Low Energy Status Research Articles

Importance of Intracellular Energy Status on High-Hydrostatic-Pressure Inactivation of sake Yeast Saccharomyces cerevisiae.

The HHP inactivation behaviors of Niigata sake yeast Saccharomyces cerevisiae strain S9arg and its aerobic respiratory-deficient mutant strains were investigated after cultivating them in a YPD media containing 2% to 15% glucose, as well as in moromi mash, in a laboratory-scale sake brewing process. The piezotolerance of strain S9arg, shown after cultivation in a YPD medium containing 2% glucose, decreased to become piezosensitive with increasing glucose concentrations in YPD media. In contrast, the piezosensitivity of a mutant strain UV1, shown after cultivation in the YPD medium containing 2% glucose, decreased to become piezotolerant with increasing glucose concentrations in the YPD medium. The intracellular ATP concentrations were analyzed for an S. cerevisiae strain with intact aerobic respiratory ability, as well as for strain UV1. The higher concentration of ATP after cultivation suggested a higher energy status and may be closely related to higher piezotolerance for the yeast strains. The decreased piezotolerance of strain S9arg observed after a laboratory-scale sake brewing test may be due to a lower energy status resulting from a high glucose concentration in moromi mash during the early period of brewing, as well as a lower aeration efficiency during the brewing process, compared with cultivation in a YPD medium containing 2% glucose.

Identification and characterization of CXCL13 producers in bone tissue

Abstract The bone serves as a reservoir for several immune cell subsets in response to the low-energy status such as fasting. We previously demonstrated that naïve B cells transiently migrate from Peyer’s patches to the bone marrow during fasting in mice. This B-cell dynamics is attributed to upregulation of CXCL13 in the bone during fasting. However, CXCL13 producers in the bone remain to be determined. We observed that lineage-negative population from the bone is responsible for Cxcl13 expression. To further clarify the CXCL13 producers, we performed single-cell RNA-sequencing of bone linage-negative cells from Ad libitum-fed mice and fasting mice. UMAP analysis manifested that the numbers of fibroblasts and multipotent stem cells (MSCs) were increased in the fasting group. Interestingly, Cxcl13-producing cells were identified as osteogenic-MSCs characterized by expressions of Sca-1 (immature cells marker), Sema3c, and Dcn (osteogenic cells maker). This population also expressed an inflammatory cytokine Il6. Meanwhile, mature osteoblasts and chondrocytes expressed neither Cxcl13 nor Il6. Furthermore, co-culture with the plasma from fasting mice upregulated CXCL13 expression in osteogenic-MSCs in vitro, suggesting that a soluble factor(s) in the circulation induces CXCL13. Taken together, osteogenic-MSCs in the bone may sense nutritional status and produce CXCL13 to regulate naïve B-cell dynamics along the gut-bone axis. The pathophysiological role of CXCL13-producing osteogenic-MSCs is currently under investigation. none

High Expression of ALTERNATIVE OXIDASE 2 in Latent Axillary Buds Suggests Its Key Role in Quiescence Maintenance in Rosebush.

Most vegetative axes remain quiescent as dormant axillary buds until metabolic and hormonal signals, driven by environmental changes, trigger bud outgrowth. While the resumption of growth activity is well documented, the establishment and maintenance of quiescence is comparatively poorly understood, despite its major importance in the adaptation of plants to the seasonal cycle or in the establishment of their shape. Here, using the rosebush Rosa hybrida 'Radrazz' as a plant model, we highlighted that the quiescent state was the consequence of an internal and active energy control of buds, under the influence of hormonal factors previously identified in the bud outgrowth process. We found that the quiescent state in the non-growing vegetative axis of dormant axillary buds displayed a low energy state along with a high expression of the ALTERNATIVE OXIDASE 2 (AOX2) and the accumulation of the corresponding protein. Conversely, AOX2 expression and protein amount strongly decreased during bud burst as energy status shifted to a high state, allowing growth. Since AOX2 can deviate electrons from the cytochrome pathway in the mitochondrial respiratory chain, it could drastically reduce the formation of ATP, which would result in a low energy status unfavorable for growth activities. We provide evidence that the presence/absence of AOX2 in quiescent/growing vegetative axes of buds was under hormonal control and thus may constitute the mechanistic basis of both quiescence and sink strength manifestation, two important aspects of budbreak.

Low Energy Status under Methionine Restriction Is Essentially Independent of Proliferation or Cell Contact Inhibition.

Nonlimited proliferation is one of the most striking features of neoplastic cells. The basis of cell division is the sufficient presence of mass (amino acids) and energy (ATP and NADH). A sophisticated intracellular network permanently measures the mass and energy levels. Thus, in vivo restrictions in the form of amino acid, protein, or caloric restrictions strongly affect absolute lifespan and age-associated diseases such as cancer. The induction of permanent low energy metabolism (LEM) is essential in this process. The murine cell line L929 responds to methionine restriction (MetR) for a short time period with LEM at the metabolic level defined by a characteristic fingerprint consisting of the molecules acetoacetate, creatine, spermidine, GSSG, UDP-glucose, pantothenate, and ATP. Here, we used mass spectrometry (LC/MS) to investigate the influence of proliferation and contact inhibition on the energy status of cells. Interestingly, the energy status was essentially independent of proliferation or contact inhibition. LC/MS analyses showed that in full medium, the cells maintain active and energetic metabolism for optional proliferation. In contrast, MetR induced LEM independently of proliferation or contact inhibition. These results are important for cell behaviour under MetR and for the optional application of restrictions in cancer therapy.

Glutamine, glutamate, and aspartate differently modulate energy homeostasis of small intestine under normal or low energy status in piglets.

Weaning stress may cause reduced energy intake for maintenance of mucosal structure. Gln, Glu, and Asp are major energy sources for the small intestine. This study investigated whether Gln, Glu, and Asp improve the intestinal morphology via regulating the energy metabolism in weaning piglets. A total of 198 weaned piglets were assigned to 3 treatments: Control (Basal diet + 1.59% L-Ala); T1 (Basal diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp); T2 (Low energy diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp). Jejunum and ileum were obtained on d 5 or 21 post-weaning. T1 enhanced growth performance. T1 and T2 treatments improved small intestinal morphology by increasing villus height, goblet cell number and decreasing crypt depth. Days post-weaning affected the efficacy of T2, but not T1, on energy metabolism. At normal energy supplementation, Gln, Glu, and Asp restored small intestinal energy homeostasis via replenishing the Krebs' cycle and down-regulating the AMPK (adenosine monophosphate activated protein kinase) pathway. As these are not sufficient to maintain the intestinal energy-balance of piglets fed with a low energy diet on d 5 post-weaning, the AMPK, glycolysis, beta-oxidation, and mitochondrial biogenesis are activated to meet the high energy demand of enterocytes. These data indicated that Gln, Glu, and Asp could restore the energy homeostasis of intestinal mucosa of weaning piglets under normal energy fed. Low energy feeding may increase the susceptibility of piglets to stress, which may decrease the efficacy of Gln, Glu, and Asp on the restoration of energy balance. These findings provide new information on nutritional intervention for insufficient energy intake in weaning piglets.

Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors.

Simple SummaryChildhood cancer survivors (CCS) display a higher risk of developing second malignant tumors and chronic diseases compared with aged-matched controls because of chemo/radiotherapy. This early frailty seems associated with accelerated cell aging, a process correlated with altered mitochondrial energy production. Therefore, this work aims to shed light on the mechanisms involved in chemo/radiotherapy-induced early aging, morbidities, and the risk of developing second tumors in CCS through a biochemical and molecular approach. The identification of crucial mechanisms involved in the CCS chemo/radiotherapy-related pathological conditions will allow identifying therapeutic targets to develop appropriate risk-based care and interventions, minimize morbidities, and maximize the quality of life in the cancer survivor population. Survival rates of childhood cancer patients have improved over the past four decades, although cancer treatments increase the risk of developing chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in childhood cancer survivors (CCS). Biochemical, proteomic, and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, the results being compared with those obtained on MNCs of 154 healthy subjects. CCS-MNCs showed inefficient oxidative phosphorylation associated with low energy status, and increased lipid peroxidation and lactate fermentation compared with age-matched normal controls. According to a mathematical model based on biochemical parameters, CCS-MNCs showed significantly higher metabolic ages than their real ages. The dysfunctional metabolism of CCS-MNCs is associated with lower expression levels of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-alpha, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. In conclusion, our study identified some biochemical and molecular alterations possibly contributing to the pathophysiology of aging and metabolic deficiencies in CCS. These results identify new targets for pharmacological interventions to restore mitochondrial function, slowing down the aging-associated pathologies in CCS.

Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function.

The AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis. Although much has been learned on how low energy status and glucose starvation activate AMPK, how AMPK activity is properly controlled in vivo is still poorly understood. Here we report that UHRF1, an epigenetic regulator highly expressed in proliferating and cancer cells, interacts with AMPK and serves to suppress AMPK activity under both basal and stressed conditions. As a nuclear protein, UHRF1 promotes AMPK nuclear retention and strongly suppresses nuclear AMPK activity toward substrates H2B and EZH2. Importantly, we demonstrate that UHRF1 also robustly inhibits AMPK activity in the cytoplasm compartment, most likely as a consequence of AMPK nucleocytoplasmic shuttling. Mechanistically, we found that UHRF1 has no obvious effect on AMPK activation by upstream kinases LKB1 and CAMKK2 but inhibits AMPK activity by acting as a bridging factor targeting phosphatase PP2A to dephosphorylate AMPK. Hepatic overexpression of UHRF1 showed profound effects on glucose and lipid metabolism in wild-type mice but not in those with the liver-specific knockout of AMPKα1/α2, whereas knockdown of UHRF1 in adipose tissue led to AMPK activation and reduced sizes of adipocytes and lipogenic activity, highlighting the physiological significance of this regulation in glucose and lipid metabolism. Thus, our study identifies UHRF1 as a novel AMPK gate-keeper with critical roles in cellular metabolism.

Dynamical Behavior Analysis of a Time-Delay SIRS-L Model in Rechargeable Wireless Sensor Networks

The traditional SIRS virus propagation model is used to analyze the malware propagation behavior of wireless rechargeable sensor networks (WRSNs) by adding a new concept: the low-energy status nodes. The SIRS-L model has been developed in this article. Furthermore, the influence of time delay during the charging behavior of the low-energy status nodes needs to be considered. Hopf bifurcation is studied by discussing the time delay that is chosen as the bifurcation parameter. Finally, the properties of the Hopf bifurcation are explored by applying the normal form theory and the center manifold theorem.

Inhibition of Low Oxygen on Aroma Biosynthesis of 'Benihoppe' Strawberry Fruit Accompanied by Low Energy Status During Storage and Subsequent Shelf-Life

Inhibition of Low Oxygen on Aroma Biosynthesis of 'Benihoppe' Strawberry Fruit Accompanied by Low Energy Status During Storage and Subsequent Shelf-Life

Overcoming Energetic Barriers in Acetogenic C1 Conversion.

Currently one of the biggest challenges for society is to combat global warming. A solution to this global threat is the implementation of a CO2-based bioeconomy and a H2-based bioenergy economy. Anaerobic lithotrophic bacteria such as the acetogenic bacteria are key players in the global carbon and H2 cycle and thus prime candidates as driving forces in a H2- and CO2-bioeconomy. Naturally, they convert two molecules of CO2 via the Wood-Ljungdahl pathway (WLP) to one molecule of acetyl-CoA which can be converted to different C2-products (acetate or ethanol) or elongated to C4 (butyrate) or C5-products (caproate). Since there is no net ATP generation from acetate formation, an electron-transport phosphorylation (ETP) module is hooked up to the WLP. ETP provides the cell with additional ATP, but the ATP gain is very low, only a fraction of an ATP per mol of acetate. Since acetogens live at the thermodynamic edge of life, metabolic engineering to obtain high-value products is currently limited by the low energy status of the cells that allows for the production of only a few compounds with rather low specificity. To set the stage for acetogens as production platforms for a wide range of bioproducts from CO2, the energetic barriers have to be overcome. This review summarizes the pathway, the energetics of the pathway and describes ways to overcome energetic barriers in acetogenic C1 conversion.

Normal Structure and Function of Endothecium Chloroplasts Maintained by ZmMs33-Mediated Lipid Biosynthesis in Tapetal Cells Are Critical for Anther Development in Maize

Genic male sterility (GMS) is critical for heterosis utilization and hybrid seed production. Although GMS mutants and genes have been studied extensively in plants, it has remained unclear whether chloroplast-associated photosynthetic and metabolic activities are involved in the regulation of anther development. In this study, we characterized the function of ZmMs33/ZmGPAT6, which encodes a member of the glycerol-3-phosphate acyltransferase (GPAT) family that catalyzes the first step of the glycerolipid synthetic pathway. We found that normal structure and function of endothecium (En) chloroplasts maintained by ZmMs33-mediated lipid biosynthesis in tapetal cells are crucial for maize anther development. ZmMs33 is expressed mainly in the tapetum at early anther developmental stages and critical for cell proliferation and expansion at late stages. Chloroplasts in En cells of wild-type anthers function as starch storage sites before stage 10 but as photosynthetic factories since stage 10 to enable starch metabolism and carbohydrate supply. Loss of ZmMs33 function inhibits the biosynthesis of glycolipids and phospholipids, which are major components of En chloroplast membranes, and disrupts the development and function of En chloroplasts, resulting in the formation of abnormal En chloroplasts containing numerous starch granules. Further analyses reveal that starch synthesis during the day and starch degradation at night are greatly suppressed in the mutant anthers, leading to carbon starvation and low energy status, as evidenced by low trehalose-6-phosphate content and a reduced ATP/AMP ratio. The energy sensor and inducer of autophagy, SnRK1, was activated to induce early and excessive autophagy, premature PCD, and metabolic reprogramming in tapetal cells, finally arresting the elongation and development of mutant anthers. Taken together, our results not only show that ZmMs33 is required for normal structure and function of En chloroplasts but also reveal that starch metabolism and photosynthetic activities of En chloroplasts at different developmental stages are essential for normal anther development. These findings provide novel insights for understanding how lipid biosynthesis in the tapetum, the structure and function of En chloroplasts, and energy and substance metabolism are coordinated to maintain maize anther development.

Indirect effect of different dietary protein to energy ratio of bait fish mori diets on growth performance, body composition, nitrogen metabolism and relative AMPK & mTOR pathway gene expression of Chinese perch

Chinese perch (Siniperca chuatsi) is an important economic freshwater carnivorous fish. Commonly feeds on other live fish or bait fish, and accept an artificial diet only after standard training. The feeding habit of Chinese perch caused high aquaculture costs and consumer prices. However, only a few studies are conducted on Chinese perch live feed (bait fish) or live feed (mori) feeds. Therefore, the present study was conducted to investigate the effect of live feed (mori) and live feed (mori) feeds protein to energy ratio on Chinese perch. Three Iso-energetic diets (16 kJ/g) with graded levels of P/E ratios (19.79, 22.19 and 24.46 mg protein/kJ) each with a protein level of 28.18 %, 31.36 %, and 33.91 % (named A, B, and C) were formulated. Two separate experimental tanks systems were used. In one tanks system, a total of 90 kg live bait fish C. mrigala were distributed into three groups (triplicate tanks (1000 L) for each group) and fed with respective P/E ratio diets. In another tanks system, a total of 270 Chinese perch (30 fish/tank) were divided into three groups (triplicate tanks for each group), distributed into 9 (1000-L) fiberglass tanks and fed with assigned live bait fish at 4 % fish wet body weight, twice a day for 8 weeks. The results showed that P/E ratio in bait fish diets significantly affected bait fish and Chinese perch growth performance, feed utilization, body composition, nitrogen metabolism, protein synthesis, and energy homeostasis. Bait fish in Group A showed significantly lower weight gain (WG), specific growth rate (SGR), and higher Viscerosomatic index (VSI) and Hepatosomatic index (HSI) as compared to other groups. Correspondingly, bait fish in Group A showed significantly low whole-body crude protein and high lipid contents as compared to other groups. Similarly, Chinese perch in Group A, showed significantly lower WG, SGR, protein efficiency ratio (PER) and highest feed intake (FI), feed conversion ratio (FCR), VSI, HSI, and Intraperitoneal fat (IPF), as compared to other groups. Furthermore, Chinese perch in Group A, showed significantly lower whole body and muscle crude protein, and higher lipid contents as compared to other groups. Similarly, the nitrogen metabolism enzyme activities (ALT, AST, GDH, AMPD) and gene expression of GDH and AMPD in Group A of Chinese perch, were significantly lower than other groups. Moreover, the AMPK and mTOR pathways gene expression showed a low energy status and protein catabolism in Group A of Chinese perch as compared to other groups. From our results, we conclude that the P/E ratio in bait fish diet significantly affected bait fish and Chinese perch growth performance and nutrients metabolism.

1 Assessing the energy status of porcine embryos by means of biodynamic imaging

Assisted reproductive technologies are powerful tools for enhancing production in livestock or treating infertility in humans. Unfortunately, the success rate of the technologies is rather low. A major reason for the poor efficiency is the lack of methods to reliably assess the developmental potential of the embryos before transfer into recipients. Therefore, a noninvasive method to ensure the selection of only the best embryos for transfer would be highly desirable. Biodynamic imaging is a compelling new microscopy that uses intracellular Doppler spectroscopy to perform label-free, noninvasive optical measurements of cellular fitness. The aim of this study was to investigate whether biodynamic imaging can be used to assess the energy status of the embryos, which may be indicative of their viability. Porcine oocytes matured invitro were parthenogenetically activated by an electrical pulse and cultured for 2 days. The parthenotes were then divided into two groups, and approximately half of them were incubated for an additional 2 days in the presence of 20mM sodium azide. Sodium azide is an inhibitor of oxidative phosphorylation and is known to block ATP production. The rest of the embryos were cultured without sodium azide and used as a control to indicate normal ATP levels. At the end of the culture period embryos that reached the 8- to 16-cell stage were evaluated by our biodynamic imaging system to assess their energy status, after which they were lysed and their ATP contents were determined by means of a bioluminescence assay. A total of 68 embryos (32 treated with the inhibitor and 36 control) were evaluated. The ATP content analysis showed that the control embryos had significantly more ATP than those treated with sodium azide as determined by Student's t-test (5.04±1.07 vs. 1.31±0.57; P<0.05). A correlative study was then completed where biodynamic biomarkers were used to classify embryos to estimate the ability of biodynamic imaging to identify embryos with high or low energy status. A set of 13 biomarkers representing each embryo as a feature vector was used to train a classifier. We found that the cross-validated classifier had a sensitivity and specificity of ~80%. In addition, a receiver-operator curve constructed by varying the ATP threshold of the independent bioluminescence assay had an area-under-the-curve of 0.81. These results indicate that biodynamic imaging is able to determine the energy status of the embryos noninvasively and has great potential in the assessment of embryo viability.

Loss of BRUCE reduces cellular energy level and induces autophagy by driving activation of the AMPK-ULK1 autophagic initiating axis.

Autophagy is an intracellular catabolic system. It delivers cellular components to lysosomes for degradation and supplies nutrients that promote cell survival under stress conditions. Although much is known regarding starvation-induced autophagy, the regulation of autophagy by cellular energy level is less clear. BRUCE is an ubiquitin conjugase and ligase with multi-functionality. It has been reported that depletion of BRUCE inhibits starvation-induced autophagy by blockage of the fusion step. Herein we report a new function for BRUCE in the dual regulation of autophagy and cellular energy. Depletion of BRUCE alone (without starvation) in human osteosarcoma U2OS cells elevated autophagic activity as indicted by the increased LC3B-II protein and its autophagic puncta as well as further increase of both by chloroquine treatment. Such elevation results from enhanced induction of autophagy since the numbers of both autophagosomes and autolysosomes were increased, and recruitment of ATG16L onto the initiating membrane structure phagophores was increased. This concept is further supported by elevated lysosomal enzyme activities. In contrast to starvation-induced autophagy, BRUCE depletion did not block fusion of autophagosomes with lysosomes as indicated by increased lysosomal cleavage of the GFP-LC3 fusion protein. Mechanistically, BRUCE depletion lowered the cellular energy level as indicated by both a higher ratio of AMP/ATP and the subsequent activation of the cellular energy sensor AMPK (pThr-172). The lower energy status co-occurred with AMPK-specific phosphorylation and activation of the autophagy initiating kinase ULK1 (pSer-555). Interestingly, the higher autophagic activity by BRUCE depletion is coupled with enhanced cisplatin resistance in human ovarian cancer PEO4 cells. Taken together, BRUCE depletion promotes induction of autophagy by lowering cellular energy and activating the AMPK-ULK1-autophagy axis, which could contribute to ovarian cancer chemo-resistance. This study establishes a BRUCE-AMPK-ULK1 axis in the regulation of energy metabolism and autophagy, as well as provides insights into cancer chemo-resistance.

Settings The Role of Low Blood Glucose Level of Mothers with Severe Preeclampsia in Fetal Growth Restriction: a Mini-Study

Background. The number of patients with severe preeclampsia continues to increase worldwide. Blood glucose is significantly decreased in severe preeclampsia patients, starting at the sudden onset of high blood pressure. This depicts the state of low placental energy status in preeclampsia patients with intrauterine growth restriction (IUGR), due to either glycolysis or ischemia disorders resulting from decreased maternal placental blood flow. Aim. To observe the relationship between mother’s random blood glucose level with fetal growth restriction complications during acute onset of severe preeclampsia. Methods. A cross-sectional study, random sampling involving twenty-one pregnant women with severe preeclampsia who underwent cesarean section at Permata Bunda Hospital, Malang, Indonesia. Data were taken from medical records, which included: mother’s random blood glucose, blood pressure, proteinuria, and complete blood count. Fetal data includes body weight and length. The data were obtained at the subjects’ initial admission in the emergency room during the acute phase of the preeclampsia. Result. Maternal blood glucose had a negative and significant relationship with systolic blood pressure (r = -0.843, p < 0.0001) and with newborn body weight (r = 0.465, p = 0.034) in the acute onset of severe preeclampsia. Conclusion. The blood glucose level of patients at the acute onset of preeclampsia is inversely correlated with systolic blood pressure. The blood glucose level is also correlated with fetal weight. However, due to the chronic nature of IUGR, future studies should analyze the relationship between blood glucose, blood pressure, and fetal growth through multiple stages of pregnancy

Evaluation of electrofishing adopted by Egyptian fish farmers

Upon the demand of a private fish farmer, this study was applied to assess the influence of electro-fishing adopted by some Egyptian fish farmers on the fish welfare and quality. Therefore, a total of 60 Nile tilapia (Oreochromis niloticus) were sampled; from which 30 were stunned by electrofishing and the remainders by conventional fishing. Biochemical analysis (oxidative stress and energy status), meat quality based on total bacterial count (TBC) and pathological alterations were assessed. Biochemical analysis in both liver and muscle tissue showed that electro-stunned fish exhibited low oxidative stress and high energy status. Meat of electro-stunned fish showed an acceptable limit of TBC (Max. limit 107) while the histopathological examination revealed various tissue reactions. These were in the form of congestion in branchial, hepatoportal, brain and splenic blood vessels with edema in brain and pericardium. In addition, there was mild inflammatory reaction together with the presence of eosinophilic granular cells and perivascular melanophores aggregation in both branchial and muscular tissue.As a consequence of this work, we recommend the use of electrofishing method in Egypt after modifying the current tool by reducing applied voltage. Further studies and more optimization are needed to cover both fish farmers and animal welfare issues, and take in consideration the human safety precautions.

Impact of sow energy status during farrowing on farrowing kinetics, frequency of stillborn piglets, and farrowing assistance.

Farrowing duration is rather long in sows most likely due to selection for large litters, and we hypothesized that prolonged farrowings would compromise sow energy status during farrowing and in turn the farrowing process. Two studies were performed as follows: 1) to evaluate whether sow energy status during farrowing compromise the farrowing kinetics (FK, i.e., farrowing duration and birth intervals) and 2) to study the underlying mechanisms potentially affecting stillbirth rate and farrowing assistance. In study-1, parameters affecting FK were characterized based on data from a total of 166 farrowings from 7 feeding trials focused on sow colostrum production. The data were screened for associations with FK using the CORR procedure of SAS. Traits that were correlated with the FK at P < 0.05 were included in a multivariate regression model. Time since last meal until the onset of farrowing greatly affected the farrowing duration (r = 0.76; n = 166; P < 0.001) and a broken-line model was fitted to describe that relationship. According to the model, farrowing duration was constant (3.8 ± 1.5 h) if the farrowing started before the breakpoint (3.13 ± 0.34 h after the last meal), whereas farrowing duration increased to 9.3 h if the farrowing started 8 h after the last meal. Subsequently, sows were divided into 3 categories based on that trait (≤3, 3 to 6, and >6 h) to evaluate the impact on birth intervals, farrowing assistance, and stillbirth rate. Birth intervals (P < 0.001), odds for farrowing assistance (P < 0.001), and odds for stillbirth (P = 0.02) were low, intermediate, and high when time since last meal was ≤3, 3 to 6, and >6 h, respectively. In study-2, blood samples were collected once or twice each week in late gestation and each hour during farrowing to measure arterial concentrations and uterine extractions of plasma metabolites. Time since last meal was strongly negatively correlated with arterial glucose 1 h after the onset of farrowing (r= -0.96; n = 9; P < 0.001). Glucose appeared to be the key energy metabolite for oxidative metabolism of gravid uterus. In conclusion, the present study strongly suggests that a substantial proportion of sows suffer from low-energy status at the onset farrowing and that this negatively affects the farrowing process. Transferring this knowledge into practice, the results suggest that sows should be fed at least 3 daily meals in late gestation.

Transcriptomic analysis of transgressive segregants revealed the central role of photosynthetic capacity and efficiency in biomass accumulation in sugarcane

Sugarcane is among the most efficient crops in converting solar energy into chemical energy. However, due to its complex genome structure and inheritance, the genetic and molecular basis of biomass yield in sugarcane is still largely unknown. We created an F2 segregating population by crossing S. officinarum and S. spontaneum and evaluated the biomass yield of the F2 individuals. The F2 individuals exhibited clear transgressive segregation in biomass yield. We sequenced transcriptomes of source and sink tissues from 12 selected extreme segregants to explore the molecular basis of high biomass yield for future breeding of high-yielding energy canes. Among the 103,664 assembled unigenes, 10,115 and 728 showed significant differential expression patterns between the two extreme segregating groups in the top visible dewlap leaf and the 9th culm internode, respectively. The most enriched functional categories were photosynthesis and fermentation in the high-biomass and the low-biomass groups, respectively. Our results revealed that high-biomass yield was mainly determined by assimilation of carbon in source tissues. The high-level expression of fermentative genes in the low-biomass group was likely induced by their low-energy status. Group-specific expression alleles which can be applied in the development of new high-yielding energy cane varieties via molecular breeding were identified.

Silica nanoparticles induce cardiotoxicity interfering with energetic status and Ca2+ handling in adult rat cardiomyocytes.

Recent evidence has shown that nanoparticles that have been used to improve or create new functional properties for common products may pose potential risks to human health. Silicon dioxide (SiO2) has emerged as a promising therapy vector for the heart. However, its potential toxicity and mechanisms of damage remain poorly understood. This study provides the first exploration of SiO2-induced toxicity in cultured cardiomyocytes exposed to 7- or 670-nm SiO2 particles. We evaluated the mechanism of cell death in isolated adult cardiomyocytes exposed to 24-h incubation. The SiO2 cell membrane association and internalization were analyzed. SiO2 showed a dose-dependent cytotoxic effect with a half-maximal inhibitory concentration for the 7 nm (99.5 ± 12.4 µg/ml) and 670 nm (>1,500 µg/ml) particles, which indicates size-dependent toxicity. We evaluated cardiomyocyte shortening and intracellular Ca2+ handling, which showed impaired contractility and intracellular Ca2+ transient amplitude during β-adrenergic stimulation in SiO2 treatment. The time to 50% Ca2+ decay increased 39%, and the Ca2+ spark frequency and amplitude decreased by 35 and 21%, respectively, which suggest a reduction in sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity. Moreover, SiO2 treatment depolarized the mitochondrial membrane potential and decreased ATP production by 55%. Notable glutathione depletion and H2O2 generation were also observed. These data indicate that SiO2 increases oxidative stress, which leads to mitochondrial dysfunction and low energy status; these underlie reduced SERCA activity, shortened Ca2+ release, and reduced cell shortening. This mechanism of SiO2 cardiotoxicity potentially plays an important role in the pathophysiology mechanism of heart failure, arrhythmias, and sudden death.NEW & NOTEWORTHY Silica particles are used as novel nanotechnology-based vehicles for diagnostics and therapeutics for the heart. However, their potential hazardous effects remain unknown. Here, the cardiotoxicity of silica nanoparticles in rat myocytes has been described for the first time, showing an impairment of mitochondrial function that interfered directly with Ca2+ handling.

Promotion of glucose utilization by insulin enhances granulosa cell proliferation and developmental competence of porcine oocyte grown in vitro.

In vitro culture of the oocyte granulosa cell complexes (OGCs) from early antral follicles (EAFs) shows granulosa cell (GC) proliferation, but to a lesser extent than that observed in vivo during follicle development. As the number of GCs closely relates to energy sufficiency of the oocytes, enhancement of GC proliferation influences oocyte development. GC proliferation depends on glycolysis and insulin-mediated AKT/mTOR signaling pathway; therefore, addition of culture medium containing insulin and glucose may potentially promote GC proliferation and hence improve oocyte development. In the present study, we assessed the effect of exogenous insulin and glucose concentration on GC proliferation and oocyte energy status as well as developmental abilities of porcine oocytes grown in vitro. In the presence of 5.5 mM of glucose (Low), a comparison of 10 versus 20 μg/ml insulin showed that high insulin enhanced GC proliferation but exhausted glucose from the medium, which resulted in low energy status including lipid and adenosine triphosphate of the oocyte. Whereas, in the presence of 20 μg/ml insulin, medium with 11 mM glucose (High) enhanced GC proliferation and oocyte energy status as well as developmental ability up to the blastocyst stage. Considering that there was no difference in OGCs development observed with medium (10 μg/ml insulin) containing 5.5 versus 11 mM glucose, we concluded that the combination of high insulin and glucose enhanced GC proliferation and energy status of oocytes as well as the developmental ability of the oocytes grown in vitro.