Exometabolome profiling reveals activation of the carnitine buffering pathway in fed-batch cultures of CHO cells co-fed with glucose and lactic acid

Adjustments to CHO cell physiology were recently observed during implementation of a Raman spectroscopy-based glucose and lactate control strategy. To further understand how these cells, under monoclonal antibody (mAb) production conditions, utilized the extra lactic acid fed, we performed a comprehensive semi-quantitative and time-dependent analysis of the exometabolome. This study focused on the CHO cell's metabolic shift from the fifth day of culture. We compared relative levels of extracellular metabolites in the absence or presence of a 2 g/L lactic acid setpoint while glucose was kept at 4 g/L. Our hypothesis is that extra lactic acid would supply more pyruvate, favoring oxidative phosphorylation. We subsequentially uncovered several carnitine derivatives as biomarkers of the simultaneous activation of TCA anaplerotic pathways as well as a carbon-buffering pathway. CHO cells exhibited a balance between intermediates from (i) amino acid catabolism, (ii) fatty acid β-oxidation, and (iii) pyruvate from glycolysis and lactic acid; and the secretion of their intermediate carnitine derivatives. In addition, 3-hydroxy-methyl-glutaric acid (HMG) and mevalonate syntheses were found as biomarkers of alternative acyl group removal. Together, under a limited capacity to assimilate the surplus of acyl-CoA groups as well as an ability to maintain the acyl-CoA: free CoA ratio for proper and continuous functioning of the TCA cycle, CHO cells activate the carnitine-buffering system, HMG, and mevalonate pathways.     

Similarity-based gene detection: using COGs to find evolutionarily-conserved ORFs

Background  

Experimental verification of gene products has not kept pace with the rapid growth of microbial sequence information. However, existing annotations of gene locations contain sufficient information to screen for probable errors. Furthermore, comparisons among genomes become more informative as more genomes are examined. We studied all open reading frames (ORFs) of at least 30 codons from the genomes of 27 sequenced bacterial strains. We grouped the potential peptide sequences encoded from the ORFs by forming Clusters of Orthologous Groups (COGs). We used this grouping in order to find homologous relationships that would not be distinguishable from noise when using simple BLAST searches. Although COG analysis was initially developed to group annotated genes, we applied it to the task of grouping anonymous DNA sequences that may encode proteins.     

Human Love Styles and Attitudes toward Pets

Pets have a positive influence on humans’ physical and psychological wellbeing, as well as their close relationships. In general, people who hold a positive view of people in turn hold a favorable view of pets. Despite this, previous studies on the relationship between love toward people and love toward pets were inconclusive. In this study, we take a fresh look at the nexus of the domains of love and pets by exploring whether people’s views of love with a romantic partner are associated with attitudes toward their pets. To answer this question, we administered scales to assess human love styles and attitudes toward pets. Participants completed measures on their attitudes toward romantic love, romantic relationship satisfaction, amount of social support, self-esteem, and attitudes toward pets. Human love styles assessed include Eros (passionate), Ludus (game-playing), Storge (friendship), Pragma (practical), Mania (obsessive), and Agape (selfless). Factor analyses of the pet attitudes measure revealed two factors—positive and negative attitudes toward pets. An erotic love style was linked to the endorsement of favorable pet attitudes, while a ludic love style was associated with the endorsement of unfavorable pet attitudes. Subsequent gender-specific correlations indicated that favorable pet attitudes were associated with high levels of social support for men, but low levels of support for women. Future research might address whether pets are instrumental in the development of love styles, whether love styles change after adoption of a pet, and if attitudes toward a romantic partner are similar to attitudes toward a particularly close companion animal.     

Mycoplasma pneumoniae respiratory disease symposium: summation and significance

The symposium on M. pneumoniae respiratory disease has examined the clinical expression of infection in adults and children, the pathophysiologic disturbances which occur, and the laboratory diagnosis by isolation and serology. That these infections are very common has been well documented; however, a variable incidence over periods of several years tends to minimize importance of the disease for many clinicians. While good laboratory diagnostic methods exist, they provide retrospective insight predominantly and are not useful for early diagnosis or therapeutic decision making. Development of rapid diagnostic methods which are sensitive and specific is an important goal for future research. Success would facilitate our understanding and control of M. pneumoniae disease.