The CELLULOSE SYNTHASE-LIKE C (CSLC) family is an ancient lineage within the CELLULOSE SYNTHASE/CELLULOSE SYNTHASE-LIKE (CESA/CSL) polysaccharide synthase superfamily that is thought to have arisen before the dive...The CELLULOSE SYNTHASE-LIKE C (CSLC) family is an ancient lineage within the CELLULOSE SYNTHASE/CELLULOSE SYNTHASE-LIKE (CESA/CSL) polysaccharide synthase superfamily that is thought to have arisen before the divergence of mosses and vascular plants. As studies in the flowering plant Arabidopsis have suggested synthesis of the (1,4)-β-glucan backbone of xyloglucan (XyG), a wall polysaccharide that tethers adjacent cellulose microfibrils to each other, as a probable function for the CSLCs, CSLC function was investigated in barley (Hordeum vulgate L.), a species with low amounts of XyG in its walls. Four barley CSLCgenes were identified (designated HvCSLC1-4). Phylogenetic analysis reveals three well supported clades of CSLCs in flowering plants, with barley having representatives in two of these clades. The four barley CSLCs were expressed in various tissues, with in situ PCR detecting transcripts in all cell types of the coleoptile and root, including cells with primary and secondary cell walls. Co-expression analysis showed that HvCSLC3 was coordinately expressed with putative XyG xylosyltransferase genes. Both immuno-EM and membrane fractionation showed that HvCSLC2 was located in the plasma membrane of barley suspension-cultured cells and was not in internal membranes such as endoplasmic reticulum or Golgi apparatus. Based on our current knowledge of the sub-cellular locations of polysaccharide synthesis, we conclude that the CSLC family probably contains more than one type of polysaccharide synthase.展开更多
Colorectal cancer(CRC),a widespread malignancy,is closely associated with tumor microenvironmental hydrogen peroxide(H_(2)O_(2))levels.Some clinical trials targeting H_(2)O_(2)for cancer treatment have revealed its pa...Colorectal cancer(CRC),a widespread malignancy,is closely associated with tumor microenvironmental hydrogen peroxide(H_(2)O_(2))levels.Some clinical trials targeting H_(2)O_(2)for cancer treatment have revealed its paradoxical role as a promoter of cancer progression.Investigating the dynamics of cancer cell H_(2)O_(2)eustress at the single–cell level is crucial.In this study,non–contact hopping probe mode scanning ion conductance microscopy(HPICM)with high-sensitive Pt–functionalized nanoelectrodes was employed to measure dynamic extracellular to intracellular H_(2)O_(2)gradients in individual colorectal cancer Caco–2cells.We explored the relationship between cellular mechanical properties and H_(2)O_(2)gradients.Exposure to 0.1 or 1 mmol/L H_(2)O_(2)eustress increased the extracellular to intracellular H_(2)O_(2)gradient from 0.3 to 1.91 or 3.04,respectively.Notably,cellular F–actin–dependent stiffness increased at 0.1 mmol/L but decreased at 1 mmol/L H_(2)O_(2)eustress.This H_(2)O_(2)–induced stiffness modulated AKT activation positively and glutathione peroxidase 2(GPX2)expression negatively.Our findings unveil the failure of some H_(2)O_(2)-targeted therapies due to their ineffectiveness in generating H_(2)O_(2),which instead acts eustress to promote cancer cell survival.This research also reveals the complex interplay between physical properties and biochemical signaling in cancer cells'antioxidant defense,illuminating the exploitation of H_(2)O_(2)eustress for survival at the single–cell level.Inhibiting GPX and/or catalase(CAT)enhances the cytotoxic activity of H_(2)O_(2)eustress against CRC cells,which holds significant promise for developing innovative therapies targeting cancer and other H_(2)O_(2)-related inflammatory diseases.展开更多
The epididymis is a single convoluted tubule lined by a pseudostratified epithelium. Specialized epididymal epithelial cells, the so-called principal, basal, narrow, and clear cells, establish a unique luminal environ...The epididymis is a single convoluted tubule lined by a pseudostratified epithelium. Specialized epididymal epithelial cells, the so-called principal, basal, narrow, and clear cells, establish a unique luminal environment for the maturation and storage of spermatozoa. The epididymis is functionally and structurally divided into several segments and sub-segments that create regionally distinct luminal environments. This organ is immature at birth, and epithelial cells acquire their fully differentiated phenotype during an extended postnatal period, but the factors involved in this complex process remain incompletely characterized. In the adult epididymis, the establishment of an acidic luminal pH and low bicarbonate concentration in the epididymis contributes to preventing premature activation of spermatozoa during their maturation and storage. Clear cells are proton-secreting cells throughout the epididymis, but principal cells have distinct acid/base transport properties, depending on their localization within the epididymis. Basal cells are located in all epididymal segments, but they have a distinct morphology depending on the segment and species examined. How this structural plasticity of basal cells is regulated is discussed here. Also, the role of luminal factors and androgens in the regulation of epithelial cells is reviewed in relation to their respective localization in the proximal versus distal regions of the epididymis. Finally, we describe a novel role for CFTR in tubulogenesis and epithelial cell differentiation.展开更多
The shortfin mako shark(Isurus oxyrinchus)is one of the fastest marine fishes,reaching speeds of up to 70 km·h^-1.Their speed is related to the skin surface design composed of dermal denticles.Denticles vary in s...The shortfin mako shark(Isurus oxyrinchus)is one of the fastest marine fishes,reaching speeds of up to 70 km·h^-1.Their speed is related to the skin surface design composed of dermal denticles.Denticles vary in size and shape according to placement on the body and minimize turbulence around the body.The objective of this study is to analyze the interaction between seawater flow and denticles on the dorsal fin.High-resolution microscopy(scanning electron microscopy and confocal microscopy)were used to measure defined parts of the dermal denticles.These measurements,along with ratios based on length-to-width define three morphologies(rounded,semi-rounded,long)that were 3D reconstructed.Computational fluid dynamics simulated fluid passage over reconstructed denticles and describe hy-drodynamic efficiency under different conditions.An increase in angle of inclination produced a relevant increase in the drag coefficient,especially for high velocity inlets.The lowest drag coefficient values were found in long and semi-rounded,followed by rounded mor-phologies.The hydrodynamic behavior of shark skin demonstrates a relation to the morphological characteristics of dermal denticles on the dorsal fin.It is concluded that the best hydroefficiency relies on the rounded morphology and may serve to design hydrodynamically efficient surfaces or manmade assemblies.展开更多
Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in...Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in Caucasians caused by the mutation of CFTR,has shown bone disorder as a key clinical manifestation,which currently lacks effective therapeutic options.Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice.Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant,and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice.We further demonstrate that magnesium ion enters osteocytes,increases intracellular cAMP level and activates ATF4,a key transcription factor known to regulate Wnt/β-catenin signaling.In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice.In addition,oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice.Together,these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease.Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.展开更多
The names of the authors were incorrect in the published paper and should be revised as"Patricia Feman-dez-Waid,Guzman Diez,Inigo Bidaguren,Urtzi Izagirre,Jesus Maria Blanco,Manu Soto".
文摘The CELLULOSE SYNTHASE-LIKE C (CSLC) family is an ancient lineage within the CELLULOSE SYNTHASE/CELLULOSE SYNTHASE-LIKE (CESA/CSL) polysaccharide synthase superfamily that is thought to have arisen before the divergence of mosses and vascular plants. As studies in the flowering plant Arabidopsis have suggested synthesis of the (1,4)-β-glucan backbone of xyloglucan (XyG), a wall polysaccharide that tethers adjacent cellulose microfibrils to each other, as a probable function for the CSLCs, CSLC function was investigated in barley (Hordeum vulgate L.), a species with low amounts of XyG in its walls. Four barley CSLCgenes were identified (designated HvCSLC1-4). Phylogenetic analysis reveals three well supported clades of CSLCs in flowering plants, with barley having representatives in two of these clades. The four barley CSLCs were expressed in various tissues, with in situ PCR detecting transcripts in all cell types of the coleoptile and root, including cells with primary and secondary cell walls. Co-expression analysis showed that HvCSLC3 was coordinately expressed with putative XyG xylosyltransferase genes. Both immuno-EM and membrane fractionation showed that HvCSLC2 was located in the plasma membrane of barley suspension-cultured cells and was not in internal membranes such as endoplasmic reticulum or Golgi apparatus. Based on our current knowledge of the sub-cellular locations of polysaccharide synthesis, we conclude that the CSLC family probably contains more than one type of polysaccharide synthase.
基金supported by Japan Society for the Promotion of Science KAKENHI(21H01770,22K04890)the World Premier International Research Center Initiative(WPI),MEXT,Japan。
文摘Colorectal cancer(CRC),a widespread malignancy,is closely associated with tumor microenvironmental hydrogen peroxide(H_(2)O_(2))levels.Some clinical trials targeting H_(2)O_(2)for cancer treatment have revealed its paradoxical role as a promoter of cancer progression.Investigating the dynamics of cancer cell H_(2)O_(2)eustress at the single–cell level is crucial.In this study,non–contact hopping probe mode scanning ion conductance microscopy(HPICM)with high-sensitive Pt–functionalized nanoelectrodes was employed to measure dynamic extracellular to intracellular H_(2)O_(2)gradients in individual colorectal cancer Caco–2cells.We explored the relationship between cellular mechanical properties and H_(2)O_(2)gradients.Exposure to 0.1 or 1 mmol/L H_(2)O_(2)eustress increased the extracellular to intracellular H_(2)O_(2)gradient from 0.3 to 1.91 or 3.04,respectively.Notably,cellular F–actin–dependent stiffness increased at 0.1 mmol/L but decreased at 1 mmol/L H_(2)O_(2)eustress.This H_(2)O_(2)–induced stiffness modulated AKT activation positively and glutathione peroxidase 2(GPX2)expression negatively.Our findings unveil the failure of some H_(2)O_(2)-targeted therapies due to their ineffectiveness in generating H_(2)O_(2),which instead acts eustress to promote cancer cell survival.This research also reveals the complex interplay between physical properties and biochemical signaling in cancer cells'antioxidant defense,illuminating the exploitation of H_(2)O_(2)eustress for survival at the single–cell level.Inhibiting GPX and/or catalase(CAT)enhances the cytotoxic activity of H_(2)O_(2)eustress against CRC cells,which holds significant promise for developing innovative therapies targeting cancer and other H_(2)O_(2)-related inflammatory diseases.
文摘The epididymis is a single convoluted tubule lined by a pseudostratified epithelium. Specialized epididymal epithelial cells, the so-called principal, basal, narrow, and clear cells, establish a unique luminal environment for the maturation and storage of spermatozoa. The epididymis is functionally and structurally divided into several segments and sub-segments that create regionally distinct luminal environments. This organ is immature at birth, and epithelial cells acquire their fully differentiated phenotype during an extended postnatal period, but the factors involved in this complex process remain incompletely characterized. In the adult epididymis, the establishment of an acidic luminal pH and low bicarbonate concentration in the epididymis contributes to preventing premature activation of spermatozoa during their maturation and storage. Clear cells are proton-secreting cells throughout the epididymis, but principal cells have distinct acid/base transport properties, depending on their localization within the epididymis. Basal cells are located in all epididymal segments, but they have a distinct morphology depending on the segment and species examined. How this structural plasticity of basal cells is regulated is discussed here. Also, the role of luminal factors and androgens in the regulation of epithelial cells is reviewed in relation to their respective localization in the proximal versus distal regions of the epididymis. Finally, we describe a novel role for CFTR in tubulogenesis and epithelial cell differentiation.
文摘The shortfin mako shark(Isurus oxyrinchus)is one of the fastest marine fishes,reaching speeds of up to 70 km·h^-1.Their speed is related to the skin surface design composed of dermal denticles.Denticles vary in size and shape according to placement on the body and minimize turbulence around the body.The objective of this study is to analyze the interaction between seawater flow and denticles on the dorsal fin.High-resolution microscopy(scanning electron microscopy and confocal microscopy)were used to measure defined parts of the dermal denticles.These measurements,along with ratios based on length-to-width define three morphologies(rounded,semi-rounded,long)that were 3D reconstructed.Computational fluid dynamics simulated fluid passage over reconstructed denticles and describe hy-drodynamic efficiency under different conditions.An increase in angle of inclination produced a relevant increase in the drag coefficient,especially for high velocity inlets.The lowest drag coefficient values were found in long and semi-rounded,followed by rounded mor-phologies.The hydrodynamic behavior of shark skin demonstrates a relation to the morphological characteristics of dermal denticles on the dorsal fin.It is concluded that the best hydroefficiency relies on the rounded morphology and may serve to design hydrodynamically efficient surfaces or manmade assemblies.
基金supported in part by Theme-based Research Scheme of Hong Kong(No.T13-402/17 N)Health and Medical Research Fund of Hong Kong(15161441 and 18190481)+3 种基金Early Career Scheme of Hong Kong(No.24104517)Start-up fund at the Hong Kong Polytechnic UniversityNational Natural Science Foundation of China(81802152)Natural Science Foundation of Guangdong Province(2019A1515012224 and 2021A1515011204).
文摘Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in Caucasians caused by the mutation of CFTR,has shown bone disorder as a key clinical manifestation,which currently lacks effective therapeutic options.Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice.Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant,and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice.We further demonstrate that magnesium ion enters osteocytes,increases intracellular cAMP level and activates ATF4,a key transcription factor known to regulate Wnt/β-catenin signaling.In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice.In addition,oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice.Together,these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease.Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.
文摘The names of the authors were incorrect in the published paper and should be revised as"Patricia Feman-dez-Waid,Guzman Diez,Inigo Bidaguren,Urtzi Izagirre,Jesus Maria Blanco,Manu Soto".