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STUDY QUESTION What are the associations between baseline BMI (Study 1) and change in body weight (Study 2) with the likelihood of pregnancy in women with polycystic ovary syndrome (PCOS). SUMMARY ANSWER In women with PCOS, higher baseline BMI was associated with a lower chance of pregnancy; however, weight loss was associated with an increased chance of pregnancy versus maintaining a stable weight or gaining weight. WHAT IS KNOWN ALREADY Two studies in large cohorts of Danish women with the intention to become pregnant showed a decline in fecundability ratios with higher BMI. Furthermore, a meta-analysis found that overweight/obesity significantly worsened metabolic and reproductive outcomes in women with PCOS. STUDY DESIGN, SIZE, DURATION Data were extracted from the UK Clinical Practice Research Datalink GOLD database. Patients included women aged 18–45 years with BMI ≥18.5 (Study 1) or ≥25 kg/m2 (Study 2) at time of PCOS diagnosis (index date). The primary outcome was the time to first pregnancy recorded during 36-months' follow-up, analysed with Cox proportional hazard models and presented as hazard ratios (HRs). PARTICIPANTS/MATERIALS, SETTING, METHODS Study 1 included 9955 women with PCOS. Study 2 included 7593 women with PCOS and median BMI of 34.0 kg/m2. MAIN RESULTS AND THE ROLE OF CHANCE Higher BMI was associated with a lower chance of pregnancy in the 3 years following diagnosis. It was estimated that 41% of women with normal weight (18.5–24.9 kg/m2) would become pregnant compared to 17% of women with obesity class III (BMI ≥40.0 kg/m2) during follow-up. Furthermore, the chance of pregnancy for women with obesity class III was estimated to be 63% lower than for women with normal weight, with the same age and glycaemic status (HR 0.37, 95% CI 0.31–0.44; P  < 0.0001). A significant inverse association was found between BMI change and chance of pregnancy: 10% weight loss was estimated to increase the chance of pregnancy by 68% for women with baseline BMI of 40 kg/m2 (HR 1.68, 95% CI 1.49–1.90). LIMITATIONS, REASONS FOR CAUTION Multiple factors influence the chance of pregnancy (the ability and willingness to become pregnant), which was addressed by exclusion criteria employed. The real-world nature of the study means that use of non-prescription contraceptives was not available. Bias may have been introduced by the fact that only around 40% of women with PCOS in the CPRD GOLD database had their BMI recorded during the year prior to PCOS diagnosis. BMI categories used in the analyses may not be applicable to women of all ethnicities. The study population was only representative of women in the UK and results may not be generalizable to other regions. PCOS diagnoses were based on codes entered into the system by primary care providers, and no information was available regarding the criteria used for diagnosis, although symptoms used to diagnose PCOS have not changed over time. WIDER IMPLICATIONS OF THE FINDINGS Our observations provide further evidence of the benefits of weight loss in women with overweight/obesity and PCOS who are seeking to become pregnant. STUDY FUNDING/COMPETING INTEREST(S) Novo Nordisk A/S. A.H.B. declares fees for consultancy from Novo Nordisk. P.N.L. and C.L.H. are employees of Novo Nordisk. V.S. and A.V. are employees of, and hold shares in, Novo Nordisk. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Microbial consortia can be used to catalyze complex biotransformations. Tools to control the behavior of these consortia in a technical environment are currently lacking. In the present study, a synthetic biology approach was used to build a model consortium of two Saccharomyces cerevisiae strains where growth and expression of the fluorescent marker protein EGFP by the receiver strain is controlled by the concentration of α‐factor pheromone, which is produced by the emitter strain. We have developed a quantitative experimental and theoretical framework to describe population dynamics in the model consortium. We measured biomass growth and metabolite production in controlled bioreactor experiments, and used flow cytometry to monitor changes of the subpopulations and protein expression under different cultivation conditions. This dataset was used to parameterize a segregated mathematical model, which took into account fundamental growth processes, pheromone‐induced growth arrest and EGFP production, as well as pheromone desensitization after extended exposure. The model was able to predict the growth dynamics of single‐strain cultures and the consortium quantitatively and provides a basis for using this approach in actual biotransformations. [ABSTRACT FROM AUTHOR]

Abstract: The ability of Kluyveromyces marxianus for converting lactose into ethyl acetate offers a chance for the economical reuse of whey. Iron plays a significant role in this process as ester synthesis requires a low intracellular iron content, xFe. The iron content in turn is decreased by growth due to cell expansion and increased by iron uptake. Thus, the iron‐uptake rate, ψ, is important for the considered process. Iron uptake by K. marxianus DSM 5422 was studied in aerobic cultivation on a whey‐borne medium with varied initial iron content, in part combined with a feed of iron under intensive growth conditions. A possible precipitation of iron that would pretend iron uptake was verified not to have occurred. Regularly measured dissolved iron concentrations, CFe,L, allowed the xFe and ψ parameters to be obtained by model‐based iron balancing. The achieved data were used for establishing a ψ(CFe,L, xFe) model. Mathematical simulations based on this iron‐uptake model reproduced the performed cultivation processes. The created iron‐uptake model allows for a future predictive system to be developed for the optimization of biotechnological ester production. [ABSTRACT FROM AUTHOR]

ABSTRACT Plant cell suspensions are frequently considered to be heterogeneous with respect to growth in terms of progression of the cells through the cell cycle and biomass accumulation. Thus, segregated data of fractions in different cycle phases during cultivation is needed to develop robust production processes. Bromodeoxyuridine (BrdU) incorporation and BrdU-antibodies or 5-ethynyl-2′-deoxyuridine (EdU) click-it chemistry are frequently used to acquire such information. However, their use requires centrifugation steps that cannot be readily applied to sensitive cells, particularly if nuclei have to be extracted from the protective cellular milieu and envelopes for DNA analysis. Therefore, we have established a BrdU-Hoechst stain quenching protocol for analyzing nuclei directly isolated from delicate plant cell suspension cultures. After adding BrdU to test Harpagophytum procumbens cell suspension cultures the cell cycle distribution could be adequately resolved using its incorporation for the following 72 h (after which BrdU slowed biomass accumulation). Despite this limitation, the protocol allows resolution of the cell cycle distribution of cultures that cannot be analyzed using commonly applied methods due to the cells' fragility. The presented protocol enabled analysis of cycling heterogeneities in H. procumbens batch cultivations, and thus should facilitate process control of secondary metabolite production from fragile plant in vitro cultures. Biotechnol. Bioeng. 2016;113: 1244-1250. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The influence of Salvia officinalis L. hairy roots derived phenolic acids on the growth of two typical cellulose degrading moulds, Chaetomium globosum and Trichoderma viride, was examined. For this, 26 hairy root lines of S. officinalis were induced and investigated with regard to the production of phenolic acids. Pure, commercial phenolic acids, analogues to that biosynthesised in the hairy root cultures, were solved in 96% ethanol and applied to malt extract agar plates. The fungal cultures were transferred to the agar plates, and fungal growth was observed 5 and 12 days after inoculation. The hairy root line A produced the highest amount of total phenolic acids (1582.0µg/g), while line B produced the highest amount of sinapic acid (262.8µg/g). Trans-cinnamic and salicylic acid showed antifungal activity to the growth of C. globosum. The growth of this strain was inhibited by vanillic, pcoumaric and sinapic acid. Moreover, it was observed that sinapic acid prevented the spore formation of C. globosum. Protocatechuic, sinapic, and salicylic acid inhibited the growth of T. viride minimal. Furthermore, only sinapic acid inhibited the spore formation of this mould. The investigations have shown antifungal activity of six S. officinalis hairy root derived phenolic acids on malt extract agar plates. [ABSTRACT FROM AUTHOR]

In this study, Nocardia iowensis was used to transform oleanolic acid (OA) into oleanane derivatives. The first derivative, which was found after 24 h of cultivation, was the known and already described OA methyl ester. After 1 week, two other derivatives (oleanonic acid methyl ester and an unknown metabolite) were identified as new products of a biotransformation by N. iowensis. These oleanane metabolites were characterized by HPLC, HPLC-ESI-MS, and HPLC-1H NMR spectroscopy. The biotransformation was performed by suspended and immobilized cells (ICs) of N. iowensis. Cells immobilized in alginate beads were used in order to prepare a continuous process. The substrate uptake of free and ICs was similar, whereas the peak area of OA methyl ester of the ICs was only about 10% of the native cells. However, the final product (oleanonic acid methyl ester) concentrations were similar in both approaches, whereas the unknown metabolite 3 was only detected transiently in the medium of ICs. Based on these results, a new biosynthetic pathway for the biotechnological production of oleanonic acid methyl ester is proposed. [ABSTRACT FROM AUTHOR]