42 research outputs found
Hifâ1alpha stabilisation is protective against infection in zebrafish comorbid models
Multiâdrugâresistant tuberculosis is a worldwide problem, and there is an urgent need for hostâderived therapeutic targets, circumventing emerging drug resistance. We have previously shown that hypoxiaâinducible factorâ1α (Hifâ1α) stabilisation helps the host to clear mycobacterial infection via neutrophil activation. However, Hifâ1α stabilisation has also been implicated in chronic inflammatory diseases caused by prolonged neutrophilic inflammation. Comorbid infection and inflammation can be found together in disease settings, and it remains unclear whether Hifâ1α stabilisation would be beneficial in a holistic disease setting. Here, we set out to understand the effects of Hifâ1α on neutrophil behaviour in a comorbid setting by combining two wellâcharacterised in vivo zebrafish models â TB infection (Mycobacterium marinum infection) and sterile injury (tailfin transection). Using a local Mm infection near to the tailfin wound site caused neutrophil migration between the two sites that was reduced during Hifâ1α stabilisation. During systemic Mm infection, wounding leads to increased infection burden, but the protective effect of Hifâ1α stabilisation remains. Our data indicate that Hifâ1α stabilisation alters neutrophil migration dynamics between comorbid sites and that the protective effect of Hifâ1α against Mm is maintained in the presence of inflammation, highlighting its potential as a hostâderived target against TB infection
Corrosion of the alloys Magnox AL80, Magnox ZR55 and pure magnesium in air containing water vapour
Diet and feeding activity of Acestrorhynchus lacustris (LĂŒtken, 1875) (Characiformes, Acestrorhynchidae) in the water reservoir at RibeirĂŁo Claro, SP
Trophic ecology of Hemigrammus marginatus Ellis, 1911 (Characiformes, Characidae) in a conserved tropical stream
Diet and ecomorphology of Leporinus reticulatus (Characiformes: Anostomidae) from the upper Rio Juruena, MT, Brazil: ontogenetic shifts related to the feeding ecology
Ecologia e ontogenia da alimentação de Astyanax janeiroensis (Osteichthyes, Characidae) de um riacho costeiro do Sudeste do Brasil
Uso de recursos alimentares por peixes imaturos e adultos de espĂ©cies piscĂvoras em uma planĂcie de inundação neotropical
Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1â11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely