The metabolic syndrome (MetS) is a constellation of vascular and metabolic abnormalities that commonly occur together and increase risk for cardiovascular disease (CVD) and type II diabetes (T2DM). Having MetS, especially during middle-age, increases the risk for dementia in later life. Because of these issues, prevention of MetS has become an important public health initiative. Abdominal obesity is causally linked to MetS; therefore, increased efforts to prevent obesity and to better understand what predicts weight gain is of extreme importance. Related research suggests that altered processing of food reward in the brain of obese persons is a possible mechanism related to overeating. Therefore, the study aimed to investigate potential differences in brain response according to metabolic status during pleasantness evaluation of sweet and bitter tastes when hungry and sated. Fifteen healthy middle-aged (44-54 years old) adults and sixteen middle-aged adults with MetS were recruited from the San Diego community. The subjects participated in two functional magnetic resonance imaging (fMRI) scans: (1) after a 12-hour fast; and (2) after a nutritional preload. While in the scanner, participants rated the pleasantness of caffeine (bitter) and sucrose (sweet) solutions. Data were analyzed using voxelwise linear mixed-effects modeling and region of interest (ROI) analyses. Exploratory analyses were also conducted to examine associations between ROI activation and adiposity, and differential brain responses in participants diagnosed with T2DM. The results suggest that middle-aged individuals with MetS have decreased brain responses during pleasantness evaluation of sweet and bitter tastes in regions involved in sensory and higher-level taste processing. Additionally, hypothalamic activation was positively associated with adiposity when hungry, and negatively associated with adiposity when sated. This suggests the presence of altered hypothalamic functioning in obese middle-aged adults. It is speculated that this is due to altered hormonal nutrient signaling and/or chronic overeating. Finally, the results suggest that insulin resistance plays a large role in central taste processing during pleasantness evaluation. It is hypothesized that altered fMRI responses in participants with T2DM may be related to greater disinhibition in combination with increased necessity for dietary monitoring and carbohydrate restrictions in these individuals

Acinetobacter baumannii is a Gram-negative opportunistic pathogen that causes diverse infections, including pneumonia, bacteremia, and wound infections. Due to multiple intrinsic and acquired antimicrobial-resistance mechanisms, A. baumannii isolates are commonly multidrug resistant, and infections are notoriously difficult to treat. The World Health Organization recently highlighted carbapenem-resistant A. baumannii as a "critical priority" for the development of new antimicrobials because of the risk to human health posed by this organism. Therefore, it is important to discover the mechanisms used by A. baumannii to survive stresses encountered during infection in order to identify new drug targets. In this study, by use of in vivo imaging, we identified hydrogen peroxide (H2O2) as a stressor produced in the lung during A. baumannii infection and defined OxyR as a transcriptional regulator of the H2O2 stress response. Upon exposure to H2O2, A. baumannii differentially transcribes several hundred genes. However, the transcriptional upregulation of genes predicted to detoxify hydrogen peroxide is abolished in an A. baumannii strain in which the transcriptional regulator oxyR is genetically inactivated. Moreover, inactivation of oxyR in both antimicrobial-susceptible and multidrug-resistant A. baumannii strains impairs growth in the presence of H2O2 OxyR is a direct regulator of katE and ahpF1, which encode the major H2O2-degrading enzymes in A. baumannii, as confirmed through measurement of promoter binding by recombinant OxyR in electromobility shift assays. Finally, an oxyR mutant is less fit than wild-type A. baumannii during infection of the murine lung. This work reveals a mechanism used by this important human pathogen to survive H2O2 stress encountered during infection.

A complex interplay between multiple chromatin modifiers is critical for cells to regulate chromatin structure and accessibility during essential DNA-templated processes such as transcription. However, the coordinated activities of these chromatin modifiers in the regulation of gene expression are not fully understood. We previously determined that the budding yeast histone H4 methyltransferase Set5 functions together with Set1, the H3K4 methyltransferase, in specific cellular contexts. Here, we sought to understand the relationship between these evolutionarily conserved enzymes in the regulation of gene expression. We generated a comprehensive genetic interaction map of the functionally uncharacterized Set5 methyltransferase and expanded the existing genetic interactome of the global chromatin modifier Set1, revealing functional overlap of the two enzymes in chromatin-related networks, such as transcription. Furthermore, gene expression profiling via RNA-Seq revealed an unexpected synergistic role of Set1 and Set5 in repressing transcription of Ty transposable elements and genes located in subtelomeric regions. This study uncovers novel pathways in which the methyltransferase Set5 participates and, more importantly, reveals a partnership between Set1 and Set5 in transcriptional repression near repetitive DNA elements in budding yeast. Together, our results define a new functional relationship between histone H3 and H4 methyltransferases, whose combined activity may be implicated in preserving genomic integrity.

A complex interplay between multiple chromatin modifiers is critical for cells to regulate chromatin structure and accessibility during essential DNA-templated processes such as transcription. However, the coordinated activities of these chromatin modifiers in the regulation of gene expression are not fully understood. We previously determined that the budding yeast histone H4 methyltransferase Set5 functions together with Set1, the H3K4 methyltransferase, in specific cellular contexts. Here, we sought to understand the relationship between these evolutionarily conserved enzymes in the regulation of gene expression. We generated a comprehensive genetic interaction map of the functionally uncharacterized Set5 methyltransferase and expanded the existing genetic interactome of the global chromatin modifier Set1, revealing functional overlap of the two enzymes in chromatin-related networks, such as transcription. Furthermore, gene expression profiling via RNA-Seq revealed an unexpected synergistic role of Set1 and Set5 in repressing transcription of Ty transposable elements and genes located in subtelomeric regions. This study uncovers novel pathways in which the methyltransferase Set5 participates and, more importantly, reveals a partnership between Set1 and Set5 in transcriptional repression near repetitive DNA elements in budding yeast. Together, our results define a new functional relationship between histone H3 and H4 methyltransferases, whose combined activity may be implicated in preserving genomic integrity.