Anticipating future conditions via trajectory sensitivity

Plants are known to be highly responsive to environmental heterogeneity and normally allocate more biomass to organs that grow in richer patches. However, recent evidence demonstrates that plants can discriminately allocate more resources to roots that develop in patches with increasing nutrient levels, even when their other roots develop in richer patches. Responsiveness to the direction and steepness of spatial and temporal trajectories of environmental variables might enable plants to increase their performance by improving their readiness to anticipated resource availabilities in their immediate proximity. Exploring the ecological implications and mechanisms of trajectory-sensitivity in plants is expected to shed new light on the ways plants learn their environment and anticipate its future challenges and opportunities.Key words: Gradient perception, phenotypic plasticity, anticipatory responses, plant behavior, plant learningNatural environments present organisms with myriad challenges of surviving and reproducing under changing conditions.¹ Depending on its extent, predictability and costs, environmental heterogeneity may select for various combinations of genetic differentiation and phenotypic plasticity.^2–6 However, phenotypic plasticity is both limited and costly.⁷ One of the main limitations of phenotypic plasticity is the lag between the perception of the environment and the time the products of the plastic responses are fully operational.⁷ For instance, the developmental time of leaves may significantly limit the adaptive value of their plastic modification due to mismatches between the radiation levels and temperatures prevailing during their development and when mature and fully functional.^8,9 Accordingly, selection is expected to promote responsiveness to cues that bear information regarding the probable future environment.^9,10Indeed, anticipatory responses are highly prevalent, if not universal, amongst living organisms. Whether through intricate cerebral processes, such as in vertebrates, nervous coordination, as in Echinoderms,¹¹ or by relatively rudimentary non-neural processes, such as in plants¹² and bacteria,¹³ accumulating examples suggest that virtually all known life forms are able to not only sense and plastically respond to their immediate environment but also anticipate probable future conditions via environmental correlations.¹⁰Perhaps the best known example of plants'' ability to anticipate future conditions is their responsiveness to spectral red/far-red cues, which is commonly tightly correlated with future probability of light competition.¹⁴ Among others, plants have been shown to respond to cues related to anticipated herbivory^15,16 and nitrogen availability.¹⁷ Imminent stress is commonly anticipated by the perception of a prevailing stress. For example, adaptation to anticipated severe stress was demonstrated to be inducted by early priming by sub-acute drought,¹⁸ root competition¹⁹ and salinity.²⁰Future conditions can also be anticipated by gradient perception: because resource and stress levels are often changing along predictable spatial and temporal trajectories, spatio-temporal dynamics of environmental variables might convey information regarding anticipated growth conditions (Fig. 1). For example, the order of changes in day length, rather than day length itself, are known to assist plants in differentiating fall from spring and thus avoid blooming in the wrong season.²¹ In addition, responsiveness to environmental gradients as such, i.e., sensitivity to the direction and steepness of environmental trajectories, independently from the stationary levels of the same factors, has been demonstrated in higher organisms, such as the perception of acceleration in contrast to velocity;²² and the dynamics of skin temperature in contrast to stationary skin temperature;²³ where the adaptive value of the second-order derivatives of environmental factors is paramount. Similar perception capabilities have also been demonstrated in rudimentary life forms such as bacteria (reviewed in refs. ¹³ and ²⁴) and plants.^25,26 Specifically, perception of environmental trajectories might assist organisms to both anticipate future conditions and better utilize the more promising patches in their immediate environment.^27,28Open in a separate windowFigure 1Trajectory sensitivity in plants. The hypothetical curves depict examples of spatio-temporal trajectories of resource availability, which might be utilized by plants to increase foraging efficiency in newly-encountered patches. When young or early-in-the-season (segment 1–2), plants are expected to allocate more resources to roots that experience the most promising (steepest increases or shallowest decreases) resource availabilities (e.g., allocating more resources to organs in INC-1 than INC-2). In addition, plants are predicted to avoid allocation to roots experiencing decreasing trajectories (DEC, segment 1–2); although temporarily more abundant with resources, such DEC patches are expected to become poorer than alternative patches in the longer run (segment 2–3).²⁹ However, responsiveness to environmental trajectories is only predicted where the expected period of resource uptake is relatively long, e.g., when plants are still active in segment 2–3, a stipulation which might not be fulfilled in e.g., short-living annuals with life span shorter than segment 1–2.In a recent study, Pisum plants have been demonstrated to be sensitive to temporal changes in nutrient availabilities. Specifically, plants allocated greater biomass to roots growing under dynamically-improving nutrient levels than to roots that grew under continuously higher, yet stationary or deteriorating, nutrient availabilities.²⁹ Allocation to roots in poorer patches might seem maladaptive if only stationary nutrient levels are accounted for, and indeed-almost invariably, plants are known to allocate more resources to organs that experience higher (non-toxic) resource levels (reviewed in ref. ³³). Accordingly, the new findings suggest that rather than merely responding to the prevailing nutrient availabilities, root growth and allocation are also responsive to trajectories of nutrient availabilities (Fig. 1).¹⁰Although Shemesh et al.²⁹ demonstrated trajectory-sensitivity of individual roots to temporal gradient of nutrient availabilities, it is likely that this sensitivity helps plants sense spatial gradients, whereby root tips perceive changes in growth conditions as they move through space.³⁴ Interestingly, because the trajectory-sensitivity was observed when whole roots were subjected to changing nutrient levels, it is likely that trajectory sensitivity in roots is based on the integration of sensory inputs perceived by yet-to-be-determined parts of the root over time, i.e., temporal sensitivity/memory (e.g. reviewed in ref. ³⁵), rather than on the integration of sensory inputs at different locations on the same individual roots (i.e., spatial sensitivity).Besides the direction of change, it is hypothesized that plants are also sensitive to the steepness of environmental trajectories (Fig. 1). This might be especially crucial in short-living annuals, which are expected to only be responsive to trajectories steep enough to be indicative of changes in growth conditions before the expected termination of the growth season (Fig. 1).Studying responsiveness to environmental variability is pivotal for understanding the ecology and evolution of any living organism. However, until recently most attention has been given to the study of responses to stationary spatial and temporal heterogeneities in growth conditions. Exploring the ecological implications and mechanisms of trajectory sensitivity in plants is expected to shed new light on the ways plants learn their immediate environment and anticipate its future challenges and opportunities.     

A Unified Approach to Multi‐item Reliability

Summary The reliability of multi‐item scales has received a lot of attention in the psychometric literature, where a myriad of measures like the Cronbach's α or the Spearman–Brown formula have been proposed. Most of these measures, however, are based on very restrictive models that apply only to unidimensional instruments. In this article, we introduce two measures to quantify the reliability of multi‐item scales based on a more general model. We show that they capture two different aspects of the reliability problem and satisfy a minimum set of intuitive properties. The relevance and complementary value of the measures is studied and earlier approaches are placed in a broader theoretical framework. Finally, we apply them to investigate the reliability of the Positive and Negative Syndrome Scale, a rating scale for the assessment of the severity of schizophrenia.     

An abelisaurid humerus from the Upper Cretaceous of India

The Lameta Formation (Upper Cretaceous, Maastrichtian) of India has yielded abundant fossils of abelisaurid theropods, including bones from the cranium, vertebral column, pectoral and pelvic girdles, and hindlimb. However, the forelimbs of Indian abelisaurids remain unknown. Here we describe an abelisaurid humerus from exposure of the Lameta Formation near the village of Rahioli in northwestern India. This new material exhibits derived traits that are distinctive of Abelisauridae, for example an articular head that is hemispherical in proximal view, thus establishing the specimen as the first abelisaurid humerus from India.     

The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase

Hsp70-Hsp40-NEF and possibly Hsp100 are the only known molecular chaperones that can use the energy of ATP to convert stably pre-aggregated polypeptides into natively refolded proteins. However, the kinetic parameters and ATP costs have remained elusive because refolding reactions have only been successful with a molar excess of chaperones over their polypeptide substrates. Here we describe a stable, misfolded luciferase species that can be efficiently renatured by substoichiometric amounts of bacterial Hsp70-Hsp40-NEF. The reactivation rates increased with substrate concentration and followed saturation kinetics, thus allowing the determination of apparent V(max)' and K(m)' values for a chaperone-mediated renaturation reaction for the first time. Under the in vitro conditions used, one Hsp70 molecule consumed five ATPs to effectively unfold a single misfolded protein into an intermediate that, upon chaperone dissociation, spontaneously refolded to the native state, a process with an ATP cost a thousand times lower than expected for protein degradation and resynthesis.     

The plasma membrane Ca2+ pump isoform 4a differs from isoform 4b in the mechanism of calmodulin binding and activation kinetics: implications for Ca2+ signaling

The inhibition by the regulatory domain and the interaction with calmodulin (CaM) vary among plasma membrane calcium pump (PMCA) isoforms. To explore these differences, the kinetics of CaM effects on PMCA4a were investigated and compared with those of PMCA4b. The maximal apparent rate constant for CaM activation of PMCA4a was almost twice that for PMCA4b, whereas the rates of activation for both isoforms showed similar dependence on Ca2+. The inactivation of PMCA4a by CaM removal was also faster than for PMCA4b, and Ca2+ showed a much smaller effect (2- versus 30-fold modification). The rate constants of the individual steps that determine the overall rates were obtained from stopped-flow experiments in which binding of TA-CaM was observed by changes in its fluorescence. TA-CaM binds to two conformations of PMCA4a, an "open" conformation with high activity, and a "closed" one with lower activity. Compared with PMCA4b (Penheiter, A. R., Bajzer, Z., Filoteo, A. G., Thorogate, R., T?r?k, K., and Caride, A. J. (2003) Biochemistry 41, 12115-12124), the model for PMCA4a predicts less inhibition in the closed form and a much faster equilibrium between the open and closed forms. Based on the available kinetic parameters, we determined the constants to fit the shape of a Ca2+ signal in PMCA4b-overexpressing Chinese hamster ovary cells. Using the constants for PMCA4a, and allowing small variations in parameters of other systems contributing to a Ca2+ signal, we then simulated the effect of PMCA4a on the shape of a Ca2+ signal in Chinese hamster ovary cells. The results reproduce the published data (Brini, M., Coletto, L., Pierobon, N., Kraev, N., Guerini, D., and Carafoli, E. (2003) J. Biol. Chem. 278, 24500-24508), and thereby demonstrate the importance of altered regulatory kinetics for the different functional properties of PMCA isoforms.     

Dual role of SnoN in mammalian tumorigenesis

SnoN is an important negative regulator of transforming growth factor beta signaling through its ability to interact with and repress the activity of Smad proteins. It was originally identified as an oncoprotein based on its ability to induce anchorage-independent growth in chicken embryo fibroblasts. However, the roles of SnoN in mammalian epithelial carcinogenesis have not been well defined. Here we show for the first time that SnoN plays an important but complex role in human cancer. SnoN expression is highly elevated in many human cancer cell lines, and this high level of SnoN promotes mitogenic transformation of breast and lung cancer cell lines in vitro and tumor growth in vivo, consistent with its proposed pro-oncogenic role. However, this high level of SnoN expression also inhibits epithelial-to-mesenchymal transdifferentiation. Breast and lung cancer cells expressing the shRNA for SnoN exhibited an increase in cell motility, actin stress fiber formation, metalloprotease activity, and extracellular matrix production as well as a reduction in adherens junction proteins. Supporting this observation, in an in vivo breast cancer metastasis model, reducing SnoN expression was found to moderately enhance metastasis of human breast cancer cells to bone and lung. Thus, SnoN plays both pro-tumorigenic and antitumorigenic roles at different stages of mammalian malignant progression. The growth-promoting activity of SnoN appears to require its ability to bind to and repress the Smad proteins, while the antitumorigenic activity can be mediated by both Smad-dependent and Smad-independent pathways and requires the activity of small GTPase RhoA. Our study has established the importance of SnoN in mammalian epithelial carcinogenesis and revealed a novel aspect of SnoN function in malignant progression.     

Effects of functional constraints and opportunism on the functional structure of a vertebrate predator assemblage

1. Within mainstream ecological literature, functional structure has been viewed as resulting from the interplay of species interactions, resource levels and environmental variability. Classical models state that interspecific competition generates species segregation and guild formation in stable saturated environments, whereas opportunism causes species aggregation on abundant resources in variable unsaturated situations. 2. Nevertheless, intrinsic functional constraints may result in species-specific differences in resource-use capabilities. This could force some degree of functional structure without assuming other putative causes. However, the influence of such constraints has rarely been tested, and their relative contribution to observed patterns has not been quantified. 3. We used a multiple null-model approach to quantify the magnitude and direction (non-random aggregation or divergence) of the functional structure of a vertebrate predator assemblage exposed to variable prey abundance over an 18-year period. Observed trends were contrasted with predictions from null-models designed in an orthogonal fashion to account independently for the effects of functional constraints and opportunism. Subsequently, the unexplained variation was regressed against environmental variables to search for evidence of interspecific competition. 4. Overall, null-models accounting for functional constraints showed the best fit to the observed data, and suggested an effect of this factor in modulating predator opportunistic responses. However, regression models on residual variation indicated that such an effect was dependent on both total and relative abundance of principal (small mammals) and alternative (arthropods, birds, reptiles) prey categories. 5. In addition, no clear evidence for interspecific competition was found, but differential delays in predator functional responses could explain some of the unaccounted variation. Thus, we call for caution when interpreting empirical data in the context of classical models assuming synchronous responses of consumers to resource levels.     

Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels

Mutations in the parkin gene result in an autosomal recessive juvenile-onset form of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment of ubiquitin onto specific substrate proteins. Defects in the ubiquitination of parkin substrates are therefore believed to lead to neurodegeneration in Parkinson's disease. Here, we identify the PSD-95/Discs-large/Zona Occludens-1 (PDZ) protein PICK1 as a novel parkin substrate. We find that parkin binds PICK1 via a PDZ-mediated interaction, which predominantly promotes PICK1 monoubiquitination rather than polyubiquitination. Consistent with monoubiquitination and recent work implicating parkin in proteasome-independent pathways, parkin does not promote PICK1 degradation. However, parkin regulates the effects of PICK1 on one of its other PDZ partners, the acid-sensing ion channel (ASIC). Overexpression of wild-type, but not PDZ binding- or E3 ubiquitin-ligase-defective parkin abolishes the previously described, protein kinase C-induced, PICK1-dependent potentiation of ASIC2a currents in non-neuronal cells. Conversely, the loss of parkin in hippocampal neurons from parkin knockout mice unmasks prominent potentiation of native ASIC currents, which is normally suppressed by endogenous parkin in wild-type neurons. Given that ASIC channels contribute to excitotoxicity, our work provides a mechanism explaining how defects in parkin-mediated PICK1 monoubiquitination could enhance ASIC activity and thereby promote neurodegeneration in Parkinson's disease.     

The CK1 gene family: expression patterning in zebrafish development

Protein kinase CK1 is a ser/thr protein kinase family which has been identified in the cytosol cell fraction, associated with membranes as well as in the nucleus. Several isoforms of this gene family have been described in various organisms: CK1alpha, CK1beta, CK1delta, CK1epsilon and CK1gamma. Over the last decade, several members of this family have been involved in development processes related to wnt and sonic hedgehog signalling pathways. However, there is no detailed temporal information on the CK1 family in embryonic stages, even though orthologous genes have been described in several different vertebrate species. In this study, we describe for the first time the cloning and detailed expression pattern of five CK1 zebrafish genes. Sequence analysis revealed that zebrafish CK1 proteins are highly homologous to other vertebrate orthologues. Zebrafish CK1 genes are expressed throughout development in common and different territories. All the genes studied in development show maternal and zygotic expression with the exception of CK1epsilon. This last gene presents only a zygotic component of expression. In early stages of development CK1 genes are ubiquitously expressed with the exception of CK1epsilon. In later stages the five CK1 genes are expressed in the brain but not in the same way. This observation probably implicates the CK1 family genes in different and also in redundant functions. This is the first time that a detailed comparison of the expression of CK1 family genes is directly assessed in a vertebrate system throughout development.