The IPCC’s reductive Common Era temperature history

J.E. acknowledges support by the Gutenberg Research College, J.E. M.T. and U.B. by the project AdAgrif (CZ.02.01.01/00/22_008/0004635) and ERC (AdG 882727), J.E.S. by the US NSF (OISE-1743738, AGS-2101214 and AGS-2303352), K.J.A. by the US NSF (AGS-1803946 and AGS-2102993), K.A. by the ARC (FT200100102), R.D. by the US NSF (OPP-2112314, OPP-2124885, and AGS-2102759), S.G and M. Stoffel by the SNSF (Sinergia CRSII5_183571), F.C.L. by the SRC (grant no. 2018-01272), Marianne and Marcus Wallenberg Foundation (grant no. MMW 2022-0114) and Swedish Collegium for Advanced Study (Pro Futura Scientia XIII Fellow), LS by the German Research Foundation (SCHN 1645/1-1), M. Sigl by the ERC (CoG 820047), and R.W. by the NSF-NERC (NE/W007223/1).Common Era temperature variability has been a prominent component in Intergovernmental Panel on Climate Change reports over the last several decades and was twice featured in their Summary for Policymakers. A single reconstruction of mean Northern Hemisphere temperature variability was first highlighted in the 2001 Summary for Policymakers, despite other estimates that existed at the time. Subsequent reports assessed many large-scale temperature reconstructions, but the entirety of Common Era temperature history in the most recent Sixth Assessment Report of the Intergovernmental Panel on Climate Change was restricted to a single estimate of mean annual global temperatures. We argue that this focus on a single reconstruction is an insufficient summary of our understanding of temperature variability over the Common Era. We provide a complementary perspective by offering an alternative assessment of the state of our understanding in high-resolution paleoclimatology for the Common Era and call for future reports to present a more accurate and comprehensive assessment of our knowledge about this important period of human and climate history.Peer reviewe

Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns

Clostridium collagenase has provided superior clinical results in achieving digestion of immediate and accumulating devitalized collagen tissue. Recent studies suggest that debridement via Clostridium collagenase modulates a cellular response to foster an anti-inflammatory microenvironment milieu, allowing for a more coordinated healing response. In an effort to better understand its role in burn wounds, we evaluated Clostridium collagenase’s ability to effectively minimize burn progression using the classic burn comb model in pigs. Following burn injury, wounds were treated with Clostridium collagenase or control vehicle daily and biopsied at various time points. Biopsies were evaluated for factors associated with progressing necrosis as well as inflammatory response associated with treatment. Data presented herein showed that Clostridium collagenase treatment prevented destruction of dermal collagen. Additionally, treatment with collagenase reduced necrosis (HMGB1) and apoptosis (CC3a) early in burn injuries, allowing for increased infiltration of cells and protecting tissue from conversion. Furthermore, early epidermal separation and epidermal loss with a clearly defined basement membrane was observed in the treated wounds. We also show that collagenase treatment provided an early and improved inflammatory response followed by faster resolution in neutrophils. In assessing the inflammatory response, collagenase-treated wounds exhibited significantly greater neutrophil influx at day 1, with macrophage recruitment throughout days 2 and 4. In further evaluation, macrophage polarization to MHC II and vascular network maintenance were significantly increased in collagenase-treated wounds, indicative of a pro-resolving macrophage environment. Taken together, these data validate the impact of clostridial collagenases in the pathophysiology of burn wounds and that they complement patient outcomes in the clinical scenario

How pH Modulates the Reactivity and Selectivity of a Siderophore-Associated Flavin Monooxygenase

Flavin-containing monooxygenases (FMOs) catalyze the oxygenation of diverse organic molecules using O₂, NADPH, and the flavin adenine dinucleotide (FAD) cofactor. The fungal FMO SidA initiates peptidic siderophore biosynthesis via the highly selective hydroxylation of l-ornithine, while the related amino acid l-lysine is a potent effector of reaction uncoupling to generate H₂O₂. We hypothesized that protonation states could critically influence both substrate-selective hydroxylation and H₂O₂ release, and therefore undertook a study of SidA’s pH-dependent reaction kinetics. Consistent with other FMOs that stabilize a C4a-OO­(H) intermediate, SidA’s reductive half reaction is pH independent. The rate constant for the formation of the reactive C4a-OO­(H) intermediate from reduced SidA and O₂ is likewise independent of pH. However, the rate constants for C4a-OO­(H) reactions, either to eliminate H₂O₂ or to hydroxylate l-Orn, were strongly pH-dependent and influenced by the nature of the bound amino acid. Solvent kinetic isotope effects of 6.6 ± 0.3 and 1.9 ± 0.2 were measured for the C4a-OOH/H₂O₂ conversion in the presence and absence of l-Lys, respectively. A model is proposed in which l-Lys accelerates H₂O₂ release via an acid–base mechanism and where side-chain position determines whether H₂O₂ or the hydroxylation product is observed