Expression of CCAAT/Enhancer Binding Proteins (C/EBP) is Associated with Squamous Differentiation in Epidermis and Isolated Primary Keratinocytes and is Altered in Skin Neoplasms

The epidermis is a stratified squamous epithelium composed primarily of keratinocytes that undergo sequential changes in gene expression during differentiation. CCAAT/enhancer binding proteins (C/EBP) are members of the bZIP family of DNA binding proteins/transcription factors. Northern analysis demonstrated that C/EBPα, C/EBPβ, and C/EBPδ mRNA are expressed in mouse epidermis and their mRNA levels were generally greater than those observed in other tissues known to express high levels of C/EBP. Western analysis of isolated epidermal cell nuclei demonstrated the presence of a 42 and 30 kDa C/EBPα protein and 35 kDa C/EBPβ protein. Immunohistochemical localization of C/EBPα and C/EBPβ in intact interfollicular epidermis revealed that C/EBPβ expression is exclusive to the nuclei of a three-cell cluster of suprabasal keratinocytes that is morphologically consistent with the central column of the epidermal proliferative unit, and that C/EBPα is expressed in the nuclei and cytoplasm of suprabasal keratinocytes and weakly expressed in a perinuclear manner in some basal keratinocytes. In squamous cell carcinomas the expression of C/EBPα and C/EBPβ was greatly diminished as both the intensity of nuclear staining and the number of cells expressing C/EBPα and C/EBPβ were reduced. In isolated primary mouse keratinocytes, calcium-induced differentiation was accompanied by specific temporal changes in the expression of C/EBPα, C/EBPβ, and C/EBPδ mRNA and C/EBPα and C/EBPβ protein. These results implicate a role for the C/EBP family in the regulation of genes involved in or specifically expressed during the process of squamous differentiation in epidermis

Effects of 17-β-Estradiol and ICI 182 780 on Hair Growth in Various Strains of Mice

17-β-Estradiol (10nmol per 200 μ1 acetone) applied topically twice weekly to the clipped dorsal surface of C57BL/6 or C3H female mouse skin prevented hair growth, as previously described in the CD-1 mouse strain. Twice weekly topical application of the estrogen receptor antagonist, ICI 182 780 (10nmol per 200 μ1 acetone), induced the telogenanagen transition and produced early pigmentation appearance in skin and hair growth in C57BL/6 and C3H female mice. Whereas twice weekly topical application of 10nmol 17-β-estradiol blocked hair growth, the intraperitoneal administration of this dose twice weekly did not block hair growth, suggesting a direct cutaneous effect of 17-β-estradiol. We also evaluated the effect of 17-α-estradiol, 17-β-estradiol, and ICI 182 780 on hair growth in male mice. As observed in female mice, 17-β-estradiol was a potent inhibitor of hair growth and ICI 182 780 stimulated hair growth; however, unlike the results previously observed in female mice, 17-α-estradiol was a potent inhibitor of hair growth in male mice. These results demonstrate that (i) the route of administration of 17-β-estradiol is critical for its ability to block hair growth; (ii) C57BL/6 and C3H mice, two commonly employed mouse strains for hair growth studies, responded to 17-β-estradiol and ICI 182 780 in a manner similar to that described in CD-1 mice; and (iii) the hair follicles of male and female mice respond similarly to 17-β-estradiol and ICI 182 780, but display striking sex differences in the response to 17-α-estradiol on hair growth

Effect of dietary ascorbate on covalent binding of benzene to bone marrow and hepatic tissue in vivo

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26047/1/0000120.pd

Novel DNA methylation profiles associated with key gene regulation and transcription pathways in blood and placenta of growth-restricted neonates

BB/H012494/1/ Biotechnology and Biological Sciences Research Counci

C/EBPα and C/EBPβ Are Required for Sebocyte Differentiation and Stratified Squamous Differentiation in Adult Mouse Skin

C/EBPα and C/EBPβ are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPα and C/EBPβ in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPα or C/EBPβ alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPα and C/EBPβ in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPα and C/EBPβ in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3) and melanocortin 5 receptor (MC5R), two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPα and C/EBPβ are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal

Release from sheep-grazing appears to put some heart back into upland vegetation:A comparison of nutritional properties of plant species in long-term grazing experiments

Rewilding or wilding is a popularised means for enhancing the conservation value of marginal land. In the British uplands, it will involve a reduction, or complete removal, of livestock grazing (sheep), based on the belief that grazing has reduced plant species diversity, the ‘Wet Desert’ hypothesis. The hope is that if livestock is removed, diversity will recover. If true, we hypothesise that the species extirpated/reduced by grazing and then recover on its removal would more nutritious compared to those that persisted. We test this hypothesis at Moor House National Nature Reserve (North‐Pennines), where seven sets of paired plots were established between 1953 and 1967 to compare ungrazed/sheep‐grazed vegetation. Within these plot‐pairs, we compared leaf properties of seven focal species that occurred only, or were present in much greater abundance, in the absence of grazing to those of 10 common species that were common in both grazed and ungrazed vegetation. Each sample was analysed for macro‐nutrients, micro‐nutrients, digestibility, palatability and decomposability. We ranked the species with respect to 22 variables based on effect size derived from Generalised Linear Modelling (GLM) and compared species using a Principal Components Analysis. We also assessed changes in abundance of the focal species through time using GLMs. Our results support the ‘Wet Desert’ hypothesis, that is, that long‐term sheep grazing has selectively removed/reduced species like our focal ones and on recovery, they were more nutritious (macro‐nutrients, some micro‐nutrients) palatable, digestible and decomposable than common species. Measured changes in abundance of the focal species suggest that their recovery will take 10–20 years in blanket bog and 60 years in high‐altitude grasslands. Collectively, these results suggest that sheep grazing has brought about biotic homogenization, and its removal in (re)wilding schemes will reverse this process eventually! The ‘white woolly maggots’ have eaten at least part of the heart out of the highlands/uplands, and it will take some time for recovery

Cost analysis and outcomes of endoscopic, minimal access and open pancreatic necrosectomy.

To assess both individual patient and institutional costs as well as outcomes in patients with pancreatic necrosis who underwent either endoscopic, minimal access or open pancreatic necrosectomy. These data can be used to evaluate clinical effectiveness with a view to informing local health care providers. Intervention for infected pancreatic necrosis is associated with a high morbidity, mortality and long hospital stays. Minimal access surgical step-up approaches have been the gold standard of care, however endoscopic approaches are now offered preferentially. All patients undergoing endoscopic (EN), minimal access retroperitoneal (MARPN) and open (OPN) necrosectomy at a single institution from April 2015-March 2017 were included. Patients were selected for intervention based on morphology and position of the necrosis and on clinical factors. Patient level costing systems were used to determine inpatient and outpatient costs. 86 patients were included: 38 underwent EN, 35 MARPN and 13 OPN. Pre-operative APACHEII was 6 vs 9 vs 9 (p=0.017) and CRP 107 vs 204 vs 278, (p=0.012), respectively. Post-operative stay was 19 days for EN vs. 41 for MARPN vs. 42 for OPN (p=0.007). Complications occurred in 68.4%, 68.6% and 46.2% (p=0.298) while mortality was 10.5%, 22.9% and 15.4% (p=0.379) respectively. Mean total cost was £31,364 for EN, £52,770 for MARPN (p=0.008) and £60,346 for OPN. Ward and critical care costs for EN were lower than for MARPN (ward: £9,430 vs. £14,033, p=0.024; critical care: £5,317 vs. £16,648, p=0.056)