Effects of maternal age and environmental enrichment on learning ability and brain size.

It is well known that maternal age at reproduction affects offspring lifespan and some other fitness-related traits, but it remains understudied whether maternal senescence affects how offspring respond to their environments. Early environment often plays a significant role in the development of an animal's behavioral phenotype. For example, complex environments can promote changes in cognitive ability and brain morphology in young animals. Here, we study whether and how maternal effect senescence influences offspring plasticity in cognition, group behavior, and brain morphology in response to environmental complexity. For this, juvenile 3-spined sticklebacks from young and old mothers (i.e. 1-yr and 2-yr-old) were exposed to different levels of environmental enrichment and complexity (i.e. none, simple, and complex), and their behavior, cognitive ability, and brain size were measured. Exposing fish to enriched conditions improved individual learning ability assessed by a repeated detour-reaching task, increased the size of the whole brain, and decreased aggressive interactions in the shoal. Maternal age did not influence the inhibitory control, learning ability, and group behavioral responses of offspring to the experimental environmental change. However, maternal age affected how some brain regions of offspring changed in response to environmental complexity. In offspring from old mothers, those exposed to the complex environment had larger telencephalons and cerebellums than those who experienced simpler environments. Our results suggest that maternal effect senescence may influence how offspring invest in brain functions related to cognition in response to environmental complexity.

Longan extract suppresses food intake through regulation of POMC/AgRP neuronal activities and endoplasmic reticulum stress in hypothalamus of db/db mice.

Type 2 diabetes mellitus (T2DM) is one of the biggest public health issues worldwide and closely related to development of other chronic diseases such as cardiovascular diseases, cancer and neurodegenerative diseases. Considerable percentage of T2DM patients undergo have suffered from binge eating disorder which exacerbates insulin resistance and metabolic challenges. Longan (Dimocarpus longan L.) and its constituents are reported for their various health benefits. However, it is still unknown whether longan fruit supplementation can ameliorate glucose homeostasis and binge eating disorder found in T2DM. The current study aimed to investigate whether longan fruit extract (LE) supplementation can improve diabetic hyperglycemia through modulation of feeding center located in hypothalamus of db/db T2DM mice. As a result, LE supplementation ameliorated fasting blood glucose levels and reduced excessive epididymal fat accumulation. In addition, LE administration improved glucose tolerance and insulin sensitivity in db/db mice. Especially, LE supplemented mice showed less food consumption which was in line with increase of pro-opiomelanocortin (POMC) neuronal activities and decrease of agouti-related peptide (AgRP) neuronal activities. Furthermore, LE supplementation reduced hypothalamic endoplasmic reticulum (ER) stress which was stimulated in db/db mice. As ER stress is a crucial factor involving in appetite control and glucose homeostasis, the effect of LE supplementation on circulating glucose levels and feeding behavior might be mediated by suppression of hypothalamic ER stress. Collectively, these findings suggest that LE could be a potential nutraceutical for improvement of T2DM as well as patients with satiety issues.

Maternal effect senescence via reduced DNA repair ability in the three-spined stickleback.

Maternal effect senescence, a decline in offspring viability with maternal age, has been documented across diverse animals, but its mechanisms remain largely unknown. Here, we test maternal effect senescence and explore its possible molecular mechanisms in a fish. We compared the levels of maternal mRNA transcripts of DNA repair genes and mtDNA copies in eggs and the levels of DNA damage in somatic and germline tissues between young and old female sticklebacks. We also tested, in an in vitro fertilization experiment, whether maternal age and sperm DNA damage level interactively influence the expression of DNA repair genes in early embryos. Old females transferred less mRNA transcripts of DNA repair genes into their eggs than did young females, but maternal age did not influence egg mtDNA density. Despite a higher level of oxidative DNA damage in the skeletal muscle, old females had a similar level of damage in the gonad to young females, suggesting the prioritization for germline maintenance during ageing. The embryos of both old and young mothers increased the expression of DNA repair genes in response to an increased level of oxidative DNA damage in sperm used for their fertilization. The offspring of old mothers showed higher rates of hatching, morphological deformity and post-hatching mortality and had smaller body size at maturity. These results suggest that maternal effect senescence may be mediated by reduced capacity of eggs to detect and repair DNA damages, especially prior to the embryonic genomic activation.

Inhibition of α-synuclein aggregation by MT101-5 is neuroprotective in mouse models of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, after Alzheimer's disease, and becomes increasingly prevalent with age. α-Synuclein (α-syn) forms the major filamentous component of Lewy bodies, which are pathological hallmarks of α-synucleinopathies such as PD. We evaluated the neuroprotective effects of MT101-5, a standardized herbal formula that consists of an ethanolic extract of Genkwae Flos, Clematidis Radix, and Gastrodiae Rhizoma, against α-synuclein-induced cytotoxicity in vivo. MT101-5 protected against behavioral deficits and loss of dopaminergic neurons in human α-syn-overexpressing transgenic mice after treatment with 30 mg/kg/day for 5 months. We investigated transcriptomic changes within MT101-5 mechanisms of action (MOA) suppressing α-syn aggregation in an α-synuclein preformed fibril (α-syn PFF) mouse model of sporadic PD. We found that inhibition of α-syn fibril formation was associated with changes in transcripts in mitochondrial biogenesis, electron transport, chaperones, and proteasomes following treatment with MT101-5. These results suggest that the mixed herbal formula MT101-5 may be used as a pharmaceutical agent for preventing or improving PD.

Does the match between individual and group behavior matter in shoaling sticklebacks?

In animals living in groups, the social environment is fundamental to shaping the behaviors and life histories of an individual. A mismatch between individual and group behavior patterns may have disadvantages if the individual is incapable of flexibly changing its state in response to the social environment that influences its energy gain and expenditure. We used different social groups of juvenile three-spined sticklebacks (Gasterosteus aculeatus) with experimentally manipulated compositions of individual sociability to study the feedback between individual and group behaviors and to test how the social environment shapes behavior, metabolic rate, and growth. Experimentally created unsociable groups, containing a high proportion of less sociable fish, showed bolder collective behaviors during feeding than did corresponding sociable groups. Fish within groups where the majority of members had a level of sociability similar to their own gained more mass than did those within mismatched groups. Less sociable individuals within sociable groups tended to have a relatively low mass but a high standard metabolic rate. A mismatch between the sociability of an individual and that of the majority of the group in which it is living confers a growth disadvantage probably due to the expression of nonadaptive behaviors that increase energetic costs.

Mitochondrial DNA content in eggs as a maternal effect.

The transmission of detrimental mutations in animal mitochondrial DNA (mtDNA) to the next generation is avoided by a high level of mtDNA content in mature oocytes. Thus, this maternal genetic material has the potential to mediate adaptive maternal effects if mothers change mtDNA level in oocytes in response to their environment or body condition. Here, we show that increased mtDNA abundance in mature oocytes was associated with fast somatic growth during early development but at the cost of increased mortality in three-spined sticklebacks. We also examined whether oocyte mtDNA and sperm DNA damage levels have interacting effects because they can determine the integrity of mitochondrial and nuclear genes in offspring. The level of oxidative DNA damage in sperm negatively affected fertility, but there was no interacting effect of oocyte mtDNA abundance and sperm DNA damage. Oocyte mtDNA level increased towards the end of the breeding season, and the females exposed to warmer temperatures during winter produced eggs with increased mtDNA copies. Our results suggest that oocyte mtDNA level can vary according to the expected energy demands for offspring during embryogenesis and early growth. Thus, mothers can affect offspring development and viability through the context-dependent effects of oocyte mtDNA abundance.

Relationships between male secondary sexual traits, physiological state and offspring viability in the three-spined stickleback.

BACKGROUND: Sexual signals produced by males play a central role in sexual selection, but the relationship between these traits and the quality of the bearer are often ambiguous. Secondary sexual traits may represent genetic quality of the bearer, resulting in positive relationships with physiological state, or may be costly to produce, showing trade-off with physiological state. A number of studies have explored the relationships between secondary sexual traits and other functional traits, but few have studied their fitness consequences. We studied the link between diverse physiological traits and both morphological and behavioural sexual traits and examined how their interplay influences offspring viability in the three-spined stickleback. RESULTS: Male sticklebacks showing nest building and courtship behaviour were smaller than those not investing in reproductive activities. There was no evidence that the expression of red nuptial colouration and the quality of courtship behaviour of males are positively related to their metabolic rates, swim ability, oxidative damage and mtDNA copy number. However, individuals showing larger red nuptial colour areas had higher levels of oxidative DNA damage in their sperm. Male courtship behaviour and aggressiveness, but not red colour area, were good predictors of offspring hatching and survival. CONCLUSIONS: Our results suggest that, in our study population at the southern edge of the species' distribution, sexual colouration of male sticklebacks was not a good indicator of their body state, but both courtship quality and aggressiveness during the courtship are reliable cues of their gamete quality, influencing the viability of their offspring. Thus, females that choose mates based on their courtship behaviour will have high fitness. In the study population, which represents a fast pace-of-life with high reproductive rate and short lifespan, sexual ornaments of males may not honestly signal their physiological and physical state because they invest at maximum in a single reproductive season despite high costs.

Smart mating: the cognitive ability of females influences their preference for male cognitive ability.

Cognitive abilities may be crucial for individuals to respond appropriately to their social and natural environment, thereby increasing fitness. However, the role of cognitive traits in sexual selection has received relatively little attention. Here, we studied 1) whether male secondary sexual traits (colour, courtship, and nest) reflect their cognitive ability, 2) whether females choose mates based on males' and their own cognitive abilities, and 3) how the interplay between secondary sexual traits and cognitive ability determines male attractiveness in the three-spined stickleback (Gasterosteus aculetaus). For this, we first evaluated the cognitive ability of sexually mature males and females in a detour-reaching task. Then, female preference was repeatedly assessed in a dichotomous-choice test, where the female was exposed to two males with contrasting performances (relatively good and bad) in the detour-reaching task. Female preference for better performing males was affected by the female's own cognitive ability. Females with relatively medium-low cognitive ability preferred males with high ability, whereas females with high ability showed no preference. We also found that males with higher cognitive abilities built more elaborated nests, but showed weaker red nuptial colouration. To our knowledge, this is among the first results that illustrate how cognitive traits of both sexes influence female mate preference, which has implications for the strength and direction of sexual selection.

Trap versus net: Behavioural sampling bias caused by capture method in three-spined sticklebacks.

Wild-caught animals are often used in behavioural or other biological studies. However, different capture methods may target individuals that differ in behaviour, life history and morphology, thereby giving rise to sampling biases. Here, we investigated whether juvenile three-spined sticklebacks caught in a natural population by passive and active sampling methods using frequently used tools (i.e. trap and hand net) differ in behaviours related to cognition and personality. The fish caught by traps were more prone to take risks and shoal (i.e. bolder and more sociable), but smaller in size and mass than the fish caught by hand nets. Individual variation in boldness was greater in the fish caught by hand nets, suggesting that this active sampling method may capture more representative samples of the natural population. Our results show the importance of capture method to avoid sampling bias in behavioural studies using wild-caught animals.

Environment-induced changes in reproductive strategies and their transgenerational effects in the three-spined stickleback.

An organism may increase its fitness by changing its reproductive strategies in response to environmental cues, but the possible consequences of those changes for the next generation have rarely been explored. By using an experiment on the three-spined stickleback (Gasterosteus aculeatus), we studied how changes in the onset of breeding photoperiod (early versus late) affect reproductive strategies of males and females, and life histories of their offspring. We also explored whether telomeres are involved in the within- and transgenerational effects. In response to the late onset of breeding photoperiod, females reduced their investment in the early clutches, but males increased their investment in sexual signals. Costs of increased reproductive investment in terms of telomere loss were evident only in the late females. The environmentally induced changes in reproductive strategies affected offspring growth and survival. Most notably, offspring growth rate was the fastest when both parents experienced a delayed (i.e., late) breeding photoperiod, and survival rate was the highest when both parents experienced an advanced (i.e., early) breeding photoperiod. There was no evidence of transgenerational effects on offspring telomere length despite positive parents-offspring relationships in this trait. Our results highlight that environmental changes may impact more than one generation by altering reproductive strategies of seasonal breeders with consequences for offspring viability.

Effect of lignin-blocking agent on enzyme hydrolysis of acid pretreated hemp waste.

Hemp wastes (stems and branches), fractionated after hemp flower extraction for the production of cannabidiol oil, were utilized as a potentially renewable resource for the sugar flatform process. Hydrolysis of cellulose from the acid pretreated hemp biomass using a commercial enzyme was tested and evaluated for its chemical composition, morphological change, and sugar recovery. Acid pretreated hemp stems and branches, containing 1% glucan (w/v) solids, were hydrolyzed for 72 h using 25 mg enzyme protein per g glucan. A 54% glucose conversion was achieved from the treated branches versus a 71% yield from the treated stems. Raw branches and stems yielded 35% and 38% glucose, respectively. Further tests with a lignin-blocking additive (e.g. bovine serum albumin) resulted in a 72% glucose yield increase for stem hydrolysis using 10 mg enzyme protein per g glucan. While pretreatment promotes amorphous hemicellulose decrease and cellulose decomposition, it causes enzyme inhibition/deactivation due to potential inhibitors (phenols and lignin-derived compounds). This study confirms the addition of non-catalytic proteins enhances the cellulose conversion by avoiding non-productive binding of enzymes to the lignin and lignin-derived molecules, with lignin content determining the degree of inhibition and conversion efficiency.

Heat-responsive and time-resolved transcriptome and metabolome analyses of Escherichia coli uncover thermo-tolerant mechanisms.

Current understanding of heat shock response has been complicated by the fact that heat stress is inevitably accompanied by changes in specific growth rates and growth stages. In this study, a chemostat culture was successfully performed to avoid the physico-chemical and biological changes that accompany heatshock, which provided a unique opportunity to investigate the full range of cellular responses to thermal stress, ranging from temporary adjustment to phenotypic adaptation at multi-omics levels. Heat-responsive and time-resolved changes in the transcriptome and metabolome of a widely used E. coli strain BL21(DE3) were explored in which the temperature was upshifted from 37 to 42 °C. Omics profiles were categorized into early (2 and 10 min), middle (0.5, 1, and 2 h), and late (4, 8, and 40 h) stages of heat stress, each of which reflected the initiation, adaptation, and phenotypic plasticity steps of the stress response. The continued heat stress modulated global gene expression by controlling the expression levels of sigma factors in different time frames, including unexpected downregulation of the second heatshock sigma factor gene (rpoE) upon the heat stress. Trehalose, cadaverine, and enterobactin showed increased production to deal with the heat-induced oxidative stress. Genes highly expressed at the late stage were experimentally validated to provide thermotolerance. Intriguingly, a cryptic capsular gene cluster showed considerably high expression level only at the late stage, and its expression was essential for cell growth at high temperature. Granule-forming and elongated cells were observed at the late stage, which was morphological plasticity occurred as a result of acclimation to the continued heat stress. Whole process of thermal adaptation along with the genetic and metabolic changes at fine temporal resolution will contribute to far-reaching comprehension of the heat shock response. Further, the identified thermotolerant genes will be useful to rationally engineer thermotolerant microorganisms.

A single amino acid substitution in aromatic hydroxylase (HpaB) of Escherichia coli alters substrate specificity of the structural isomers of hydroxyphenylacetate.

BACKGROUND: A broad range of aromatic compounds can be degraded by enteric bacteria, and hydroxyphenylacetic acid (HPA) degrading bacteria are the most widespread. Majority of Escherichia coli strains can use both the structural isomers of HPA, 3HPA and 4HPA, as the sole carbon source, which are catabolized by the same pathway whose associated enzymes are encoded by hpa gene cluster. Previously, we observed that E. coli B REL606 grew only on 4HPA, while E. coli B BL21(DE3) grew on 3HPA as well as 4HPA. RESULTS: In this study, we report that a single amino acid in 4-hydroxyphenylacetate 3-hydroxylase (HpaB) of E. coli determines the substrate specificity of HPA isomers. Alignment of protein sequences encoded in hpa gene clusters of BL21(DE3) and REL606 showed that there was a difference of only one amino acid (position 379 in HpaB) between the two, viz., Arg in BL21(DE3) and Cys in REL606. REL606 cells expressing HpaB having Arg379 could grow on 3HPA, whereas those expressing HpaB with Gly379 or Ser379 could not. Structural analysis suggested that the amino acid residue at position 379 of HpaB is located not in the active site, but in the vicinity of the 4HPA binding site, and that it plays an important role in mediating the entrance and stable binding of substrates to the active site. CONCLUSIONS: The arginine residue at position 379 of HpaB is critical for 3HPA recognition. Information regarding the effect of amino acid residues on the substrate specificity of structural isomers can facilitate in designing hydoxylases with high catalytic efficiency and versatility.

Impact of small RNA RaoN on nitrosative-oxidative stress resistance and virulence of Salmonella enterica serovar Typhimurium.

RaoN is a Salmonella-specific small RNA that is encoded in the cspH-envE intergenic region on Salmonella pathogenicity island-11. We previously reported that RaoN is induced under conditions of acid and oxidative stress combined with nutrient limitation, contributing to the intramacrophage growth of Salmonella enterica serovar Typhimurium. However, the role of RaoN in nitrosative stress response and virulence has not yet been elucidated. Here we show that the raoN mutant strain has increased susceptibility to nitrosative stress by using a nitric oxide generating acidified nitrite. Extending previous research on the role of RaoN in oxidative stress resistance, we found that NADPH oxidase inhibition restores the growth of the raoN mutant in LPS-treated J774A.1 macrophages. Flow cytometry analysis further revealed that the inactivation of raoN leads to an increase in the intracellular level of reactive oxygen species (ROS) in Salmonella-infected macrophages, suggesting that RaoN is involved in the inhibition of NADPH oxidase-mediated ROS production by mechanisms not yet resolved. Moreover, we evaluated the effect of raoN mutation on the virulence in murine systemic infection and determined that the raoN mutant is less virulent than the wild-type strain following oral inoculation. In conclusion, small regulatory RNA RaoN controls nitrosative-oxidative stress resistance and is required for virulence of Salmonella in mice.

Attractive male sticklebacks carry more oxidative DNA damage in the soma and germline.

Trade-offs between the expression of sexual signals and the maintenance of somatic and germline tissues are expected when these depend upon the same resources. Despite the importance of sperm DNA integrity, its trade-off with sexual signalling has rarely been explored. We experimentally tested the trade-off between carotenoid-based sexual coloration and oxidative DNA damage in skeletal muscle, testis and sperm by manipulating reproductive schedule (early vs. late onset of breeding) in male three-spined sticklebacks. Oxidative DNA damage was measured as the amount of 8-hydroxy-2-deoxyguanosine in genomic DNA. Irrespective of the experimentally manipulated reproductive schedule, individuals investing more in red coloration showed higher levels of oxidative DNA damage in muscle, testis and sperm during the peak breeding season. Our results show that the expression of red coloration traded off against the level of oxidative DNA damage possibly due to the competing functions of carotenoids as colorants and antioxidants. Thus, female sticklebacks may risk fertility and viability of offspring by choosing redder, more deteriorated partners with decreased sperm DNA integrity. The evolution of sexual signal may be constrained by oxidative DNA damage in the soma and germline.

Overexpression of YbeD in Escherichia coli Enhances Thermotolerance.

Heat-resistant microbial hosts are required for bioprocess development using high cell density cultivations at the industrial scale. We report that the thermotolerance of Escherichia coli can be enhanced by overexpressing ybeD, which was known to encode a hypothetical protein of unknown function. In the wild-type E. coli BL21(DE3), ybeD transcription level increased over five-fold when temperature was increased from 37°C to either 42°C or 46°C. To study the function of ybeD, a deletion strain and an overexpression strain were constructed. At 46°C, in comparison to the wild type, the ybeD-deletion reduced cell growth half-fold, and the ybeD-overexpression promoted cell growth over two-fold. The growth enhancement by ybeD-overexpression was much more pronounced at 46°C than 37°C. The ybeD-overexpression was also effective in other E. coli strains of MG1655, W3110, DH10B, and BW25113. These findings reveal that ybeD gene plays an important role in enduring high-temperature stress, and that ybeD-overexpression can be a prospective strategy to develop thermotolerant microbial hosts.

Overexpression of YbeD in Escherichia coli Enhances Thermotolerance.

Heat-resistant microbial hosts are required for bioprocess development using high cell density cultivations at the industrial scale. We report that the thermotolerance of Escherichia coli can be enhanced by overexpressing ybeD, which was known to encode a hypothetical protein of unknown function. In the wild type E. coli BL21(DE3), ybeDtranscription level increased over five-fold when temperature was increased from 37°C to either 42°C or 46°C. To study the function of ybeD, a deletion strain and an overexpression strain were constructed. At 46°C, in comparison to the wild type, the ybeD-deletion reduced cell growth half-fold, and the ybeD-overexpression promoted cell growth over two-fold. The growth enhancement by ybeD-overexpression was much more pronounced at 46°C than 37°C. The ybeD-overexpression was also effective in other E. coli strains of MG1655, W3110, DH10B, and BW25113. These findings reveal that ybeD gene plays an important role in enduring high-temperature stress, and that ybeD-overexpression can be a prospective strategy to develop thermotolerant microbial hosts.

Redox-regulation and life-history trade-offs: scavenging mitochondrial ROS improves growth in a wild bird.

It has been proposed that animals usually restrain their growth because fast growth leads to an increased production of mitochondrial reactive oxygen species (mtROS), which can damage mitochondrial DNA and promote mitochondrial dysfunction. Here, we explicitly test whether this occurs in a wild bird by supplementing chicks with a mitochondria-targeted ROS scavenger, mitoubiquinone (mitoQ), and examining growth rates and mtDNA damage. In the yellow-legged gull Larus michahellis, mitoQ supplementation increased the early growth rate of chicks but did not reduce mtDNA damage. The level of mtDNA damage was negatively correlated with chick mass, but this relationship was not affected by the mitoQ treatment. We also found that chick growth was positively correlated with both mtDNA copy number and the mitochondrial enzymatic activity of citrate synthase, suggesting a link between mitochondrial content and growth. Additionally, we found that MitoQ supplementation increased mitochondrial content (in males), altered the relationship between mtDNA copy number and damage, and downregulated some transcriptional pathways related to cell rejuvenation, suggesting that scavenging mtROS during development enhanced growth rates but at the expense of cellular turnover. Our study confirms the central role of mitochondria modulating life-history trade-offs during development by other mechanisms than mtROS-inflicted damage.

Carry-over effects of early thermal conditions on somatic and germline oxidative damages are mediated by compensatory growth in sticklebacks.

Most studies of climate change impacts focus on the effects of summer temperatures, which can immediately impact fitness of breeders, but winter temperatures are expected to have a greater impact on development and growth of animals with long-lasting consequences. Exposure to warmer temperatures can increase cellular oxidative damage in ectotherms. Yet, it is unknown whether thermal stress during early life has prolonged effects on oxidative status during adulthood. In an experiment using F1 fish originated from a wild three-spined stickleback population at the southern edge of its European distribution, we examined whether experimental thermal conditions experienced in winter had carry-over effects on oxidative status and telomere length, a marker of accumulated stress, in the soma and germline during adulthood. For this, oxidative DNA damage, enzymatic antioxidant activities and telomere length were measured three months after the termination of the temperature manipulation. In addition, we tested whether such delayed effects, if any, were due to individuals' compensatory growth after experiencing unfavourable growth conditions in winter. Warm acclimation during winter induced increased levels of oxidative DNA damage in muscle and sperm and increased enzymatic antioxidant defences in muscle during the breeding season. Telomere length of adult fish was not influenced by thermal conditions experienced during early life. Winter temperature manipulation influenced fish to alter the temporal pattern of growth trajectories across the juvenile and adult stages. Fish reared in warm winter conditions grew at a slower rate than the controls during the period of temperature manipulation then accelerated body mass gain to catch up during the breeding season. Faster somatic growth during the breeding season incurred a higher cost in terms of oxidative damage in the warm-treated individuals. For the first time, we experimentally show the long-lasting detrimental effects of thermal stress on and the positive link between catch-up growth and oxidative DNA damage in the soma and germline. Winter temperature increases due to climate change can reduce fertility and survival of fish by inducing catch-up growth. The detrimental effects of winter climate change may accumulate across generations through the pre-mutagenic DNA damage in the germline.

La mayoría de los estudios sobre los efectos del cambio climático se centran en los efectos de las temperaturas estivales, ya que estas pueden afectar de forma inmediata a la eficacia biológica de los individuos reproductores. No obstante, es esperable que las temperaturas invernales tengan un mayor impacto a largo plazo debido a sus efectos durante el desarrollo y el crecimiento temprano. Aunque la exposición a temperaturas más elevadas puede aumentar el daño oxidativo celular en ectotermos, todavía se desconoce si un estrés térmico durante el desarrollo temprano tiene efectos a largo plazo sobre el estado oxidativo en la edad adulta. En este experimento, en el que usamos la F1 procedente de una población de pez espinoso situada al borde sur de su distribución, examinamos los efectos a largo plazo de las condiciones térmicas invernales sobre los niveles de estrés oxidativo y longitud telomérica de la línea somática y germinal en la edad adulta. Además, evaluamos si tales efectos a largo plazo, si los hubo, se relacionaron con las tasa de crecimiento de los individuos. La aclimatación cálida durante el invierno indujo un aumento de los niveles de daño oxidativo en al ADN del músculo y los espermatozoides durante la estación reproductora, así como un aumento de las defensas antioxidantes enzimáticas en el músculo. La longitud telomérica adulta no se vio influenciada por las condiciones térmicas experimentadas durante el desarrollo temprano. La manipulación de la temperatura invernal alteró la trayectoria de crecimiento de los peces a lo largo de la fase juvenil y adulta. Los peces criados en condiciones invernales cálidas crecieron a un ritmo más lento que los controles durante el período de manipulación pero posteriormente mostraron una mayor tasa de crecimiento. Este crecimiento compensatorio se completó durante la temporada de reproducción. Este crecimiento compensatorio durante la temporada de reproducción tuvo un coste más elevado, en términos de daño oxidativo, en los individuos que experimentaron una condiciones invernales más cálidas. Por primera vez mostramos experimentalmente que el estrés termino temprano tiene efectos perjudiciales a largo plazo, y que existe una relación positiva entre la tasa de crecimiento compensatorio y los niveles de daño oxidativo en el ADN de las línea somática y germinal. El aumento de las temperaturas invernales debido al cambio climático podría reducir la fertilidad y la supervivencia de las poblaciones de peces al inducir cambios en las tasas de crecimiento. Además, los efectos perjudiciales del cambio climático invernal podrían ser trans-generacionales como consecuencia de la acumulación de daños pre-mutagénicos en el ADN de la línea germinal.

Metabolic network reconstruction and phenome analysis of the industrial microbe, Escherichia coli BL21(DE3).

Escherichia coli BL21(DE3) is an industrial model microbe for the mass-production of bioproducts such as biofuels, biorefineries, and recombinant proteins. However, despite its important role in scientific research and biotechnological applications, a high-quality metabolic network model for metabolic engineering is yet to be developed. Here, we present the comprehensive metabolic network model of E. coli BL21(DE3), named iHK1487, based on the latest genome reannotation and phenome analysis. The metabolic model consists of 1,164 unique metabolites, 2,701 metabolic reactions, and 1,487 genes. The model was validated and improved by comparing the simulation results with phenome data from phenotype microarray tests. Previous transcriptome profile data was incorporated during model reconstruction, and flux prediction was simulated using the model. iHK1487 was simulated to explore the metabolic features of BL21(DE3) such as broad spectrum amino acid utilization and enhanced flux through the upper glycolytic pathway and TCA cycle. iHK1487 will contribute to systematic understanding of cellular physiology and metabolism of E. coli BL21(DE3) and highlight its biotechnological applications.