We earlier identified a lysine to arginine transition at residue 303 (K303R) in estrogen receptor alpha (ERalpha) in invasive breast cancers, which confers resistance to the aromatase inhibitor (AI) anastrozole (Ana) when expressed in MCF-7 breast cancer cells. Here, we show that AI resistance arises through an enhanced cross talk of the insulin-like growth factor receptor-1 (IGF-1R)/insulin receptor substrate (IRS)-1/Akt pathway with ERalpha, and the serine (S) residue 305 adjacent to the K303R mutation has a key function in mediating this cross talk. The ERalpha S305 residue is an important site that modifies response to tamoxifen; thus, we questioned whether this site could also influence AI response. We generated stable transfectants-expressing wild-type, K303R ERalpha or a double K303R/S305A mutant receptor, and found that the AI-resistant phenotype associated with expression of the K303R mutation was dependent on activation of S305 within the receptor. Ana significantly reduced growth in K303R/S305A-expressing cells. Preventing S305 phosphorylation with a blocking peptide inhibited IGF-1R/IRS-1/Akt activation and also restored AI sensitivity. Our data suggest that the K303R mutation and the S305 ERalpha residue may be a novel determinant of AI response in breast cancer, and blockade of S305 phosphorylation represents a new therapeutic strategy for treating tumors resistant to hormone therapy.Oncogene advance online publication, 25 January 2010; doi:10.1038/onc.2009.520.

ABSTRACT: BACKGROUND: The Tientsin Albino 2 (TA2) mouse is an inbred strain originating from the Kunming strain. It has a high incidence of spontaneous breast cancer without the need for external inducers or carcinogens. Until now, the mechanism of carcinogenesis has remained unclear. In this study, we investigate differential gene expression, especially the expression of decorin, EGFR and cyclin D1, during mammary gland epithelial cell carcinogenesis in TA2 mice. METHODS: Gene expression profiles of spontaneous breast cancer and matched normal mammary gland tissues in TA2 mice were ascertained using an Affymetrix Mouse 430 2.0 array. Twelve mammary tissue samples from five month-old female TA2 mice (Group A), as well as 28 samples from mammary (Group B) and cancer tissues (Group C) of spontaneous breast cancer-bearing TA2 mice, were subsequently used to detect the expression of decorin, EGFR and cyclin D1 by real-time PCR and immunohistochemical methods. RESULTS: Several imprinted genes, oncogenes and tumor suppressor genes were differentially expressed between normal mammary gland tissues and breast cancer tissues of TA2 mice. The imprinted gene decorin and the oncogene EGFR were down-regulated in tumor tissues, while the oncogene cyclin D1 was up-regulated. Immunohistochemistry showed that samples in Group A showed high decorin expression more frequently than those in Group B (P<0.05). More tissue samples in Group B than Group A were positive for nuclear EGFR, and tissue samples in Group B more frequently showed high nuclear EGFR expression than those in Group A or Group C (P<0.05). The labeling index for cyclin D1 in Group C was significantly higher than in Group B. Mammary tissues of Group A expressed the highest level of decorin mRNA (P<0.05), and mammary tissues of Group B expressed the highest level of EGFR mRNA (P<0.05), while cancer tissues expressed the highest level of cyclin D1 mRNA (P<0.05). CONCLUSIONS: The expression of decorin, EGFR and cyclin D1 in mammary epithelial cells changes with increasing age. The abnormal expression of them may partly contribute to the genesis of spontaneous breast cancer in TA2 mice.

This review updates the knowledge in the research field of cardiac lymphatic vessels by collecting both scientific evidence and hypotheses, including cardiac lymphatic vessel anatomy and lymph flow, the mechanism of cardiac lymphatic pumping, pathological findings and mechanisms of cardiac injury caused by lymph flow impairment, cardiac functional improvement by increasing lymph flow in the heart in patients with myocardial infarction, and the mechanisms of lymphangiogenesis.

Summary With 20 figures and 5 tables Although yaks play an important role as companion or pack and draught animals on Chinese plateaus in alpine and sub-alpine regions, morphological studies and anatomical data on the lung of yak are sparse. To provide anatomical descriptions and morphometric data, 10 one-day-old yaks were examined by means of dissection, light and electron microscopy. The measurements of lung were made on dissected specimens and histological sections. Unequal dichotomous branching was demonstrated in the dissected tracheobronchial tree. The diameters of bronchial airways and height of epithelium were measured, and showed that the variation of diameters in airways was always greater than that of height of epithelium. In addition, the thickness of muscularis, cartilage and adventitia was examined, as well as the number of goblet and Clara cells in airways. Ultrastructural studies showed that the surface epithelium was mainly composed of goblet, ciliated, Clara and basal cells, similar to that in other domestic animals. Under electron microscope, two distinctive types of ciliated cells could be seen in the tracheobronchial epithelium. The first type contained some mitochondria, distended smooth endoplasmic reticulum (SER), little rough endoplasmic reticulum (RER) and numerous vacuoles in electron-lucent cytoplasm. The second type had dense cytoplasm with abundant mitochondria, RER and no vacuoles. Both types were rich of glycogen granules. The goblet cells in neonatal yak lung had the following characteristic features: dentate nucleus in dense cytoplasm, with stacks of RER and numerous dense membrane-bounded mucous droplets, which were round or oval, often with an electron-lucent core. The droplets were not confluent. Glycogen granules were numerous, and Golgi complex was occasionally present. Clara cells were dome-shaped and usually protruded into the airway lumen. Large amounts of SER and many secretory droplets were found within the cytoplasm. Several typical 'clefts' were also found in the cytoplasm.

A series of La, Ta double substituted Sr(1-x)La(x)Ti(1-x)Ta(x)O(3), with x = 0.01, 0.05 and 0.10, and La, Nb double substituted Sr(0.90)La(0.10)Ti(0.90)Nb(0.10)O(3) for comparison were investigated in this project. Rietveld refinements were performed to check for purity and symmetry reduction. Electronic structure calculations indicate n-type conduction with steep and flat bands in the vicinity of the Fermi level for x = 0.125. Seebeck coefficient, electrical conductivity, and thermal conductivity measurements on hot-pressed and spark-plasma-sintered samples were performed over a wide range of temperatures. Best results were obtained by spark-plasma-sintering of double substituted Sr(0.99)La(0.01)Ti(0.99)Ta(0.01)O(3) with a thermoelectric figure-of-merit of 0.13 at 660 K.

Contents The objective of this study was to investigate the developmental morphology of yak oocytes from the primordial follicle to the tertiary follicle. Yak oocytes from resting primordial (n = 6), activated primordial (n = 12), primary (n = 9), secondary (n = 7) and early tertiary (n = 5) follicles were processed and analysed by light and transmission electron microscopy. The resting primordial follicular oocyte was characterized by relatively smooth surface on the oolemma, the accumulation of free and organelle-related smooth (SER) and rough endoplasmic reticulum (RER), round or oval mitochondria, and polyribosomes on the surface of the RER and throughout the ooplasm. The activated primordial follicular oocyte was dominated by numerous coated pits and coated vesicles on the oolemma, and round mitochondria. Up to the secondary follicular stage the oocyte displayed an increase in the number of microvilli, polyribosome, Golgi complexes and mitochondria with distinct cristae. During the secondary follicular stage, formation of the zona pellucida, development of a desmosome-like connection between the oocyte and the granulosa cells, formation of the cortical granules in the oocyte and elongated mitochondria in nearly all oocytes were seen. In the early tertiary follicular oocyte, the perivitelline space was present and a decrease in free SER and RER in the ooplasm occurred; finally, the nucleus migrated from an eccentric to a peripheral location. In conclusion, the growth of the yak oocyte is associated with the relocation and modulation of a number of cytoplasmic organelles as well as the development of oocyte-specific structures such as the zona pellucida, desmosome-like connection and cortical granules.

Epidermolysis bullosa simplex (EBS) is a group of inherited skin diseases, characterized by the formation of intraepidermal blisters. We performed genetic analysis of the keratin 5 (KRT5) gene in two Chinese pedigrees. One novel missense mutation was identified in a patient with sporadic EBS (general, non-Dowling-Meara). Sequence analysis showed a heterozygous T > A transition at nucleotide 1730 of KRT5, changing phenylalanine (Phe) to tyrosine (Tyr) at position 577 of the keratin 5 (K5). In addition, two recurrent mutations c.1649delG (p.Gly550AlafsX77) and c.508G >(p.Glu170Lys) in KRT5 were identified in Chinese patients with mottled pigmentation EBS and localized EBS, respectively. None of the mutations were found in any unaffected family members or in an additional 100 unrelated control samples. These results suggest that these mutations are pathogenic and might be one of the potential causes of EBS in these Chinese patients.

OBJECTIVE: To synthesise N-sulfanil-4-aminobutyric acid mother nucleus derivative of sulfonamides, and its artificial antigens in order to explore the methods of preparation were discussed. METHODS: N-sulfanil-4-aminobutyric acid was synthesized and confirmed by 1HNMR, 13CNMR, IR, ESI-MS. N-sulfanil-4-aminobutyric acid artificial antigen was synthesized by the methods of active ester coupling, and was identified by UV scan. Single factor test and orthogonal test design methods L9(3(3)) were employed to study the influence of the factors such as the initial molar ratio of reagents, activate hapten time and the coupling time to the coupling rate, as to determine the optimal reaction conditions for synthesis. The obtained results showed that the initial molar ratio of hapten to BSA 50:1, activated hapten time 6 hours, coupling time 4 hours. The artificial antigen was prepared by the optimal reaction conditions. The artificial antigen was injected into Balb/c mice and the blood samples were obtained from tails of Balb/c mice after the 5th injection and detected by iELISA method. RESULTS: The structure of N-sulfanil-4-aminobutyric acid was correct. The artificial antigen was prepared. CONCLUSION: Antigens was acquired successfully.

A novel 3D porous aromatic framework (PAF) based on a tetraphenylmethane block and a triangular triazine ring been designed and synthesized, with 1109 m(2) g(-1) Langmuir surface area, and shows selective sorption of benzene.