Timing Performance Error in Rewarded and Non-Rewarded Tasks

The literature on human and nonhuman animal interval timing disagrees about whether perceived time is a linear or power function of real time, and to what extent reward influences timing performance. Two competing computational learning and timing models, Temporal Difference (TD, Schultz, 2013) and Sometimes Competing Retrieval (SOCR, Stout & Miller, 2007) are reviewed. The present experiments investigate human interval timing error in both reward and non-reward conditions. The experiments were simulated by a computational model to identify both the function that describes the effect of interval duration on the distribution of variance (e.g., scalar or linear) and the relative predictive power of the SOCR and TD models, and the effects of reward on interval timing. Specifically, it was hypothesized that 1) timing variability is scalar, not linear, 2) that a modified SOCR model explains the data, and 3) that interval timing performance is less variable in rewarding situations than in non-rewarding situations. Timing trials involved the presentation of a reference duration; participants then produced their estimate of that duration while under cognitive load (random number generation and serial math tasks) through key presses on a computer. The results failed to support these hypotheses. However, reward produced a nonsignificant tendency towards early responding. Finally, suggestions for further research, including further computational modeling and investigation of the neural substrata of reward and timing are discussed

The role of low-level image features in the affective categorization of rapidly presented scenes

It remains unclear how the visual system is able to extract affective content from complex scenes even with extremely brief (\u3c 100 millisecond) exposures. One possibility, suggested by findings in machine vision, is that low-level features such as unlocalized, two-dimensional (2-D) Fourier spectra can be diagnostic of scene content. To determine whether Fourier image amplitude carries any information about the affective quality of scenes, we first validated the existence of image category differences through a support vector machine (SVM) model that was able to discriminate our intact aversive and neutral images with ~ 70% accuracy using amplitude-only features as inputs. This model allowed us to confirm that scenes belonging to different affective categories could be mathematically distinguished on the basis of amplitude spectra alone. The next question is whether these same features are also exploited by the human visual system. Subsequently, we tested observers’ rapid classification of affective and neutral naturalistic scenes, presented briefly (~33.3 ms) and backward masked with synthetic textures. We tested categorization accuracy across three distinct experimental conditions, using: (i) original images, (ii) images having their amplitude spectra swapped within a single affective image category (e.g., an aversive image whose amplitude spectrum has been swapped with another aversive image) or (iii) images having their amplitude spectra swapped between affective categories (e.g., an aversive image containing the amplitude spectrum of a neutral image). Despite its discriminative potential, the human visual system does not seem to use Fourier amplitude differences as the chief strategy for affectively categorizing scenes at a glance. The contribution of image amplitude to affective categorization is largely dependent on interactions with the phase spectrum, although it is impossible to completely rule out a residual role for unlocalized 2-D amplitude measures

Perception of a conserved family of plant signalling peptides by the receptor kinase HSL3

Plant genomes encode hundreds of secreted peptides; however, relatively few have been characterised. We report here an uncharacterised, stress‐induced family of plant signalling peptides, which we call CTNIPs. Based on the role of the common co‐receptor BRASSINOSTEROID INSENSITIVE 1‐ASSOCIATED KINASE 1 (BAK1) in CTNIP‐induced responses, we identified in Arabidopsis thaliana the orphan receptor kinase HAESA‐LIKE 3 (HSL3) as the CTNIP receptor via a proteomics approach. CTNIP binding, ligand‐triggered complex formation with BAK1, and induced downstream responses all involve HSL3. Notably, the HSL3‐CTNIP signalling module is evolutionarily conserved amongst most extant angiosperms. The identification of this novel signalling module will further shed light on the diverse functions played by plant signalling peptides and will provide insights into receptor-ligand co‐evolution

Proinsulin Atypical Maturation and Disposal Induces Extensive Defects in Mouse Ins2+/Akita β-Cells

Because of its low relative folding rate and plentiful manufacture in β-cells, proinsulin maintains a homeostatic balance of natively and plentiful non-natively folded states (i.e., proinsulin homeostasis, PIHO) through the integration of maturation and disposal processes. PIHO is susceptible to genetic and environmental influences, and its disorder has been critically linked to defects in β-cells in diabetes. To explore this hypothesis, we performed polymerase chain reaction (PCR), metabolic-labeling, immunoblotting, and histological studies to clarify what defects result from primary disorder of PIHO in model Ins2+/Akita β-cells. We used T antigen-transformed Ins2+/Akita and control Ins2+/+ β-cells established from Akita and wild-type littermate mice. In Ins2+/Akita β-cells, we found no apparent defect at the transcriptional and translational levels to contribute to reduced cellular content of insulin and its precursor and secreted insulin. Glucose response remained normal in proinsulin biosynthesis but was impaired for insulin secretion. The size and number of mature insulin granules were reduced, but the size/number of endoplasmic reticulum, Golgi, mitochondrion, and lysosome organelles and vacuoles were expanded/increased. Moreover, cell death increased, and severe oxidative stress, which manifested as increased reactive oxygen species, thioredoxin-interacting protein, and protein tyrosine nitration, occurred in Ins2+/Akita β-cells and/or islets. These data show the first clear evidence that primary PIHO imbalance induces severe oxidative stress and impairs glucose-stimulated insulin release and β-cell survival as well as producing other toxic consequences. The defects disclosed/clarified in model Ins2+/Akita β-cells further support a role of the genetic and stress-susceptible PIHO disorder in β-cell failure and diabetes

Killing of Escherichia coli by Crohn's Disease Monocyte-derived Macrophages and Its Enhancement by Hydroxychloroquine and Vitamin D

BACKGROUND: Crohn's disease (CD) is associated with defective innate immunity, including impaired neutrophil chemotaxis, and mucosal invasion by bacteria, particularly adherent and invasive Escherichia coli that replicate inside macrophage phagolysosomes. We compared CD and healthy control (HC) macrophages for their abilities to kill E. coli and generate neutrophil chemoattractants and also assessed the effects of hydroxychloroquine (HCQ) and vitamin D on killing of phagocytosed E. coli. METHODS: Peripheral blood monocyte-derived macrophages from CD and HC were compared for bacterial killing and generation of neutrophil chemoattractants in response to CD-derived E. coli. Escherichia coli replication was also assessed in the presence and absence of HCQ, alone and with antibiotics, and vitamin D. RESULTS: Monocyte-derived macrophages from patients with CD were similar to HC in allowing replication of phagocytosed CD-derived E. coli: HM605 {CD: N = 10, mean fold replication in 3 hr = 1.08 (95% confidence interval [CI], 0.39–1.78); HC: N = 9, 1.50 (95% CI, 1.02–1.97); P = 0.15} and also in generation of neutrophil chemoattractants in response to E. coli (mean fold chemotaxis relative to control: CD = 2.55 [95% CI, 2.31–2.80]; HC = 2.65 [95% CI, 2.46–2.85], P = 0.42). HCQ and 1,25 OH(2)-vitamin D(3) both caused dose-dependent inhibition of intramacrophage E. coli replication 3-hour postinfection; HCQ: 73.9% inhibition (P < 0.001) at 1 μg/mL, accompanied by raised intraphagosomal pH, and 1,25 OH(2)-vitamin D(3): 80.7% inhibition (P < 0.05) at 80 nM. HCQ had synergistic effects with doxycycline and ciprofloxacin. CONCLUSIONS: CD and HC macrophages perform similarly in allowing replication of phagocytosed E. coli and generating neutrophil chemoattractants. Replication of phagocytosed E. coli was substantially decreased by HCQ and vitamin D. These warrant further therapeutic trials in CD in combination with relevant antibiotics

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.This work was supported by the following grants: NHGRIU54HG003273 to R.A.G; EU Marie Curie ITN #215781 “Evonet” to M.A.; a Wellcome Trust Value in People (VIP) award to C.B. and Wellcome Trust graduate studentship WT089615MA to J.E.G; Marine rhythms of Life” of the University of Vienna, an FWF (http://www.fwf.ac.at/) START award (#AY0041321) and HFSP (http://www.hfsp.org/) research grant (#RGY0082/2010) to KT-­‐R; MFPL Vienna International PostDoctoral Program for Molecular Life Sciences (funded by Austrian Ministry of Science and Research and City of Vienna, Cultural Department -­‐Science and Research to T.K; Direct Grant (4053034) of the Chinese University of Hong Kong to J.H.L.H.; NHGRI HG004164 to G.M.; Danish Research Agency (FNU), Carlsberg Foundation, and Lundbeck Foundation to C.J.P.G.; U.S. National Institutes of Health R01AI55624 to J.H.W.; Royal Society University Research fellowship to F.M.J.; P.D.E. was supported by the BBSRC via the Babraham Institute;This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pbio.100200

The Arabidopsis leucine-rich repeat receptor kinase MIK2/LRR-KISS connects cell wall integrity sensing, root growth and response to abiotic and biotic stresses

Plants actively perceive and respond to perturbations in their cell walls which arise during growth, biotic and abiotic stresses. However, few components involved in plant cell wall integrity sensing have been described to date. Using a reverse-genetic approach, we identified the Arabidopsis thaliana leucine-rich repeat receptor kinase MIK2 as an important regulator of cell wall damage responses triggered upon cellulose biosynthesis inhibition. Indeed, loss-of-function mik2 alleles are strongly affected in immune marker gene expression, jasmonic acid production and lignin deposition. MIK2 has both overlapping and distinct functions with THE1, a malectin-like receptor kinase previously proposed as cell wall integrity sensor. In addition, mik2 mutant plants exhibit enhanced leftward root skewing when grown on vertical plates. Notably, natural variation in MIK2 (also named LRR-KISS) has been correlated recently to mild salt stress tolerance, which we could confirm using our insertional alleles. Strikingly, both the increased root skewing and salt stress sensitivity phenotypes observed in the mik2 mutant are dependent on THE1. Finally, we found that MIK2 is required for resistance to the fungal root pathogen Fusarium oxysporum. Together, our data identify MIK2 as a novel component in cell wall integrity sensing and suggest that MIK2 is a nexus linking cell wall integrity sensing to growth and environmental cues