Rethinking the role of theory in exploratory experimentation

To explain their role in discovery and contrast them with theory-driven research, philosophers of science have characterized exploratory experiments in terms of what they lack: namely, that they lack direction from what have been called “local theories” of the target system or object under investigation. I argue that this is incorrect: it’s not whether or not there is direction from a local theory that matters, but instead how such a theory is used to direct an experiment that matters. Appealing to contemporary exploratory experiments that involve the use of experimental techniques—specifically, examples where scientists explore the interaction of neural activity and human behavior by magnetically stimulating brains—I argue that local theories of a target system can inform auxiliary hypotheses in exploratory experiments, which direct these experiments. These examples illustrate how local theories can direct the exploration of target systems where researchers do not aim to evaluate these theories.     

Ionic mechanisms underlying tonic and phasic firing behaviors in retinal ganglion cells

In the retina, the firing behaviors that ganglion cells exhibit when exposed to light stimuli are very important due to the significant roles they play in encoding the visual information. However, the detailed mechanisms, especially the intrinsic properties that generate and modulate these firing behaviors is not completely clear yet. In this study, 2 typical firing behaviors—i.e., tonic and phasic activities, which are widely observed in retinal ganglion cells (RGCs)—are investigated. A modified computational model was developed to explore the possible ionic mechanisms that underlie the generation of these 2 firing patterns. Computational results indicate that the generation of tonic and phasic activities may be attributed to the collective actions of 2 kinds of adaptation currents, i.e., an inactivating sodium current and a delayed-rectifier potassium current. The concentration of magnesium ions has crucial but differential effects in the modulation of tonic and phasic firings, when the model neuron is driven by N-methyl-D-aspartate (NMDA) -type synaptic input instead of constant current injections. The proposed model has robust features that account for the ionic mechanisms underlying the tonic and phasic firing behaviors, and it may also be used as a good candidate for modeling some other firing patterns in RGCs.     

Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell

Vascular endothelial cells (ECs) play significant roles in regulating circulatory functions. Mechanical stimuli, including the stretch and shear stress resulting from circulatory pressure and flow, modulate EC functions by activating mechanosensors, signaling pathways, and gene and protein expressions. Mechanical forces with a clear direction (e.g., the pulsatile shear stress and the uniaxial circumferential stretch existing in the straight part of the arterial tree) cause only transient molecular signaling of pro-inflammatory and proliferative pathways, which become downregulated when such directed mechanical forces are sustained. In contrast, mechanical forces without a definitive direction (e.g., disturbed flow and relatively undirected stretch seen at branch points and other regions of complex geometry) cause sustained molecular signaling of pro-inflammatory and proliferative pathways. The EC responses to directed mechanical stimuli involve the remodeling of EC structure to minimize alterations in intracellular stress/strain and elicit adaptive changes in EC signaling in the face of sustained stimuli; these cellular events constitute a feedback control mechanism to maintain vascular homeostasis and are atheroprotective. Such a feedback mechanism does not operate effectively in regions of complex geometry, where the mechanical stimuli do not have clear directions, thus placing these areas at risk for atherogenesis. The mechanotransduction-induced EC adaptive processes in the straight part of the aorta represent a case of the "Wisdom of the Cell," as a part of the more general concept of the "Wisdom of the Body" promulgated by Cannon, to maintain cellular homeostasis in the face of external perturbations.     

Gender Differences in Emotional Responses to Cooperative and Competitive Game Play

Previous research indicates that males prefer competition over cooperation, and it is sometimes suggested that females show the opposite behavioral preference. In the present article, we investigate the emotions behind the preferences: Do males exhibit more positive emotions during competitive than cooperative activities, and do females show the opposite pattern? We conducted two experiments where we assessed the emotional responses of same-gender dyads (in total 130 participants, 50 female) during intrinsically motivating competitive and cooperative digital game play using facial electromyography (EMG), skin conductance, heart rate measures, and self-reported emotional experiences. We found higher positive emotional responses (as indexed by both physiological measures and self-reports) during competitive than cooperative play for males, but no differences for females. In addition, we found no differences in negative emotions, and heart rate, skin conductance, and self-reports yielded contradictory evidence for arousal. These results support the hypothesis that males not only prefer competitive over cooperative play, but they also exhibit more positive emotional responses during them. In contrast, the results suggest that the emotional experiences of females do not differ between cooperation and competition, which implies that less competitiveness does not mean more cooperativeness. Our results pertain to intrinsically motivated game play, but might be relevant also for other kinds of activities.     

Motivational dependence of centrifugal "tuning" influences on taste receptors

Bioelectrical activity was registered in the central sector of the glossopharyngeal nerve. The impulsation was processed on a specialized computer "ATAK-350" in the real-time regimen. Interval histogramms were made, based on the result of survey of 500 inter-impulse intervals. It has been established that during a 4-day food deprivation bimodal distribution of inter-impulse intervals takes place. The first maximum occurs within 10-15 ms, the second--within 190-200 ms. After the irritation of the stomach by the rubber balloon, containing 1.5-2.0 ml of water, monomolar distribution of inter-impulse intervals (with the maximum in the range of 55-60 ms) takes place. It is believed that specific motivating excitement is manifested not only in central structures, but also involves peripheral receptor structure and tunes them to accept adequate stimuli.     

Lift as a mechanism of patch initiation in mussel beds

The mussel Mytilus californianus is the dominant competitor for space in the mid-intertidal zone of wave-swept rocky shores in the Pacific Northwest where it forms extensive tightly packed beds. The rate at which patches are formed in these beds, can play an important rôle in community ecology by controlling the establishment and persistence of fugitive species. Despite the biological importance of physical disturbance, the mechanism of patch initiation has not been adequately explained. Battering by logs can create patches, but is the predominant mechanism only on shores near active logging sites. In other areas, it has been speculated that the hydrodynamic forces associated with storm waves somehow cause patches to form. However, the forces acting along the direction of flow — drag and the acceleration reaction — are unlikely to initiate patch formation. Here, it is suggested that fluid-dynamic lift forces imposed on mussel beds by breaking waves are sufficient to dislodge individual mussels and trigger patch formation. Arguments are presented suggesting that the likelihood of dislodgment by lift is consistent with the observed rate of patch formation in the absence of log battering.     

Gaining the upper hand: Economic mobility among immigrant and domestic minorities

Labour market experiences of three immigrant minorities in the United States are reviewed and contrasted with the three principal theories bearing on ethnic poverty and economic mobility: cultural assimilation, human capital acquisition, and industrial restructuring. Although there is support for each, they do not account satisfactorily for the experiences of many ethnic groups, in particular those who have progressed on the basis of socially embedded small entrepreneurship. An alternative conceptualization is suggested by these experiences that highlights the significance of community level variables and, in particular, alternative sources of social capital. The character of these processes is examined. Its implications for theories and policy towards ethnic minorities are discussed.     

Modeling the biomechanics of fetal movements

Fetal movements in the uterus are a natural part of development and are known to play an important role in normal musculoskeletal development. However, very little is known about the biomechanical stimuli that arise during movements in utero, despite these stimuli being crucial to normal bone and joint formation. Therefore, the objective of this study was to create a series of computational steps by which the forces generated during a kick in utero could be predicted from clinically observed fetal movements using novel cine-MRI data of three fetuses, aged 20–22 weeks. A custom tracking software was designed to characterize the movements of joints in utero, and average uterus deflection of \(6.95 \pm 0.41\) mm due to kicking was calculated. These observed displacements provided boundary conditions for a finite element model of the uterine environment, predicting an average reaction force of \(0.52 \pm 0.15\) N generated by a kick against the uterine wall. Finally, these data were applied as inputs for a musculoskeletal model of a fetal kick, resulting in predicted maximum forces in the muscles surrounding the hip joint of approximately 8 N, while higher maximum forces of approximately 21 N were predicted for the muscles surrounding the knee joint. This study provides a novel insight into the closed mechanical environment of the uterus, with an innovative method allowing elucidation of the biomechanical interaction of the developing fetus with its surroundings.     

Regulation of TRP channels by phosphorylation

The transient receptor potential (TRP) channels are a group of Ca2+-permeable cation channels (except TRPM4 and TRPM5) that function as cellular sensors of various internal and external stimuli. Most of these channels are expressed in the nervous system and they play a key role in sensory physiology. They may respond to temperature, pressure, inflammatory agents, pain, osmolarity, taste and many other stimuli. Recent development indicates that the activity of these channels is regulated by protein phosphorylation and dephosphorylation of serine, threonine, and tyrosine residues. In this review, we present a comprehensive summary of the literature regarding the TRP channel regulation by different protein kinases.     

Pattern orthogonalization via channel decorrelation by adaptive networks

The early processing of sensory information by neuronal circuits often includes a reshaping of activity patterns that may facilitate further processing in the brain. For instance, in the olfactory system the activity patterns that related odors evoke at the input of the olfactory bulb can be highly similar. Nevertheless, the corresponding activity patterns of the mitral cells, which represent the output of the olfactory bulb, can differ significantly from each other due to strong inhibition by granule cells and peri-glomerular cells. Motivated by these results we study simple adaptive inhibitory networks that aim to separate or even orthogonalize activity patterns representing similar stimuli. Since the animal experiences the different stimuli at different times it is difficult for the network to learn the connectivity based on their similarity; biologically it is more plausible that learning is driven by simultaneous correlations between the input channels. We investigate the connection between pattern orthogonalization and channel decorrelation and demonstrate that networks can achieve effective pattern orthogonalization through channel decorrelation if they simultaneously equalize their output levels. In feedforward networks biophysically plausible learning mechanisms fail, however, for even moderately similar input patterns. Recurrent networks do not have that limitation; they can orthogonalize the representations of highly similar input patterns. Even when they are optimized for linear neuronal dynamics they perform very well when the dynamics are nonlinear. These results provide insights into fundamental features of simplified inhibitory networks that may be relevant for pattern orthogonalization by neuronal circuits in general.     

Analysis of the neuronal selectivity underlying low fMRI signals

BACKGROUND: A prevailing assumption in neuroimaging studies is that relatively low fMRI signals are due to weak neuronal activation, and, therefore, they are commonly ignored. However, lower fMRI signals may also result from intense activation by highly selective, albeit small, subsets of neurons in the imaged voxel. We report on an approach that could form a basis for resolving this ambiguity imposed by the low (mm range) spatial resolution of fMRI. Our approach employs fMR-adaptation as an indicator for highly active neuronal populations even when the measured fMRI signal is low.RESULTS: In this study, we first showed that fMRI-adaptation is diminished when overall neuronal activity is lowered substantially by reducing image contrast. We then applied the same adaptation paradigm, but this time we lowered the fMRI signal by changing object shape. While the overall fMRI signal in category-related regions such as the face-related pFs was drastically reduced for non-face stimuli, the adaptation level obtained for these stimuli remained high. We hypothesize that the relatively greater adaptation level following exposure to "nonoptimal" object shapes is indicative of small subsets of neurons responding vigorously to these "nonoptimal" objects even when the overall fMRI activity is low.CONCLUSIONS: Our results show that fMR-adaptation can be used to differentiate between neuronal activation patterns that appear similar in the overall fMRI signal. The results suggest that it may be possible to employ fMR-adaptation to reveal functionally heterogeneous islands of activity, which are too small to image using conventional imaging methods.     

Mode of Operation of Ampullae of Lorenzini of the Skate, Raja

Ampullae of Lorenzini are sensitive electroreceptors. Applied potentials affect receptor cells which transmit synaptically to afferent fibers. Cathodal stimuli in the ampullary lumen sometimes evoke all-or-none "receptor spikes," which are negative-going recorded in the lumen, but more frequently they evoke graded damped oscillations. Cathodal stimuli evoke nerve discharge, usually at stimulus strengths subthreshold for obvious receptor oscillations or spikes. Anodal stimuli decrease any ongoing spontaneous nerve activity. Cathodal stimuli evoke long-lasting depolarizations (generator or postsynaptic potentials) in afferent fibers. Superimposed antidromic spikes are reduced in amplitude, suggesting that the postsynaptic potentials are generated similarly to other excitatory postsynaptic potentials. Anodal stimuli evoke hyperpolarizations of nerves in preparations with tonic activity and in occasional silent preparations; presumably tonic release of excitatory transmitter is decreased. These data are explicable as follows: lumenal faces of receptor cells are tonically (but asynchronously) active generating depolarizing responses. Cathodal stimuli increase this activity, thereby leading to increased depolarization of and increased release of transmitter from serosal faces, which are inexcitable. Anodal stimuli act oppositely. Receptor spikes result from synchronized receptor cell activity. Since cathodal stimuli act directly to hyperpolarize serosal faces, strong cathodal stimuli overcome depolarizing effects of lumenal face activity and are inhibitory. Conversely, strong anodal stimuli depolarize serosal faces, thereby causing release of transmitter, and are excitatory. These properties explain several anomalous features of responses of ampullae of Lorenzini.     

Genetic drift as a directional factor: biasing effects and a priori predictions

The adequacy of Elliott Sober’s analogy between classical mechanics and evolutionary theory—according to which both theories explain via a zero-force law and a set of forces that alter the zero-force state—has been criticized from various points of view. I focus here on McShea and Brandon’s claim that drift shouldn’t be considered a force because it is not directional. I argue that there are a number of different theses that could be meant by this, and show that one of those theses—the idea that drift cannot bias populations to be taken somewhere in the evolutionary space from one generation to the next—is actually false. Not only has this thesis been implicitly assumed in the discussion of the force analogy thus far, but it is also commonly found in a wider range of philosophical and biological texts. I argue that correcting this view, and the usual images associated with it, will thereby bring heuristic benefits that impact the force analogy discussion, but that also go beyond it.     

The Psychology of the Self-Actualizing Personality in the Work of Abraham Maslow

The second and third quarters of this century saw the appearance of a number of different concepts of personality in foreign psychology. Most of these were spawned by pathopsychology as a result of attempts to understand the personality of the neurotic and as a practical offshoot of psychotherapy. Although these theories were generalizations based on studies of the psychopathological personality, they began to be propagated by their creators as general theories of personality. Material gathered from the investigation of mental patients was used as the foundation for what are now standard personality tests — the Rorschach test and the Thematic Apperception Test (TAT) — used chiefly to discover neurotic tendencies in the individual. An extremely exaggerated evaluation of the significance of the pathopsychological method has been the hallmark of personality theory in foreign psychology. Yet the neurotic and, even more so, the pathological personality are qualitatively, not quantitatively, distinct from the personality of a normal human being. We must therefore concur with Maslow, who shows how the "study of mutilated, sickly, immature and unhealthy subjects will also give rise to a mutilated psychology and philosophy" (9, p. 234).     

Animal cells in turbulent fluids: details of the physical stimulus and the biological response

Animal cells in large scale bioreactors are subjected to a variety of fluid forces for which they are not adapted by evolution. In severe cases the result is cell death, but under more modest agitation conditions an increasing number of nonlethal responses affecting growth rate, metabolism, and product formation have been reported. The forces causing these responses have not been characterized because particle-turbulence interactions are extremely complex. The current understanding of the microscopic structure of turbulence in an infinite liquid and in boundary layers shows that an average shear stress alone is not likely to be adequate to describe the bioreactor environment. Combining knowledge of the physical stimuli and the biological responses will lead to better ways of limiting cell damage and possibly to using physical stresses as a means of specifically modifying cell behavior.     

Situational Specificity in Alpine-marmot Alarm Communication

We studied the degree to which alpine marmot (Marmota marmota L.) alarm calls function as communication about specific external stimuli. Alpine marmots emit variable alarm calls when they encounter humans, dogs, and several species of aerial predators. The first part of the study involved observations and manipulations designed to document contextual variation in alarm calls. Alarm calls varied along several acoustic parameters, but only along one that we examined, the number of notes per call, was significantly correlated with the type of external stimulus. Marmots were more likely to emit single-note alarm calls as their first or only call in response to an aerial stimulus, and multiple-note alarm calls when first calling to a terrestrial stimulus. This relationship was not without exceptions; there was considerable variation in the number of notes they emitted to both aerial and terrestrial stimuli, and a single stimulus type — humans — elicited a wide range of acoustic responses. The second part of the study involved playing back three types of alarm calls to marmots and observing their responses. Marmots did not have overtly different responses to the three types of played-back alarm calls. Our results are consistent with the hypotheses that: 1. Alarm calls do not refer to specific external stimuli; 2. Alarm calls function to communicate the degree of risk a caller experiences; and 3. Alarm calls require additional contextual cues to be properly interpreted by conspecifics.     

Activity of central neurons of the electroreceptor system ofGlyptosternum reticulatum

Two types of electroreceptive neurons — tonic and phasic — were found in acute experiments with extracellular recording of unit activity from the lateral lobes of the medulla in the Turkestan catfishGlyptosternum reticulatum. Tonic neurons were more sensitive to the potential gradient in water (the threshold for most neurons was 1–6 µV/cm) than phasic neurons, they possessed spontaneous activity (mean frequency 4–10 spikes/sec), and their response characteristics depended significantly on the intensity and duration of stimulation. Phasic neurons had no spontaneous activity; their sensitivity was about one order of magnitude lower than that of the tonic neurons, and the response was independent of the parameters of the stimuli. The probable mechanisms of differentiation of neurons into two types, with a possible link with the characteristics of the receptor formations or with the functional organization of the corresponding brain centers, are discussed.     

Role of gastrocnemius activation in knee joint biomechanics: gastrocnemius acts as an ACL antagonist

Gastrocnemius is a premier muscle crossing the knee, but its role in knee biomechanics and on the anterior cruciate ligament (ACL) remains less clear when compared to hamstrings and quadriceps. The effect of changes in gastrocnemius force at late stance when it peaks on the knee joint response and ACL force was initially investigated using a lower extremity musculoskeletal model driven by gait kinematics—kinetics. The tibiofemoral joint under isolated isometric contraction of gastrocnemius was subsequently analyzed at different force levels and flexion angles (0°–90°). Changes in gastrocnemius force at late stance markedly influenced hamstrings forces. Gastrocnemius acted as ACL antagonist by substantially increasing its force. Simulations under isolated contraction of gastrocnemius confirmed this role at all flexion angles, in particular, at extreme knee flexion angles (0° and 90°). Constraint on varus/valgus rotations substantially decreased this effect. Although hamstrings and gastrocnemius are both knee joint flexors, they play opposite roles in respectively protecting or loading ACL. Although the quadriceps is also recognized as antagonist of ACL, at larger joint flexion and in contrast to quadriceps, activity in gastrocnemius substantially increased ACL forces (anteromedial bundle). The fact that gastrocnemius is an antagonist of ACL should help in effective prevention and management of ACL injuries.