Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies

Big Data for the Greater Good: An Introduction

Big Data, perceived as one of the breakthrough technological developments of our times, has the potential to revolutionize essentially any area of knowledge and impact on any aspect of our life. Using advanced analytics techniques such as text analytics, machine learning, predictive analytics, data mining, statistics, and natural language processing, analysts, researchers, and business users can analyze previously inaccessible or unusable data to gain new insights resulting in better and faster decisions, and producing both economic and social value; it can have an impact on employment growth, productivity, the development of new products and services, traffic management, spread of viral outbreaks, and so on. But great opportunities also bring great challenges, such as the loss of individual privacy. In this chapter, we aim to provide an introduction into what Big Data is and an overview of the social value that can be extracted from it; to this aim, we explore some of the key literature on the subject. We also call attention to the potential ‘dark’ side of Big Data, but argue that more studies are needed to fully understand the downside of it. We conclude this chapter with some final reflections

Manson's schistosomiasis in the undernourished mouse: some recent findings

This paper deals with current knowledge of the interrelationships between Schistosoma infection and malnutrition. It emphasizes the relevance of these investigations in the face of dynamic and evolving changes occurring in population diets and changes in the epidemiological patterns of schistosomiasis in endemic countries. The paper further discusses the basis for continuing the studies on this subject and the reasons why it represents a misunderstood association. This review also focuses on the cellular and humoral immune responses in the undernourished mouse model infected with Schistosoma mansoni, with updated information on the immune response in wild-type and iNOS knockout mice concerning soluble egg antigen specific antibodies and kinetics of IFN-γ, IL-4, IL-10 and IL-13 cytokines, in the chronic phase of Manson's schistosomiasis. There is indication that schistosome-infected undernourished mice are able to develop a humoral immune response, but antibody titres are much lower than in the control animals. Cytokine production (IFN-γ, IL-4, IL-10) is lower in the undernourished mice, but as infection progresses to the chronic phase its kinetics run an antagonistic course when compared to that of well-nourished animals. Marked variation in the secretion of IL-13 (a fibrogenic cytokine) could explain why undernourished mice do not develop liver "pipe-stem" fibrosis described in previous papers on well-nourished animals

Quantifying Food Waste in the Hospitality Sector and Exploring Its Underlying Reasons—A Case Study of Lahore, Pakistan

Given that about 40% of the total food produced globally is lost or wasted, there is an urgent need to understand what, where, why and how much food waste is generated. In this study, we collected the much-needed primary empirical data from the restaurants, hotels and caterers of Lahore, Pakistan through surveys and live tracking/diaries. Specifically, two key performance indicators, waste per customer (g) and percentage waste per day (%), were measured. Waste per customer was found to be 79.9 g (survey) and 73.4 g (live tracking) for restaurants, 138.4 g for hotels and 140.0 g for caterers. Similarly, the percentage of waste per day (%) was found to be 15% (survey) and 17% (live tracking) for restaurants. Results revealed that customer plate leftovers were reported to be the primary source of food waste, followed by inaccurate customer forecasting. Given the food waste levels identified in this study, the development and adoption of a national goal and target aimed at food waste reduction could usefully guide the efforts of all stakeholders. To achieve this, we need to build the capacity of all the relevant stakeholders on food loss and waste measurements and ensure national food waste reporting