The characterization of the saddle shaped nickel(III) porphyrin radical cation: an explicative NMR model for a ferromagnetically coupled metallo-porphyrin radical

Ni(III)(OETPP˙)(Br)2 is the first Ni(III) porphyrin radical cation with structural and (1)H and (13)C paramagnetic NMR data for porphyrinate systems. Associating EPR and NMR analyses with DFT calculations as a new model is capable of clearly determining the dominant state from two controversial spin distributions in the ring to be the Ni(III) LS coupled with an a1u spin-up radical

Prioritization of Biomarker Targets in Human Umbilical Cord Blood: Identification of Proteins in Infant Blood Serving as Validated Biomarkers in Adults

Background: Early diagnosis represents one of the best lines of defense in the fight against a wide array of human diseases. Umbilical cord blood (UCB) is one of the first easily available diagnostic biofluids and can inform about the health status of newborns. However, compared with adult blood, its diagnostic potential remains largely untapped

Impact of ROS-Induced Damage of TCA Cycle Enzymes on Metabolism and Virulence of Salmonella enterica serovar Typhimurium

Noster J, Persicke M, Chao T-C, et al. Impact of ROS-Induced Damage of TCA Cycle Enzymes on Metabolism and Virulence of Salmonella enterica serovar Typhimurium. FRONTIERS IN MICROBIOLOGY. 2019;10: 762.Salmonella enterica serovar Typhimurium (STM) is exposed to reactive oxygen species (ROS) originating from aerobic respiration, antibiotic treatment, and the oxidative burst occurring inside the Salmonella-containing vacuole (SCV) within host cells. ROS damage cellular compounds, thereby impairing bacterial viability and inducing cell death. Proteins containing iron-sulfur (Fe-S) clusters are particularly sensitive and become non-functional upon oxidation. Comprising five enzymes with Fe-S clusters, the TCA cycle is a pathway most sensitive toward ROS. To test the impact of ROS-mediated metabolic perturbations on bacterial physiology, we analyzed the proteomic and metabolic profile of STM deficient in both cytosolic superoxide dismutases (Delta sodAB). Incapable of detoxifying superoxide anions (SOA), endogenously generated SOA accumulate during growth. Delta sodAB showed reduced abundance of aconitases, leading to a metabolic profile similar to that of an aconitase-deficient strain (Delta acnAB). Furthermore, we determined a decreased expression of acnA in STM Delta sodAB. While intracellular proliferation in RAW264.7 macrophages and survival of methyl viologen treatment were not reduced for STM Delta acnAB, proteomic profiling revealed enhanced stress response. We conclude that ROS-mediated reduced expression and damage of aconitase does not impair bacterial viability or virulence, but might increase ROS amounts in STM, which reinforces the bactericidal effects of antibiotic treatment and immune responses of the host

Association between estradiol levels in early pregnancy and risk of preeclampsia after frozen embryo transfer

IntroductionThe failure of remodeling the spiral arteries is associated with the pathogenesis of preeclampsia. Estradiol (E2) plays a crucial role in placentation and may be involved in the development of preeclampsia. However, there is a lack of data in this area. This study aims to assess the association between serum estradiol levels in early pregnancy and the risk of preeclampsia.MethodsWe conducted a retrospective cohort study on patients who conceived after frozen embryo transfer (FET) using data from a database at a university-affiliated in vitro fertilization center. The study period spanned from January 1, 2010, to December 31, 2020. Multivariable logistic regression analyses were performed to determine the adjusted effect of E2 levels on the risk of preeclampsia. We compared the odds ratios of preeclampsia across quartiles of E2 levels and assessed their significance.ResultsSerum E2 levels at the fifth gestational week were significantly different between women with and without preeclampsia after FET programmed cycles (607.5 ± 245.4 vs. 545.6 ± 294.4 pg/ml, p=0.009). A multivariable logistic regression model demonstrated that E2 levels in early pregnancy were independent risk factors for preeclampsia. We observed an increased odds ratio of preeclampsia with increasing quartiles of estradiol levels after adjusting for potential confounders in FET programmed cycles. When comparing quartiles 3 and 4 (E2 > 493 pg/ml at the fifth gestational week) to quartiles 1 and 2, the odds ratios of preeclampsia were significantly higher.ConclusionWe found that serum E2 levels in early pregnancy may impact the risk of preeclampsia, particularly following FET programmed cycles. The association between E2 levels in early pregnancy and preeclampsia deserves further investigation

Transcriptome Changes in Relation to Manic Episode

Bipolar disorder (BD) is highly heritable and well known for its recurrent manic and depressive episodes. The present study focused on manic episode in BD patients and aimed to investigate state-specific transcriptome alterations between acute episode and remission, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and micro-RNAs (miRNAs), using microarray and RNA sequencing (RNA-Seq) platforms. BD patients were enrolled with clinical information, and peripheral blood samples collected at both acute and remission status spanning for at least 2 months were confirmed by follow-ups. Symptom severity was assessed by Young Mania Rating Scale. We enrolled six BD patients as the discovery samples and used the Affymetrix Human Transcriptome Array 2.0 to capture transcriptome data at the two time points. For replication, expression data from Gene Expression Omnibus that consisted of 11 BD patients were downloaded, and we performed a mega-analysis for microarray data of 17 patients. Moreover, we conducted RNA sequencing (RNA-Seq) in additional samples of 7 BD patients. To identify intraindividual differentially expressed genes (DEGs), we analyzed data using a linear model controlling for symptom severity. We found that noncoding genes were of majority among the top DEGs in microarray data. The expression fold change of coding genes among DEGs showed moderate to high correlations (∼0.5) across platforms. A number of lncRNAs and two miRNAs (MIR181B1 and MIR103A1) exhibited high levels of gene expression in the manic state. For coding genes, we reported that the taste function-related genes, including TAS2R5 and TAS2R3, may be mania state-specific markers. Additionally, four genes showed a nominal p-value of less than 0.05 in all our microarray data, mega-analysis, and RNA-Seq analysis. They were upregulated in the manic state and consisted of MS4A14, PYHIN1, UTRN, and DMXL2, and their gene expression patterns were further validated by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). We also performed weight gene coexpression network analysis to identify gene modules for manic episode. Genes in the mania-related modules were different from the susceptible loci of BD obtained from genome-wide association studies, and biological pathways in relation to these modules were mainly related to immune function, especially cytokine–cytokine receptor interaction. Results of the present study elucidated potential molecular targets and genomic networks that are involved in manic episode. Future studies are needed to further validate these biomarkers for their roles in the etiology of bipolar illness

Microfluidic single-cell analysis of intracellular compounds

Biological analyses traditionally probe cell ensembles in the range of 103–106 cells, thereby completely averaging over relevant individual cell responses, such as differences in cell proliferation, responses to external stimuli or disease onset. In past years, this fact has been realized and increasing interest has evolved for single-cell analytical methods, which could give exciting new insights into genomics, proteomics, transcriptomics and systems biology. Microfluidic or lab-on-a-chip devices are the method of choice for single-cell analytical tools as they allow the integration of a variety of necessary process steps involved in single-cell analysis, such as selection, navigation, positioning or lysis of single cells as well as separation and detection of cellular analytes. Along with this advantageous integration, microfluidic devices confine single cells in compartments near their intrinsic volume, thus minimizing dilution effects and increasing detection sensitivity. This review overviews the developments and achievements of microfluidic single-cell analysis of intracellular compounds in the past few years, from proof-of-principle devices to applications demonstrating a high biological relevance