Partial Reduction of 3-Heteroatom Substituted 2-Furoic Acids: The Role of an ortho Group in Viability and Stereoselectivity.

ChemInform ◽  
2003 ◽  
Vol 34 (2) ◽  
Author(s):  
Timothy J. Donohoe ◽  
Andrew A. Calabrese ◽  
Jean-Baptiste Guillermin ◽  
Christopher S. Frampton ◽  
Daryl Walter
Author(s):  
Timothy J. Donohoe ◽  
Andrew A. Calabrese ◽  
Jean-Baptiste Guillermin ◽  
Christopher. S. Frampton ◽  
Daryl Walter

2019 ◽  
Vol 7 (10) ◽  
pp. 452 ◽  
Author(s):  
Xu ◽  
Guo ◽  
Li ◽  
Zhang ◽  
Wu ◽  
...  

Cryptosporidium parvum is a protozoan parasite that can cause moderate-to-severe diarrhea. Insulinase-like proteases (INS) are one of the largest protein families within the small proteome of the pathogen. However, their roles in C. parvum biology remain un-elucidated. In this study, a member of the protein family, INS-15 of C. parvum encoded by cgd3_4260, was cloned, expressed and characterized to understand its function. INS-15 and its domain I were expressed in Escherichia coli and polyclonal antibodies against the domain I and one specific polypeptide were prepared in rabbits. The role of INS-15 protein in the C. parvum invasion was preliminarily studied. Recombinant INS-15 protein and its domain I were successfully expressed in E. coli, together with various degraded products. The cgd3_4260 gene had a peak expression at 2 h of in vitro C. parvum culture, while the INS-15 protein was expressed in the mid-anterior region of sporozoites and the area of merozoites opposite to the nucleus. Anti-INS-15 domain I antibodies reduced the invasion of C. parvum sporozoites by over 40%. The anterior location of INS-15 in invasion stages and partial reduction of in vitro growth indicate that INS-15 plays some roles in the invasion or early development of C. parvum.


2016 ◽  
Vol 113 (43) ◽  
pp. E6704-E6711 ◽  
Author(s):  
Takahiro Kawanabe ◽  
Sonoko Ishikura ◽  
Naomi Miyaji ◽  
Taku Sasaki ◽  
Li Min Wu ◽  
...  

Hybrid vigor or heterosis refers to the superior performance of F1 hybrid plants over their parents. Heterosis is particularly important in the production systems of major crops. Recent studies have suggested that epigenetic regulation such as DNA methylation is involved in heterosis, but the molecular mechanism of heterosis is still unclear. To address the epigenetic contribution to heterosis in Arabidopsis thaliana, we used mutant genes that have roles in DNA methylation. Hybrids between C24 and Columbia-0 (Col) without RNA polymerase IV (Pol IV) or methyltransferase I (MET1) function did not reduce the level of biomass heterosis (as evaluated by rosette diameter). Hybrids with a mutation in decrease in dna methylation 1 (ddm1) showed a decreased heterosis level. Vegetative heterosis in the ddm1 mutant hybrid was reduced but not eliminated; a complete reduction could result if there was a change in methylation at all loci critical for generating the level of heterosis, whereas if only a proportion of the loci have methylation changes there may only be a partial reduction in heterosis.


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 955 ◽  
Author(s):  
Vinee Purohit ◽  
Diane M. Simeone ◽  
Costas A. Lyssiotis

Reactive oxygen species (ROS) are chemically active free radicals produced by partial reduction of oxygen that can activate discrete signaling pathways or disrupt redox homeostasis depending on their concentration. ROS interacts with biomolecules, including DNA, and can cause mutations that can transform normal cells into cancer cells. Furthermore, certain cancer-causing mutations trigger alterations in cellular metabolism that can increase ROS production, resulting in genomic instability, additional DNA mutations, and tumor evolution. To prevent excess ROS-mediated toxicity, cancer-causing mutations concurrently activate pathways that manage this oxidative burden. Hence, an understanding of the metabolic pathways that regulate ROS levels is imperative for devising therapies that target tumor cells. In this review, we summarize the dual role of metabolism as a generator and inhibitor of ROS in cancer and discuss current strategies to target the ROS axis.


2019 ◽  
Vol 28 (24) ◽  
pp. 4053-4066 ◽  
Author(s):  
Bernadette C Holdener ◽  
Christopher J Percival ◽  
Richard C Grady ◽  
Daniel C Cameron ◽  
Steven J Berardinelli ◽  
...  

Abstract Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene. Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs). Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily. Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets. To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles. Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development. The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS. In addition, we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly. We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function. Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.


1968 ◽  
Vol 46 (10) ◽  
pp. 1173-1183 ◽  
Author(s):  
S. Sasaki ◽  
T. T. Kozlowski

The role of photosynthetically active cotyledons on development of young red pine (pinus resinosa Ait.) seedlings, and especially on growth of primary needles, was studied over a 30-day period. Photosynthesis of cotyledons, as measured with an infrared CO2 analyzer, was variously reduced by photosynthesis-inhibiting herbicides (atrazine, simazine, propazine, monuron), by reduced light intensity, or by combinations of these. When photosynthesis of cotyledons was completely eliminated shortly after seed germination, the primary needles failed to expand, and dry weight production by seedlings was inhibited. Partial reduction of photosynthesis by herbicides, low light intensity, or both of these was followed by proportional decrease in expansion of primary needles and reduction in dry weight increment of seedlings. Reduced photosynthesis in cotyledons inhibited expansion of primary needles rather than formation of their primordia which occurred early in ontogeny. Growth of cotyledons appeared to utilize carbohydrate reserves to a large extent as cotyledons of many plants emerged even in the dark.


RSC Advances ◽  
2015 ◽  
Vol 5 (14) ◽  
pp. 10816-10825 ◽  
Author(s):  
T. Kavinkumar ◽  
D. Sastikumar ◽  
S. Manivannan

Partial reduction of graphene oxide (GO) was accomplished through heat treatment at 110 and 220 °C. Role of various oxygen functional groups in graphene and their gas sensing and electrical properties at room temperature were reported.


1991 ◽  
Vol 274 (3) ◽  
pp. 679-685 ◽  
Author(s):  
M Mantle

The role of the disulphide-bound 118 kDa glycoprotein of rat intestinal mucin is unknown, although it has been proposed to serve as a ‘link’ component for the mucin monomers. The present studies investigated release or destruction of the 118 kDa glycoprotein (monitored by gel electrophoresis and Western-blot analysis) during progressive breakdown of the mucin polymer (assessed by Sepharose 2B chromatography). H2O2 gradually destroyed the 118 kDa glycoprotein and dissociated the mucin polymer into components of similar size to the monomers. After 3 h, mucin samples contained almost no 118 kDa glycoprotein or its breakdown products, but 50% of the mucin was still eluted in the void volume of a Sepharose 2B column. Although mild trypsinolysis had little effect on the Sepharose 2B elution profile of the mucin, the 118 kDa glycoprotein was completely cleaved into 54-56 kDa and 60-66 kDa fragments which remained disulphide-bound to the high-molecular-mass mucin. Increasing levels of thiol reduction resulted in progressive loss of disulphide bonds, release of the 118 kDa glycoprotein and depolymerization of the mucin. Although approx. 40% of the mucin in partially reduced samples was recovered in the Sepharose 2B void volume, this material contained no 118 kDa glycoprotein and apparently consisted of disulphide-bound mucin monomers. Thus the 118 kDa glycoprotein may be destroyed by H2O2, extensively cleaved by trypsin or released by reduction without completely dissociating the mucin into monomers. Therefore the 118 kDa glycoprotein may not function as a ‘link’ component for all of the mucin monomers in the native polymer.


2011 ◽  
Vol 15 (6) ◽  
pp. 678-685 ◽  
Author(s):  
Pravin Salunke ◽  
Manish Sharma ◽  
Harsimrat Bir Singh Sodhi ◽  
Kanchan K. Mukherjee ◽  
Niranjan K. Khandelwal

Object Patient age at presentation with congenital atlantoaxial dislocation (CAAD) is variable. In addition, the factors determining irreducibility or reducibility in these patients remain unclear. The facets appear to contribute to the stability of the joint, albeit to an unknown extent. The objective of this paper was to study the characteristics of C1–2 facets in these patients and their bearing on the clinicoradiological presentation and management. Methods Twenty-four patients with CAAD were studied. Fifteen patients had irreducible CAAD (IrAAD); 3 of these patients experienced incomplete reduction after traction, and 9 had reducible CAAD (RAAD). The images (CT scans of the craniovertebral junction in a neutral position) obtained in the parasagittal, axial, and coronal planes were studied with respect to the C1–2 facets and were compared with 32 control scans. The inferior sagittal and coronal C-1 facet angles were measured. The lordosis of the cervical spine (cervical spine angle calculated on radiographs of the cervical spine, neutral view) in these patients was compared with normal. The management of these patients is described. Results The inferior sagittal C-1 facet angle and at least one coronal angle in patients with IrAAD were significantly acute compared with those in patients with RAAD and the control population. A significant correlation was found between age and the acuteness of the inferior sagittal C-1 facet angle (that is, the more acute the angle, the earlier the presentation). The lordosis of the cervical spine was exaggerated in patients with IrAAD. Three patients with IrAAD who had smaller acute angles experienced a partial reduction after traction and a complete reduction after intraoperative distraction of the facets, thereby avoiding a transoral procedure. An inferior sagittal C-1 facet angle of more than 150° in the sagittal plane predicted reducibility. Drilling a wedge off the facet in the sagittal plane to make the inferior sagittal C-1 facet angle 150° can reduce the C1–2 joint intraoperatively by posterior approach alone. Conclusions The acuteness of the inferior C-1 sagittal facet angles possibly determines the age at presentation and reducibility. The coronal angles determine the telescoping of C-2 within C-1. Patients with IrAAD can be treated using a posterior approach alone with the exception of those with extremely acute angles or a retroflexed dens. The exaggerated lordosis of the cervical spine in these patients is a compensatory phenomenon.


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