Identification of an estrogen-regulated circadian mechanism necessary for breast acinar morphogenesis

Altered estrogen receptor α (ERA) signaling and altered circadian rhythms are both features of breast cancer. By using a method to entrain circadian oscillations in human cultured cells, we recently reported that the expression of key clock genes oscillates in a circadian fashion in ERA-positive breast epithelial cells but not in breast cancer cells, regardless of their ERA status. Moreover, we reported that ERA mRNA oscillates in a circadian fashion in ERA-positive breast epithelial cells, but not in ERA-positive breast cancer cells. By using ERA-positive HME1 breast epithelial cells, which can be both entrained in vitro and can form mammary gland-like acinar structures in three-dimensional (3D) culture, first we identified a circuit encompassing ERA and an estrogen-regulated loop consisting of two circadian clock genes, PER2 and BMAL1. Further, we demonstrated that this estrogen-regulated circuit is necessary for breast epithelial acinar morphogenesis. Disruption of this circuit due to ERA-knockdown, negatively affects the estrogen-sustained circadian PER2-BMAL1 mechanism as well as the formation of 3D HME1 acini. Conversely, knockdown of either PER2 or BMAL1, by hampering the PER2-BMAL1 loop of the circadian clock, negatively affects ERA circadian oscillations and 3D breast acinar morphogenesis. To our knowledge, this study provides the first evidence of the implication of an ERA-circadian clock mechanism in the breast acinar morphogenetic process.     

The median preoptic nucleus exhibits circadian regulation and is involved in food anticipatory activity in rabbit pups

Rabbit pups are a natural model to study food anticipatory activity (FAA). Recently, we reported that three areas in the forebrain – the organum vasculosum of lamina terminalis, median preoptic nucleus (MnPO) and medial preoptic area – exhibit activation during FAA. Here, we examined the PER1 protein profile of these three forebrain regions in both nursed and fasted subjects. We found robust PER1 oscillations in the MnPO in nursed subjects, with high PER1 levels during FAA that persisted in fasted subjects. In conclusion, our data indicate that periodic nursing is a strong signal for PER1 oscillations in MnPO and future experiments are warranted to explore the specific role of this area in FAA.     

门诊患者倍他乐克不规范用药分析

目的：针对门诊患者使用倍他乐克不规范的原因进行分析,为临床规范用药提供参考。方法：搜集2011年7月本院心内科普通门诊服用倍他乐克的患者病例,分析其中用药不当的原因以及各种具体表现。结果：373例使用倍他乐克的患者中,不规范用药者占9.39%,包括了用量、用法不正确、擅自减量、停药以及拒绝用药等12种用药不当的具体表现。在不规范用药的患者中,有9人随访间隔时间明显短于其余患者（P〈0.05）,但未被告知调整药物剂量。有8位患者年龄显著高于其余患者（P〈0.05）,由于独居或行动不便,随访间隔时间明显长于其余患者（P〈0.05）。结论：倍他乐克使用不规范的情况并不少见,应当加强临床医师的教育以及对患者的宣教,增加用药的依从性,提高倍他乐克用药的规范性与合理性。     

Dissolved organic matter (DOM) release by phytoplankton in the contemporary and future ocean

The partitioning of organic matter (OM) between dissolved and particulate phases is an important factor in determining the fate of organic carbon in the ocean. Dissolved organic matter (DOM) release by phytoplankton is a ubiquitous process, resulting in 2–50% of the carbon fixed by photosynthesis leaving the cell. This loss can be divided into two components: passive leakage by diffusion across the cell membrane and the active exudation of DOM into the surrounding environment. At present there is no method to distinguish whether DOM is released via leakage or exudation. Most explanations for exudation remain hypothetical; as while DOM release has been measured extensively, there has been relatively little work to determine why DOM is released. Further research is needed to determine the composition of the DOM released by phytoplankton and to link composition to phytoplankton physiological status and environmental conditions. For example, the causes and physiology of phytoplankton cell death are poorly understood, though cell death increases membrane permeability and presumably DOM release. Recent work has shown that phytoplankton interactions with bacteria are important in determining both the amount and composition of the DOM released. In response to increasing CO₂ in the atmosphere, climate change is creating increasingly stressful conditions for phytoplankton in the surface ocean, including relatively warm water, low pH, low nutrient supply and high light. As ocean physics and chemistry change, it is hypothesized that a greater proportion of primary production will be released directly by phytoplankton into the water as DOM. Changes in the partitioning of primary production between the dissolved and particulate phases will have bottom-up effects on ecosystem structure and function. There is a need for research to determine how these changes affect the fate of organic matter in the ocean, particularly the efficiency of the biological carbon pump.     

Higher scores in the extraversion personality trait are associated with a functional polymorphism in the PER3 gene in healthy subjects

A polymorphism in the PER3 (period circadian clock 3) gene has been associated with neuropsychiatric disorders and endophenotypes. We evaluated the possible association of personality domains with the PER3 polymorphism in a sample of healthy subjects: 271 individuals were evaluated with the Big Five Inventory and genotyped for the PER3 Variable Number Tandem Repeat (VNTR) polymorphism. We found a significant association between the PER3 polymorphism and the extraversion personality trait (p = 0.0093). The 5/5 genotype carriers showed higher scores for extraversion. This is the first time that a significant association between the PER3 VNTR polymorphism and extraversion is reported.     

Impact of Ataxin-2 knock out on circadian locomotor behavior and PER immunoreaction in the SCN of mice

In Drosophila melanogaster, Ataxin-2 is a crucial activator of Period and is involved in the control of circadian rhythms. However, in mammals the function of Ataxin-2 is unknown despite its involvement in the inherited neurogenerative disease Spinocerebellar Ataxia type 2 in humans. Therefore, we analyzed locomotor behavior of Atxn2-deficient mice and their WT littermates under entrained- and free-running conditions as well as after experimental jet lag. Furthermore, we compared the PER1 and PER2 immunoreaction (IR) in the SCN. Atxn2^?/? mice showed an unstable rhythmicity of locomotor activity, but the level of PER1 and PER2 IR in the SCN did not differ between genotypes.     

全球气候变化对四川盆地可能蒸散率(PER)的影响模拟

针对目前全球气候在降水和温度方面异常变化的情况 ,本文在利用信息技术对四川盆地的可能蒸散率 (PER)在未来 5种水热组合下的变化情况进行了模拟。结果表明 ,在全球气候变化的条件下 ,当温度升高时 ,四川省PER值将增高 ,分布区域将以 4个气候敏感区为核心 ,由东南向西北方向扩增 ,但随着降水量的增加 ,PER值将降低 ,分布区域将沿东南方向逐渐缩减     

Development of a polishing step using a hydrophobic interaction membrane adsorber with a PER.C6®‐derived recombinant antibody

Membrane chromatography has already proven to be a powerful alternative to polishing columns in flow‐through mode for contaminant removal. As flow‐through utilization has expanded, membrane chromatography applications have included the capturing of large molecules, including proteins such as IgGs. Such bind‐and‐elute applications imply the demand for high binding capacity and larger membrane surface areas as compared to flow‐through applications. Given these considerations, a new Sartobind Phenyl? membrane adsorber was developed for large‐scale purification of biomolecules based on hydrophobic interaction chromatography (HIC) principles. The new hydrophobic membrane adsorber combines the advantages of membrane chromatography—virtually no diffusion limitation and shorter processing time—with high binding capacity for proteins comparable to that of conventional HIC resins as well as excellent resolution. Results from these studies confirmed the capability of HIC membrane adsorber to purify therapeutic proteins with high dynamic binding capacities in the range of 20 mg‐MAb/cm³‐membrane and excellent impurity reduction. In addition the HIC phenyl membrane adsorber can operate at five‐ to ten‐fold lower residence time when compared to column chromatography. A bind/elute purification step using the HIC membrane adsorber was developed for a recombinant monoclonal antibody produced using the PER.C6® cell line. Loading and elution conditions were optimized using statistical design of experiments. Scale‐up is further discussed, and the performance of the membrane adsorber is compared to a traditional HIC resin used in column chromatography. Biotechnol. Bioeng. 2010; 105: 296–305. © 2009 Wiley Periodicals, Inc.     

Perception,regulation, and fitness effects of pollen phytosterols in the bumble bee,Bombus terrestris

Premise

Many flowering plants depend on insects for pollination and thus attract pollinators by offering rewards, mostly nectar and pollen. Bee pollinators rely on pollen as their main nutrient source. Pollen provides all essential micro- and macronutrients including substances that cannot be synthesized by bees themselves, such as sterols, which bees need for processes such as hormone production. Variations in sterol concentrations may consequently affect bee health and reproductive fitness. We therefore hypothesized that (1) these variations in pollen sterols affect longevity and reproduction in bumble bees and (2) can thus be perceived via the bees' antennae before consumption.

Methods

We studied the effect of sterols on longevity and reproduction of Bombus terrestris workers in feeding experiments and investigated sterol perception using chemotactile proboscis extension response (PER) conditioning.

Results

Workers could perceive several sterols (cholesterol, cholestenone, desmosterol, stigmasterol, β-sitosterol) via their antennae but not differentiate between them. However, when sterols were presented in pollen, and not as a single compound, the bees were unable to differentiate between pollen differing in sterol content. Additionally, different sterol concentrations in pollen neither affected pollen consumption nor brood development or worker longevity.

Conclusions

Since we used both natural concentrations and concentrations higher than those found in pollen, our results indicate that bumble bees may not need to pay specific attention to pollen sterol content beyond a specific threshold. Naturally encountered concentrations might fully support their sterol requirements and higher concentrations do not seem to have negative effects.

     

A review of processing of feed ingredients to enhance diet digestibility in finfish

Replacement of fish meal with plant proteins in aquaculture diets presents several problems. Firstly, aquaculture diets, particularly diets for carnivorous fish species, are nutrient dense and may contain up to 450 g crude protein (CP)/kg. Such diets preclude the use of ingredients with only moderate CP content, such as pulses including peas and faba beans or oilseed meals including canola/rapeseed meal and flax. Secondly, virtually all crops contain heat-labile and heat-stable secondary compounds including protease inhibitors, tannins, lectins, phytate, dietary fibre and starch. Removal of heat-labile secondary compounds may be accomplished by extrusion or other heat treatment. However, elimination of heat-stable secondary compounds, and increasing the nutrient concentration of diets, requires fractionation of crops. Fractionation technologies range from low technology processes such as dehulling to medium technologies such as air classification to sophisticated technologies such as aqueous and solvent protein purification. Studies on the nutritional value of processed plant proteins in various fish species have consistently shown improved digestibility and growth compared to feeding unprocessed ingredients. This review examines effects of processing technologies on nutritional properties of soybean meal, canola meal, peas, lupins and flax in aquaculture diets.