Biological Responsiveness to Pheromones Provides Fundamental and Unique Insight into Olfactory Function

When exposed to the odor of conspecifics, most organisms exhibitan adaptive behavioral response, particularly if the individualsare sexually mature. Evidence increasingly suggests that behavioralresponsiveness to these odors, which are termed ‘pheromones’,reflects neuroethological mechanisms associated with olfactoryfunction. Reproductive pheromones, which are the best understood,are commonly used by both invertebrates and vertebrates. Inboth instances they are generally comprised of mixtures of compoundsand behavioral responsiveness to them is largely instinctual,sexually-dimorphic, and attributable to a specialized component(s)of the olfactory system. While pheromonal responsiveness insome systems (e.g. moths) appears highly stereotypic and symptomaticof a relatively simple ‘labeled line’, behavioralresponsiveness of other animals (e.g. rodents) can be modifiedby experience, suggesting a more complex underlying centralmechanism. In any case, our understanding of these fascinatingsystems is progressing only because of an active dialogue betweenbehavioral and neurological investigations. This review brieflyexamines how behavioral studies have provided fundamental insightinto the neuroethology of olfactory function by drawing comparisonsbetween some of the better understood sex pheromone systemswhich have been described in heliothine moths, the goldfish,and the pig. Many similarities between invertebrate and vertebratepheromone systems are noted. Chem. Senses 21, 245–256,1996.     

Olfactory Attraction of the Hornet Vespa velutina to Honeybee Colony Odors and Pheromones

Since the beginning of the last century, the number of biological invasions has continuously increased worldwide. Due to their environmental and economical consequences, invasive species are now a major concern. Social wasps are particularly efficient invaders because of their distinctive biology and behavior. Among them, the yellow-legged hornet, Vespa velutina, is a keen hunter of domestic honeybees. Its recent introduction to Europe may induce important beekeeping, pollination, and biodiversity problems. Hornets use olfactory cues for the long-range detection of food sources, in this case the location of honeybee colonies, but the exact nature of these cues remains unknown. Here, we studied the orientation behavior of V. velutina workers towards a range of hive products and protein sources, as well as towards prominent chemical substances emitted by these food sources. In a multiple choice test performed under controlled laboratory conditions, we found that hornets are strongly attracted to the odor of some hive products, especially pollen and honey. When testing specific compounds, the honeybee aggregation pheromone, geraniol, proved highly attractive. Pheromones produced by honeybee larvae or by the queen were also of interest to hornet workers, albeit to a lesser extent. Our results indicate that V. velutina workers are selectively attracted towards olfactory cues from hives (stored food, brood, and queen), which may signal a high prey density. This study opens new perspectives for understanding hornets’ hunting behavior and paves the way for developing efficient trapping strategies against this invasive species.     

Pheromones as time cues for circadian rhythms in fish

Almost all living organisms, including fish, exhibit circadian rhythms. They synchronize their circadian clocks with the solar clock through the mediation of photic or non-photic zeitgebers. Pheromones are the major chemicals responsible for communication among the conspecifics. Pheromones are secreted by a sender and perceived by receiver (s), thus evoking a species specific response and in turn affecting the behavior of receiver (s). Can a pheromone act as a zeitgeber in fish? In this mini review attempts have been made to address the question.     

鱼类信息素研究概况

信息素在鱼类的生活史中起重要的作用。根据其功能差异,可以将信息素分为报警、社会组织和繁殖三大类。焦虑信息素和报警信息素在鱼类中具有提醒同种个体逃离捕食的功能,其中骨鳔鱼类的报警信息素可能是一些嘌呤或蝶呤类的物质;胆汁酸可能在鱼类的个体识别、亲缘选择以及洄游等方面起主要的作用;性信息素则具有同步繁殖活动的重要功能,在硬骨鱼类中,现已发现的性信息素几乎都是被释放到体外的性激素及其代谢产物,而雄性海七鳃鳗(Petromyzon marinus)使用胆汁酸吸引异性。     

The Functioning of Species-Specific Olfactory Pheromones in the Biology of a Mosquito-Eating Jumping Spider from East Africa

Having unique, complex eyes and vision based on exceptional spatial acuity, salticid spiders are known for their vision-based predatory and mating strategies. Yet Evarcha culicivora, the salticid we consider here, is known for predatory and mating strategies based strongly on the interplay of vision and olfaction. This unusual East African species feeds indirectly on vertebrate blood by choosing blood-carrying female mosquitoes as preferred prey, which it can identify by sight and by smell. Moreover, E. culicivora’s mating strategy is unusual because, unlike the prevailing general pattern among spiders, where males are more active in courtship and females are more active in mate choice, both roles are characteristic of both sexes of E. culicivora. There is also an unusual relationship between diet and mating in this species, with blood meals making both sexes more attractive as potential mates. However, findings from the present study demonstrate that, regardless of source-spider diet and even when restricted to using chemoreception in the absence of seeing another spider, both sexes can discriminate between opposite-sex conspecifics and opposite-sex heterospecifics. Yet there is no evidence that diet (blood versus no blood) influences the attractiveness of opposite-sex heterospecific individuals to E. culicivora. Evidence that the odor of opposite-sex conspecifics is salient to E. culicivora comes from three different experimental designs (retention testing, choice testing and courtship-initiation testing). The effective odor source can be either the presence of the spider or the presence of the spider’s draglines alone.     

Pheromones: fish fear factor

Fish, like many other animals, panic when another individual is injured. Now, the chemical nature of a substance that mediates this reaction has been uncovered.     

Potential Role of Transient Receptor Potential Channel M5 in Sensing Putative Pheromones in Mouse Olfactory Sensory Neurons

Based on pharmacological studies of chemosensory transduction in transient receptor potential channel M5 (TRPM5) knockout mice it was hypothesized that this channel is involved in transduction for a subset of putative pheromones in mouse olfactory sensory neurons (OSNs). Yet, in the same study an electroolfactogram (EOG) in the mouse olfactory epithelium showed no significant difference in the responses to pheromones (and odors) between wild type and TRPM5 knockout mice. Here we show that the number of OSNs expressing TRPM5 is increased by unilateral naris occlusion. Importantly, EOG experiments show that mice lacking TRPM5 show a decreased response in the occluded epithelia to putative pheromones as opposed to wild type mice that show no change upon unilateral naris occlusion. This evidence indicates that under decreased olfactory sensory input TRPM5 plays a role in mediating putative pheromone transduction. Furthermore, we demonstrate that cyclic nucleotide gated channel A2 knockout (CNGA2-KO) mice that show substantially decreased or absent responses to odors and pheromones also have elevated levels of TRPM5 compared to wild type mice. Taken together, our evidence suggests that TRPM5 plays a role in mediating transduction for putative pheromones under conditions of reduced chemosensory input.     

昆虫嗅觉相关蛋白及嗅觉识别机理研究概述

嗅觉是昆虫产生行为的基础之一,在长期进化的过程中昆虫形成了复杂的嗅觉系统,完成这一过程,需要有多种与嗅觉相关的蛋白参与,包括气味结合蛋白、化学感受蛋白、气味受体和感觉神经元膜蛋白等。了解昆虫感受外界信息的嗅觉机制可以帮助我们更好地理解昆虫识别配偶、天敌及寻找食物来源、产卵场地等行为特征,为进一步调控昆虫的行为、防控害虫侵袭、保护和利用有益昆虫奠定基础。本文综述了昆虫嗅觉相关的几类重要蛋白的生化特性和生理功能,并对昆虫气味分子的识别机制、气味分子在昆虫体内运输机制的最新研究进展进行了概述。     

P-type ATPases as drug targets: Tools for medicine and science

P-type ATPases catalyze the selective active transport of ions like H⁺, Na⁺, K⁺, Ca²⁺, Zn²⁺, and Cu²⁺ across diverse biological membrane systems. Many members of the P-type ATPase protein family, such as the Na⁺,K⁺-, H⁺,K⁺-, Ca²⁺-, and H⁺-ATPases, are involved in the development of pathophysiological conditions or provide critical function to pathogens. Therefore, they seem to be promising targets for future drugs and novel antifungal agents and herbicides. Here, we review the current knowledge about P-type ATPase inhibitors and their present use as tools in science, medicine, and biotechnology. Recent structural information on a variety of P-type ATPase family members signifies that all P-type ATPases can be expected to share a similar basic structure and a similar basic machinery of ion transport. The ion transport pathway crossing the membrane lipid bilayer is constructed of two access channels leading from either side of the membrane to the ion binding sites at a central cavity. The selective opening and closure of the access channels allows vectorial access/release of ions from the binding sites. Recent structural information along with new homology modeling of diverse P-type ATPases in complex with known ligands demonstrate that the most proficient way for the development of efficient and selective drugs is to target their ion transport pathway.     

CEP Biomarkers as Potential Tools for Monitoring Therapeutics

Background

Carboxyethylpyrrole (CEP) adducts are oxidative modifications derived from docosahexaenoate-containing lipids that are elevated in ocular tissues and plasma in age-related macular degeneration (AMD) and in rodents exposed to intense light. The goal of this study was to determine whether light-induced CEP adducts and autoantibodies are modulated by pretreatment with AL-8309A under conditions that prevent photo-oxidative damage of rat retina. AL-8309A is a serotonin 5-HT_1A receptor agonist.

Methods

Albino rats were dark adapted prior to blue light exposure. Control rats were maintained in normal cyclic light. Rats were injected subcutaneously 3x with 10 mg/kg AL-8309A (2 days, 1 day and 0 hours) before light exposure for 6 h (3.1 mW/cm², λ=450 nm). Animals were sacrificed immediately following light exposure and eyes, retinas and plasma were collected. CEP adducts and autoantibodies were quantified by Western analysis or ELISA.

Results

ANOVA supported significant differences in mean amounts of CEP adducts and autoantibodies among the light + vehicle, light + drug and dark control groups from both retina and plasma. Light-induced CEP adducts in retina were reduced ~20% following pretreatment with AL-8309A (n = 62 rats, p = 0.006) and retinal CEP immunoreactivity was less intense by immunohistochemistry. Plasma levels of light-induced CEP adducts were reduced at least 30% (n = 15 rats, p = 0.004) by drug pretreatment. Following drug treatment, average CEP autoantibody titer in light exposed rats (n = 22) was unchanged from dark control levels, and ~20% (p = 0.046) lower than in vehicle-treated rats.

Conclusions

Light-induced CEP adducts in rat retina and plasma were significantly decreased by pretreatment with AL-8309A. These results are consistent with and extend previous studies showing AL-8309A reduces light-induced retinal lesions in rats and support CEP biomarkers as possible tools for monitoring the efficacy of select therapeutics.     

bisFabs: Tools for rapidly screening hybridoma IgGs for their activities as bispecific antibodies

Bispecific antibodies are a growing class of therapeutic molecules. Many of the current bispecific formats require DNA engineering to convert the parental monoclonal antibodies into the final bispecific molecules. We describe here a method to generate bispecific molecules from hybridoma IgGs in 3–4 d using chemical conjugation of antigen-binding fragments (Fabs) (bisFabs). Proteolytic digestion conditions for each IgG isotype were analyzed to optimize the yield and quality of the final conjugates. The resulting bisFabs showed no significant amounts of homodimers or aggregates. The predictive value of murine bisFabs was tested by comparing the T-cell redirected cytotoxic activity of a panel of antibodies in either the bisFab or full-length IgG formats. A variety of antigens with different structures and expression levels was used to extend the comparison to a wide range of binding geometries and antigen densities. The activity observed for different murine bisFabs correlated with those observed for the full-length IgG format across multiple different antigen targets, supporting the use of bisFabs as a screening tool. Our method may also be used for the screening of bispecific antibodies with other mechanisms of action, allowing for a more rapid selection of lead therapeutic candidates.     

Medicine for the City: Perspective and Solidarity as Tools for Making Urban Health

The United States has pursued policies of urban upheaval that have undermined social organization, dispersed people, particularly African Americans, and increased rates of disease and disorder. Healthcare institutions have been, and can be, a part of this problem or a part of the solution. This essay addresses two tools that healthcare providers can use to repair the urban ecosystem—perspective and solidarity. Perspective addresses both our ability to envision solutions and our ability to see in the space in which we move. Solidarity is our ability to appreciate our fellowship with other people, a mindset that is at the heart of medical practice. These two tools lay the foundation for structurally competent healthcare providers to act in a restorative manner to create a health-giving built environment.     

人工转录因子研究进展

转录因子是真核表达调控中非常重要的一类反式作用因子,通常由DNA结合结构域与效应结构域两部分组成,研究发现这两个结构域可以各自独立发生作用。基于转录因子的这种结构特点,可以人为地选择针对特定序列的DNA结合结构域与具有特定作用的效应结构域构建人工转录因子。目前人工转录因子的DNA结合结构域多为C₂H₂ 型锌指结构,每一个锌指单元由大约30个氨基酸组成,识别DNA双螺旋大沟中相连的3bp序列,并可通过氢键作用与相应的碱基结合;多个锌指可以串联成簇,从而识别并结合较长的DNA序列区域。常见的人工转录因子的效应结构域有激活结构域以及抑制结构域,不同的效应结构域赋予人工转录因子不同的功能。目前人工转录因子已经在基础研究、药物设计以及基因治疗等领域得到了广泛的应用。