ISAD Committee on Chronotherapeutics in Affective Disorders

Sleep and Biological Rhythms -     

Anaerobic incorporation of radioactivity from 2,3-14C-succinic acid into citric acid cycle intermediates and related compounds in the sea musselMytilus edulis L.

Summary Sea mussels were exposed to nitrogen for various periods (0, 1, 3 and 6 days) and subsequently injected with 2,3-¹⁴C-succinic acid. After 2.5 h anaerobic incubation concentrations of succinate, some amino acids and volatile fatty acids were determined as well as the distribution of radioactivity.Conversion of the precursor decreased from 80 to 40%, due to increased dilution with endogenous succinate, accumulated during the anaerobic preincubation period.More than 80% of the activity of the converted 2,3-¹⁴C-succinic acid was incorporated into malate, aspartate, glutamate, alanine and propionate. This indicates that succinate is not only an end product of anaerobic glycogen breakdown, but remains an active intermediate of the tricarboxylic acid cycle, which can still operate under anaerobic conditions.Concentration and radioactivity of propionate were markedly increased after prolonged anoxia, which gives evidence that succinate is actively converted to propionate during anaerobiosis.Observed accumulation of glutamate during anoxia is explained by incomplete oxidation of pyruvate, which leaves the tricarboxylic acid cycle at the stage of 2-ketoglutarate.     

Glycoalkaloid Profile in Potato Haploids Derived from Solanum tuberosum–S. bulbocastanum Somatic Hybrids

Cultivated and wild potato species synthesize a wide variety of steroidal glycoalkaloids (GA) that may affect either human health or biotic stress resistance. Therefore, GA composition must be a major criterion in the evaluation of breeding products when species genomes are merged and/or manipulated. This work reports the results of GA analysis performed on unique haploid (2n=2x=24) plants obtained from tetraploid (2n=4x=48) Solanum bulbocastanum–S. tuberosum hybrids through in vitro anther culture. Glycoalkaloids were extracted from tubers and analyzed by HPLC. Haploids generally showed the occurrence of parental GA. However, in several cases loss of parental GA and gain of new GA lacking in the parents was observed. It may be hypothesized that new GA profiles of our haploids is the result of either genetic recombination or combinatorial biochemistry events. To highlight differences between haploids and parents, soluble proteins and antioxidant activities were also determined. Both were always higher in haploids compared to their parents. The nature of the newly formed GAs will be further investigated, because they may represent new metabolites that can be used against pest and diseases, or are useful for human health.     

Relationship between polycomb‐group protein BMI‐1 and phosphatases regulating AKT phosphorylation level in endometrial cancer

The PI3K/AKT pathway is frequently activated in endometrial carcinoma. BMI‐1 (B‐lymphoma Mo‐MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI‐1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in endometrial cancer. The expression of proteins and mRNAs was investigated in endometrial cancer specimens and samples of non‐neoplastic endometrial tissue by Western blot and RT‐PCR, respectively. The impact of BMI‐1 down‐regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI‐1 depletion caused increase in PHLPP1 and PHLPP2 (PH domain and leucine‐rich repeat protein phosphatases 1/2) expression and decrease in phospho‐AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI‐1 was lower compared to tumours less advanced and without lymph node metastasis. There were significant inverse correlations between BMI‐1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI‐1 and PHLPP1/PHLPP2 expression was observed in PTEN positive but not PTEN negative cancers. Low PHLPP2 expression in tumours predicted poorer overall survival. BMI‐1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression.     

Plant community composition steers grassland vegetation via soil legacy effects

Soil legacy effects are commonly highlighted as drivers of plant community dynamics and species co‐existence. However, experimental evidence for soil legacy effects of conditioning plant communities on responding plant communities under natural conditions is lacking. We conditioned 192 grassland plots using six different plant communities with different ratios of grasses and forbs and for different durations. Soil microbial legacies were evident for soil fungi, but not for soil bacteria, while soil abiotic parameters did not significantly change in response to conditioning. The soil legacies affected the composition of the succeeding vegetation. Plant communities with different ratios of grasses and forbs left soil legacies that negatively affected succeeding plants of the same functional type. We conclude that fungal‐mediated soil legacy effects play a significant role in vegetation assembly of natural plant communities.     

Associations between sensitivity to antibiotics,disinfectants and heavy metals in natural,clinical and laboratory isolates of Escherichia coli

Bacteria in nature often encounter non-antibiotic antibacterials (NAAs), such as disinfectants and heavy metals, and they can evolve resistance via mechanisms that are also involved in antibiotic resistance. Understanding whether susceptibility to different types of antibacterials is non-randomly associated across natural and clinical bacteria is therefore important for predicting the spread of resistance, yet there is no consensus about the extent of such associations or underlying mechanisms. We tested for associations between susceptibility phenotypes of 93 natural and clinical Escherichia coli isolates to various NAAs and antibiotics. Across all compound combinations, we detected a small number of non-random associations, including a trio of positive associations among chloramphenicol, triclosan and benzalkonium chloride. We investigated genetic mechanisms that can explain such associations using genomic information, genetic knockouts and experimental evolution. This revealed some mutations that are selected for by experimental exposure to one compound and confer cross-resistance to other compounds. Surprisingly, these interactions were asymmetric: selection for chloramphenicol resistance conferred cross-resistance to triclosan and benzalkonium chloride, but selection for triclosan resistance did not confer cross-resistance to other compounds. These results identify genetic changes involved in variable cross-resistance across antibiotics and NAAs, potentially contributing to associations in natural and clinical bacteria.     

Communicative roots of complex sociality and cognition

Mammals living in more complex social groups typically have large brains for their body size and many researchers have proposed that the primary driver of the increase in brain size through primate and hominin evolution was the selection pressures associated with sociality. Many mammals, and especially primates, use flexible signals that show a high degree of voluntary control and these signals may play an important role in forming and maintaining social relationships between group members. However, the specific role that cognitive skills play in this complex communication, and how in turn this relates to sociality, is still unclear. The hypothesis for the communicative roots of complex sociality and cognition posits that cognitive demands behind the communication needed to form and maintain bonded social relationships in complex social settings drives the link between brain size and sociality. We review the evidence in support of this hypothesis and why key features of cognitively complex communication such as intentionality and referentiality should be more effective in forming and maintaining bonded relationships as compared with less cognitively complex communication. Exploring the link between cognition, communication and sociality provides insights into how increasing flexibility in communication can facilitate the emergence of social systems characterised by bonded social relationships, such as those found in non‐human primates and humans. To move the field forward and carry out both within‐ and among‐species comparisons, we advocate the use of social network analysis, which provides a novel way to describe and compare social structure. Using this approach can lead to a new, systematic way of examining social and communicative complexity across species, something that is lacking in current comparative studies of social structure.