Observation of edge states derived from topological helix chains.

Introducing the concept of topology has revolutionized materials classification, leading to the discovery of topological insulators and Dirac-Weyl semimetals1-3. One of the most fundamental theories underpinning topological materials is the Su-Schrieffer-Heeger (SSH) model4,5, which was developed in 1979-decades before the recognition of topological insulators-to describe conducting polymers. Distinct from the vast majority of known topological insulators with two and three dimensions1-3, the SSH model predicts a one-dimensional analogue of topological insulators, which hosts topological bound states at the endpoints of a chain4-8. To establish this unique and pivotal state, it is crucial to identify the low-energy excitations stemming from bound states, but this has remained unknown in solids because of the absence of suitable platforms. Here we report unusual electronic states that support the emergent bound states in elemental tellurium, the single helix of which was recently proposed to realize an extended version of the SSH chain9,10. Using spin- and angle-resolved photoemission spectroscopy with a micro-focused beam, we have shown spin-polarized in-gap states confined to the edges of the (0001) surface. Our density functional theory calculations indicate that these states are attributed to the interacting bound states originating from the one-dimensional array of SSH tellurium chains. Helices in solids offer a promising experimental platform for investigating exotic properties associated with the SSH chain and exploring topological phases through dimensionality control.

Enhancement of paraben-fungicidal activity by sulforaphane, a cruciferous vegetable-derived isothiocyanate, via membrane structural damage in Saccharomyces cerevisiae.

Parabens have been widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, foods and beverages. Commonly, methyl-, ethyl-, propyl- and butylparaben are used independently or in combination to maintain the quality of industrial products, and they are considered to have low toxicity. However, recent evidence has suggested that parabens are toxic in mammalian cells, and parabens have been associated with allergic-contact dermatitis, breast cancer and changes in testosterone levels. Sulforaphane, a cruciferous vegetable-derived isothiocyanate, was effective in decreasing the growth inhibitory concentrations of ethyl-, propyl-, butyl- and methylparaben in the yeast Saccharomyces cerevisiae. The sulforaphane-enhanced fungicidal effects of methylparaben were deemed to be caused by drastic cell membrane damage and the leakage of internal substances, such as nucleotides, from S. cerevisiae cells. Moreover sulforaphane markedly decreased the minimum concentration of methyl- and ethylparaben required to inhibit the growth of various microbes, such as the pathogenic yeast that causes severe mycosis, Candida albicans; the filamentous fungi Aspergillus niger; and the Gram-negative bacterium Escherichia coli. Enhanced antimicrobial activity from the beneficial components of edible plants may increase paraben efficacy at low concentrations and minimize preservative-induced side effects in consumers. SIGNIFICANCE AND IMPACT OF THE STUDY: Sulforaphane, a natural and beneficial cruciferous vegetable-derived isothiocyanate, increased the ability of parabens to disrupt fungal cell membranes. Paraben-containing products have been reported to cause allergic contact dermatitis and drug hypersensitivity; therefore, methods to preserve organic products that may reduce the concentrations of parabens are both timely and necessary. In this study, we found that the combined antimicrobial effects of sulforaphane and parabens had the potential to reduce the paraben concentration needed to preserve organic products, thereby indicating that paraben toxicity may be reduced without affecting its activity as a preservative.

Relationship between arthroscopic findings of synovitis and levels of tumour necrosis factor-alpha and matrix metalloproteinases in synovial lavage fluid from patients with unilateral high mandibular condyle fractures.

Arthrocentesis has an effect of washing out inflammatory products that accumulate in the joint compartment of a dysfunctional temporomandibular joint (TMJ). The procedure removes inflammatory cytokines, which are pain-causing substances, for early reduction of TMJ pain and quick recovery of jaw function, thus increasing the possibility of a successful rehabilitation. The aim of this study was to investigate the relationship between arthroscopy synovitis grade in patients with unilateral high condylar fractures and concentrations of the pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha as well as of matrix metalloproteinases (MMPs) in washed-out synovial fluid (SF) samples obtained from those patients. A total of 26 patients with unilateral high condylar fractures who underwent arthrocentesis for a therapeutic purpose were examined. SF samples were collected before performing arthroscopy to determine synovitis grade. The detection rates and concentrations of TNF-alpha and MMPs were determined, and their association with synovitis grade was analysed. TNF-alpha was detected in 23 and MMP-3 in 22 of the TMJs. There was a correlation between synovitis grade and concentration of TNF-alpha in the fracture group. Furthermore, the concentrations of TNF-alpha and MMP-3 were significantly higher as compared to the control group, comprised of TMJs on the non-fracture side of the same patients, while a correlation was also noted between TNF-alpha concentration and synovitis grade in the fracture group. The present findings may provide a biological/biochemical rationale for arthrocentesis as a reasonable treatment modality for high condylar fractures.

Experimental comparison between tractional and compressive stress on temporomandibular joint.

OBJECTIVE: We experimentally compared the effects of compressive and tractional mechanical stress on the temporomandibular joint (TMJ) of rabbits to assess the etiology of progressive condylar resorption. MATERIALS AND METHODS: We performed a cortical osteotomy using custom-made devices that were lengthened by 0.25 mm every 12 h for 1 week after surgery. During this time, the rabbit TMJ was under compressive or tractional mechanical stress. The samples in each group were examined using micro-computed tomography and histological staining. RESULTS: Scores for the area of bone resorption were higher in the compressive group than in the tractional group. Moreover, scores for the depth of bone resorption were higher in the compressive group than those in the tractional group. We observed a significantly higher prevalence of resorption in the subcondylar bone in the compressive group than in the tractional group. There were substantially more cells that were positive for tartrate-resistant acid phosphatase in the compressive group than in the control and tractional groups. CONCLUSIONS: The outcomes here suggest that excessive mechanical stress, particularly compressive mechanical stress, may significantly affect morphological bone change findings in the TMJ.

Therapeutic implication of genetic variants of IL13 and STAT4 in airway remodelling with bronchial asthma.

BACKGROUND: Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched. OBJECTIVE: We determined the effects of high-dose inhaled corticosteroids (ICSs) on decreased pulmonary function in asthmatic Japanese patients with variants of IL13 and STAT4 during long-term treatments with low to mild doses of ICS. METHODS: In this study, 411 patients with bronchial asthma who were receiving ICSs and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations. The effects of 2 years of high-dose ICSs administered to asthmatic patients who were homozygous for IL13 AA of rs20541 or STAT4 TT of rs925847 and who progressed to airway remodelling were investigated. RESULTS: High-dose ICS treatment increased the pulmonary function of patients homozygous for IL13 AA of rs20541 but not of patients homozygous for STAT4 TT of rs925847. The increased concentrations of the mediators IL23, IL11, GMCSF, hyaluronic acid, IL24, and CCL8 in bronchial lavage fluid (BLF) were diminished after high-dose ICS treatment in patients homozygous for IL13 AA of rs20541. CONCLUSION AND CLINICAL RELEVANCE: IL13 AA of rs20541 and STAT4 TT of rs925847 are potential genomic biomarkers for predicting lower pulmonary function. The administration of high-dose ICSs to asthmatic patients with genetic variants of IL13 AA may inhibit the advancement of airway remodelling. The genetic variants of STAT4 TT did not respond to high-dose ICSs. Therefore, using medications other than ICSs must be considered even during the initial treatment of bronchial asthma. These genetic variants may aid in the realization of personalized and phenotype-specific therapies for bronchial asthma.

Egg collagen content is increased by a diet supplemented with wood charcoal powder containing wood vinegar liquid.

The aims of the present study were to examine whether collagen exists in egg, particularly in egg yolk; to establish a Fourier transform-near infrared (FT-NIR) measurement method for collagen in egg and to assess the possibility of increasing the collagen content by feeding hens a diet containing wood charcoal powder containing wood vinegar liquid (WCV). The collagen in eggs from 67-week-old hens fed on the dietary 0 and 9.9 g/kg WCV diets was investigated using a combination of histochemical, matrix-assisted laser desorption ionisation with time-of-flight mass spectrometry (MALDI-TOF MS), Fourier transform infrared (FT-IR) and FT-NIR approaches. All approaches used to identify collagen in egg yolk yielded positive results. The collagen in egg yolk measured using colorimetry, collagen in egg yolk, egg white and eggshell membrane using FT-NIR and collagen in egg yolk determined by treating the egg yolk with collagenase were abundant after feeding a dietary WCV (p<0.05). These results suggest that egg yolk contains collagen, that the collagen in egg can be measured using FT-NIR, and that the collagen content of egg yolk can be increased by feeding dietary WCV diets.

Effect of replacing corn with whole-grain paddy rice and brown rice in broiler diets on growth performance and intestinal morphology.

The present study was conducted to investigate replacing corn with whole-grain paddy rice (WPR) and whole-grain brown rice (BR) in broiler chicken diets and its effect on growth performance and histological structures of the intestinal villi. Marshall Chunky male chicks (14 days old) were divided into five groups with four replicates of four chicks each. In the dietary treatments, corn in the basal diet was replaced with WPR and BR. The chickens received five experimental diets consisting of corn, WPR and BR in ratios of 100:0:0 (Control), 50:0:50 (50Corn + 50BR), 50:25:25 (50Corn + 25WPR + 25BR), 25:50:25 (25Corn + 50WPR + 25BR) and 0:50:50 (50WPR + 50BR) respectively. Feed and water were provided ad libitum for 35 day. No significant differences were found in feed intake, body weight gain and feed efficiency among the treatment groups. The relative weights of the gizzard in the 50Corn + 25WPR + 25BR, 25Corn + 50WPR + 25BR and 50WPR + 50BR groups were significantly higher than that of the Control and 50Corn + 50BR groups (p < 0.05). The gizzard pH of the experimental groups was lower than those of Control (p < 0.05). The ileal crypt of birds on the Control diets was deeper (p < 0.05) than those observed in the experimental birds. Moreover, the ileal villus height: crypt depth ratio increased (p < 0.05) in the 50WPR + 50BR group (p < 0.05) compared with the Control group. No specific changes were observed in the epithelial cells on the duodenal apical surface among the groups except that the villus of the 25Corn + 50WPR + 25BR group had cell clusters. The jejunal and ileal villus apical surface of the experimental groups showed similar morphology to the Control group. These findings suggest that WPR and BR can totally replace corn in broiler diets without negatively affecting growth performance.

Marked improvement of insulin sensitivity without enhancement of GLP-1 and insulin secretion after Roux-en-Y gastric bypass surgery in a mildly obese patient with diabetes.

Roux-en-Y gastric bypass is an option of treatment for morbidly obese patients with diabetes. However, the value of the operation in mildly obese patients is not established. We report the first prospective systematic endocrine and metabolic analysis in a mildly obese patient who underwent a Roux-en-Y gastric bypass. In a 49-year-old man with BMI 32.6 kg/m(2) having type 2 diabetes, intramucosal gastric cancer was treated by partial gastrectomy with Roux-en-Y gastric bypass. Pre-operatively, he received 53 U/day insulin and the HbA1c value was 63 mmol/mol: meal tolerance test showed diabetic hyperglycemia and low insulin sensitivity with attenuated insulin secretion and normal glucagon-like peptide 1(7-36) secretion. After the operation, hypoglycemic agent was stopped. Body weight reduced from 84.0 to 77.0 kg within 2 weeks and increased thereafter to 79.4 kg at 4 months later, when the degree of hyperglycemia was unchanged as indexed by a HbA1c value of 62 mmol/mol. Upon repeated meal tolerance test, no increase of glucagon-like peptide 1 and insulin secretion, but significantly improved hepatic and peripheral insulin sensitivity were found, compared to the preoperative meal tolerance test. Marked dissociation of endocrine and metabolic effects of Roux-en-Y gastric bypass, that is, absence of increased glucagon-like peptide 1/insulin secretion with improvement of insulin sensitivity, was found in a mildly obese patient with type 2 diabetes.

Oral administration of bovine lactoferrin attenuates ultraviolet B-induced skin photodamage in hairless mice.

Lactoferrin (LF) is recognized as a host defensive glycoprotein, especially for newborn infants. The aim of this study was to investigate whether orally administered LF had protective activity against UV-induced skin damage in hairless mice. Transepidermal water loss and skin hydration were evaluated in nonirradiated mice, UVB-irradiated mice, and UVB-irradiated and LF-administered mice. Supplementation with LF (1,600 mg/kg per day) effectively suppressed the increase in transepidermal water loss, reduction in skin hydration, aberrant epidermal hyperplasia, and cell apoptosis induced by UV irradiation. Although no significant changes in superoxide dismutase-like activity or malondialdehyde levels were observed in the skin with both UV irradiation and LF administration, UV-stimulated IL-1ß levels in the skin were significantly suppressed by the administration of LF. Oral supplementation with LF has the potential to reduce IL-1ß levels and prevent UV-induced skin damage. Further studies are needed to elucidate the relationships between the antiinflammatory effects and skin protective function of LF.

Clinical comparison between arthrocentesis and conventional conservative treatment with maxillomandibular fixation for unilateral high condylar fractures.

This study aimed to compare the effects of arthrocentesis and conventional closed reduction for unilateral mandibular condyle fractures. A total of 30 patients with unilateral condylar fractures were evaluated. Patients with a high condylar fracture and magnetic resonance evidence of joint effusion (JE) were divided into two groups: those treated with intra-articular irrigation and betamethasone injection (group I) and those given conservative treatment and rigid maxillomandibular fixation (MMF) (group II). All patients were assessed for mandibular range of motion (ROM), protrusive movements, lateral excursion movements on the fractured and non-fractured sides, pain in the temporomandibular joint and malocclusion, both before and after treatment. There were no significant differences in regard to protrusion, lateral excursion movement and incidence of malocclusion at 12 months after treatment between the groups (P > 0.05). In group I, ROM and joint pain showed good improvement from the early stages of treatment, and those patients had better outcomes as compared to group II for those parameters at 1 and 3 months after injury. The present findings indicate that arthrocentesis may be more effective and provide faster healing than conventional closed reduction.

Effects of whole-grain paddy rice replacement with or without enzyme addition on broiler performance and intestinal morphology.

To investigate the effect of replacing maize with whole-grain paddy rice (WPR) in broiler chicken diets, with or without enzyme addition, on growth performance and histological structures of the intestinal villi, 14-d-old Marshall Chunky male chicks were divided into 4 groups with 4 replicates of 4 chicks each. The experimental diets containing different concentrations of WPR were as follows: (1) 0 g/kg (Control); (2) 141.5 g/kg, grower, and 125.0 g/kg, finisher (25WPR); (3) 283.0 g/kg, grower, and 250.0 g/kg, finisher (50WPR); (4) 283.0 g/kg, grower, and 250.0 g/kg, finisher, and enzyme supplementation (50WPR + enzyme). All diets were formulated to be isocaloric and isonitrogenous and provided ad libitum for 35 d. There were no differences among the diets on the growth performance and digestive organ size. The villus height and cell mitosis number of all intestinal segments did not change in any treatment. The ileal villus area, duodenal cell area, duodenal and jejunal goblet cell number in the 50WPR group increased significantly relative to the control but not when enzyme was included. In the scanning electron microscope results, all experimental groups showed clear protuberant cells and cell clusters on the villus apical surface of the duodenum. In the jejunum, cell clusters and areas having cells with no microvilli were frequently found in both the 50WPR and 50WPR + enzyme groups. In conclusion, broilers fed on diets replacing maize with WPR showed hypertrophied villi of duodenum and ileum and epithelial cells in duodenum and jejunum, especially in the 50WPR group, without negatively affecting growth performance. These findings suggest that WPR can replace maize up to a level of 50% (283.0 g/kg, starter, and 250.0 g/kg, finisher) in broiler diets without enzyme supplementation. However, further studies are needed to improve our knowledge of the influence of WPR on higher numbers of birds.

Effect of dietary mannanase-hydrolysed copra meal on growth performance and intestinal histology in broiler chickens.

We investigated mannanase-hydrolysed copra meal (MCM), which contains ß-1,4-mannobiose (MNB), for its capacity to improve growth performance and activate intestinal villus function. Seven-day-old chicks were separated into four flocks with an equal mean body weight and then fed a basal diet (control) or a diet supplemented with 0.02% or 0.1% MCM. After 7 weeks, the feed intake and body weight were determined and then used to calculate the feed efficiency (FE). Moreover, the intestinal segments were examined by light microscopy and scanning electron microscopy (SEM) for cellular and morphological changes in the villus. Although feed intake was not significantly different among the experimental groups, the body weight gain and FE were significantly higher in the 0.1% MCM group than in the control group (p < 0.05), while feed intake tended to be higher in the 0.02% and 0.1% MCM groups. The cellular area of the ileum was significantly higher in the 0.02% and 0.1% groups in relation to that in the control group (p < 0.05). Furthermore, the cellular area of the duodenum and the jejunum tended to be higher in the 0.02% and 0.1% MCM groups. For the correlation analysis, a significant correlation was observed between the dosage of MCM and the cell area of the duodenum, jejunum and ileum. Moreover, the number of mitotic cells was higher in the 0.1% MCM group. As shown by SEM, the cells at the villi tips were protuberant in appearance in the 0.02% and 0.1% MCM treatments when compared with the relatively flat cells of the control. On the duodenal villus surface of the 0.1% MCM group, some cells devoid of microvilli were observed, suggesting that the increased protuberance of these cells represents increased absorption activity. Although intestinal villus height and area did not significantly differ among groups, the levels of these parameters tended to increase in the experimental groups relative to the control. The present morphological findings reveal that MNB might be effective for activating intestinal absorptive function, and that the functional activation promotes the growth of the chickens.

Weekly teriparatide injections successfully treated advanced bisphosphonate-related osteonecrosis of the jaws.

This study investigated whether weekly teriparatide (TPTD) injections are as effective as daily teriparatide injections for the treatment of stage 3 bisphosphonate-related osteonecrosis of the jaws (BRONJ) and compared serum markers of bone turnover between the two treatment regimens. Daily TPTD treatment has recently been reported to be effective for BRONJ, but there are no reports describing the effectiveness of weekly TPTD injections. We report two patients with stage 3 BRONJ. One patient was successfully treated with weekly TPTD injections and the other with daily TPTD injections. Changes in the levels of serum N-telopeptide of type I collagen (s-NTX) and serum N-terminal propeptide of type I collagen (P1NP) were studied. Two patients with stage 3 BRONJ that was refractory to conservative treatment were treated with TPTD. Their medical records were reviewed and the patients were interviewed. There was complete mucosal coverage of the intraoral defects after 3 months of TPTD treatment in both patients. Progressive bone regeneration in an area of mandibular fracture was identified after 4 months of treatment. The s-NTX level increased slightly in both patients. This is the first report of successful treatment of stage 3 BRONJ with weekly TPTD injections. Either daily or weekly TPTD injections may effectively treat stage 3 BRONJ and should be considered before or perhaps even in lieu of undertaking major resection and reconstruction.

Identification of milk proteins enhancing the antimicrobial activity of lactoferrin and lactoferricin.

Lactoferrin (LF) is known as an iron-binding antimicrobial protein present in exocrine secretions such as milk and releases the potent antimicrobial peptide lactoferricin (LFcin) by hydrolysis with pepsin. The antimicrobial activity of LF and LFcin has been studied well; however, their cooperative action with other milk proteins remains to be elucidated. In this study, we identified milk proteins enhancing the antimicrobial activity of bovine LF and LFcin against gram-negative bacteria, gram-positive bacteria, and fungi. As the target fraction, we isolated a minor milk protein fraction around 15 kDa, which was identified as bovine RNase 5 (angiogenin-1), RNase 4, and angiogenin-2 by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. As these proteins are collectively known as the RNase A family, we referred to the target protein fraction as milk RNase of 15 kDa (MR15). The number of colony-forming units of Escherichia coli and other pathogenic microorganisms with the addition of MR15 to LF (MR15:LF ratio=16:1,000) was dramatically lowered than that with LF alone. On the other hand, MR15 itself did not show any reductions in the number of colony-forming units at the concentrations tested. Similarly, the antimicrobial activities of LFcin against various microorganisms were significantly enhanced by the addition of MR15. These results suggest that LF and MR15 may be concomitantly acting antimicrobial agents in milk.

Effects of dietary red pepper on egg yolk colour and histological intestinal morphology in laying hens.

To evaluate the effect of three kinds of red pepper supplementation 'Kagawa Hontaka' produced at Shiwaku Islands (KHS), Miki (KHM) and Takanotsume (TKT) on production performance, egg quality and intestinal histology in laying hens. A total of 32 laying hens (39 weeks of age) were randomly allotted to four groups, each comprising eight hens. Birds were fed a basal diet supplemented with red pepper at 0% (control), 0.5% KHS, 0.5% KHM and 0.5% TKT, respectively. Compared with the control group, no significant difference (p > 0.05) in feed consumption, final body weight, hen-day production, egg mass, feed efficiency, shell-breaking strength, shell thickness, shell ratio, albumen ratio, yolk ratio and Haugh units was observed among the experimental groups. Roche yolk colour fan (RYCF) value increased significantly in all experimental groups (p < 0.05). Furthermore, the KHS and KHM groups showed higher RYCF values than the TKT group (p < 0.05). Spectrophotometric measurements of yolk colour, redness (a*) and yellow index (YI) values were higher in the KHS and KHM groups (p < 0.0001). The yellowness (b*) value was lower in the TKT group (p < 0.05). The lightness (L*) value was lower in the KHS and KHM groups (p < 0.05). Villus height, villus area, cell area and cell mitosis in all intestinal segments tended to be higher in all experimental groups. Jejunal cell area and cell mitosis were higher in experimental groups than in the control group (p < 0.05). The cells on the villus tip surface were protuberated in all experimental groups. In conclusion, the KHS, KHM and TKT groups showed hypertrophied intestinal villi and epithelial cell functions. These results indicate that dietary red pepper has stimulating effect on intestinal villi and the structure of epithelial cells, and the 0.5% KHS and KHM groups improved in egg yolk colour.

Antiferromagnetic topological insulator with selectively gapped Dirac cones.

Antiferromagnetic (AF) topological materials offer a fertile ground to explore a variety of quantum phenomena such as axion magnetoelectric dynamics and chiral Majorana fermions. To realize such intriguing states, it is essential to establish a direct link between electronic states and topology in the AF phase, whereas this has been challenging because of the lack of a suitable materials platform. Here we report the experimental realization of the AF topological-insulator phase in NdBi. By using micro-focused angle-resolved photoemission spectroscopy, we discovered contrasting surface electronic states for two types of AF domains; the surface having the out-of-plane component in the AF-ordering vector displays Dirac-cone states with a gigantic energy gap, whereas the surface parallel to the AF-ordering vector hosts gapless Dirac states despite the time-reversal-symmetry breaking. The present results establish an essential role of combined symmetry to protect massless Dirac fermions under the presence of AF order and widen opportunities to realize exotic phenomena utilizing AF topological materials.

Effects of fermented plant product on growth performance, some blood variables, carcase characteristics, and intestinal histology in broilers.

1. Fermented plant product (FPP) is a natural fermented food which is produced from a mixture of fermented fruit and vegetables, and rice bran (1:9). 2. To investigate the effects of FPP on growth performance, some blood variables, carcase characteristics and intestinal histology were determined in 192 broilers. They were divided into 4 groups, with 4 replicates of 12 chicks each; the chicks were provided ad libitum access to a diet consisting of 0, 0·5, 2·0 and 4·0% dietary FPP. 3. The crude protein and metabolisable energy concentrations of these diets were adjusted to 230 g CP/kg and 13·40 MJ ME/kg for the 7 to 21 d old chicks, and 200 g CP/kg and 13·40 MJ ME/kg for the 22 to 49 d old chicks, respectively. 4. At 49 d of age, feed intake, body weight gain and feed efficiency tended to increase with increase in FPP concentrations. Feed intake increased in the 4·0% dietary FPP group, BW gain increased in the 2·0% and 4·0% dietary FPP groups and feed efficiency increased in all experimental groups. 5. There were no differences among diets in the blood variables and carcase characteristics, except for total visceral organ weight, increased in all experimental groups. 6. Most of the intestinal villus heights, villus areas, epithelial cell areas and cell mitosis tended to increase with increase in FPP concentrations; duodenal villus height and cell mitosis in the 2·0 and 4·0% dietary FPP groups, and jejunal cell mitosis in all experimental groups were significantly increased. Compared with flat cells on the villus apical surface in the 0% FPP group, all experimental groups had protuberant cells in all intestinal parts. 7. In conclusion, hypertrophy of the villi and epithelial cells was observed in the present study, indicating improved growth performance, especially in the 4·0% dietary FPP group. Furthermore, increased total visceral organ weights suggested that FPP has no harmful effects on broilers.

Analysis of the interactions between two molecules that are required for the expression of Ly-2 suppressor cell activity. Three different types of focusing events may be needed to deliver the suppressive signal.

We described a T suppressor factor made by an I-J- Ly-2 T cell (Ly-2 TsF) that expresses biological activity only when its acceptor cell shares H-2-linked polymorphic genes with the cells that made the Ly-2 TsF (or when the producer cell had differentiated in a thymic environment where the gene products of the acceptor cell were expressed). The Ly-2 TsF requires the presence of I-J+ Ly-1 cells in the assay culture to express its suppressive activity, although removal of the I-J+ Ly-1 cells in the assay cultures with an I-J+ soluble factor derived from them. This I-J+ molecule not only fails to bind antigen but is also antigen nonspecific in that it can come from Ly-1 cells making factors of irrelevant specificities. For the I-J+ molecule to replace the activity of the I-J+ Ly-1 cell in the assay population, in restoring suppressive function in cultures depleted of I-J+ Ly-1 cells, it must share genetic polymorphisms linked to the I-J subregion with the Ly-2 TsF and genetic polymorphisms linked to Igh-V with the target cell. These results indicate that an I-J+ antigen-nonspecific molecule combines with an antigen-specific Ly-2 TsF via an I-J- anti-I-J "type" of interaction. The resultant molecular complex is focused on a cell surface receptor of the acceptor cell. This focusing event is controlled by the antigen-nonspecific I-J+ molecule, and the precise interaction with the receptor on the acceptor cell is controlled by Igh-V-linked polymorphic gene products. The antigenic specificity of the interaction is controlled by a receptor for antigen on the I-J- component of the complex. Thus, three focusing events are required for Ly-2 TsF to express biologic activity: (a) the Ly-2 TsF must be focused on an acceptor cell that has the same antigenic specificity (most likely via an antigen bridge); (b) it must also be focused onto an I-J+ antigen-nonspecific molecule that we refer to as a "schlepper" molecule (most likely via an I-J anti-I-J bridge); and (c) the schlepper molecule must focus the molecular complex on an Igh-V-controlled receptor on the antigen-specific target cell.

Homologies between cell interaction molecular controlled by major histocompatibility complex- and Igh-V-linked genes that T cells use for communication. Tandem "adaptive" differentiation of producer and acceptor cells.

We have asked the question: how do partner cells in immunoregulatory interactions between T cell subsets acquire the ability to recognize and react appropriately with one another? In particular, we have asked whether these communication events are completely determined by the cell's genetic constitution, or whether the recognition events can be learned during ontogeny. We have found that the T cells of parent into F1 chimeras and homozygous nude mice with F1 thymus grafts not only learn to react with genetically disparate acceptor cells, but that the receptors on the acceptor cells themselves learn to react with genetically disparate producer cells. This learning process can overcome both major histocompatibility complex- and immunoglobulin heavy chain variable region-linked restricted communication between T cell subsets. We interpret these findings to indicate that thymic elements can start a cascade of differential events. The thymic elements, whether endogenous or passively acquired, select from a pool of producer cells those that will react appropriately with the thymic selecting cells, and these cells become expanded. Then, the private markers (idiotype) on the expanded pool of producer cells act as selecting and expanding elements that choose from a pool of acceptor cells those that recognize the producer cells idiotype as self. This second differentiational event, although apparently thymus evidence that this type of acceptor cell differentiation could also take place during the course of an immune response.

Molecular composition of an antigen-specific, Ly-1 T suppressor inducer factor. One molecule binds antigen and is I-J-; another is I-J+, does not bind antigen, and imparts an Igh-variable region-linked restriction.

Immunized Ly-1+2-T cells (Ly-1 cells) make an antigen-specific soluble suppressor product (Lyl-1 TsiF) that will induce Ly-2+ cells to express suppressive activity but only if the Ly-2+ and the Ly-1 producer cell share genetic polymorphisms that are linked to the Igh locus and in particular that part where the Igh-V (or VH) is encoded. Ly-1 TsiF can be separated into entities, one binds antigen and does not express I-J determinants, and the other is I-J+ and does not bind antigen. Neither of these "subfactors" has biological activity, but a 50:50 mixture of them reconstitutes biological activity that expresses the antigen specificity of the antigen-binding molecule. Any of the three heterologous erythrocytes (antigens) studied can be used for immunization to produce the I-J+ nonantigen-binding factor, i.e., the I-J+ moiety makes no contribution to the factor's specificity. It does, however, determine the intact factor's Igh-V linked restriction. Thus, the antigen combining site of the factor is irrelevant to the factor's Igh-V restriction but crucial for its specificity. The I-J+ molecule does not bind antigen nor influence the factor's antigen specificity but expresses the Igh-V polymorphism (or anti-Igh-V polymorphism) that is required for the transmission of an inductive signal to the factor's Ly-2+ acceptor cell.