Studies relating to protein expression in the uterus of the cow

End of project reportEmbryo loss is a major cause of reproductive wastage in the cow. The majority of embryo loss occurs in the first 16 days after fertilisation when the embryo is critically dependent on the maternal uterine environment for survival. Despite the central role of uterine fluid in the normal growth and development of the embryo, there is limited information on the protein composition of these fluids. The main objectives of the studies in this thesis were to examine the protein composition of the bovine uterus during the oestrous cycle and to examine the relationship between the concentration of systemic progesterone and uterine protein expression in the cow. In the first study, the concentration of retinol-binding protein (RBP) in the bovine uterus was found to vary across the cycle and was 5-15-fold higher (P0.05) of the cycle, which was surprising given that previous studies have indicated that uterine RBP gene expression was positively associated with the concentration of systemic progesterone. In the second study, IGF binding protein 2 (IGFBP-2), IGFBP-3, IGFBP-4 and IGFBP-5 were identified in uterine fluid on days 3, 7, 11 and 15 of the oestrous cycle. There was a local effect on the concentration of IGFBPs where the concentration was greater on the ipsilateral side than that on the contralateral side for IGFBP-2 (P<0.05), 3 (P<0.01) and 5 (P<0.01) on day 15. This difference is a further indication of a local controlling mechanism regulating proteins between the uterine horns. Similar to RBP expression this study could find no significant relationship between the concentration of systemic progesterone and IGFBP concentrations on Day 7 of the oestrous cycle. In the third study, changes in the global pattern of uterine proteins between Days 3 and Day 15 of the oestrous cycle were examined using two-dimensional electrophoresis (2-DE). Six proteins were found to be upregulated on Day 15 compared to Day 3. Three proteins of these were identified as aldose reductase, plakoglobin and heat shock protein 27 while the other three proteins were identified as bovine serum albumin. Aldose reductase, an enzyme directly involved in the production of sorbitol and indirectly of fructose, was 10-fold higher (P<0.0001) on Day 15 compared to Day 3. Plakoglobin (Pg) was upregulated 2.3-fold (P<0.0001) on Day 15 compared to Day 3. Pg is a component of cellular junctions and its up-regulation may have a role in the uterine glandular epithelium. Heat shock protein 27 (Hsp27) was higher on Day 15 than on Day 3 (P<0.01) and Hsp27 was 1.4-fold higher in the ipsilateral compared to the contralateral uterine horn (P<0.01). Hsp27 may be secreted in response to potential stresses in the uterus or act as a molecular chaperone. On Day 7 there was no difference (P<0.05) in the pattern of proteins secreted between cows with low (2.7±0.10ng/ml) and high (4.8±0.13 ng/ml) concentrations of systemic progesterone on Day 7. The results of these studies have shown that dramatic changes occur in protein expression across the bovine oestrous cycle. Additionally, it emphasises the need for gene studies to be followed with protein studies as an adjunct or complementary tool. Proteins have a wide range of essential roles in the uterus and together these studies provide novel information on protein expression in the uterus of the cow

Spark: A navigational paradigm for genomic data exploration

Biologists possess the detailed knowledge critical for extracting biological insight from genome-wide data resources, and yet they are increasingly faced with nontrivial computational analysis challenges posed by genome-scale methodologies. To lower this computational barrier, particularly in the early data exploration phases, we have developed an interactive pattern discovery and visualization approach, Spark, designed with epigenomic data in mind. Here we demonstrate Spark's ability to reveal both known and novel epigenetic signatures, including a previously unappreciated binding association between the YY1 transcription factor and the corepressor CTBP2 in human embryonic stem cells

Improving communication between postgraduate researchers and the university library: a case study at De Montfort University Library and Learning Services

A well-established postgraduate researcher development program has existed at De Montfort University for many years. Library and Learning Services include modules on literature searching skills and critical appraisal. However, we recognized that researchers seemed to be disengaged with the services on offer. This concern informed a research project that considered the ways we could communicate better with researchers based on their needs. This paper explores the essential components of successful communication, such as context, timeliness and communication channels. An action-research approach was taken including focus groups and online surveys. The outcomes highlighted three significant crisis points, emphasizing the key times when researchers might need some intervention. The findings of this research identified the distinct needs of Postgraduate Researchers (PGRs) and how relevant and timely communication from the library can meet these needs. It also considers the impact of how communication has improved with researchers as a result of some of our interventions

Assessing debris flows using LIDAR differencing: 18 May 2005 Matata event, New Zealand

The town of Matata in the Eastern Bay of Plenty (New Zealand) experienced an extreme rainfall event on the 18 May 2005. This event triggered widespread landslips and large debris flows in the Awatarariki and Waitepuru catchments behind Matata. The Light Detection and Ranging technology (LIDAR) data sets flown prior to and following this event have been differenced and used in conjunction with a detailed field study to identify the distribution of debris and major sediment pathways which, from the Awatarariki catchment, transported at least 350,000 ± 50,000 m3 of debris. Debris flows were initially confined to stream valleys and controlled by the density and hydraulic thrust of the currents, before emerging onto the Awatarariki debris fan where a complex system of unconfined sediment pathways developed. Here, large boulders, clasts, logs and entire homes were deposited as the flows decelerated. Downstream from the debris fan, the pre-existing coastal foredune topography played a significant role in deflecting the more dilute currents that in filled lagoonal swale systems in both directions. The differenced LIDAR data have revealed several sectors characterised by significant variation in clast size, thickness and volume of debris as well as areas where post-debris flow cleanup and grading operations have resulted in man-made levees, sediment dumps, scoured channels and substantial graded areas. The application of differenced LIDAR data to a debris flow event demonstrates the techniques potential as a precise and powerful tool for hazard mapping and assessment

Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors

Altres ajuts: This work has also been supported by a "Marató TV3" grant (20141210 to J.F. and 044412 to R.B.).Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by ill-defined mechanisms. Here we report a large metabolomics study of plasma and cerebrospinal fluid, showing in independent cohorts that people with DS produce elevated levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent immunosuppressive and neurotoxic properties, respectively. Immune cells of people with DS overexpress IDO1, the rate-limiting enzyme in the kynurenine pathway (KP) and a known interferon (IFN)-stimulated gene. Furthermore, the levels of IFN-inducible cytokines positively correlate with KP dysregulation. Using metabolic tracing assays, we show that overexpression of IFN receptors encoded on chromosome 21 contribute to enhanced IFN stimulation, thereby causing IDO1 overexpression and kynurenine overproduction in cells with T21. Finally, a mouse model of DS carrying triplication of IFN receptors exhibits KP dysregulation. Together, our results reveal a mechanism by which T21 could drive immunosuppression and neurotoxicity in DS

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

INVASIVESNET towards an International Association for Open Knowledge on Invasive Alien Species

In a world where invasive alien species (IAS) are recognised as one of the major threats to biodiversity, leading scientists from five continents have come together to propose the concept of developing an international association for open knowledge and open data on IAS—termed “INVASIVESNET”. This new association will facilitate greater understanding and improved management of invasive alien species (IAS) and biological invasions globally, by developing a sustainable network of networks for effective knowledge exchange. In addition to their inclusion in the CBD Strategic Plan for Biodiversity, the increasing ecological, social, cultural and economic impacts associated with IAS have driven the development of multiple legal instruments and policies. This increases the need for greater co-ordination, co-operation, and information exchange among scientists, management, the community of practice and the public. INVASIVESNET will be formed by linking new and existing networks of interested stakeholders including international and national expert working groups and initiatives, individual scientists, database managers, thematic open access journals, environmental agencies, practitioners, managers, industry, non-government organisations, citizens and educational bodies. The association will develop technical tools and cyberinfrastructure for the collection, management and dissemination of data and information on IAS; create an effective communication platform for global stakeholders; and promote coordination and collaboration through international meetings, workshops, education, training and outreach. To date, the sustainability of many strategic national and international initiatives on IAS have unfortunately been hampered by time-limited grants or funding cycles. Recognising that IAS initiatives need to be globally coordinated and ongoing, we aim to develop a sustainable knowledge sharing association to connect the outputs of IAS research and to inform the consequential management and societal challenges arising from IAS introductions. INVASIVESNET will provide a dynamic and enduring network of networks to ensure the continuity of connections among the IAS community of practice, science and management

Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript

Advances in genome sequencing have resulted in the identification of the causes for numerous rare diseases. However, many cases remain unsolved with standard molecular analyses. We describe a family presenting with a phenotype resembling inherited thrombocytopenia 2 (THC2). THC2 is generally caused by single nucleotide variants that prevent silencing of ANKRD26 expression during hematopoietic differentiation. Short-read whole-exome and genome sequencing approaches were unable to identify a causal variant in this family. Using long-read whole-genome sequencing, a large complex structural variant involving a paired-duplication inversion was identified. Through functional studies, we show that this structural variant results in a pathogenic gain-of-function WAC-ANKRD26 fusion transcript. Our findings illustrate how complex structural variants that may be missed by conventional genome sequencing approaches can cause human disease