DNA target selection by calichemicin

Thesis (Ph. D.)--Massachusetts Institute of Technology, Division of Toxicology, 1998.Vita.Includes bibliographical references (leaves 133-140, 143).by Aaron A. Salzberg.Ph.D

Effectiveness of the Swachh Bharat Mission and barriers to ending open defecation in India: a systematic review

In 2016, nearly 60% of the population of India practiced open defecation (OD), which was 4 times the global rate, and reducing OD in India will be essential in meeting Sustainable Development Goal (SDG) 6.2 and improving global public health. The government of India launched the Swachh Bharat Mission (SBM) in 2014 with one key goal for all Indian states to achieve OD-free (ODF) status by 2019. Despite reports from the Government of India on the success of SBM, the true ODF status of Indian states is still unknown. A systematic review of peer-reviewed literature was conducted to assess the impact of SBM on OD in India, evaluate the barriers to reducing OD, and provide recommendations for future interventions to reduce or eliminate OD in India. A total of 237 publications were screened, and 22 were selected for inclusion. While the Prime Minister declared India ODF in 2019, studies suggest that the government monitoring system overestimates numbers of ODF villages and toilet coverage. Reasons for households’ continued OD practice include financial constraints, lack of water supply, governmental mistrust, cultural beliefs, and personal preference. Community incentives and penalties have been used to encourage proper sanitation practices with varying success. Overarching strategies and approaches that have worked well across study districts to reduce OD include high involvement of district leadership and innovative behavior-change and local community mobilization campaigns

Effects of environmental conditions on healthcare worker wellbeing and quality of care: A qualitative study in Niger

Environmental conditions (water, sanitation, hygiene, waste management, cleaning, energy, building design) are important for a safe and functional healthcare environment. Yet their full range of impacts are not well understood. In this study, we assessed the impact of environmental conditions on healthcare workers’ wellbeing and quality of care, using qualitative interviews with 81 healthcare workers at 26 small healthcare facilities in rural Niger. We asked participants to report successes and challenges with environmental conditions and their impacts on wellbeing (physical, social, mental, and economic) and quality of care. We found that all environmental conditions contributed to healthcare workers’ wellbeing and quality of care. The norm in facilities of our sample was poor environmental conditions, and thus participants primarily reported detrimental effects. We identified previously documented effects on physical health and safety from pathogen exposure, but also several novel effects on healthcare workers’ mental and economic wellbeing and on efficiency, timeliness, and patient centeredness of care. Key wellbeing impacts included pathogen exposure for healthcare workers, stress from unsafe and chaotic working environments, staff dissatisfaction and retention challenges, out-of-pocket spending to avoid stockouts, and uncompensated labor. Key quality of care impacts included pathogen exposure for patients, healthcare worker time dedicated to non-medical tasks like water fetching (i.e., reduced efficiency), breakdowns and spoilage of equipment and supplies, and patient satisfaction with cleanliness and privacy. Inefficiency due to time lost and damaged supplies and equipment likely have substantial economic value and warrant greater consideration in research and policy making. Impacts on staff retention and care efficiency also have implications for health systems. We recommend that future research and decision making for policy and practice incorporate more holistic impact measures beyond just healthcare acquired infections and reconsider the substantial contribution that environmental conditions make to the safety of healthcare facilities and strength of health systems

Spatiotemporal Structure of Molecular Evolution of H5N1 Highly Pathogenic Avian Influenza Viruses in Vietnam

BackgroundVietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10): e3462) demonstrated that there have been at least six independent H5N1 introductions into Vietnam and there were nine newly emerged reassortants from 2001 to 2007 in Vietnam. H5N1 viruses in Vietnam cluster distinctly around Hanoi and Ho Chi Minh City. However, the nature of the relationship between genetic divergence and geographic patterns is still unclear.Methodology/Principal FindingsIn this study, we hypothesized that genetic distances between H5N1 viruses in Vietnam are correlated with geographic distances, as the result of distinct population and environment patterns along Vietnam's long north to south longitudinal extent. Based on this hypothesis, we combined spatial statistical methods with genetic analytic techniques and explicitly used geographic space to explore genetic evolution of H5N1 highly pathogenic avian influenza viruses at the sub-national scale in Vietnam. Our dataset consisted of 125 influenza viruses (with whole genome sets) isolated in Vietnam from 2003 to 2007. Our results document the significant effect of space and time on genetic evolution and the rise of two regional centers of genetic mixing by 2007. These findings give insight into processes underlying viral evolution and suggest that genetic differentiation is associated with the distance between concentrations of human and poultry populations around Hanoi and Ho Chi Minh City.Conclusions/SignificanceThe results show that genetic evolution of H5N1 viruses in Vietnamese domestic poultry is highly correlated with the location and spread of those viruses in geographic space. This correlation varies by scale, time, and gene, though a classic isolation by distance pattern is observed. This study is the first to characterize the geographic structure of influenza viral evolution at the sub-national scale in Vietnam and can shed light on how H5N1 HPAIVs evolve in certain geographic settings

Eliminating lead exposure from drinking water—A global call to action

Each year, approximately 900,000 people die from exposure to lead [1]. But the full impacts of lead exposure are far more insidious. Lead is a potent neurotoxin that impairs brain function and irreversibly harms children’s cognitive development. Any exposure to lead can be damaging. Recent studies estimate that 800 million children globally (approximately 1 in 3) have blood lead concentrations above 5 micrograms per deciliter and that lead exposure may be responsible for 30% of all intellectual disabilities of unknown origin [2, 3]. Lead exposure increases disease burden, estimated at over 21 million disability-adjusted life years (DALYs) yearly, primarily due to cardiovascular diseases and mental disorders. This disease burden attributed to lead has increased globally since 1990, because of population growth and aging [4]. Additional research has shown evidence of a direct dose-response relationship between children’s blood lead levels and reductions in IQ which decreases lifetime earnings [5, 6]. This makes lead a public health threat and a key environmental risk factor that exacerbates long-term inequalities affecting especially marginalized groups. Important sources of exposure include batteries, paint, food containers, drinking water systems, and leaded gasoline (now banned in all countries)

Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote

The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance

The COMBREX Project: Design, Methodology, and Initial Results

© 2013 Brian P. et al.Prior to the “genomic era,” when the acquisition of DNA sequence involved significant labor and expense, the sequencing of genes was strongly linked to the experimental characterization of their products. Sequencing at that time directly resulted from the need to understand an experimentally determined phenotype or biochemical activity. Now that DNA sequencing has become orders of magnitude faster and less expensive, focus has shifted to sequencing entire genomes. Since biochemistry and genetics have not, by and large, enjoyed the same improvement of scale, public sequence repositories now predominantly contain putative protein sequences for which there is no direct experimental evidence of function. Computational approaches attempt to leverage evidence associated with the ever-smaller fraction of experimentally analyzed proteins to predict function for these putative proteins. Maximizing our understanding of function over the universe of proteins in toto requires not only robust computational methods of inference but also a judicious allocation of experimental resources, focusing on proteins whose experimental characterization will maximize the number and accuracy of follow-on predictions.COMBREX is funded by a GO grant from the National Institute of General Medical Sciences (NIGMS) (1RC2GM092602-01).Peer Reviewe

Electromagnetic Biostimulation of Living Cultures for Biotechnology, Biofuel and Bioenergy Applications

The surge of interest in bioenergy has been marked with increasing efforts in research and development to identify new sources of biomass and to incorporate cutting-edge biotechnology to improve efficiency and increase yields. It is evident that various microorganisms will play an integral role in the development of this newly emerging industry, such as yeast for ethanol and Escherichia coli for fine chemical fermentation. However, it appears that microalgae have become the most promising prospect for biomass production due to their ability to grow fast, produce large quantities of lipids, carbohydrates and proteins, thrive in poor quality waters, sequester and recycle carbon dioxide from industrial flue gases and remove pollutants from industrial, agricultural and municipal wastewaters. In an attempt to better understand and manipulate microorganisms for optimum production capacity, many researchers have investigated alternative methods for stimulating their growth and metabolic behavior. One such novel approach is the use of electromagnetic fields for the stimulation of growth and metabolic cascades and controlling biochemical pathways. An effort has been made in this review to consolidate the information on the current status of biostimulation research to enhance microbial growth and metabolism using electromagnetic fields. It summarizes information on the biostimulatory effects on growth and other biological processes to obtain insight regarding factors and dosages that lead to the stimulation and also what kind of processes have been reportedly affected. Diverse mechanistic theories and explanations for biological effects of electromagnetic fields on intra and extracellular environment have been discussed. The foundations of biophysical interactions such as bioelectromagnetic and biophotonic communication and organization within living systems are expounded with special consideration for spatiotemporal aspects of electromagnetic topology, leading to the potential of multipolar electromagnetic systems. The future direction for the use of biostimulation using bioelectromagnetic, biophotonic and electrochemical methods have been proposed for biotechnology industries in general with emphasis on an holistic biofuel system encompassing production of algal biomass, its processing and conversion to biofuel

Effectiveness of the Swachh Bharat Mission and barriers to ending open defecation in India: a systematic review

In 2016, nearly 60% of the population of India practiced open defecation (OD), which was 4 times the global rate, and reducing OD in India will be essential in meeting Sustainable Development Goal (SDG) 6.2 and improving global public health. The government of India launched the Swachh Bharat Mission (SBM) in 2014 with one key goal for all Indian states to achieve OD-free (ODF) status by 2019. Despite reports from the Government of India on the success of SBM, the true ODF status of Indian states is still unknown. A systematic review of peer-reviewed literature was conducted to assess the impact of SBM on OD in India, evaluate the barriers to reducing OD, and provide recommendations for future interventions to reduce or eliminate OD in India. A total of 237 publications were screened, and 22 were selected for inclusion. While the Prime Minister declared India ODF in 2019, studies suggest that the government monitoring system overestimates numbers of ODF villages and toilet coverage. Reasons for households’ continued OD practice include financial constraints, lack of water supply, governmental mistrust, cultural beliefs, and personal preference. Community incentives and penalties have been used to encourage proper sanitation practices with varying success. Overarching strategies and approaches that have worked well across study districts to reduce OD include high involvement of district leadership and innovative behavior-change and local community mobilization campaigns