediated transformation was observed in rat brain. By analysing H2O2 formation, monoamine oxidase A activity in rat brain mitochondria could be measured. In rat whole brain and in human frontal cortex, putamen, cerebellum and white matter of five brains monoamine oxidase activity was determined by the stereoselective measurement of the production of citalopram propionate. All substrates were metabolised by both forms of MAO, except in rat brain, where monoamine oxidase B activity could not be detected. Apparent Km and Vmax of S-citalopram biotransformation in human frontal cortex by monoamine oxidase B were found to be 266 microM and 6.0 pmol min(-1) mg(-1) protein and by monoamine oxidase A 856 microM and 6.4 pmol min(-1) mg(-1) protein, respectively. These Km values are in the same range as those for serotonin and dopamine metabolism by monoamine oxidases. Thus, the biotransformation of citalopram in the rat and human brain occurs mainly through monoamine oxidases and not, as in the liver, through cytochrome P-450.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Historia de Vida de Andrés Díaz de Rábago S.J. (1947-1957): O cómo la Guerra Civil China cambió la estructura de la Compañía de Jesús en Asia.

Peer-reviewed

Neuromotor performance of normally developing left-handed children and adolescents.

Neuromotor functioning - i.e., timed performance and quality of movements - was examined in 66 left-handed children and adolescents between 5 and 18.5 years by means of the Zurich Neuromotor Assessment. Quality of movements was assessed by the degree and the frequency of associated movements. Results were compared to normative data from 593 right-handers. The overall scores for timed motor performance were similar for left-handers and right-handers, while left-handers had more associated movements than right-handers with both sides. In agreement with previous studies in adults, we found that left-handed children were less lateralized than right-handers. They performed faster with their non-dominant side and slower with their dominant side. This finding was roughly independent of age, which may indicate that handedness does not reflect long-term effects of previous motor experience, but may be primarily attributed to genetic factors.

Nevera, mp3, mòbil... quin és el seu paper actual?

Des dels seus inicis, l’ésser humà ha tingut una sèrie de necessitats. Ha requerit d’aliment per sobreviure, d’un sostre on refugiar-se, de roba per vestirse, etc. Conforme han passat els anys, ha anat generant tècniques per a millorar la seva estància al planeta, des del descobriment del foc per escalfarse fins al desenvolupament de màquines complexes. És per això, que ha anat introduint invents a la seva vida que han cobert les necessitats sorgides al llarg del temps.El treball que desenvolupem a continuació es centra en un seguit d’aparells que han sorgit al llarg del segle XX i que han revolucionat la nostra vida. Concretament, els set aparells escollits com a objecte del nostre estudi són: la nevera, la rentadora, l’automòbil, la televisió, el reproductor d’àudio portàtil, el telèfon mòbil i l’ordinador.L’aparició d’electrodomèstics, com la nevera o la rentadora, no només ens ha permès dedicar menys esforç a les tasques domèstiques, sinó també estalviarnos temps a l’hora de realitzar-les. Aquest fet, que ara potser ni tan sols considerem, va ser del tot determinant a l’època que van sorgir, ja que va permetre alliberar mà d’obra domèstica promovent la inserció al mercat laboral d’un sector de la població com el del sexe femení.Per la seva banda, la introducció de l’automòbil també ha estat un gran avenç. Aquest, ha revolucionat la manera de desplaçar-nos, proporcionant-nos una autonomia fins aleshores impensable.Aquest mateix patró segueixen la resta d’altres aparells escollits; tots van provocar un canvi profund a la societat amb la seva aparició i, encara avui, segueixen mantenint un paper destacat al nostre dia a dia. La importància que tenen a les nostres vides ha estat la motivació que ens ha conduït a dur a terme un treball que els tingués com a protagonistes.El nostre treball consta de dues parts:A la primera, de caràcter teòric, ens hem proposat estudiar la història d’aquests aparells, és a dir, hem volgut donar resposta a una sèrie de preguntes com: quan van aparèixer, quins van ser els seus creadors i quines transformacions han anat experimentant al llarg del temps, entre d’altres.A la segona part, més pràctica, hem realitzat un treball de camp (les característiques del qual expliquem detalladament a l’apartat següent) amb l’objectiu d’analitzar la rellevància que tenen aquests aparells a la societat actual. És a dir, hem volgut saber quins aparells, dels escollits, són els més valorats per la població avui dia i quins són els que menys. Pensem que l’ús que els enquestats fan d’aquests béns serà un criteri clau a l’hora de puntuarlos, encara que no l’únic. Hem realitzat aquest anàlisi diferenciant els individus per franges d’edat i sexes. A més, també hem treballat altres qüestions comserien, entre d’altres, si el seu ús s’entén com una necessitat o va encaminat cap a l’oci; quant temps triguen els usuaris a renovar-los, quin és el motiu, etc. En relació amb aquesta segona part, hem formulat un seguit d’hipòtesis amb l’objectiu de contrastar-les posteriorment amb els resultats de les enquestes.Les hipòtesis són:- Avui dia, els individus donen més importància a aquells aparells que són més moderns, (entenent com a tals, aquells que han sorgit més recentment i estan lligats a les noves tecnologies i la innovació contínua), com poden ser l’ordinador i el telèfon mòbil, que els electrodomèstics més tradicionals com serien la nevera o la rentadora. Tot això, a més, considerant que pel que fa als primers, entenem que part del seu ús està destinat a l’oci; mentre que pels segons el seu ús està motivat per una necessitat, com seria l’alimentació en el cas de la nevera.- Pel que fa a les franges d’edat, les valoracions mostraran diferències importants en els diversos aparells. Entre la franja més jove (de 16 a 25 anys) i la de més edat (més de 60 anys), les valoracions seran més extremes, gairebé oposades.- Pel que fa als dos sexes, les valoracions que donin als aparells seran molt semblants.Hem considerat que per a dur a terme un bon anàlisi, el més adequat és presentar la informació de cada aparell per separat. És per això que cada bé constitueix un apartat independent que consta d’una primera part referent a la seva història, i una segona referent als resultats obtinguts de les enquestes.A continuació, hem procedit a ajuntar els resultats extrets dels diferents aparells i a presentant-los de forma conjunta per a comparar-los. Així, hem pogut contrastar les nostres hipòtesis inicials i hem raonat possibles causes que justificarien dels resultats obtinguts.

"El Precio de la muerte" : anàlisi del mercat funerari a la ciutat de Barcelona

Heu contractat alguna vegada un servei funerari? Encara que la resposta de molts de nosaltres és que no, és ben segur que algun cop en la nostra vida ho haurem de fer i potser és millor pensar quin tipus de servei estarem contractant abans que arribi el moment de fer-ho. “El precio de la muerte” és un treball on s’ha fet un anàlisi del mercat funerari a Barcelona i la seva utilitat rau en el fet de que aquest tipus de serveis, encara avui dia, segueix sent molt desconegut i és per això que aquí donarem respostes a les principals preguntes que pugui tenir el lector. Si voleu saber en qui recau la responsabilitat d’oferir aquest servei, com es fixen els preus o qui es queda els 10 milions d’euros que dona de benefici una empresa d’aquest tipus no dubteu en llegir aquest treball, i aquesta i moltes preguntes més trobaran resposta.Finalment, ens plau pensar que l’esforç de reunir aquesta informació serveixi als consumidors per afrontar un tràmit tan forçós des d’una posició d’igualtat davant l’empresa oferidora, i evitar així preus abusius i serveis innecessaris.

A China em África- que Desenvolvimento Comum? o caso Cabo Verde

Depois de alcançada a ideologia de Estado e ter defenido assim a sua posição política, com as conhecidas consequências acarretadas, a nova RPC de Mao Zedong caminha, depois da sua morte, para um outro processo de mudança, a mudança económica. A administração Deng assume as responsabilidades de abertura do dragão asiático ao mundo, pela implementação de um conjunto de reformas que conduzam ao desenvolvimento económico. Em algumas cidades, consideradas como “laboratórios experimentais”, apesar das contrariedades constantes à actividade privada levada a cabo, o impacto das reformas foi tão intenso que essas passaram a ser consideradas como modelos de desenvolvimento. São exemplos os casos de Wenzhou, Sunan, e de algumas regiões do Sul da China. Todos esses casos têm em comum os factores envolvidos, que são: o Estado/PCC; as autoridades locais; as famílias; as empresas familiares e a capacidade empreendedora das mesmas. Esse desenvolvimento da China, sem precedentes, faz com que a potência procure fora do seu território recursos que dêem prosseguimento ao mesmo, nesse contexto, encontra em África um novo parceiro. A cooperação entre África e China, apesar de não recente, é a partir de então intensificada, numa relação que se pretende de igualdade e de ganhos comuns. Sempre com vários pontos que definem o objectivo desta parceria, destaca-se o desenvolvimento comum como aquele que perdura desde a era maoísta. Com esse objectivo China investe em África, oferece condições de parceria aliciantes e compromete-se em transmitir ao continente o seu modelo de desenvolvimento. Mas, tendo em conta que África, apesar de poder aprender com o desenvolvimento chinês, não pode fazer depender do discurso chinês o seu desenvolvimento, consideramos os mesmos factores destacados no caso da China, o caminho prosseguido pelo continente para um desenvolvimento sustentável, e analisámos o caso específico de Cabo Verde, onde a presença chinesa, a sua actuação empreendedora e competitividade se fazem sentir na vida diária dos cabo-verdianos, com algumas lições a transmitir para o desenvolvimento futuro do país, perspectivando este futuro a curto, médio-prazo.

Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation.

Previous studies demonstrated that peroxisome-proliferator-activated receptor (PPAR)-alpha or PPAR-delta activation stimulates keratinocyte differentiation, is anti-inflammatory, and improves barrier homeostasis. Here we demonstrate that treatment of cultured human keratinocytes with ciglitazone, a PPAR-gamma activator, increases involucrin and transglutaminase 1 mRNA levels. Moreover, topical treatment of hairless mice with ciglitazone or troglitazone increases loricrin, involucrin, and filaggrin expression without altering epidermal morphology. These results indicate that PPAR-gamma activation stimulates keratinocyte differentiation. Additionally, PPAR-gamma activators accelerated barrier recovery following acute disruption by either tape stripping or acetone treatment, indicating an improvement in permeability barrier homeostasis. Treatment with PPAR-gamma activators also reduced the cutaneous inflammatory response that is induced by phorbol 12-myristate-13-acetate, a model of irritant contact dermatitis and oxazolone, a model of allergic contact dermatitis. To determine whether the effects of PPAR-gamma activators are mediated by PPAR-gamma, we next examined animals deficient in PPAR-gamma. Mice with a deficiency of PPAR-gamma specifically localized to the epidermis did not display any cutaneous abnormalites on inspection, but on light microscopy there was a modest increase in epidermal thickness associated with an increase in proliferating cell nuclear antigen (PCNA) staining. Key functions of the skin including permeability barrier homeostasis, stratum corneum surface pH, and water-holding capacity, and response to inflammatory stimuli were not altered in PPAR-gamma-deficient epidermis. Although PPAR-gamma activators stimulated loricrin and filaggrin expression in wild-type animals, however, in PPAR-gamma-deficient mice no effect was observed indicating that the stimulation of differentiation by PPAR-gamma activators is mediated by PPAR-gamma. In contrast, PPAR-gamma activators inhibited inflammation in both PPAR-gamma-deficient and wild-type mouse skin, indicating that the inhibition of cutaneous inflammation by these PPAR-gamma activators does not require PPAR-gamma in keratinocytes. These observations suggest that thiazolidindiones and perhaps other PPAR-gamma activators maybe useful in the treatment of cutaneous disorders.