Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity.

Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

Dislocation of the coxo-femoral joint in dairy cows.

Coxo-femoral dislocation was diagnosed in 40 dairy cows. Of the 40 cases, 19 were in a cranio-dorsal direction, 2 caudo-dorsal, 17 caudo-ventral (into the obturator foramen), and 2 cranio-ventral. Thirty cases (75%) were successfully treated by closed reduction. Most cows were treated within 12 h of the dislocation occurring. Treatment was less successful in cases of caudo-ventral dislocation and unsuccessful cases predominated among cows with concurrent obstetrical paralysis or milk fever, and very heavy Friesians.

Evaluation of a regimen using a progesterone releasing intravaginal device (CIDR) and PMSG as a treatment for post partum anoestrus in dairy cattle.

Anoestrous dairy cows in seasonally calving herds in the Macalister Irrigation District of Gippsland, Victoria were treated at the start of the mating period with a progesterone releasing intravaginal device (CIDR). The CIDR was inserted for 7 days and 400 IU of PMSG was injected intramuscularly at removal. There was no clinically useful difference among cows receiving the CIDR, a placebo and untreated cows in the interval from treatment to either first oestrus or conception, the conception rate to first service or percent pregnant by the end of mating. Analyses of data from 2-year-old cows, older cattle, cows calved at least 45 days or cows calved at least 55 days and cows treated 3 weeks after the start of mating did not show improved reproductive performance following treatment with the CIDR.

A clinical trial using a regimen which includes a norgestomet implant and norgestomet plus oestradiol valerate injection as a treatment for anoestrus in dairy cows.

In seasonally calving dairy herds in the Macalister Irrigation Area of Gippsland, Victoria, cows that had not been observed in oestrus by the start of the mating season and which had inactive ovaries based on rectal palpation and progesterone assay were treated with a hormonal treatment (n = 49). Mature cows had calved at least 40 days previously and 2-year-olds had been calved at least 60 days. The treatment consisted of a norgestomet implant and a norgestomet and oestradiol injection on day 1; prostaglandin analogue Prosolvin) on day 8; withdrawal of implant on day 10 and an injection of PMSG; and fixed time artificial insemination 54 to 56 h after implant withdrawal. This treatment was called the Syncro-mate regimen. Control cows (n = 46) were injected with water on days 1, 8 and 10 and artificially inseminated or served by a bull when seen on heat. Forty seven percent of the treated cows became pregnant within 14 days from the start of treatment compared with 20% of control cows (P less than 0.01). There was an effect of age group on the response to treatment. A greater proportion of 2-year-old cows than mature cows became pregnant within 14 days of treatment (79% of 19 v. 27% of 20; Chi square interaction, treatment by age, 6.4, P less than 0.05). In the younger cows there was also a gain of 22 days in the treatment to conception interval over the control cows (P less than 0.001). It was concluded that the Syncro-mate regimen can be an effective treatment for post partum anoestrus in dairy cows under certain conditions.

Investigation of purulent vaginal discharge in cows, with particular reference to Haemophilus somnus.

The relationship between vaginal discharge, site of inflammation in the reproductive tract and species of bacteria isolated was examined in cows that were either normal, subfertile, or had had an abnormal parturition. Microbiological and cytological examinations were performed on uterine swabs from 221 cows and cervical swabs from 107 cows. There were 167 subferitle cows, 144 of which had failed to conceive to 3 or more services (FTC) and 23 of which had not had a visible oestrus since calving (NVO). Metritis was diagnosed in 22% of the FTC cows, 48% of the NVO cows, and 12% of the cows with abnormal parturition. Fifty percent of cows with metritis had purulent vaginal discharge. However, only 25% of a total of 91 cows with vaginal discharge had metritis; the remainder had cervicitis. Fifty-four percent of subfertile cows had cervicitis without metritis. Mixed infection with aerobes and anaerobes was significantly correlated with uterine inflammation and was found in 20% of cows with metritis. The rate of isolation of H.somnus from inflamed uteruses (22%) and inflamed cervixes (39%) was significantly greater than the isolation rate from normal uteruses (8%) and cervixes (10%). No bacteria were isolated from 50% of inflamed uteruses and 37% of inflamed cervixes. The number of subfertile cows with or without metritis that subsequently conceived was not significantly different.