束旁核、中央中核对皮层体感觉区伤害性反应单位的影响

实验在清醒麻痹的猫上进行。先用记录诱发电位的方法,证明大脑皮层第 I 体感觉区(SI区)同一部位可接受来自外周神经、丘脑束旁核(Pf)和中央中核(CM)的上传信号;然后在这一皮层部位寻找在强电流刺激腓总神经时出现伤害性反应的神经元。在所观察的24个单位中,有20个单位如果先给予 Pf 刺激,可看到上述伤害性反应明显增强,增强的百分率平均在90.0%以上;在这同一组皮层单位,如果预先刺激 CM,有21个单位的伤害性反应明显减弱,反应抑制都在-55.6%以上。Pf 刺激本身对所观察单位的自发放电影响不明显,但 CM 刺激可明显抑制它们的自发放电。     

Genetic mapping and protein product diversity of the self-incompatibility locus in wild tomato (Lycopersicon peruvianum)

Phenotypic diversity of self-incompatibility (S) alleles within nine natural populations ofLycopersicon peruvianum was investigated. Only 7 incompatible responses were observed of a total of 276 unique combinations tested, on the basis of controlled pollinations, indicating the large number of alleles that exist within these populations. Molecular weight polymorphism for specific major stylar proteins observed on SDS-PAGE was also evident in two of the populations examined. Five proteins were shown to map to theS locus and to be associated with differentS alleles through controlled pollinations and segregation of the proteins. Two of theseS related proteins had been described previously in terms of spatial and temporal expression consistent with their involvement in self-incompatibility (Mauet al., Planta 169, 184–191, 1986). A mapping population derived from a fully compatible cross was used to establish linkage of theS locus to two DNA markers,CD15 andTG184, that lie on chromosome 1. The order of the markers and estimates of map distances are given.     

A peculiar toxicity manifested by platinum(II)amines in rats: Gastric distension after intraperitoneal administration

Metoclopramide i.p. reduces the gastric distension consistently seen in rats given cisplatin i.p. at effective immunosuppressant doses (6 mg/kg). Many other immunosuppressant/oncolytic platinum amines also engendered gastric distension but certain dimers and 1,2-cyclohexanediaminoplatinum (II) compounds did not. This phenomenon appears to be due to paralysis of gastric emptying (without appetite suppression).     

Tacrine derivatives stimulate human glioma SF295 cell death and alter important proteins related to disease development: An old drug for new targets

Glioblastoma is the most common and aggressive glioma, characterized by brain invasion capability. Being very resistant to the current therapies, since even under treatment, surgery, and chemotherapy with temozolomide (TMZ), patients achieve a median survival of one year. In the search for more effective therapies, new molecules have been designed. For nervous system cancers, molecules able to cross the blood-brain barrier are handled with priority. Accordingly, tacrine was chosen for this study and the inclusion of spiro-heterocyclic rings was done in its structure resulting in new compounds. Cytotoxic activity of tacrine derivatives was assayed using glioblastoma cell line (SF295) as well as analyzing cell death mechanism. Increased caspases activities were observed, confirming apoptosis as cell death type. Some derivatives also increased reactive oxygen species formation and decreased the mitochondrial membrane potential. Moreover, compounds acted on several glioblastoma-related proteins including p53, HLA-DR, beta-catenin, Iba-1, MAP2c, Olig-2, and IDH1. Therefore, tacrine derivatives presented promising results for the development of new glioblastoma therapy, particularly to treat those patients resistant to TMZ.     

Do homomorphic and heteromorphic self-incompatibility systems have the same sporophytic mechanism?

The view put forward by some authors that flowering plant self-incompatibility mechanisms of the homomorphic sporophytic and heteromorphic sporophytic types have a close evolutionary relationship, with one form being evolved from the other, or both forms directly evolved from ancestors with homomorphic gametophytic incompatibility, is challenged. A review is provided of the various facets of each of the three main self-incompatibility systems, including a detailed summary of our current knowledge of the rejection mechanism, to demonstrate that the implicit assumption that these systems have a common S locus, and also evolutionary theories linking the systems, need to be treated with considerable caution.     

Erythrocyte morphological states, phases, transitions and trajectories

Morphological response (MR) of red blood cells represents a triphasic sequence of spontaneously occurring shape transformation between different shape states upon transfer the cells into isotonic sucrose solution in the order: S₀ (initial discoid shape in physiological saline) → S₁ (echinocytic shape at the beginning of MR, phase 1) → S₂ (intermediate discoid shape, phase 2) → S₃ (final stomatocytic shape, phase 3). In this paper, the dynamics of cell shape changes was investigated by non-invasive light fluctuation method and optical microscopy. Among 12 possible transitions between four main shape states, we experimentally demonstrate here an existence of nine transitions between neighbour or remote states in this sequence. Based on these findings and data from the literature, we may conclude that red blood cells are able to change their shape through direct transitions between four main states except transition S₁ → S₀, which has not been identified yet. Some shape transitions and their temporal sequence are in accord with predictions of bilayer couple concept, whereas others for example transitions between remote states S₃ → S₁, S₁ → S₃ and S₃ → S₀ are difficult to explain based solely on the difference in relative surface areas of both leaflets of membrane suggesting more complex mechanisms involved. Our data show that MR could represents a phenomenon in which the major role can play pH and chloride-sensitive sensor and switching mechanisms coupled with transmembrane signaling thus involving both cytoskeleton and membrane in coordinated shape response on changes in cell ionic environment.     

Protein C inhibitor regulates both cathepsin L activity and cell-mediated tumor cell migration

Background

Protein C inhibitor (PCI) is a plasma serine protease inhibitor (serpin) that regulates several serine proteases in coagulation including thrombin and activated protein C. However, the physiological role of PCI remains under investigation. The cysteine protease, cathepsin L, has a role in many physiological processes including cardiovascular diseases, blood vessel remodeling, and cancer.

Methods and results

We found that PCI inhibits cathepsin L with an inhibition rate (k₂) of 3.0 × 10⁵ M⁻¹ s⁻¹. Whereas, the PCI P1 mutant (R354A) inhibits cathepsin L at rates similar to wild-type PCI, mutating the P2 residue results in a slight decrease in the rate of inhibition. We then assessed the effect of PCI and cathepsin L on the migration of human breast cancer (MDA-MB-231) cells. Cathepsin L was expressed in both the cell lysates and conditioned media of MDA-MB-231 cells. Wound-induced and transwell migration of MDA-MB-231 cells was inhibited by exogenously administered wtPCI and PCI P1 but not PCI P14 mutant. In addition, migration of MDA-MB-231 cells expressing wtPCI was significantly decreased compared to non-expressing MDA-MB-231 cells or MDA-MB-231 cells expressing the PCI P14 mutant. Downregulation of cathepsin L by either a specific cathepsin L inhibitor or siRNA technology also resulted in a decrease in the migration of MDA-MB-231 cells.

Conclusions

Overall, our data show that PCI regulates tumor cell migration partly by inhibiting cathepsin L.

General significance

Consequently, inhibiting cathepsin L by serpins like PCI may be a new pathway of regulating hemostasis, cardiovascular and metastatic diseases.