No abstract

To obtain additional data concerning uranium mining and nonmalignant respiratory diseases, we conducted a prevalence survey of 192 long-term New Mexico uranium miners. Survey procedures included spirometry, completion of a respiratory symptoms questionnaire, physical examination and interpretation of available chest x rays. Total duration of underground uranium mining was used as the exposure index. Of the major respiratory symptoms, only the prevalence of dyspnea increased significantly with duration of uranium mining. With linear multiple-regression analysis, small but statistically significant effects of mining were found for two spirometric parameters, the forced expiratory volume in one sec and the maximal midexpiratory flow. By the 1980 International Labor Organization (ILO) U/C classification, 12 of 143 participants with x rays available for interpretation had at least category 1/0 pneumoconiosis. The opacities were predominantly nodular and compatible with silicosis.

Four batches of ear-rot damaged maize grain and a batch of reportedly sound maize were assessed by rat and pig growth assay and digestibility determination in pigs. All batches were the yellow hybrid, Dekalb XL81, except one which was a white variety, Dekalb DS456W. The fungus most frequently isolated from damaged kernels was Fusarium monilifome, with the exception of one batch where Diplodia maydis was equally prevalent. Traces of aflatoxin were detected in two samples but ochratoxin A, sterigmatocystin, zearalenone, T-2 toxin, deoxynivalenol, nivalenol, diacetoxyscirpenol and moniliformin were not detected. In the growth assays, no illness was apparent in any of the rats but scouring, vomiting and a persistent and generalized muscle tremor were observed in a number of pigs. Diets based on sound maize resulted in better (P < 0.05) growth performance of both rats and pigs than those based on mouldy maize. The apparent digestibility of the sound maize was better than each batch of mouldy yellow maize, but no better than the batch of mouldy white maize. Differences in nutritive value between the batches of maize were more closely related to the degree of fungal damage and the nature of the endosperm than to either the proximate chemical or amino acid composition of the grain. The muscle tremor observed in some pigs might have been due to undetected mycotoxins.

The responses of Hyline (WLxNH) and Tegel (WLxAO) strain laying hens offered six 'response' diets ranging in isoleucine content from 2.8 to 8.6 g kg-1 were examined. The required range of isoleucine content was obtained by formulating a summit diet containing a surplus of all essential amino acids, but a lesser surplus of isoleucine, and blending it in appropriate proportions with a basal diet, structured similarly to the summit diet, but deficient in all essential amino acids and protein. To test that isoleucine was the first limiting nutrient in the 'response' diets, an additional six 'test' diets were given. These were identical to the 'response' diets except for the addition of L-isoleucine which raised the total isoleucine content of each by an amount equivalent to the difference between two adjacent 'response' treatments. The 12 diets were given from 30 to 46 weeks of age (phase 1) and again from 54 to 70 weeks of age (phase 2) following an intervening recovery period. Responses to the diets, determined on data from the final 4 weeks of each phase, were attributed to differences in isoleucine intake. The apparent efficiencies of utilization of isoleucine for egg synthesis and for maintenance were similar for both strains. The daily isoleucine requirement of individual laying hens was estimated to be 9.91 mg g-l egg output plus 33.56 mg kg-1 liveweight per day. Curves describing the egg output response to isoleucine intake were calculated using the Reading model and optimum isoleucine intakes were derived for various liveweights, egg outputs and ratios of input costs and output values. For example, for a flock of hens with an average weight of 2 kg and producing an average of 50 g daily egg mass, the optimum isoleucine intake varied between 581 and 684 mg d-l.

23As CDK13 mel acts via a dominant negative mechanism and no CDK13 mel mutations are 126 observed in the Cyclin binding domain, we hypothesized that Cyclin binding is required for 127 CDK13 mel dominant negative activity. To test whether the canonical CDK13 Cyclin, 128 CCNK 18,22,23 , or the related CCNT1 are required for CDK13 mel dominant negative 129 melanomagenesis in vivo, we co-injected vectors that express melanocyte-specific CDK13 mel and 130 melanocyte-specific CRISPR of ccnK or ccnT1 in the mitfa -/-; BRAF; p53 -/zebrafish melanoma 131 model. ccnK melanocyte-specific CRISPR expedited melanoma in the presence of CDK13 W878L , 132 but not alone ( Figure S1L-M). ccnT1 melanocyte-specific CRISPR suppressed CDK13 W878L and 133 CDK13 R860Q oncogenesis but had no effect by itself ( Figure 1K-L, S1O). PCR across the 134 CRISPR cut site confirmed indels directed by the ccnT1, ccnK, and control gRNAs (Figure 135 S1N). These data indicate that CDK13 mel oncogenesis requires CCNT1 for its dominant negative 136 oncogenic activity. 137 Mutant CDK13 binds chromatin in a dominant negative manner. 138As CDK13 is localized in the nucleus 24 and CDK13 WT can phosphorylate the RNAPII 139