Neutrophil Chemotaxis in Multiple Chemoattractant Gradients

Chemotaxis, the phenomenon in which cells move in response to extracellular chemical gradients, plays a prominent role in the mammalian immune response. During this process, a number of chemical signals, called chemoattractants, are produced at or proximal to sites of infection and diffuse into the surrounding tissue. Immune cells sense these chemoattractants and move in the direction where their concentration is greatest, thereby locating the source of attractants and their associated targets. Leading the assault against new infections is a specialized class of leukocytes (white blood cells) known as neutrophils, which normally circulate in the bloodstream. Upon activation, these cells emigrate out of the vasculature and navigate through interstitial tissues toward target sites. There they phagocytose bacteria and release a number of proteases and reactive oxygen intermediates with antimicrobial activity. Neutrophils recruited by infected tissue in vivo are likely confronted by complex chemical environments consisting of a number of different chemoattractant species. These signals may include end target chemicals produced in the vicinity of the infectious agents, and endogenous chemicals released by local host tissues during the inflammatory response. To successfully locate their pathogenic targets within these chemically diverse and heterogeneous settings, activated neutrophils must be capable of distinguishing between the different signals and employing some sort of logic to prioritize among them. This ability to simultaneously process and interpret mulitple signals is thought to be essential for efficient navigation of the cells to target areas. In particular, aberrant cell signaling and defects in this functionality are known to contribute to medical conditions such as chronic inflammation, asthma and rheumatoid arthritis. To elucidate the biomolecular mechanisms underlying the neutrophil response to different chemoattractants, a number of efforts have been made toward understanding how cells respond to different combinations of chemicals. Most notably, recent investigations have shown that in the presence of both end target and endogenous chemoattractant variants, the cells migrate preferentially toward the former type, even in very low relative concentrations of the latter. Interestingly, however, when the cells are exposed to two different endogenous chemical species, they exhibit a combinatorial response in which distant sources are favored over proximal sources. Some additional results also suggest that cells located between two endogenous chemoattractant sources will respond to the vectorial sum of the combined gradients. In the long run, this peculiar behavior could result in oscillatory cell trajectories between the two sources. To further explore the significance of these and other observations, particularly in the context of physiological conditions, we introduce in this work a simplified phenomenological model of neutrophil chemotaxis. In particular, this model incorporates a trait commonly known as directional persistence - the tendency for migrating neutrophils to continue moving in the same direction (much like momentum) - while also accounting for the dose-response characteristics of cells to different chemical species. Simulations based on this model suggest that the efficiency of cell migration in complex chemical environments depends significantly on the degree of directional persistence. In particular, with appropriate values for this parameter, cells can improve their odds of locating end targets by drifting through a network of attractant sources in a loosely-guided fashion. This corroborates the prediction that neutrophils randomly migrate from one chemoattractant source to the next while searching for their end targets. These cells may thus use persistence as a general mechanism to avoid being trapped near sources of endogenous chemoattractants - the mathematical analogue of local maxima in a global optimization problem. Moreover, this general foraging strategy may apply to other biological processes involving multiple signals and long-range navigation.

A pilot study on the productivity and behavior of the gestating sow housed in a flex stall

Animal welfare is a controversial topic in modern animal agriculture, partly because it generates interest from both the scientific community and the general public. The housing of gestating sows, particularly individual housing, is one of the most critical concerns in farm animal welfare. We hypothesize that the physical size of the standard gestation stall may limit movement and evoke demands and challenges on the sow to affect the physiological and psychological well-being of the individually housed sow. Thus, improvements in the design of the individual gestation stall system that allow more freedom to move, such as increasing stall width or designing a stall that could accommodate the changing size of the pregnant sow, may improve sow welfare. The objective of this pilot study was to evaluate the effects of a width adjustable stall (FLEX) on productivity and behavior of dry sows. The experiment consisted of 3 replications (block 1, n=4 sows; block 2, n=4 sows; block 3, n=8 sows), and multi-parious sows were allotted to either a FLEX stall or standard gestation stall for 1 gestation period. Sow mid-girth (top of the back to bottom of the udder) was measured 5-6 times throughout gestation to determine the best time points for FLEX stall width expansions. FLEX stall width was adjusted according to mid-girth measurements, and expanded to achieve an additional 2 cm of space between the bottom of the sow’s udder and floor of the stall so that sows could lie in full lateral recumbency without touching the sides of the stall. Productivity data recorded included: sow body weight (BW) and BW gain, number of piglets born and born alive, proportions of piglets stillborn, mummified, lost between birth and weaning, and weaned, and litter and mean piglet birth BW, weaning BW, and average BW gain from birth-to-weaning. Lesions were recorded on d 21 and d 111 of gestation. Sub-pilot behavior data were observed and registered for replicate 1 sows using continuous video-records for the l2 hour lights on period (period 1, 0600-1000; period 2, 1000-1400; period 3, 1400-1800) prior FLEX stall adjustment and 12 hour lights on period post adjustment on d 21, 22, 23, 43, 44, 45, 93, 94, 95. A randomized complete block design with a 2 × 2 factorial arrangement for treatments was used to analyze sow productivity and performance traits. Data were analyzed using the Mixed Models procedure of SAS. A preliminary analysis of data means and numerical trends was used to analyze sow behavior measurements. Sows housed in a FLEX stall had more (P < 0.05) total born and a tendency for more piglets born alive (P = 0.06) than sows housed in a standard stall. Sow body weight also tended to be higher (P = 0.06) for sows housed in a FLEX stall compared to sows housed in a standard stall. There were numerical trends for mean durations of sit, lay, lay (OUT), and eat behaviors to be greater for sows housed in a FLEX stall compared with sows housed in a standard stall. The mean duration of lay (IN) behavior tended to be numerically less for sows housed in a FLEX stall compared with sows housed in a standard stall. There were numerical trends for the mean durations of stand and drink behaviors to be greater for sows housed in a standard stall compared with sows housed in a FLEX stall. The mean frequencies of postural changes and mean durations of oral-nasal-facial and sham-chew behaviors were numerically similar between types of gestation stall. Mean durations and numerical trends indicate that time of day influenced all of the behaviors assessed in this study. The results of this pilot study indicate that the adjustable FLEX stall may affect sow productivity and behavior differently than the standard gestation stall, and thus potentially improve sow well-being. Future research should continue to compare the new FLEX stall design to current housing systems in use and examine physiological traits and immune status in addition to behavioral and productivity traits to assess the effects that this housing system has on the overall welfare of the gestating sow.