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"Berg, Michael"
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Global analysis and prediction of fluoride in groundwater
The health of millions of people worldwide is negatively impacted by chronic exposure to elevated concentrations of geogenic fluoride in groundwater. Due to health effects including dental mottling and skeletal fluorosis, the World Health Organization maintains a maximum guideline of 1.5 mg/L in drinking water. As groundwater quality is not regularly tested in many areas, it is often unknown if the water in a given well or spring contains harmful levels of fluoride. Here we present a state-of-the-art global fluoride hazard map based on machine learning and over 400,000 fluoride measurements (10% of which >1.5 mg/L), which is then used to estimate the human population at risk. Hotspots indicated by the groundwater fluoride hazard map include parts of central Australia, western North America, eastern Brazil and many areas of Africa and Asia. Of the approximately 180 million people potentially affected worldwide, most reside in Asia (51–59% of total) and Africa (37–46% of total), with the latter representing 6.5% of the continent’s population. Africa also contains 14 of the top 20 affected countries in terms of population at risk. We also illuminate and discuss the key globally relevant hydrochemical and environmental factors related to fluoride accumulation.
A global fluoride hazard prediction map was created using machine learning and over 400,000 fluoride measurements, this shows ~180 million people are potentially affected by chronic fluoride exposure worldwide, mostly in Asia and Africa.
Journal Article
U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
In eukaryotes, U1 small nuclear ribonucleoprotein (snRNP) forms spliceosomes in equal stoichiometry with U2, U4, U5 and U6 snRNPs; however, its abundance in human far exceeds that of the other snRNPs. Here we used antisense morpholino oligonucleotide to U1 snRNA to achieve functional U1 snRNP knockdown in HeLa cells, and identified accumulated unspliced pre-mRNAs by genomic tiling microarrays. In addition to inhibiting splicing, U1 snRNP knockdown caused premature cleavage and polyadenylation in numerous pre-mRNAs at cryptic polyadenylation signals, frequently in introns near (<5 kilobases) the start of the transcript. This did not occur when splicing was inhibited with U2 snRNA antisense morpholino oligonucleotide or the U2-snRNP-inactivating drug spliceostatin A unless U1 antisense morpholino oligonucleotide was also included. We further show that U1 snRNA–pre-mRNA base pairing was required to suppress premature cleavage and polyadenylation from nearby cryptic polyadenylation signals located in introns. These findings reveal a critical splicing-independent function for U1 snRNP in protecting the transcriptome, which we propose explains its overabundance.
Moonlighting U1 protects pre-mRNAs
Splicing — the production of messenger RNAs from large precursors (pre-mRNAs) by the removal of RNA segments known as introns — is carried out by protein–RNA complexes called snRNPs. A spliceosome contains equal amounts of the U1, U2, U4, U5 and U6 snRNPs, but U1 snRNP levels far exceed those needed for spliceosomes, leading to the idea that 'spare' U1s might have splicing-independent functions. One such function has now been found that involves an interaction between U1 snRNA and some pre-mRNAs that contain introns with cryptic polyadenylation sites. This protects nascent pre-mRNAs from injury by averting premature termination and polyadenylation.
Splicing is carried out by a collection of protein–RNA complexes known as snRNPs. The spliceosome contains equal quantities of the U1, U2, U4, U5 and U6 snRNPs, but the U1 snRNP is made in levels excess to the amounts needed to form spliceosomes, leading to the idea that excess U1s might have splicing independent functions. Here it is shown that the U1 snRNA interacts with some pre mRNAs whose introns have cryptic polyadenylation sites. This interaction prevents premature termination and polyadenylation of the pre mRNA.
Journal Article
Prevalence and predictors of early COVID-19 behavioral intentions in the United States
In a March 2020 study of COVID-19, higher levels of self-efficacy, perceived severity, and the belief that medical professionals play an important role in individuals’ health outcomes were each positively correlated with intentions to follow prevention guidelines.
Abstract
Despite early warnings and calls for action, COVID-19 infection rates continue to climb in many areas of the United States. The current study examined participants’ reported likelihood of engaging in eight behaviors designated by the Centers for Disease Control and Prevention as critical for the prevention of COVID-19 at the outset of the epidemic. Self-efficacy, perceived threat, and internal and external health locus of control were explored as potential predictors of those behaviors. In addition, demographic and contextual factors, such as age, gender, political identity, and whether or not participants were currently living under a quarantine advisory, were recorded for analysis. Overall, participants reported high engagement with the prevention behaviors. Higher levels of self-efficacy, perceived severity of the illness, and external locus of control in regard to medical professionals were all positively associated with plans to take the recommended precautions. Based on the results, it appears that messaging regarding COVID-19 prevention may be particularly effective when it focuses on the high risk of the illness, the ease with which the prevention behaviors can be taken, and a reassurance that the medical establishment has individuals’ best health in mind when it makes its specific recommendations.
While numerous countries have succeeded in reducing the spread of COVID-19, the number of new cases in the United States remains high, even relative to other populations also heavily impacted by the disease [1]. Although it would be difficult to pinpoint a single cause or explanation for the epidemic’s course in the USA, at the heart of its spread, like the spread of all infectious diseases, is noncompliance with preventative measures. The current research served as a preliminary exploration of the prevalence and predictors of eight COVID-19 prevention behaviors. A brief survey was sent out at the end of March 2020 to 350 U.S. residents in order to assess the likelihood of their engaging in various prevention behaviors recommended at that time and several related psychosocial factors. The psychological factors assessed included health locus of control (HLOC) beliefs, self-efficacy, and perceived threat. In addition, a handful of demographic and contextual factors, such as age, gender, political identity, and whether or not they were working outside the home or were currently living under a quarantine advisory, were recorded for examination.
Journal Article
Predictors of COVID-19 vaccine intentions in the United States: the role of psychosocial health constructs and demographic factors
Abstract
Background
On December 21, 2020, a study was conducted to investigate a range of psychosocial health constructs and demographic variables potentially associated with intentions toward accepting or forgoing the coronavirus (COVID-19) vaccine.
Purpose
The goal of the study was to identify predictors of forgoing COVID-19 vaccination at the time of the initial rollout.
Methods
A cross-sectional, representative online survey of 350 U.S. residents was conducted using the online crowdsourcing site Prolific to assess vaccine intentions, health attitudes, and demographic information. Variables examined included demographic factors and health constructs corresponding to each of the elements of the health belief model (perceived severity, susceptibility, benefits, barriers, and cues to action), the theory of planned behavior (attitudes, subjective norms, and perceived behavioral control), attitudes toward vaccines in general, and trust in the COVID-19 vaccine approval process.
Results
After using hierarchical linear regression to control for demographics, the health constructs uniquely associated with the likelihood to forgo vaccination were perceived barriers, general attitudes toward the COVID-19 vaccine, subjective norms, and trust in the vaccine approval process. Significant demographic predictors of vaccine reluctance included being female, politically conservative, and more religious.
Conclusions
The current research identified three demographic factors and four health constructs uniquely associated with vaccine acceptance. These findings reveal that the constructs contained within the health belief model and theory of planned behavior can be used to predict COVID-19 vaccination intentions, and can be supplemented with an assessment of general vaccine attitudes and attitudes toward the vaccine approval process.
Journal Article
Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection
Hepatitis C virus (HCV) and human pegivirus (HPgV), formerly GBV-C, are the only known human viruses in the Hepacivirus and Pegivirus genera, respectively, of the family Flaviviridae. We present the discovery of a second pegivirus, provisionally designated human pegivirus 2 (HPgV-2), by next-generation sequencing of plasma from an HCV-infected patient with multiple bloodborne exposures who died from sepsis of unknown etiology. HPgV-2 is highly divergent, situated on a deep phylogenetic branch in a clade that includes rodent and bat pegiviruses, with which it shares <32% amino acid identity. Molecular and serological tools were developed and validated for high-throughput screening of plasma samples, and a panel of 3 independent serological markers strongly correlated antibody responses with viral RNA positivity (99.9% negative predictive value). Discovery of 11 additional RNA-positive samples from a total of 2440 screened (0.45%) revealed 93-94% nucleotide identity between HPgV-2 strains. All 12 HPgV-2 RNA-positive cases were identified in individuals also testing positive for HCV RNA (12 of 983; 1.22%), including 2 samples co-infected with HIV, but HPgV-2 RNA was not detected in non-HCV-infected individuals (p<0.0001), including those singly infected by HIV (p = 0.0075) or HBV (p = 0.0077), nor in volunteer blood donors (p = 0.0082). Nine of the 12 (75%) HPgV-2 RNA positive samples were reactive for antibodies to viral serologic markers, whereas only 28 of 2,429 (1.15%) HPgV-2 RNA negative samples were seropositive. Longitudinal sampling in two individuals revealed that active HPgV-2 infection can persist in blood for at least 7 weeks, despite the presence of virus-specific antibodies. One individual harboring both HPgV-2 and HCV RNA was found to be seronegative for both viruses, suggesting a high likelihood of simultaneous acquisition of HCV and HPgV-2 infection from an acute co-transmission event. Taken together, our results indicate that HPgV-2 is a novel bloodborne infectious virus of humans and likely transmitted via the parenteral route.
Journal Article