Homeostatic proliferation and survival of naïve and memory T cells.

The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady-state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naïve cells, rapid elimination of effector cells after pathogen clearance, and long-term survival of memory cells. The reduction of T-cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia-induced proliferation and restoration of normal T-cell levels. Such expansion is governed by the interaction of TCR with self-peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL-7. These same ligands, i.e. p/MHC molecules and IL-7, maintain naïve T lymphocytes as resting cells under steady-state T-cell-sufficient conditions. Unlike naïve cells, typical "central" memory T cells rely on a combination of IL-7 and IL-15 for their survival in interphase and for occasional cell division without requiring signals from p/MHC molecules. Other memory T-cell subsets are less quiescent and include naturally occurring activated memory-phenotype cells, memory cells generated during chronic viral infections, and effector memory cells. These subsets of activated memory cells differ from central memory T cells in their requirements for homeostatic proliferation and survival. Thus, the factors controlling T-cell homeostasis can be seen to vary considerably from one subset to another as described in detail in this review.

Declining diversity of egg-associated bacteria during development of naturally spawned whitefish embryos (Coregonus spp.)

Fish eggs are associated with microbes, whose roles range from mutualism to parasitism. Recent laboratory experiments have shown that the taxonomic composition of associated microbial communities on the egg influences embryonic development. Host genetics also plays an important role in determining the consequences for embryonic growth and survival in this interaction. Moreover, it has been found that the importance of host genetics increases during embryogenesis. These findings suggest that during embryogenesis, the host increasingly influences the composition of its associated microbial community. However, little is known about the composition of microbial communities associated with naturally spawned eggs in the wild. We sampled fertilized whitefish eggs (Coregonus spp.) of different developmental stages from six sub-Alpine lakes and used a universal primer pair and 454 pyrosequencing in order to describe the taxonomic composition of egg-associated bacterial communities. We found bacterial communities on early embryos to be very diverse and to resemble the bacterial composition of the surrounding water environment. The bacterial communities on late embryos were significantly less diverse than on early embryos and displayed a clear shift in taxonomic composition that corresponded poorly with the bacterial composition of the surrounding water environment. The main bacterial components on whitefish eggs in this study were Proteobacteria, Actinobacteria, and Firmicutes, while the five most common families were Leuconostocaceae, Streptococcaceae, Comamonadaceae, Oxalobacteraceae and Moraxellaceae. Their putative relationships with the host are discussed. We conclude that natural symbiotic bacterial communities become more specialized during embryogenesis because of specific interactions with their embryo host.

Lämpöpumppujen vaikutukset sähköverkkoliiketoiminnan kannalta

Energiatehokkuus sekä ilmastonmuutos ovat aiheuttaneet pyrkimyksen vähentää kokonaisenergiankulutuksia erilaisissa rakennuksissa. Lämmitysjärjestelmissä tämä on näkynyt voimakkaana lämpöpumppumäärien kasvuna. Lämpöpumput vaikuttavat erilaisissa rakennus- ja lämmitystyypeissä myös sähköenergiankulutukseen. Lämpöpumppujen käytöstä saadaan eniten hyötyä lämmityskustannuksiin sähkölämmitteisissä rakennuksissa. Seurauksena on, että tällaisen rakennuksen sähkönkulutus ja siten myös sähkölasku pienenevät. Toisaalta muihin kuin sähkölämmitteisiin rakennuksiin asennettu lämpöpumppu kasvattaa sähköenergiankulutusta. Lämpöpumppuihin integroitu jäähdytysominaisuus myös tavallisesti lisää sähkönkulutusta. Tämän tutkimuksen tarkoituksena on selvittää, kuinka lämpöpumput vaikuttavat sähköenergiankulutukseen. Vaikutuksia tutkitaan sähköverkkoyhtiöiden kannalta sähköenergian ja liikevaihdon osalta. Tarkastelussa käytetään neljää yleisintä lämpöpumpputyyppiä, ja niiden toimintaa verrataan eri rakennustyyppien lämmitysjärjestelmiin. Työssä käsitellään lämpöpumppujen toimintaa ja käytettävyyttä muiden lämmitysmenetelmien korvaajina tai lisänä. Tämän kirjallisen työn lisäksi on tehty laskentaohjelma, joka on perusteena työssä esitetyille tuloksille. Sen tarkoituksena on selvittää lämpöpumppujen vaikutukset sähköverkkoliiketoimintaan energiayhtiöissä. Vaikutukset yksittäiseen energiayhtiöön ovat eniten riippuvaisia lämpöpumppujen asennuskohteista, lämpöpumppujen toiminnasta ja lämpöpumpputyypistä. Kuluttajat tulevat määräämään vaikutusten suuruuden, koska lämpöpumppujen lukumäärällä ja käytöllä on sähköenergiankulutukseen huomattava merkitys. Vaikutus sähköenergiaan energiayhtiöiden kannalta voi yleisesti ottaen olla 2020-luvulle mentäessä merkittävä. Tutkittavassa verkkoyhtiössä vaikutuksen sähköenergiaan arvioidaan olevan 10 % luokkaa yhdeltä vuodelta verrattuna tämän päivän kokonaissähköenergiankulutukseen. Vaikutus verkkoliikevaihtoon on arviolta puolet pienempi. Tällaiset tulokset edellyttävät lämpöpumppumäärän moninkertaistumista nykyisestä, mikä on myös odotettavissa.

Et s’il était possible d’obtenir justice en ligne ?

Peut-être mieux connu sous son appellation anglaise d' «online dispute resolution» ou ODR, le règlement en ligne des différends réfère à la migration, vers Internet, des modes alternatifs de résolution des conflits, dont font entre autres partie la négociation, la conciliation, la médiation et l'arbitrage. Cet article présente d'abord brièvement les quatre procédés d'ODR les plus souvent rencontrés en pratique, soit la négociation  automatisée, la négociation en ligne assistée par ordinateur, la médiation en ligne et l'arbitrage en ligne. Il examine ensuite les types de conflits qui trouvent actuellement une solution par l'entremise de l'Internet, conflits qui peuvent naître aussi bien sur la Toile qu'hors ligne. On y aborde, en troisième lieu, les avantages de la résolution en ligne des litiges, lesquels ont trait à la modicité, la rapidité, la souplesse et la convivialité, en insistant sur l'attrait tout particulier que cette nouvelle forme de justice présente pour les conflits résultant de la cyberconsommation. Puis, après un survol des arguments les plus souvent cités à l'encontre du règlement électronique des différends, on fait état du phénomène d'institutionnalisation de la résolution en ligne, qui investit aujourd'hui les cours de justice.

Arachidonic acid actions on functional integrity and attenuation of the negative effects of palmitic acid in a clonal pancreatic beta-cell line

Chronic exposure of pancreatic beta-cells to saturated non-esterified fatty acids can lead to inhibition of insulin secretion and apoptosis. Several previous studies have demonstrated that saturated fatty acids such as PA (palmitic acid) are detrimental to beta-cell function compared with unsaturated fatty acids. In the present study, we describe the effect of the polyunsaturated AA (arachidonic acid) on the function of the clonal pancreatic beta-cell line BRIN-BD11 and demonstrate AA-dependent attenuation of PA effects. When added to beta-cell incubations at 100 mu M, AA can stimulate cell proliferation and chronic (24 h) basal insulin secretion. Microarray analysis and/or real-time PCR indicated significant AA-dependent up-regulation of genes involved in proliferation and fatty acid metabolism [e.g. Angptl (angiopoietin-like protein 4), Ech1 (peroxisomal Delta(3.5),Delta(2.4)-dienoyl-CoA isomerase), Cox-1 (cyclo-oxygenase-1) and Cox-2, P < 0.05]. Experiments using specific COX and LOX (lipoxygenase) inhibitors demonstrated the importance of COX-1 activity for acute (20 min) stimulation of insulin secretion, suggesting that AA metabolites may be responsible for the insulinotropic effects. Moreover, concomitant incubation of AA with PA dose-dependently attenuated the detrimental effects of the saturated fatty acid, so reducing apoptosis and decreasing parameters of oxidative stress [ROS (reactive oxygen species) and NO levels] while improving the GSH/GSSG ratio. AA decreased the protein expression of iNOS (inducible NO synthase), the p65 subunit of NF-kappa B (nuclear factor kappa B) and the p47 subunit of NADPH oxidase in PA-treated cells. These findings indicate that AA has an important regulatory and protective beta-cell action, which may be beneficial to function and survival in the `lipotoxic` environment commonly associated with Type 2 diabetes mellitus.

CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

ABSTRACT: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (P450c21, CYP21) accounts for about 95% of all CAH cases. The incidence of CYP21 gene mutations has been extensively studied in the last years, but in Brazil it has been investigated only in Southeast Brazilian patients. This study is the first report on the distribution of CYP21 mutations in patients from the Amazon region. Direct sequencing of the CYP21 gene identified at least one mutation in 96% of the studied chromosomes. The most common mutations found were IVS2-13A/C > G (36%), Q318X (12%), V281L (12%), 1760_1761insT (9%), Cluster E6 (7%), and P30L (7%). The worldwide most common mutations were identified among patients from the Amazon region at frequencies that may be expected for a population resulting from the admixture of Europeans (predominantly Portuguese), African Blacks and Amerindians, in proportions that differ from those estimated for South Brazilian populations. Interethnic mixture may explain the differences in the frequencies of some mutations between Brazilian patients from the Amazon and from the Southeast of the country. However, the differences found may also be due to variation in the number of patients with the different clinical forms of 21-hydroxylase deficiency in the studies carried out so far.

Retrocrural space involvement on computed tomography as a predictor of mortality and disease severity in acute pancreatitis

BACKGROUND Because computed tomography (CT) has advantages for visualizing the manifestation of necrosis and local complications, a series of scoring systems based on CT manifestations have been developed for assessing the clinical outcomes of acute pancreatitis (AP), including the CT severity index (CTSI), modified CTSI, etc. Despite the internationally accepted CTSI having been successfully used to predict the overall mortality and disease severity of AP, recent literature has revealed the limitations of the CTSI. Using the Delphi method, we establish a new scoring system based on retrocrural space involvement (RCSI), and compared its effectiveness at evaluating the mortality and severity of AP with that of the CTSI. METHODS We reviewed CT images of 257 patients with AP taken within 3-5 days of admission in 2012. The RCSI scoring system, which includes assessment of infectious conditions involving the retrocrural space and the adjacent pleural cavity, was established using the Delphi method. Two radiologists independently assessed the RCSI and CTSI scores. The predictive points of the RCSI and CTSI scoring systems in evaluating the mortality and severity of AP were estimated using receiver operating characteristic (ROC) curves. PRINCIPAL FINDINGS The RCSI score can accurately predict the mortality and disease severity. The area under the ROC curve for the RCSI versus CTSI score was 0.962±0.011 versus 0.900±0.021 for predicting the mortality, and 0.888±0.025 versus 0.904±0.020 for predicting the severity of AP. Applying ROC analysis to our data showed that a RCSI score of 4 was the best cutoff value, above which mortality could be identified. CONCLUSION The Delphi method was innovatively adopted to establish a scoring system to predict the clinical outcome of AP. The RCSI scoring system can predict the mortality of AP better than the CTSI system, and the severity of AP equally as well.

The four hunchbacks, or, The beggars of Tivoli : a farcetta in one act /

"Performed for the first time, Monday, April 18th 1825, at the East-London theatre. (To which is prefixed the original tale.).

The book of common worship,

Henry Van Dyke, chairman of the assembly's committee. cf. Pref., p. vi.

The four Corners in Japan,

Illus. t.-p.

The four Corners in California /

Illustrations signed Wuanita Smith.

The four million /

Mode of access: Internet.

The four million [stories]

Mode of access: Internet.

The four knaves: a series of satirical tracts,

With reproduction of the title-page of the London edition of 1611 of The Knave of clubbs, of the title-page of the London edition of 1613 of The knave of harts, and of the original title-page of More knaves yet? The knaves of spades and diamonds.

The four Gospels of the New Testament in Greek from the Text of Griesbach : with a lexicon in English of all the words contained in them : designed for the use of schools.

"This edition ... has been perpared in consequence of the new arrangement of the studies in Greek preparatory to admission into the University at Cambridge."--preface.