A temperature-dependent conformational shift in p38{alpha} MAPK substrate-binding region associated with changes in substrate phosphorylation profile Protein Structure and Folding

Febrile-range hyperthermia worsens and hypothermia mitigates lung injury, and temperature dependence of lung injury is blunted by inhibitors of p38 mitogen-activated protein kinase (MAPK). Of the two predominant p38 isoforms, p38α is proinflammatory and p38β is cytoprotective. Here, we analyzed the temperature dependence of p38 MAPK activation, substrate interaction, and tertiary structure. Incubating HeLa cells at 39.5 °C stimulated modest p38 activation, but did not alter tumor necrosis factor-α (TNFα)-induced p38 activation. In in vitro kinase assays containing activated p38α and MAPK-activated kinase-2 (MK2), MK2 phosphorylation was 14.5-fold greater at 39.5 °C than at 33 °C. By comparison, we observed only 3.1- and 1.9-fold differences for activating transcription factor-2 (ATF2) and signal transducer and activator of transcription-1α (STAT1α) and a 7.7-fold difference for p38β phosphorylation of MK2. The temperature dependence of p38α:substrate binding affinity, as measured by surface plasmon resonance, paralleled substrate phosphorylation. Hydrogen–deuterium exchange MS (HDX-MS) of p38α performed at 33, 37, and 39.5 °C indicated temperature-dependent conformational changes in an α helix near the common docking and glutamate:aspartate substrate-binding domains at the known binding site for MK2. In contrast, HDX-MS analysis of p38β did not detect significant temperature-dependent c...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Signal Transduction Source Type: research

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Conclusion These results show that the use of body-temperature and humidified insufflation gas for laparoscopy can help to prevent intraoperative hypothermia. PMID: 31523097 [PubMed]
Source: Geburtshilfe und Frauenheilkunde - Category: OBGYN Tags: Geburtshilfe Frauenheilkd Source Type: research
In conclusion, fast hypothermia was successfully induced by CRRT and significantly alleviated the severity of PCAS in a porcine model.
Source: Shock - Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
CONCLUSIONS: Adolescent mice self-administered both alcohol and edible THC to a degree sufficient to acutely impact locomotor activity. However, only edible THC consumption had lasting effects during short-term abstinence. Thus, this adolescent co-use model could be used to explore sex differences in self-administration as well as the impact substance co-use might have on other domains such as mood and cognition. PMID: 31524960 [PubMed - as supplied by publisher]
Source: Alcoholism, Clinical and Experimental Research - Category: Addiction Authors: Tags: Alcohol Clin Exp Res Source Type: research
Publication date: Available online 14 September 2019Source: Nitric OxideAuthor(s): Thomas Uray, Philip E. Empey, Tomas Drabek, Jason P. Stezoski, Keri Janesko-Feldman, Travis Jackson, Robert H. Garman, Francis Kim, Patrick M. Kochanek, Cameron DezfulianAbstractIntroductionBesides therapeutic hypothermia or targeted temperature management no novel therapies have been developed to improve outcomes of patients after cardiac arrest (CA). Recent studies suggest that nitrite reduces neurological damage after asphyxial CA. Nitrite is also implicated as a new mediator of remote post conditioning produced by tourniquet inflation-de...
Source: Nitric Oxide - Category: Chemistry Source Type: research
Conclusion: Local application of therapeutic hypothermia is clinically feasible both through the facial recess and myringotomy approaches without limiting optimal surgical visualization.
Source: Otology and Neurotology - Category: ENT & OMF Tags: COCHLEAR IMPLANTS Source Type: research
CONCLUSIONS Both methods demonstrated to have neuroprotective properties, although full-body cooling provides a broader area of protection. Recently, head cooling combined with some body cooling has been applied, which is the most promising approach. The challenge for the future is to find ways of improving the effectiveness of the treatment.RESUMO INTRODU ÇÃO A possibilidade de a hipotermia ter um papel terapêutico durante ou após a reanimação da asfixia perinatal grave tem sido um foco de pesquisa de longa data. Estudos desenhados em torno desse fato mostraram que a hipotermia cer...
Source: Revista da Associacao Medica Brasileira - Category: General Medicine Source Type: research
Authors: El Farissi M, Keulards DCJ, van 't Veer M, Zelis JM, Berry C, De Bruyne B, Engstrøm T, Fröbert O, Piroth Z, Oldroyd KG, Tonino PAL, Pijls NHJ, Otterspoor LC PMID: 31498112 [PubMed - as supplied by publisher]
Source: EuroIntervention - Category: Cardiovascular & Thoracic Surgery Tags: EuroIntervention Source Type: research
Patients with accidental hypothermia without vital signs increasingly receive venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, there is limited knowledge regarding the efficacy of this advanced rewarming method. We aimed to determine whether VA-ECMO improved outcomes in patients with accidental hypothermia without vital signs, using a large nationwide inpatient database in Japan.
Source: Resuscitation - Category: Emergency Medicine Authors: Tags: Clinical paper Source Type: research
CONCLUSION: A novel aEEG background pattern in infants with HIE was reported. The PST pattern likely indicates a suppressed background pattern and may be linked to unfavorable outcomes. Further multicenter validation study is needed to clarify its clinical significance. PMID: 31493771 [PubMed - as supplied by publisher]
Source: Pediatric Research - Category: Pediatrics Authors: Tags: Pediatr Res Source Type: research
We report results of a pilot study in patients over the age of 65 undergoing hemiarthroplasty following fractured neck of femur.AimTo establish the recruitment and data management strategies needed for a full trial comparing post-operative infection rates associated with forced air versus resistive fabric warming.MethodsParticipants were randomised 1:1 in permuted blocks to forced air or resistive fabric warming. Hypothermia was defined as a temperature of
Source: Journal of Hospital Infection - Category: Infectious Diseases Source Type: research
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