The complexities of breast cancer desmoplasia

The stromal, or 'desmoplastic', responses seen histologically in primary breast carcinomas can vary from being predominantly cellular (fibroblasts/myofibroblasts) with little collagen to being a dense acellular tissue. The mechanisms underlying the stromal response are complex; paracrine activation of myofibroblasts by growth factors is important but the contribution of cytokines/chemokines should not be ignored. A recent xenograft study has proposed that platelet-derived growth factor (PDGF) is the initiator of the desmoplastic response, but this has not been confirmed by (limited) analyses in vivo. Further studies are required to elaborate the mechanisms of the desmoplastic response, to determine its role in breast cancer progression and whether it is the same for all carcinomas

Nocturnal plant respiration is under strong non-temperature control

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: The leaf respiration data measured as part of this study and collected from the literature together with annual gridded JULES output generated in simulations of this study are available at https://doi.org/10.5281/zenodo.7037530. WFDEI meteorological forcing data is available at the DATAGURU website for climate-related data at Lund University (https://DATAGURU.lu.se, then go to “Explore available datasets”). This allows extraction of data from the global domain, a user-defined grid box or region for a specified time interval. Ftp downloads are possible via the unix/linux command line, site = ftp.iiasa.ac.at, username = rfdata and password = forceDATA, this takes the user to the WATCH Forcing DATA files, then switch to the WFDEI directory using: ‘cd WFDEI’. The /WFDEI directory includes files listing grid box elevations and locations Annual CO2 concentrations are available at https://gml.noaa.gov/ccgg/trends/gl_data.html Source data are provided with this paper.Code availability: Python code for data analysis is available under https://doi.org/10.5281/zenodo.7037530. This study uses JULES, two branches of JULES-vn5.2. https://code.metoffice.gov.uk/trac/jules/browser/main/branches/dev/linamercado/r14338_circadian at revision 22682 for TDQ10 simulations and https://code.metoffice.gov.uk/trac/jules/browser/main/branches/dev/douglasclark/vn5.2_diurnal_resp at revision 22681 for simulations with constant Q10 which are available on the Met Office Science Repository System (MOSRS; https://code.metoffice.gov.uk/trac/jules; registration required https://jules.jchmr.org/content/getting-started). Simulations were performed using Rose suites u-ce999 (new formulation) and u-ce859 for simulations with constant Q10, and u-bs101 (with new formulation) and u-ce767 for simulations with TDQ10 also available through MOSRS.Most biological rates depend on the rate of respiration. Temperature variation is typically considered the main driver of daily plant respiration rates, assuming a constant daily respiration rate at a set temperature. Here, we show empirical data from 31 species from temperate and tropical biomes to demonstrate that the rate of plant respiration at a constant temperature decreases monotonically with time through the night, on average by 25% after 8 h of darkness. Temperature controls less than half of the total nocturnal variation in respiration. A new universal formulation is developed to model and understand nocturnal plant respiration, combining the nocturnal decrease in the rate of plant respiration at constant temperature with the decrease in plant respiration according to the temperature sensitivity. Application of the new formulation shows a global reduction of 4.5 -6 % in plant respiration and an increase of 7-10% in net primary production for the present-day.Natural Environment Research Council (NERC)University of ExeterMet Office Hadley Centre Climate Programm

Distinct cardioprotective mechanisms of immediate, early and delayed ischaemic postconditioning

Cardioprotection against ischaemia/reperfusion injury in mice can be achieved by delayed ischaemic postconditioning (IPost) applied as late as 30 min after the onset of reperfusion. We determined the efficacy of delayed IPost in a rat model of myocardial infarction (MI) and investigated potential underlying mechanisms of this phenomenon. Rats were subjected to 20, 30 or 45 min of coronary artery occlusion followed by 120 min of reperfusion (I/R). Immediate and early IPost included six cycles of I/R (10/10 s) applied 10 s or 10 min after reperfusion onset. In the second series of experiments, the rats were subjected to 30 min of coronary occlusion followed by IPost applied 10 s, 10, 30, 45 or 60 min after the onset of reperfusion. Immediate and early IPost (applied 10 s or 10 min of reperfusion) established cardioprotection only when applied after a period of myocardial ischaemia lasting 30 min. Delayed IPost applied after 30 or 45 min of reperfusion reduced infarct sizes by 36 and 41 %, respectively (both P < 0.01). IPost applied 60 min after reperfusion onset was ineffective. Inhibition of RISK pathway (administration of ERK1/2 inhibitor PD-98059 or PI3K inhibitor LY-294002) abolished cardioprotection established by immediate IPost but had no effect on cardioprotection conferred by early IPost. Blockade of SAFE pathway using JAK/STAT inhibitor AG490 had no effect on the immediate or early IPost cardioprotection. Blockade of mitochondrial KATP (mitoKATP) channels (with 5-Hydroxydecanoate) abolished cardioprotection achieved by immediate and early IPost, but had no effect on cardioprotection when IPost was applied 30 or 45 min into the reperfusion period. Immediate IPost increased phosphorylation of PI3K-AKT and ERK1/2. Early or delayed IPost had no effect on phosphorylation of PI3K-AKT, ERK1/2 or STAT3. These data show that in the rat model, delayed IPost confers significant cardioprotection even if applied 45 min after onset of reperfusion. Cardioprotection induced by immediate and early postconditioning involves recruitment of RISK pathway and/or mitoKATP channels, while delayed postconditioning appears to rely on a different mechanism