BACKGROUND AND PURPOSEChemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain. EXPERIMENTAL APPROACHEffects of single, intrathecal, perineural and s.c. injections of the PKR antagonist PC1, or of 1 week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated in mice with chronic constriction of the sciatic nerve (CCI). Expression and localization of PROK2 and of its receptors at peripheral and central level was evaluated 10 days after CCI, following treatment for 1 week with saline or PC1. IL-1β and IL-10 levels, along with glia activation, were evaluated. KEY RESULTSSubcutaneous, intrathecal and perineural PC1 acutely abolished the CCI-induced hyperalgesia and allodynia. At 10 days after CCI, PROK2 and its receptor PKR2 were up-regulated in nociceptors, in Schwann cells and in activated astrocytes of the spinal cord. Therapeutic treatment with PC1 (s.c., 1 week) alleviated established thermal hyperalgesia and allodynia, reduced the injury-induced overexpression of PROK2, significantly blunted nerve injury-induced microgliosis and astrocyte activation in the spinal cord and restored the physiological levels of proinflammatory and anti-inflammatory cytokines in periphery and in spinal cord. CONCLUSION AND IMPLICATIONSThe prokineticin system contributes to pain modulation via neuron-glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression. AbbreviationsCFA, complete Freund's adjuvant; PC1, prokineticin receptor antagonist; PKR1, prokineticin receptor 1; PKR2, prokineticin receptor 2; PROK2, prokineticin 2
The guidance of human sperm cells under confinement in quasi 2D microchambers is investigated using a purely physical method to control their distribution. Transport property measurements and simulations are performed with dilute sperm populations, for which effects of geometrical guidance and concentration are studied in detail. In particular, a trapping transition at convex angular wall features is identified and analyzed. We also show that highly efficient microratchets can be fabricated by using curved asymmetric obstacles to take advantage of the spermatozoa specific swimming strategy.PACS numbers: 87.17. Jj, 87.18.Hf, 87.17.Aa, 87.17.Rt Understanding sperm dynamics under confining microgeometries is a general problem and a major challenge both from the basic biophysics and the complex fluids points of view. It is also crucial for microfluidics and biomedical control applications. Our knowledge of the swimming cell motilities in unbounded media cannot be directly extrapolated to their behavior in complex environments such as those found in the oviduct or in the labon-a-chip microfluidic devices used to control and analyze small samples or for in-vitro reproduction procedures. In these cases, the characteristic length scales are of the same order as the cell size, i.e. a few micrometers. Under these circumstances, confined self-propelled microorganisms undergo substantial changes in their locomotion habits, adapting their dynamics to intricate porous media or to solid surfaces vicinity [1], reducing their speed close to boundaries [2] or adjusting their morphology and motility in very narrow channels [3].It has been shown that microswimmers with very different propulsion systems are similarly attracted to the walls and to swim parallel to the surface [2,[4][5][6][7][8][9][10][11]. It is believed that this attractive force has hydrodynamic origin although other possible mechanisms have been proposed [12][13][14]. Several models have been introduced to describe the swimming along surfaces (see Ref.[15] and references therein). Interestingly, the direct observation of the cell-wall attraction (see Fig. 1) have led to the design of ratchet devices that guide and sort self-propelled cells using asymmetric obstacles [16,17]. In particular, different microfluidic devices have been created to either increase sperm cell quality or enhance their concentration [18][19][20]. The creation of inhomogeneous distributions of swimmer populations via asymmetric obstacles has been shown to be particularly efficient for run-and-tumble bacteria [16,[21][22][23]. Alternative ways of achieving nonuniform distributions have also been obtained combining symmetric funnels and flux [24]. Nowadays, numerous theoretical treatments are available to account for the effects of asymmetric obstacles on active particles distributions [25][26][27][28]. Tumbles, rotational diffusion and collisions are efficient mechanisms for separating the cells from the surface, thus permitting bacteria to be reinserted into the bulk of the confining micro...
Many bacterial species use flagella for self-propulsion in aqueous media. In the soil, which is a complex and structured environment, water is found in microscopic channels where viscosity and water potential depend on the composition of the soil solution and the degree of soil water saturation. Therefore, the motility of soil bacteria might have special requirements. An important soil bacterial genus is Bradyrhizobium, with species that possess one flagellar system and others with two different flagellar systems. Among the latter is B. diazoefficiens, which may express its subpolar and lateral flagella simultaneously in liquid medium, although its swimming behaviour was not described yet. These two flagellar systems were observed here as functionally integrated in a swimming performance that emerged as an epistatic interaction between those appendages. In addition, each flagellum seemed engaged in a particular task that might be required for swimming oriented toward chemoattractants near the soil inner surfaces at viscosities that may occur after the loss of soil gravitational water. Because the possession of two flagellar systems is not general in Bradyrhizobium or in related genera that coexist in the same environment, there may be an adaptive tradeoff between energetic costs and ecological benefits among these different species.
We study both experimentally and theoretically the driven motion of domain walls in extended amorphous magnetic films patterned with a periodic array of asymmetric holes. We find two crossed-ratchet effects of opposite sign that change the preferred sense for domain wall propagation, depending on whether a flat or a kinked wall is moving. By solving numerically a simple phi(4) model we show that the essential physical ingredients for this effect are quite generic and could be realized in other experimental systems involving elastic interfaces moving in multidimensional ratchet potentials.
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