Cis association of Ly49A with MHC class I restricts natural killer cell inhibition.

Natural killer (NK) cell function is negatively regulated by inhibitory receptors interacting with major histocompatibility complex class I molecules expressed on target cells. Here we show that the inhibitory Ly49A NK cell receptor not only binds to its H-2D(d) ligand expressed on potential target cells (in trans) but also is constitutively associated with H-2D(d) in cis (on the same cell). Cis association and trans interaction occur through the same binding site. Consequently, cis association restricts the number of Ly49A receptors available for binding of H-2D(d) on target cells and reduces NK cell inhibition through Ly49A. By lowering the threshold at which NK cell activation exceeds NK cell inhibition, cis interaction allows optimal discrimination of normal and abnormal host cells.

Evaluación poblacional de Gari solida (Gray, 1828) en bahía Independencia-Pisco, junio 2010

En junio 2010, se efectuó la evaluación poblacional de almeja Gari solida en los principales bancos naturales de bahía Independencia: El Ancla, Pan de Azúcar y La Pampa para determinar su distribución, concentración, estructura por tamaños y magnitud poblacional. Los resultados evidenciaron una disminución de la biomasa y población, respecto a agosto del 2008, en 44,9% y 56,2%, respectivamente. La densidad por unidad de muestreo fluctuó entre 1 y 47 ind.m-2, las mayores densidades medias se encontraron en Pan de Azúcar (5,06 ind.m-2), La Pampa (2,42 ind.m-2) y menor densidad en El Ancla (0,57 ind.m-2). La biomasa total se calculó en 336,96 t (± 19,9%) y la población en 8,48 millones de individuos (± 19,85%), el 22,1% de la biomasa correspondió a ejemplares con tamaño mínimo de extracción (TME ≥75 mm). Las tallas de 792 ejemplares analizados fluctuaron entre 4 y 95 mm de longitud valvar, con moda en 65 mm y media en 57,5 mm. El rendimiento promedio del pie con respecto al peso total fue de 1: 9,5.

Sistema radicular do capim-Marandu, considerando as combinações de doses de nitrogênio e de enxofre

Um sistema radicular bem desenvolvido na gramínea forrageira é necessário para a formação e sustentação da planta e, como conseqüência, para a boa produtividade da pastagem. Objetivou-se avaliar características radiculares da Brachiaria brizantha cv. Marandu, em resposta a combinações de doses de N e S na solução nutritiva, empregando sílica como substrato, num experimento realizado em casa de vegetação no período de setembro a dezembro de 2001. Utilizou-se o esquema fatorial 5² fracionado, com 13 combinações de N e S, em mg L-1, respectivamente: 14 e 3,2; 14 e 32; 14 e 80; 126 e 12,8; 126 e 64; 210 e 3,2; 210 e 32; 210 e 80; 336 e 12,8; 336 e 64; 462 e 3,2; 462 e 32 e 462 e 80, as quais foram distribuídas segundo o delineamento de blocos ao acaso, com quatro repetições. Foram realizados dois cortes nas plantas. Após o segundo corte, as raízes foram separadas do substrato e avaliadas. A concentração de N e os acúmulos de N e de S nas raízes do capim mostraram-se dependentes da interação entre as doses de N e S. A dose de N foi determinante para o comprimento, superfície, produção de massa seca, relação comprimento:massa seca e concentração de S no tecido das raízes da forrageira. A produção de massa seca, o comprimento, a superfície das raízes e o acúmulo total de N e de S nas plantas do capim tiveram significativas correlações entre si.

Loss of Memo, a novel FGFR regulator, results in reduced lifespan.

Memo is a widely expressed 33-kDa protein required for heregulin (HRG)-, epidermal growth factor (EGF)-, and fibroblast growth factor (FGF)-induced cell motility. Studies in mouse embryonic fibroblasts, wild-type or knockout for Memo, were performed to further investigate the role of Memo downstream of FGFR. We demonstrated that Memo associates with the FGFR signalosome and is necessary for optimal activation of signaling. To uncover Memo's physiological role, Memo conditional-knockout mice were generated. These animals showed a reduced life span, increased insulin sensitivity, small stature, graying hair, alopecia, kyphosis, loss of subcutaneous fat, and loss of spermatozoa in the epididymis. Memo-knockout mice also have elevated serum levels of active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), and calcium compared to control littermates expressing Memo. In summary, the results from in vivo and in vitro models support the hypothesis that Memo is a novel regulator of FGFR signaling with a role in controlling 1,25(OH)2D production and normal calcium homeostasis.

Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer.

Background:It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.Methods:We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.Results:Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.Conclusion:Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

Is the obesity epidemic exaggerated? Clues from a developing country

Rapid response to: Patrick Basham and John Luik. Is the obesity epidemic exaggerated? Yes. BMJ 2008; 336: 244. doi: 10.1136/bmj.39458.495127.AD

A mutation in the gene encoding the vaccinia virus 37,000-M(r) protein confers resistance to an inhibitor of virus envelopment and release.

Plaque formation in vaccinia virus is inhibited by the compound N1-isonicotinoyl-N2-3-methyl-4-chlorobenzoylhydrazine (IMCBH). We have isolated a mutant virus that forms wild-type plaques in the presence of the drug. Comparison of wild-type and mutant virus showed that both viruses produced similar amounts of infectious intracellular naked virus in the presence of the drug. In contrast to the mutant, no extracellular enveloped virus was obtained from IMCBH-treated cells infected with wild-type virus. Marker rescue experiments were used to map the mutation conferring IMCBH resistance to the mutant virus. The map position coincided with that of the gene encoding the viral envelope antigen of M(r) 37,000. Sequence analysis of both wild-type and mutant genes showed a single nucleotide change (G to T) in the mutant gene. In the deduced amino acid sequence, the mutation changes the codon for an acidic Asp residue in the wild-type gene to one for a polar noncharged Tyr residue in the mutant.

L'interprète communautaire: une pièce centrale dans le puzzle de la consultation interculturelle [The community interpreter: a central piece in the puzzle of the intercultural consultation]

As a consequence of growing global migration, physicians in French speaking Switzerland often face communicational difficulties with allophone patients. This paper first discusses advantages and shortcomings of various ways of dealing with this kind of situations. The indication of using professional interpreters will be addressed, as well as some specific therapeutic, linguistic and relational features of triadic consultations involving a physician, a patient and an interpreter. Finally, useful practical information and advices are provided to clinicians in order to help them optimize their consultations with allophone patients.

Tricky and terrible T-cell tumors: these are thrilling times for testing: molecular pathology of peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) encompass a group of rare and usually clinically aggressive diseases. The classification and diagnosis of these diseases are compounded by their marked pathological heterogeneity and complex clinical features. With the exception of ALK-positive anaplastic large cell lymphoma (ALCL), which is defined on the basis of ALK rearrangements, genetic features play little role in the definition of other disease entities. In recent years, hitherto unrecognized chromosomal translocations have been reported in small subsets of PTCLs, and genome-wide array-based profiling investigations have provided novel insights into their molecular characteristics. This article summarizes the current knowledge on the best-characterized genetic and molecular alterations underlying the pathogenesis of PTCLs, with a focus on recent discoveries, their relevance to disease classification, and their management implications from a diagnostical and therapeutical perspective.

Retrospective analysis of stored dried blood spots from children with cystic fibrosis and matched controls to assess the performance of a proposed newborn screening protocol in Switzerland.

BACKGROUND: Newborn screening (NBS) for Cystic Fibrosis (CF) has been introduced in many countries, but there is no ideal protocol suitable for all countries. This retrospective study was conducted to evaluate whether the planned two step CF NBS with immunoreactive trypsinogen (IRT) and 7 CFTR mutations would have detected all clinically diagnosed children with CF in Switzerland. METHODS: IRT was measured using AutoDELFIA Neonatal IRT-Kit in stored NBS cards. RESULTS: Between 2006 and 2009, 66 children with CF were reported, 4 of which were excluded for various reasons (born in another country, NBS at 6 months, no informed consent). 98% (61/62) had significantly higher IRT compared to matched control group. There was one false negative IRT result in an asymptomatic child with atypical CF (normal pancreatic function and sweat test). CONCLUSIONS: All children but one with atypical CF would have been detected with the planned two step protocol.

Characterization of spontaneous gacS and gacA regulatory mutants of Pseudomonas fluorescens biocontrol strain CHAO.

In Pseudomonasfluorescens strain CHAO, the response regulator gene gacA controls expression of extracellular enzymes and antifungal secondary metabolites, which are important for this strain's biocontrol activity in the plant rhizosphere. Two Tn5 insertion mutants of strain CHA0 that had the same pleiotropic phenotype as gacA mutants were complemented by the gacS sensor kinase gene of P. syringae pv. syringae as well as that of P. fluorescens strain Pf-5, indicating that both transposon insertions had occurred in the gacS gene of strain CHA0. This conclusion was supported by Southern hybridisation using a gacS probe from strain Pf-5. Overexpression of the wild-type gacA gene partially compensated for the gacS mutation, however, the overexpressed gacA gene was not stably maintained, suggesting that this is deleterious to the bacterium. Strain CHA0 grown to stationary phase in nutrient-rich liquid media for several days accumulated spontaneous pleiotropic mutants to levels representing 1.25% of the population; all mutants lacked key antifungal metabolites and extracellular protease. Half of 44 spontaneous mutants tested were complemented by gacS, the other half were restored by gacA. Independent point and deletion mutations arose at different sites in the gacA gene. In competition experiments with mixtures of the wild type and a gacA mutant incubated in nutrient-rich broth, the mutant population temporarily increased as the wild type decreased. In conclusion, loss of gacA function can confer a selective advantage on strain CHA0 under laboratory conditions.