Quantum Wave-Particle Duality in Free-Electron-Bound-Electron Interaction.

We present a comprehensive relativistic quantum-mechanical theory for interaction of a free electron with a bound electron in a model, where the free electron is represented as a finite-size quantum electron wave packet (QEW) and the bound electron is modeled by a quantum two-level system (TLS). The analysis reveals the wave-particle duality nature of the QEW, delineating the point-particle-like and wavelike interaction regimes and manifesting the physical reality of the wave function dimensions when interacting with matter. This QEW size dependence may be used for interrogation and coherent control of superposition states in a TLS and for enhancement of cathodoluminescence and electron energy-loss spectroscopy in electron microscopy.

Application of Wigner Distribution Function for THz Propagation Analysis.

The construction of a transmission line (TL) for a wide tunable broad-spectrum THz radiation source is not a simple task. We present here a platform for the future use of designs of the TL through our homemade simulations. The TL is designed to be a component of the construction of an innovative accelerator at the Schlesinger Family Center for Compact Accelerators, Radiation Sources and Applications (FEL). We developed a three-dimensional space-frequency tool for the analysis of a radiation pulse. The total electromagnetic (EM) field on the edge of the source is represented in the frequency domain in terms of cavity eigenmodes. However, any pulse can be used regardless of its mathematical function, which is the key point of this work. The only requirement is the existence of the original pulse. This EM field is converted to geometric-optical ray representation through the Wigner transform at any desired resolution. Wigner's representation allows us to describe the dynamics of field evolution in future propagation, which allows us to determine an initial design of the TL. Representation of the EM field by rays gives access to the ray tracing method and future processing, operating in the linear and non-linear regimes. This allows for fast work with graphics cards and parallel processing, providing great flexibility and serving as future preparation that enables us to apply advanced libraries such as machine learning. The platform is used to study the phase-amplitude and spectral characteristics of multimode radiation generation in a free-electron laser (FEL) operating in various operational parameters.

The dynamics between limited-term and lifelong coinfecting bacterial parasites in wild rodent hosts.

Interactions between coinfecting parasites may take various forms, either direct or indirect, facilitative or competitive, and may be mediated by either bottom-up or top-down mechanisms. Although each form of interaction leads to different evolutionary and ecological outcomes, it is challenging to tease them apart throughout the infection period. To establish the first step towards a mechanistic understanding of the interactions between coinfecting limited-term bacterial parasites and lifelong bacterial parasites, we studied the coinfection of Bartonella sp. (limited-term) and Mycoplasma sp. (lifelong), which commonly co-occur in wild rodents. We infected Bartonella- and Mycoplasma-free rodents with each species, and simultaneously with both, and quantified the infection dynamics and host responses. Bartonella benefited from the interaction; its infection load decreased more slowly in coinfected rodents than in rodents infected with Bartonella alone. There were no indications for bottom-up effects, but coinfected rodents experienced various changes, depending on the infection stage, in their body mass, stress levels and activity pattern, which may further affect bacterial replication and transmission. Interestingly, the infection dynamics and changes in the average coinfected rodent traits were more similar to the chronic effects of Mycoplasma infection, whereas coinfection uniquely impaired the host's physiological and behavioral stability. These results suggest that parasites with distinct life history strategies may interact, and their interaction may be asymmetric, non-additive, multifaceted and dynamic through time. Because multiple, sometimes contrasting, forms of interactions are simultaneously at play and their relative importance alternates throughout the course of infection, the overall outcome may change under different ecological conditions.

Effects of parasite pressure on parasite mortality and reproductive output in a rodent-flea system: inferring host defense trade-offs.

Evaluating host resistance via parasite fitness helps place host-parasite relationships within evolutionary and ecological contexts; however, few studies consider both these processes simultaneously. We investigated how different levels of parasite pressure affect parasite mortality and reproductive success in relationship to host defense efforts, using the rodent Gerbillus nanus and the flea Xenopsylla conformis as a host-parasite system. Fifteen immune-naïve male rodents were infested with 20, 50, or 100 fleas for four weeks. During this time number of new imagoes produced per adult flea (our flea reproductive output metric), flea mortality, and change in circulating anti-flea immunoglobulin G (our measure of adaptive immune defense) were monitored. Three hypotheses guided this work: (1) increasing parasite pressure would heighten host defenses; (2) parasite mortality would increase and parasite reproductive output would decrease with increasing investment in host defense; and (3) hosts under high parasite pressure could invest in behavioral and/or immune responses. We predicted that at high infestation levels (a) parasite mortality would increase; (b) flea reproductive output per individual would decrease; and (c) host circulating anti-flea antibody levels would increase. The hypotheses were partially supported. Flea mortality significantly increased and flea reproductive output significantly decreased as flea pressure increased. Host adaptive immune defense did not significantly change with increasing flea pressure. Therefore, we inferred that investment in host behavioral defense, either alone or in combination with density-dependent effects, may be more efficient at increasing flea mortality and decreasing flea reproductive output than antibody production during initial infestation in this system.

Immunization and Host Responses to MB-1, a Live Hatchery Vaccine against Infectious Bursal Disease.

MB-1 is an attenuated infectious bursal disease virus vaccine. Previously, we observed a temporal delay of vaccine virus replication in the bursae of chicks due to maternally derived antibodies (MDAs). The mechanism that allowed its survival despite MDA neutralization remained unclear. We hypothesized that after vaccination at 1 day of age (DOA), the MB-1 virus penetrates and resides in local macrophages that are then distributed to lymphoid organs. Furthermore, MB-1's ability to survive within macrophages ensures its survival during effective MDA protection. PCR analysis of lymphoid organs from chicks with MDA, vaccinated on 1 DOA, demonstrated that the MB-1 virus was identified at low levels solely in the spleen pre-14 days of age. Fourteen days after vaccination, the virus was identified using PCR in the bursa, with viral levels increasing with time. The possible delay in viral colonization of the bursa was attributed to the presence of anti-IBDV capsid VP2 maternal IgA and IgY in the bursa interstitium. These indicate that during the period of high MDA levels, a small but viable MB-1 viral reservoir was maintained in the spleen, which might have served to colonize the bursa after MDA levels declined. Thereafter, individual immunization of chicks against Gumboro disease was achieved.

Increased serum levels of advanced glycation end products due to induced molting in hen layers trigger a proinflammatory response by peripheral blood leukocytes.

Induced molting (IM), a severe detriment to animal welfare, is still used in the poultry industry in some countries to increase or rejuvenate egg production and is responsible for several physiological perturbations, possibly including reactive oxidative stress, a form of metabolic stress. Because metabolic stress has been shown to induce a proinflammatory response involved in attempts to restore homeostasis, we hypothesized that similar responses followed IM. To confirm this hypothesis, we initially confirmed the establishment of oxidative stress during IM in 75-wk-old layers by demonstrating increased production of advanced glycation end products (AGE). Concomitant with increased oxidative metabolites, cellular stress was demonstrated in peripheral blood leukocytes (PBL) by increased levels of stress gene products (the glucocorticoid receptor, sirtuin-1, and heat shock protein 70 mRNA). Increased expression of stress proteins in PBL was followed by a proinflammatory response as demonstrated by increased levels of proinflammatory gene products (IL-6 and IL-1ß mRNA); increased expression of these gene products was also demonstrated in direct response to AGE in vitro, thus establishing a direct link between oxidative and cellular stress. To establish a possible pathway for inducing a proinflammatory response by PBL, we showed that AGE increased a time dependent expression of galactin-3, Toll-like receptor-4, and nuclear factor - κB, all involved in the proinflammatory activation pathway. In vivo, AGE formed complexes with increased levels of circulating acute phase proteins (lysozyme and transferrin), products of a proinflammatory immune response, thereby demonstrating an effector response to cope with the consequences of oxidative stress. Thus, the harmful consequences of IM for animal welfare are extended here by demonstrating the activation of a resource-demanding proinflammatory response.

Obsessive-compulsive symptoms are related to reduced awareness of emotional valence.

BACKGROUND: The Seeking Proxies for Internal States (SPIS) model of OCD asserts that obsessive-compulsive (OC) tendencies are associated with attenuated access to internal states. Here we explore the implications of this model for awareness of emotional valence. METHODS: In Study 1, participants with high and low OC tendencies (n = 30 in each group) rated how they felt while viewing different pictures with positive, neutral, or negative valence taken from the International Affective Picture System. Study 2 replicated Study 1 among non-selected participants (n = 99) that rated positive and negative pictures chosen from the recently developed Basic-Emotions Nencki Affective Picture System. In both studies, mean deviation from norm ratings (of each picture system) served as the primary outcome measure. RESULTS: Study 1 showed that high OC participants' mean deviation score was significantly higher, compared with low OC participants, across positive, neutral, and negative pictures (p=.01). Follow-up analyses revealed that while no group difference emerged for mean valence rating (p=.16), groups differed on the mean standard deviation of ratings within each valence category (p=.002). In Study 2, only OC tendencies, not depressive or anxiety symptoms, were positively correlated with mean deviation from norm ratings (p=.026). Dividing the sample to high and low OC groups based on an OC cutoff score yielded similar group differences to those observed in Study 1 (p<.001). LIMITATIONS: Analog samples and a relative small sample size (Study 1). CONCLUSIONS: This study suggests that OC symptoms are associated with reduced awareness of emotional valence, possibly emanating from a noisier emotional perception.

Innate immune functions of avian intestinal epithelial cells: Response to bacterial stimuli and localization of responding cells in the developing avian digestive tract.

Intestinal epithelial cells are multi-tasked cells that participate in digestion and absorption as well as in protection of the digestive tract. While information on the physiology and immune functions of intestinal epithelial cells in mammals is abundant, little is known of their immune function in birds and other species. Our main objectives were to study the development of anti-bacterial innate immune functions in the rapidly developing gut of the pre- and post-hatch chick and to determine the functional diversity of epithelial cells. After establishing primary intestinal epithelial cell cultures, we demonstrated their capacity to uptake and process bacteria. The response to bacterial products, LPS and LTA, induced expression of pro-inflammatory cytokine genes (IL-6, IL-18) as well as the expression of the acute phase proteins avidin, lysozyme and the secretory component derived from the polymeric immunoglobulin receptor. These proteins were then localized in gut sections, and the goblet cell was shown to store avidin, lysozyme as well as secretory component. Lysozyme staining was also located in a novel rod-shaped intestinal cell, situated at different loci along the villus, thus deviating from the classical Paneth cell in the mammal, that is restricted to crypts. Thus, in the chicken, the intestinal epithelium, and particularly goblet cells, are committed to innate immune protection. The unique role of the goblet cell in chicken intestinal immunity, as well as the unique distribution of lysozyme-positive cells highlight alternative solutions of gut protection in the bird.

Avoiding handling-induced stress in poultry: use of uniform parameters to accurately determine physiological stress.

Due to increase in awareness of poultry welfare and concomitant legislation, it has become necessary to determine poultry's response to stress, with minimal harm and maximum reliability. Several methods to determine the response to physiological stress were developed throughout the years to identify stressors and to measure stress in poultry. The most commonly used are plasma corticosterone levels and peripheral blood heterophil/lymphocyte ratio (H/L ratio). However, the value of these responses to determine a state of stress has been questioned in several instances, as these parameters are increased during the process of bird handling and blood sampling irrespective of the general state of stress. Due to these limitations, it appears that the classic stress markers might be sub-optimal in evaluating stress in poultry, particularly those encountered in high-stress environments. Thus, there is a continuing need for stress indicators, preferably indicators that are quantitative, highly repeatable, not influenced by handling and sampling, determined in peripheral blood, represent an initial response to the stressor, and do not daily fluctuate. As the immune system has been shown to rapidly respond to stress, we assessed pro-inflammatory gene expression in peripheral blood cells as an indicator for stress. We initially show that while corticosterone plasma levels and the H/L ratio were responsive to handling and blood sampling, pro-inflammatory gene expression (lysozyme, IL-1ß, IL-6, and HSP-70) was not. We then determined the expression of the same pro-inflammatory genes during acute stress (transit) in layer pullets (hen and turkey) and during chronic stress (different caging densities of layers utilizing 2, 3, and 4 hens/cage). While gene expression was significantly and highly elevated during transit, the effect of differing caging densities on gene expression was minimal; collectively, this might indicate that expression of pro-inflammatory genes is more responsive to acute stress than to chronic stressors. We propose to use pro-inflammatory gene expression in peripheral blood cells to measure responses to stress in poultry.

Transport-related stress and its resolution in turkey pullets: activation of a pro-inflammatory response in peripheral blood leukocytes.

The transportation process is one of the most stressful practices in poultry and livestock management. Extensive knowledge is available on the impact of transport on stress and animal welfare; however, little is known on the impact of transport on the physiology of turkey pullets, their welfare and health, and even less on the process of homeostatic recovery in the post-transport new environment. The main focus of this manuscript was to focus on trauma, stress, and recovery following transport of turkey pullets from nurseries to pullet farms. Specifically, we determined the physiological consequences of transport, the temporal restoration of homeostasis and its effects on immune system function. We hypothesized that stress signaling by stress hormones would directly activate circulating turkey blood leukocytes (TBL), thus inducing a pro-inflammatory response directed towards tissue repair and recovery. Extensive blood analyses prior to transit and during the collecting, transit, and post-transit stages revealed extensive stress (elevated heat shock protein 70) and blunt-force trauma (internal bleeding and muscle damage as well as limb fractures). TBL were shown to increase mRNA expression of cortisol and adrenergic receptors during transit, thus indicating a possible direct response to circulating stress hormones. Consequently, TBL were shown to increase mRNA expression of pro-inflammatory cytokines, as well as that of serum inflammatory proteins (lysozyme and transferrin) partaking in reducing oxygen radicals as demonstrated by consumption of these proteins. The flare-up due to transit related stress diminished with time until 10 d post-transit, a time at which most parameters returned to resting levels. Though general and vaccine-specific antibody levels were not altered by transport-related stress, the physical and physiological injury caused during transport may explain the susceptibility of turkey pullets to opportunist pathogens in the immediate post-transit period.

Development and adaptations of innate immunity in the gastrointestinal tract of the newly hatched chick.

The intestinal immune system in Gallus species must rapidly adapt to the omnivorous onset of an adult diet and to colonization by commensal bacteria. Yet, acquired immune functions in Gallus digestive tract fully develop only towards the end of the first week post-hatch. This raises the question of immune protection in the digestive tract during the first week of life. We postulated that in addition to protection conferred by maternal antibodies, the gut is protected by a functionally sufficient innate immune system at hatch. We studied granulocyte distribution in the gut as well as expression of functional genes representing different cells and activities of the innate immune system in chicken hatchlings. These included pro-inflammatory cytokines and chemokines (IL-1beta, IL-8, K203), antibacterial beta-defensins, Gallinacin 1 and 2, and presenilin 1. We demonstrate innate preparedness in the developing chick gut in two circumstances: The first is independent of intestinal exposure to feed and bacteria and is manifested by heterophil maturation in situ. This gut-specific extramedullary granulopoietic process is reported for the first time in the chick, and is supported by beta-defensin and presenilin 1 gene expression. The second is responsive to environmental stimuli, and is demonstrated by gradual development of pro-inflammatory functions: Exposure of the gut to feed and bacteria triggered a low but significant increase in IL-1beta, IL-8 and K203. This resulted in the possible recruitment of bone marrow-derived heterophils as demonstrated by elevation of beta-defensin gene expression. The pro-inflammatory activity in the developing gut also explains the later recruitment of lymphocytes.

Impaired immune responses in broiler hatchling hindgut following delayed access to feed.

One of the key stimulators of intestinal development in the chick is physical exposure to feed, while feed withholding delays the onset of gut development. A delay of 24-72 h in onset of feeding is quite common in the poultry industry due to variation in hatching time and hatchery treatments. As intestinal development occurs in concert with the development of the gut associated lymphoid tissue (GALT), we investigated the effects of short term feed withholding on development of GALT in broiler hatchlings. GALT activity was determined by antibody production (systemic and locally in the gut), distribution of B and T lymphocytes in the gut, expression of lymphocyte specific genes, and distribution of B and T lymphocytes in the cloacal bursa. Our findings show that while development of GALT in the foregut (duodenum, jejunum, ileum) was only slightly and temporarily impeded by feed withholding, GALT activity in the hindgut and the gut-related cloacal bursa was significantly delayed during the first 2 weeks of life: Systemic and intestinal antibody responses following rectal immunization to antigen were lower, colonization of the hindgut (cecum and colon) by T and B lymphocytes was delayed, as well as the expression of chIL-2 mRNA in hindgut T lymphocytes. We also found that the increase of B and T population size in the cloacal bursa was delayed with time. Full recovery occurred from 2 weeks of age. The 2-week vulnerable period should be seriously considered in circumstances where hatchlings are in transit for extended periods from hatcheries to farms.

Establishment of immune competence in the avian GALT during the immediate post-hatch period.

Population dynamics of intestinal lymphocytes and the temporal development of lymphocyte functions were studied in broiler chicks during the first 2 weeks post-hatch. This period is of major immunological importance as the chick is immediately exposed to environmental antigens and pathogens. We show that the gut-associated lymphoid tissue contains functionally immature T and B lymphocytes at hatch, and that function is attained during the first 2 weeks of life as demonstrated by mRNA expression of both ChIL-2 and ChIFNgamma. Functional maturation occurred in two stages: the first-during the first week post-hatch, and the second during the second week, which was also accompanied by an increase in lymphocyte population, as determined by expression of antigen receptor genes. Evidence is presented to show that in the intestinal milieu cellular immune responses mature earlier, and are a prerequisite for humoral responses. Hence, the lack of antibody response in young chicks is primarily due to immaturity of T lymphocytes.

Role of goblet cells and mucin layer in protecting maternal IgA in precocious birds.

Immune protection of the gut in early life depends on provision of maternal antibodies, particularly that of IgA. In precocial birds (in this study Gallus gallus domesticus) the egg provides the only source of maternal antibodies, IgA inclusive. The gut-life of IgA in hatchlings is expected to be brief due to antigen binding and intestinal washout, and maternal IgA is likely to be depleted prior to immune independence at 7-10 days of age in the domestic fowl. We followed the track of maternal IgA in mucosal surfaces of the fowl and describe for the first time a mechanism that might provide the means to extend the active period of maternal IgA in the gut. Maternal IgA was located in the gut, lung, and cloacal bursa in embryos and hatchlings prior to the appearance of endogenic IgA positive plasma cells (D3 in the bursa or D7 in the gut and lung); the source of IgA was most probably the yolk, as the plasma was devoid of IgA till D7 post-hatch. The levels of maternal IgA decreased with time, but were still easily determined at the onset of endogenous IgA production following maturation of the adaptive immune system. Persistence of maternal IgA in the gut was enabled by goblet cell up-take by a yet un-described mechanism, and its consequent release in a mucin-like layer on enterocyte apical surfaces.

Regional and global changes in TCRalphabeta T cell repertoires in the gut are dependent upon the complexity of the enteric microflora.

The repertoire of gut associated T cells is shaped by exposure to microbes, including the natural enteric microflora. Previous studies compared the repertoire of gut associated T cell populations in germ free (GF) and conventional mammals often focussing on intra-epithelial lymphocyte compartments. Using GF, conventional and monocolonised (gnotobiotic) chickens and chicken TCRbeta-repertoire analysis techniques, we determined the influence of microbial status on global and regional enteric TCRbeta repertoires. The gut of conventionally reared chickens exhibited non-Gaussian distributions of CDR3-lengths with some shared over-represented peaks in neighbouring gut segments. Sequence analysis revealed local clonal over-representation. Germ-free chickens exhibited a polyclonal, non-selected population of T cells in the spleen and in the gut. In contrast, gnotobiotic chickens exhibited a biased repertoire with shared clones evident throughout the gut. These data indicate the dramatic influence of enteric microflora complexity on the profile of TCRbeta repertoire in the gut at local and global levels.

Expression pattern of prokineticin 1 and its receptors in bovine ovaries during the estrous cycle: involvement in corpus luteum regression and follicular atresia.

Prokineticin 1 (PROK1), also termed endocrine gland-derived vascular endothelial growth factor (endocrine gland-derived VEGF), is a newly identified protein assigned with diverse biologic functions. It binds two homologous G protein-coupled receptors, PROKR1 and PROKR2. To better understand the roles of PROK1 and its receptors in ovarian function, their expression was determined in follicles and corpora lutea (CLs) at different developmental stages. PROK1 mRNA levels were low at early luteal stage and midluteal stage, but increased sharply during natural or induced luteolysis. High PROK1 mRNA levels also were found in atretic follicles. This profile of PROK1 expression was opposite to that of the well-established angiogenic factor VEGF. Of the two receptor-type expressions, PROKR1 but not PROKR2 was correlated positively with its ligand. Immunohistochemical staining revealed that PROK1 was located mainly within the muscular layer of arterioles, and during regression it also was localized to macrophages and steroidogenic cells. The expression pattern of ITGB2 mRNA, a leukocyte cell marker, overlapped that of PROK1, thus suggesting that leukocyte infiltration may explain the elevated expression of PROK1 in atretic follicles and regressing CL. Indeed, flow cytometry analyses showed that nearly all beta-2 integrin chain (ITGB2)-positive cells also were stained with anti-PROK1 and that significantly more ITGB2/PROK1 double-stained cells were present in degenerating follicles and CL. Furthermore, when challenged in vitro with PROK1, adherent, mononuclear cell numbers and TNF levels were elevated, indicating that PROK1 triggers monocyte activation. Together, these data suggest that PROK1, acting via PROKR1, may be involved in the recruitment of monocytes to regressing CL and atretic follicles and their consequent activation therein.

Differential expression of prokineticin receptors by endothelial cells derived from different vascular beds: a physiological basis for distinct endothelial function.

Prokineticins (PKs), multifunctional secreted proteins, activate two endogenous G protein-coupled receptors (R) termed PK-R1 and PK-R2. It was suggested that PK1 acts selectively on the endothelium of endocrine glands, yet PK-Rs were also found in endothelial cells (EC) derived from other tissues. Therefore we examined here the characteristics of PK - system in EC derived from different vascular beds. Corpus luteum (CL)-derived EC (LEC) expressed both PK-R1 and PK-R2. In contrast, EC from the aorta (BAEC) only expressed PK-R1. Interestingly, also EC from brain capillaries (BCEC) expressed only PK-R1. The distinct pattern of PK-R expression may define EC phenotypic heterogeneity. Regulation of receptor expression also differed in BAEC and LEC: TNFalpha markedly reduced PK-R1 only in BAEC, but serum removal decreased PK-R1 in both cell types. Therefore, if cells were initially serum-starved, the anti-apoptotic effect of PKs was retained only in LEC. Yet, addition of PKs concomitant with serum removal enhanced the proliferation and survival of both BAEC and LEC. Immunohistochemical staining showed that in CL and aorta PK1 was expressed in smooth muscle cells in vessel walls, suggesting a paracrine mode of action. PK1 enhanced the net paracellular transport (measured by electrical resistance and Mannitol transport) in LEC but not in BAEC or BCEC. Collectively, these findings indicate that PKs serve as mitogens and survival factors for microvascular (LEC) and macrovascular (BAEC) EC. However, the distinct expression and function of PK receptors suggest different physiological roles for these receptors in various EC types.

Maternal antibodies block induction of oral tolerance in newly hatched chicks.

Oral antigens administered to newly hatched chicks induce oral tolerance. Some of the antigens encountered via the gut during this period are pathogen-derived, and should not be tolerogenic. As chicks are protected in early life by maternal antibodies, we assumed that the same antibodies also served to prevent tolerance by blocking the relevant antigen. We used bovine serum albumin (BSA) as a model antigen, and initially showed that tolerance was invariably generated in chicks younger than 3 days of age. We then showed that tolerance and its prevention were due to circulatory BSA: intravenous BSA induced tolerance, BSA was present in serum of previously fed chicks, and tolerance was completely blocked in chicks containing high levels of maternal anti-BSA. These findings indicate that tolerance in the young chick is probably generated in central lymphoid organs, and that maternal antibodies block access of antigen to these organs, thereby preserving immune competence.