Dynamic perceptual changes in audiovisual simultaneity

Background

The timing at which sensory input reaches the level of conscious perception is an intriguing question still awaiting an answer. It is often assumed that both visual and auditory percepts have a modality specific processing delay and their difference determines perceptual temporal offset.

Methodology/Principal Findings

Here, we show that the perception of audiovisual simultaneity can change flexibly and fluctuates over a short period of time while subjects observe a constant stimulus. We investigated the mechanisms underlying the spontaneous alternations in this audiovisual illusion and found that attention plays a crucial role. When attention was distracted from the stimulus, the perceptual transitions disappeared. When attention was directed to a visual event, the perceived timing of an auditory event was attracted towards that event.

Conclusions/Significance

This multistable display illustrates how flexible perceived timing can be, and at the same time offers a paradigm to dissociate perceptual from stimulus-driven factors in crossmodal feature binding. Our findings suggest that the perception of crossmodal synchrony depends on perceptual binding of audiovisual stimuli as a common event.     

Interface sliding as illustrated by the multiple quaternary structures of liganded hemoglobin

Initial crystallographic studies suggested that fully liganded mammalian hemoglobin can adopt only a single quaternary structure, the quaternary R structure. However, more recent crystallographic studies revealed the existence of a second quaternary structure for liganded hemoglobin, the quaternary R2 structure. Since these quaternary structures can be crystallized, both must be energetically accessible structures that coexist in solution. Unanswered questions include (i) the relative abundance of the R and R2 structures under various solution conditions and (ii) whether other quaternary structures are energetically accessible for the liganded alpha(2)beta(2) hemoglobin tetramer. Although crystallographic methods cannot directly answer the first question, they represent the most direct and most accurate approach to answering the second question. We now have determined and refined three different crystal structures of bovine carbonmonoxyhemoglobin. These structures provide clear evidence that the dimer-dimer interface of liganded hemoglobin has a wide range of energetically accessible structures that are related to each other by a simple sliding motion. The dimer-dimer interface acts as a "molecular slide bearing" that allows the two alpha beta dimers to slide back and forth without greatly altering the number or the nature of the intersubunit contacts. Since the general stereochemical features of this interface are not unusual, it is likely that interface sliding of the kind displayed by fully liganded hemoglobin plays important structural and functional roles in many other protein assemblies.     

Hip and Knee Strength Is Not Affected in 12-16 Year Old Adolescents with Patellofemoral Pain - A Cross-Sectional Population-Based Study

Background

One of the rationales behind using strength training in the treatment of adolescents with Patellofemoral Pain (PFP) is that reduced strength of the lower extremity is a risk factor for PFP and a common deficit. This rationale is based on research conducted on adolescents >15 years of age but has never been investigated among young adolescents with PFP.

Objectives

To compare isometric muscle strength of the lower extremity among adolescents with PFP compared to age- and gender-matched pain-free adolescents.

Methods

In 2011 a population-based cohort (APA2011-cohort) consisting of 768 adolescents aged 12–15 years from 8 local schools was formed. In September 2012, all adolescents who reported knee pain in September 2011 were offered a clinical examination if they still had knee pain. From these, 20 adolescents (16 females) were diagnosed with PFP. Pain-free adolescents from the APA2011-cohort (n = 20) were recruited on random basis as age- and gender-matched pairs. Primary outcome was isometric knee extension strength normalized to body weight (%BW) and blinded towards subject information. Secondary outcomes included knee flexion, hip abduction/adduction and hip internal/external rotation strength. Demographic data included Knee Injury and Osteoarthritis Outcome Score (KOOS) and symptom duration.

Results

Adolescents with PFP reported long symptom duration and significantly worse KOOS scores compared to pain-free adolescents. There were no significant differences in isometric knee extension strength (Δ0.3% BW, p = 0.97), isometric knee flexion strength (Δ0.4% BW, p = 0.84) or different measures of hip strength (Δ0.4 to 1.1% BW, p>0.35).

Conclusion

Young symptomatic adolescents with PFP between 12 and 16 years of age did not have decreased isometric muscle strength of the knee and hip. These results question the rationale of targeting strength deficits in the treatment of adolescents with PFP. However, strength training may still be an effective treatment for those individuals with PFP suffering from strength deficits.     

Interaction of fluorescent molecular rotors with blood plasma proteins

Many disease states have associated blood viscosity changes. Molecular rotors, fluorescent molecules with viscosity sensitive quantum yields, have recently been investigated as a new method for biofluid viscosity measurement. Current viscometer measurements are complicated by proteins adhering to surfaces and forming air-surface layers. It is unknown at this time what effects proteins may have on biofluid viscosity measurements using molecular rotors. To answer this question, binding affinities to blood plasma proteins were investigated by equilibrium dialysis for four hydrophilic molecular rotors. Aqueous solutions of 9-[(2-cyano-2-hydroxy-carbonyl)vinyl]julolidine (CCVJ) and three derivatives were prepared and dialyzed against solutions of bovine source albumin, fibrinogen and immunoglobulin G approximating normal physiologic concentrations and fresh-frozen human plasma. After equilibration, dye concentration on each side of the dialysis membrane was assessed by spectrophotometry. The relative binding affinity of the four dyes to the proteins and to the plasma was compared. Affinity of all dyes was highest for albumin. The bound dye fraction showed little change in relation to protein concentration in the physiological concentration range. Diol, the most hydrophilic molecular rotor tested showed the lowest affinity for albumin. This study indicates that hydrophilic molecular rotors are well-suited for biofluid viscosity measurement.     

Scavenging of soluble organic matter from the prebiotic oceans.

The existence of hot or cold "nutrient broth" or "primeval soup" is challenged on the basis of the recent geochemistry of soluble organic carbon in the oceans. Most of the dissolved organic carbon is recycled quickly by organisms, but the residual, biologically refractive, organic matter is efficiently scavenged from the oceans (residence time of 1000 to 3500 years) by nonbiologically mediated chemical and physical processes, such as adsorption on sinking minerals, polymerization and aggregation to humic type polymers or by aggregation to particulate matter through bubbling and sinking of this material to the ocean bottom. Since there is no reason to believe that such nonbiological scavenging was not operative in the prebiotic oceans as well, then the prolonged existence of "organic soup" is very doubtful. The question of the origin of life is thus assumed to be related to solid-liquid interfacial activity, and the answer may be associated with sediment-water interaction rather than with solution chemistry.     

The primary structure of the lymphocyte pore-forming protein perforin: partial amino acid sequencing and determination of isoelectric point

The murine lymphocyte pore-forming protein (PFP) was purified to apparent homogeneity by successive steps of liquid chromatography. Monospecific antibodies were raised against purified PFP that detect only one protein band in murine CTL lines. 25% of the primary sequence of PFP (134 amino acids) was determined by amino terminal analysis of the purified protein and of some of its enzymatic cleavage products. These primary sequences were identical to sequences deduced by cDNA cloning. By isoelectric focusing, PFP was found to have a pI of 6.4. On the chromatofocusing column Mono P, however, PFP was found to elute at pH 4.7. This suggests a tertiary structure for monomeric PFP that is enriched in surface acidic amino acids.     

162 Dominant forces in protein folding

In the first part of this talk, I will discuss the need for a paradigm shift from hydrophobic (HφO) to a hydrophilic ((HφI) based theory of protein folding. Next, I will discuss the various types of solvent-induced forces that are exerted on various groups on the protein. It is argued, both theoretically and by simulations, that the HφI–HφI solvent-induced forces are likely to be the strongest. Therefore, it is suggested that these forces are also the forces that force the protein to fold, in a short time, along a narrow range of pathways. This paradigm shift also answers Levinthal’s question about the factors that “speed” and “guide” the folding of proteins.     

Metabolism of p-fluorophenylalanine in p-fluorophenylalanine sensitive and resistant tobacco cell cultures

The metabolism of D- and L-p-fluorophenylalanine (PFP) in DL-PFP resistant and sensitive tobacco cell cultures (Nicotiana tabacum), cell lines TX4 and TX1, respectively, has been compared. The amino acid analogue was taken up at a lower rate by the resistant cell line TX4. Incorporation of PFP into protein was also considerably reduced in TX4 cells, compared to TX1 cells. This, however, resulted mainly from a diminished availability of PFP due to a more rapid conversion of PFP by TX4 cells. TX1 cells and TX4 cells converted PFP qualitatively in the same way. The only detectable metabolite of D-PFP was N-malonyl-D-PFP, while all metabolites of L-PFP were identified as sequent products of the initial deamination of L-PFP by the enzyme phenylalanine ammonia-lyase (PAL). As TX4 cells were endowed with higher PAL-activity than TX1 cells, the resistant cells were able to metabolize L-PFP more rapidly to give, e.g., p-fluorocinnamoyl glucose ester and p-fluorocinnamoyl putrescine. In the presence of the specific PAL-inhibitor -aminooxy--phenylpropionic acid TX4 cells were slightly more sensitive to PFP. This suggests that the better detoxification contributes to the acquired resistance. The use of PFP as specific indicator for cell lines with increased PAL-activity, and hence increased levels of phenolic compounds, is discussed.Abbreviations AOPP -aminooxy--phenylpropionic acid - MCW methanol:chloroform:water - PAL phenylalanine ammonia-lyase - PFP p-fluorophenylalanine - Phe phenylalanine     

Predator migration in response to prey density: What are the consequences?

A predator-prey metapopulation model with two identical patches and only migration of the predator is investigated. Local predator-prey interaction is described by the so-called Rosenzweig-MacArthur model, while the migration term of the predator is put in a nonlinear form, which is derived by extending the Holling time budget argument to migration. In particular, a dimensionless parameter theta is introduced to quantify the migration tendency of predators while they are handling their prey, which gives rise to a family of models connecting two extremes: predators have no inclination to migrate while handling prey (theta = 0) and standard diffusion (theta = 1). Various aspects of the model, including changes in the number and the stability of equilibria and limit cycles, are investigated. We then focus on the key question: "Does spatial structure lead to a substantial damping of the violent oscillations exhibited by many predator-prey models?". It is known that the answer is "yes" if one adopts standard diffusion (theta = 1). However, we present substantial evidence that the answer is "no" if one takes theta = 0. We conclude that the migration submodel is an important constituent of a spatial predator-prey model and that the issue deserves scrutiny, both experimentally and theoretically.     

Rheological behaviors and miscibility of mixture solution of polyaniline and cellulose dissolved in an aqueous system

In our previous work, supramolecular films composed of hydrophilic cellulose and hydrophobic polyaniline (PANI) dissolved in NaOH/urea aqueous solution at low temperature through rearrangement of hydrogen bonds have been constructed. To further understand the miscibility and processability of the complex solution, the dynamic rheological behaviors of the PANI/cellulose complex solution were investigated, for the first time, in the present work. Transmission electron microscope (TEM) results demonstrated that the inclusion complexes consisted of PANI and cellulose, existed in the aqueous solution, showing a good miscibility. Time-temperatures superposition (tTs) results indicated that the PANI/cellulose solution exhibited a homogeneous system, and the complex solution was more stable than the cellulose solution in the temperature range from 5 to 25 °C. Winter-Chambon theory was proved to be capable of describing the gelation behavior of the PANI/cellulose complex solution. The relaxation exponent at the gel point was calculated to be 0.74, lower than the cellulose solution, indicating strong interactions between PANI and cellulose chains. Relatively larger flow activation energy of the PANI/cellulose solution suggested the formation and rupture of linkages in "junction zones" during the gelation processes. Furthermore, PANI/cellulose gels could form at elevated temperature as a result of the physical cross-linking and chain entanglement, and it was a thermoirreversible process. Moreover, the PANI/cellulose solution remained a liquid state for a long time at the temperature range from 0 to 8 °C, which is important for the industry process.     

Hydrophobic Collapse of Trigger Factor Monomer in Solution

Trigger factor (TF) is a chaperone, found in bacterial cells and chloroplasts, that interacts with nascent polypeptide chains to suppress aggregation. While its crystal structure has been resolved, the solution structure and dynamics are largely unknown. We performed multiple molecular dynamics simulations on Trigger factor in solution, and show that its tertiary domains display collective motions hinged about inter-domain linkers with minimal or no loss in secondary structure. Moreover, we find that isolated TF typically adopts a collapsed state, with the formation of domain pairs. This collapse of TF in solution is induced by hydrophobic interactions and stabilised by hydrophilic contacts. To determine the nature of the domain interactions, we analysed the hydrophobicity of the domain surfaces by using the hydrophobic probe method of Acharya et al. [1], [2], as the standard hydrophobicity scales predictions are limited due to the complex environment. We find that the formation of domain pairs changes the hydrophobic map of TF, making the N-terminal and arm2 domain pair more hydrophilic and the head and arm1 domain pair more hydrophobic. These insights into the dynamics and interactions of the TF domains are important to eventually understand chaperone-substrate interactions and chaperone function.     

Person and number syncretisms in Dutch

The aim of this paper is to make sense of the typologically quite exceptional pattern of person neutralization in the plural as we find it in Dutch verbal paradigms. We argue that Dutch, and most of its dialects, have a structural pattern of syncretism in their verbal paradigm: there are no person-distinctions in the plural. The main question of this paper is: where does this structural pattern of neutralization in Dutch come from, if we cannot explain it as a typologically wellattested pattern? As a first step, note that although the pattern is typologically quite odd, it conforms to another well-known generalization about paradigms: neutralization occurs in the marked half of the paradigm (see e.g. Nevins 2009). Further, we need to explain why this pattern occurs precisely in the Netherlands at this particular point in time. To this, we argue that this pattern arises as the result of a particular language acquisition strategy together with reduced evidence from the input for the fully inflected forms, probably as a result of dialect contact. This reduced evidence causes the third person, being the most frequent form, to dominate the other plural forms. In combination with limited paradigm splitting (Pinker, 1996), this explains the uniform plural that we find in most Dutch dialects.     

Cytosolic ATP-Dependent Phosphofructokinase from Spinach

ATP-dependent 6-phosphofructokinase (PFK) activity is present in both chloroplastic and in nonchloroplastic fractions isolated from spinach protoplasts. The activity in the extra-chloroplastic fraction was stimulated 2- to 3.5-fold by 25 mm inorganic phosphate (Pi), the chloroplast-associated activity was inhibited 2- to 5-fold. The Pi stimulated activity was ATP-dependent and was not an artifact due to the presence of fructose 6-P, Pi, pyrophosphatase, and pyrophosphate fructose 6-P 1-phosphotransferase (PFP). PFK activities, which expressed characteristics similar to those separated from protoplasts, could be separated following ammonium sulfate fractionation of crude extracts; the ammonium sulfate treatment also separated both PFK activities from PFP. It is concluded that spinach leaves contain a cytosolic PFK. This activity is relatively stable, is stimulated by Pi over a wide pH range, is not a result of the transformation of another enzyme activity, and has an activity that is similar to, or slightly less than, that of the cytosolic PFP.     

Laboratory animal-based collaborations and contracts beyond the border

There is a 'dollars crunch' at your institution. At a management meeting a discussion develops around the idea of outsourcing some of the future animal-based work to a facility located in another country. As a leader of the laboratory animal program, you need to answer the question: "What do we need to consider before agreeing to an overseas contract to complement our internal efforts?" The author sets out to answer this question as it relates to issues of animal care and use, regulatory and ethical concerns, legal obligations, and oversight of the work. The article focuses on international contracts and collaborations, but many of the principles discussed are also applicable to interinstitutional collaborations and contracts within the country where the laboratory animal program is based.     

Pulsed-field electrophoretic fingerprinting of Salmonella indiana and its epidemiological applicability

Eight Xba I-generated pulsed-field profile (PFP) types and four subtypes within one of the most common PFP types have been identified in Salmonella indiana from patients, poultry and human food in England and Wales in the three-year period from January 1994 to December 1996. Two PFP types have predominated, PFP X1 and PFP X2. Although the PFP X1 type was identified throughout the study period, the PFP X2 type was not identified until late 1995, subsequently becoming the most common PFP type in humans in the first six months of 1996 with a significant distribution in elderly patients. It is concluded that PFGE can be used in support of epidemiological investigations for the subdivision of Salm. indiana . Furthermore, as both conditions and interpretation criteria can be easily standardized, it is suggested that for many salmonella serotypes, PFGE can provide the basis for a definitive scheme of genotypic subtyping suitable for epidemiological investigations at both a national and international level.     

Monitoring clinical trials based on predictive probability of significance

At a given point in a clinical trial, investigators may ask the question: "What is the likelihood of a significant result if the trial were continued?" One possible answer to this question is to examine a predictive probability of the significant difference with further patient accrual. [See, for example, Choi, Smith, and Becker (1985, Controlled Clinical Trials 6, 280-288).] This paper proposes and investigates the approach in trials for comparing the means of two normal populations. Two methods for calculating the predictive probability are examined. The results indicate that the predictive probability can be a useful conservative measure in monitoring trials.     

What is an organism? An immunological answer

The question, "What is an organism?," formerly considered as essential in biology, has now been increasingly replaced by a larger question, "What is a biological individual?" On the grounds that i) individuation is theory-dependent, and ii) physiology does not offer a theory, biologists and philosophers of biology have claimed that it is the theory of evolution by natural selection that tells us what counts as a biological individual. Here I show that one physiological field, immunology, offers a theory that makes possible a biological individuation based on physiological grounds. I give a new answer to the question of the individuation of an organism by linking together the evolutionary and the immunological approaches to biological individuation.     

Pulsed-field electrophoretic fingerprinting of Salmonella indiana and its epidemiological applicability

Eight Xba I-generated pulsed-field profile (PFP) types and four subtypes within one of the most common PFP types have been identified in Salmonella indiana from patients, poultry and human food in England and Wales in the three-year period from January 1994 to December 1996. Two PFP types have predominated, PFP X1 and PFP X2. Although the PFP X1 type was identified throughout the study period, the PFP X2 type was not identified until late 1995, subsequently becoming the most common PFP type in humans in the first six months of 1996 with a significant distribution in elderly patients. It is concluded that PFGE can be used in support of epidemiological investigations for the subdivision of Salm. indiana. Furthermore, as both conditions and interpretation criteria can be easily standardized, it is suggested that for many salmonella serotypes, PFGE can provide the basis for a definitive scheme of genotypic subtyping suitable for epidemiological investigations at both a national and international level.     

Fructose-1,6-Bisphosphate Is an Allosteric Activator of Pyrophosphate:Fructose-6-Phosphate 1-Phosphotransferase

The activity of highly purified pyrophosphate:fructose-6-phosphate 1-phosphotransferase (PFP) from barley (Hordeum vulgare) leaves was studied under conditions where the catalyzed reaction was allowed to approach equilibrium. The activity of PFP was monitored by determining the changes in the levels of fructose-6-phosphate, orthophosphate, and fructose-1,6-bisphosphate (Fru-1,6-bisP). Under these conditions PFP activity was not dependent on activation by fructose-2,6-bisphosphate (Fru-2,6-bisP). Inclusion of aldolase in the reaction mixture temporarily restored the dependence of PFP on Fru-2,6-bisP. Alternatively, PFP was activated by Fru-1,6-bisP in the presence of aldolase. It is concluded that Fru-1,6-bisP is an allosteric activator of barley PFP, which can substitute for Fru-2,6-bisP as an activator. A significant activation was observed at a concentration of 5 to 25 [mu]M Fru-1,6-bisP, which demonstrates that the allosteric site of barley PFP has a very high affinity for Fru-1,6-bisP. The high affinity for Fru-1,6-bisP at the allosteric site suggests that the observed activation of PFP by Fru-1,6-bisP constitutes a previously unrecognized in vivo regulation mechanism.