Evidence for distinct polygenic regulation of antibody responses to some unrelated antigens in lines of mice selected for high or low antibody responses to somatic antigen of Salmonella

The effect of the selective breeding of mice for high or low antibody production to complex immunogens is largely nonspecific, since it modifies the responsiveness of high (H) and low (L) lines to many antigens unrelated to the selection antigen. However, the nonspecific effect of the polygenic control operating in these lines is not a general feature. For example, the group of genes in selection IV, carried out for responsiveness to somatic antigen of Salmonella, does not modify the responses to sheep erythrocytes (SE). Despite equivalent responses in H and L mice of selection IV, a large variability was found in individual responses of F₂ interline hybrids, which demonstrates the presence of alleles with high or low effect on responses to SE. A selective breeding (Selection IV-A) was therefore initiated from this F₂ population for responsiveness to SE. A progressive interline divergence occurred during the first seven generations of selection; the interline separation was due to polygenic regulation (about four independent loci from a preliminary estimate).Equivalent responses to the s antigen of Salmonella are observed in the two lines. This constitutes additional evidence for distinct polygenic regulation of responses to SE and to somatic antigen. Moreover, the pattern of responses to several unrelated antigens (nonspecific effect) also differs between Selections IV and IV-A.Abbreviations H high responder lines - L low responder lines - s somatic antigen of Salmonella - f flagellar antigen of Salmonella - R response to selection - S selection differential - F₀ foundation population - h² heritability (realized) - RGG rabbit gamma globulin - CE chicken erythrocyte - HE human erythrocyte - PE pigeon erythrocyte - SE sheep erythrocyte     

Synaptonemal complexes with modified lateral elements in Sordaria humana: development of and relationship to the “recombination nodules”

Meiotic prophase in Sordaria humana has been analyzed by three-dimensional reconstructions of 3 leptotene, 2 zygotene, 10 pachytene and 3 diplotene nuclei. Several notable features emerged. The lateral components of the synaptonemal complexes (SC) are hollow tubes which show dilations of variable sizes from late leptotene to early diplotene. These bulges occur before pairing. Their number decreases as soon as the SC are completely formed, but their mean size increases. Bulges can be present in all parts of the lateral components including telomeres and nucleolar organizer region, but their distribution along bivalents is not random. The remarkably uniform width of the SC central region, normally observed in other species is not observed in S. humana. Although as a general rule the bulges rarely affect the homologous components at identical sites, they often either fill or partially cover the central region. The recombination nodules are not clearly connected with the bulges. This work provides also additional insight into the development of both SC and the nodules. At late leptotene, the homologues are aligned before SC formation. One case of interlocking has been observed at early pachytene. Nodules are present from zygotene to diplotene. They are not evenly distributed along the bivalents during pachytene. The mean number of nodules, constant from late pachytene to diplotene, is equal to the mean number of chiasmata.     

Découverte de Stringocephaluseet autres Stringocephalidae (Brachiopodes Terebratulida)) dans le Givétien d'Afghanistan

A lot of Stringocephalidae have been discovered,for the first time, in the Givetian of Afghanistan. Among these we have identified: Stringocephalus aff. burtini (Defrance)), St. (Parastringocephalus) dewalense n. sp., Rensselandia aff. circularis (Holzapfel)). The locality is situated in Hazarajat, in a Devonian sequence which is more than one thousand meters thick and the age of which ranges from Gedinnian (probable) to Frasnian.     

Distribution and movement of toxaphene in anaerobic saline marsh soils

The biological oxygen demand (BOD) of filtered water from Lake Wingra, Wisconsin is significantly higher in the littoral zone than in the pelagial zone. Laboratory experiments indicate that BOD is not influenced by water temperature at the time of sampling or by enrichment with nitrate or ammonia. Rather, enrichment with macrophyte leachate sharply increases BOD, and enrichment with phosphate produces a small but significant increase in BOD. We conclude that high BOD in littoral waters of the lake is an indication of production of labile organic matter in the water by dense beds of the macrophyte Myriophyllum spicatum.     

Interaction ofH-2 and nonH-2 linked genes in the regulation of antibody response to a threshold dose of sheep erythrocytes

The antibody response to a threshold dose (¹⁰) of SE was studied in the High responder line (H) and the Low responder line (L) of mice obtained by bidirectional selective breeding for the character quantitative agglutinin response to an optimal dose of SE, and in interline hybrids: F₁, F₁ and both backcrosses. Whereas the interline difference in agglutinin responses at the optimal dose is due to the additive effect of about ten independently segregating loci, one of which isH-2 linked, the responsiveness to the threshold dose is determined by the effect of two loci. The direction of the dominance effect also varies with the antigen dose: high responsiveness is partially dominant at the optimal dose while at the threshold dose nonresponder character is partially dominant. The role of theH-2 linked locus was investigated. It has been demonstrated that on an identical background (equivalent to that of F₁ hybrids) this locus is responsible for 12% of the interline difference at the optimal antigen dose, and for 61% at the threshold antigen dose. For the two antigen doses, the quantitative effect of theH-2 locus is in agreement with the estimate of the number of loci obtained by variance analysis. The intervention of a second gene, non-H-2 linked, in the regulation of responsiveness to 10⁶ SE is demonstrated by appropriate assortative matings. The interaction between the two genes is discussed.     

Primary Cilia Are Lost in Preinvasive and Invasive Prostate Cancer

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Little is known about the role of primary cilia in preinvasive and invasive prostate cancer. However, reduced cilia expression has been observed in human cancers including pancreatic cancer, renal cell carcinoma, breast cancer, cholangiocarcinoma, and melanoma. The aim of this study was to characterize primary cilia expression in preinvasive and invasive human prostate cancer, and to investigate the correlation between primary cilia and the Wnt signaling pathway. Human prostate tissues representative of stages of prostate cancer formation (normal prostate, prostatic intraepithelial neoplasia (PIN), and invasive prostate cancer (including perineural invasion)) were stained for ciliary proteins. The frequency of primary cilia was determined. A decrease in the percentage of ciliated cells in PIN, invasive cancer and perineural invasion lesions was observed when compared to normal. Cilia lengths were also measured to indirectly test functionality. Cilia were shorter in PIN, cancer, and perineural invasion lesions, suggesting dysfunction. Primary cilia have been shown to suppress the Wnt pathway. Increased Wnt signaling has been implicated in prostate cancer. Therefore, we investigated a correlation between loss of primary cilia and increased Wnt signaling in normal prostate and in preinvasive and invasive prostate cancer. To investigate Wnt signaling in our cohort, serial tissue sections were stained for β-catenin as a measure of Wnt signaling. Nuclear β-catenin was analyzed and Wnt signaling was found to be higher in un-ciliated cells in the normal prostate, PIN, a subset of invasive cancers, and perineural invasion. Our results suggest that cilia normally function to suppress the Wnt signaling pathway in epithelial cells and that cilia loss may play a role in increased Wnt signaling in some prostate cancers. These results suggest that cilia are dysfunctional in human prostate cancer, and increase Wnt signaling occurs in a subset of cancers.     

Structural heterogeneity in the basal regions of the teeth of the red-backed salamander,Plethodon cinereus (Amphibia,Plethodontidae)

Ultrastructural and histochemical features of marginal (monostichous) teeth associated with the jawbones are compared with those of palatal (polystichous) teeth that compose two patches in the roof of the mouth. The apices and uncalcified regions are similar in both kinds of teeth, but the basal regions display distinctive differences. While bases (pedestals) of marginal teeth are essentially hollow cylinders that attach to the jawbones by their labial faces, bases of teeth in palatal patches are fused to form two horizontal plates which lack direct attachment to underlying bone. The plates are separated from each other by a pulp-filled space containing fibroblasts, blood vessels, and vertically oriented elements resembling bony spicules. Cylindrical pedestals like those of marginal teeth project from the ventral plate. While the identity of the material composing the basal regions remains controversial, the following evidence suggests that it is similar to “bone of attachment” (Tomes, '23): most of it, unlike dentin, does not develop in direct association with an enamel organ; alcian blue stains the bases of developing teeth but stains dentin, developing dentin, enamel, or mature bone very weakly (if at all); bases of teeth in palatal patches develop in isolation from the parasphenoid bone and thus cannot be considered extensions of it; and marginal teeth attach directly to the jawbones, but the material composing their bases does not blend with the bone. Structural heterogeneity of the basal regions appears to be linked to functional differences exhibited by these two types of teeth.     

Abnormal Whole Blood Thrombi in Humans with Inherited Platelet Receptor Defects

To delineate the critical features of platelets required for formation and stability of thrombi, thromboelastography and platelet aggregation measurements were employed on whole blood of normal patients and of those with Bernard-Soulier Syndrome (BSS) and Glanzmann’s Thrombasthenia (GT). We found that separation of platelet activation, as assessed by platelet aggregation, from that needed to form viscoelastic stable whole blood thrombi, occurred. In normal human blood, ristocetin and collagen aggregated platelets, but did not induce strong viscoelastic thrombi. However, ADP, arachidonic acid, thrombin, and protease-activated-receptor-1 and -4 agonists, stimulated both processes. During this study, we identified the genetic basis of a very rare double heterozygous GP1b deficiency in a BSS patient, along with a new homozygous GP1b inactivating mutation in another BSS patient. In BSS whole blood, ADP responsiveness, as measured by thrombus strength, was diminished, while ADP-induced platelet aggregation was normal. Further, the platelets of 3 additional GT patients showed very weak whole blood platelet aggregation toward the above agonists and provided whole blood thrombi of very low viscoelastic strength. These results indicate that measurements of platelet counts and platelet aggregability do not necessarily correlate with generation of stable thrombi, a potentially significant feature in patient clinical outcomes.