X-linked hypophosphatemia(XLH)represents the most common form of familial hypophosphatemia.Although significant advances have been made in the treatment of bone pathology,patients undergoing therapy continue to experi...X-linked hypophosphatemia(XLH)represents the most common form of familial hypophosphatemia.Although significant advances have been made in the treatment of bone pathology,patients undergoing therapy continue to experience significantly decreased oral health-related quality of life.The following study addresses this persistent oral disease by further investigating the effect of DMP1 expression on the differentiation of XLH dental pulp cells.Dental pulp cells were isolated from the third molars of XLH and healthy controls and stable transduction of full-length human DMP1 were achieved.RNA sequencing was performed to evaluate the genetic changes following the induction of odontogenic differentiation.RNAseq data shows the upregulation of inhibitors of the canonical Wnt pathway in XLH cells,while constitutive expression of full-length DMP1 in XLH cells reversed this effect during odontogenic differentiation.These results imply that inhibition of the canonical Wnt pathway may contribute to the pathophysiology of XLH and suggest a new therapeutic strategy for the management of oral disease.展开更多
This work examines the physiologic basis of stress tolerance in bacterial strains of the genus Rhodanobacter that dominate in the acidic and highly metal contaminated near-source subsurface zone of the Oak Ridge Integ...This work examines the physiologic basis of stress tolerance in bacterial strains of the genus Rhodanobacter that dominate in the acidic and highly metal contaminated near-source subsurface zone of the Oak Ridge Integrated Field Research Challenge(ORIFRC)site.Tolerance of R.denitrificans to levels of different stresses were studied in synthetic groundwater medium and R2A broth.Two strains of R.denitrificans,strains 2APBS1T and 116-2,tolerate low to circumneutral pH(4–8),high Uranium(1 mmol/L),elevated levels of nitrate(400 mmol/L)and high NaCl(2.5%).A combination of physiologic traits,such as growth at low pH,increased growth in the presence of high organics concentration,and tolerance of high concentrations of nitrate,NaCl and heavy metals is likely responsible for dominance of Rhodanobacter at the ORIFRC site.Furthermore,extended incubation times and use of low carbon media,better approximating site groundwater conditions,are critical for accurate determination of stress responses.This study expands knowledge of the ecophysiology of bacteria from the genus Rhodanobacter and identifies methodological approaches necessary for acquiring accurate tolerance data.展开更多
基金our funding sources U.S.Department of Health&Human Services,NIH,NIDCR T32 DE018381[Multidisciplinary Oral Science Training Program]DE028193[E.G.]+1 种基金R01 DE031737 and DE 028531[A.G.]the Brodie Endowment Fund。
文摘X-linked hypophosphatemia(XLH)represents the most common form of familial hypophosphatemia.Although significant advances have been made in the treatment of bone pathology,patients undergoing therapy continue to experience significantly decreased oral health-related quality of life.The following study addresses this persistent oral disease by further investigating the effect of DMP1 expression on the differentiation of XLH dental pulp cells.Dental pulp cells were isolated from the third molars of XLH and healthy controls and stable transduction of full-length human DMP1 were achieved.RNA sequencing was performed to evaluate the genetic changes following the induction of odontogenic differentiation.RNAseq data shows the upregulation of inhibitors of the canonical Wnt pathway in XLH cells,while constitutive expression of full-length DMP1 in XLH cells reversed this effect during odontogenic differentiation.These results imply that inhibition of the canonical Wnt pathway may contribute to the pathophysiology of XLH and suggest a new therapeutic strategy for the management of oral disease.
基金the US Department of Energy(Grant Nos.DE-FG02-00ER62986 and DE-FG02-07ER64373 to J.E.K.)the Department of Biotechnology,Govt.of India(Grant No.BT/Coord.II/01/03/2016)for their support.Fellowship funding for one of the authors(Dr.Pooja Singh)by the Department of Science and Technology(DST),Government of India,is greatly acknowledged.
文摘This work examines the physiologic basis of stress tolerance in bacterial strains of the genus Rhodanobacter that dominate in the acidic and highly metal contaminated near-source subsurface zone of the Oak Ridge Integrated Field Research Challenge(ORIFRC)site.Tolerance of R.denitrificans to levels of different stresses were studied in synthetic groundwater medium and R2A broth.Two strains of R.denitrificans,strains 2APBS1T and 116-2,tolerate low to circumneutral pH(4–8),high Uranium(1 mmol/L),elevated levels of nitrate(400 mmol/L)and high NaCl(2.5%).A combination of physiologic traits,such as growth at low pH,increased growth in the presence of high organics concentration,and tolerance of high concentrations of nitrate,NaCl and heavy metals is likely responsible for dominance of Rhodanobacter at the ORIFRC site.Furthermore,extended incubation times and use of low carbon media,better approximating site groundwater conditions,are critical for accurate determination of stress responses.This study expands knowledge of the ecophysiology of bacteria from the genus Rhodanobacter and identifies methodological approaches necessary for acquiring accurate tolerance data.
