Accounting for spatial sampling patterns in Bayesian phylogeography

Statistical phylogeography provides useful tools to characterize and quantify the spread of organisms during the course of evolution. Analyzing georeferenced genetic data often relies on the assumption that samples are preferentially collected in densely populated areas of the habitat. Deviation from this assumption negatively impacts the inference of the spatial and demographic dynamics. This issue is pervasive in phylogeography. It affects analyses that approximate the habitat as a set of discrete demes as well as those that treat it as a continuum. The present study introduces a Bayesian modeling approach that explicitly accommodates for spatial sampling strategies. An original inference technique, based on recent advances in statistical computing, is then described that is most suited to modeling data where sequences are preferentially collected at certain locations, independently of the outcome of the evolutionary process. The analysis of georeferenced genetic sequences from the West Nile virus in North America along with simulated data shows how assumptions about spatial sampling may impact our understanding of the forces shaping biodiversity across time and space.

Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption

COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as “Cluster 5” that contained mutations in the spike protein. However, the functional properties of these “Cluster 5” mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks.

Investigation of the Genetically Modified Organism (GMO) Existence in Baby Foods on the Market in Turkey

It is called Organism Genetically Modified Organism (GMO) which is obtained by biotechnological methods to modify the genetic sequences of living things, to improve their existing properties and / or to gain new features. Baby milk and baby continue milk, which the babies consume during their first month of the life, can also contain products such as soy, corn, rice according to their derivatives. It is thought that GMO screening should also be done in baby formulas that contain these components which are extensively produced in the genus modified organism class in the world. In this study, in 2011 released the proposed baby milk in Turkey and baby continue in milk, Ash, moisture, total fat, carbohydrates, protein analysis and real time PCR GMO screening was conducted. As a result of the GMO scan, no product containing the p35S, tNOS and pFMV isomers was found.

Natural Bred ε2-Phages Have an Improved Host Range and Virulence against Uropathogenic Escherichia coli over Their Ancestor Phages

Alternative treatments for Escherichia coli infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 E. coli strains reflecting the diversity of strains found in UTI, including sequence type 131, 73 and 69. The plaquing host range (PHR) was between 13 and 63%. In contrast, the kinetic host range (KHR), describing the percentage of strains for which growth in suspension was suppressed for 24 h, was between 0% and 19%, substantially lower than the PHR. To improve the phage host range and their efficacy, we bred the phages by mixing and propagating cocktails on a subset of E. coli strains. The bred phages, which we termed evolution-squared ε2-phages, of a mixture of Myoviridae have KHRs up to 23% broader compared to their ancestors. Furthermore, using constant phage concentrations, Myoviridae ε2-phages suppressed the growth of higher bacterial inocula than their ancestors did. Thus, the ε2-phages were more virulent compared to their ancestors. Analysis of the genetic sequences of the ε2-phages with the broadest host range reveals that they are mosaic intercrossings of 2–3 ancestor phages. The recombination sites are distributed over the whole length of the genome. All ε2-phages are devoid of genes conferring lysogeny, antibiotic resistance, or virulence. Overall, this study shows that ε2-phages are remarkably more suitable than the wild-type phages for phage therapy.

Molecular detection of parvovirus in Manchurian chipmunks (Tamias sibiricus asiaticus) captured in Korea

Cross-species transmission of viral diseases alarms our global community for its potential of novel pandemic events. Of various viral pathogens noted recently, parvoviruses have posed public health threats not only to humans but to wild animals. To investigate the prevalence of parvoviruses in wild Manchurian chipmunks, here we detected genetic fragments of the nonstructural protein of parvovirus by polymerase chain reaction in wild Manchurian chipmunk specimens captured in the central and southern regions of South Korea and compared their sequence homology with references. Of a total of 348 specimens examined, chipmunk parvovirus (ChpPV)-specific gene fragments were detected with a 31.32 % rate (109 chipmunks of 348) in their kidney, liver, lung, and spleen samples, and the chipmunks captured in Gangwon Province exhibited the highest positive rate (45.37%), followed by Gyeongsang (35.29%), Gyeonggi (31.03%), Chungcheong (20.00%), and Jeolla (19.70%). When compared with the reference sequences registered in GenBank, a partial ChpPV sequence showed 97.70% identity to the previously reported Korean strain at the nucleic acid level. In the phylogenetic analysis, ChpPV exhibited closer relationship to primate parvoviruses, erythroviruses, and bovine parvovirus than to adeno-associated viruses. Despite limited sample size and genetic sequences examined in this study, our results underline the prevalence of ChpPV in Korea and emphasize the need of close surveillance of parvoviruses in wild animals.

Pharmacogenetic in Anesthesia Drugs

Pharmacogenetics seeks to elucidate the variations in individual's genetic sequences in order to better understand the differences seen in pharmacokinetics, drug metabolism, and efficacy between patients. This area of research is rapidly accelerating, aided by the use of novel and more economical molecular technologies. A substantial evidence base is being generated with the hopes that in the future it may be used to generate personalised treatment regimens in order to improve patient comfort and safety and reduce incidences of morbidity and mortality.

Complex structural variations in non-human primate hepatitis B virus

Background Recent genome sequence technology has revealed a novel type of genetic rearrangement referred to as complex structural variations (SVs). Previous studies have elucidated the complex SVs in human hepatitis B viruses (HBVs). In this study, we investigated the existence of complex SVs in HBVs from non-human primates (NHPs). Methods Searches for nucleotide sequences of NHP HBV were conducted using the PubMed, and genetic sequences were retrieved from databases. The candidate genetic sequences harboring complex SVs were analyzed using the CLUSTALW program and MAFFT. Additional bioinformatical analyses were performed to determine strains with complex SVs and to elucidate characteristics of NHP HBV strains. Results One hundred and fifty-four HBV strains from NHPs were identified from databases. SVs and complex SVs were observed in 11 (7.1%) strains. Three gibbon HBV (GiHBV) strains showed complex SVs consisting of an insertion and a deletion in the pre-S1 region. One GiHBV strain possessed a 6-nt insertion, which are normally specific to human HBV genotype A (HBV/A) in the Core region, and further analyses clarified that the 6-nt insertion was not caused by recombination, but rather by simple insertion. Another chimpanzee HBV strain showed complex SVs in the pre-S1 region, which were composed of human HBV/E, G-specific polymorphic SV, and an additional 6-nt insertion. Conclusions In this study, complex SVs were observed in HBV strains from NHPs, in addition to human HBV strains, as shown in previous studies. These data suggest that complex SVs could also be found in other members of hepadnaviruses, and may play a role in their genetic diversity.

Modeling Plasmodium falciparum Diagnostic Test Sensitivity Using Machine Learning With Histidine-Rich Protein 2 Variants

Malaria, predominantly caused by Plasmodium falciparum, poses one of largest and most durable health threats in the world. Previously, simplistic regression-based models have been created to characterize malaria rapid diagnostic test performance, though these models often only include a couple genetic factors. Specifically, the Baker et al., 2005 model uses two types of particular repeats in histidine-rich protein 2 (PfHRP2) to describe a P. falciparum infection, though the efficacy of this model has waned over recent years due to genetic mutations in the parasite. In this work, we use a dataset of 100 P. falciparum PfHRP2 genetic sequences collected in Ethiopia and derived a larger set of motif repeat matches for use in generating a series of diagnostic machine learning models. Here we show that the usage of additional and different motif repeats in more sophisticated machine learning methods proves effective in characterizing PfHRP2 diversity. Furthermore, we use machine learning model explainability methods to highlight which of the repeat types are most important with regards to rapid diagnostic test sensitivity, thereby showcasing a novel methodology for identifying potential targets for future versions of rapid diagnostic tests.

MicroRNAs in Lupus Nephritis–Role in Disease Pathogenesis and Clinical Applications

MicroRNAs (miRs) are non-coding small RNAs that act as epigenetic modulators to regulate the protein levels of target mRNAs without modifying the genetic sequences. The role of miRs in the pathogenesis of lupus nephritis (LN) is increasingly recognized and highly complex. Altered levels of different miRs are observed in the blood, urine and kidney tissues of murine LN models and LN patients. Accumulating evidence suggests that these miRs can modulate immune cells and various key inflammatory pathways, and their perturbations contribute to the aberrant immune response in LN. The dysregulation of miRs in different resident renal cells and urinary exosomes can also lead to abnormal renal cell proliferation, inflammation and kidney fibrosis in LN. While miRs may hold promise in various clinical applications in LN patients, there are still many potential limitations and safety concerns for their use. Further studies are worthwhile to examine the clinical utility of miRs in the diagnosis, disease activity monitoring, prognostication and treatment of LN.

Hepatitis B Transmission: Is Vertical Transmission the Major Route in Intermediate Endemic Areas? A Proof-of-Concept Study Based on Mother–Child Genotypes

The route of hepatitis B transmission is believed to be horizontal in India, though pediatric studies showed mother as source in the majority of chronic HBV (CHB) cases. We aimed at establishing the fact that mother–child transmission is the main route of acquisition by documenting genotypically identical viruses in mother–child pairs. Blood samples of consecutive children (≤18 years) with CHB and high DNA (>10,000 IU/mL) and their positive mother were collected from January 2013 to December 2015. Polymerase chain reaction (PCR) products of HBV-DNA were amplified and sequenced by using BigDye Terminator Cycle Sequencing Kit v3.1 and aligned with previously described sequences in the region of interest for genotypes A to G by using BioEdit software. Phylogenetic tree was generated using p-distance algorithm in MEGA software version 6. Genotyping of 59 (33 children and 26 mothers) subjects include genotype A in 24 (40.7%) and genotype D in 35 (59.3%). Both mother–child pair genotyping was possible in 25. The median age of 25 children (20 males) was 9 (interquartile range, IQR: 4–11). The distribution of genotypes among mother–child pairs was similar. The concordance between children and their mothers was 24 of 25 (96%). Evolutionary analyses showed significant similarities between mother and child sequences for both genotype A and D, suggesting thereby the same virus. In conclusion, mother–baby transmission seems to be the major route of acquisition of HBV in children in India and near-complete homology in genetic sequences between mother–child pairs is definite proof for that. However, a larger epidemiological study is required to substantiate our findings.