The daily rhythm of feeding-fasting and meal-timing are emerging as important determinants of health. Circadian rhythm research in animal models and retrospective analyses of human nutrition data have shown that reduced length of overnight fasting or increased late night eating increases risk for metabolic diseases including obesity and diabetes. However, the daily rhythm in eating pattern in humans is rarely measured. Traditional methods to collect nutrition information through food diary and food log pay little attention to the timing of eating which may also change from day to day. We adopted a novel cell-phone based approach to longitudinally record all events of food and beverage intake in adults. In a feasibility study daily food-eating patterns of 93 healthy individuals were recorded for 21 days using camera phones. Analysis of the daily eating patterns of these individuals indicates deviation from conventional assumption that people eat three meals-a-day within a 12 h interval. We found that eating events are widespread throughout the day, with 30% consumed in evening and late night hours. There was little difference in eating pattern between weekdays and weekends. In this cohort more than 50% of people spread their caloric intake events over 15 h or longer. One decile of the cohort who were spouses of shift-workers or had flexible work schedule spread their caloric intake over 20 h. Although the nutrition quality and diversity of food consumed is different between South-East Asian and Western countries, such overall disruption of daily eating-fasting rhythm is similar. Therefore, in view of hypothesis that disrupted daily eating pattern may contribute to the global increase in metabolic diseases and modification of daily eating pattern is a potential modifiable behavior to contain these diseases, monitoring eating pattern is an important aspect of lifestyle.

We sought a new approach to treating infections by intracellular bacteria, namely, by altering host cell functions that support their growth. We screened a library of 640 Food and Drug Administration (FDA)-approved compounds for agents that render THP-1 cells resistant to infection by four intracellular pathogens. We identified numerous drugs that are not antibiotics but were highly effective in inhibiting intracellular bacterial growth with limited toxicity to host cells. These compounds are likely to target three kinds of host functions: (i) G protein-coupled receptors, (ii) intracellular calcium signals, and (iii) membrane cholesterol distribution. The compounds that targeted G protein receptor signaling and calcium fluxes broadly inhibited Coxiella burnetii , Legionella pneumophila , Brucella abortus , and Rickettsia conorii , while those directed against cholesterol traffic strongly attenuated the intracellular growth of C. burnetii and L. pneumophila . These pathways probably support intracellular pathogen growth so that drugs that perturb them may be therapeutic candidates. Combining host- and pathogen-directed treatments is a strategy to decrease the emergence of drug-resistant intracellular bacterial pathogens. IMPORTANCE Although antibiotic treatment is often successful, it is becoming clear that alternatives to conventional pathogen-directed therapy must be developed in the face of increasing antibiotic resistance. Moreover, the costs and timing associated with the development of novel antimicrobials make repurposed FDA-approved drugs attractive host-targeted therapeutics. This paper describes a novel approach of identifying such host-targeted therapeutics against intracellular bacterial pathogens. We identified several FDA-approved drugs that inhibit the growth of intracellular bacteria, thereby implicating host intracellular pathways presumably utilized by bacteria during infection.

Summary: In the intracellular pathogen Brucella abortus, the general stress response (GSR) signalling system determines survival under acute stress conditions in vitro, and is required for long‐term residence in a mammalian host. To date, the identity of the Brucella sensor kinase(s) that function to perceive stress and directly activate GSR signalling have remained undefined. We demonstrate that the flavin‐binding sensor histidine kinase, LovhK (bab2_0652), functions as a primary B. abortus GSR sensor. LovhK rapidly and specifically phosphorylates the central GSR regulator, PhyR, and activates transcription of a set of genes that closely overlaps the known B. abortus GSR regulon. Deletion of lovhK severely compromises cell survival under defined oxidative and acid stress conditions. We further show that lovhK is required for cell survival during the early phase of mammalian cell infection and for establishment of long‐term residence in a mouse infection model. Finally, we present evidence that particular regions of primary structure within the two N‐terminal PAS domains of LovhK have distinct sensory roles under specific environmental conditions. This study elucidates new molecular components of a conserved signalling pathway that regulates B. abortus stress physiology and infection biology.

We hypothesized differences in molecular strategies for similar journeys that migrants undertake to reproduce in spring and to overwinter in autumn. We tested this in redheaded buntings ( Emberiza bruniceps ) photoinduced into spring and autumn migratory states, with winter and summer non-migratory states as controls. Compared with controls, buntings fattened, gained weight and showed Zugunruhe (nocturnal migratory restlessness) in the migratory state. Spring migration was associated with greater fat and body mass, and higher intensity of Zugunruhe , compared with autumn migration. Circulating corticosterone levels were higher in spring, while T3 levels were higher in autumn. Hypothalamic expression of thyroid hormone-responsive ( dio2 , dio3 ), light-responsive ( per2 , cry1 , adcyap1 ) and th (tyrosine hydroxylase, involved in dopamine biosynthesis) genes showed significant changes with transition from non-migratory to the migratory state. There were significantly higher mRNA expressions in autumn, except for higher th levels in the spring. Furthermore, the expression patterns of dnmt3a (not dnmt3b ) and tet2 genes suggested an epigenetic difference between the non-migrant and migrant periods, and the spring and autumn migrant periods. These results demonstrate for the first time seasonal transition in hypothalamic gene expressions, and suggest differences in regulatory strategies at the transcriptional level for spring and autumn migrations in songbirds.