Oncogenes and human cancer

The first demonstrations that cancer could have an infectious nature was by Ellerman and Bang (1) ~ who showed that leukemia in chickens was transmissible with cell-free extracts and by Rous (2), who found in a similar fashion that naturally occurring chicken sarcomas were transmissible. Although they were able to show that these cell-free extracts contained a transmissible agent~ the idea that this induced cancer was received by the scientific world at that time with great skepticism. The interest in oncogenic viruses was strongly enhanced in the early 60's by the isolation of mammalian tumor viruses and the general acceptance that at least some of these viruses were tumorigenic. The discovery of the reverse transcriptase enzyme in RNA tumor viruses (3,4), gave a logical explanation for how these viruses became integrated in the chromosomes of eukaryotic cells. Taxonomically, oncogenic viruses are members of diverse families. DNA viruses (herpes-, adeno- and papovaviruses) as well as many members of the retrovirus family (containing RNA such as the type C RNA viruses) are capable of inducing tumors. For the retroviruses two different routes to become transforming (oncogenic) have become clear. The majority of these viruses (the acute type C RNA transforming viruses) 11 acquire11 certain genetic sequences (oncogenes) from their host, which are necessary to initiate and maintain the malignant transformation of the cell by the virus. Other retroviruses integrate their genome nearby oncogenic sequences in the chromosome of their host. Independent of the exact mechanism, these viruses share the capability of inducing tumorigenesis by triggering the transcription of certain sequences, and it is the proteins encoded by these sequences which are necessary to maintain the neoplastic phenotype of the infected cell The accumulating number of independent isolates of tumorigenic retroviruses induced in the mid-70's a worldwide search for these viruses in humans. Only very recently the isolation of a human tumor T-cell leukemia retrovirus (HTLV) was reported (5,6). Another approach was initiated in the beginning of the 80's, with the finding that the acquired sequences of retroviruses are strongly conserved among species. In general, the cellular homologs of these sequences were easily detectable and could be studied in more detail by molecular cloning, using the oncogenic acquired sequences of retroviruses as probes. This approach seems to be very fruitful and will be discussed in more detail below. Although the oncogenic potential of the acquired sequences in a number of these viruses in vertebrates is well estabished, the involvement of their human cellular homologs in human tumorigenesis has been and will be a rich source for discussion. However, at the moment they provide us the best available model for the induction of human cancer at the molecular leve

Towards Dynamic Catalogues

The International LOFAR Telescope is designed to carry out unique science in the spatial, spectral, polarisation and temporal domains. The Transients Key Science Project aims to study all transient and variable sources detected by LOFAR. One of its products will be an up-to-date catalogue of all sources detected by LOFAR, i.e. a spectral light-curve database, with real-time capabilities, and expected to grow gradually with 50−100 TB/yr. The response time to transient and variable events depends strongly on the query execution plans of the algorithms that search the LOFAR light-curve database for previous (non-)detections in the spatial, spectral, polarisation and temporal domains. Here we show how the Transients Key Science Project of LOFAR approaches these challenges by using column-stores, sharded databases and implementing the new array query language SciQL (pronounced as ’cycle’)

Bcr is a substrate for Transglutaminase 2 cross-linking activity

<p>Abstract</p> <p>Background</p> <p>Breakpoint cluster region (Bcr) is a multi-domain protein that contains a C-terminal GTPase activating protein (GAP) domain for Rac. Transglutaminase 2 (TG2) regulates Bcr by direct binding to its GAP domain. Since TG2 has transglutaminase activity that has been implicated in the response to extreme stress, we investigated if Bcr can also act as a substrate for TG2.</p> <p>Results</p> <p>We here report that activation of TG2 by calcium caused the formation of covalently cross-linked Bcr. Abr, a protein related to Bcr but lacking its N-terminal oligomerization domain, was not cross-linked by TG2 even though it forms a complex with it. A Bcr mutant missing the first 62 amino acid residues remained monomeric in the presence of activated TG2, showing that this specific domain is necessary for the cross-linking reaction. Calcium influx induced by a calcium ionophore in primary human endothelial cells caused cross-linking of endogenous Bcr, which was inhibited by the TG2 inhibitor cystamine. Treatment of cells with cobalt chloride, a hypoxia-mimetic that causes cellular stress, also generated high molecular weight Bcr complexes. Cross-linked Bcr protein appeared in the TritonX-100-insoluble cell fraction and further accumulated in cells treated with a proteasome inhibitor.</p> <p>Conclusions</p> <p>Bcr thus represents both an interacting partner under non-stressed conditions and a target of transglutaminase activity for TG2 during extreme stress.</p

Tail posture and motion as a possible indicator of emotional state in pigs

In the current study, the aim was to investigate whether tail posture and motion can be an indicator of the emotional state of pigs and if the tail posture of the pig is affected by social breeding value (SBV), coping style and/or housing. Emotional state can be defined in two dimensions: valence and arousal. Two batches of 96 finishing pigs were studied in a one generation selection experiment with a 2x2 set up and were housed in a barren or straw bedded pen. In each pen, 6 pigs (3 male, 3 female) were housed. A back-test was done to determine the coping style of the pigs with two categories; high resister and low resister pigs. When possible, each pen held 3 high resisters and 3 low resisters pigs. Furthermore, half of the pens contained pigs with low SBV and the other half contained high SBV pigs. Tail condition scores were determined weekly. A novel environment test (150 sec) with a small arena was performed at 3.5 weeks of age to test the fearfulness of the pigs. Behaviours and vocalisations were recorded together with the tail posture and motion. Four different tail posture and motion categories were recorded; curled tail, hanging tail, tail between legs and tail wagging. Furthermore, home pen observations were performed to link behaviours to a tail posture or motion. The most performed tail posture in the novel environment test and the home pen observations was a hanging tail posture (60%), while curled tail was performed 30% of the time and tail between the legs and tail wagging occurred both 5% of the time. A curled tail was linked with active behaviour (high arousal), whilst a hanging tail was linked with inactive behaviour (low arousal). No effect of SBV or coping style was found in the novel environment test on the tail postures and motion. In the home pen observations, low SBV pigs showed more tail between the legs than high SBV pigs (P<0.05). High resisters kept their tail curled more often than low resisters (P<0.01). Also, high resister pigs with a low SBV showed a curled tail more often than the other treatment groups (P<0.05). Tail between the legs occurred more often in barren housed pigs than in enriched housed pigs (P<0.05), which could link this tail posture to a negative emotional state. Housing had an effect on the tail condition score; barren housed pigs without straw had more tail damage than enriched pigs (P<0.0001). Positive correlations were found between eating/drinking and a curled tail, social behaviour and tail between legs, and negative social behaviour and manipulation with a wagging tail (P<0.0001). To conclude, a curled tail could be linked to a positive emotional state, with high arousal. A hanging tail may be linked to a neutral state, neither positive nor negative. Pigs with their tail between the legs may be associated with a negative emotional state and low to medium arousal. Tail wagging can be associated with a negative emotional state, with high arousal. However, conclusions should be made carefully, because still little is known about the link between emotional states and behaviour. Positive tests could be done to make the link between a positive emotional state and a certain tail posture more clear. Also, tests that elicit a more fearful response than the novel arena test could confirm results from the current study

Just-in-time Data Distribution for Analytical Query Processing

Distributed processing commonly requires data spread across machines using a priori static or hash-based data allocation. In this paper, we explore an alternative approach that starts from a master node in control of the complete database, and a variable number of worker nodes for delegated query processing. Data is shipped just-in-time to the worker nodes using a need to know policy, and is being reused, if possible, in subsequent queries. A bidding mechanism among the workers yields a scheduling with the most efficient reuse of previously shipped data, minimizing the data transfer costs. Just-in-time data shipment allows our system to benefit from locally available idle resources to boost overall performance. The system is maintenance-free and allocation is fully transparent to users. Our experiments show that the proposed adaptive distributed architecture is a viable and flexible alternative for small scale MapReduce-type of settings

Chronic activation of the 5-HT(2) receptor reduces 5-HT neurite density as studied in organotypic slice cultures

The serotonin system densely innervates the brain and is implicated in psychopathological processes. Here we studied the effect of serotonin and serotonin pharmacological compounds on the outgrowth of serotonergic projections using organotypic slice co-cultures of hippocampus and dorsal raphe nuclei. Immunocytochemical analysis showed that several serotonergic neurites had grown into the target slice within 7 days in culture, after which the neurite density stabilized. These projections expressed the serotonin-synthesizing enzyme Tryptophan hydroxylase and the serotonin transporter and contained several serotonin-positive varicosities that also accumulated presynaptic markers. Chronic application of a 5-HT(2) agonist reduced the serotonergic neurite density, without effects on survival of serotonergic neurons. In contrast, application of a 5-HT(1A) agonist or the serotonin transporter inhibitor fluoxetine did not affect serotonergic neurite density. We conclude that serotonergic connectivity was reproduced in vitro and that the serotonin neurite density is inhibited by chronic activation of the 5-HT(2) receptor