Design and synthesis of tricyclic tetrahydroquinolines as a new series of nonsteroidal selective androgen receptor modulators (SARMs)

Some tricyclic tetrahydroquinolines (THQs) were found to have the potential of a new series of nonsteroidal selective androgen receptor modulators (SARMs). Compound 5b was first designed and synthesized under our hypothesis based on a four-point pharmacophoric requirement of the 3-carbonyl, 18-methyl, 17-hydroxyl, and 13-quaternary carbon groups of dihydrotestosterone (DHT). It was revealed that this compound exhibits not only a strong androgen receptor (AR) agonistic activity (EC₅₀ = 9.2 nM) but also the highest selectivity in binding affinity to AR among the steroid hormone receptors. Furthermore, this compound showed a weak virilizing effect with retention of the desired anabolic effect as compared with DHT in vivo.     

Dynamics of energy utilization in male and female turkeys during growth

Determining energy utilization in growing animals enables to adjust the nutritional constraints to nutrient requirements while maximizing the ratio between lean retention and fat retention to improve feed efficiency. In turkey production, the important sexual dimorphism and differences between strains may contribute to differences in basal energy metabolism and the partitioning of energy retention between protein and lipid. The objective of this study was to determine the dynamics of energy utilization in males and females of a heavy strain of turkeys fed ad libitum from 1 to 23 weeks of age. Heat production (HP) was determined by indirect calorimetry and retained energy (RE) was calculated as the difference between metabolizable energy (ME) intake and HP. The RE as protein was determined by a nitrogen balance, while the remaining RE was assumed to be lipid. A modeling procedure allowed partitioning HP between fasting HP (FHP), activity-related HP and thermic effect of feeding. A multiple regression analysis was used to estimate the maintenance energy expenditure (ME(m)) and the energy efficiencies of protein and lipid retention (k(p) and k(f), respectively). Results were expressed either per day or per kg BW(0.75) per day. In comparison with females, males consumed more feed (440 v. 368 g/day), grew faster (163 v. 147 g/day) and retained more protein (38 v. 28 g/day) during the experimental period. Expressed per kg BW(0.75) per day, ME intake decreased linearly with increasing age and was not affected by gender. Similarly, RE as protein decreased with increasing age and tended to be greater in males than in females, whereas RE as lipid increased with increasing age and was lower in males than in females. In addition, HP decreased with increasing age and was greater in males than in females, because of greater activity-related HP and FHP (47% and 9% greater in males compared with females). The FHP averaged 417 kJ/(kg BW)(0.75) per day during the first 3 weeks of age and decreased to 317 and 277 kJ/(kg BW)(0.75) per day in males and females, respectively, from 20 weeks of age onwards. Similar to FHP, ME(m) was lower in females than in males ((586 to 12 × BW) and (586 to 5 × BW) kJ/(kg BW)(0.75) per day, respectively) and the k(p) and k(f) were estimated at 0.63 and 0.87, respectively. This study shows that the partitioning of RE and HP differs between genders in growing turkeys, which likely results in differences in nutrient requirements.     

Comparisons of germination traits of alpine plants between fellfield and snowbed habitats

We examined the seed-germination responses of 27 alpine species with reference to habitat type (fellfield and snowbed), temperature (five regimes), and light requirement. About 70% of species showed >40% germination at warm temperatures without cold stratification. However, a moist-chilling treatment markedly improved the germination percentages in most species, especially under cool conditions. Thus, cold stratification effectively reduced the temperature requirement for germination. Patterns of germination response within species were not consistent between the fellfield and snowbed habitats for species inhabiting both habitats. For interspecific comparisons, there were no significant differences in germination responses to the temperature regimes and the cold stratification between the fellfield and snowbed species. Also, germination speed and the length of germinating period did not differ between fellfield and snowbed species. Most species (86%) showed a requirement for light for germination without cold stratification. Although the extent of the light requirement was reduced after cold stratification in some species, the light requirement of most small-seeded species remained. The combination of cold stratification and the light requirement is a major factor determining the seedling emergence and formation of seed banks in alpine plants. However, habitat-specific patterns of germination traits were less clear, suggesting similar germination traits in fellfield and snowbed plants, at least under controlled conditions in the laboratory.     

Effect of Screening Out Implausible Energy Intake Reports on Relationships between Diet and BMI

Objective: We present an updated method for identifying physiologically implausible dietary reports by comparing reported energy intake (rEI) with predicted energy requirements (pER), and we examine the impact of excluding these reports. Research Methods and Procedures: Adult data from the Continuing Survey of Food Intakes by Individuals 1994 to 1996 were used. pER was calculated from the dietary reference intake equations. Within‐subject variations and errors in rEI [coefficient of variation (CV) ～ 23%] over 2 days (d), pER (CV ～ 11%), and measured total energy expenditure (mTEE; doubly labeled water, CV ～ 8.2%) were propagated, where ±1 SD = . Thus, a report was identified as implausible if rEI was not within 78% to 122% of pER. Multiple cut‐offs between ±1 and ±2 SD were tested. Results: %rEI/pER = 81% in the total sample (n = 6499) and progressively increased to 95% in the ±1 SD sample (n = 2685). The ±1 to 1.4 SD samples yielded rEI‐weight associations closest to the theoretical relationship (mTEE to weight). Weak or spurious diet—BMI associations were present in the total sample; ±1 to 1.4 SD samples showed the strongest set of associations and provided the maximum n while maintaining biological plausibility. Discussion: Our methodology can be applied to different data sets to evaluate the impact of implausible rEIs on health outcomes. Implausible rEIs reduce the overall validity of a sample, and not excluding them may lead to inappropriate conclusions about potential dietary causes of health outcomes such as obesity.     

Exogenous AdoMet and its analogue sinefungin differentially influence DNA cleavage by R.EcoP15I--usefulness in SAGE

While it has been demonstrated that AdoMet is required for DNA cleavage by Type III restriction enzymes, here we show that in the presence of exogenous AdoMet, the head-to-head oriented recognition sites are cleaved only on a supercoiled DNA. On a linear DNA, exogenous AdoMet strongly drives methylation while inhibiting cleavage reaction. Strikingly, AdoMet analogue sinefungin results in cleavage at all recognition sites irrespective of the topology of DNA. The cleavage reaction in the presence of sinefungin is ATP dependent. The site of cleavage is comparable with that in the presence of AdoMet. The use of EcoP15I restriction in presence of sinefungin as an improved tool for serial analysis of gene expression is discussed.     

Performance of a substratum-irradiated photosynthetic biofilm reactor for the removal of sulfide from wastewater

The performance of a sulfide-removal system based on biofilms dominated by green sulfur bacteria (GSB) has been investigated. The system was supplied with radiant energy in the band 720-780 nm, and fed with a synthetic wastewater. The areal net sulfide removal rate and the efficacy of the incident radiant energy for sulfide removal have been characterized over ranges of bulk sulfide concentration (1.6-11.5 mg L(-1)) and incident irradiance (0.21-1.51 W m(-2)). The areal net sulfide removal rate increased monotonically with both increasing incident irradiance and increasing bulk sulfide concentration. The efficacy of the radiant energy for sulfide removal (the amount of sulfide removed per unit energy supplied) also increased monotonically with rising bulk sulfide concentration, but exhibited a maximum value with respect to incident irradiance. The maximum observed values of this net removal rate and this efficacy were, respectively, 2.08 g m(-2) d(-1) and 2.04 g W(-1) d(-1). In-band changes in the spectral composition of the radiant energy affected this efficacy only slightly. The products of sulfide removal were sulfate and elemental-S. The elemental-S was scarcely released into the liquid, however, and reasons for this, such as sulfur reduction and polysulfide formation, are considered. Between 1.45 and 3.85 photons were needed for the net removal of one electron from S-species. Intact samples of the biofilm were characterized by microscopy, and their thicknesses lay between 39 +/- 9 and 429 +/- 57 microm. The use of the experimentally determined rates and efficacies for the design of a pilot-scale system is illustrated.     

实验猴饲料盘的改进和应用

目的探讨对当前实验猴养殖场广泛使用的饲料盘进行改进,减少饲料浪费。方法在对实验猴采食习性进行观察的基础上,提出饲料盘改进办法,并对改进前后饲料浪费情况进行分析。结果新型饲料盘饲料浪费量明显少于旧饲料盘,增大新型饲料盘面积,饲料浪费量也明显减少。结论改进型饲料盘具有制作简单,容易清洁,大大减少饲料浪费等特点,值得在实验猴养殖场推广应用。     

Detecting un-authorized genetically modified organisms (GMOs) and derived materials

Genetically modified plants, in the following referred to as genetically modified organisms or GMOs, have been commercially grown for almost two decades. In 2010 approximately 10% of the total global crop acreage was planted with GMOs (James, 2011). More than 30 countries have been growing commercial GMOs, and many more have performed field trials. Although the majority of commercial GMOs both in terms of acreage and specific events belong to the four species: soybean, maize, cotton and rapeseed, there are another 20 + species where GMOs are commercialized or in the pipeline for commercialization. The number of GMOs cultivated in field trials or for commercial production has constantly increased during this time period. So have the number of species, the number of countries involved, the diversity of novel (added) genetic elements and the global trade. All of these factors contribute to the increasing complexity of detecting and correctly identifying GMO derived material. Many jurisdictions, including the European Union (EU), legally distinguish between authorized (and therefore legal) and un-authorized (and therefore illegal) GMOs. Information about the developments, field trials, authorizations, cultivation, trade and observations made in the official GMO control laboratories in different countries around the world is often limited, despite several attempts such as the OECD BioTrack for voluntary dissemination of data. This lack of information inevitably makes it challenging to detect and identify GMOs, especially the un-authorized GMOs. The present paper reviews the state of the art technologies and approaches in light of coverage, practicability, sensitivity and limitations. Emphasis is put on exemplifying practical detection of un-authorized GMOs. Although this paper has a European (EU) bias when examples are given, the contents have global relevance.     

Estimation of the tryptophan requirement in piglets by meta-analysis

There is no consensus concerning the Trp requirement for piglets expressed relative to Lys on a standardized ileal digestible basis (SID Trp : Lys). A meta-analysis was performed to estimate the SID Trp : Lys ratio that maximizes performance of weaned piglets between 7 and 25 kg of BW. A database comprising 130 experiments on the Trp requirement in piglets was established. The nutritional values of the diets were calculated from the composition of feed ingredients. Among all experiments, 37 experiments were selected to be used in the meta-analysis because they were designed to express the Trp requirement relative to Lys (e.g. Lys was the second-limiting amino acid in the diet) while testing at least three levels of Trp. The linear-plateau (LP), curvilinear-plateau (CLP) and asymptotic (ASY) models were tested to estimate the SID Trp : Lys requirement using average daily gain (ADG), average daily feed intake (ADFI) and gain-to-feed ratio (G : F) as response criteria. A multiplicative trial effect was included in the models on the plateau value, assuming that the experimental conditions affected only this parameter and not the requirement or the shape of the response to Trp. Model choice appeared to have an important impact on the estimated requirement. Using ADG and ADFI as response criteria, the SID Trp : Lys requirement was estimated at 17% with the LP model, at 22% with the CLP model and at 26% with the ASY model. Requirement estimates were slightly lower when G : F was used as response criterion. The Trp requirement was not affected by the composition of the diet (corn v. a mixture of cereals). The CLP model appeared to be the best-adapted model to describe the response curve of a population. This model predicted that increasing the SID Trp : Lys ratio from 17% to 22% resulted in an increase in ADG by 8%.