Global placental gene expression in gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is thought to modify the pattern of placental transcriptome. In a microarray study and a confirmatory quantitative real-time reverse transcription-polymerase chain reaction study, we investigated global placental gene expression in GDM. STUDY DESIGN: Ribonucleic acid was extracted from placental samples collected from 19 GDM cases and 21 controls. Oligonucleotide probes representing 22,000 genes were used to measure gene expression. Differential gene expression was evaluated using the Student t test, fold change assessment, and significance analysis of microarrays. Path analysis was used to assess functions and functional relationships of differentially expressed genes. RESULTS: Sixty-six genes participating in cell functions involving cell activation, immune response, organ development, and regulation of cell death were differentially expressed in GDM placentas. These genes include previously described candidate genes (eg, LEP, CEBPA, and MIF), genes with related functions (eg, ADFP), and novel genes (eg, AQP3). CONCLUSION: Expression of genes responsible for diverse biologic processes are modified in GDM.

Differential placental gene expression in preeclampsia.

OBJECTIVE: Candidate genes that are associated with preeclampsia have not been described fully. We conducted microarray and confirmatory quantitative real time polymerase chain reaction studies to investigate global placental gene expression in preeclampsia. STUDY DESIGN: RNA was extracted from placental samples that were collected from 18 preeclampsia cases and 18 normotensive control subjects. Oligonucleotide probes that represented 22,000 genes were used to measure gene expression in each sample. Differential gene expression was evaluated with the Student t test, fold change assessment, and significance analysis of microarrays. Functions and functional relationships of differentially expressed genes were evaluated. RESULTS: Genes (n = 58) that participated in immune system, inflammation, oxidative stress, signaling, growth, and development pathways were expressed differentially in preeclampsia. These genes included previously described candidate genes (such as leptin), potential candidate genes with related functions (such as CYP11A) and novel genes (such as CDKN1C). CONCLUSION: Expression of genes (both candidate and novel) with diverse functions is associated with preeclampsia risk, which reflects the complex pathogenesis.

Estimating the burden of paratyphoid a in Asia and Africa.

Despite the increasing availability of typhoid vaccine in many regions, global estimates of mortality attributable to enteric fever appear stable. While both Salmonella enterica serovar Typhi (S. Typhi) and serovar Paratyphi (S. Paratyphi) cause enteric fever, limited data exist estimating the burden of S. Paratyphi, particularly in Asia and Africa. We performed a systematic review of both English and Chinese-language databases to estimate the regional burden of paratyphoid within Africa and Asia. Distinct from previous reviews of the topic, we have presented two separate measures of burden; both incidence and proportion of enteric fever attributable to paratyphoid. Included articles reported laboratory-confirmed Salmonella serovar classification, provided clear methods on sampling strategy, defined the age range of participants, and specified the time period of the study. A total of 64 full-text articles satisfied inclusion criteria and were included in the qualitative synthesis. Paratyphoid A was commonly identified as a cause of enteric fever throughout Asia. The highest incidence estimates in Asia came from China; four studies estimated incidence rates of over 150 cases/100,000 person-years. Paratyphoid A burden estimates from Africa were extremely limited and with the exception of Nigeria, few population or hospital-based studies from Africa reported significant Paratyphoid A burden. While significant gaps exist in the existing population-level estimates of paratyphoid burden in Asia and Africa, available data suggest that paratyphoid A is a significant cause of enteric fever in Asia. The high variability in documented incidence and proportion estimates of paratyphoid suggest considerable geospatial variability in the burden of paratyphoid fever. Additional efforts to monitor enteric fever at the population level will be necessary in order to accurately quantify the public health threat posed by S. Paratyphi A, and to improve the prevention and treatment of enteric fever.

Adipocytokine expression in placentas from pre-eclamptic and chronic hypertensive patients.

OBJECTIVE: Growing evidence suggests that concentration of the adipocytokines leptin and adiponectin may be affected by risk of hypertension during pregnancy. Leptin and leptin receptor gene expression has been studied in placentas obtained from pre-eclamptic patients, but not in those with chronic high blood pressure (CHBP). Adiponectin receptors remain unstudied in placentas obtained from hypertensive patients. METHODS: Therefore, we investigated relative mRNA expression of selected adipocytokine genes (leptin, leptin receptors (LEPRA, LEPRB, LEPRC, LEPRD) and adiponectin receptors (ADIPOR1, ADIPOR2)) in placental tissues from women with pre-eclampsia (n = 6) or CHBP (n = 8). Placentas from 28 normotensive patients were analyzed as controls. mRNA extracted from biopsies taken from the maternal and fetal sides of the placenta was investigated using real-time polymerase chain reaction. RESULTS: Compared with controls, significant increases in leptin mRNA expression were seen in placentas from pre-eclamptic patients on the maternal (p = 0.01) and fetal (p = 0.02) sides, and in placentas from CHBP mothers on the fetal side (p = 0.001). Maternal-side tissue from CHBP patients was not significantly different from that of controls (p = 0.08), but this might be due to the small sample size. No significant differences were seen in mRNA expression for most of the adipocytokine receptors tested for hypertensive cases compared with controls. However, there was a decrease in LEPRC (pre-eclamptic, maternal side, p = 0.03) and LEPRD (pre-eclamptic, maternal side, p = 0.01; CHBP, fetal side, p = 0.009) in case-control analysis. CONCLUSIONS: This pilot study shows that increases seen in leptin expression in placentas from hypertensive mothers might be a consequence of defects in placentation associated with this disease, and motivates further region-specific adipocytokine gene expression analysis across this organ.

Targeted gene expression in Drosophila dopaminergic cells using regulatory sequences from tyrosine hydroxylase.

Dopamine (DA) is the only catecholaminergic neurotransmitter in the fruit fly Drosophila melanogaster. Dopaminergic neurons have been identified in the larval and adult central nervous system (CNS) in Drosophila and other insects, but no specific genetic tool was available to study their development, function, and degeneration in vivo. In Drosophila as in vertebrates, the rate-limiting step in DA biosynthesis is catalyzed by the enzyme tyrosine hydroxylase (TH). The Drosophila TH gene (DTH) is specifically expressed in all dopaminergic cells and the corresponding mutant, pale (ple), is embryonic lethal. We have performed ple rescue experiments with modified DTH transgenes. Our results indicate that partially redundant regulatory elements located in DTH introns are required for proper expression of this gene in the CNS. Based on this study, we generated a GAL4 driver transgene, TH-GAL4, containing regulatory sequences from the DTH 5' flanking and downstream coding regions. TH-GAL4 specifically expresses in dopaminergic cells in embryos, larval CNS, and adult brain when introduced into the Drosophila genome. As a first application of this driver, we observed that in vivo inhibition of DA release induces a striking hyperexcitability behavior in adult flies. We propose that TH-GAL4 will be useful for studies of the role of DA in behavior and disease models in Drosophila.