315 research outputs found

    Insulin-like growth factor 1 receptors in human breast tumour: localisation and quantification by histo-autoradiographic analysis.

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    To assess the precise role of IGF1 in benign and malignant breast diseases, we analysed the tissular localisation, characterised, and quantified specific insulin-like growth factor 1 (IGF1) binding sites in these heterogenous tissues, using histo-autoradiographic analysis (HAA). The 125I-IGF1 binding was performed on frozen tissue sections and analysed using 3H Ultrofilm autoradiography coupled to computerised image analysis. Competitive binding experiments using unlabelled IGF1, IGF2 and insulin showed that the tissues exhibited typical type I IGF binding sites. This specificity was confirmed by the use of alpha IR-3 monoclonal antibody, as inhibitor of 125I-IGF1 binding. IGF1 binding sites were detected in 18 human primary breast cancers, 12 benign breast tumours and two normal breast tissues. Using HAA we found that the human breast carcinomas studied exhibit a specific and high binding capacity for 125I-IGF1 exclusively localised on the proliferative epithelial component. The 125I-IGF1 binding activity of benign breast tumours or normal breast tissue was significantly lower than in cancerous tissues. There was a significant correlation between IGF1-R concentrations detected with HAA and those detected with a classical biochemical method. Moreover, HAA could be useful in further detailing whether a tumour is IGF1-R positive or negative HAA appears to be a useful method for the detection of growth factor receptors, specially in small biopsy specimens

    Changes in feeding behavior and patch use by herbivores in response to the introduction of a new predator

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    Top-order carnivores are naturally returning, or are being reintroduced, in a number of places where they have previously been extirpated. To explore how prey species adjust their antipredator behavior in response to these predators, we measured giving-up densities (GUDs) in experimental feeding patches and time spent vigilant for greater kudu (Tragelaphus strepsiceros), sable antelope (Hippotragus niger), and warthogs (Phacochoerus africanus) before and after an introduction of wild dogs (Lycaon pictus). Before the introduction, the only predators in the system were cheetahs (Acinonyx jubatus). After the release, none of the prey species changed their microhabitat preference, in that they all preferred open grasslands to mixed tree and bush-clumps and bush-clumps. However, kudu and sable fed more intensively (i.e., achieved lower GUDs) and had lower vigilance in open grasslands, while reducing their feeding effort (i.e., higher GUDs) and increasing their vigilance near denser vegetation. When the wild dogs denned in the study site, potentially increasing contact with the prey species, the time kudu spent vigilant and their GUDs increased significantly across all patches, and continued to increase over time. In contrast, sable and warthogs stopped feeding from the experimental patches altogether during this period. The change in feeding intensity and vigilance levels by kudu likely reflected an additive antipredator response to both cheetahs and wild dogs, whereas sable and warthogs only responded to the increased risk from the wild dogs. Our results indicate that the addition of wild dogs influenced the foraging-safety trade-off for the 3 prey species, but that the antipredator behaviors utilized by these species to mitigate predation risk varied within the newly established 2-predator system.The National Research Foundation (grant number 77582 to AMS), UKZN, GreenMatter, and the Tswalu Foundation.http://jmammal.oxfordjournals.org2019-04-03hj2018Mammal Research InstituteZoology and Entomolog

    Functional outcome is tied to dynamic brain states after mild to moderate traumatic brain injury

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    The current study set out to investigate the dynamic functional connectome in relation to long-term recovery after mild to moderate traumatic brain injury (TBI). Longitudinal resting-state functional MRI data were collected (at 1 and 3 months postinjury) from a prospectively enrolled cohort consisting of 68 patients with TBI (92% mild TBI) and 20 healthy subjects. Patients underwent a neuropsychological assessment at 3 months postinjury. Outcome was measured using the Glasgow Outcome Scale Extended (GOS-E) at 6 months postinjury. The 57 patients who completed the GOS-E were classified as recovered completely (GOS-E = 8; n = 37) or incompletely (GOS-E < 8; n = 20). Neuropsychological test scores were similar for all groups. Patients with incomplete recovery spent less time in a segregated brain state compared to recovered patients during the second visit. Also, these patients moved less frequently from one meta-state to another as compared to healthy controls and recovered patients. Furthermore, incomplete recovery was associated with disruptions in cyclic state transition patterns, called attractors, during both visits. This study demonstrates that poor long-term functional recovery is associated with alterations in dynamics between brain networks, which becomes more marked as a function of time. These results could be related to psychological processes rather than injury-effects, which is an interesting area for further work. Another natural progression of the current study is to examine whether these dynamic measures can be used to monitor treatment effects

    The continuous flowering gene in rose is a floral inhibitor

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    In rose, RoKSN, a TFL1 homologue, is a key regulator of continuous flowering. To study the function of this gene in planta, protocols of plant transformation are needed. We complemented tfl1 Arabidopsis mutants and ectopically expressed RoKSN in a continuous-flowering rose. In Arabidopsis, RoKSN complemented the tfl1 mutant by rescuing late flowering and indeterminate growth. In continuous-flowering rose, the ectopic expression of RoKSN led to the absence of flowering. In these transgenic roses, a study of genes implied in the floral regulation was carried out. The floral activator transcripts decreased whereas the FD transcription factor is up-regulated. We conclude that RoKSN is a floral repressor and could regulate the expression of transcripts as RoFT and RoFD. These results could strengthen a mechanism of competitive interactions of RoFT and RoKSN with a common partner, FD to move towards flowering or vegetative developments

    RoKSN, a floral repressor, forms protein complexes with RoFD and RoFT to regulate vegetative and reproductive development in rose

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    FT/TFL1 family members have been known to be involved in the development and flowering in plants. In rose, RoKSN, a TFL1 homologue, is a key regulator of flowering, whose absence causes continuous flowering. Our objectives are to functionally validate RoKSN and to explore its mode of action in rose.We complemented Arabidopsis tfl1 mutants and ectopically expressed RoKSN in a continuous-flowering (CF) rose. Using different protein interaction techniques, we studied RoKSN interactions with RoFD and RoFT and possible competition. In Arabidopsis, RoKSN complemented the tfl1 mutant by rescuing late flowering and indeterminate growth. In CF roses, the ectopic expression of RoKSN led to the absence of flowering. Different branching patterns were observed and some transgenic plants had an increased number of leaflets per leaf. In these transgenic roses, floral activator transcripts decreased. Furthermore, RoKSN was able to interact both with RoFD and the floral activator, RoFT. Protein interaction experiments revealed that RoKSN and RoFT could compete with RoFD for repression and activation of blooming, respectively. We conclude that RoKSN is a floral repressor and is also involved in the vegetative development of rose. RoKSN forms a complex with RoFD and could compete with RoFT for repression of flowering

    A genome-wide approach reveals novel imprinted genes expressed in the human placenta

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    Genomic imprinting characterizes genes with a monoallelic expression, which is dependent on the parental origin of each allele. Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive. We used a high-throughput strategy by diverting the classical use of genotyping microarrays to compare the genotypes of mRNA/cDNA vs. genomic DNA to identify new genes presenting monoallelic expression, starting from human placental material. After filtering of data, we obtained a list of 1,082 putative candidate monoallelic SNPs located in more than one hundred candidate genes. Among these, we found known imprinted genes, such as IPW, GRB10, INPP5F and ZNF597, which contribute to validate the approach. We also explored some likely candidates of our list and identified seven new imprinted genes, including ZFAT, ZFAT-AS1, GLIS3, NTM, MAGI2, ZC3H12Cand LIN28B, four of which encode zinc finger transcription factors. They are, however, not imprinted in the mouse placenta, except for Magi2. We analyzed in more details the ZFAT gene, which is paternally expressed in the placenta (as ZFAT-AS1, a non-coding antisense RNA) but biallelic in other tissues. The ZFAT protein is expressed in endothelial cells, as well as in syncytiotrophoblasts. The expression of this gene is, moreover, downregulated in placentas from complicated pregnancies. With this work we increase by about 10% the number of known imprinted genes in humans

    LSST: from Science Drivers to Reference Design and Anticipated Data Products

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    (Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2^2 field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5σ\sigma point-source depth in a single visit in rr will be ∌24.5\sim 24.5 (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg2^2 with ÎŽ<+34.5∘\delta<+34.5^\circ, and will be imaged multiple times in six bands, ugrizyugrizy, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg2^2 region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to r∌27.5r\sim27.5. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

    Arabidopsis leucine-rich repeat receptor–like kinase NILR1 is required for induction of innate immunity to parasitic nematodes

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    Plant-parasitic nematodes are destructive pests causing losses of billions of dollars annually. An effective plant defence against pathogens relies on the recognition of pathogen-associated molecular patterns (PAMPs) by surface-localised receptors leading to the activation of PAMP-triggered immunity (PTI). Extensive studies have been conducted to characterise the role of PTI in various models of plant-pathogen interactions. However, far less is known about the role of PTI in roots in general and in plant-nematode interactions in particular. Here we show that nematode-derived proteinaceous elicitor/s is/are capable of inducing PTI in Arabidopsis in a manner dependent on the common immune co-receptor BAK1. Consistent with the role played by BAK1, we identified a leucine-rich repeat receptor-like kinase, termed NILR1 that is specifically regulated upon infection by nematodes. We show that NILR1 is essential for PTI responses initiated by nematodes and nilr1 loss-of-function mutants are hypersusceptible to a broad category of nematodes. To our knowledge, NILR1 is the first example of an immune receptor that is involved in induction of basal immunity (PTI) in plants or in animals in response to nematodes. Manipulation of NILR1 will provide new options for nematode control in crop plants in future
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