Genetic evaluations for mixed-breed populations

An all-breed animal model was developed for routine genetic evaluations of US dairy cattle. Data sets from individual breeds were combined, and records from crossbred cows were included. About 1% of recent cows were first-generation crossbreds. The numbers of cows with records since 1960 ranged from 10 to 22 million for the 6 traits analyzed, which were milk, fat, protein, somatic cell score, productive life, and daughter pregnancy rate. Programs were modified to account for general heterosis, to group unknown parents separately by breed, to adjust variances separately by breed, and to adjust data to a 36-mo age equivalent instead of a mature equivalent. Convergence rate of the all-breed model was similar to that of the previous within-breed animal model. Estimated breed differences were similar to those obtained previously from phenotypic breed means or from studies of crossbred cows and their herd-mates. Genetic evaluations from the all-breed and within-breed systems had high correlations: >0.99 for recent Holsteins and slightly <0.99 for other breeds. Predicted transmitting abilities will be converted back to the within-breed bases for purebred animals and to the breed of sire base for crossbred animals so that most purebred breeders will not be affected by the change to a multibreed model. Evaluations of crossbred animals from the multibreed model can include accurate information for both parents. Reliabilities also increase for purebred relatives because of the additional crossbred records and in mixed breed herds because cows of other breeds are additional contemporaries. Another benefit of the multibreed model is that breed differences are routinely estimated and updated. More research and education may be needed on using the new evaluations in the design of breeding programs. Implementation is expected in May 2007.     

Development of a national genetic evaluation for cow fertility

A national fertility evaluation was developed based on pregnancy rate, which measures the percentage of nonpregnant cows becoming pregnant within each 21-d opportunity period. Data for evaluation are days open, which are calculated as date pregnant minus previous calving date. Date pregnant is determined from last reported breeding or from subsequent calving minus expected gestation length. Success or failure of last breeding can be confirmed by veterinary diagnosis or a report that the cow was sold because of infertility. Data are adjusted for parity and calving season within geographic region and time period and evaluated. Fertility records are considered complete at 250 d in milk, and lower and upper limits of 50 and 250 d are applied to days open. For calculation of genetic evaluations, days open are converted to pregnancy rate by the linear formula pregnancy rate = 0.25 (233 - days open). Evaluations are expressed as predicted transmitting ability for daughter pregnancy rate, and calculation is done with an animal model. Genetic correlations among several fertility measures and other evaluated traits were estimated from 3 large data sets. Correlation with days open was less for nonreturn rate than for days to first breeding, probably because nonreturn rate had lower heritability. Cow fertility was negatively correlated with yield but is a major component of longevity. Thus, recent selection for longevity may have slowed the long-term decline in fertility. Direct selection for fertility could halt or reverse the decline.     

Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas

Elevated expression of the neurotrophin-3 (NT-3) receptor TrkC by childhood medulloblastomas is associated with favorable clinical outcome. Here, we provide evidence that TrkC is more than simply a passive marker of prognosis. We demonstrate that: (a) medulloblastomas undergo apoptosis in vitro when grown in the presence of NT-3; (b) overexpression of TrkC inhibits the growth of intracerebral xenografts of a medulloblastoma cell line in nude mice; and (c) trkC expression by individual tumor cells is highly correlated with apoptosis within primary medulloblastoma biopsy specimens. TrkC-mediated NT-3 signaling promotes apoptosis by activating multiple parallel signaling pathways and by inducing immediate-early gene expression of both c-jun and c-fos. Considered collectively, these results support the conclusion that the biological actions of TrkC activation affect medulloblastoma outcome by inhibiting tumor growth through the promotion of apoptosis.     

Polymeric display of immunogenic epitopes from herpes simplex virus and transmissible gastroenteritis virus surface proteins on an enteroadherent fimbria

Polydnaviruses are the only known group of mutualistic viruses. They are required for successful parasitization in many braconid and ichneumonid parasitoids. The intimacy of this mutualistic association is indicated by the integration and vertical transmission of polydnaviruses in wasp genomes and by their asymptomatic, developmentally regulated replication. The evolution of this mutualism raises several interesting issues that require a better understanding of the viral genome and viral replication. To develop probes for virus replication and morphogenesis, we have begun to characterize several viral structural proteins. A 699 bp cDNA encoding the p12 viral structural protein was cloned and sequenced. The p12 gene localizes to viral segment Y and encodes a predicted protein of 92 amino acids that does not encode a signal peptide and is unrelated to known peptide or nucleic acid sequences. The p12 mRNA is detected at the onset of virus replication. mRNA titers increase with increasing rates of virus replication. Polyclonal antisera raised against histidine-tagged p12 protein expressed in bacteria reacted specifically with the p12 polypeptide in Western blots of CsPDV virions. The p12 polypeptide was not detected in non-replicative wasp or lepidopteran tissues by Western blot analyses but was readily detected in protein extracts of wasp ovaries. The data indicate that the p12 gene is a viral gene encoding a virion protein and provides a specific probe for virus replication that will be useful for studying the evolution of this group of mutualistic viruses.     

Rat mandibular distraction osteogenesis: II. Molecular analysis of transforming growth factor beta-1 and osteocalcin gene expression

Distraction osteogenesis is a powerful technique capable of generating viable osseous tissue by the gradual separation of osteotomized bone edges. Although the histologic and ultrastructural changes associated with this process have been extensively delineated, the molecular events governing these changes remain essentially unknown. We have devised a rat model of mandibular distraction osteogenesis that facilitates molecular analysis of this process. Such information has significant clinical implications because it may enable targeted therapeutic manipulations designed to accelerate osseous regeneration. In this study, we have evaluated the expression of transforming growth factor beta-1, a major regulator of osteogenesis during endochondral bone formation and development, and osteocalcin, an abundant noncollagenous extracellular matrix protein implicated in the regulation of mineralization and bone turnover. The right hemimandible of 36 adult male rats was osteotomized, and a customized distraction device was applied. Animals were allowed to recover and, after a 3-day latency period, were distracted at a rate of 0.25 mm twice daily for 6 days followed by a 2- or 4-week consolidation period. Distraction regenerate was harvested after the latency period, days 2, 4, or 6 of distraction, and after 2 or 4 weeks of consolidation and processed for Northern analysis (n = 4 at each time point) and immunohistochemical localization of TGF-beta1 (n = 2 at each time point). Six sham-operated animals (i.e., skin incision without osteotomy) were also killed (immediately postoperatively), and the mandibles were harvested and prepared in a similar fashion. Equal loading and transfer of RNA for Northern analysis was ensured by stripping and probing membranes with a probe against GAPDH (a housekeeping gene). Our results demonstrate that the spatial and temporal patterns of TGF-beta1 mRNA expression and protein production coincide with osteoblast migration, differentiation, and extracellular matrix synthesis. In addition, we demonstrate that TGF-beta1 production may be an important regulator of vasculogenesis during mandibular distraction osteogenesis. Finally, we have shown that osteocalcin gene expression coincides temporally with mineralization during rat mandibular distraction osteogenesis.     

Acquisition of incidental information during instruction for a response-chain skill

We examined the acquisition of incidental information and observational learning of incidental information by adolescents with moderate intellectual disabilities during school-directed systematic instruction. Effectiveness of constant time-delay instruction for vocational-skill acquisition was evaluated within a multiple-probe design across six dyads. Dyadic instructional arrangements allowed the assessment of incidental information acquired through observation. The constant time-delay procedure was effective in teaching the target vocational skill. In addition, participants acquired and retained approximately 50% of the incidental information to which they were exposed during the consequent events of constant time-delay instruction either through direct verbal presentation or through observation of their peers' instruction.     

基矛电磁波的低流速测量中干扰因素分析研究

介绍了电磁渡测量流速的基本原理一多普勒效应．分析了影响低流速测量的主要干扰因素一发射泄漏干扰和旁瓣干扰。根据接收信号中发射泄漏干扰不变的特性,提出了去均值滤波的方法来消除干扰,对数据进行预处理;根据旁瓣干扰的信号特性,提出了通过频谱加窗和二次加权平均法构造频域带通滤波器来抑制干扰的方法,在仿真比较完各个窗函数的性能之后,选定布莱克曼窗来进行频谱加窗。仿真分析表明,旁瓣干扰经频域带通滤波后得到了很好的抑制。最后通过实验测试验证了这些方法在流速测量中的显著效果。     

Assessment of antifungal activities of fluconazole and amphotericin B administered alone and in combination against Candida albicans by using a dynamic in vitro mycotic infection model

We evaluated the pharmacodynamic activities of fluconazole and amphotericin B given alone and in combination against Candida albicans by using an in vitro model of bloodstream infection that simulates human serum pharmacokinetic parameters for these antifungals. Fluconazole was administered as a bolus into the model to simulate regimens of 200 mg every 24 h (q24 h) and 400 mg q24 h. Amphotericin B was administered at doses producing the peak concentration (2.4 micrograms/ml) observed with a regimen of 1 mg/kg of body weight q24 h. A combination regimen of fluconazole (400 mg q24 h) and amphotericin B (1 mg/kg q24 h) administered simultaneously and as a staggered regimen (amphotericin B bolus given 8 h after fluconazole bolus) was also simulated in the model to characterize possible antagonism between these agents. Fluconazole alone and amphotericin B alone demonstrated fungistatic (< 99.9% reduction in numbers of CFU per milliliter from the starting inoculum) and fungicidal (> 99.9% reduction) activity, respectively. When fluconazole and amphotericin B were administered simultaneously, fungicidal activity similar to that observed with amphotericin B alone was observed. Staggered administration of fluconazole and amphotericin B, however, resulted in a substantial reduction of the fungicidal activity of amphotericin B, producing fungistatic activity similar to that observed with noncombination fluconazole regimens. These results demonstrate the usefulness of this model for comparing the in vitro pharmacodynamic characteristics of different antifungal regimens and support the theory of azole-polyene antagonism. The effects of this antagonism on the in vivo activity and clinical usefulness of combination antifungal therapy, however, remain to be determined.     

Developing a brief measure of smoking in the home: description and preliminary evaluation

The insulin-like growth factors (IGF-I and IGF-II) play a key role in cellular proliferation and are involved in cellular transformation. The expression of the IGF-I receptor has been demonstrated in a variety of human tumor cell lines including ovarian cancer cells. Phosphorothioate antisense oligodeoxynucleotides (S-ODNs) were analyzed for their potential to suppress the IGF-I receptor in the NIH: OVCAR-3 ovarian cancer cell line. The application of the antisense S-ODN reduced potently the cell growth of unstimulated NIH:OVCAR-3 cells, whereas sense and mismatch S-ODNs were without any effect. This effect resembled that of the monoclonal antibody (MAb) alphaIR-3. In contrast to the antisense compound, this MAb only partially inhibited the IGF-I-induced proliferation of ovarian cancer cells. The concentration of the antisense S-ODN to exhibit an identical inhibition of cell proliferation was reduced to 50 nM when the oligonucleotides were delivered by the cationic lipid formulation lipofectin. The specificity of the antisense S-ODN action was confirmed by reduction of the receptor protein and of the receptor mRNA, as assayed by flow cytometry and by Northern blot hybridizations. Our data demonstrate the potency of antisense S-ODNs to target the IGF-I receptor message and show that antisense strategies against the IGF-I receptor may provide new strategies for the therapy of ovarian cancer.