Interference between cues of the same outcome in a non-causally framed scenario

Retroactive interference between cues of the same outcome (i.e., IbC) occurs when the behavioral expression of an association between a cue and an outcome (e.g., A → O1) is reduced due to the later acquisition of an association between a different cue and the same outcome (e.g., B → O1). Though this interference effect has been traditionally explained within an associative framework, there is recent evidence showing that IbC effect may be better understood in terms of the operation of higher order causal reasoning processes. The results from Experiments 1 and 2 showed an IbC effect in a learning task within a game scenario suggesting non-causal relationships between events. Thus, these results showed that IbC may have a diverse origin, one of them being of an associative nature.     

Pavlovian backward conditioned inhibition in humans: summation and retardation tests

Two experiments using human participants investigated whether a Pavlovian backward inhibitory treatment (nonreinforced trials in phase 1 followed by reinforced trials in phase 2; i.e., AX- followed by A+) produces a stimulus which can pass summation and retardation tests for inhibition. The rationale for conducting these experiments was that previous demonstrations of Pavlovian backward inhibition informed participants about the nature of the outcome before starting the experiment. According to some theoretical views, this is a potential confound. In the present experiments we used a predictive task in which participants had no knowledge about the outcome until phase 2, when reinforcement occurred. The results of Experiment 1 (summation test) and Experiment 2 (retardation test) provide a clear demonstration of backward conditioned inhibition.     

Cardiac function in spontaneously diabetic BB rats treated with low and high dose insulin

Cardiac abnormalities observed in animals with drug-induced diabetes may be due to the direct cardiotoxic effect of the drugs or factors not related to the diabetic state. The purpose of this investigation was to examine cardiac sarcoplasmic reticular (SR) calcium transport and heart function in the BB rat, a strain in which diabetes occurs spontaneously and clearly resembles insulin-dependent diabetes in humans. Complete insulin withdrawal for 2 or 4 days from BB diabetic rats leads to a spectrum of metabolic derangements including a loss of body weight, hyperglycemia, and elevated triglyceride levels confirming the insulin dependence of this model. The present study involved treating BB diabetic rats with a low (hyperglycemic) and high (normoglycemic) insulin dose for 12 weeks after the detection of glycosuria. The hearts from these animals were then isolated, and SR Ca2+ transport and heart function (using isolated perfused working hearts) were examined and compared with BB nondiabetic littermates or Wistar controls. Strain-related differences were found in ATP-dependent SR Ca2+ transport between the Wistar and BB rats. There were, however, no significant diabetes-related differences in SR Ca2+ transport between the low dose insulin treated diabetic group (LD) and the high dose insulin treated diabetic group (HD) or the nondiabetic littermates. Plasma lipid concentrations of the LD and HD BB rats and nondiabetic littermates were also generally higher than those of control Wistar rats indicating strain-related but not diabetes-related differences. In addition, there were no differences in cardiac function between the LD and BB nondiabetic littermates or Wistar controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Associative interference between cues and between outcomes presented together and presented apart: an integration

In recent years, 'stimulus competition' in the study of acquired behavior has referred exclusively to (a) associative competition between cues trained in compound (e.g. overshadowing and blocking). Rarely cited are older experiments cast in the verbal learning tradition, now complemented with data from humans and rats in Pavlovian preparations, that demonstrate (b) competition between cues separately trained with a common outcome (i.e. proactive and retroactive interference). Similarly neglected are numerous examples of (c) competition between outcomes separately trained with a common cue within the verbal learning literature (also proactive and retroactive interference) as well as within the Pavlovian literature (i.e. counterconditioning). Recent data demonstrate (d) competition between outcomes trained in compound, thereby completing the four cells of a 2x2 matrix (competing stimuli trained together vs. trained apart and the competing stimuli being cues or outcomes) which highlights the ubiquitous nature of associative stimulus interference/competition. Most contemporary theories of acquired behavior can account for the phenomena in one or at most two cells of this matrix. Whether a common mechanism underlies the phenomena in all four cells of the matrix is currently unclear, but until such time as data preclude a common mechanism, parsimony encourages efforts to develop a model that encompasses all four cells. Here we offer a tentative model that addresses all four cells, albeit with two processes.     

Cannabinoid inhibition improves memory in food-storing birds, but with a cost

Food-storing birds demonstrate remarkable memory ability in recalling the locations of thousands of hidden food caches. Although this behaviour requires the hippocampus, its synaptic mechanisms are not understood. Here we show the effects of cannabinoid receptor (CB1-R) blockade on spatial memory in food-storing black-capped chickadees (Poecile atricapilla). Intra-hippocampal infusions of the CB1-R antagonist SR141716A enhanced long-term memory for the location of a hidden food reward, measured 72 h after encoding. However, when the reward location changed during the retention interval, birds that had received SR141716A during initial learning showed impairments in recalling the most recent reward location. Thus, blocking CB1-R activity may lead to more robust, long-lasting memories, but these memories may be a source of proactive interference. The relationship between trace strength and interference may be important in understanding neural mechanisms of hippocampal function in general, as well as understanding the enhanced memory of food-storing birds.     

Performance Analysis of Flexible Manufacturing Systems with a Single Discrete Material-Handling Device

We present an analytical model for performance prediction of flexible manufacturing systems (FMSs) with a single discrete material-handling device (MHD). This configuration of FMS is significant for many reasons: it is commonly found in industry, it simplifies material-handling control, it is amenable to analytical modeling, and it forms a building block for more complex systems. Standard queueing models are inadequate to analyze this configuration because of the need to take into consideration many nontrivial issues such as state-dependent routing, interference from the MHD, and the analysis of the MHD. To account for state-dependent routing, we develop an iterative method that is built around mean value analysis. To analyze the MHD interference, we use two queueing network models. In the first, we ignore queueing at the MHD but model the interference from the MHD by inflating the station service times. The second network models the queueing for the MHD and estimates the blocking (inflation) times needed for the first model. By iterating between the two networks, we are able to predict the performance of this configuration of FMS. Our analytical estimates are validated against discrete event simulation and shown to be quite accurate for initial system design.     

Transcranial Direct Current Stimulation Improves Ipsilateral Selective Muscle Activation in a Frequency Dependent Manner

Failure to suppress antagonist muscles can lead to movement dysfunction, such as the abnormal muscle synergies often seen in the upper limb after stroke. A neurophysiological surrogate of upper limb synergies, the selectivity ratio (SR), can be determined from the ratio of biceps brachii (BB) motor evoked potentials to transcranial magnetic stimulation prior to forearm pronation versus elbow flexion. Surprisingly, cathodal transcranial direct current stimulation (c-TDCS) over ipsilateral primary motor cortex (M1) reduces (i.e. improves) the SR in healthy adults, and chronic stroke patients. The ability to suppress antagonist muscles may be exacerbated at high movement rates. The aim of the present study was to investigate whether the selective muscle activation of the biceps brachii (BB) is dependent on altering frequency demands, and whether the c-tDCS improvement of SR is dependent on task frequency. Seventeen healthy participants performed repetitive isometric elbow flexion and forearm pronation at three rates, before and after c-tDCS or sham delivered to ipsilateral left M1. Ipsilateral c-tDCS improved the SR in a frequency dependent manner by selectively suppressing BB antagonist excitability. Our findings confirm that c-tDCS is an effective tool for improving selective muscle activation, and provide novel evidence for its efficacy at rates of movement where it is most likely to benefit task performance.     

Uncoupling store-operated Ca2+ entry and altered Ca2+ release from sarcoplasmic reticulum through silencing of junctophilin genes

Junctophilin (JP) mediates the close contact between cell surface and intracellular membranes in muscle cells ensuring efficient excitation-contraction coupling. Here we demonstrate that disruption of triad junction structure formed by the transverse tubular (TT) invagination of plasma membrane and terminal cisternae of sarcoplasmic reticulum (SR) by reduction of JP expression leads to defective Ca2+ homeostasis in muscle cells. Using adenovirus with small hairpin interference RNA (shRNA) against both JP1 and JP2 genes, we could achieve acute suppression of JPs in skeletal muscle fibers. The shRNA-treated muscles exhibit deformed triad junctions and reduced store-operated Ca2+ entry (SOCE), which is likely due to uncoupled retrograde signaling from SR to TT. Knockdown of JP also causes a reduction in SR Ca2+ storage and altered caffeine-induced Ca2+ release, suggesting an orthograde regulation of the TT membrane on the SR Ca2+ release machinery. Our data demonstrate that JPs play an important role in controlling overall intracellular Ca2+ homeostasis in muscle cells. We speculate that altered expression of JPs may underlie some of the phenotypic changes associated with certain muscle diseases and aging.     

Sociality influences cultural complexity

Archaeological and ethnohistorical evidence suggests a link between a population''s size and structure, and the diversity or sophistication of its toolkits or technologies. Addressing these patterns, several evolutionary models predict that both the size and social interconnectedness of populations can contribute to the complexity of its cultural repertoire. Some models also predict that a sudden loss of sociality or of population will result in subsequent losses of useful skills/technologies. Here, we test these predictions with two experiments that permit learners to access either one or five models (teachers). Experiment 1 demonstrates that naive participants who could observe five models, integrate this information and generate increasingly effective skills (using an image editing tool) over 10 laboratory generations, whereas those with access to only one model show no improvement. Experiment 2, which began with a generation of trained experts, shows how learners with access to only one model lose skills (in knot-tying) more rapidly than those with access to five models. In the final generation of both experiments, all participants with access to five models demonstrate superior skills to those with access to only one model. These results support theoretical predictions linking sociality to cumulative cultural evolution.     

Dephosphorylation of inner arm 1 is associated with ciliary reversals in Tetrahymena thermophila

In many organisms, depolarizing stimuli cause an increase in intraciliary Ca2+, which results in reversal of ciliary beat direction and backward swimming. The mechanism by which an increase in intraciliary Ca2+ causes ciliary reversal is not known. Here we show that Tetrahymena cells treated with okadaic acid or cantharidin to inhibit protein phosphatases do not swim backwards in response to depolarizing stimuli. We also show that both okadaic acid and cantharidin inhibit backward swimming in reactivated, extracted cell models treated with Ca2+. In contrast, treatment of whole cells or extracted cell models with protein kinase inhibitors has no effect on backward swimming. These results suggest that a component of the axonemal machinery is dephosphorylated during ciliary reversal. The phosphorylation state of inner arm dynein 1 (I1) was determined before and after cells were exposed to depolarizing conditions that induce ciliary reversal. An I1 intermediate chain is phosphorylated in forward swimming cells but is dephosphorylated in cells treated with a depolarizing stimulus. Our results suggest that dephosphorylation of Tetrahymena inner arm dynein 1 may be an essential part of the mechanism of ciliary reversal in response to increased intraciliary Ca2+.     

Abnormal rapid Ca2+ release from sarcoplasmic reticulum of malignant hyperthermia susceptible pigs.

Using the rapid filtration technique to investigate Ca2+ movements across the sarcoplasmic reticulum (SR) membrane, we compare the initial phases of Ca2+ release and Ca2+ uptake in malignant hyperthermia susceptible (MHS) and normal (N) pig SR vesicles. Ca2+ release is measured from passively loaded SR vesicles. MHS SR vesicles present a 2-fold increase in the initial rate of calcium release induced by 0.3 microM Ca2+ (20.1 +/- 2.1 vs. 6.3 +/- 2.6 nmol mg-1 s-1). Maximal Ca2+ release is obtained with 3 microM Ca2+. At this optimal concentration, rate of Ca2+ efflux in absence of ATP is 55 and 25 nmol mg-1 s-1 for MHS and N SR, respectively. Ca(2+)-induced Ca2+ release is inhibited by Mg2+ in a dose-dependent manner for both MHS and N pig SR vesicles (K1/2 = 0.2 mM). Caffeine (5 mM) and halothane (0.01% v/v) increase the Ca2+ sensitivity of Ca(2+)-induced Ca2+ release. ATP (5 mM) strongly enhances the rate of Ca2+ efflux (to about 20-40-fold in both MHS and N pig SR vesicles). Furthermore, both types of vesicles do not differ in their high-affinity site for ryanodine (Kd = 12 nM and Bmax = 6 pmol/mg), lipid content, ATPase activity and initial rate of Ca2+ uptake (0.948 +/- 0.034 vs. 0.835 +/- 0.130 mumol mg-1 min-1 for MHS and N SR, respectively). Our results show that MH syndrome is associated to a higher rate of Ca2+ release in the earliest phase of the calcium efflux.     

Interaction of low-dose irradiation with subsequent mutagenic treatment: role of mitotic delay

Experiments were carried out with human lymphocytes to test whether there was any relation between the changes that conditioning treatment can produce in cell progression or in mitotic delay induced by the challenge dose and the presence of an ‘adaptive response’ (AR). In experiments in which the cells were successively fixed after the challenge dose, the interaction between conditioning treatment and challenge was of the same sign for all the fixation times: therefore it is likely that modifications of the cytogenetic damage in primed cells is not a mere reflection of stage sensitivity. In experiments in which using 1 Gy as conditioning treatment we induced a drastic extension of G₂, we did not observe any AR; therefore, even if conditioning treatment can induce modifications in the cell-cycle phases before and/or after challenge, there is probably no link between these modifications and the presence of an AR.     

Species specificity in ribosome biogenesis: a nonconserved phosphoprotein is required for formation of the large ribosomal subunit in Trypanosoma brucei

In the protozoan parasite Trypanosoma brucei, the large rRNA, which is a single 3.4- to 5-kb species in most organisms, is further processed to form six distinct RNAs, two larger than 1 kb (LSU1 and LSU2) and four smaller than 220 bp. The small rRNA SR1 separates the two large RNAs, while the remaining small RNAs are clustered at the 3' end of the precursor rRNA. One would predict that T. brucei possesses specific components to carry out these added processing events. We show here that the trypanosomatid-specific nucleolar phosphoprotein NOPP44/46 is involved in this further processing. Cells depleted of NOPP44/46 by RNA interference had a severe growth defect and demonstrated a defect in large-ribosomal-subunit biogenesis. Concurrent with this defect, a significant decrease in processing intermediates, particularly for SR1, was seen. In addition, we saw an accumulation of aberrant processing intermediates caused by cleavage within either LSU1 or LSU2. Though it is required for large-subunit biogenesis, we show that NOPP44/46 is not incorporated into the nascent particle. Thus, NOPP44/46 is an unusual protein in that it is both nonconserved and required for ribosome biogenesis.     

Effect of sensory-motor latencies and active muscular stiffness on stability for an ankle-hip model of balance on a balance board

To achieve human upright posture (UP) and avoid falls, the central nervous system processes visual, vestibular, and proprioceptive information to activate the appropriate muscles to accelerate or decelerate the body’s center of mass. In this process, sensory-motor (SM) latencies and muscular deficits, even in healthy older adults, may cause falls. This condition is worse for people with chronic neuromuscular deficits (stroke survivors, patients with multiple sclerosis or Parkinson’s disease). One therapeutic approach is to recover or improve quiet UP by utilizing a balance board (BB) (a rotating surface with a tunable stiffness and time delay), where a patient attempts to maintain UP while task difficulty is manipulated. While BBs are commonly used, it is unclear how UP is maintained or how changes in system parameters such as SM latencies and BB time delay affect UP stability. To understand these questions, it is important that mathematical models be developed with enough degrees-of-freedom to capture the many responses evoked during the maintenance of UP on a BB. This paper presents an ankle-hip model of balance on a BB, which is used to study the combined effect of SM latencies and active muscular stiffness of the ankle and hip joints, and the BB stiffness and time delay on UP stability. The analysis predicts that people with proprioceptive, visual, vestibular loss, or increased SM latencies may show either leaning postures or larger body-sway. The results show that the BB time delay and the visual and vestibular feedback have the largest impact on UP stability.     

Associations of the IGF2 gene with growth and meat efficiency in Large White pigs

The insulin-like growth factor 2 gene (IGF2) has been described in several studies as a candidate gene for meat efficiency in pigs. IGF2 is a member of the growth factors family and has an effect on development of muscle tissue. The effect of IGF2 gene polymorphism on meat efficiency was analysed in a population of 121 Large White pigs. A PCR-based test and RFLP methods were used for detection of genotypes. Allele A, lacking the restriction site, was characterised by the presence of a 0.9-kb fragment. In allele B, the amplimer was cut into a 0.8-kb fragment and some barely detectable fragments. The statistical analysis was carried out according to the General Linear Model procedure. The genotype frequencies observed were: 1.65%, 33.88%, 64.46% for AA, AB and BB genotypes, respectively. There was a significant difference (P < or = 0.05) between the AB and BB genotypes in live weight before the test. A significant association between AB and BB genotypes and body weight before the test was found. No significant difference in other traits of growth and meat efficiency was observed (P > 0.05).     

The combined effect of color and odor on flower choice behavior of bumble bees in flower mimicry systems

Food-deceptive flowers are pollinated by animals that expecta reward but are cheated. Such plants profit from their similarityto rewarding plants and should develop signals that hinderdiscrimination. We use artificial rewarding model flowers andnonrewarding mimicking flowers that present similar visual cues. We test how additional scent cues change flower choiceof the mimic by bumble bees (Bombus terrestris) in two situations:(1) both flower types are simultaneously present and can becompared by the pollinator, and (2) both flower types are encounteredsuccessively in the absence of each other. We find that insituation 1, discrimination learning is greater if scents areused as cues for identifying the mimic, whether the mimic hasa different scent or if it is scentless while the model isscented. In situation 2, a generalization task, a scented mimicis avoided faster than a scentless one. Discrimination of themimic is poorest if it has the same scent as the model, thusdemonstrating a potential for scent mimicry, which has not yet been proved to exist among differently rewarding flowers. Thus,the best strategy for a mimic would be to have the same scentas the model, but this strategy may not be used due to evolutionaryconstraints. Alternatively, if there are several potentialmodels, then having no scent would be a better strategy thanmimicking just one of the models. In situation 1 flower discriminationby color cues is enhanced in the mere presence of scent, comparedto unscented controls, even if the scent does not provide a distinguishable cue itself. The results indicate that the presenceof scent may enhance color discrimination by improving attentiontowards visual cues and/or that combined color/odor cues maylead to better memory formation and retrieval.     

Behavioral compensations in a positional learning and memory task by aged monkeys

The present experiment assessed learning and memory of a positional task by evaluating behavioral strategies as well as accuracy of a task in four young and four aged monkeys. They were tested in a delayed response (DR) task that has been widely used to study animal models of aging. The task consisted of two phases; an acquisition of the task and a positional memory test with five delay times (1-30 s). There was no clear difference between age groups in the number of trials needed for acquisition of the task. However, an analysis of behavior revealed differences in behavioral characteristics displayed during testing. The young monkeys showed various irrelevant behaviors during the execution of the task. In contrast, the aged monkeys consistently concentrated on the task exhibiting no behaviors irrelevant to the task. These results showed than the aged monkeys' performance was supported by a different behavioral strategy from the young monkeys. The results of the memory test were similar to those of the acquisition on the accuracy and the behavior. The aged monkeys depended on behavioral cues to preserve their positional memory, especially during the task. The present study suggests that cognitive impairments in aged monkeys can be compensated for by employing behavioral strategies.     

Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis

Herpetic stromal keratitis (HSK) is a chronic inflammatory process in corneal stroma that results from recurrent HSV type 1 infection. We used the murine model of HSK to demonstrate the importance of the interaction between an inducible T cell costimulatory receptor, 4-1BB, and its ligand, 4-1BB ligand (4-1BBL), in the development of this disease. In BALB/c mice, HSK ordinarily induced by infection with the RE strain of herpes was prevented by blocking 4-1BB/4-1BBL interaction, either by deleting 4-1BB (in mutant 4-1BB(-/-) mice) or by introducing mAbs against 4-1BBL. The majority of T cells infiltrating the infected corneas were 4-1BB(+) activated effector cells that expressed cell surface markers CD44, CD25, and/or CD62L, as well as chemokine receptors CCR1, CCR2, and CCR5, and a limited number of TCR Vbeta chains (Vbeta8.1/8.2, Vbeta8.3, Vbeta10b, and Vbeta5.1/5.2, in order of abundance). Analysis of cell surface phenotypes showed that the failure to develop HSK in the 4-1BB(-/-) mice was associated with a reduced expression of CD62L at the time of T cell migration into the corneal stroma.