Human piRNAs Are Under Selection in Africans and Repress Transposable Elements

Piwi-interacting RNAs (piRNAs) are a recently discovered class of 24- to 30-nt noncoding RNAs whose best-understood function is to repress transposable elements (TEs) in animal germ lines. In humans, TE-derived sequences comprise ∼45% of the genome and there are several active TE families, including LINE-1 and Alu elements, which are a significant source of de novo mutations and intrapopulation variability. In the “ping-pong model,” piRNAs are thought to alternatively cleave sense and antisense TE transcripts in a positive feedback loop. Because piRNAs are poorly conserved between closely related species, including human and chimpanzee, we took a population genomics approach to study piRNA function and evolution. We found strong statistical evidence that piRNA sequences are under selective constraint in African populations. We then mapped the piRNA sequences to human TE sequences and found strong correlations between the age of each LINE-1 and Alu subfamily and the number of piRNAs mapping to the subfamily. This result supports the idea that piRNAs function as repressors of TEs in humans. Finally, we observed a significant depletion of piRNA matches in the reverse transcriptase region of the consensus human LINE-1 element but not of the consensus mouse LINE-1 element. This result suggests that reverse transcriptase might have an endogenous role specific to humans. Overall, our results elucidate the function and evolution of piRNAs in humans and highlight the utility of population genomics analysis for studying this rapidly evolving genetic system

Early gas kick detection in vertical wells via transient multiphase flow modelling: A review

Gas influx from reservoir into the wellbore during drilling, tripping, or other operations, is a hazard. In the early stages, the influx may be nearly undetectable, but the kick can rapidly change from a seemingly steady condition to one of extremely high flow rate. The resulting uncontrolled release of large amounts of gas on the drilling rig can ignite and explode; causing loss of life, loss of asset, and contamination of environment. A kick perturbs the system; analysis of the resulting transient flow could lead to significant improvement in timely detection of a kick. Timely detection is essential to avoid blowouts. Early detection also allows better characterization of potential blowout, allowing improved response and mitigation efforts. Early gas-kick prediction and analysis through dynamic multiphase flow can lead to significant progress in detection and controlling of High Pressure High Temperature (HPHT) drilling of deep wells, which is vital to prevent gas blowout risk. This review paper aims to provide the current state-of-the-art on the early gas-kick simulation models based on transient multiphase flow to determine the bottom hole pressure and gas kick size and to employ appropriate mitigation plans. A comprehensive literature review on early kick detection showed that the transient one-dimensional two-phase models are prominently researched considering some aspects of heat transfer, gas solubility and homogenous flows. The reported transient two-phase (G-L) flow models are found to be limited to 1-D flow with limited range of operating conditions. Future studies towards more sophisticated 2-D and 3-D simulations of transient multiphase (G-L) flow models using computational fluid dynamics (CFD) tools are recommended. 2-D and 3-D flow simulations using advanced turbulence models can potentially enhance the accuracy in the calculations of phase velocity, temperature and pressure patterns within the annuli of wellbore and can advance the early gas-kick detection process.This publication was jointly supported by International Research Collaboration Co Fund Grant [ IRCC-2019-012 ], Qatar University and Texas A&M University at Qatar. The findings achieved herein are solely the responsibility of the authors.Scopu

ECAT11/L1td1 Is Enriched in ESCs and Rapidly Activated During iPSCGeneration, but It Is Dispensable for the Maintenance and Induction of Pluripotency

The principal factors that lead to proliferation and pluripotency in embryonic stem cells (ESCs) have been vigorously investigated. However, the global network of factors and their full signaling cascade is still unclear. In this study, we found that ECAT11 (L1td1) is one of the ESC-associated transcripts harboring a truncated fragment of ORF-1, a component of theL1 retrotransposable element. We generated an ECAT11 knock-in mouse by replacing its coding region with green fluorescent protein. In the early stage of development, the fluorescence was observed at the inner cell mass of blastocysts and epiblasts. Despite this specific expression, ECAT11-null mice grow normally and are fertile. In addition, ECAT11 was dispensable for both the proliferation and pluripotency of ESCs.We found rapid and robust activation of ECAT11 in fibroblasts after the forced expression of transcription factors that can give rise pluripotency in somatic cells.However, iPS cells could be established from ECAT11-null fibroblasts. Our data demonstrate thedispensability of ECAT11/L1td1 in pluripotency, despite its specific expression

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Increased waterborne blaNDM-1 resistance gene abundances associated with seasonal human pilgrimages to the Upper Ganges River

Antibiotic resistance (AR) is often rooted in inappropriate antibiotic use, but poor water quality and inadequate sanitation exacerbate the problem, especially in emerging countries. An example is increasing multi-AR due to mobile carbapenemases, such as NDM-1 protein (coded by blaNDM-1 genes), which can produce extreme drug-resistant phenotypes. In 2010, NDM-1 positive isolates and blaNDM-1 genes were detected in surface waters across Delhi and have since been detected across the urban world. However, little is known about blaNDM-1 levels in more pristine locations, such as the headwaters of the Upper Ganges River. This area is of particular interest because it receives massive numbers of visitors during seasonal pilgrimages in May/June, including visitors from urban India. Here we quantified blaNDM-1 abundances, other AR genes (ARG) and coliform bacteria in sediments and water column samples from seven sites in the Rishikesh-Haridwar region of the Upper Ganges and five sites on the Yamuna River in Delhi to contrast blaNDM-1 levels and water quality conditions between season and region. Water quality in the Yamuna was very poor (e.g., anoxia at all sites), and blaNDM-1 abundances were high across sites in water (5.4 ± 0.4 log(blaNDM-1·mL-1); 95% confidence interval) and sediment (6.3 ± 0.7 log(blaNDM-1·mg-1)) samples from both seasons. In contrast, water column blaNDM-1 abundances were very low across all sites (2.1 ± 0.6 log(blaNDM-1·mL-1)) in February in the Upper Ganges and water quality was good (e.g., near saturation oxygen). However, per capita blaNDM-1 levels were 20 times greater in June in the Ganges water column relative to February and blaNDM-1 levels significantly correlated with fecal coliform levels (r=0.61; p=0.007). Given waste management infrastructure is limited in Rishikesh-Haridwar; data imply blaNDM-1 levels are higher in visitor's wastes than local residents, which results in seasonally higher blaNDM-1 levels in the river. Pilgrimage areas without adequate waste treatment are possible "hot spots" for AR transmission, and waste treatment must be improved to reduce broader AR dissemination via exposed returning visitors

A Call for Action: The Application of the International Health Regulations to the Global Threat of Antimicrobial Resistance

Stephen Harbarth and colleagues argue that the International Health Regulations (IHR) should be applied to the global health threat of antimicrobial resistance

Catalytic and Non-Catalytic Roles for the Mono-ADP-Ribosyltransferase Arr in the Mycobacterial DNA Damage Response

Recent evidence indicates that the mycobacterial response to DNA double strand breaks (DSBs) differs substantially from previously characterized bacteria. These differences include the use of three DSB repair pathways (HR, NHEJ, SSA), and the CarD pathway, which integrates DNA damage with transcription. Here we identify a role for the mono-ADP-ribosyltransferase Arr in the mycobacterial DNA damage response. Arr is transcriptionally induced following DNA damage and cellular stress. Although Arr is not required for induction of a core set of DNA repair genes, Arr is necessary for suppression of a set of ribosomal protein genes and rRNA during DNA damage, placing Arr in a similar pathway as CarD. Surprisingly, the catalytic activity of Arr is not required for this function, as catalytically inactive Arr was still able to suppress ribosomal protein and rRNA expression during DNA damage. In contrast, Arr substrate binding and catalytic activities were required for regulation of a small subset of other DNA damage responsive genes, indicating that Arr has both catalytic and noncatalytic roles in the DNA damage response. Our findings establish an endogenous cellular function for a mono-ADP-ribosyltransferase apart from its role in mediating Rifampin resistance