Non‐nutritional uses of food in traditional Appalachian culture

Food has both nutritional and non‐nutritional functions and this paper reports some non‐nutritional uses of food in traditional Appalachian culture. The emphasis is upon occult and non‐occult uses of food in folk medicine. Specific examples of rituals are presented as collected in Appalachia. It is suggested that these traditions have been maintained due to the strength of the reference groups.     

Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts

Mice deficient in Schnurri-3 (SHN3; also known as HIVEP3) display increased bone formation, but harnessing this observation for therapeutic benefit requires an improved understanding of how SHN3 functions in osteoblasts. Here we identified SHN3 as a dampener of ERK activity that functions in part downstream of WNT signaling in osteoblasts. A D-domain motif within SHN3 mediated the interaction with and inhibition of ERK activity and osteoblast differentiation, and knockin of a mutation in Shn3 that abolishes this interaction resulted in aberrant ERK activation and consequent osteoblast hyperactivity in vivo. Additionally, in vivo genetic interaction studies demonstrated that crossing to Lrp5^–/– mice partially rescued the osteosclerotic phenotype of Shn3^–/– mice; mechanistically, this corresponded to the ability of SHN3 to inhibit ERK-mediated suppression of GSK3β. Inducible knockdown of Shn3 in adult mice resulted in a high–bone mass phenotype, providing evidence that transient blockade of these pathways in adults holds promise as a therapy for osteoporosis.     

Work Problems and Accommodations Reported by Persons Who Are Postpolio or Have a Spinal Cord Injury

A number of studies have documented early functional declines in persons with a disability. The purpose of this study was to document (1) whether employees who are aging with their disability have experienced new work problems as a consequence of functional declines and (2) whether their work problems are being accommodated adequately. Ninety-six individuals with a disability (50 who are postpolio and 46 who had a spinal cord injury) were interviewed by phone. Each had worked at least 5 years postonset and was either currently working or unemployed for less than 5 years at the time of the interview. Forty-nine of the 50 persons who are postpolio reported they had experienced functional declines in recent years, and 41 of the 50 rated the severity of their disability greater than it was when they first began working. As a result of the functional declines they had experienced, most (90.9%) of their work problems were new and would not have been significant problems for them when they first began working. The situation was very different for the group with spinal cord injuries. Only a few members of that group had experienced functional declines that were causing new problems at work. A total of 480 work problems were reported by study participants. Three out of every eight problems did not have an accommodation satisfactory to the employee. The primary reason why a satisfactory solution was not provided was that no accommodation had been identified. Employers were generally supportive of the employee's need for accommodation; they paid for 59.1% of the accommodations that had a cost and refused to provide an accommodation for only 18 of the 480 problems.     

Comparative analysis of genes regulated by PML/RAR alpha and PLZF/RAR alpha in response to retinoic acid using oligonucleotide arrays

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations involving retinoic acid receptor alpha (RAR alpha) and its fusion partners including promyelocytic leukemia (PML) and promyelocytic leukemia zinc finger (PLZF). Using oligonucleotide arrays, we examined changes in global gene expression mediated by the ectopic expression of either PML/RAR alpha (retinoid-sensitive) or PLZF/RAR alpha (retinoid-resistant) in U937 cells. Of more than 5000 genes analyzed, 16 genes were commonly up-regulated, and 57 genes were down-regulated by both fusion proteins suggesting their role in the APL phenotype. In our APL model, for example, TNFAIP2, TNFR2, ELF4, RAR gamma, and HoxA1 were down-regulated by both fusion proteins in the absence of retinoic acid (RA). RA strongly up-regulated these genes in PML/RAR alpha, but not in PLZF/RAR alpha expressing U937 cells. Expression studies in NB4, retinoid-resistant NB4-R2, normal human CD34+ cells, and APL patient samples strongly suggest their role in the regulation of granulocytic differentiation. Furthermore, combined treatment with tumor necrosis factor alpha (TNF alpha) and RA synergistically enhanced granulocytic differentiation in NB4 cells but not in NB4-R2 cells. Our data indicate that APL pathogenesis and retinoid-induced granulocytic differentiation of APL cells involve genes in the cell death pathway, and that cooperation between the RA and TNFalpha signaling pathways exists. Targeting both the retinoid-dependent differentiation and the cell death pathways may improve leukemic therapy, especially in retinoid-resistant acute myeloid leukemia.