Welcome to “2010 Bio-X International Translational Medicine Symposium”

<正>It is our great pleasure to announce 2010 Bio-X International Translational Medicine Symposium (ITMS) with the theme "Pharmacogenomics and Personalized Medicine" organized by Shanghai Jiao Tong University and General     

Can species‐specific prey responses to chemical cues explain prey susceptibility to predation?

The perception of danger represents an essential ability of prey for gaining an informational advantage over their natural enemies. Especially in complex environments or at night, animals strongly rely on chemoreception to avoid predators. The ability to recognize danger by chemical cues and subsequent adaptive responses to predation threats should generally increase prey survival. Recent findings suggest that European catfish (Silurus glanis) introduction induce changes in fish community and we tested whether the direction of change can be attributed to differences in chemical cue perception. We tested behavioral response to chemical cues using three species of freshwater fish common in European water: rudd (Scardinius erythrophthalmus), roach (Rutilus rutilus), and perch (Perca fluviatilis). Further, we conducted a prey selectivity experiment to evaluate the prey preferences of the European catfish. Roach exhibited the strongest reaction to chemical cues, rudd decreased use of refuge and perch did not alter any behavior in the experiment. These findings suggest that chemical cue perception might be behind community data change and we encourage collecting more community data of tested prey species before and after European catfish introduction to test the hypothesis. We conclude that used prey species can be used as a model species to verify whether chemical cue perception enhances prey survival.     

Do cavity‐nesting primates reduce scent marking before retirement to avoid attracting predators to sleeping sites?

The largest population of endangered golden lion tamarins (Leontopithecus rosalia, GLTs) decreased from approximately 330 to 220 individuals between 1995 and 2000 due to a dramatic increase in predation at sleeping sites. We used behavioral data from eight social groups in this population to test two hypotheses: First, if GLTs attempt to mitigate the risk of predation at sleeping sites, they should reduce their rates of scent marking just prior to retirement. Second, if the benefits of scent marking prior to entering the sleeping site merit an increase in the rate of marking, then tamarins should increase their rate of pre-retirement scent marking during the breeding season, when such behavior would have its greatest impact on reproductive fitness. We used a generalized linear model (GLM) repeated-measures analysis to compare rates of daytime scent marking with rates of marking just prior to retirement for males and females. In addition, we compared scent marking prior to retiring in the nonbreeding season to marking rates before retirement in the breeding season for males and both sexes considered concurrently. Contrary to our expectations, GLTs significantly increased their rates of scent marking during the 30 min prior to entering their sleeping site-an observation driven by an increase in male (but not female) rates of marking. Rates of marking before entering the sleeping site were greater in the nonbreeding season compared to the breeding season, when both sexes were considered concomitantly and when males were evaluated alone. We conclude that GLTs do not attempt to minimize predation risk by decreasing scent marking in the period before they enter their sleeping site, and that tamarins do not scent mark at this time of day in order to transmit information about reproductive status or to control reproduction of subordinates. We speculate that scent marking in the 30 min prior to entering sleeping sites may serve to reduce predation risk by enabling tamarin groups to return quickly to favored sleeping sites in the evening when crepuscular predators are active.     

Solvent‐accessible surface area: How well can be applied to hot‐spot detection?

A detailed comprehension of protein‐based interfaces is essential for the rational drug development. One of the key features of these interfaces is their solvent accessible surface area profile. With that in mind, we tested a group of 12 SASA‐based features for their ability to correlate and differentiate hot‐ and null‐spots. These were tested in three different data sets, explicit water MD, implicit water MD, and static PDB structure. We found no discernible improvement with the use of more comprehensive data sets obtained from molecular dynamics. The features tested were shown to be capable of discerning between hot‐ and null‐spots, while presenting low correlations. Residue standardization such as _relSASA_i or _rel/resSASA_i, improved the features as a tool to predict ΔΔG_binding values. A new method using support machine learning algorithms was developed: SBHD (Sasa‐Based Hot‐spot Detection). This method presents a precision, recall, and F1 score of 0.72, 0.81, and 0.76 for the training set and 0.91, 0.73, and 0.81 for an independent test set. Proteins 2014; 82:479–490. © 2013 Wiley Periodicals, Inc.     

Which Call Parameters Signal Threat to Conspecifics in White‐Throated Magpie‐Jay Mobbing Calls?

Abstract Variation in signals often encodes additional information beyond that provided by the main signal. Many species communicate degree of threat using such signal variation. However, multiple signal parameters often covary with threat level, and it is unclear whether receivers are using variation along one or more parameters when assessing threat level. White-throated magpie-jays ( Calocitta formosa ) vary several call parameters when mobbing, and here I report on an experiment testing whether such variation contains information used by conspecific receivers, and which parameters are salient to receivers. I collected data on natural mobbing sequences in two threat contexts and found that mobbing calls were highly variable in both length and inter-call interval, but on average, both parameters were shorter in high threat contexts, while call frequency did not differ. To determine how jays respond to such between-context variation, I conducted a playback experiment in which call length and inter-call interval were independently varied in a factorial design. This is one of the first studies to my knowledge to deconstruct and independently test covarying signal parameters in an anti-predator signaling system. Magpie-jays responded more often to treatments with either short call lengths or short inter-call intervals, in concordance with the natural calling data. However, the two parameters did not appear to act independently; responses were not additive, and short calls at short inter-call intervals elicited no stronger of a response than short calls at long intervals or long calls at short intervals. Receivers can use either parameter when assessing threat level. These data demonstrate that mobbing can signal threat level, that call length and call rate are redundant, and that receivers need not use both to determine whether to approach.     

Proteasomal dysfunction induced by 4‐hydroxy‐2,3‐trans‐nonenal,an end‐product of lipid peroxidation: a mechanism contributing to neurodegeneration?

4-Hydroxy-2,3-trans-nonenal (HNE) is a neurotoxic unsaturated aldehyde end-product of lipid peroxidation. The addition of HNE to NT-2 and SK-N-MC cell lines induces apoptosis and we now investigated the time-course of events occurring prior to apoptosis. Treatment of both NT-2 and SK-N-MC cell lines with HNE led to HNE association with the proteasome, increased levels of protein carbonyls and ubiquitinated proteins, and decreased proteasomal function. There was also decreased metabolic activity, cytochrome c release and activation of caspase 3, followed by apoptotic changes including chromatin condensation, cell shrinkage and DNA fragmentation and laddering. Overexpression of mutant superoxide dismutase 1 proteins associated with amyotrophic lateral sclerosis decreased proteasomal activities in the absence of HNE and accelerated the apoptosis induced by HNE. By contrast, overexpression of wild-type superoxide dismutase 1 did not affect basal levels of proteasomal activity. The data suggest that accumulation of ubiquitinated proteins and impairment of proteasomal function are important events in HNE toxicity. We propose that the proteasomal system is a significant target of HNE neurotoxicity in a wide range of neurodegenerative diseases, especially if abnormal proteins are being expressed.     

Passive immunization against oral AIDS virus transmission: An approach to prevent mother‐to‐infant HIV‐1 transmission?

To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T.W. Baba, J. Koch, E.S. Mittler et al: AIDS Res Hum Retroviruses 10:351-357, 1994). We protected four neonates from oral SHIV-vpu+ challenge by ante- and postpartum treatment with a synergistic triple combination of immunoglobulin (Ig) G1 human anti-HIV-1 neutralizing monoclonal antibodies (mAbs) (T.W. Baba, V. Liska, R. Hofmann-Lehmann et al: Nature Med 6:200-206, 2000), which recognize the CD4-binding site of Env, a glycosylation-dependent gp120, or a linear gp41 epitope. Two neonates that received only postpartum mAbs were also protected from oral SHIV-vpu+ challenge, indicating that postpartum treatment alone is sufficient. Next, we evaluated a similar mAb combination against SHIV89.6P, which encodes env of primary HIV89.6. One of four mAb-treated neonates was protected from infection and two maintained normal CD4+ T-cell counts. We conclude that the epitopes recognized by the three mAbs are important determinants for achieving protection. Combination immunoprophylaxis with synergistic mAbs seems promising to prevent maternal HIV-1 transmission in humans.     

Should China subsidize cofiring to meet its 2020 bioenergy target? A spatio‐techno‐economic analysis

China has developed ambitious bioenergy installation targets as part of its broader goals to increase its renewable energy‐generating capacity and decarbonize its economy. A key target feedstock for bioenergy is the 800 million tonnes of agricultural residues that China produces each year. At present, the main financial incentive to support bioenergy generation from agricultural residues is a feed‐in‐tariff provided for bioenergy that is produced by units that take 80% or more of their feedstock energy from biomass. Although this policy has catalysed the construction of many bioenergy units, there are reports that these projects are experiencing serious financial and technical problems, leading to low operational efficiency and even closure. An alternative option for China's agricultural residues is cofiring with coal in existing power stations. However, this is currently unprofitable for power station operators, as cofiring is not eligible for financial assistance through the bioenergy feed‐in‐tariff. In the light of China's ambitious target to install 30GW of bioenergy generation capacity by 2020, this study investigates the extent to which extension of the bioenergy feed‐in‐tariff to include cofiring could contribute towards this goal. The results suggest that 39% of China's straw energy resources are located within 50 km of a power station. Assuming cofiring ratios of up to 10% coal energy replacement, an annual 89–117TWh of electricity could be generated by cofiring agricultural residues collected within 50 km radii of power stations. If China extends its bioenergy subsidies to include cofiring, an annual 62–92TWh can be produced at an internal rate of return of 8% or more. This equates to 42–62% of the bioenergy generation that China might expect if it met its 2020 target of installing 30GW of bioenergy capacity. Overall, this indicates a strong case for the Chinese government to extend its existing bioenergy feed‐in‐tariff to include cofiring at low energy replacement ratios.     

A new paradigm in molecular recognition? specific antibody binding to membrane‐inserted HIV‐1 epitopes

The conserved membrane proximal external region (MPER), adjacent to the transmembrane domain (TMD) of human immunodeficiency virus type-1 (HIV-1) gp41 glycoprotein subunit, is accessible to the broadly neutralizing 4E10 and 2F5 monoclonal antibodies (mAbs) and, therefore, constitutes a potential target for vaccine design. This gp41 domain is postulated to be functional during the Env glycoprotein-mediated fusion reaction by destabilizing the highly rigid viral envelope. To perform this task, the aromatic-rich MPER is believed to insert into the interfacial region of the viral membrane external monolayer, thereby inducing the restructuring of the lipid bilayer required for fusion-pore opening. This model predicts that: (i) 2F5 and 4E10 mAbs are capable of binding epitopes inserted into the membrane interface; (ii) in-membrane binding will result in effective blocking of MPER membrane activity; and (iii) both processes, in-membrane recognition and blocking of membrane activity, can be modulated by altering both the lipid composition and the MPER amino acid sequence. We review here recently reported experimental data consistent with those predictions, and further speculate on their relevance for prospective anti-HIV vaccine development.     

Life‐history innovation to climate change: can single‐brooded migrant birds become multiple breeders?

When climatic conditions change and become outside the range experienced in the past, species may show life‐history innovations allowing them to adapt in new ways. We report such an innovation for pied flycatchers Ficedula hypoleuca. Decades of breeding biological studies on pied flycatchers have rarely reported multiple breeding in this long‐distance migrant. In two populations, we found 12 recent incidents of females with second broods, all produced by extremely early laying females in warm springs. As such early first broods are a recent phenomenon, because laying dates have gradually advanced over time, this innovation now allows individual females to enhance their reproductive success considerably. If laying dates continue advancing, potentially more females may become multiple breeders and selection for early (and multiple) breeding phenotypes increases, which may accelerate adaptation to climatic change.     

Exploring lake ecosystems: hierarchy responses to long‐term change?

Shifts in climate regime have provoked substantial trophic‐ and species‐dependent changes within ecosystems. With growing concerns of present global warming, we examined potential lake ecosystem responses, natural hierarchy responses (i.e. immediate responses at lower system levels as opposed to delayed responses at higher system levels), and possible shifts among abiotic (physics, nutrients) and biotic (phytoplankton, zooplankton) system components. Specifically, we analyzed decadal data collected from Müggelsee, a lake in Berlin, Germany, for climate‐induced abiotic and biotic changes, their timing and type, and classified them as abrupt permanent, gradual permanent, abrupt temporary, or monotonic. We further categorized variable changes as a function of system hierarchy, including lake physics (ice, temperature, stratification), nutrients (phosphorus, nitrogen, silicate), plankton, and levels of integration (i.e. species, taxonomic groups, and total plankton). Contrary to current theory, data suggest abrupt responses did not occur in a hierarchy‐dependent manner, nor was a clear pattern observed among functional system‐based categories. Abrupt permanent changes were the most prominent response pattern observed, suggesting they may be driven by large‐scale climatic oscillations and by surpassed thresholds, as noted in previous case studies. Gradual changes coincided with affected abiotic parameters spanning an expansive time range; for example, climatic effects in spring preceded changes in nutrient limitation. Variables displaying no long‐term changes pointed to compensation processes caused by, e.g., simultaneously acting forces of warming trends and climate‐independent changes in trophic state. Nevertheless, the complexity of response patterns at the single system level manifested clear chronological regime shifts in abiotic and biotic parameters in spring and, to a lesser extent, in summer. With regard to projected global warming, the majority of currently unaffected system levels may face impending thermal thresholds, achievement of which would result in an accelerated shift in ecosystem state.     

Is Mass‐based Metabolism Rate Proportional to Surface Area in Plant Leaves? A Data Re‐analysis

We re-analyzed two large published databases on leaf traits of plant species from seven different biomes, and determined the scaling relationship between leaf metabolism rate (mass-based photosynthesis capacity, Amass, and mass-based dark respiration, Rdmass) and specific leaf area (SLA) across biomes, using a standardized major axis (SMA) method. Overall pooled data produced a scaling exponent of 1.33 for the relationship between Amass and SLA, significantly larger than 1.0; and 1.04 between Rdmass and SLA. The scaling exponent of the relationship between Amass and SLA ranged between 1.23 (in tropical forest) and 1.66 (in alpine biome), and it was significantly larger in alpine (1.66) and grass/meadow (1.52) biomes than in tropical forest (1.23) and wetland (1.27). The exponent of the relationship between Rdmass and SLA, however,was much smaller in wetland (1.05) than in temperate forest (1.29) and tropical rainforest (1.65). In general, the predicated universal scaling relationship that the mass-based metabolism rate should be proportional to surface area in organisms is not applicable at the leaf-level in plants. Rather, the large slope difference of the relationship between leaf metabolism rate and SLA found among biomes indicates that the strength of the selective forces driving the scaling relationship is different among the biomes. The result basically suggests the importance of increasing SLA to plant carbon gain in stressful environments and to carbon loss in favorable habitats, and therefore has an important implication for survival strategies of plants in different biomes.     

Is Dietary Fat Intake Related to Liking or Household Availability of High‐ and Low‐Fat Foods?

Objectives : Despite the increasing availability of low‐ and reduced‐fat foods, Americans continue to consume more fat than recommended, which may be a contributing factor to the obesity epidemic. This investigation examined relationships between liking and household availability of high‐ and low‐fat foods and their association with dietary fat intake. Research Methods and Procedures : A food frequency questionnaire assessed percent calories from fat consumed over the past year in 85 men and 80 women. Participants reported their degree of liking 22 “high‐fat foods” (>45% calories from fat) and 22 “low‐fat foods” (<18% calories from fat), and the number and percentage (number of high‐ or low‐fat foods/total number of foods × 100) of these high‐ and low‐fat foods in their homes. Results : Hierarchical regression analyses examined the ability of liking and household availability of low‐ and high‐fat foods to predict percent dietary fat intake. After controlling for age, sex, and BMI, liking ratings for high‐ and low‐fat foods and the interaction of liking for low‐fat foods by the percentage of low‐fat foods in the household were significant predictors of percent dietary fat consumed. Greater liking of high‐fat foods and lower liking of low‐fat foods, both alone and combined with a lower percentage of low‐fat foods in the home, were predictive of higher dietary fat intake. Discussion : Interventions designed to reduce dietary fat intake should target both decreasing liking for high‐fat foods and increasing liking for low‐fat foods, along with increasing the proportion of low‐fat foods in the household.     

Do plant communities exist? Evidence from scaling‐up local species‐area relations to the regional level

Abstract. One long tradition in ecology is that discrete communities exist, at least in the sense that there are areas of relatively uniform vegetation, with more rapid change in species composition between them. The alternative extreme view is the Self‐similarity concept – that similar community variation occurs at all spatial scales. We test between these two by calculating species‐area curves within areas of vegetation that are as uniform as can be found, and then extrapolating the within‐community variation to much larger areas, that will contain many ‘communities’. Using the Arrhenius species‐area model, the extrapolations are remarkably close to the observed number of species at the regional/country level. We conclude that the type of heterogeneity that occurs within ‘homogeneous’ communities is sufficient to explain species richness at much larger scales. Therefore, whilst we can speak of ‘communities’ for convenience, the variation that certainly exists at the ‘community’ level can be seen as only a larger‐scale manifestation of micro‐habitat variation.     

Post‐fire seed predation: Does distance to unburnt vegetation matter?

Human‐induced changes to fire regimes result in smaller, more patchy fires in many peri‐urban areas, with a concomitant increase in potential edge effects. In sclerophyll vegetation, many structurally dominant serotinous plants rely on the immediate post‐fire environment for recruitment. However, there is little information about how fire attributes affect seed predation or recruitment for these species. We examined the influence of distance to unburnt vegetation on post‐dispersal seed predation for five serotinous species from sclerophyll vegetation in the Sydney region, south‐eastern Australia; Banksia serrata L.f., Banksia spinulosa Sm. var. spinulosa, Hakea gibbosa (Sm.) Cav., Hakea teretifolia (Salisb.) Britten (all Proteaceae) and Allocasuarina distyla (Vent.) L. Johnson (Casuarinaceae). We used cafeteria trials and differential exclusion of vertebrates and invertebrates to test whether rates of seed removal for these five species differed among (i) unburnt, (ii) burnt‐edge (approx. 10 m from unburnt vegetation) and (iii) burnt‐interior (approx. 100 m from unburnt vegetation) locations. When all animals had access to seeds, seeds were removed at lower rates from burnt‐interior areas than from other locations. Vertebrates (small mammals) showed this pattern markedly the first time the experiment was run, but in a repeat trial this effect disappeared. Rate of seed removal by invertebrates differed among plant species but we did not detect any such differences for removal by vertebrates. Overall rates of seed removal also differed significantly between the two fires studied. Our results indicate that small mammal seed predation can be substantial for large‐seeded serotinous shrubs, and that differences in the perimeter: area ratio, severity or size of a fire are likely to affect seed predation.