Childhood and Adolescent Body Fat and Its Relationship with Health Outcome in 50 Year Old Males and Females: The Wroclaw Growth Study

The aim of the study was to estimate the association between relative weight in childhood and adolescence and its relationship with adult health outcome. Longitudinal data of the body mass index (BMI) from the Wroc³aw Growth Study (WGS) covering ages 8 to 18 and then a follow-up at 50 were used. At the age of 50, 124 males and 139 females in the longitudinal study underwent medical examination. Systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TCH), high density lipoprotein cholesterol level (HDL), low density lipoprotein cholesterol level (LDL), triglyceride level (TGL) and fasting glucose level (GLUC) were assessed by using standard techniques. The values of BMI were standardised with the LMS method. Multiple linear regression was used to assess the relationship between health parameters and BMI at ages 8–18, adjusted for BMI at the age of 50, separately for different age categories and parameters, except for blood pressure where the usage of anti-hypertension medication was additionally used as a control variable. In males total cholesterol concentration showed a significant negative correlation with standardised BMI at ages 9–12 and 16 and 17. In females, only blood pressure showed a significant negative relationship with standardised BMI in all age categories reaching the highest values at age 15. The BMI in childhood and adolescence have only a weak effect on health outcome at age 50

Isozyme-Specific Ligands for O-acetylserine sulfhydrylase, a Novel Antibiotic Target

Conceived and designed the experiments: FS PC BC ES AM. Performed the experiments: FS RS ES PF SR. Analyzed the data: FS BC ES PF GEK PFC AM. Contributed reagents/materials/analysis tools: PC PB GC. Wrote the paper: FS GEK BC AM.The last step of cysteine biosynthesis in bacteria and plants is catalyzed by O-acetylserine sulfhydrylase. In bacteria, two isozymes, O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, have been identified that share similar binding sites, although the respective specific functions are still debated. O-acetylserine sulfhydrylase plays a key role in the adaptation of bacteria to the host environment, in the defense mechanisms to oxidative stress and in antibiotic resistance. Because mammals synthesize cysteine from methionine and lack O-acetylserine sulfhydrylase, the enzyme is a potential target for antimicrobials. With this aim, we first identified potential inhibitors of the two isozymes via a ligand- and structure-based in silico screening of a subset of the ZINC library using FLAP. The binding affinities of the most promising candidates were measured in vitro on purified O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B from Salmonella typhimurium by a direct method that exploits the change in the cofactor fluorescence. Two molecules were identified with dissociation constants of 3.7 and 33 µM for O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, respectively. Because GRID analysis of the two isoenzymes indicates the presence of a few common pharmacophoric features, cross binding titrations were carried out. It was found that the best binder for O-acetylserine sulfhydrylase-B exhibits a dissociation constant of 29 µM for O-acetylserine sulfhydrylase-A, thus displaying a limited selectivity, whereas the best binder for O-acetylserine sulfhydrylase-A exhibits a dissociation constant of 50 µM for O-acetylserine sulfhydrylase-B and is thus 8-fold selective towards the former isozyme. Therefore, isoform-specific and isoform-independent ligands allow to either selectively target the isozyme that predominantly supports bacteria during infection and long-term survival or to completely block bacterial cysteine biosynthesis.Yeshttp://www.plosone.org/static/editorial#pee

Social variation in menarcheal age in big-city girls from Upper Silesia in 1981

An intriguing social gradient of menarcheal age was found among girls from twelve different social groups defined by father’s occupation and occupational status. Menarcheal age was also found to depend upon parental education and family size

Rational Design, Synthesis, and Preliminary Structure–Activity Relationships of α‑Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella typhimurium <i>O</i>‑Acetylserine Sulfhydrylase

Cysteine is a building block for several biomolecules that are crucial for living organisms. The last step of cysteine biosynthesis is catalyzed by <i>O</i>-acetylserine sulfydrylase (OASS), a highly conserved pyridoxal 5′-phosphate (PLP)-dependent enzyme, present in different isoforms in bacteria, plants, and nematodes, but absent in mammals. Beside the biosynthesis of cysteine, OASS exerts a series of “moonlighting” activities in bacteria, such as transcriptional regulation, contact-dependent growth inhibition, swarming motility, and induction of antibiotic resistance. Therefore, the discovery of molecules capable of inhibiting OASS would be a valuable tool to unravel how this protein affects the physiology of unicellular organisms. As a continuation of our efforts toward the synthesis of OASS inhibitors, in this work we have used a combination of computational and spectroscopic approaches to rationally design, synthesize, and test a series of substituted 2-phenylcyclopropane carboxylic acids that bind to the two S. typhymurium OASS isoforms at nanomolar concentrations