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Purpose: The preimplantation genetic testing for aneuploidy (PGT-A) platform is not currently available for small copy-number variants (CNVs), especially those < 1 Mb. Through strategies used in PGT for monogenic disease (PGT-M), this study intended to perform PGT for families with small pathogenic CNVs. Methods: Couples who carried small pathogenic CNVs and underwent PGT at the Reproductive and Genetic Hospital of CITIC-Xiangya (Hunan, China) between November 2019 and April 2023 were included in this study. Haplotype analysis was performed through two platforms (targeted sequencing and whole-genome arrays) to identify the unaffected embryos, which were subjected to transplantation. Prenatal diagnosis using amniotic fluid was performed during 18–20 weeks of pregnancy. Results: PGT was successfully performed for 20 small CNVs (15 microdeletions and 5 microduplications) in 20 families. These CNVs distributed on chromosomes 1, 2, 6, 7, 13, 15, 16, and X with sizes ranging from 57 to 2120 kb. Three haplotyping-based PGT-M strategies were applied. A total of 89 embryos were identified in 25 PGT cycles for the 20 families. The diagnostic yield was 98.9% (88/89). Nineteen transfers were performed for 17 women, resulting in a 78.9% (15/19) clinical pregnancy rate after each transplantation. Of the nine women who had healthy babies, eight accepted prenatal diagnosis and the results showed no related pathogenic CNVs. Conclusion: Our results show that the extended haplotyping-based PGT-M strategy application for small pathogenic CNVs compensated for the insufficient resolution of PGT-A. These three PGT-M strategies could be applied to couples with small pathogenic CNVs. [ABSTRACT FROM AUTHOR]

The Yanchang gas field is located in the Ordos Basin of central China to the southeast of the Yishan Slope, covers an exploration area of 2.6×10 km and has approximately 3.5×10 m of gas reserves. The gas field is dominated by lithologic gas reservoirs but also has a few structural gas reservoirs. Sand bodies were deposited in the Carboniferous Benxi Formation around offshore barrier islands and in distributary channel fillings in the delta front of the P s and P s divisions of the Permian Shanxi Formation. The P h division of the Shihezi Formation contains the main reservoirs. The depths of the reservoirs are between 1 970 and 3 500 m. The Yanchang gas field can be classified as a typical tight sandstone gas reservoir filed because its porosity is lower than 10% and permeability lower than 1 mD. The discovery and development of the Yanchang gas field has led to a great increase in total natural gas reserves in the Ordos Basin. Its exploration has improved methods of locating large gas fields in deep-water depositional environments in the south part of the basin. [ABSTRACT FROM AUTHOR]

As an extension of previous work in Wang et al. (Ocean Dyn 64:1447-1456, ), this article presents significant waveheights of swell inverted from a 13 month dataset of two high-frequency (HF) phased array radars. As an important intermediate variable in the calculation of significant waveheights, relative swell directions obtained by two different methods from a single radar station are also presented. The impact of the inaccuracy of relative swell direction on the calculation of waveheight is investigated and an alternative way of using constant swell direction is proposed. Radar-inverted swell significant waveheights using different ranges of relative swell directions are investigated. Results are assessed by WAVEWATCH III model hind casts. Analysis of the complete database shows that radar-inverted swell significant waveheights agree reasonably well with model estimates with large scatter. Standard deviation of the difference between the two estimations increases with waveheight, whereas the relative standard deviation, normalized by waveheight, keeps nearly constant. The constant direction scheme of waveheight inversion gives good estimations except for energetic swell exceeding the small perturbation assumption. Statistical analysis suggests that radar measurement uncertainty explains a considerable part of the difference between radar and model estimates. Swell estimates from both radar stations are consistent. This enables combined use of both radar spectra at common radar cells. Use of double spectra solves the ambiguity of relative swell direction, i.e., absolute swell direction is obtained, and effectively improves the accuracy of swell direction by the least-squares method. [ABSTRACT FROM AUTHOR]

This article presents long period ocean wave (swell) frequencies inverted from a 13-month dataset of high-frequency (HF) phased array radars and an assessment of these estimates by comparison with WAVEWATCH III model data. The method of swell frequency inversion from high-frequency radar sea echo Doppler spectra is described. Radar data were collected from a two-site HF Wellen Radar (WERA) radar system on the west coast of Brittany (France) operating at 12 MHz. A standard beam-forming processing technique has been used to obtain Doppler spectra of processed radar cells. Swell frequencies are obtained from the frequencies of particular spectral peaks of the second-order continuum in hourly averaged Doppler spectra. The data coverage of effective Doppler spectra considered for swell frequency estimates shows the influence of islands and shallow water effects. Swell estimates from both radar stations are in good agreement. The comparison of radar-derived results to WAVEWATCH III (WW3) estimates shows that radar measurements agree quite well with model results. The bias and standard deviation between two estimates are very small for swells with frequency less than 0.09 Hz (period >11 s), whereas radar estimates are generally lower than model estimates for shorter swells, along with higher standard deviation. Statistical analysis suggests that radar measurement uncertainty explains most of the difference between radar and model estimates. For each swell event, time series of frequency exhibits a quasi-linear frequency increase which is associated with the dispersive property of wave phase velocity. The use of swell frequency estimates from both radars on common radar cells only slightly increases the accuracy of swell frequency measurement. [ABSTRACT FROM AUTHOR]

Liquid Ni-31.7%Sn-2.5%Ge alloy was highly undercooled by up to 238 K (0.17T) with glass fluxing and drop tube techniques. The dendritic growth velocity of primary NiSn compound shows a power-law relation to undercooling and achieves a maximum velocity of 380 mm/s. The addition of Ge reduces its growth velocity as compared with the binary NiSn alloy. A structural transition from coarse dendrites into equiaxed grains occurs once undercooling exceeds a critical value of about 125 K, which is accompanied by both grain refinement and solute trapping. The NiSn intermetallic compound behaves like a normal solid solution phase showing nonfaceted growth during rapid solidification. [ABSTRACT FROM AUTHOR]

Purpose: A successful osseointegration relies on the interplay of implant surface and surrounding bone marrow cells. This study was undertaken to investigate the impact of age and gender on the bone marrow composition. Methods: Bone marrow aspirates were obtained from the discarded metaphysis region of the femoral head in 24 patients with total hip replacement. Flow cytometry was used to measure the expression of Stro-1 cells and BMP receptors (BMPRs)-expressing cells. ELISA was used to measure bone marrow aspirate bone morphology protein7 (BMP7) concentration. Results: Our data demonstrates that there are diverse bone marrow profiles (Stro-1 cell and BMPRs cells). There are no differences of Stro-1 cells, BMPRs cells, and BMP7 concentration between male and female patients. Though there are slight increases in the number of Stro-1 cells and BMPRs cells in younger patients (<70 years old) than those of old patients (≥70 years old), the difference is not statistically significant. However, we found a close association between the Stro-1 cells, BMPR1a cells and BMP7 concentration. In addition, a correlation exists between the number of Stro-1 cells and BMIs of these patients. Conclusion: Our data suggests that the age and gender of THR patients have little impact on their bone marrow osteogenic potential. The significance of the number of the Stro-1 with BMPRs expression on the implant fixation and osseointegration warrants further investigation. [ABSTRACT FROM AUTHOR]

The Western Depression of the Liaohe Basin is the major exploration area of the Liaohe Oilfield, and its main source rocks consist of the third and fourth members of the Shahejie Formation (Es and Es). These source rocks are widely distributed in the depression, with semi-deep lake and fan delta as the main sedimentary facies, brown oil shale and black gray-dark gray mudstone as the main rocks, and a total thickness of 270-1450 m. The kerogens are mainly of the types I and II, and partly of the type IIB and least of the type III. The R values range from 0.4%-0.8%, indicating an evolution stage from immature to mature. The maturity of Es source rocks is relatively high, reaching the early mature stage, but their distribution and thickness are lower than those of Es. Besides, according to biomarker analysis, it is thought that the source rocks of Es and Es are characterized by mixed input, and most of the source rocks were formed in the brackish water-saline and strongly oxygen-free environment. Furthermore, the Qingshui, Niuxintuo and Chenjia sags are believed to possess greater potential for hydrocarbon generation and expulsion, for they are source rocks with a larger thickness, have higher organic carbon contents, belong to better organic matter types and possess higher maturities. [ABSTRACT FROM AUTHOR]

Lipase has high economic importance and is widely used in biodiesel, food, detergents, cosmetics, and pharmaceutical industries. The rapid development of synthetic biology and system biology has not only paved the way for comprehensively understanding the efficient operation mechanism of Aspergillus niger cell factories but also introduced a new technological system for creating and optimizing high-efficiency A. niger cell factories. In this review, all relevant data on microbial lipase enzyme sources and general properties are gathered and updated. The relationship between A. niger strain morphology and protein production is discussed. The safety of A. niger strain is investigated to ensure product safety. The biotechnologies and factors influencing lipase expression in A. niger are summarized. This review focuses on various strategies to improve lipase expression in A. niger. The summary of these methods and the application of the gene editing technology CRISPR/Cas9 system can further improve the efficiency of constructing the engineered lipase-producing A. niger. [ABSTRACT FROM AUTHOR]

In this work, we synthesized K2Ti6O13 nanowires coated with sulfur-doped carbon for the first time, with fulvic acid and cystine as the carbon source, which exhibit higher capacity and rate performance compared with pure potassium titanate. Via analyzing the cyclic voltammetry curves obtained at different scan rates, it is revealed that the capacity increase is due to the improved ion diffusivity induced by the carbon coating. Moreover, cystine is demonstrated to be a better carbon source than fulvic acid. [ABSTRACT FROM AUTHOR]

Purpose: To identify the genetic cause of patients with primary ciliary dyskinesia (PCD) and male infertility from two unrelated Han Chinese families. Methods: We conducted whole-exome sequencing of three individuals with PCD and male infertility from two unrelated Chinese families, and performed a targeted look-up for DNAAF6 variants in our previously reported cohort of 442 individuals (219 with isolated oligoasthenospermia and 223 fertile controls). Ultrastructural and immunostaining analyses of patients' spermatozoa were performed. The pathogenicity of the variants was validated using patient's spermatozoa and HEK293T cells. Intracytoplasmic sperm injection (ICSI) treatment was conducted in two patients. Results: We identified one novel hemizygous frameshift variant (NM_173494, c.319_329del: p.R107fs) of DNAAF6 gene (previously named PIH1D3) in family 1 and one novel hemizygous missense variant (c.290G>T: p.G97V) in family 2. No hemizygous deleterious variants in DNAAF6 were detected in the control cohort of 442 individuals. Ultrastructural and immunostaining analyses of patients' spermatozoa showed the absence of outer and inner dynein arms in sperm flagella. Both variants were proven to lead to DNAAF6 protein degradation in HEK293T cells. Both patients carrying DNAAF6 variants underwent one ICSI cycle and delivered one healthy child each. Conclusion: We identified novel DNAAF6 variants causing male infertility and PCD in Han Chinese patients. This finding extended the spectrum of variants in DNAAF6 and revealed new light on the impact of DNAAF6 variants in sperm flagella. [ABSTRACT FROM AUTHOR]

Severe asthenozoospermia is a common cause of male infertility. Recent studies have revealed that SPEF2 mutations lead to multiple morphological abnormalities of the sperm flagella (MMAF) without primary ciliary dyskinesia (PCD) symptoms in males, but PCD phenotype was also found in one female individual. Therefore, whether there is a phenotypic continuum ranging from infertile patients with PCD to MMAF patients with no or low noise PCD manifestations remains elusive. Here, we performed whole-exome sequencing in 47 patients with severe asthenozoospermia from 45 unrelated Chinese families. We identified four novel biallelic mutations in SPEF2 (8.9%, 4/45) in six affected individuals (12.8%, 6/47), while no deleterious biallelic variants in SPEF2 were detected in 637 controls, including 219 with oligoasthenospermia, 195 with non-obstructive azoospermia, and 223 fertile controls. Notably, all six patients exhibited PCD-like symptoms, including recurrent airway infections, bronchitis, and rhinosinusitis. Ultrastructural analysis revealed normal 9 + 2 axonemes of respiratory cilia but consistently abnormal 9 + 0 axoneme or disordered accessory structures of sperm flagella, indicating different roles of SPEF2 in sperm flagella and respiratory cilia. Subsequently, a Spef2 knockout mouse model was used to validate the PCD-like phenotype and male infertility, where the subfertility of female Spef2−/− mice was found unexpectedly. Overall, our data bridge the link between MMAF and PCD based on the association of SPEF2 mutations with both infertility and PCD in males and provide basis for further exploring the molecular mechanism of SPEF2 during spermiogenesis and ciliogenesis. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the pathogenic role of anti-neutrophil cytoplasmic antibodies (ANCAs) in patients with IgA nephropathy (IgAN). A total of 2390 patients with biopsy-confirmed IgAN were analyzed retrospectively. Thirty-five IgAN patients with ANCA and 40 IgAN patients without ANCA were enrolled. According to the Birmingham Vasculitis Activity Score (BVAS) items, the ANCA-positive patients were further divided into two subgroups which with or without systemic symptoms. The cumulative renal survival rate was calculated using Kaplan-Meier analysis. Comparisons between groups were made using the log rank test. Among the 35 ANCA-positive patients, 14 (40%) had systemic symptoms. Compared with ANCA-positive patients without systemic symptoms, ANCA-positive patients with systemic symptoms had a shorter duration of disease (1.0 [IQR, 0.3-6.8] vs. 6.0 [IQR, 2.0-21.0], P = 0.011); showed worse renal function with lower levels of eGFR (24.2 [IQR, 11.7-74.9] vs. 100.1 [IQR, 59.6-130.2] mL/min/1.73 m2, P = 0.002), serum albumin (30.4 [IQR, 27.4-34.8] vs. 41.5 [IQR, 35.1-44.4] g/L, P = 0.001), and hemoglobin (96.1 ± 21.5 vs. 118.2 ± 22.4 g/L, P = 0.006); and presented relatively higher incidences of rapidly deteriorating kidney function (28.6 vs. 0.0%, P = 0.039) and moderate-to-severe tubular atrophy (78.6 vs. 23.8%, P = 0.001). Kaplan-Meier analysis had shown that ANCA-positive patients with systemic symptoms had lower cumulative renal survival rate compared with both ANCA-positive patients without systemic symptoms and ANCA-negative patients (log rank = 14.40, P < 0.001). Evaluation of systemic symptoms is a simple, readily available clinical tool to predictive the pathogenic role of ANCA in IgAN. [ABSTRACT FROM AUTHOR]

One-dimensional CaMoO:RE (RE = Eu, Sm, Dy, Tb) nanofibers were successfully synthesized through a facile supersaturated recrystallization process. These CaMoO:Ln nanofibers have the length ranging from 40 to 70 nm and the width of nearly 2 nm. Under UV excitation, these single-doped CaMoO nanofibers shown stronger emission, and the photoluminescence quantum efficiency is 25.7% (CaMoO:Eu), 22.4% (CaMoO:Sm), 23.2% (CaMoO:Dy) and 27.7% (CaMoO:Tb), respectively. Moreover, our work reveals that various emission colors can be obtained and tuned from pure red to delight green via co-doping Tb and Eu in the CaMoO host, and the energy transfer properties from Tb to Eu are also demonstrated. Finally, we apply the green CaMoO:Tb, red CaMoO:Eu and white CaMoO:0.05Tb, 0.02Eu for LED devices, and these nanofiber-based LEDs present high efficiency and stability, which indicates the promising application in future optoelectronic fields. [ABSTRACT FROM AUTHOR]

Purpose: Posterior tibial slope that is created during proximal tibial resection in total knee arthroplasty has emerged as an important factor in the mechanics of the knee joint and the surgical outcome. But the ideal degree of posterior tibial slope for recovery of the knee joint function and preventions of complications remains controversial and should vary in different racial groups. The objective of this paper is to investigate the effects of posterior tibial slope on contact stresses in the tibial polyethylene component of total knee prostheses.Methods: Three-dimensional finite element analysis was used to calculate contact stresses in tibial polyethylene component of total knee prostheses subjected to a compressive load. The 3D finite element model of total knee prosthesis was constructed from the images produced by 3D scanning technology. Stresses in tibial polyethylene component were calculated with four different posterior tibial slopes (0°, 3°, 6° and 9°).Results: The 3D finite element model of total knee prosthesis we presented was well validated. We found that the stress distribution in the polythene as evaluated by the distributions of the von Mises stress, the maximum principle stress, the minimum principle stress and the Cpress were more uniform with 3° and 6° posterior tibial slopes than with 0° and 9° posterior tibial slopes. Moreover, the peaks of the above stresses and trends of changes with increasing degree of knee flexion were more ideal with 3° and 6° posterior slopes.Conclusions: The results suggested that the tibial component inclination might be favourable to 7°-10° so far as the stress distribution is concerned. The range of the tibial component inclination also can decrease the wear of polyethylene. Chinese posterior tibial slope is bigger than in the West, and the current domestic use of prostheses is imported from the West, so their demands to tilt back bone cutting can lead to shorten the service life of prostheses; this experiment result is of important clinical significance, guiding orthopaedic surgeon after the best angle to cut bone. [ABSTRACT FROM AUTHOR]

Alumina composites reinforced with multiwalled carbon nanotubes (MWCNTs) at up to 3.7 vol% are prepared by a precursor method followed by a spark plasma sintering. We systematically and quantitatively investigate the effects of acid-treatment time of the MWCNTs on not only bending strength and fracture toughness of the composites but also on the mechanical strength and dispersibility of the MWCNTs, the grain size of the alumina matrix, and the interfacial strength between MWCNT and alumina. The main objective of this study is to evaluate how these parameters influence the mechanical properties with the aid of multiple regression analysis. We demonstrate that the matrix grain size, the mechanical strength of the MWCNTs, and the interfacial strength have little impact on the mechanical properties for the composites prepared in this study. On the other hand, the dispersibility of MWCNTs has the significant influence on the mechanical properties. Both the dispersibility of the MWCNTs and the mechanical properties of the composites increase as the acid-treatment time increases up to 2 h at low MWCNT content (0.9 vol%). Conversely, at a higher amount of MWCNTs, the degradation in the mechanical properties is shown to be associated with the deterioration of MWCNTs' dispersibility. As MWCNT agglomerates are anticipated to act as imperfections, they may override the effects of the strength of MWCNTs, matrix grain size, and interfacial strength. By means of the multiple regression analysis, we quantitatively show that improving MWCNTs' dispersibility is one of the most important factors in enhancing the mechanical properties of MWCNT/alumina composites. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to (1) explore the needs of cancer patients regarding common nursing professional social support from the perspective of physicians and nurses, (2) identify what type of needs clinical nurses actually fulfill and what remains to be improved, and (3) analyze the potential reasons for the gap between the identified needs and those that are fulfilled. Methods: A qualitative approach using focus group interviews was adopted to explore the perception and provision of cancer patients' needs regarding nursing professional social support. A purposive sample of 32 health care professionals was recruited from two teaching hospitals in Anhui province, China. Five focus group interviews were conducted and all interviews were tape-recorded and transcribed verbatim. A content analysis was performed with the data. Results: The healthcare professionals perceived various nursing professional support needs of cancer patients; these include informational, emotional/psychological, and technical support needs; the mobilization of social resources; and palliative care during certain stages. The findings also indicated that there are still many unmet needs, especially needs related to the mobilization of social resources and palliative care. The reasons for the deficiencies in the fulfillment of these needs varied and included both subjective and objective aspects, such as the patients' lack of awareness of how to search for professional support, a shortage of professional staff, and the lack of a culturally appropriate assessment tool. Conclusions: Cancer patients' supportive care needs were not always fully provided by nurses, even when these needs were identified by healthcare professionals. Nursing professional social support needs should be assessed quickly and effectively so that the appropriate interventions can be offered to cancer patients. [ABSTRACT FROM AUTHOR]

One of the most important tasks of evaluating natural resources of petroliferous basins is to determine the organic matter abundance of source rocks in the basin. The usual method for assessing the organic carbon content of source rocks is based on laboratory analyses. There is a deviation in calculating organic carbon content due to the heterogeneous distribution of organic matter and the artificial factors when sampling. According to the continuous characteristics of information logging, the conventional logging curves (mainly acoustics and resistivity, etc.) were calibrated with the organic carbon experimental data of cores, cuttings or sidewall cores. The organic carbon content of source rocks of the 4 (Es) and 3 (Es) members of the Shahejie Formation in western sag in the Liaohe depression was estimated directly by a great amount of continuous data including resistivity and acoustic logging, etc. Comparison between the results from computer processing and lab analysis of logging data shows that the organic carbon contents derived from the computer processing of logging data have the same reliability and accuracy as the lab analysis results. The present data show that this method is suitable to evaluate the source rocks of western sag in the Liaohe depression and has great potential in evaluating natural resources of sedimentary basins in the future. On the basis of logging data of source rocks, experimental data and existing geochemical analyses of the Liaohe Oilfield, the corresponding total organic carbon (TOC) isograms of source rocks were plotted. The source rocks of Es and Es of the Shahejie Formation are thought to be beneficial to hydrocarbon accumulation due to the high TOC. [ABSTRACT FROM AUTHOR]

In this report, the sulfated polysaccharide (SJP) from the body wall of the sea cucumber Stichopus japonicas was extracted and tested for its capacity to affect migration and differentiation of neural stem/progenitor cells. SJP is an intensely sulfated polysaccharide with a molecular weight of 1.79 × 10 Da that is capable of promoting neurosphere attachment and migration in a dose-dependent manner. Moreover, SJP effectively maintains cell viability even after being deprived of mitogens. Our current results demonstrate that neurosphere are differentiated into neuronal and glial cells when exposed to SJP. These effects were accompanied by an up-regulation of the adhesion molecule, N-cadherin. In addition, we observed that blocking of PI3K activity inhibited N-cadherin-mediated activity. This SJP-induced up-regulation of N-cadherin mediates neurosphere adhesion migration and differentiation via the PI3K/Akt signaling pathway. These results suggest that SJP could be used as a therapeutic agent to mobilize neuroblast migration under conditions of brain injury and disease. [ABSTRACT FROM AUTHOR]

Purpose: A successful osseointegration relies on the interplay of implant surface and surrounding bone marrow cells. This study was undertaken to investigate the impact of age and gender on the bone marrow composition.Methods: Bone marrow aspirates were obtained from the discarded metaphysis region of the femoral head in 24 patients with total hip replacement. Flow cytometry was used to measure the expression of Stro-1(+) cells and BMP receptors (BMPRs)-expressing cells. ELISA was used to measure bone marrow aspirate bone morphology protein7 (BMP7) concentration.Results: Our data demonstrates that there are diverse bone marrow profiles (Stro-1(+) cell and BMPRs(+) cells). There are no differences of Stro-1(+) cells, BMPRs(+) cells, and BMP7 concentration between male and female patients. Though there are slight increases in the number of Stro-1(+) cells and BMPRs(+) cells in younger patients (<70 years old) than those of old patients (≥ 70 years old), the difference is not statistically significant. However, we found a close association between the Stro-1(+) cells, BMPR1a cells and BMP7 concentration. In addition, a correlation exists between the number of Stro-1(+) cells and BMIs of these patients.Conclusion: Our data suggests that the age and gender of THR patients have little impact on their bone marrow osteogenic potential. The significance of the number of the Stro-1(+) with BMPRs expression on the implant fixation and osseointegration warrants further investigation. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that amplification and overexpression of the Ki-ras gene is associated with mammary tumor progression in C3(1)/SV40Tag transgenic mice (Liu et al., 1998). To further evaluate the functional significance of the Ki-ras proto-oncogene in mammary cancer development, in vivo studies were conducted to examine the effect of Ki-ras gene dosage on tumor progression. The lack of one normal Ki-ras allele C3(1)/SV40Tag transgenic mice resulted in significantly delayed mammary intraepithelial neoplasia (MIN) formation as well as in a decreased number of mammary gland carcinomas. However, despite the retardation of tumor development by reduced Ki-ras gene dosage, overall survival was only modestly affected. This appears to be due to several factors including significant mammary tumor growth associated with Ki-ras gene amplification and over-expression that occurs during the advanced stage of oncogenesis in mice carrying either one or two normal Ki-ras alleles. The retardation of tumor progression due to the haploid loss of Ki-ras did not appear to be related to accelerated apoptosis, or a reduced rate of cell proliferation at the tumor stages examined. These data strongly suggest that the gene dosage of Ki-ras affects tumor promotion at an early stage of mammary tumor progression in this SV40 Tag-induced model of mammary oncogenesis. Oncogene (2001) 20, 2044–2049. [ABSTRACT FROM AUTHOR]

The 5′ flanking region of the C3(1) component of the rat prostate steroid binding protein (PSBP) has been used to successfully target the expression of the SV40 large T-antigen (Tag) to the epithelium of both the mammary and prostate glands resulting in models of mammary and prostate cancers which histologically resemble the human diseases. Atypia of the mammary ductal epithelium develops at about 8 weeks of age, progressing to mammary intraepithelial neoplasia (resembling human ductal carcinoma in situ [DCIS]) at about 12 weeks of age with the development of invasive carcinomas at about 16 weeks of age in 100% of female mice. The carcinomas share features to what has been classified in human breast cancer as infiltrating ductal carcinomas. All FVB/N female mice carrying the transgene develop mammary cancer with about a 15% incidence of lung metastases. Approximately 10% of older male mice develop anaplastic mammary carcinomas. Unlike many other transgenic models in which hormones and pregnancy are used to induce a mammary phenotype, C3(1)/Tag mice develop mammary tumors in the mammary epithelium of virgin animals without hormone supplementation or pregnancy. Although mammary tumor development appears hormone-responsive at early stages, invasive carcinomas are hormone-independent, which corresponds to the loss of estrogen receptor-α expression during tumor progression. Molecular and biologic factors related to mammary tumor progression can be studied in this model since lesions evolve over a predictable time course. Genomic alterations have been identified during tumor progression, including an amplification of the distal portion of chromosome 6 containing ki-ras and loss of heterozygosity (LOH) in other chromosomal regions. We have demonstrated that stage specific alterations in the expression of genes which are critical regulators of the cell cycle and apoptosis are functionally important in vivo. C3(1)/Tag mice appear useful for testing... [ABSTRACT FROM AUTHOR]