Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic?

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Pharmaceutical pollution of the world's rivers

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals

Disulfide-Linked Dinitroxides for Monitoring Cellular Thiol Redox Status through Electron Paramagnetic Resonance Spectroscopy

Intracellular thiol–disulfide redox balance is crucial to cell health, and may be a key determinant of a cancer’s response to chemotherapy and radiation therapy. The ability to assess intracellular thiol–disulfide balance may thus be useful not only in predicting responsiveness of cancers to therapy, but in assessing predisposition to disease. Assays of thiols in biology have relied on colorimetry or fluorimetry, both of which require UV–visible photons, which do not penetrate the body. Low-frequency electron paramagnetic resonance imaging (EPRI) is an emerging magnetic imaging technique that uses radio waves, which penetrate the body well. Therefore, in combination with tailored imaging agents, EPRI affords the opportunity to image physiology within the body. In this study, we have prepared water-soluble and membrane-permeant disulfide-linked dinitroxides, at natural isotopic abundance, and with D,¹⁵N-substitution. Thiols such as glutathione cleave the disulfides, with simple bimolecular kinetics, to yield the monomeric nitroxide species, with distinctive changes in the EPR spectrum. Using the D,¹⁵N-substituted disulfide-dinitroxide and EPR spectroscopy, we have obtained quantitative estimates of accessible intracellular thiol in cultured human lymphocytes. Our estimates are in good agreement with published measurements. This suggests that in vivo EPRI of thiol–disulfide balance is feasible. Finally, we discuss the constraints on the design of probe molecules that would be useful for in vivo EPRI of thiol redox status

Predicting the dynamic performance of seats

The transmission of vibration to people through seats was studied with the final objective of being able to predict the dynamic performance of seats. It was necessary to investigate both the dynamic response and the subjective response of a person sitting on a seat, in addition to the dynamic response of the seat itself. Initial experiments were conducted to investigate the effect of variables, such as the magnitude of the vibration and the posture of the body, on the transmission of vibration through a seat. Seat transmissibilities measured in a laboratory with vertical-only vibration were shown to be similar to those measured in a vehicle with multiple vibration. Frequency response functions were determined for the transmission of multiple axis translational vehicle vibration to the cushion and the backrest of a seat. The apparent mass of the seated body was measured as a pre-requisite for the prediction of seat transmissibilities. It was found that the resonance frequency of the body decreased when the magnitude of the vibration was increased. Increased muscle tension tended to have the opposite effect. The apparent masses of sixty people - men, women and children - were very similar once they were normalised to remove the effect of the different static weights on the seat. Some correlations with the body characteristics were significant - such as that between the normalised apparent mass at resonance and total body mass. A method of measuring the dynamic stiffness of a seat using a rigid indenter instead of a person to load the seat was developed. The results, in conjunction with measurements of the apparent mass of the body, were used to predict seat transmissibilities. Predicted seat transmissibilities were shown to be similar to transmissibilities that were measured with a person sitting on the seat. It was investigated how the weight of a person and the magnitude of the vibration could affect predicted seat transmissibilities. The discomfort caused by vibration transmitted to a seated person was measured using a novel method of adjustment. It was investigated whether the discomfort caused by simultaneous vertical and fore-and-aft vibration could be predicted from the discomfort that would have been caused if the vibration in each axis had occurred separately. A root-sum-square summation procedure was found to be the best

Diet and the evolution of ADH7 across seven orders of mammals

Dietary variation within and across species drives the eco-evolutionary responsiveness of genes necessary to metabolize nutrients and other components. Recent evidence from humans and other mammals suggests that sugar-rich diets of floral nectar and ripe fruit have favoured mutations in, and functional preservation of, the ADH7 gene, which encodes the ADH class 4 enzyme responsible for metabolizing ethanol. Here we interrogate a large, comparative dataset of ADH7 gene sequence variation, including that underlying the amino acid residue located at the key site (294) that regulates the affinity of ADH7 for ethanol. Our analyses span 171 mammal species, including 59 newly sequenced. We report extensive variation, especially among frugivorous and nectarivorous bats, with potential for functional impact. We also report widespread variation in the retention and probable pseudogenization of ADH7. However, we find little statistical evidence of an overarching impact of dietary behaviour on putative ADH7 function or presence of derived alleles at site 294 across mammals, which suggests that the evolution of ADH7 is shaped by complex factors. Our study reports extensive new diversity in a gene of longstanding ecological interest, offers new sources of variation to be explored in functional assays in future study, and advances our understanding of the processes of molecular evolution