The Human Genome Project: its relevance to ocular disease

This article describes the history of the Human Genome Project, how the human genome was sequenced, and analyses the likely impact which the results will have on the diagnosis, scientific understanding and, ultimately, treatment of ocular disease in the future.

The 'cancer cachectic factor'

The object of this study was to summarize information on catabolic factors produced by tumours which lead to tissue catabolism in cancer cachexia and to use this information for the development of effective therapy. The study population was made up of patients with cancer cachexia and weight loss greater than 1 kg month-1. They had a varied range of carcinomas, particularly pancreatic, but also of the breast, ovary, lung, colon and rectum. Cachectic factors were isolated by standard biochemical methods, and the mechanism of tissue catabolism was evaluated in vitro and in vivo. We isolated a 24-kDa sulphated glycoprotein produced by cachexia-inducing murine and human tumours, which induces catabolism of myofibrillar proteins in skeletal muscle and for this reason has been named proteolysis-inducing factor (PIF). PIF was shown to be present in a diverse range of carcinomas in patients whose rate of weight loss exceeded 1.0 kg month-1. Administration of PIF to normal mice produced a rapid decrease in body weight, which arose primarily from a loss of skeletal muscle, accompanied by increased mRNA levels for ubiquitin, the ubiquitin-carrier protein (E214k), and proteasome subunits. This suggests that PIF induces protein catabolism through an increased expression of the key components of the ATP-ubiquitin-dependent proteolytic pathway. The action of PIF was attenuated both in vitro and in vivo by eicosapentaenoic acid (EPA). Oral EPA has been found to stabilize the body weight of patients with advanced pancreatic cancer and, when combined with an energy- and protein-rich nutritional supplement, to produce weight gain arising solely from an increase in lean body mass. Nutritional supplementation alone is unable to reverse the process of muscle wasting in cancer patients, since this arises from activation of the ubiquitin proteasome pathway by PIF, which is independent of nutrient intake. EPA is able to down-regulate the increased expression of this pathway and prevents muscle wasting in cancer patients.

Cancer therapy combining the modalities of hyperthermia and chemotherapy: In vitro cellular response after rapid heat accumulation in the cancer cell

Hyperthermia is usually used at a sub-lethal level in cancer treatment to potentiate the effects of chemotherapy. The purpose of this study is to investigate the role of heating rate in achieving synergistic cell killing by chemotherapy and hyperthermia. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. The cytotoxicity, mode of cell death, induction of thermal tolerance and P-gp mediated MDR following the two different modes of heating were studied. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. A slow rate hyperthermia was provided by a cell culture incubator. The results show that the potentiating effect of hyperthermia to chemotherapy can be maximized by increasing the rate of heating as evident by the results from the cytotoxicity assay. When delivered at the same thermal dose, a rapid increase in temperature from 37°C to 43°C caused more cell membrane damage than gradually heating the cells from 37°C to 43°C and thus allowed for more intracellular accumulation of the chemotherapeutic agents. Different modes of cell death are observed by the two hyperthermia delivery methods. The rapid rate laser-ICG hyperthermia @ 43°C caused cell necrosis whereas the slow rate incubator hyperthermia @ 43°C induced very mild apoptosis. At 43°C a positive correlation between thermal tolerance and the length of hyperthermia exposure is identified. This study shows that by increasing the rate of heating, less thermal dose is needed in order to overcome P-gp mediated MDR.

Genetically engineering the mouse genome to study the role of the Phosphotyrosyl Phosphatase Activator (PTPA) gene in the response to oxidative stress

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Genetically engineering the mouse genome to study the role of the Phosphotyrosyl Phosphatase Activator (PTPA) gene in the response to oxidative stress

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Contribution to the ethnobotanical study of antidiabetic medicinal plants of the Central Middle Atlas region (Morocco)

An ethnobotanical survey of medicinal plants was carried out in the Central Middle Atlas in the years 2013 and 2014 to establish the catalog of medicinal plants used in traditional medicine in the treatment of diabetes. Thus, 1560 people were interviewed, using questionnaires. The latter enabled us to gather information on traditional healing practices of the local population including scientific name, French name, vernacular name, plant parts used , therapeutic indications , revenues and mode of administration. The results show that 76 medicinal species were inventoried in the study area. These plant species are included into 67 genus and 40 families. The most represented families are: Lamiaceae (12 species), Asteraceae and Brassicaceae species with 14 each. Of 76 medicinal species found in the region, four species are reported for the first time in the traditional treatment of diabetes in Morocco. They are Pistacia atlantica, Ptychotis verticillata, Anacyclus pyrethrum, Alyssum spinosum, Cistus albidus, Juniperus thurifera, Ephedra nebrodensis, Thymus algeriensis, Th. munbyanus, Th. zygis, Abelmoschus esculentus, Fraxinus augustifolia, Sorghum vulgare and, Eriobotrya japonica. The leaves are the most used organs (38%). The decoction is the dominant mode of preparation (50%) and administration is mostly for oral use (97%).

Banana agronomy – can unravelling the Musa genome help?

Unravelling the Musa genome allows genes and alleles linked to desired traits to be identified. Short stature and early flowering are desirable agronomic features of banana, as they are of bread wheat (Triticum aestivum). In wheat they were achieved through knowledge of the physiology and genetics of vernalization and photoperiod during development. Bananas and plantains have a facultative long-day response to photoperiod, as do wheat and wall cress (Arabidopsis thaliana). Using keyword searches of the genome of Musa acuminata 'Pahang' we found homologues of the genes of either T. aestivum or Arabidopsis that govern responses to vernalization and photoperiod. This knowledge needs to be interpreted in the context of plant development. Bananas have juvenile, mid-vegetative and reproductive phases of development. Leaf and bunch 'clocks' operate concurrently throughout the juvenile and mid-vegetative phases. In the mid-vegetative phase the plant becomes sensitive to photoperiod. Increased sensitivity to photoperiod reduces the overall pace of the bunch clock without affecting the leaf clock. Separation of the clocks changes the link between leaf number and time of flowering. The 'critical' quantitative trait for the time of flowering is the pace of the bunch clock up to bunch initiation. For bunch size it is the duration of the subsequent phase of female hand formation. Plants with either a short juvenile phase or a faster bunch clock in the mid-vegetative phase will produce fewer leaves and bunch early. In turn, independent manipulation of hand number per bunch and/or fruit per hand will provide manageable bunches with appropriate fruit size. Using published data we explore relationships between plant height, leaf number, bunch weight and hand number among bananas and plantains. Identifying and then manipulating the appropriate genes in Musa opens opportunities for earlier flowering, leading to plants with desirable agronomic qualities.

National evaluation of NHS genetics service investments: emerging issues from the cancer genetics pilots

In seeking to fulfil the ambition of the 2003 genetics white paper, Our Inheritance, Our Future, to ‘mainstream’ genetic knowledge and practices, the Department of Health provided start-up funding for pilot services in various clinical areas, including seven cancer genetics projects. To help to understand the challenges encountered by such an attempt at reconfiguring the organization and delivery of services in this field, a programme-level evaluation of the genetics projects was commissioned to consider the organizational issues faced. Using a qualitative approach, this research has involved comparative case-study work in 11 of the pilot sites, including four of the seven cancer genetics pilots. In this paper, the researchers present early findings from their work, focusing in particular on the cancer genetics pilots. They consider some of the factors that have influenced how the pilots have sought to address pre-existing sector, organizational and professional boundaries to these new ways of working. The article examines the relationship between these factors and the extent to which pilots have succeeded in setting up boundary-spanning services, dealing with human-resource issues and creating sustainable, ‘mainstreamed’ provision which attracts ongoing funding in a volatile NHS commissioning environment where funding priorities do not always favour preventive, risk-assessment services.

Beyond the human genome: microbes, metaphors and what it means to be human in an interconnected post-genomic world

Four years after the completion of the Human Genome Project, the US National Institutes for Health launched the Human Microbiome Project on 19 December 2007. Using metaphor analysis, this article investigates reporting in English-language newspapers on advances in microbiomics from 2003 onwards, when the word “microbiome” was first used. This research was said to open up a “new frontier” and was conceived as a “second human genome project”, this time focusing on the genomes of microbes that inhabit and populate humans rather than focusing on the human genome itself. The language used by scientists and by the journalists who reported on their research employed a type of metaphorical framing that was very different from the hyperbole surrounding the decipherment of the “book of life”. Whereas during the HGP genomic successes had been mainly framed as being based on a unidirectional process of reading off information from a passive genetic or genomic entity, the language employed to discuss advances in microbiomics frames genes, genomes and life in much more active and dynamic ways.

Test vector generation for the phase II ATLAS event filter trigger upgrade

In the near future, the LHC experiments will continue to be upgraded as the LHC luminosity will increase from the design 1034 to 7.5 × 1034, with the HL-LHC project, to reach 3000 × f b−1 of accumulated statistics. After the end of a period of data collection, CERN will face a long shutdown to improve overall performance by upgrading the experiments and implementing more advanced technologies and infrastructures. In particular, ATLAS will upgrade parts of the detector, the trigger, and the data acquisition system. It will also implement new strategies and algorithms for processing and transferring the data to the final storage. This PhD thesis presents a study of a new pattern recognition algorithm to be used in the trigger system, which is a software designed to provide the information necessary to select physical events from background data. The idea is to use the well-known Hough Transform mathematical formula as an algorithm for detecting particle trajectories. The effectiveness of the algorithm has already been validated in the past, independently of particle physics applications, to detect generic shapes in images. Here, a software emulation tool is proposed for the hardware implementation of the Hough Transform, to reconstruct the tracks in the ATLAS Trigger and Data Acquisition system. Until now, it has never been implemented on electronics in particle physics experiments, and as a hardware implementation it would provide overall latency benefits. A comparison between the simulated data and the physical system was performed on a Xilinx UltraScale+ FPGA device.

What can digital transcript profiling reveal about human cancers?

Important biological and clinical features of malignancy are reflected in its transcript pattern. Recent advances in gene expression technology and informatics have provided a powerful new means to obtain and interpret these expression patterns. A comprehensive approach to expression profiling is serial analysis of gene expression (SAGE), which provides digital information on transcript levels. SAGE works by counting transcripts and storing these digital values electronically, providing absolute gene expression levels that make historical comparisons possible. SAGE produces a comprehensive profile of gene expression and can be used to search for candidate tumor markers or antigens in a limited number of samples. The Cancer Genome Anatomy Project has created a SAGE database of human gene expression levels for many different tumors and normal reference tissues and provides online tools for viewing, comparing, and downloading expression profiles. Digital expression profiling using SAGE and informatics have been useful for identifying genes that have a role in tumor invasion and other aspects of tumor progression.