Large Scale Gene Function Discovery to Support Human Health: The International Mouse Phenotyping Consortium (IMPC)

2013 ◽  
Vol 94 (12) ◽  
pp. 2819-2827 ◽  
Author(s):  
Rona Wilson ◽  
Karen Dobie ◽  
Nora Hunter ◽  
Cristina Casalone ◽  
Thierry Baron ◽  
...  

The transmission of bovine spongiform encephalopathy (BSE) to humans, leading to variant Creutzfeldt–Jakob disease has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health. Until recently, TSE disease in cattle was thought to be caused by a single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. To model the risk to human health, we previously inoculated these two forms of atypical BSE (BASE and BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in these mice. However, despite the absence of TSE pathology, upon subpassage of some BASE-challenged HuTg mice, a TSE was observed in recipient gene-targeted bovine PrP Tg (Bov6) mice but not in HuTg mice. Disease transmission from apparently healthy individuals indicates the presence of subclinical BASE infection in mice expressing human PrP that cannot be identified by current diagnostic methods. However, due to the lack of transmission to HuTg mice on subpassage, the efficiency of mouse-to-mouse transmission of BASE appears to be low when mice express human rather than bovine PrP.


2020 ◽  
Vol 12 (2) ◽  
Author(s):  
O. Yevtushevska ◽  
L. Holovachenko ◽  
J. Rudnichenko

Human has been influencing the environment since ancient times, but never has this impact been asintense as in the last century. The use of natural resources is currently occurring at such a large scale and atsuch a rapid rate that the natural reproduction of the environments used is not ensured. As a result, the mu ltifaceted centuries-old human activity has left deep traces on the modern soil and vegetation, air and waterenvironment, wildlife. Today, more and more consumers in the world are aware of the benefits and preferproducts that have a positive impact on the environment and human health. The environmental safety ofagri-food products, whether it is finished products, crop products or livestock products, is a global issue, as itcovers not only human health but also the country's economy. The standard of living of citizens, social acti vity of the person depend on quality of production, and also there is an influence on demographic aspect ofhis existence. Therefore, to ensure a high standard of living, the state must pay more attention to the environmental safety of finished products. The scientific work investigates and highlights the features and currentstate of the market for clean products in Ukraine, determines the level of populations attitude to organicproducts, outlines ways to improve the market for organic products in Ukraine.


Author(s):  
Abhinav Singh ◽  
Utsha Sinha ◽  
Deepak Kumar Sharma

The development and expansion of mankind in addition to the advancement of technology have a substantial impact on the environment. The construction, design, and operation of buildings account for a large consumption of natural resources. Due to the exploitation of natural resources on a large scale through these buildings, it has become necessary to have a better-designed building for the efficient use of resources. The concept of “green building” solves the aforementioned issues apart from promoting eco-friendly activities. IoT makes the idea of having buildings that are energy sufficient possible through networked sensors that not only help in managing the assets better but also reducing harmful impacts on human health and the environment. This chapter talks about the concept of the green building and the smart automation achieved through IoT as well as cloud architecture for the green building also referred to as green cloud. While it explains the basic cloud architecture in green building, it also proposes future challenges for the aforementioned subject.


Author(s):  
Glenn Geher ◽  
Nicole Wedberg

In recent years, the evolutionary approach to health and medicine has led to major advances in our understanding of physical and mental health. A core concept in this area pertains to evolutionary mismatch, which helps explain why people gravitate toward unhealthy diets and sedentary lifestyles. Further, several common mismatches can help us understand issues with mental health. For instance, the large-scale prevalence of highly addictive cell phones and related technologies ultimately has adverse psychological consequences for people for various reasons. If we want to understand issues of human health, we must utilize an evolutionary perspective. Practices like selflessness, virtuosity, temperance, altruism, and even diet and exercise are nothing new. By studying facets of positive psychology through an evolutionary lens, it can be seen more clearly how these positive emotions and practices of healthy living have been adaptive for humans all along.


2020 ◽  
Vol 22 (8) ◽  
Author(s):  
Barbara De Berardis ◽  
Magda Marchetti ◽  
Anna Risuglia ◽  
Federica Ietto ◽  
Carla Fanizza ◽  
...  

AbstractIn recent years, the introduction of innovative low-cost and large-scale processes for the synthesis of engineered nanoparticles with at least one dimension less than 100 nm has led to countless useful and extensive applications. In this context, gold nanoparticles stimulated a growing interest, due to their peculiar characteristics such as ease of synthesis, chemical stability and optical properties. This stirred the development of numerous applications especially in the biomedical field. Exposure of manufacturers and consumers to industrial products containing nanoparticles poses a potential risk to human health and the environment. Despite this, the precise mechanisms of nanomaterial toxicity have not yet been fully elucidated. It is well known that the three main routes of exposure to nanomaterials are by inhalation, ingestion and through the skin, with inhalation being the most common route of exposure to NPs in the workplace. To provide a complete picture of the impact of inhaled gold nanoparticles on human health, in this article, we review the current knowledge about the physico-chemical characteristics of this nanomaterial, in the size range of 1–100 nm, and its toxicity for pulmonary structures both in vitro and in vivo. Studies comparing the toxic effect of NPs larger than 100 nm (up to 250 nm) are also discussed.


mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Michelle Spoto ◽  
Changhui Guan ◽  
Elizabeth Fleming ◽  
Julia Oh

ABSTRACT The CRISPR/Cas system has significant potential to facilitate gene editing in a variety of bacterial species. CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) represent modifications of the CRISPR/Cas9 system utilizing a catalytically inactive Cas9 protein for transcription repression and activation, respectively. While CRISPRi and CRISPRa have tremendous potential to systematically investigate gene function in bacteria, few programs are specifically tailored to identify guides in draft bacterial genomes genomewide. Furthermore, few programs offer open-source code with flexible design parameters for bacterial targeting. To address these limitations, we created GuideFinder, a customizable, user-friendly program that can design guides for any annotated bacterial genome. GuideFinder designs guides from NGG protospacer-adjacent motif (PAM) sites for any number of genes by the use of an annotated genome and FASTA file input by the user. Guides are filtered according to user-defined design parameters and removed if they contain any off-target matches. Iteration with lowered parameter thresholds allows the program to design guides for genes that did not produce guides with the more stringent parameters, one of several features unique to GuideFinder. GuideFinder can also identify paired guides for targeting multiplicity, whose validity we tested experimentally. GuideFinder has been tested on a variety of diverse bacterial genomes, finding guides for 95% of genes on average. Moreover, guides designed by the program are functionally useful—focusing on CRISPRi as a potential application—as demonstrated by essential gene knockdown in two staphylococcal species. Through the large-scale generation of guides, this open-access software will improve accessibility to CRISPR/Cas studies of a variety of bacterial species. IMPORTANCE With the explosion in our understanding of human and environmental microbial diversity, corresponding efforts to understand gene function in these organisms are strongly needed. CRISPR/Cas9 technology has revolutionized interrogation of gene function in a wide variety of model organisms. Efficient CRISPR guide design is required for systematic gene targeting. However, existing tools are not adapted for the broad needs of microbial targeting, which include extraordinary species and subspecies genetic diversity, the overwhelming majority of which is characterized by draft genomes. In addition, flexibility in guide design parameters is important to consider the wide range of factors that can affect guide efficacy, many of which can be species and strain specific. We designed GuideFinder, a customizable, user-friendly program that addresses the limitations of existing software and that can design guides for any annotated bacterial genome with numerous features that facilitate guide design in a wide variety of microorganisms.


2020 ◽  
Vol 8 (2) ◽  
pp. 197
Author(s):  
Shomeek Chowdhury ◽  
Stephen S. Fong

The impact of microorganisms on human health has long been acknowledged and studied, but recent advances in research methodologies have enabled a new systems-level perspective on the collections of microorganisms associated with humans, the human microbiome. Large-scale collaborative efforts such as the NIH Human Microbiome Project have sought to kick-start research on the human microbiome by providing foundational information on microbial composition based upon specific sites across the human body. Here, we focus on the four main anatomical sites of the human microbiome: gut, oral, skin, and vaginal, and provide information on site-specific background, experimental data, and computational modeling. Each of the site-specific microbiomes has unique organisms and phenomena associated with them; there are also high-level commonalities. By providing an overview of different human microbiome sites, we hope to provide a perspective where detailed, site-specific research is needed to understand causal phenomena that impact human health, but there is equally a need for more generalized methodology improvements that would benefit all human microbiome research.


2013 ◽  
Vol 8 (8) ◽  
pp. 1551-1566 ◽  
Author(s):  
Huaiyu Mi ◽  
Anushya Muruganujan ◽  
John T Casagrande ◽  
Paul D Thomas

2020 ◽  
Vol 12 ◽  
Author(s):  
Ramon da Silva Raposo ◽  
Daniel Vieira Pinto ◽  
Ricardo Moreira ◽  
Ronaldo Pereira Dias ◽  
Carlos Alberto Fontes Ribeiro ◽  
...  

Worldwide environmental tragedies of anthropogenic origin causing massive release of metals and other pollutants have been increasing considerably. These pollution outbreaks affect the ecosystems and impact human health. Among those tragedies, recent large-scale environmental disasters in Brazil strongly affected riverside populations, leading to high-risk exposure to methylmercury (MeHg). MeHg is highly neurotoxic to the developing brain. This toxicant causes neural stem cell dysfunction and neurodevelopmental abnormalities. However, less is known about the effects of MeHg in the postnatal neurogenic niche, which harbors neural stem cells and their progeny, in the adult brain. Therefore, taking in consideration the impact of MeHg in human health it is urgent to clarify possible associations between exposure to mercury, accelerated cognitive decline, and neurodegenerative diseases. In this perspectives paper, we discuss the neurotoxic mechanisms of MeHg on postnatal neurogenesis and the putative implications associated with accelerated brain aging and early-onset cognitive decline in populations highly exposed to this environmental neurotoxicant.


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