Landscape of transcription in human cells.

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

Biblia [Vetus et Novum Testamentum].

La Bible s’ouvre par deux compositions poétiques d’Alcuin qui encadrent l’Épître de saint Jérôme à Paulinus, « Frater Ambrosius... » (ff. 1-2r : Monumenta Germaniae Historica, Poetae latinae, I, 1, p. 287, LXVIII-LXX, v. 1-200 ; ff. 4r-v : Monumenta Germaniae Historica, Poetae latinae, I, 1, p. 283-284, LXV, I-III). La fin manque: la Bible s'interrompt à la fin de l'Epître de saint Paul aux Colossiens.

Distribuição, abundância e diversidade de Simuliidae (Diptera) em uma bacia hidrográfica impactada no sul do Brasil

Este estudo foi realizado na bacia do rio Caí, no Rio Grande do Sul, em duas áreas com diferentes estados de conservação ambiental: uma fortemente alterada pela intensa avicultura e suinocultura e outra mais conservada. Para padronizar as coletas das larvas e pupas de simulídeos foram utilizados substratos artificiais, instalados nos arroios por períodos de 14 dias. Em todos os pontos de amostragens foram feitas coletas simultâneas de água para análise físico-química e microbiológica. Na área mais conservada foram coletadas onze espécies com as seguintes freqüências: Psaroniocompsa incrustata (42,95%), P. auripellita (17,66%), Chirostilbia pertinax (16,86%), Inaequalium subclavibranchium (8,43%), I. nogueirai (5,80%), P. anamariae (3,69%), I. clavibranchium (1,58%), C. riograndense (0,92%), Lutzsimulium hirticosta (0,92%), I. botulibranchium (0,79%), Thyrsopelma itaunense (0,40%). Na área de maior impacto foram coletadas apenas seis espécies: C. pertinax (84,31%), C. riograndense (7,52%), T. itaunense (4,68%), P. incrustata (2,94%), I. subclavibranchium (0,33%), Ectemnaspis dinellii (0,22%). As concentrações de Nitrato e Nitrito na água foram os fatores que melhor permitem distinguir os pontos amostrados. A concentração de nitrato esteve significativamente relacionada com C. pertinax (r²= 0,54; P < 0,03) e com T. itaunense (r²= 0,55; P < 0,03) e nitrito com C. riograndense (r²= 0,64; P < 0,02). Essas informações podem ser úteis aos programas de controle integrado dos simulídeos, atualmente em execução em pelo menos 170 municípios no Rio Grande do Sul.

Morfologia comparada da genitália masculina de Galerucini (Coleoptera, Chrysomelidae, Galerucinae)

A morfologia da genitália, especialmente a do macho, tem sido muito utilizada para elucidar problemas taxonômicos e evolutivos de crisomelídeos e paticularmente em Galerucini. Nesta contribuição, representantes de gêneros de Galerucini das subtribos que ocorrem nas Regiões Neotropical e Neártica foram selecionados para estudo. Descrições comparativas e ilustrações da genitália masculina são apresentadas para as espécies: Coelomera lanio (Dalman, 1823) e Dircema nigripenne (Fabricius, 1792) (Subtribo Galerucina); Exora encaustica (Germar, 1824) e Uaupesia amazona (Weise, 1921) (Subtribo Metacyclina); Paranapiacaba teinturieri (Allard, 1894) e Isotes eruptiva (Bechyné, 1955) (Subtribo Luperina). O spiculum gastrale está presente nas espécies estudadas de Metacyclina e Luperina. No lobo médio, as estruturas basais em forma de gancho direcionadas ventralmente só não ocorrem em P. teinturieri e em I. eruptiva, que possuem um processo em forma de capuz protegendo o orifício basal. A fenestra sub-basal é observada em C. lanio e em U. amazona; o flagellum, um esclerito do saco interno, ocorre somente em U. amazona. O conhecimento da morfologia da genitália masculina em Galerucini ainda é incipiente e deve ser ampliado, com a inclusão de inúmeros gêneros ainda não estudados.

Fanconi-Bickel syndrome and autosomal recessive proximal tubulopathy with hypercalciuria (ARPTH) are allelic variants caused by GLUT2 mutations.

CONTEXT: Many inherited disorders of calcium and phosphate homeostasis are unexplained at the molecular level. OBJECTIVE: The objective of the study was to identify the molecular basis of phosphate and calcium abnormalities in two unrelated, consanguineous families. PATIENTS: The affected members in family 1 presented with rickets due to profound urinary phosphate-wasting and hypophosphatemic rickets. In the previously reported family 2, patients presented with proximal renal tubulopathy and hypercalciuria yet normal or only mildly increased urinary phosphate excretion. METHODS: Genome-wide linkage scans and direct nucleotide sequence analyses of candidate genes were performed. Transport of glucose and phosphate by glucose transporter 2 (GLUT2) was assessed using Xenopus oocytes. Renal sodium-phosphate cotransporter 2a and 2c (Npt2a and Npt2c) expressions were evaluated in transgenically rescued Glut2-null mice (tgGlut2-/-). RESULTS: In both families, genetic mapping and sequence analysis of candidate genes led to the identification of two novel homozygous mutations (IVS4-2A>G and R124S, respectively) in GLUT2, the gene mutated in Fanconi-Bickel syndrome, a rare disease usually characterized by renal tubulopathy, impaired glucose homeostasis, and hepatomegaly. Xenopus oocytes expressing the [R124S]GLUT2 mutant showed a significant reduction in glucose transport, but neither wild-type nor mutant GLUT2 facilitated phosphate import or export; tgGlut2-/- mice demonstrated a profound reduction of Npt2c expression in the proximal renal tubules. CONCLUSIONS: Homozygous mutations in the facilitative glucose transporter GLUT2, which cause Fanconi-Bickel syndrome, can lead to very different clinical and biochemical findings that are not limited to mild proximal renal tubulopathy but can include significant hypercalciuria and highly variable degrees of urinary phosphate-wasting and hypophosphatemia, possibly because of the impaired proximal tubular expression of Npt2c.

Systematic Assessment of Factors Influencing Preferences of Crohn's Disease Patients in Selecting an Anti-TNF agent (CHOOSE TNF TRIAL)

Background a nd A ims: I nfliximab (IFX), adalimumab (ADA)and certolizumab pegol (CZP) have similar efficacy for inductionand maintenance of clinical response and remission in Crohn'sdisease (CD). Given the comparable nature of t hese drugs,patients' p references m ay i nfluence the choice o f the product.Goal: to identify factors contributing to CD patients' decision inselecting one anti-TNF agent over the others.Methods: A p rospectdive s urvey was performed a mong a nti-TNF-naïve CD patients. Prior to completion of a questionnaire,patients were provided with a description of the three anti-TNFagents f ocusing on indications, route of administration, s ideeffects, and scientific evidence of efficacy and safety.Results: One hundred patients (47f/53m, mean age 45±16yrs)completed the questionnaire. Disease location was ileal, colonicand ileocolonic in 33%, 40% and 27% of patients, respectively.Thirty-six percent preferred ADA as medication of choice, while28% and 2 5% p referred CZP and IFX; 11% were u ndecided.Patients' decision in selecting an anti-TNF drug was influencedby t he following f actors: side effects ( 76%), p hysician'srecommendation (66%), route of administration (54%), efficacydata (52%), time required for therapy administration (27%),recommendations by other CD patients (21%) and interactionswith other medications (12%).Conclusions: T he majority of p atients p referred anti-TNFmedications t hat were a dministered by s ubcutaneous i njectionrather t han b y intravenous i nfusion. Side effect profile andphysicians' r ecommendation are t wo m ajor factors influencingthe patients' s election of a specific anti-TNF d rug. Patients'concerns about safety and lifestyle habits should be taken intoaccount when prescribing anti-TNF drugs.

Assessment of vaccine-induced CD4 T cell responses to the 119-143 immunodominant region of the tumor-specific antigen NY-ESO-1 using DRB1*0101 tetramers.

Abstract: Purpose: NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is presently viewed as an important model antigen for the development of generic anticancer vaccines. The ESO119-143 region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we generated DRB1*0101/ESO119-143 tetramers and used them to assess CD4 T-cell responses in vaccinated patients expressing DRB1*0101 (DR1). Experimental Design: We generated tetramers of DRB1*0101 incorporating peptide ESO119-143 using a previously described strategy. We assessed ESO119-143-specific CD4 T cells in peptide-stimulated post-vaccine cultures using the tetramers. We isolated DR1/ESO119-143 tetramer(+) cells by cell sorting and characterized them functionally. We assessed vaccine-induced CD4(+) DR1/ESO119-143 tetramer(+) T cells ex vivo and characterized them phenotypically. Results: Staining of cultures from vaccinated patients with DR1/ESO119-143 tetramers identified vaccine-induced CD4 T cells. Tetramer(+) cells isolated by cell sorting were of T(H)1 type and efficiently recognized full-length ESO. We identified ESO123-137 as the minimal optimal epitope recognized by DR1-restricted ESO-specific CD4 T cells. By assessing DR1/ESO119-143 tetramer(+) cells using T cell receptor (TCR) beta chain variable region (V beta)-specific antibodies, we identified several frequently used V beta. Finally, direct ex vivo staining of patients' CD4 T cells with tetramers allowed the direct quantification and phenotyping of vaccine-induced ESO-specific CD4 T cells. Conclusions: The development of DR1/ESO119-143 tetramers, allowing the direct visualization, isolation, and characterization of ESO-specific CD4 T cells, will be instrumental for the evaluation of spontaneous and vaccine-induced immune responses to this important tumor antigen in DR1-expressing patients

Uma nova espécie de Sigara Fabricius (Hemiptera, Heteroptera, Corixidae) e redescrição das espécies do gênero com registro no Estado do Rio Grande do Sul, Brasil

Uma nova espécie de Sigara Fabricius (Hemiptera, Heteroptera, Corixidae) e redescrição das espécies do gênero com registro no Estado do Rio Grande do Sul, Brasil. Os corixídeos representam o maior grupo de percevejos aquáticos conhecido, com cerca de 40 espécies ocorrentes no Brasil. Grande parte das espécies de Sigara ocorre na Região Neotropical, 11 delas foram registradas no Brasil até o momento. A distribuição e taxonomia das espécies ocorrentes no Rio Grande do Sul são pouco conhecidas. Sete espécies foram registradas e redescritas: Sigara (Tropocorixa) chrostowskii, S. (T.) denseconscripta, S. (T.) dita, S. (T.) hungerfordi, S. (T.) platensis, S. (T.) schadei e S. (T.) townsendi. Três espécies foram registradas pela primeira vez no Estado: S. (T.) dita, S. (T.) hungerfordi e S. (T.) townsendi. Sigara (T.) schadei nunca tinha sido registrada no Brasil. Sigara (T.) bachmanni, sp. nov. é descrita com base em exemplares coletados no nordeste do Estado. Essa nova espécie é similar à S. (T.) hungerfordi por apresentar o comprimento do sintilipso menor que 0,9 vezes a largura de um olho, o metaxifo mais largo que comprido e a gena estreita; pode ser distinguida das demais pela presença de um gancho curto no ápice do parâmero direito dos espécimes do sexo masculino e pela presença da margem da região preapical denteada. Uma chave de identificação para as espécies de Sigara ocorrentes no Rio Grande do Sul é fornecida. Apesar das características relativas ao aspecto geral do parâmero direito e do número de espinhos e forma da pala serem usados na definição das espécies, S. (T.) chrostowskii e S. (T.) townsendi mostraram consideráveis variações nessas características e foram redescritas neste estudo.

Comparative abundance and diversity of Dryininae (Hymenoptera, Dryinidae) in three savannah phytophysiognomies in southeastern Brazil, under three sampling methods

Comparative abundance and diversity of Dryininae (Hymenoptera, Dryinidae) in three savannah phytophysiognomies in southeastern Brazil, under three sampling methods. This study aimed to assess the abundance and diversity of Dryininae in riparian vegetation, Brazilian savannah, and savannah woodland vegetation at the Estação Ecológica de Jataí, in Luiz Antônio, State of São Paulo, Brazil, by using Moericke, Malaise, and light traps. The sampling was carried out from December 2006 to November 2009, and 371 specimens of Dryininae were caught, with the highest frequencies in spring and summer. Fourteen species of Dryinus Latreille, 1804 and one of Thaumatodryinus Perkins, 1905 were identified. The highest frequencies of Dryinus in the riparian vegetation differed significantly from those obtained in the Brazilian savannah and savannah woodland vegetation. In the riparian vegetation, the highest number of Dryinus was collected using light traps and the interactions between abundance and the collection method used were significant. The number of specimens of Dryinus collected in the Brazilian savannah and savannah woodland vegetation using Malaise traps did not differ significantly from those obtained using Moericke traps. Males significantly outnumbered females in the sex ratio of Dryinus. The species diversity of Dryinus based on females collected using Malaise traps was high in the Brazilian savannah. Furthermore, high species richness of female Dryinus was observed in riparian vegetation (six species) and Brazilian savannah (five). The light trap was the most successful method for sampling diversity of Dryininae.

Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injury.

Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine alpha-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission.

Informe del consultor para el Proyecto FAO/PER/76/022 cubriendo el trabajo de abril /mayo 1979

El proyecto se inició en mayo de 1978 y se terminó en diciembre de 1981. Sus objetivos principales con establecer las bases científicas para la administración racional de las pesquerías peruanas de aguas continentales y para su óptima utilización.

Four functionally distinct populations of human effector-memory CD8+ T lymphocytes.

In humans, the pathways of memory and effector T cell differentiation remain poorly defined. We have dissected the functional properties of ex vivo effector-memory (EM) CD45RA-CCR7- T lymphocytes present within the circulating CD8+ T cell pool of healthy individuals. Our studies show that EM T cells are heterogeneous and are subdivided based on differential CD27 and CD28 expression into four subsets. EM(1) (CD27+CD28+) and EM(4) (CD27-CD28+) T cells express low levels of effector mediators such as granzyme B and perforin and high levels of CD127/IL-7Ralpha. EM(1) cells also have a relatively short replicative history and display strong ex vivo telomerase activity. Therefore, these cells are closely related to central-memory (CD45RA-CCR7+) cells. In contrast, EM(2) (CD27+CD28-) and EM(3) (CD27-CD28-) cells express mediators characteristic of effector cells, whereby EM(3) cells display stronger ex vivo cytolytic activity and have experienced larger numbers of cell divisions, thus resembling differentiated effector (CD45RA+CCR7-) cells. These data indicate that progressive up-regulation of cytolytic activity and stepwise loss of CCR7, CD28, and CD27 both characterize CD8+ T cell differentiation. Finally, memory CD8+ T cells not only include central-memory cells but also EM(1) cells, which differ in CCR7 expression and may therefore confer memory functions in lymphoid and peripheral tissues, respectively.