Synergistic action of GA-binding protein and glucocorticoid receptor in transcription from the mouse mammary tumor virus promoter.

B lymphocytes are among the first cells to be infected by mouse mammary tumor virus (MMTV), and they play a crucial role in its life cycle. To study transcriptional regulation of MMTV in B cells, we have analyzed two areas of the long terminal repeat (LTR) next to the glucocorticoid receptor binding site, fp1 (at position -139 to -146 from the cap site) and fp2 (at -157 to -164). Both showed B-cell-specific protection in DNase I in vitro footprinting assays and contain binding sites for Ets transcription factors, a large family of proteins involved in cell proliferation and differentiation and oncogenic transformation. In gel retardation assays, fp1 and fp2 bound the heterodimeric Ets factor GA-binding protein (GABP) present in B-cell nuclear extracts, which was identified by various criteria: formation of dimers and tetramers, sensitivity to pro-oxidant conditions, inhibition of binding by specific antisera, and comigration of complexes with those formed by recombinant GABP. Mutations which prevented complex formation in vitro abolished glucocorticoid-stimulated transcription from an MMTV LTR linked to a reporter gene in transiently transfected B-cell lines, whereas they did not affect the basal level. Exogenously expressed GABP resulted in an increased level of hormone response of the LTR reporter plasmid and produced a synergistic effect with the coexpressed glucocorticoid receptor, indicating cooperation between the two. This is the first example of GABP cooperation with a steroid receptor, providing the opportunity for studying the integration of their intracellular signaling pathways.

Allergic bronchopulmonary aspergillosis: the hunt for a diagnostic serological marker in cystic fibrosis patients.

The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis patients remains challenging, mainly owing to overlapping symptoms of the underlying lung disease with clinical symptoms of ABPA. In addition, a varying mixture of diagnostic criteria, including clinical status, radiological findings and immunological measurements, has led to confusion and differing recommendations. In order to help simplify as well as standardize the diagnostic criteria for ABPA, different serological markers have been evaluated in the last 20 years and their usefulness has been assessed in many clinical studies. This review presents current diagnostic criteria of ABPA, with a special focus on serum markers supporting the diagnosis and explains why the hunt for a serological marker for ABPA is still ongoing.

Safety of artemether-lumefantrine exposure in first trimester of pregnancy: an observational cohort.

BACKGROUND: There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy. METHODS: Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery. RESULTS: 2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]). CONCLUSION: Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.

In BALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease.

In contrast to intact BALB/c mice, BALB/c mice rendered deficient in Vbeta4+ CD4+ T cells develop a Th1 response to infection with Leishmania major and are resistant. Vbeta4-deficient BALB/c mice are unable to generate the early IL-4 transcription occurring in Vbeta4 Valpha8 CD4+ T cells of BALB/c mice within 1 day of infection. Here we demonstrate that treatment of Vbeta4-deficient BALB/c mice with IL-4 during the first 64 h after infection instructs Th2 cell development and susceptibility to infection. The demonstrated inability of IL-4 to reverse the resistant phenotype of BALB/c mice treated with anti-CD4 mAb the day before infection suggest that these effects of IL-4 require its interaction with CD4+ T cells. In contrast to draining lymph node cells from BALB/c mice, cells from Vbeta4-deficient BALB/c mice remain responsive to IL-12 following infection. Strikingly, administration of IL-4 to Vbeta4-deficient BALB/c mice renders their lymph node cells unresponsive to IL-12 by down-regulating IL-12R beta2-chain expression. This study directly demonstrates that in BALB/c mice IL-4 is necessary and sufficient to initiate the molecular events steering Th2 cell maturation and susceptibility to L. major.

De la perception à l'apprentissage [From perception to learning]

Dans le domaine de la perception, l'apprentissage est contraint par la présence d'une architecture fonctionnelle constituée d'aires corticales distribuées et très spécialisées. Dans le domaine des troubles visuels d'origine cérébrale, l'apprentissage d'un patient hémi-anopsique ou agnosique sera limité par ses capacités perceptives résiduelles, mais un déficit de reconnaissance visuelle de nature apparemment perceptive, peut également être associé à une altération des représentations en mémoire à long terme. Des réseaux neuronaux distincts pour la reconnaissance - cortex temporal - et pour la localisation des sons - cortex pariétal - ont été décrits chez l'homme. L'étude de patients cérébro-lésés confirme le rôle des indices spatiaux dans un traitement auditif explicite du « where » et dans la discrimination implicite du « what ». Cette organisation, similaire à ce qui a été décrit dans la modalité visuelle, faciliterait les apprentissages perceptifs. Plus généralement, l'apprentissage implicite fonde une grande partie de nos connaissances sur le monde en nous rendant sensible, à notre insu, aux règles et régularités de notre environnement. Il serait impliqué dans le développement cognitif, la formation des réactions émotionnelles ou encore l'apprentissage par le jeune enfant de sa langue maternelle. Le caractère inconscient de cet apprentissage est confirmé par l'étude des temps de réaction sériels de patients amnésiques dans l'acquisition d'une grammaire artificielle. Son évaluation pourrait être déterminante dans la prise en charge ré-adaptative. [In the field of perception, learning is formed by a distributed functional architecture of very specialized cortical areas. For example, capacities of learning in patients with visual deficits - hemianopia or visual agnosia - from cerebral lesions are limited by perceptual abilities. Moreover a visual deficit in link with abnormal perception may be associated with an alteration of representations in long term (semantic) memory. Furthermore, perception and memory traces rely on parallel processing. This has been recently demonstrated for human audition. Activation studies in normal subjects and psychophysical investigations in patients with focal hemispheric lesions have shown that auditory information relevant to sound recognition and that relevant to sound localisation are processed in parallel, anatomically distinct cortical networks, often referred to as the "What" and "Where" processing streams. Parallel processing may appear counterintuitive from the point of view of a unified perception of the auditory world, but there are advantages, such as rapidity of processing within a single stream, its adaptability in perceptual learning or facility of multisensory interactions. More generally, implicit learning mechanisms are responsible for the non-conscious acquisition of a great part of our knowledge about the world, using our sensitivity to the rules and regularities structuring our environment. Implicit learning is involved in cognitive development, in the generation of emotional processing and in the acquisition of natural language. Preserved implicit learning abilities have been shown in amnesic patients with paradigms like serial reaction time and artificial grammar learning tasks, confirming that implicit learning mechanisms are not sustained by the cognitive processes and the brain structures that are damaged in amnesia. In a clinical perspective, the assessment of implicit learning abilities in amnesic patients could be critical for building adapted neuropsychological rehabilitation programs.]

Fifth-order cyclicity and organic matter contents relationship (Lower Eocene, Pyrenees)

The Upper Limestone Member of the Corones Formation of the Spanish Pyrenees consists of various units (Lower and Upper Foraminifera Units, Shale Unit, Cherty-ostracode Unit, Ostracode Unit and Chara-ostracode Unit) and offers strong facies and lateral thickness (20 to 80 m) variations. Detailed facies analyses, fifth-order cycles and organic geochemical determinations in the central domain of the Corones platform carbonates (Cherty-ostracode Unit), lower Eocene in age, were carried out to establish a case of close relationship between variations in organic matter productivity and cyclicity with annual period. The Cherty-ostracode Unit displays a continuous and pervasive fifth-order cyclicity, represented by 5 cycles. Each cycle consists of a lower part (mollusc facies) and an upper part (laminated ostracode facies). The calculated fifth-order cycle period ranges from about 17,000 to 28,000 years, which falls within the Milankovitch Band. Variations in organic matter content related to these carbonate cycles have been established. The lower mollusc facies members show a low organic carbon content and Hydrogen Index (HI) below 0.6% in weight and 261, respectively. By contrast, the upper laminated ostracode facies members show high organic carbon contents (up to 2% in weight) and high HI (between 164 and 373), and are also characterized by important silicification processes (the content in chert is up to 30%). The organic geochemistry resulting from these organic rich levels reflects a contribution of algal marine input.

Estimating Design-Flood Discharges for Streams in Iowa Using Drainage-Basin and Channel-Geometry Characteristics, HR-322, 1993

Drainage-basin and channel-geometry multiple-regression equations are presented for estimating design-flood discharges having recurrence intervals of 2, 5, 10, 25, 50, and 100 years at stream sites on rural, unregulated streams in Iowa. Design-flood discharge estimates determined by Pearson Type-III analyses using data collected through the 1990 water year are reported for the 188 streamflow-gaging stations used in either the drainage-basin or channel-geometry regression analyses. Ordinary least-squares multiple-regression techniques were used to identify selected drainage-basin and channel-geometry regions. Weighted least-squares multiple-regression techniques, which account for differences in the variance of flows at different gaging stations and for variable lengths in station records, were used to estimate the regression parameters. Statewide drainage-basin equations were developed from analyses of 164 streamflow-gaging stations. Drainage-basin characteristics were quantified using a geographic-information-system (GIS) procedure to process topographic maps and digital cartographic data. The significant characteristics identified for the drainage-basin equations included contributing drainage area, relative relief, drainage frequency, and 2-year, 24-hour precipitation intensity. The average standard errors of prediction for the drainage-basin equations ranged from 38.6% to 50.2%. The GIS procedure expanded the capability to quantitatively relate drainage-basin characteristics to the magnitude and frequency of floods for stream sites in Iowa and provides a flood-estimation method that is independent of hydrologic regionalization. Statewide and regional channel-geometry regression equations were developed from analyses of 157 streamflow-gaging stations. Channel-geometry characteristics were measured on site and on topographic maps. Statewide and regional channel-geometry regression equations that are dependent on whether a stream has been channelized were developed on the basis of bankfull and active-channel characteristics. The significant channel-geometry characteristics identified for the statewide and regional regression equations included bankfull width and bankfull depth for natural channels unaffected by channelization, and active-channel width for stabilized channels affected by channelization. The average standard errors of prediction ranged from 41.0% to 68.4% for the statewide channel-geometry equations and from 30.3% to 70.0% for the regional channel-geometry equations. Procedures provided for applying the drainage-basin and channel-geometry regression equations depend on whether the design-flood discharge estimate is for a site on an ungaged stream, an ungaged site on a gaged stream, or a gaged site. When both a drainage-basin and a channel-geometry regression-equation estimate are available for a stream site, a procedure is presented for determining a weighted average of the two flood estimates.

Variations of the carcinoembryonic antigen level in the plasma of patients with gynecologie cancers during therapy

In 63 patients with histologically proved gynecologie carcinoma, circulating carcinoembryonic antigen (CEA) was determined by radioimmunoassay before and at two intervals after treatment. Thirty-one patients of 63 had CEA values over 2.5 ng. per milliliter before treatment. In general, the CEA levels were low compared to those found in endodermal carcinoma. The percentage of elevated CEA values was slightly higher in cases of carcinoma of the cervix and corpus uteri than in those of carcinoma of the ovary. All patients with CEA levels greater than 2.5 ng. per milliliter treated by complete surgical resection of tumor showed a drop of CEA levels to below 2.5 ng. per milliliter seven weeks after operation. In contrast, patients with palliative therapy showed no change in CEA values. About half of the patients treated with a complete course of internal and external radiotherapy showed a drop of CEA levels to below 2.5 ng. per milliliter, whereas the other patients showed fluctuating CEA values. No correlation between clinical status and evolution of CEA levels in these patients could be drawn at the present time. The CEA test seems to be of little value for the earl of diagnosis of gynecologie carcinoma but appears to be interesting for the evaluation of therapy and the follow-up of patients with diagnosed cases.

Iowa Department of Transportation Major Items - Preliminary Quantity Report, April 15, 2014; With Addendums

Weekly letting report.

Cono-spondylar dysplasia: Clinical, radiographic, and molecular findings of a previously unreported disorder.

We report on a consanguineous Arab family in which three sibs had an unusual skeletal dysplasia characterized by anterior defects of the spine leading to severe lumbar kyphosis and marked brachydactyly with cone epiphyses. The clinical phenotype also included dysmorphic facial features, epilepsy, and developmental delay. This constellation likely represents a previously undescribed skeletal dysplasia, most probably inherited in an autosomal recessive pattern. A homozygosity mapping approach has thus far failed to unearth the responsible gene as the region shared by these three sibs is 27.7 Mb in size and contains over 200 genes with no obvious candidate.

Construction and Maintenance Practices to Minimize the Potential Liability of Counties for Roads in Rural Subdivisions, HR-221, 1981

In an earlier research project, HR-204, the magnitude and nature of highway related tort claims against counties in Iowa were investigated. However, virtually all of the claims identified in that research resulted from incidents that occurred in areas with predominantly agricultural land use. With recent increases in the rural non-farm population, many traditionally urban problems are also appearing in built-up areas under county jurisdiction. This trend is expected to continue so that counties must anticipate a change in the nature of the tort claims they will encounter. Problems that heretofore have been unique to cities may become commonplace in areas for which counties are responsible. The research reported here has been directed toward an investigation of those problems in rural subdivisions that lead to claims growing out of the provision of highway services by counties. Lacking a sufficient database among counties for the types of tort claims of interest in this research, a survey was sent to 259 cities in Iowa in order to identify highway related problems leading to those claims. The survey covered claims during a five year period from 1975 to 1980. Over one-third of the claims reported were based on alleged street defects. Another 34 percent of the claims contained allegations of damages due to backup of sanitary sewers or defects in sidewalks. By expanding the sample from the 164 cities that responded to the survey, it was estimated that a total of $49,000,000 in claims had been submitted to all 259 cities. Over 34% of this amount resulted from alleged defects in the use of traffic signs, signals, and markings. Another 42% arose from claims of defects in streets and sidewalks. Payments in settlement of claims were about 13.4% of the amount asked for those claims closed during the period covered by the survey. About $9,000,000 in claims was pending on June 30, 1980 according to the information furnished. Officials from 23 cities were interviewed to provide information on measures to overcome the problems leading to tort claims. On the basis of this information, actions have been proposed that can be undertaken by counties to reduce the potential for highway-related claims resulting from their responsibilities in rural subdivisions and unincorporated communities. Suggested actions include the eight recommendations contained in the final report for the previous research under HR-204. In addition, six recommendations resulted from this research, as follows: 1. Counties should adopt county subdivision ordinances. 2. A reasonable policy concerning sidewalks should be adopted. 3. Counties should establish and implement a system for setting road maintenance priorities. 4. Counties should establish and implement a procedure for controlling construction or maintenance activities within the highway right of way. 5. Counties should establish and implement a system to record complaints that are received relating to highway maintenance and to assure timely correction of defective conditions leading to such complaints. 6. Counties should establish and implement a procedure to ensure timely advice of highway defects for which notice is not otherwise received.

Avaliação de seis variedades de uvas sem sementes no Submédio São Francisco

Este trabalho teve como objetivo avaliar aspectos relacionados ao desenvolvimento vegetativo e produtivo das plantas, às características físicas e à composição química dos frutos de seis variedades de uvas sem sementes nas condições do Submédio São Francisco. Os dados foram registrados durante os anos de 1997 e 1998. As variedades utilizadas foram enxertadas sobre o porta-enxerto IAC 572 (`Jales'). O delineamento experimental foi inteiramente casualizado, com parcelas subdivididas nos ciclos de produção. Houve diferenças significativas na resposta da maioria das variedades entre as épocas de poda. O peso médio dos cachos variou entre 164,8 g na variedade Marroo Seedless, e 203,5 g na `Beauty Seedless'. O diâmetro médio das bagas foi superior a 15,7 mm em todas as variedades. Foram obtidos teores de sólidos solúveis compreendidos entre 14,05ºBrix na variedade Canner e 19,6ºBrix na `Vênus', enquanto a acidez total titulável foi inferior a 0,91 g de ácido tartárico/100 mL de suco, resultando em adequadas relações SST/ATT, que variaram entre 19,05 na variedade Beauty Seedless a 28,57 na `Vênus'. As variedades Vênus e Marroo Seedless foram as mais produtivas, com produtividades anuais de 24 t/ha e 20 t/ha, respectivamente.