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Background: Three subsets of human monocytes in circulation have been identified and their characterization is still ill-defined. Although glucose and lipid intakes have been demonstrated to exert pro-inflammatory effects on mononuclear cells (MNCs) of healthy subjects, characterization of monocytes phenotypes following macronutrient (glucose, protein, and lipid) intake in humans remains to be determined. Methods: Thirty-six healthy, normal weight volunteers were recruited in the study. Subjects were randomly assigned into three groups, each group consisting of 12 participants. Each group drank equal calories (300 kcal) of either glucose or lipids or Whey proteins. Each subject served as his own control by drinking 300 mL of water 1 week before or after the caloric intake. Baseline blood samples were drawn at 0, 1, 2 and 3-hour intervals post caloric or water intakes. MNCs were isolated, and the expression levels of different cluster of differentiation (CD) markers (CD86, CD11c, CD169, CD206, CD163, CD36, CD68, CD11b, CD16, and CD14) and IL-6 were measured by RT-qPCR. Results: Equicaloric intake of either glucose or lipids or Whey proteins resulted in different monocyte phenotypes as demonstrated by changes in the expression levels of CD and polarization markers. Whey proteins intake resulted in significant mRNA upregulation in MNCs of CD68 and CD11b at 1, 2, and 3 hrs post intake while mRNA of IL-6 was significantly inhibited at 1 hr. Lipids intake, on the other hand, resulted in mRNA upregulation of CD11b at 2 and 3 hrs and CD206 at 1, 2 and 3 hrs. There were no significant changes in the other CD markers measured (CD86, CD163, CD169, CD36, CD16 and CD14) following either Whey proteins or lipids intakes. Glucose intake did not alter mRNA expression of any marker tested except CD206 at 3 hrs. Conclusions: Macronutrient intake alter the expression levels of polarization markers in MNCs of human subjects. A distinct population of different monocytes phenotypes may result in human circulation following the intake of different macronutrients. Further studies are required to characterize the immunomodulatory effects of macronutrients intake on monocytes phenotypes and their characteristics in humans.

The genetic and biochemical aspects of the essential Mycobacteriumtuberculosis MtrAB two-component regulatory signal transduction (2CRS) system have not been extensively investigated. We show by bacterial two-hybrid assay that the response regulator (RR) MtrA and the sensor kinase MtrB interact. We further demonstrate that divalent metal ions [Mg²+, Ca²+ or both] promote MtrB kinase autophosphorylation activity, but only Mg²+ promotes phosphotransfer to MtrA. Replacement of the conserved aspartic acid residues at positions 13 and 56 with alanine (D13A), glutamine (D56E) or asparagine (D56N) prevented MtrA phosphorylation, indicating that these residues are important for phosphorylation. The MtrA(D56E) and MtrA(D13A) proteins bound to the promoter of fbpB, the gene encoding antigen 85B protein, efficiently in the absence of phosphorylation, whereas MtrA(D56N) did not. We also show that M.tuberculosismtrA merodiploids overproducing MtrA(D13A), unlike cells overproducing wild-type MtrA, grow poorly in nutrient broth and show reduced expression of fbpB. These latter findings are reminiscent of a phenotype associated with MtrA overproduction during intramacrophage growth. Our results suggest that MtrA(D13A) behaves like a constitutively active response regulator and that further characterization of mtrA merodiploid strains will provide valuable clues to the MtrAB system.

Objective.To identify the frequency of typical (headache and dizziness) and common atypical (ear fullness, pressure, pain, tinnitus, facial fullness, and nasal congestion) migraine symptoms as chief complaints among patients presenting to otolaryngology clinic.Methods.This is a descriptive study of prospectively collected data from a general otolaryngology practice. Typical migraine presentations were diagnosed by applying international headache society (IHS) criteria for migraine headache and Neuhauser’s criteria for migrainous vertigo. Atypical otologic and rhinologic migraine symptoms were diagnosed using individualized criteria. Charts were reviewed at 6-month interval from the first presentation.Results.Out of 1002 consecutive patients, 10.8% presented with “migrainous chief complaint.” All migrainous chief complaint patients had a history of headache but not all of them presented with headache. Corrected female to male ratio in the migraine group was 3 to 1; age distributions were significantly different between the migraine and nonmigraine groups by applyingt-test. Out of the atypical complaints, 86% of the patients had a history of concomitant typical presentation.Conclusion. Actual diagnostic criteria for migraine do not satisfy the diversity of its presentation. Investigating the history of migraine is enough to diagnose most atypical presentations. Sound knowledge about migraine seems essential for any ENT practitioner.

Efficient proliferation of Mycobacterium tuberculosis (Mtb) inside macrophage requires that the essential response regulator MtrA be optimally phosphorylated. However, the genomic targets of MtrA have not been identified. We show by chromatin immunoprecipitation and DNase I footprinting that the chromosomal origin of replication, oriC, and the promoter for the major secreted immunodominant antigen Ag85B, encoded by fbpB, are MtrA targets. DNase I footprinting analysis revealed that MtrA recognizes two direct repeats of GTCACAgcg-like sequences and that MtrA approximately P, the phosphorylated form of MtrA, binds preferentially to these targets. The oriC contains several MtrA motifs, and replacement of all motifs or of a single select motif with TATATA compromises the ability of oriC plasmids to maintain stable autonomous replication in wild type and MtrA-overproducing strains, indicating that the integrity of the MtrA motif is necessary for oriC replication. The expression of the fbpB gene is found to be down-regulated in Mtb cells upon infection when these cells overproduce wild type MtrA but not when they overproduce a nonphosphorylated MtrA, indicating that MtrA approximately P regulates fbpB expression. We propose that MtrA is a regulator of oriC replication and that the ability of MtrA to affect apparently unrelated targets, i.e. oriC and fbpB, reflects its main role as a coordinator between the proliferative and pathogenic functions of Mtb.