Néel transition of lattice fermions in a harmonic trap: a real-space dynamic mean-field study.

We study the magnetic ordering transition for a system of harmonically trapped ultracold fermions with repulsive interactions in a cubic optical lattice, within a real-space extension of dynamical mean-field theory. Using a quantum Monte Carlo impurity solver, we establish that antiferromagnetic correlations are signaled, at strong coupling, by an enhanced double occupancy. This signature is directly accessible experimentally and should be observable well above the critical temperature for long-range order. Dimensional aspects appear less relevant than naively expected.

Scc-1, a novel colon cancer susceptibility gene in the mouse: linkage to CD44 (Ly-24, Pgp-1) on chromosome 2.

Mutations of proto-oncogenes and tumor-suppressor genes lead to neoplastic development. Some germline mutations of these genes increase the tumor susceptibility of their carriers, but the relationship between genes controlling tumor susceptibility and the known oncogenes and tumor-suppressor genes remains unelucidated. Moreover, as tumor susceptibility in mouse is controlled by multiple genes, their identification has been virtually impossible. We therefore developed a new system, the recombinant congenic strains (RCS), which separates individual susceptibility genes into different RC strains, thus facilitating their analysis. To map genes controlling the development of colon cancer, we used the Balb/c-c-STS (CcS/Dem) RC strains. Owing to several unidentified genes, Balb/cHeA mice are relatively resistant and STS/A mice highly susceptible to 1,2-dimethylhydrazine-(DMH)-induced colon adenocarcinomas. Each CcS/Dem strain carries a different subset of about 12.5% of genes of the STS strain on the Balb/c background, and individual STS susceptibility genes became segregated into different RC strains. Using CcS-19, one of the highly susceptible RC strains, we mapped a novel colon tumor susceptibility gene, Scc-1, different from the oncogenes and tumor-suppressor genes known to be involved in colon tumorigenesis, in the vicinity of CD44 (Ly-24, Pgp-1) on chromosome 2. The mapping of the Scc-1 gene indicates that the RCS system can be used to map and study the presently unknown genes which control cancer development.

Immunocytochemical and flow cytofluorimetric detection of intracellular IL-4, IL-5 and IFN-gamma: applications using blood- and airway-derived cells.

We have compared an immunocytochemical and a flow cytofluorimetric method to detect intracellular IFN-gamma, IL-4 and IL-5 in T-cell clones, peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage fluid (BALF) cells. Intracellular bound cytokine-specific antibodies were visualized either with amino-ethyl carbazole (for immunocytochemistry), or with fluorescent antibodies (for flow cytofluorimetry). The staining was inhibited with recombinant cytokines and corresponded qualitatively and quantitatively to cytokine levels in the supernatants of T-helper-0 (Th0), Th1 and Th2 clones. In analysing in vitro stimulated cells, sufficient signal in the fluorimetric assay was only obtained after the addition of monensin to the cultures. We then observed a good correlation between immunocytochemical (with no monensin added) and the flow cytofluorimetric staining for all three cytokines (PBMC, IFN-gamma and IL-4, rho = 0.9, no IL-5 detectable; clones, IL-5, rho = 0.81, all three p < 0.05). However, compared to flow cytometry, a greater percentage of positively stained cells was frequently observed using immunocytochemistry. In BALF cells, the immunocytochemical method was able to detect significant percentages of positive cells without in vitro stimulation of the cells, in contrast to the flow cytofluorimetric method. In BALF cells from sarcoidosis patients, T-cells were mainly IFN-gamma-positive (immunocytochemically assessed), both with (mean +/- SEM, 39.7 +/- 9.8%), and without (3.5 +/- 1.3%) in vitro stimulation. In BALF cells from allergic subjects, the immunocytochemical method showed lymphocytes positive for IFN-gamma (40.3 +/- 8.3%), IL-4 (19.1 +/- 0.49) and IL-5 (6.1 +/- 3.1). We conclude that both methods can be used to assess the production of IFN-gamma, IL-4 or IL-5 at the single-cell level in T-cell clones, PBMC and cells from the BALF. The high sensitivity and the low number of cells required for the immunocytochemical method indicate that this method can provide detailed information on cytokine production of airway-derived cells in diseases with airway inflammation such as sarcoidosis and asthma.

Qualitative and quantitative aspects of anti-H-2Ld sera.

Two anti-H-2Ld sera were analyzed, BALB/c-H-2dm2 anti-BALB/cBy and (C3H X BALB/c-H-2dm2)F1 anti-BALB/cHe, the latter also containing anti-Qa antibodies. Their reaction patterns were compared with an anti-Qa serum (C3H X BALB/cBy)F1 anti-BALB/cHe. Four H-2 specificities could be detected by the anti-H-2Ld sera, two already known (H-2.64, H-2.65) and two new specificities (H-2.81, H-2.82). According to their reaction pattern H-2.64, H-2.81, and H-2.82 can be regarded as members of the H-2.28 family of specificities. A quantitative difference in the expression of these H-2 specificities exists in different haplotypes. The cells of the strain against which the sera were made (BALB/cHe and BALB/cBy, respectively) did not give the highest titers with the antisera and had a relatively low absorbing capacity. The H-2dx haplotype carries two new specificities of the H-2.28 family, namely, H-2.81 and H-2.82. Lysostrip tests showed that the antibodies against those specificities cap the H-2.1-positive H-2Ddx molecules, suggesting that these molecules may react with both anti-H-2.1-like and anti-H-2.28-like antibodies. The H-2 specificities detected by the BALB/c-H-2dm2 anti-BALB/cBy serum were detected also in liver, kidney, spleen, heart, and lung tissue. New information on the strain distribution of Qa-2 was obtained from the experiments and a quantitative difference in Qa-2 antigens between H-2 congenic strains was observed as well. The H-2b strains react with these antibodies with higher titers than the strains carrying the H-2d haplotype.

Differential induction of rat hepatic glutathione S-transferase isoenzymes by hexachlorobenzene and benzyl isothiocyanate. Comparison with induction by phenobarbital and 3-methylcholanthrene.

Male Wistar rats were treated with hexachlorobenzene, benzyl isothiocyanate, phenobarbital or 3-methylcholanthrene. Hepatic cytosolic glutathione S-transferase (GST) activity was determined with the substrates 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, ethacrynic acid and trans-4-phenyl-3-buten-2-one. Cytosolic glutathione peroxidase activity was measured with cumene hydroperoxide. GST activity toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene and ethacrynic acid was enhanced by all compounds, hexachlorobenzene and 3-methylcholanthrene causing the largest and the smallest increase respectively. Trans-4-phenyl-3-buten-2-one-conjugating activity exhibited only small changes, while peroxidase activity with cumeme hydroperoxide was not changed by any of the inducing agents. GST isoenzymes were purified on S-hexylglutathione Sepharose 6B and separated by means of FPLC-chromatofocusing, to evaluate effects on the GST isoenzyme pattern. Hexachlorobenzene and phenobarbital both caused an increase in the relative amounts of subunits 1 and 3 when compared with subunits 2 and 4 respectively. For 3-methylcholanthrene only induction of subunit 1 was observed, possibly due to the relatively low induction levels of total GST activity. In benzyl isothiocyanate-treated animals, an induction of subunit 3 was found as well as an increase in the relative amount of subunit 2. Thus, benzyl isothiocyanate behaves differently from hexachlorobenzene, phenobarbital and 3-methylcholanthrene as an inducing agent of rat hepatic glutathione S-transferases.

Stem cell CD44v isoforms promote intestinal cancer formation in Apc(min) mice downstream of Wnt signaling.

A gene signature specific for intestinal stem cells (ISCs) has recently been shown to predict relapse in colorectal cancer (CRC) but the tumorigenic role of individual signature genes remains poorly defined. A prominent ISC-signature gene is the cancer stem cell marker CD44, which encodes various splice variants comprising a diverse repertoire of adhesion and signaling molecules. Using Lgr5 as ISC marker, we have fluorescence-activated cell sorting-purified ISCs to define their CD44 repertoire. ISCs display a specific set of CD44 variant isoforms (CD44v), but remarkably lack the CD44 standard (CD44s) isoform. These CD44v also stand-out in transformed human ISCs isolated from microadenomas of familial adenomatous polyposis patients. By employing knock-in mice expressing either CD44v4-10 or CD44s, we demonstrate that the CD44v isoform, but not CD44s, promotes adenoma initiation in Apc(Min/+)mice. Our data identify CD44v as component of the ISCs program critical for tumor initiation, and as potential treatment target in CRC.

Supersolid bose-fermi mixtures in optical lattices.

We study a mixture of strongly interacting bosons and spinless fermions with on-site repulsion in a three-dimensional optical lattice. For this purpose we develop and apply a generalized dynamical mean-field theory, which is exact in infinite dimensions and reliably describes the full range from weak to strong coupling. We restrict ourselves to half filling. For weak Bose-Fermi repulsion a supersolid forms, in which bosonic superfluidity coexists with charge-density wave order. For stronger interspecies repulsion the bosons become localized while the charge-density wave order persists. The system is unstable against phase separation for weak repulsion among the bosons.

Effect of ventilation strategy and surfactant on inflammation in experimental pneumonia.

This study explored, the inflammatory response during experimental pneumonia in surfactant-depleted animals as a function of ventilation strategies and surfactant treatment. Following intratracheal instillation of Group B streptococci (GBS), surfactant-depleted piglets were treated with conventional (positive-end expiratory pressure (PEEP) of 5 cmH2O, tidal volume 7 mL x kg(-1)) or open lung ventilation. During the latter, collapsed alveoli were recruited by applying high peak inspiratory pressures for a short period of time, combined with high levels of PEEP and the smallest possible pressure amplitude. Subgroups in both ventilation arms also received exogenous surfactant. Conventionally ventilated healthy animals receiving GBS and surfactant-depleted animals receiving saline served as controls. In contrast with both control groups, surfactant-depleted animals challenged with GBS and conventional ventilation showed high levels of interleukin (IL)-8, tumour necrosis factor (TNF)-alpha and myeloperoxidase in bronchoalveolar lavage fluid after 5 h of ventilation. Open lung ventilation attenuated this inflammatory response, but exogenous surfactant did not. Systemic dissemination of the inflammatory response was minimal, as indicated by low serum levels of IL-8 and TNF-alpha. In conclusion, the current study indicates that the ventilation strategy, but not exogenous surfactant, is an important modulator of the inflammation during Group B streptococci pneumonia in mechanically ventilated surfactant-depleted animals.

Analysis of the expression of H-2 and H-2-linked antigens on mammary tumor cells.

The products of the recently discovered H-2L locus were expressed on BALB/c mammary tumor cells and behaved as histocompatibility antigens, in contrast to the products of H-2 linked loci (Qa-loci) that did not influence the acceptance or rejection of tumor transplants.

H-2L: demonstration of four new allelic products and independence of H-2D and H-2L molecules.

The H-2L molecules were detected for the first time in the Dd region products using antisera against the public specificity H-2.28. This specificity was analyzed because its presence in K as well as in D region products and its apparent allelism with another public specificity, H-2.1, indicated that these two specificities may have a special position may have a special position in the H-2 system. This was corroborated by subsequent identification of H-2L molecules in Dq and Dk products using anti-H-2.28 AND ANTI-H-2.1 sera, respectively, while none of the other previously known public or private specificities was detected on H-2L molecules. We tested the products of four D region alleles which had not been analyzed previously. In each of them we identified two distinct types of molecules: H-2D, which reacts with sera agains the D region private specificity, and H-2L, which does not react with these sera, but which is detectable either by anti-H-2.28 sera (H-2Lb, H-2Lf, H-2LS) or by anti-H-2.1 sera (H-2Ldx). This increases the number of identified H-2L alleles to seven (five H-2.8+, two H-2.1+). No association between H-2D and H-2D and H-2L molecules on the cell surface was detected in capping experiments.

A novel gene, G7e, resembling a viral envelope gene, is located at the recombinational hot spot in the class III region of the mouse MHC.

DNA sequence analysis of a segment of 15 kb, situated between G7b and G7a and present in the mouse but absent in human, revealed about 11 kb of DNA harboring a large number of repetitive sequences and 4 kb harboring a novel gene, G7e. This gene is transcribed in lymphoid tissues, having a 3-kb mRNA. The cDNA sequence of G7e shows stretches of nucleotide homology with murine leukemia virus (MuLV) envelope genes, and the predicted protein encompasses viral envelope motifs. The finding of a gene resembling MuLV envelope genes, flanked by a long terminal repeat and gag- and pol-like sequences, leads to the assumption that G7b and G7a in the mouse were separated through the insertion of a provirus, an event that might have taken place even before speciation of rat and mouse. The 15-kb interval forms a part of a 50-kb region, between Hsp70.3 and G7, where recombination preferentially takes place. Several disease susceptibility genes have been mapped to this same interval. The position of G7e in or in the vicinity of a recombinational hot spot might not be coincidental. The presence of adjacent putative recombination regulatory sequences is suggestive for the location of the crossover sites of recombination in this interval.

H-2.28, an alloantigenic marker allelic to H-2.1, is expressed on all three known types of H-2 molecules.

Each allele at the K or D region of the H-2 complex produces two kinds of "allelic" or mutually exclusive antigenic characteristics: its unique private specificity and a public specificity(ies) of either the H-2.28 or H-2.1 family. The private specificities of the K and D regions are expressed on H-2K and H-2D molecules, respectively. The D region produces another molecule, H-2L, which lacks the H-2K and H-2D private specificity but exhibits the H-2.28 or H-2.1 specificity. We analyzed the expression of the H-2.28 determinants on H-2K, H-2D, and H-2L molecules. When an antiserum against H-2.28 is used to sensitize cells where it can react with only H-2K molecules or H-2D molecules, by subsequent elution antibodies against H-2.28 are recovered that can also react with H-2L molecules. Hence, determinants reactive with antibodies against H-2.28 are present on H-2L as well as on H-2K and H-2D molecules. The expression of the H-2.28/H-2.1 polymorphism on all three known types of H-2 molecules, without some obvious relation to the private specificities, suggests that the antigenic determinants of these two kinds of allelic systems (private in contrast to H-2.28/H-2.1) may be controlled by separate genes, even when they are expressed on the same molecule.

Molecular analysis of the major MHC recombinational hot spot located within the G7c gene of the murine class III region that is involved in disease susceptibility.

Recombination within the MHC does not occur at random, but crossovers are clustered in hot spots. We previously described a recombinational hotspot within the 50-kb Hsp70.3-G7 interval in the class III region of the mouse MHC. The parental haplotypes of recombinants with crossovers in this region represent the majority of the laboratory haplotypes (a, b, d, dx, k, m, p, px, q, s, and u). Using microsatellite markers and sequence-based nucleotide polymorphisms, the breakpoint intervals of 30 recombinants were mapped to a 5-kb-long interval within the G7c gene adjacent to G7a. Recombination within the G7c hot spot does not appear to be restricted to certain haplotypes. Sequence motifs that had been suggested to be associated with site-restricted meiotic recombination were absent in the vicinity of the G7c hot spot, and hence, these sequence motifs are no prerequisite for meiotic recombination. The G7c hot spot resides in a region to which a number of disease susceptibility loci have been mapped, including susceptibility to cleft palate, experimental autoimmune allergic orchitis, and chemically induced alveolar lung tumors. The exact localization of crossovers in recombinants that have been used in functional studies is important for mapping susceptibility genes and limits the number of candidate genes.

Correlation between quantitative expression of H-2K, H-2D and MuLV antigens on spontaneous AKR lymphomas.

Thymocytes of leukemic AKR mice were analysed with a fluorescence-activated cell sorter (FACS) using monoclonal antibodies (MAbs) reactive with H-2Kk and H-2Dk and conventional hetero-antibodies against MuLV gp-70 antigens. Comparison was made with thymocytes of the low-leukemia H-2k strain C3H, as well as with thymocytes of young AKR mice, late preleukemic AKR mice (6-9 months old) and mitogen-stimulated thymocytes of young AKR mice. Expression of H-2 antigens increased on cells of the majority of tumors, on thymocytes of some late preleukemic mice and on mitogen-stimulated thymocytes. An increase in H-2K and H-2D antigens was noted: imbalance of the K/D ratio in favor of H-2D was observed mostly in tumors with relatively lower total amounts of H-2K and D antigens; ratio shifts in favor of H-2K were also found, mostly in tumors with relatively higher amounts of H-2K and D antigens. Increased expression of MuLV antigens was found on cells of all tumors and on thymocytes of several late preleukemic mice. We show that in primary spontaneous AKR leukemias, in spite of large individual differences, the expression of high amounts of MuLV gp70 is not random, but is associated with high expression of H-2K and H-2D antigens. The same phenomenon is seen in thymocytes of preleukemic mice, but in mitogen-stimulated thymus cells increase of H-2 expression is not accompanied by increase of MuLV gp70.