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Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yunha Hwang ◽  
Dirk Schulze-Makuch ◽  
Felix L. Arens ◽  
Johan S. Saenz ◽  
Panagiotis S. Adam ◽  
...  

Abstract Background The hyperarid core of the Atacama Desert is an extremely harsh environment thought to be colonized by only a few heterotrophic bacterial species. Current concepts for understanding this extreme ecosystem are mainly based on the diversity of these few species, yet a substantial area of the Atacama Desert hyperarid topsoil is covered by expansive boulder accumulations, whose underlying microbiomes have not been investigated so far. With the hypothesis that these sheltered soils harbor uniquely adapted microbiomes, we compared metagenomes and geochemistry between soils below and beside boulders across three distantly located boulder accumulations in the Atacama Desert hyperarid core. Results Genome-resolved metagenomics of eleven samples revealed substantially different microbial communities in soils below and beside boulders, despite the presence of shared species. Archaea were found in significantly higher relative abundance below the boulders across all samples within distances of up to 205 km. These key taxa belong to a novel genus of ammonia-oxidizing Thaumarchaeota, Candidatus Nitrosodeserticola. We resolved eight mid-to-high quality genomes of this genus and used comparative genomics to analyze its pangenome and site-specific adaptations. Ca. Nitrosodeserticola genomes contain genes for ammonia oxidation, the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway, and acetate utilization indicating a chemolithoautotrophic and mixotrophic lifestyle. They also possess the capacity for tolerating extreme environmental conditions as highlighted by the presence of genes against oxidative stress and DNA damage. Site-specific adaptations of the genomes included the presence of additional genes for heavy metal transporters, multiple types of ATP synthases, and divergent genes for aquaporins. Conclusion We provide the first genomic characterization of hyperarid soil microbiomes below the boulders in the Atacama Desert, and report abundant and highly adapted Thaumarchaeaota with ammonia oxidation and carbon fixation potential. Ca. Nitrosodeserticola genomes provide the first metabolic and physiological insight into a thaumarchaeal lineage found in globally distributed terrestrial habitats characterized by various environmental stresses. We consequently expand not only the known genetic repertoire of Thaumarchaeota but also the diversity and microbiome functioning in hyperarid ecosystems.


Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2056
Author(s):  
Hui Jiang ◽  
Ya-Fang Mei

Severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) has led to the coronavirus disease 2019 (COVID–19) pandemic, severely affecting public health and the global economy. Adaptive immunity plays a crucial role in fighting against SARS–CoV–2 infection and directly influences the clinical outcomes of patients. Clinical studies have indicated that patients with severe COVID–19 exhibit delayed and weak adaptive immune responses; however, the mechanism by which SARS–CoV–2 impedes adaptive immunity remains unclear. Here, by using an in vitro cell line, we report that the SARS–CoV–2 spike protein significantly inhibits DNA damage repair, which is required for effective V(D)J recombination in adaptive immunity. Mechanistically, we found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site. Our findings reveal a potential molecular mechanism by which the spike protein might impede adaptive immunity and underscore the potential side effects of full-length spike-based vaccines.


2021 ◽  
Vol 22 (19) ◽  
pp. 10439
Author(s):  
Valentina Garlatti ◽  
Sara Lovisa ◽  
Silvio Danese ◽  
Stefania Vetrano

Inflammatory Bowel Disease (IBD) comprises a series of chronic and relapsing intestinal diseases, with Crohn’s disease and ulcerative colitis being the most common. The abundant and uncontrolled deposition of extracellular matrix, namely fibrosis, is one of the major hallmarks of IBD and is responsible for the progressive narrowing and closure of the intestine, defined as stenosis. Although fibrosis is usually considered the product of chronic inflammation, the substantial failure of anti-inflammatory therapies to target and reduce fibrosis in IBD suggests that fibrosis might be sustained in an inflammation-independent manner. Pharmacological therapies targeting integrins have recently shown great promise in the treatment of IBD. The efficacy of these therapies mainly relies on their capacity to target the integrin-mediated recruitment and functionality of the immune cells at the damage site. However, by nature, integrins also act as mechanosensitive molecules involved in the intracellular transduction of signals and modifications originating from the extracellular matrix. Therefore, understanding integrin signaling in the context of IBD may offer important insights into mechanisms of matrix remodeling, which are uncoupled from inflammation and could underlie the onset and persistency of intestinal fibrosis. In this review, we present the currently available knowledge on the role of integrins in the etiopathogenesis of IBD, highlighting their role in the context of immune-dependent and independent mechanisms.


2021 ◽  
Author(s):  
Yannan Tian ◽  
Fuxing Zeng ◽  
Adrika Raybarman ◽  
Amy Carruthers ◽  
Qingrong Li ◽  
...  

AbstractIn bacteria, rescue of stalled ribosomes due to 3’-truncated mRNAs is carried out by the ubiquitous trans-translation system as well as alternative ribosome-rescue factors such as ArfA and ArfB. It is unclear, however, how the stalled ribosomes caused by ribosomal damages are rescued. Here, we report that a bacterial system composed of PrfH and RtcB not only rescues a stalled ribosome resulting from a specific damage in the decoding center but also repairs the damage afterwards. Peptide release assays reveal that PrfH is only active with the damaged ribosome, but not with the intact one. A 2.55-angstrom cryo-EM structure of PrfH in complex with the damaged 70S ribosome provides molecular insight into specific recognition of the damage site by PrfH. RNA repair assays demonstrate that PrfH-coupled RtcB efficiently repairs the damaged 30S ribosomal subunit, but not the damaged tRNAs. Thus, our studies have uncovered a biological operation by a pair of bacterial enzymes, aiming to reverse the potentially lethal damage inflicted by an invading ribotoxin for cell survival.


Author(s):  
R Tharmaraj ◽  
M Joseph Davidson ◽  
S Richard

In the present work, localised heating has been adopted at the damage site of the cold upset materials and the role of this mechanism on the workability has been analysed. Cylindrical specimens containing 96% aluminium and 4% titanium were prepared through powder metallurgy technique with an aspect ratio (height to diameter) of 1 by suitable pressures. A series of cold upsetting test was conducted and the material properties for various preforms initial relative densities (80%, 85% and 90%) were determined under the stable strain rate. The flow of metals was analysed using a finite element tool and it was observed that the metal flow starts from near the centre zone to the equatorial zone and the damage happens in the outer position because of more amount of accumulated stresses and the pores. These stresses and pores decrease the workability of the final component. Hence, the present research is intended to reduce the stresses and minimize the pores by applying a localized heating (100 °C–250 °C) at the equatorial sites of the components and thereby increasing the workability of the material. Also, heating selectively at the equatorial site of the workpiece improves the workability due to change in grain size and it was noticed that the grain size of the developed porous preforms was high for the higher heating conditions due to the growth of the grains. Therefore, the localized heating adopted in this work is a superior method to enhance the workability of the powder samples and this novel technique could be useful in improving the workability of the structural components that have extensive applications in the automobile and aerospace industries.


Talanta ◽  
2021 ◽  
pp. 122809
Author(s):  
Yan Zhang ◽  
Yun Han ◽  
Xiaoran Zou ◽  
Qinfeng Xu ◽  
Fei Ma ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ezeogo Obaji ◽  
Mirko M. Maksimainen ◽  
Albert Galera-Prat ◽  
Lari Lehtiö

AbstractHuman PARP2/ARTD2 is an ADP-ribosyltransferase which, when activated by 5′-phosphorylated DNA ends, catalyses poly-ADP-ribosylation of itself, other proteins and DNA. In this study, a crystal structure of PARP2 in complex with an activating 5′-phosphorylated DNA shows that the WGR domain bridges the dsDNA gap and joins the DNA ends. This DNA binding results in major conformational changes, including reorganization of helical fragments, in the PARP2 regulatory domain. A comparison of PARP1 and PARP2 crystal structures reveals how binding to a DNA damage site leads to formation of a catalytically competent conformation. In this conformation, PARP2 is capable of binding substrate NAD+ and histone PARylation factor 1 that changes PARP2 residue specificity from glutamate to serine when initiating DNA repair processes. The structure also reveals how the conformational changes in the autoinhibitory regulatory domain would promote the flexibility needed by the enzyme to reach the target macromolecule for ADP-ribosylation.


Author(s):  
Melissa A. Wagner ◽  
Robert K. Doe ◽  
Chuyuan Wang ◽  
Erik Rasmussen ◽  
Michael C. Coniglio ◽  
...  

AbstractTopography can have a significant influence on tornado intensity and direction by altering the near-surface inflow. However, past research involving topographic influence on tornadoes has shown significant variety in investigative approaches and conclusions. This study uses Unpiloted Aerial Systems (UAS)-based high-resolution imagery, UAS-based 3D-modeling products, and correlation analyses to examine topographical influences on a portion of the 01 May 2018 Tescott, Kansas EF3 tornado. Two new metrics, Visible Difference Vegetative Index (VDVI) gap and (VDVI) aspect ratio, are introduced to quantify damage severity using UAS-based imagery and elevation information retrieved from a UAS-based digital surface model (DSM). Areas of enhanced scour are seen along the track in areas of local elevation maxima. Correlation analysis shows that damage severity, as measured by VDVI gap and VDVI aspect ratio, are both well correlated with increasing elevation. VDVI gap is only weakly correlated with slope, while VDVI aspect ratio is not correlated with slope. These findings are statistically significant at p < 0.05. As the tornado weakened in intensity, the path became non-linear, traversing between two local elevation maxima. It is hypothesized that fast-moving intense flow formed and weakened as elevation increased over the short spatial distance. This research shows topography and surface conditions are two of many important variables that should be considered when performing tornado-damage site investigations. It also illustrates the importance of UASs in detailed tornado analysis. VDVI gap and VDVI aspect ratio can provide insight into damage severity as a function of topography.


2021 ◽  
Vol 22 (11) ◽  
pp. 5934
Author(s):  
Boleslaw T. Karwowski

As a result of external and endocellular physical-chemical factors, every day approximately ~105 DNA lesions might be formed in each human cell. During evolution, living organisms have developed numerous repair systems, of which Base Excision Repair (BER) is the most common. 5′,8-cyclo-2′-deoxyadenosine (cdA) is a tandem lesion that is removed by the Nucleotide Excision Repair (NER) mechanism. Previously, it was assumed that BER machinery was not able to remove (5′S)cdA from the genome. In this study; however, it has been demonstrated that, if (5′S)cdA is a part of a single-stranded clustered DNA lesion, it can be removed from ds-DNA by BER. The above is theoretically possible in two cases: (A) When, during repair, clustered lesions form Okazaki-like fragments; or (B) when the (5′S)cdA moiety is located in the oligonucleotide strand on the 3′-end side of the adjacent DNA damage site, but not when it appears at the opposite 5′-end side. To explain this phenomenon, pure enzymes involved in BER were used (polymerase β (Polβ), a Proliferating Cell Nuclear Antigen (PCNA), and the X-Ray Repair Cross-Complementing Protein 1 (XRCC1)), as well as the Nuclear Extract (NE) from xrs5 cells. It has been found that Polβ can effectively elongate the primer strand in the presence of XRCC1 or PCNA. Moreover, supplementation of the NE from xrs5 cells with Polβ (artificial Polβ overexpression) forced oligonucleotide repair via BER in all the discussed cases.


2021 ◽  
Vol 22 (10) ◽  
pp. 5189
Author(s):  
Joon Ho Seo ◽  
Miloni S. Dalal ◽  
Jorge E. Contreras

Neuroinflammation is a major component of central nervous system (CNS) injuries and neurological diseases, including Alzheimer’s disease, multiple sclerosis, neuropathic pain, and brain trauma. The activation of innate immune cells at the damage site causes the release of pro-inflammatory cytokines and chemokines, which alter the functionality of nearby tissues and might mediate the recruitment of leukocytes to the injury site. If this process persists or is exacerbated, it prevents the adequate resolution of the inflammation, and ultimately enhances secondary damage. Adenosine 5′ triphosphate (ATP) is among the molecules released that trigger an inflammatory response, and it serves as a chemotactic and endogenous danger signal. Extracellular ATP activates multiple purinergic receptors (P2X and P2Y) that have been shown to promote neuroinflammation in a variety of CNS diseases. Recent studies have shown that Pannexin-1 (Panx1) channels are the principal conduits of ATP release from dying cells and innate immune cells in the brain. Herein, we review the emerging evidence that directly implicates Panx-1 channels in the neuroinflammatory response in the CNS.


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