Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

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The Alarmone (p)ppGpp Regulates Primer Extension by Bacterial Primase

Primase is an essential component of the DNA replication machinery, responsible for synthesizing RNA primers that initiate leading and lagging strand DNA synthesis. Bacterial primase activity can be regulated by the starvation-inducible nucleotide (p)ppGpp. This regulation contributes to a timely inhibition of DNA replication upon amino acid starvation in the Gram-positive bacterium Bacillus subtilis. Here, we characterize the effect of (p)ppGpp on B. subtilis DnaG primase activity in vitro. Using a single-nucleotide resolution primase assay, we dissected the effect of ppGpp on the initiation, extension, and fidelity of B. subtilis primase. We found that ppGpp has a mild effect on initiation, but strongly inhibits primer extension and reduces primase processivity, promoting termination of primer extension. High (p)ppGpp concentration, together with low GTP concentration, additively inhibit primase activity. This explains the strong inhibition of replication elongation during starvation which induces high levels of (p)ppGpp and depletion of GTP in B. subtilis. Finally, we found that lowering GTP concentration results in mismatches in primer base pairing that allow priming readthrough, and that ppGpp reduces readthrough to protect priming fidelity. These results highlight the importance of (p)ppGpp in protecting replisome integrity and genome stability in fluctuating nucleotide concentrations upon onset of environmental stress.     

Detection of coccidioidal antibodies in serum of a small rodent community in Baja California,Mexico

Coccidioidomycosis (Valley Fever) represents a serious threat to inhabitants of endemic areas of North America. Despite successful clinical isolations of the fungal etiological agent, Coccidioides spp., the screening of environmental samples has had low effectiveness, mainly because of the poor characterization of Coccidioides ecological niche. We explored Valle de las Palmas, Baja California, Mexico, a highly endemic area near the U.S.–Mexico border, where we previously detected Coccidioides via culture-independent molecular methods. By testing the serum from 40-trapped rodents with ELISA, we detected antibodies against Coccidioides in two species: Peromyscus maniculatus and Neotoma lepida. This study comprises the first report of wild rodent serum tested for coccidioidal antibodies, and sets the basis to analyze this pathogen in its natural environment and explore its potential ecological niche.     

House flies delay fungal infection by fevering: at a cost

1. Many ectothermic species have evolved the ability to invoke a ‘behavioural fever’ when infected with a pathogen. The relative costs and benefits of this response, however, have rarely been quantified. 2. The aim of this study was investigate the nature and consequences of behavioural fever in the house fly, Musca domestica L., in response to infection with a possible biocontrol agent, the fungal entomopathogen, Beauveria bassiana (Balsamo) Vuillemin. 3. It was found that infected flies preferred higher temperatures and allocated more effort to thermoregulation than uninfected flies. Flies could not overcome infection but the altered thermal behaviour allowed infected flies to extend their survival and to lay more eggs relative to infected flies maintained under constant conditions. However, flies allowed to fever had lower egg viability suggesting a possible cost. 4. Under the present experimental conditions, the putative costs and benefits fever balanced one another resulting in no net change in fitness. Fever did not, therefore, limit the control potential of the fungus. We discuss whether the costs and benefits of behavioural fever might differ in other ecological contexts.     

Variation of chemical composition and antioxidant activity of essential oils of Mentha x rotundifolia (L.) Huds. (Lamiaceae) collected from different bioclimatic areas of Tunisia

The variation of the essential oils composition of 10 Tunisian Mentha x rotundifolia (L.) Huds. Populations and their antioxidant activity were assessed. Essential oils showed high percentages of oxygenated monoterpenes and sesquiterpene hydrocarbons. Rotundifolone, p-menthane-1,2,3-triol, β-caryophyllene and germacrene D were identified as main compounds at the species level. A variation in the essential oil composition was observed according to the populations and ecological factors. The populations 7, 8, 9 and 10 from the upper semi-arid bioclimatic zone and situated at high altitudes, exhibited the highest amount of rotundifolone. The populations 1, 2, 3, 4 and 5 from the lower humid showed a rotundifolone/β-caryophyllene/germacrene D chemotype. The population 6, situated at the lowest altitude, was characterized by the highest amount of p-menthane-1,2,3-triol. The level of antioxidant activity of the populations was linked to their chemical composition difference. The highest scavenging activity and the best ability to reduce ferric ions were recorded for the population 10. The most important capacity to inhibit β-carotene bleaching was revealed for the population 8. For all populations, the antioxidant activities were substantial but lower than antioxidant standards used (Trolox and BHT).The populations (7, 8, 9 and 10) from the upper semi-arid showed the best yields of essential oils and the highest contents of rotundifolone. Chemotypes within these populations could be selected for improvement programs.     

Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma

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Highlights

• •Flow cytometry analysis is used to isolate ASC speck⁽⁺⁾ NPC cells.
• •Proteome analysis of ASC speck⁽⁺⁾ NPC cells reveals enriched mitochondrial OxPhos proteins.
• •OxPhos proteins mediate NLRP3 inflammasome activation through mtROS.
• •OxPhos proteins, NDUFB8 and ATP5B are correlated with NPC local recurrence.

     

The Amount of BCL6 in B Cells Shortly after Antigen Engagement Determines Their Representation in Subsequent Germinal Centers

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DNA ADP-Ribosylation Stalls Replication and Is Reversed by RecF-Mediated Homologous Recombination and Nucleotide Excision Repair

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