Digging deep into the pockets of orphan nuclear receptors: insights from structural studies

Nuclear receptors comprise a large family of proteins that shares a common structure and mechanism of action. Members of this family, first cloned 20 years ago, are regulated by small lipophilic signaling molecules such as steroid hormones, retinoids and thyroid hormone. More recently, the characterization of proteins that resemble nuclear receptors (referred to as orphan receptors) has resulted in the determination of novel signaling pathways. However, many orphan-receptor ligands remain unidentified, and recent structural studies of the binding domains for orphan-receptor ligands suggest that not all of these receptors use ligand binding in a classical way. Notably, it is now evident that some orphan receptors lack the capacity for ligand binding, which suggests that they are regulated by alternative, ligand-independent mechanisms.     

Digging deep to open the white black box of snow root phenology

Snow roots are specialized structures recently discovered in the Caucasian alpine snow-bed plant Corydalis conorhiza. They form extensive networks that grow into snow packs against gravity, most probably to gather nitrogen from snow. Here we test the hypothesis that snow roots are true winter organs, i.e., they should already start growth early in winter to lay down the infrastructure for N capture from snow packs well before their melt-out. This would require winter surface and soil temperatures continuously close to or above freezing. Excavations of snow roots from snow packs in January and May, accompanied by temperature recordings and anatomical observations, supported our hypothesis. These findings complete the annual cycle of snow root phenology. They also emphasize the evolutionary and ecological significance of these specialized winter organs. Moreover, their likely association with a particular abiotic temperature and snow regime will facilitate the search for snow roots in other species.     

Digging deep for ancient relics: a survey of protein motifs in the intergenic sequences of four eukaryotic genomes

We have examined conserved protein motifs in the non-coding, intergenic regions ("pseudomotif patterns") and surveyed their occurrence in the fly, worm, yeast and human genomes (chromosomes 21 and 22 only). To identify these patterns, we masked out annotated genes, pseudogenes and repeat regions from the raw genomic sequence and then compared the remaining sequence, in six-frame translation, against 1319 patterns from the PROSITE database. For each pseudomotif pattern, the absolute number of occurrences is not very informative unless compared against a statistical expectation; consequently, we calculated the expected occurrence of each pattern using a Poisson model and verified this with simulations. Using a p-value cut-off of 0.01, we found 67 pseudomotif patterns over-represented in fly intergenic regions, 34 in worm, 21 in human and six in yeast. These include the zinc finger, leucine zipper, nucleotide-binding motif and EGF domain. Many of the over-represented patterns were common to two or more organisms, but there were a few that were unique to specific ones. Furthermore, we found more over-represented patterns in the fly than in the worm, although the fly has fewer pseudogenes. This puzzling observation can be explained by a higher deletion rate in the fly genome. We also surveyed under-represented patterns, finding 23 in the fly, 12 in the worm, 18 in human and two in yeast. If intergenic sequences were truly random, we would expect an equal number of over and under-represented patterns. The fact that for each organism the number of over-represented patterns is greater than the number of under-represented ones implies that a fraction of the intergenic regions consist of ancient protein fragments that, due to accumulated disablements, have become unrecognizable by conventional techniques for gene and pseudogene identification. Moreover, we find that in aggregate the over-represented pseudomotif patterns occupy a substantial fraction of the intergenic regions. Further information is available at http://pseudogene.org     

Digging deep for diversity: riparian seed bank abundance and species richness in relation to burial depth

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Mimicry: the hunting of the supergene

Mimicry is an example of an adaptation that requires the integration of several components. Genetic characterisation of a mimicry polymorphism in a butterfly reveals the expected suppression of recombination among its components, preventing the production of unfit character combinations.     

The FOX hunting system: an alternative gain-of-function gene hunting technique

We have developed a novel gain-of-function system that we have named the FOX hunting system (Full-length cDNA Over-eXpressing gene hunting system). We used normalized full-length cDNA and introduced each cDNA into Arabidopsis by in planta transformation. About 10 000 independent full-length Arabidopsis cDNAs were expressed independently under the CaMV 35S promoter in Arabidopsis. Each transgenic Arabidopsis contained on average 2.6 cDNA clones and was monitored under various categories such as morphological changes, fertility and leaf color. We found 1487 possible morphological mutants from 15 547 transformants. When 115 pale green T(1) mutants were analyzed, 59 lines represented the mutant phenotypes in more than 50% of the T(2) progeny. Characterization of two leaf color mutants revealed the significance of this approach. We also document mutants from several categories and their corresponding full-length cDNAs.     

Control of aggregation in protein refolding: the temperature-leap tactic.

The kinetics of renaturation of bovine carbonic anhydrase II (CAII) were studied from 4 degrees to 36 degrees, at the relatively high [CAII] of 4 mg/mL. Following dilution to 1 M guanidinium chloride, aggregate formation is very rapid and reduces the formation of active enzyme. The CAII activity yield at 150 min, 20 degrees (approximately 60%), is greater than that at either 4 degrees or 36 degrees. However, if refolding is conducted at 4 degrees, aggregation is reduced dramatically and 37% yield is obtained at 120 min. If the solution is then rapidly warmed to 36 degrees, the yield rises rapidly to 95% at 150 min. This is an example of the "temperature leap" tactic. These results can be understood on the basis of two slow-folding intermediate whose kinetics have been studied. Only the first of these forms aggregates. Kinetic simulations show that, at 4 degrees, the first intermediate is depleted after 120 min, and the second intermediate rapidly isomerizes to active enzyme on warming. A series of experiments was conducted where the initial (120 min) folding temperature was systematically varied, followed by a "leap" to 36 degrees for 30 additional minutes. With initial incubations from 4 degrees to 12 degrees, the final yield is > 90%, drops rapidly from 12 degrees to 20 degrees, and decreases more gradually to approximately 45% at 36 degrees. The overall results qualitatively fit the simple idea of ordinary temperature-accelerated reactions in competition with hydrophobic aggregation, which is strongly suppressed in the cold. Qualifications are discussed for the temperature-leap approach to find application in refolding other proteins.     

野生动物狩猎、贸易和狩猎持续性研究进展

过度狩猎和过度贸易是当前生物多样性保护面临的重大挑战。虎骨和犀牛角贸易、东南亚一带的活野生动物非法狩猎和贸易、俄国远东地区及中俄边境野生动物产品非法贸易、热带地区的野生动物狩猎和丛林肉食贸易以及喜马拉雅区域的野生动物非法贸易正严重威胁着全球的野生动物资源。提倡狩猎持续性是解决过度贸易和过度捕杀的途径之一。 在众多的狩猎持续性模型中,“狩猎动物避难所模型”和“空间控制模型”提倡在狩猎区建保护区,有广泛的应用前景。了解偷猎动态和特征及其对濒危动物种群的影响,协调传统医药和野生动物保护间的关系,控制边境地区的野生动物非法狩猎和贸易,以及在保护实践中运用狩猎持续性模型是未来保护关注的焦点。野生动物非法狩猎和非法贸易严重威胁着我国的生物多样性保护和持续利用,但相关的研究却比较少。建议建立野生动物捕杀和贸易的监测机构,加强相关的立法、执法和保护区管理,开展野生动物捕杀和贸易研究。     

High blood pressure: hunting the genes.

High blood pressure is a disease of unknown cause. Family history of the disease indicates higher risk, but it is not known which genes are involved or how they interact with environmental influences to produce the disorder. Molecular biology offers an approach to problems that have not so far been solved by classical physiology or biochemistry. By analysing polymorphic variation in chromosome markers such as minisatellite sequences, or by restriction fragment polymorphism analysis of candidate genes, attempts are being made to link genetic variations with hypertension. In genetically hypertensive rats, hypertension is associated with a polymorphism of the renin gene and with other loci on chromosomes 10 and 18. The role of these loci in human hypertension remains to be determined. Other genes such as sodium-lithium countertransport may be involved. Environmental factors such as stress or salt intake could influence the rate or timing of expression of certain genes and thus result in hypertension.     

Khoisan wind: hunting and healing

In this paper I draw on my findings and those of historical and recent Khoisan ethnography to attempt to explain how these southern African 'Khoi' and San peoples relate to wind and how the environmental phenomenon has informed their epistemology and ontology. I begin by fleshing out the knowledge and experience of wind among these past and recent hunter-gatherers and, pointing to continuity in wind relationships and the ideas that stem from them, I go on to demonstrate how wind weaves into Khoisan understandings of the body and illness. Despite extensive interest in Bushman healing, anthropologists have overwhelmingly concentrated on the 'trance' healing dance. My findings suggest this partiality has obscured the wider healing context in which the dance operates. Exploring the wider context, including massage, 'medicinal cuts', and witchcraft, reveals that the 'potency' conceived as central to the healing dance is, in certain contexts, equivalent to overlapping ideas of wind, arrows, and smell. Examination of the ethnography reveals that a number of the associations I make between wind and potency have been partially recognized in specific Khoisan contexts but, because comparative studies of Khoisan are difficult and unpopular, these similarities have gone largely unnoticed.     

Assessing trophy hunting in South Africa by comparing hunting and exporting databases

Trophy hunting constitutes a major part of the global wildlife tourism industry and is connected through the export of kills to international wildlife trade. Inconsistencies between kills and exports can contribute to identifying illegal trophy hunting that constitutes a major threat to biodiversity conservation. This paper quantitatively analyses to what extent the data of trophy hunting kills and of trophy exports are consistent using the example of South Africa. Data was extracted from two different sources for the year 2018. These sources were trade data reported under the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) and its Trade Database on the export of trophy items from South Africa, which is compared with the South African Professional Hunting statistics (SAPHs) containing trophy kills information for each species and the country of origin of the hunter. The data of trophy hunting kills and data of trophy hunting export was found to differ to varying degrees across the countries contributing to trophy hunting and CITES-listed trophy-hunted species. We found that both databases report hunting of the same 28 threatened taxa. On the other hand, the same data reports that hunters of 64 nationalities participated in a total of 4,726 trophy kills, while only 3,131 hunting trophy items were exported from South Africa, to 37 countries as final destinations. Among the possible reasons for the discrepancies found, we suggest that the time required to taxidermize trophy specimens may delay the items being addressed to their final destination, in addition to the dual citizenship of some hunters that should also have some influence on our results, as well as the important commercial destination of Brussels Airport. The USA show the highest absolute number of trophy hunters, followed by Spain, but Denmark is the highest driver per capita. Therefore, greater participation of these countries in conservation policies for endangered species is necessary. Additionally, a more detailed differentiation of the term “trophy” to more specific terms such as claws, skins, skulls, etc. may improve reporting systems to easier identify illegal activities related to hunting.     

The hunting of the Src

The non-receptor tyrosine kinase Src is important for many aspects of cell physiology. The viral src gene was the first retroviral oncogene to be identified, and its cellular counterpart was the first proto-oncogene to be discovered in the vertebrate genome. Src has been important, not only as an object of study in itself, but also as an entry point into the molecular genetics of cancer.     

自体CIK细胞治疗21例中晚期恶性实体瘤的肿瘤标志物变化观察

目的观察自体细胞因子诱导的杀伤细胞（CIK）过继免疫疗法治疗中晚期恶性实体肿瘤的临床疗效及肿瘤标志物变化,初步对该疗法作出评价。方法取中晚期恶性实体肿瘤患者自体外周血50ml,根据文献报道方法体外诱导扩增CIK细胞。培养约14d后,一次性回输入患者体内,观察患者CIK细胞回输前2周及回输后4周左右外周血免疫指标变化、肿瘤标志物变化、生活质量及Karnofsky评分变化,随访1年观察1年生存率。采用t检验及寿命表法进行统计分析。结果在21例接受CIK回输治疗的患者中,治疗前出现有代表意义的肿瘤标志物异常升高的患者有14例,1次回输后有8名患者出现肿瘤标志物下降,其中1名患者降至正常范围;免疫指标在CIK细胞回输后4周较回输前2周均无有统计学意义,其中CD3由70.81﹪±10.52﹪升至71.91﹪±11.09﹪,t=0.762,P=0.455;CD4由39.06﹪±11.03﹪升至39.21﹪±8.74﹪,t=0.093,P=0.927;CD8由28.75﹪±8.22﹪升至29.88﹪±10.13﹪,t=0.895,P=0.382;CD16^＋CD56^＋（即NK细胞）由15.73﹪±9.52﹪升至15.37﹪±6.66﹪,t=-0.173,P=0.865;EORTCQLQ-C30（vertion3.0）评分中总体健康状况（globalhealth）由（41.67±17.28）分上升至（46.43±17.19）分,P=0.076;以上各指标治疗前后差异均无统计学意义。但功能子量表中的躯体功能（physicalfunctioning）单项[由（62.94±17.48）分上升至（66.67±17.37）分,P=0.012]和症状子量表中的疲倦（fatigue）[由（51.33±20.03）分下降至（43.38±16.81）分,P=0.012]、疼痛（pain）[由44.44﹪±19.24﹪下降至（36.51±14.55）分,P=0.038]及食欲丧失（appetiteloss）[由（52.38±19.92）分下降至（38.09±21.82）分,P=0.016]单项差异均有统计学意义（P〈0.05）;卡氏评分由[（61.42±3.59）分上升至（62.38±4.36）分,t=1.000,P〉0.05];随访1年内有3名患者死亡,生存率约85.7﹪。结论自体CIK细胞回输治疗后肿瘤标志物有明显改变,同时对缓解晚期恶?     

Egg-laying tactic in Phyllomorpha laciniata in the presence of parasitoids

Female insects are expected to choose oviposition sites that have the best conditions for offspring development and survival. Natural enemies, such as predators and parasitoids, may have a strong influence on the selection of oviposition substrates by phytophagous insects. The golden egg bug, Phyllomorpha laciniata (Villers) (Heteroptera: Coreidae) has an unusual reproductive strategy. Females mainly use conspecifics, both males and other females, as egg-laying substrates, but occasionally they oviposit on plants as well. Survival of the eggs is higher when eggs are carried by conspecifics than when they are laid on plants, due to predation and parasitism. We investigated egg-laying behavior in the forced presence of the egg parasitoid Gryon bolivari (Giard) (Hymenoptera: Scelionidae). Specifically, we studied whether females provide egg protection by avoiding oviposition under the risk of egg parasitization. We expected a lower oviposition rate under parasitoid presence, and the eggs, if any, to be placed preferably on conspecifics and not on plants, thus ensuring higher survival of the progeny. The results show that P. laciniata 's egg-laying rate was lower when they were enclosed with parasitoids than when parasitoids were absent, especially when plants were the only substrate to oviposit on. Moreover, females showed strong preference for laying eggs on conspecifics rather than on plants. Egg-laying in P. laciniata appears to be not only influenced by the availability of conspecifics, but also by the presence of egg parasitoids. This indicates that females may be able to detect G. bolivari and avoid oviposition when parasitoids are present. We discuss the possibility of conspecifics as enemy-free space.     

The potential impacts of changes in bear hunting policy for hunting organisations in Croatia

The brown bear (Ursus arctos) in Croatia is currently being managed through trophy hunting, with quotas allocated to local hunting organisations. Human–bear conflict is present at a low level, but any losses are compensated by the hunting organisations that benefit from bear hunting. Attitudes towards bears are generally positive, and the bear population appears stable, or even increasing. Croatia's current bear hunting policy relies upon both the ecological sustainability of the quotas and the economic sustainability of the hunting organisations. To address the first of these pillars of current policy, we used a two-sex matrix model of the bear population to investigate the biological sustainability of current hunting levels. The model suggests that if the annual allocated quota were fully realised, the population would suffer a considerable decrease over 10 years. A likely explanation for the mismatch between this result and the observed stability of the population is that the bear population size is underestimated. To address the second pillar, we quantified the current structure, costs and benefits of bear hunting to hunting organisations through an interview survey with hunting managers. We found that bear hunting is a substantial component of hunting organisations' income, supporting the other activities of the organisation. Croatia's recent accession to the EU will require changes in their bear management system, potentially stopping bear trophy hunting. Therefore, we assessed the changes in hunting organisations' budgets in the absence of bear hunting. Our results demonstrate that a loss of bear trophy hunting would result in a substantial loss of income to the hunting organisations. Moving bear hunting and compensation mechanisms from local management and responsibility to a more centralised system without trophy hunting, as suggested by EU legislation, will lead to considerable uncertainties. These include how to make centralised decisions on population targets and offtake levels for population control, given the uncertainty around population estimates, and on compensation payments given the loss of the current system which relies heavily on local income from trophy hunting, local relationships and informal monetary and non-monetary compensation.