Driven translocation of a polymer: role of pore friction and crowding.

Force-driven translocation of a macromolecule through a nanopore is investigated systematically by taking into account the monomer-pore friction as well as the "crowding" of monomers on the trans-side of the membrane which counterbalance the driving force acting in the pore. The problem is treated self-consistently, so that the resulting force in the pore and the dynamics on the cis and trans sides mutually influence each other. The set of governing differential-algebraic equations for the translocation dynamics is derived and solved numerically. The analysis of this solution shows that the crowding of monomers on the trans side hardly affects the dynamics, but the monomer-pore friction can substantially slow down the translocation process. Moreover, the translocation exponent α in the translocation time-vs.-chain length scaling law, τ ∝ N(α), becomes smaller for relatively small chain lengths as the monomer-pore friction coefficient increases. This is most noticeable for relatively strong forces. Our findings show that the variety of values for α reported in experiments and computer simulations, may be attributed to different pore frictions, whereas crowding effects can generally be neglected.

Forced translocation of a polymer: Dynamical scaling versus molecular dynamics simulation.

We suggest a theoretical description of the force-induced translocation dynamics of a polymer chain through a nanopore. Our consideration is based on the tensile (Pincus) blob picture of a pulled chain and the notion of a propagating front of tensile force along the chain backbone, suggested by Sakaue [Phys. Rev. E 76, 021803 (2007); Phys. Rev. E 81, 041808 (2010); Eur. Phys. J. E 34, 135 (2011)]. The driving force is associated with a chemical potential gradient that acts on each chain segment inside the pore. Depending on its strength, different regimes of polymer motion (named after the typical chain conformation: trumpet, stem-trumpet, etc.) occur. Assuming that the local driving and drag forces are equal (i.e., in a quasistatic approximation), we derive an equation of motion for the tensile front position X(t). We show that the scaling law for the average translocation time 〈τ〉 changes from <τ> ∼ N2ν/f1/ν to <τ> ∼ N^1+ν/f (for the free-draining case) as the dimensionless force f[over ̃]R=aNνf/T (where a, N, ν, f, and T are the Kuhn segment length, the chain length, the Flory exponent, the driving force, and the temperature, respectively) increases. These and other predictions are tested by molecular-dynamics simulation. Data from our computer experiment indicate indeed that the translocation scaling exponent α grows with the pulling force f[over ̃]R, albeit the observed exponent α stays systematically smaller than the theoretically predicted value. This might be associated with fluctuations that are neglected in the quasistatic approximation.

Fractional Brownian motion approach to polymer translocation: the governing equation of motion.

We suggest a governing equation that describes the process of polymer-chain translocation through a narrow pore and reconciles the seemingly contradictory features of such dynamics: (i) a Gaussian probability distribution of the translocated number of polymer segments at time t after the process has begun, and (ii) a subdiffusive increase of the distribution variance Δ(t) with elapsed time Δ(t)∝t(α). The latter quantity measures the mean-squared number s of polymer segments that have passed through the pore Δ(t)=([s(t)-s(t=0)](2)), and is known to grow with an anomalous diffusion exponent α<1. Our main assumption [i.e., a Gaussian distribution of the translocation velocity v(t)] and some important theoretical results, derived recently, are shown to be supported by extensive Brownian dynamics simulation, which we performed in 3D. We also numerically confirm the predictions made recently that the exponent α changes from 0.91 to 0.55 to 0.91 for short-, intermediate-, and long-time regimes, respectively.

Two-dimensional perturbations in a scalar model for shear banding.

We present an analytical study of a toy model for shear banding, without normal stresses, which uses a piecewise linear approximation to the flow curve (shear stress as a function of shear rate). This model exhibits multiple stationary states, one of which is linearly stable against general two-dimensional perturbations. This is in contrast to analogous results for the Johnson-Segalman model, which includes normal stresses, and which has been reported to be linearly unstable for general two-dimensional perturbations. This strongly suggests that the linear instabilities found in the Johnson-Segalman can be attributed to normal stress effects.

Comment on 'Anomalous dynamics of unbiased polymer translocation through a narrow pore' and other recent papers by D Panja, G Barkema and R Ball.

In a recent publication of Panja et al (2007 J. Phys.: Condens. Matter 19 432202) they suggested a new interpretation of the translocation problem of polymer chain threading through a narrow pore. Here we point out some contradictions and inconsistencies in this treatment which question the plausibility of the obtained results.

Polymer translocation through a nanopore: a showcase of anomalous diffusion.

The translocation dynamics of a polymer chain through a nanopore in the absence of an external driving force is analyzed by means of scaling arguments, fractional calculus, and computer simulations. The problem at hand is mapped on a one-dimensional anomalous diffusion process in terms of the reaction coordinate s (i.e., the translocated number of segments at time t ) and shown to be governed by a universal exponent alpha=2(2nu+2-gamma(1), where nu is the Flory exponent and gamma(1) is the surface exponent. Remarkably, it turns out that the value of alpha is nearly the same in two and three dimensions. The process is described by a fractional diffusion equation which is solved exactly in the interval 02, which provide a full description of the diffusion process. The comparison of the analytic results with data derived from extensive Monte Carlo simulations reveals very good agreement and proves that the diffusion dynamics of unbiased translocation through a nanopore is anomalous in its nature.

Identification of determinants of the between-operator variation of the total protein S antigen assay: a collaborative study of the Dutch Working Group on Haemostasis Laboratory Diagnosis.

In a previous study, a between-operator variability (CVOBETWEEN) of 9.6% and 15.0%) was observed for total protein S antigen assays in 11 laboratories using a frozen or lyophilized reference plasma, respectively, and the need to standardize the use of lyophilized reference plasma was identified. The aim of the present study was to identify further determinants of this CVOBETWEEN in order to improve between-laboratory comparisons of test results for one method for protein S antigen assay. Two protocols were carried out: the first again involving local execution but using a joint standardized and detailed prescription of the technical performance in each laboratory; the second using a central session for all operators with the same prescription but with joint reagent and equipment. In the present study, improved handling of lyophilized reference plasma was included and resulted in comparable CVOBETWEEN of 10.9% and 9.6% for the use of frozen and lyophilized reference plasma for the local test performance. An improvement was found in the CVOBETWEEN in the central session compared with the standardized local performance, showing lower values for the central performance of 8.5 and 6.6% for frozen and lyophilized reference plasma, respectively. Further analysis of the difference between the local and central test performance identified the use of different curve fit options of data evaluation software as a significant source of this difference. Interestingly, the within-operator variability in the central performance was around 2% lower (5.9 and 6.0% for frozen and lyophilized plasma, respectively) than that in the local performance (8.1 and 8.0% for frozen and lyophilized plasma, respectively). Although the reduction is not statistically significant, it suggests an effect of reduction of the workload and simplification of procedures for individual operators on the within-operator variability. In this study, in which 11 operators/laboratories participated, the lowest variability between operators andwithin laboratories was obtained in the central test performance, which is suggested to be the lowest attainable variability for the measurement of total protein S antigen. The practical factors involved in local performance that require attention to reach similar levels of variability are mainly liquid handling, curve-fit procedures and simplicity of practical procedures.

The central mesencephalic grey in birds: nucleus intercollicularis and substantia grisea centralis.

The question discussed in this paper is, whether the dorsomedial part of the intercollicular nucleus and central mesencephalic grey of birds are comparable to (parts of) the periaqueductal grey in mammals. The mammalian periaqueductal grey, and the avian dorsomedial part of the intercollicular nucleus + central mesencephalic grey are each part of pathways in control of functions such as vocalization and sexual behavior. The connectivity and histochemical features of the dorsomedial intercollicular nucleus and central mesencephalic grey are partly different and also differ partly from those of the mammalian periaqueductal grey. It is suggested that these areas in mammals and birds form comparable links in the emotional motor pathway that has been defined before in mammals.

The distribution of dopamine, substance P, vasoactive intestinal polypeptide and neuropeptide Y immunoreactivity in the brain of the collared dove, Streptopelia decaocto.

This study is part of a program intended to provide the neuroanatomical framework for investigations of the role of brain areas in specific aspects of behavior in the collared dove. In the present study, the distribution of dopamine-, substance P-, vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-immunoreactivity are mapped throughout the brain of this bird. For each substance, our observations are compared with data from studies in other species of birds. Over all, our data confirm the results of previous reports, but a few differences with data from some of these studies are found. The immunohistochemical data are used in an attempt to define more precisely cell areas and their subdivisions in the avian forebrain and brainstem, and to compare these areas to nuclei in the brain of mammals.

The vestibular nuclei and vestibuloreticular connections in the mallard (Anas platyrhynchos L.). An anterograde and retrograde tracing study.

The vestibular apparatus provides information about the position and movements of the head. Craniocervical muscles position the head with respect to the upper part of the neck. Motoneurons innervating these muscles are located in the supraspinal nucleus and ventral horn of the rostral cervical cord. Premotor neurons of craniocervical muscles have been found in the medial two-thirds of the medullary reticular formation: the ventromedial part of the parvocellular reticular formation and the gigantocellular reticular formation. In the present study, projections from vestibular nuclei upon craniocervical premotor neurons were investigated using anterograde and retrograde tracers. Vestibulospinal fibers run bilaterally in the medial vestibulospinal tract and ipsilaterally in the lateral vestibulospinal tract. Vestibuloreticular projections are mainly ipsilateral, and originate from the n. vestibularis lateralis pars ventralis and pars dorsalis, and from the n. vestibularis descendens. Terminal labeling is found in the border zone between the parvocellular and gigantocellular reticular formation. These projections show that in addition to direct bilateral vestibulo-craniocervical projections an indirect vestibular pathway to craniocervical motor nuclei exists. The direct pathway probably is the neural substrate for the vestibulocollic reflex, whereas the vestibular projection upon the reticular formation might influence head orientation during various kinds of activities, such as pecking, preening and so on.

Distribution of gastrin-releasing peptide immunoreactivity in the brain of the collared dove (Streptopelia decaocto).

The distribution of immunoreactivity after applying an antibody against gastrin-releasing peptide (GRP) was studied in the brain of the collared dove (Streptopelia decaocto). In the forebrain GRP-immunoreactive (GRP-ir) cells were found in the hyperstriatum accessorium, medial and lateral parts of the neostriatum, corticoidea dorsolateralis and temporoparieto-occipitalis areas, hippocampus, pre- and parahippocampal areas and prepiriform cortex. In the brainstem, GRP-ir cells were restricted mainly to the substantia nigra and ventral tegmental nucleus. Areas with densely packed GRP-ir clusters of varicosities were the medial intermediate hyperstriatum ventrale and lateral septal nucleus; dense GRP-ir neuropil was found in the parolfactory lobe, and in the dorsal half of the intermediate and caudal archistriatum. The ventral lamina medullaris contained many GRP-ir fibers. Forebrain areas devoid of immunoreactivity were the basal nucleus, ectostriatum, rostral archistriatum, most of the paleostriatum augmentatum and the lateral bed nucleus of the stria terminalis. Moderate densities of GRP-ir elements were found in the other telencephalic areas and further in, among others, the preoptic and hypothalamic region, ventral area of Tsai, cerulean nuclei, parabrachial complex, dorsal glossopharyngeal and vagus motor nuclei and medial nuclei of the solitary complex. The observations are compared with data from the literature and the implications for the definition of specific centers within the avian brain are discussed, with emphasis on systems with a role in visceral and motivational functions and in learning.

Immunohistochemical characterization of forebrain areas in the collared dove (streptopelia decaocto).

The distribution of four neuroactive substances was studied in the telencephalon of the collared dove using enzyme- and immunohistochemistry. The distribution of acetylcholinesterase and dopamine was similar to that described in other birds. Galanin-immunoreactive fibres were found mainly in the paleostriatum primitivum , the medial part of the parolfactory lobe (LPO) and the lateral septal nucleus; galanin may interfere with acetylcholine activity. Intense gastrin releasing peptide (GRP)-immunoreactivity was found in the neuropil of LPO, the ventral paleostriatum and the caudal archistriatum; further GRP-immunoreactive varicosities were found in the neostriatum and the hyperstriatum ventrale - particularly in its medial part - whereas GRP-immunoreactive cells occurred in the medial neostriatum, the hyperstriatum accessorium and the ventral archistriatum. These data help to define more precisely several functional telencephalic systems, but no indications for specific centers with a role in vocalization were found.

Location of reticular premotor areas of a motor center innervating craniocervical muscles in the mallard (Anas platyrhynchos L.).

The supraspinal nucleus (SSp) in the mallard, which lies in the rostral spinal cord and caudal brainstem, is a motor nucleus that forms the rostral continuation of the ventral horn. It contains part of the motoneurons innervating the craniocervical muscles. Injections with horseradish peroxidase (HRP) and wheat germ agglutinin conjugated to HRP (WGA) in the SSp were used to localize the craniocervical premotor neurons in the medullary reticular formation. A mixture of WGA and HRP (WGA/HRP) or biotinylated dextran amine (BDA) were injected in the different reticular areas to test the results. Small numbers of craniocervical premotor neurons were found bilaterally in the ventromedial part of the parvocellular reticular formation (RPcvm) and in the caudal extension of RPcvm, the nucleus centralis dorsalis of the medulla oblongata, and the gigantocellular reticular formation (RGc). In a second series of experiments, WGA/HRP and BDA injections in these reticular areas were used to visualize afferent fibers and terminals in the SSp. The combination of the two types of experiments shows that RPcvm and RGc contain modest numbers of craniocervical premotor neurons. Because the reticular formation also contains jaw and tongue premotor neurons and receives a variety of sensory projections, the present results suggest that the medullary reticular formation plays a role in the coordination of complex movements (e.g., feeding). The pattern of afferent and efferent connections of the reticular formation is used to redefine its subdivisions in the myelencephalon of the mallard.

Excitability and coherence resonance in lasers with saturable absorber.

We show that a laser with a saturable absorber, described by the Yamada model, displays excitability just below threshold. A small perturbation, for example, a small input pulse, can trigger a single high output pulse, after which the system relaxes back to the off state. In order to study possible applications, such as pulse reshaping and clock recovery, approximate expressions are given for the excitability threshold and the delay between input and output pulses. Under the influence of optical noise, the system displays coherence resonance: below threshold the laser produces pulse trains with minimal jitter for a particular optimal noise level. This all-optical coherence resonance allows direct experimental verification.

The neural substrate for 'learned' and 'nonlearned' activities in birds: a discussion of the organization of bulbar reticular premotor systems with side-lights on the mammalian situation.

The reticular formation of the brainstem contains premotor systems for various musculomotor systems. In this paper, the bulbar premotor systems for jaw and tongue movements, head and neck movements, locomotion, and respiration and vocalization in birds are reviewed and compared to premotor systems in mammals. Roughly, the bulbar reticular formation can be subdivided in three longitudinal zones: a dorsolateral (RPcdl) and a ventromedial (RPcvm) parvocellular zone and a gigantocellular zone (RGc). RPcdl contains premotor neurons for the jaw and neck system, RPcvm for the jaw, tongue and neck system, and RGc for the tongue and locomotory system. RPcdl receives input from the descending sensory trigeminal system, parts of RPcvm and RGc from vestibular nuclei, whereas the tectum has a projection to the contralateral RGc. RPcdl and RPcvm receive substantial telencephalic input through the occipitomesencephalic tract. The bulbar part of the respiratory system consists of a series of cell groups in the ventrolateral reticular formation and has connections with motor centers of the vocalization system. The similarities and differences between the avian and mammalian situation are discussed. Musculomotor systems participate in various activities. It is argued that a premotor system should possess sufficient flexibility to control the participation of a motor system in the different activities. This flexibility may permit the occurrence of learning processes in terms of refining basically existing motor patterns. The emergence of new and more complex motor patterns as in vocalization requires the involvement of hierarchically higher brain centers.

The sensory trigeminal system in birds: input, organization and effects of peripheral damage. A review.

The primary sensory trigeminal system in birds comprises the mesencephalic trigeminal nucleus and the trigeminal ganglion with projections to the principal sensory nucleus (PrV) and the descending tract with its subnuclei. Other cranial nerves can contribute to PrV and the descending system that together form the somatosensory system of the head. There is also a proprioceptive component. The somatosensory system comprises a component serving tactile sense and a nociceptive component. The former processes information from many mechanoreceptors in beak and tongue; both PrV and subnuclei of the descending system are involved. The nociceptive component consists of small ganglion cells projecting presumably to layers I and II of the caudal subnucleus of the descending trigeminal system and cervical dorsal horn; this is the only trigeminal region showing immunoreactivity for substance P. The effects of amputation of the tips of the beak of chickens (debeaking) are estimated by fiber counts in electron microscopic preparations of the trigeminal branches innervating that area, and by cell counts in Nissl stained sections of the trigeminal ganglion. Our data indicate that debeaking causes a loss of exteroceptive units, but not of nociceptive units. Comparison of sections stained for the presence of substance P (immunohistochemistry) did not reveal a long-term effect on the nociceptive system suggestive of the occurrence of chronic pain.

A crossed projection from the optic tectum to craniocervical premotor areas in the brainstem reticular formation. An anterograde and retrograde tracing study in the mallard (Anas platyrhynchos L.).

The optic tectum in birds receives visual information from the contralateral retina. This information is passed through to other brain areas via the deep layers of the optic tectum. In the present study the crossed tectobulbar pathway is described in detail. This pathway forms the connection between the optic tectum and the premotor area of craniocervical muscles in the contralateral paramedian reticular formation. It originates predominantly from neurons in the ventromedial part of stratum griseum centrale and to a lesser extent from stratum album centrale. The fibers leave the tectum as a horizontal fiber bundle, and cross the midline through the caudal radix oculomotorius and rostral nucleus oculomotorius. On the contralateral side fibers turn to ventral and descend caudally in the contralateral paramedian reticular formation to the level of the obex. Labeled terminals are found in the ipsilateral medial mesencephalic reticular formation lateral to the radix and motor nucleus of the oculomotor nerve, and in the contralateral paramedian reticular formation, along the descending tract. Neurons in the medial mesencephalic reticular formation in turn project to the paramedian reticular formation. Through the crossed tectobulbar pathway visual information can influence the activity of craniocervical muscles via reticular premotor neurons.

Organization and efferent connections of the archistriatum of the mallard, Anas platyrhynchos L.: an anterograde and retrograde tracing study.

The intratelencephalic and descending connections of the archistriatum of the mallard were studied using anterograde and retrograde tracers. Autoradiography after injections of [3H]-leucine served to visualize the intratelencephalic and extratelencephalic efferent connections of the archistriatum. Horseradish peroxidase (HRP), HRP-wheatgerm agglutinin, and fluorescent tracers were used to identify the precise origin of the projections to the various terminal fields found in the anterograde experiments. Four main regions can be recognized in the archistriatum of the mallard: (1) the rostral or anterior part that is a source of contralateral intratelencephalic projections, in particular to the contralateral archistriatum; (2) the dorsal intermediate archistriatum that is the origin of a large descending fiber system, the occipitomesencephalic tract, with projections to dorsal thalamic nuclei, the medial spiriform nucleus, the intercollicular nucleus, the deep tectum, parts of the mesencephalic and bulbar reticular formation, and the subnuclei of the descending trigeminal tract. There are no direct projections to motor nuclei. This part corresponds to the somatic sensorimotor part as defined by Zeier and Karten (1971, Brain Res. 31:313-326); it also contributes to the ipsilateral intratelencephalic connections and, to a lesser degree, to contralateral intratelencephalic connections. (3) The ventral intermediate archistriatum is another region that is also a source of intratelencephalic projections, in particular of those to the lobus parolfactorius. The most lateral zone sends fibers to the septal area. (4) The caudoventral intermediate and posterior archistriatum is another region that is a source of the projections to the hypothalamus and thus corresponds to the amygdaloid part of the archistriatum as defined by Zeier and Karten; it also contributes a modest component to the occipitomesencephalic tract. The different cell populations are not spatially separated, which makes it impossible to recognize distinct subnuclei within the four main regions of the archistriatum of the mallard.

Central connections of the nucleus mesencephalicus nervi trigemini in the mallard (Anas platyrhynchos L.).

BACKGROUND: In the mallard duck, functionally distinct groups of jaw muscles are each innervated by a different subnucleus of the main trigeminal (mV) or facial (mVII) motor nucleus. The other subnuclei of mV and mVII innervate several head muscles, including lingual muscles. The reticular premotor cells of the trigeminal and facial jaw motor subnuclei occupy different areas in the parvocellular reticular formation (RPc). The cell bodies of jaw muscle spindle afferents are situated in the mesencephalic nucleus (MesV). In the present study, the central connections of MesV with jaw motor subnuclei and their premotor areas are investigated. METHODS: In a first series of experiments, horseradish peroxidase (HRP) injections were made in electrophysiologically identified trigeminal and facial subnuclei. In a second series of experiments, HRP was delivered iontophoretically at different parts of RPc. Anterograde tracing with tritiated leucine was used to confirm the central connections of MesV. Double labeling with fluorescent tracers was used to investigate whether MesV collaterals reach both the rostral and caudal parts of RPc. RESULTS: MesV projects to only two of the five different subnuclei of the trigeminal motor nucleus. The subnuclei that receive spindle afferents innervate jaw adductor muscles (mV2) or pro- and retractors of the mandible (pterygoid muscles; mV1). The three other subnuclei innervate jaw-opener muscles or other head muscles. MesV fibers also project to the rostral part of the dorsolateral RPc (RPcdl), which serves as a premotor area for the motor subnuclei of adductor and pterygoid muscles. The intermediate part of RPcdl does not contain premotor cells of mV or mVII, and a clear projection of MesV to this area is absent. The caudal part of RPcdl projects to the mV and mVII subnuclei that innervate jaw-opener muscles. This part of RPc receives a projection from the same MesV cells as the rostral RPcdl. The MesV projection to RPc does not include premotor cells of mV and mVII in the ventromedial part of RPc (RPcvm). CONCLUSIONS: Spindle afferents from jaw-closer muscles project only to mV subnuclei innervating jaw-closer muscles (mV1, mV2) and to a population of premotor cells in the rostral RPcdl that innervates these subnuclei. The mixed population of premotor cells in RPcvm, which innervates both jaw-opener and jaw-closer subnuclei, does not receive a MesV projection. However, a premotor area for jaw-opener subnuclei in the caudal part of RPcdl does receive MesV input and may serve as a relay through which proprioceptive information from jaw closer spindles can reach jaw opener muscles.