Ectopic Expression of Zmiz1 Induces Cutaneous Squamous Cell Malignancies in a Mouse Model of Cancer

Cutaneous squamous cell carcinoma (SCC) is the second most common form of cancer in the human population, yet the underlying genetic mechanisms contributing to the disease are not well understood. We recently identified Zmiz1 as a candidate oncogene in nonmelanoma skin cancer through a transposon mutagenesis screen. Here we show that transposon-induced mutations in Zmiz1 drive expression of a truncated transcript that is similar to an alternative endogenous ZMIZ1 transcript found to be overexpressed in human SCCs relative to normal skin. We also describe an original mouse model of invasive keratoacanthoma driven by skin-specific expression of the truncated Zmiz1 transcript. Unlike most mouse models, Zmiz1-induced skin tumors develop rapidly and in the absence of promoting agents such as phorbol esters. In addition, we found that the alternative Zmiz1 isoform has greater protein stability than its full-length counterpart. Finally, we provide evidence that ZMIZ1 is overexpressed in a significant percentage of human breast, ovarian, and colon cancers in addition to human SCCs, suggesting that ZMIZ1 may play a broader role in epithelial cancers

Appalachian Transition: A cross sector approach to regional transition.

Appalachia is made up of many mountains, many communities and many different sectors of work. The Appalachian Transition Fellows based out of the Highlander Education Center have spent 9 months working throughout central Appalachia to build cross sector bridges and to help further a positive growth in the region’s economy. Through the fellowship people are working with different models of transition, including value chains, worker owner cooperatives, local food initiatives, policy making, etc. In this session we will be breaking out into different groups each led by one or two fellows to talk about various ways these different models could be beneficial in different communities in Appalachia. There is value in working not only across county and state lines, but also working across economic sector boundaries. This is a workshop to understand the different models being used and to further discuss how to growth between these models for a more diverse and stronger Appalachian economy

Characterisation and quantification of changes in odorants from litter headspace of meat chickens fed diets varying in protein levels and additives

The effect of dietary crude protein (CP) and additives on odor flux from meat chicken litter was investigated using 180 day-old Ross 308 male chicks randomly allocated to five dietary treatments with three replicates of 12 birds each. A 5 × 3 factorial arrangement of treatments was employed. Factors were: diet (low CP, high CP, high CP+antibiotic, high CP+probiotic, high CP+saponin) and age (15, 29, 35 days). The antibiotic used was Zn bacitracin, the probiotic was a blend of three Bacillus subtilis strains and the saponin came from a blend of Yucca and Quillaja. Odorants were collected from litter headspace with a flux hood and measured using selective ion flow tube mass spectrometry (SIFT-MS). Litter moisture, water activity (Aw), and litter headspace odorant concentrations were correlated. The results showed that low CP group produced lower flux of dimethyl amine, trimethyl amine, H2S, NH3, and phenol in litter compared to high CP group (P < 0.05). Similarly, high CP+probiotic group produced lower flux of H2S (P < 0.05) and high CP+saponin group produced lower flux of trimethylamine and phenol in litter compared to high CP group (P < 0.05). The dietary treatments tended (P = 0.065) to have higher flux of methanethiol in high CP group compared to others. There was a diet × age interaction for litter flux of diacetyl, 3-hydroxy-2-butanone (acetoin), 3-methyl-1-butanol, 3-methylbutanal, ethanethiol, propionic acid, and hexane (P < 0.05). Concentrations of diacetyl, acetoin, propionic acid, and hexane in litter were higher from low CP group compared to all other treatments on d 35 (P < 0.05) but not on d 15 and 29. A high litter moisture increased water activity (P < 0.01) and favored the emissions of methyl mercaptan, hydrogen sulfide, dimethyl sulfide, ammonia, trimethyl amine, phenol, indole, and 3-methylindole over others. Thus, the low CP diet, Bacillus subtilis based probiotic and the blend of Yucca/Quillaja saponin were effective in reducing the emissions of some key odorants from meat chicken litter

Interactive effect of 2 dietary calcium and phytase levels on broilers challenged with subclinical necrotic enteritis: part 1 - broiler performance, gut lesions and pH, bacterial counts, and apparent ileal digestibility

This study investigated the hypothesis that high dietary calcium (Ca) would stimulate necrotic enteritis (NE) and reduce performance, gut health, and nutrient digestibility, and if increased, phytase would reduce NE. Ross 308 male broilers (n = 768) were randomly distributed to 8 treatments in a factorial arrangement. Factors were NE challenge (no or yes), phytase level (500 or 1,500 FTU/kg using 500 FTU/kg matrix values), and Ca level (0.6 or 1.0% starter, 0.5 or 0.9% grower, 0.4 or 0.8% finisher) with the same level of available P (0.40 S, 0.35 G, and 0.35 F). There were 48 pens, 16 birds per pen and 6 replications. Half of the birds were challenged with Eimeria spp on day 9 and 108 CFU per mL of Clostridium perfringens strain EHE-NE18 on day 14 and 15. Gain was higher in birds fed high phytase on day 14 (P P P P P P AID) of crude protein (CP) (P P C. perfringens count, but it decreased Lactobacillus (P Bifidobacteria (

Interactive effect of dietary calcium and phytase on broilers challenged with subclinical necrotic enteritis: 3. Serum calcium and phosphorus, and bone mineralization

Calcium is chelated by phytic acid and forms phytate-mineral complexes reducing Ca availability and the ability of phytase to hydrolyze phytate. An increased Ca concentration in the gut favors the activity of Clostridium perfringens (C. perfringens). Therefore, it was hypothesized that high dietary calcium with high dietary phytase would decrease serum Ca and P and bone mineralization during necrotic enteritis occurrence. A total of 768 one-day-old Ross 308 male chicks were randomly allocated to 8 treatments with 6 replicate pens, each housing 16 birds. A 2 × 2 × 2 factorial arrangement of treatments was applied: dietary Ca (0.6 or 1.0%), phytase (500 or 1,500 FTU/kg), and challenge (no or yes). Half of the birds (384) were challenged with Eimeria spp. on day 9 and C. perfringens strain EHE-NE18 on day 14 and 15. Blood was collected from 2 birds per pen to determine Ca, P, and parathyroid hormone in the serum. The middle toe, tibia, and femur were excised from 2 birds per pen on day 16 and 29 for determination of ash, breaking strength (BS), and mineral concentration. The challenge decreased (P + in birds regardless of dietary Ca level (day 16). There was a challenge × Ca interaction (P P P P P P

Over-processed meat and bone meal and phytase effects on broilers challenged with subclinical necrotic enteritis: Part 3. Bone mineralization and litter quality

This study was conducted to determine the effect of necrotic enteritis (NE), phytase level and meat and bone meal (MBM) processing on bone mineralization of broilers and litter quality. Ross 308 male broiler chicks (n = 768) were allotted to 48 pens with 16 birds each. There were 8 dietary treatments in a 2 × 2 × factorial arrangement. Factors were NE challenge (no or yes), phytase level (500 or 5,000 FTU/kg), and MBM (as-received or over-processed). Half of the birds were challenged with field strains of Eimeria spp. at d 9 and 108 CFU per mL of Clostridium perfringens strain EHE-NE18 on d 14 and 15. The middle toe, tibia and femur of 2 birds per pen were excised at d 16 and 29 for determination of ash, breaking strength (BS) and bone mineralization. At d 42, all were assessed for hock burns and litter was scored and assessed for dry matter (DM). At d 16, challenged birds had lower toe ash (P P P P P P P P P P P = 0.058) and fewer hock burns than those unchallenged (

Necrotic enteritis challenge and high dietary sodium level affect odorant composition or emission from broilers

Necrotic enteritis (NE) challenge and high dietary sodium (from sodium chloride) level on odor flux from broiler litter was investigated using 160 day-old Ross 308 male chicks randomly assigned to 4 dietary treatments with 4 replicates of 10 birds each. A 2 × 2 factorial arrangement of treatments was employed. Factors were: presence or absence of NE challenge and normal (1.6 g/kg) or high (4.0 g/kg) dietary sodium (Na) level. On d 20, odorants were collected from litter headspace with a flux hood and measured using selected ion flow tube mass spectrometry (SIFT-MS). On d 33, while challenge did not lead to higher mortality, it reduced feed intake by 5.48% (P P P P P P P P P = 0.05), butyric acid (P P P = 0.07), carbon disulfide (P = 0.09), indole (P = 0.10), and formic acid (P = 0.10) compared to the unchallenged group. The birds fed a high Na diet produced higher litter moisture (P P P P P P P P P

Volatile basic nitrogen measurement in digesta using a Berthelot reaction in automated Skalar instrumentation

The undigested nitrogenous fraction entering the hindgut of chickens is further metabolized by microbiota present producing volatile basic metabolites including amines and ammonia (NH3). Ammonia increases pH and may result in overgrowth of Clostridium perfringens further producing toxic metabolites that cause dysbacteriosis or necrotic enteritis (NE). There are few reports in chickens examining the production and concentration of nitrogenous metabolites in the hindgut. A Berthelot reaction using an automated flow, reaction and spectrophotometric instrumentation to detect volatile basic nitrogen in the form of NH3 from cecal contents was carried out. In the Berthelot reaction, NH3 in the sample is chlorinated to monochloramine using dichloroisocyanuric acid that then reacts with salicylate to form 5-aminosalicylate which is stable under alkaline conditions (pH 12 to 13). After oxidation and oxidative coupling, a coloured complex is formed that can be measured at 660 nm. Cecal contents were collected and pooled from 2 birds per pen with 48 pens total in each of 3 experiments and stored in sealed containers at −20 °C prior to analysis. Experiment 1 compared samples collected from birds fed either no meat and bone meal (MBM) or 6% MBM from d 0 to 14, and samples collected from birds fed either no MBM or 5% MBM from d 14 to 42. All birds were challenged with Eimeria on d 9 and C. perfringens on d 14 and 15. Experiment 2 compared cecal contents from birds fed either 0.5% or 0.9% calcium (Ca), and Exp. 3 compared unchallenged with NE challenge on d 16 and 29. Results demonstrated an increase (

Over-processed meat and bone meal and phytase effects on broilers challenged with subclinical necrotic enteritis: Part 1. Performance, intestinal lesions and pH, bacterial counts and apparent ileal digestibility

This feeding study investigated the hypothesis that over-processing of meat and bone meal (MBM) would impair the performance, gut health and ileal digestibility of nutrients in birds challenged with necrotic enteritis (NE). The effect of phytase (500 vs. 5,000 FTU/kg) was also examined using manufacturers recommended matrix values for 500 FTU for both levels. Ross 308 male broilers (n=768) were assigned to 8 diets, with 6 replicate pens per diet and 16 birds per replicate pen using a randomized design with a factorial arrangement of treatments. Factors were NE challenge (no or yes), MBM (as received or over-processed), and phytase level (500 or 5,000 FTU/kg). Half of the birds were challenged with 5,000 oo-cysts offield strains of Eimeria acervulina and Eimeria brunetti, and 2,500 oocysts of Eimeria maxima on d 9 and 108 CFU/mL of Clostridium perfringens strain EHE-NE18 on d 14 and 15 post-hatch. Challenge × MBM interactions were detected for weight gain (WG), feed conversion ratio (FCR) and feed intake (FI) at d 14, 21 and 28, showing that challenged birds fed over-processed MBM had decreased WG (PPPPP&gt;0.05) at d 28. Birds fed low phytase had increased livability (0.05) at d 28. Birds fed low phytase had increased livability (PPPPPPPPPLactobacillus spp. (PC. perfringens(