Oxidative phosphorylation efficiency, proton conductance and reactive oxygen species production of liver mitochondria correlates with body mass in frogs

ody size is a central biological parameter affecting most biological processes (especially energetics) and mitochondria is a key organelle controlling metabolism and is also the cell's main source of chemical energy. However, the link between body size and mitochondrial function is still unclear, especially in ectotherms. In this study, we investigated several parameters of mitochondrial bioenergetics in the liver of three closely related species of frogs (the common frog Rana temporaria, the marsh frog Pelophylax ridibundus and the bull frog Lithobates catesbeiana). These particular species were chosen due to their differences in adult body mass. We found that the mitochondrial coupling efficiency was markedly increased with animal size, which lead to a higher ATP production (+70%) in the larger frogs (L. catesbeiana) compared to the smaller frogs (R. temporaria). This was essentially driven by a strong negative dependence of mitochondrial proton conductance on body mass. Liver mitochondria from the larger frogs (L. catesbeiana) displayed 50% of the proton conductance of mitochondria from the smaller frogs (R. temporaria). Contrary to our prediction, the low mitochondrial proton conductance measured in L. catesbeiana was not associated with higher radical oxygen species production. Instead, liver mitochondria from the larger individuals produced significantly lower radical oxygen species than those from the smaller frogs. Collectively, the data shows that key bioenergetics parameters of mitochondria (proton leak, ATP production efficiency and radical oxygen species production) are correlated with body mass in frogs. This research expands our understanding of the relationship between mitochondrial function and the evolution of allometric scaling in ectotherms

3D models related to the publication: “Molar wear in house mice: insight into diet preferences at an ecological time scale?”

This contribution contains 3D models of upper molar rows of house mice (Mus musculus domesticus) belonging to Western European commensal and Sub-Antarctic feral populations. These two groups are characterized by different patterns of wear and alignment of the three molars along the row, related to contrasted masticatory demand in relation with their diet. These models are analyzed in the following publication: Renaud et al 2023, “Molar wear in house mice, insight into diet preferences at an ecological time scale?”, https://doi.org/10.1093/biolinnean/blad09

Characterization of High-Fat, Diet-Induced, Non-alcoholic Steatohepatitis with Fibrosis in Rats

An ideal animal model is necessary for a clear understanding of the etiology, pathogenesis, and mechanisms of human non-alcoholic steatohepatitis (NASH) and for facilitating the design of effective therapy for this condition. We aimed to establish a rat model of NASH with fibrosis by using a high-fat diet (HFD). Male Sprague–Dawley (SD) rats were fed a HFD consisting of 88 g normal diet, 10 g lard oil, and 2 g cholesterol. Control rats were fed normal diet. Rats were killed at 4, 8, 12, 16, 24, 36, and 48 weeks after HFD exposure. Body weight, liver weight, and epididymal fat weight were measured. Serum levels of fasting glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), free fatty acids (FFA), insulin, and tumor necrosis factor-alpha (TNF-α) were determined. Hepatic histology was examined by H&E stain. Hepatic fibrosis was assessed by VG stain and immunohistochemical staining for transforming growth factor beta 1 (TGF-β1), and alpha-smooth-muscle actin (α-SMA). The liver weight and liver index increased from week 4, when hepatic steatosis was also observed. By week 8, the body weight and epididymal fat weight started increasing, which was associated with increased serum levels of FFA, cholesterol, and TNF-α, as well as development of simple fatty liver. The serum ALT level increased from week 12. Steatohepatitis occurred from weeks 12 through 48. Apparent hepatic perisinosodial fibrosis did not occur until week 24, and progressed from week 36 to 48 with insulin resistance. Therefore, this novel model may be potentially useful in NASH study

Intraoperative radiotherapy (IORT) is an option for patients with localized breast recurrences after previous external-beam radiotherapy

<p>Abstract</p> <p>Background</p> <p>For patients suffering of recurrent breast cancer within the irradiated breast, generally mastectomy is recommended. The normal tissue tolerance does not permit a second full-dose course of radiotherapy to the entire breast after a second breast-conserving surgery (BCS). A novel option is to treat these patients with partial breast irradiation (PBI). This approach is based on the hypothesis that re-irradiation of a limited volume will be effective and result in an acceptable frequency of side effects. The following report presents a single center experience with intraoperative radiotherapy (IORT) during excision of recurrent breast cancer in the previously irradiated breast.</p> <p>Methods</p> <p>Between 4/02 and 11/06, 15 patients were treated for in-breast recurrences at a median of 10 years (3–25) after previous EBRT (10 recurrences in the initial tumor bed, 3 elsewhere in-breast failures, 2 invasive recurrences after previous DCIS). Additional 2 patients were selected for IORT with new primary breast cancer after previous partial breast EBRT for treatment of Hodgkin's disease. IORT with a single dose of 14.7 – 20 Gy 50 kV X-rays at the applicator surface was delivered with the Intrabeam™-device (Carl Zeiss, Oberkochen, Germany).</p> <p>Results</p> <p>After a median follow-up of 26 months (1–60), no local recurrence occurred. 14 out of 17 patients are alive and free of disease progression. Two patients are alive with distant metastases. One patient died 26 months after BCS/IORT due to pulmonary metastases diagnosed 19 months after BCS/IORT. Acute toxicity after IORT was mild with no Grade 3/4 toxicities and cosmetic outcome showed excellent/good/fair results in 7/7/3 cases.</p> <p>Conclusion</p> <p>IORT for recurrent breast cancer using low energy X-rays is a valuable option for patients with recurrent breast cancer after previous radiotherapy.</p

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

Photosynthetic and morphological traits control aquatic plant distribution according to light stress

International audienceThe eutrophication of aquatic systems resulting from human activities frequently leads to phytoplankton blooms, which decrease water transparency and therefore limit light availability for aquatic plants. However, several submerged macrophytes are able to grow despite the light competition pressure exerted by phytoplankton. Photosynthetic performance and plant morphology may be key traits allowing plant species to tolerate phytoplankton-induced light limitation in eutrophic systems. The aim of this study was to explore how morphological and photosynthetic traits allow submerged macrophytes to withstand the stress induced by decreased light in eutrophic systems. Morphological and photosynthetic traits were measured in 7 species of submerged macrophytes collected from mesotrophic to hypertrophic shallow lakes (Dombes, Ain, France). Then, we determined whether these traits were related to species occurrence in lakes according to depth and water turbidity. This study highlighted 2 strategies potentially resulting in a trade-off between morphological and photosynthetic traits. The first strategy was tolerance to reduced light and was characterized by a higher investment in leaf area and photosynthetic efficiency (initial slope of photosynthetic activity measured at low light intensities), allowing plants to use low amounts of light energy. The second strategy was to avoid the regions of reduced light and was characterized by a greater investment in vertical growth and maximum photosynthesis at high light intensities. The morphological and physiological traits favoured in turbid lakes corresponded to the avoidance strategy with a low compensation point, allowing plants to grow to the photic zone to reach the water areas where light is at a maximum. Small species exhibiting a light stress tolerance strategy may be maintained in turbid lakes subjected to disturbances, offering a window of opportunity for successful recruitment and reproduction

Consequences of electroshock-induced narcosis in fish muscle: from mitochondria to swim performance

International audienceAdult zebrafish Danio rerio were exposed to an electric shock of 3 V and 1A for 5 s delivered by field backpack electrofishing gear, to induce a taxis followed by a narcosis. The effect of such elec- tric shock was investigated on both the individual performances (swimming capacities and costs of transport) and at cellular and mitochondrial levels (oxygen consumption and oxidative balance). The observed survival rate was very high (96·8%) independent of swimming speed (up to 10 body length s−1). The results showed no effect of the treatment on the metabolism and cost of transport of the fish. Nor did the electroshock trigger any changes on muscular oxidative balance and bioenergetics even if red muscle fibres were more oxidative than white muscle. Phosphorylating respiration rates rose between (mean 1 s.e.) 11·16 ± 1·36 pmol O2 s−1 mg−1 and 15·63 ± 1·60 pmol O2 s−1 mg−1 for red muscle fibres whereas phosphorylating respiration rates only reached 8·73 ± 1·27 pmol O2 s−1 mg−1 in white muscle. Such an absence of detectable physiological consequences after electro-induced nar- cosis both at organismal and cellular scales indicate that this capture method has no apparent negative post-shock performance under the conditions of this study

Oxidative DNA damage and antioxidant defenses in the European common lizard (Lacerta vivipara) in supercooled and frozen states

The European common lizard (Lacerta vivipara) tolerates long periods at sub-zero temperatures, either in the supercooled or the frozen state. Both physiological conditions limit oxygen availability to tissues, compelling lizards to cope with potential oxidative stress during the transition from ischemic/anoxic conditions to reperfusion with aerated blood during recovery. To determine whether antioxidant defenses are implicated in the survival of lizards when facing sub-zero temperatures, we monitored the activities of antioxidant enzymes and oxidative stress either during supercooling or during freezing exposures (20 h at -2.5 degrees C) and 24 h after thawing in two organs of lizards--muscle and liver. Supercooling induced a significant increase in the total SOD and GPx activity in muscle (by 67 and 157%, respectively), but freezing had almost no effect on enzyme activity, either in muscle or in liver. By contrast, thawed lizards exhibited higher GPx activity in both organs (a 133% increase in muscle and 59% increase in liver) and a significant decrease in liver catalase activity (a 47% difference between control and thawed lizards). These data show that supercooling (but not freezing) triggers activation of the antioxidant system and this may be in anticipation of the overgeneration of oxyradicals when the temperature increases (while thawing or at the end of supercooling). Oxidative stress was assessed from the content of 8-oxodGuo and the different DNA adducts resulting from lipid peroxidation, but it was unaltered whatever the physiological state of the lizards, thus demonstrating the efficiency of the antioxidant system that has been developed by this species. Overall, antioxidant defenses appear to be part of the adaptive machinery for reptilian tolerance to sub-zero temperatures