The motility of organisms is often directed in response to environmental stimuli. Rheotaxis is the directed movement resulting from fluid velocity gradients, long studied in fish, aquatic invertebrates, and spermatozoa. Using carefully controlled microfluidic flows, we show that rheotaxis also occurs in bacteria. Excellent quantitative agreement between experiments with Bacillus subtilis and a mathematical model reveals that bacterial rheotaxis is a purely physical phenomenon, in contrast to fish rheotaxis but in the same way as sperm rheotaxis. This previously unrecognized bacterial taxis results from a subtle interplay between velocity gradients and the helical shape of flagella, which together generate a torque that alters a bacterium's swimming direction. Because this torque is independent of the presence of a nearby surface, bacterial rheotaxis is not limited to the immediate neighborhood of liquid-solid interfaces, but also takes place in the bulk fluid. We predict that rheotaxis occurs in a wide range of bacterial habitats, from the natural environment to the human body, and can interfere with chemotaxis, suggesting that the fitness benefit conferred by bacterial motility may be sharply reduced in some hydrodynamic conditions. low Reynolds number | directional motion | chirality T he effectiveness and benefit of motility are largely determined by the dependence of movement behavior on environmental stimuli. For example, chemical stimuli may affect the spreading of tumor cells (1) and allow bacteria to increase uptake by swimming toward larger nutrient concentrations (2, 3), whereas hydrodynamic stimuli can stifle phytoplankton migration (4), allow protists to evade predators (5), and change sperm-egg encounter rates for external fertilizers (6). Microorganisms exhibit a broad range of directed movement responses, called "taxes". Whereas some of these responses, such as chemotaxis (7) and thermotaxis (8), are active and require the ability to sense and respond to the stimulus, others, such as magnetotaxis (9) and gyrotaxis (4), are passive and do not imply sensing, instead resulting purely from external forces.Chemotaxis is the best studied among these directional motions: Bacteria measure chemical concentrations and migrate along gradients (Fig. 1A). For instance, chemotaxis guides Escherichia coli to epithelial cells in the human gastrointestinal tract, favoring infection (10); Rhizobium bacteria to legume root hairs in soil, favoring nitrogen fixation (2); and marine bacteria to organic matter, favoring remineralization (3). Equally as pervasive as chemical gradients in microbial habitats are gradients in ambient fluid velocity or "shear" (Fig. 1B). Although nearly every fluid environment experiences velocity gradientsfrom laminar shear in bodily conduits and soil to turbulent shear in streams and oceans-the effect of velocity gradients on bacterial motility has received negligible attention compared with chemical gradients, partly due to the difficulty of studying motility under controlled flow conditi...

We show that plane parabolic flow in a microfluidic channel causes nonmotile helically-shaped bacteria to drift perpendicular to the shear plane. Net drift results from the preferential alignment of helices with streamlines, with a direction that depends on the chirality of the helix and the sign of the shear rate. The drift is in good agreement with a model based on resistive force theory, and separation is efficient (> 80%) and fast (< 2 s). We estimate the effect of Brownian rotational diffusion on chiral separation and show how this method can be extended to separate chiral molecules.Many biochemically active molecules are naturally chiral and can only bind to target chiral molecules of a specific handedness [1]. The other enantiomer (i.e. the molecule having opposite handedness) may be inactive or cause undesirable effects. Chemical synthesis of chiral molecules usually produces a racemic mixture, with equal amounts of both enantiomers, and their separation based on chirality is of importance in fields ranging from agriculture to food and pharmaceutical industries. Currently favored approaches rely on gas, liquid or capillary electromigration chromatography [2], requiring costly chiral media. Thus, simpler, alternative approaches to chiral separation are desirable.Several alternative proposals for chiral separation exploit hydrodynamic forces. Some of these, yet untested experimentally, rely on the presence of a surface [3] or array of microvortices [4], and there has been successful chiral separation of cm-sized crystals in a rotating drum [5]. Other methods [6,7] stem from the prediction that a chiral particle in a simple shear flow experiences a lateral drift [8]. However, the feasibility of this approach has remained questionable, as measurements in Couette cells reported that the drift of mm-sized chiral objects [9] and the forces on cm-sized ones [10] differ from predictions by two orders of magnitude [9] or even in sign [10].Here we report that microscale chiral objects, three orders of magnitude smaller than previous studies [9,10], experience a lateral drift in a microfluidic shear flow and the magnitude of the drift is in agreement with our theory. Previous work has demonstrated the ability of microfluidics to separate and sort colloids by size [11], spermatozoa by motility [12], and microbes by their preference for dissolved chemicals [13]. Our method uses microchannels to sort particles by chirality. We show that an enantiomer drifts with direction determined by the local shear, demonstrate the feasibility of this method for chiral separation, and indicate how the high shear rates achievable in microchannels (> 10 6 s −1 [14]) allow it to be extended to smaller scales (< 40 nm).The origin of chirality-dependent drift at low Reynolds number can be simply understood for the case of a helix. In a shear flow, objects undergo periodic rotations known as Jeffery orbits [15]: a sphere rotates with constant angular velocity, whereas for an elongated body, such as a helix, the velocity depends on orienta...

Many motile bacteria display wiggling trajectories, which correspond to helical swimming paths. Wiggling trajectories result from flagella pushing off-axis relative to the cell body and making the cell wobble. The spatial extent of wiggling trajectories is controlled by the swimming velocity and flagellar torque, which leads to rotation of the cell body. We employ the method of regularized stokeslets to investigate the wiggling trajectories produced by flagellar bundles, which can form at many locations and orientations relative to the cell body for peritrichously flagellated bacteria. Modelling the bundle as a rigid helix with fixed position and orientation relative to the cell body, we show that the wiggling trajectory depends on the position and orientation of the flagellar bundle relative to the cell body. We observe and quantify the helical wiggling trajectories of Bacillus subtilis, which show a wide range of trajectory pitches and radii, many with pitch larger than 4 µm. For this bacterium, we show that flagellar bundles with fixed orientation relative to the cell body are unlikely to produce wiggling trajectories with pitch larger than 4 µm. An estimate based on torque balance shows that this constraint on pitch is a result of the large torque exerted by the flagellar bundle. On the other hand, multiple rigid bundles with fixed orientation, similar to those recently observed experimentally, are able to produce wiggling trajectories with large pitches.

SUMMARYSeveral studies have addressed the question of starvation effects on immune function by means of changes in lymphocyte subsets, cytokine induction or lymphocyte activation. Anorexia nervosa (AN ) patients are severely malnourished and contradictory results have been obtained regarding the accompanying immunodeficiency, including its assignation as a part of the primary nervous disorder. In the present work, an extensive immunological function examination was carried out on 40 AN patients who were compared with a control group of 14 healthy girls. The AN patients were also classified according to their nutritional status (by the Body Mass Index: BMI ), this being critical for a better understanding of these secondary immunodeficiency bases. Moreover, another immune system study was performed on five patients after refeeding. Lymphocyte subsets and function, cytokine induction and peripheral blood concentrations, and innate as well as humoral immunity were evaluated. Deregulation in the cytokine network, owing to the interaction of the central nervous (CNS ) and immune systems, seems to be the initial immune alteration in AN immunodeficiency but it has not been disproved that the immunodeficiency is a direct consequence of the original psychiatric perturbation. Spontaneous high levels of circulating interleukin-1b (IL-1b) and tumour necrosis factor-a (TNF-a) have been observed; this is probably one of the causes of the anomalies found in the T-cell subpopulations (mainly the naive CD4+CD45RA+ reduction and the cytotoxic CD8+ increase) and T-cell activation status (mainly the down-regulation of the CD2 and CD69 activation pathways). This finally leads to an impairment, not only in T-cell function but also in T-cell to B-cell co-operation. The AN specificity of these results is confirmed by the fact that these immune alterations improve after refeeding and when nutritional status becomes less critical, which also suggests that AN immunodeficiency is indeed secondary to malnutrition.

PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock.