Predictive feedback control and Fitts' law

Fitts’ law is a well established empirical formula, known for encapsulating the “speed-accuracy trade-off”. For discrete, manual movements from a starting location to a target, Fitts’ law relates movement duration to the distance moved and target size. The widespread empirical success of the formula is suggestive of underlying principles of human movement control. There have been previous attempts to relate Fitts’ law to engineering-type control hypotheses and it has been shown that the law is exactly consistent with the closed-loop step-response of a time-delayed, first-order system. Assuming only the operation of closed-loop feedback, either continuous or intermittent, this paper asks whether such feedback should be predictive or not predictive to be consistent with Fitts law. Since Fitts’ law is equivalent to a time delay separated from a first-order system, known control theory implies that the controller must be predictive. A predictive controller moves the time-delay outside the feedback loop such that the closed-loop response can be separated into a time delay and rational function whereas a non- predictive controller retains a state delay within feedback loop which is not consistent with Fitts’ law. Using sufficient parameters, a high-order non-predictive controller could approximately reproduce Fitts’ law. However, such high-order, “non-parametric” controllers are essentially empirical in nature, without physical meaning, and therefore are conceptually inferior to the predictive controller. It is a new insight that using closed-loop feedback, prediction is required to physically explain Fitts’ law. The implication is that prediction is an inherent part of the “speed-accuracy trade-off”

Temperature responses of Rubisco from Paniceae grasses provide opportunities for improving C3 photosynthesis.

Enhancing the catalytic properties of the CO2-fixing enzyme Rubisco is a target for improving agricultural crop productivity. Here, we reveal extensive diversity in the kinetic response between 10 and 37 °C by Rubisco from C3 and C4 species within the grass tribe Paniceae. The CO2 fixation rate (kcatc) for Rubisco from the C4 grasses with nicotinamide adenine dinucleotide (NAD) phosphate malic enzyme (NADP-ME) and phosphoenolpyruvate carboxykinase (PCK) photosynthetic pathways was twofold greater than the kcatc of Rubisco from NAD-ME species across all temperatures. The declining response of CO2/O2 specificity with increasing temperature was less pronounced for PCK and NADP-ME Rubisco, which would be advantageous in warmer climates relative to the NAD-ME grasses. Modelled variation in the temperature kinetics of Paniceae C3 Rubisco and PCK Rubisco differentially stimulated C3 photosynthesis relative to tobacco above and below 25 °C under current and elevated CO2. Amino acid substitutions in the large subunit that could account for the catalytic variation among Paniceae Rubisco are identified; however, incompatibilities with Paniceae Rubisco biogenesis in tobacco hindered their mutagenic testing by chloroplast transformation. Circumventing these bioengineering limitations is critical to tailoring the properties of crop Rubisco to suit future climates

C4 photosynthesis boosts growth by altering physiology, allocation and size.

C4 photosynthesis is a complex set of leaf anatomical and biochemical adaptations that have evolved more than 60 times to boost carbon uptake compared with the ancestral C3 photosynthetic type(1-3). Although C4 photosynthesis has the potential to drive faster growth rates(4,5), experiments directly comparing C3 and C4 plants have not shown consistent effects(1,6,7). This is problematic because differential growth is a crucial element of ecological theory(8,9) explaining C4 savannah responses to global change(10,11), and research to increase C3 crop productivity by introducing C4 photosynthesis(12). Here, we resolve this long-standing issue by comparing growth across 382 grass species, accounting for ecological diversity and evolutionary history. C4 photosynthesis causes a 19-88% daily growth enhancement. Unexpectedly, during the critical seedling establishment stage, this enhancement is driven largely by a high ratio of leaf area to mass, rather than fast growth per unit leaf area. C4 leaves have less dense tissues, allowing more leaves to be produced for the same carbon cost. Consequently, C4 plants invest more in roots than C3 species. Our data demonstrate a general suite of functional trait divergences between C3 and C4 species, which simultaneously drive faster growth and greater investment in water and nutrient acquisition, with important ecological and agronomic implications

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced micro- RNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these prodifferentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.Comment: 45 pages 5 figure

Why Are Some Plant Genera More Invasive Than Others?

Determining how biological traits are related to the ability of groups of organisms to become economically damaging when established outside of their native ranges is a major goal of population biology, and important in the management of invasive species. Little is known about why some taxonomic groups are more likely to become pests than others among plants. We investigated traits that discriminate vascular plant genera, a level of taxonomic generality at which risk assessment and screening could be more effectively performed, according to the proportion of naturalized species which are pests. We focused on the United States and Canada, and, because our purpose is ultimately regulatory, considered species classified as weeds or noxious. Using contingency tables, we identified 11 genera of vascular plants that are disproportionately represented by invasive species. Results from boosted regression tree analyses show that these categories reflect biological differences. In summary, approximately 25% of variation in genus proportions of weeds or noxious species was explained by biological covariates. Key explanatory traits included genus means for wetland habitat affinity, chromosome number, and seed mass

Mechanical Properties of Plant Underground Storage Organs and Implications for Dietary Models of Early Hominins

The diet of early human ancestors has received renewed theoretical interest since the discovery of elevated d13C values in the enamel of Australopithecus africanus and Paranthropus robustus. As a result, the hominin diet is hypothesized to have included C4 grass or the tissues of animals which themselves consumed C4 grass. On mechanical grounds, such a diet is incompatible with the dental morphology and dental microwear of early hominins. Most inferences, particularly for Paranthropus, favor a diet of hard or mechanically resistant foods. This discrepancy has invigorated the longstanding hypothesis that hominins consumed plant underground storage organs (USOs). Plant USOs are attractive candidate foods because many bulbous grasses and cormous sedges use C4 photosynthesis. Yet mechanical data for USOs—or any putative hominin food—are scarcely known. To fill this empirical void we measured the mechanical properties of USOs from 98 plant species from across sub-Saharan Africa. We found that rhizomes were the most resistant to deformation and fracture, followed by tubers, corms, and bulbs. An important result of this study is that corms exhibited low toughness values (mean = 265.0 J m-2) and relatively high Young’s modulus values (mean = 4.9 MPa). This combination of properties fits many descriptions of the hominin diet as consisting of hard-brittle objects. When compared to corms, bulbs are tougher (mean = 325.0 J m-2) and less stiff (mean = 2.5 MPa). Again, this combination of traits resembles dietary inferences, especially for Australopithecus, which is predicted to have consumed soft-tough foods. Lastly, we observed the roasting behavior of Hadza hunter-gatherers and measured the effects of roasting on the toughness on undomesticated tubers. Our results support assumptions that roasting lessens the work of mastication, and, by inference, the cost of digestion. Together these findings provide the first mechanical basis for discussing the adaptive advantages of roasting tubers and the plausibility of USOs in the diet of early hominins

Linking Self-Incompatibility, Dichogamy, and Flowering Synchrony in Two Euphorbia Species: Alternative Mechanisms for Avoiding Self-Fertilization?

Background: Plant species have several mechanisms to avoid selfing such as dichogamy or a self-incompatibility response. Dichogamy in a single flower may reduce autogamy but, to avoid geitonogamy, plants must show flowering synchronization among all their flowers (i.e. synchronous dichogamy). It is hypothesized that one species would not simultaneously show synchronous dichogamy and self-incompatibility because they are redundant mechanisms to reduce selfing; however, this has not been accurately assessed. Methodology/Principal Findings: This expectation was tested over two years in two natural populations of the closely related Mediterranean spurges Euphorbia boetica and E. nicaeensis, which completely avoid autogamy by protogyny at the cyathia level. Both spurges showed a high population synchrony (Z,79), and their inflorescences flower synchronously. In E. nicaeensis, there was no overlap among the cyathia in anthesis of successive inflorescence levels and the overlap between sexual phases of cyathia of the same inflorescence level was uncommon (4–16%). In contrast, E. boetica showed a high overlap among consecutive inflorescence levels (74–93%) and between sexual phases of cyathia of the same inflorescence level (48–80%). The flowering pattern of both spurges was consistent in the two populations and over the two successive years. A hand-pollination experiment demonstrated that E. nicaeensis was strictly self-compatible whereas E. boetica was partially self-incompatible. Conclusions/Significance: We propose that the complex pattern of synchronized protogyny in E. nicaeensis prevents geitonogamous crosses and, consequently, avoids selfing and inbreeding depression. In E. boetica, a high probability of geitonogamous crosses may occur but, alternatively, this plant escapes selfing through a self-incompatibility response. We posit that synchronous dichogamy and physiological self-incompatibility do not co-occur in the same species because each process is sufficiently effective in avoiding self-fertilization.España Ministerio de Ciencia y Tecnología PLO CGL2005-03731; CGL2008-02533-EEspaña Ministerio de Ciencia y Tecnología MA CGL2009-0825

Distinctive Patterns of MicroRNA Expression Associated with Karyotype in Acute Myeloid Leukaemia

Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults; however, the genetic aetiology of the disease is not yet fully understood. A quantitative expression profile analysis of 157 mature miRNAs was performed on 100 AML patients representing the spectrum of known karyotypes common in AML. The principle observation reported here is that AMLs bearing a t(15;17) translocation had a distinctive signature throughout the whole set of genes, including the up regulation of a subset of miRNAs located in the human 14q32 imprinted domain. The set included miR-127, miR-154, miR-154*, miR-299, miR-323, miR-368, and miR-370. Furthermore, specific subsets of miRNAs were identified that provided molecular signatures characteristic of the major translocation-mediated gene fusion events in AML. Analysis of variance showed the significant deregulation of 33 miRNAs across the leukaemic set with respect to bone marrow from healthy donors. Fluorescent in situ hybridisation analysis using miRNA-specific locked nucleic acid (LNA) probes on cryopreserved patient cells confirmed the results obtained by real-time PCR. This study, conducted on about a fifth of the miRNAs currently reported in the Sanger database (microrna.sanger.ac.uk), demonstrates the potential for using miRNA expression to sub-classify cancer and suggests a role in the aetiology of leukaemia

MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection

This work is licensed under a Creative Commons Attribution 4.0 International License.Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that emerged in 2012, causing severe pneumonia and acute respiratory distress syndrome (ARDS), with a case fatality rate of ~36%. When expressed in isolation, CoV accessory proteins have been shown to interfere with innate antiviral signaling pathways. However, there is limited information on the specific contribution of MERS-CoV accessory protein 4b to the repression of the innate antiviral response in the context of infection. We found that MERS-CoV 4b was required to prevent a robust NF-κB dependent response during infection. In wild-type virus infected cells, 4b localized to the nucleus, while NF-κB was retained in the cytoplasm. In contrast, in the absence of 4b or in the presence of cytoplasmic 4b mutants lacking a nuclear localization signal (NLS), NF-κB was translocated to the nucleus leading to the expression of pro-inflammatory cytokines. This indicates that NF-κB repression required the nuclear import of 4b mediated by a specific NLS. Interestingly, we also found that both in isolation and during infection, 4b interacted with α-karyopherin proteins in an NLS-dependent manner. In particular, 4b had a strong preference for binding karyopherin-α4 (KPNA4), which is known to translocate the NF-κB protein complex into the nucleus. Binding of 4b to KPNA4 during infection inhibited its interaction with NF-κB-p65 subunit. Thereby we propose a model where 4b outcompetes NF-κB for KPNA4 binding and translocation into the nucleus as a mechanism of interference with the NF-κB-mediated innate immune response

Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin