26 research outputs found
Mango (Mangifera indica. L) Malformation an Unsolved Mystery
Abstract : Mango (Mangifera indica L.) universally considered to be one of the finest fruits, and is an important crop in tropical and subtropical areas of the world. There are about 1500 varieties of mango in the world of which about 1200 are found in India. Among the known diseases of mango, mango malformation is the most serious disease. The etiology of malformation has not yet been discovered due to paucity of information and thus no effective control measure is known. This review summarizes the plausible cause of the etiology of this disease
HNF4A haploinsufficiency in MODY1 abrogates liver and pancreas differentiation from patient-derived induced pluripotent stem cells
Maturity-onset diabetes of the young 1 (MODY1) is a monogenic diabetes condition caused by heterozygous HNF4A mutations. We investigate how HNF4A haploinsufficiency from a MODY1/HNF4A mutation influences the development of foregut-derived liver and pancreatic cells through differentiation of human induced pluripotent stem cells from a MODY1 family down the foregut lineage. In MODY1-derived hepatopancreatic progenitors, which expressed reduced HNF4A levels and mislocalized HNF4A, foregut genes were downregulated, whereas hindgut-specifying HOX genes were upregulated. MODY1-derived hepatocyte-like cells were found to exhibit altered morphology. Hepatic and β cell gene signatures were also perturbed in MODY1-derived hepatocyte-like and β-like cells, respectively. As mutant HNF4A (p.Ile271fs) did not undergo complete nonsense-mediated decay or exert dominant negativity, HNF4A-mediated loss of function is likely due to impaired transcriptional activation of target genes. Our results suggest that in MODY1, liver and pancreas development is perturbed early on, contributing to altered hepatic proteins and β cell defects in patients.publishedVersio
HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells.
Maturity-onset diabetes of the young 1 (MODY1) is a monogenic diabetes condition caused by heterozygous HNF4A mutations. We investigate how HNF4A haploinsufficiency from a MODY1/HNF4A mutation influences the development of foregut-derived liver and pancreatic cells through differentiation of human induced pluripotent stem cells from a MODY1 family down the foregut lineage. In MODY1-derived hepatopancreatic progenitors, which expressed reduced HNF4A levels and mislocalized HNF4A, foregut genes were downregulated, whereas hindgut-specifying HOX genes were upregulated. MODY1-derived hepatocyte-like cells were found to exhibit altered morphology. Hepatic and β cell gene signatures were also perturbed in MODY1-derived hepatocyte-like and β-like cells, respectively. As mutant HNF4A (p.Ile271fs) did not undergo complete nonsense-mediated decay or exert dominant negativity, HNF4A-mediated loss of function is likely due to impaired transcriptional activation of target genes. Our results suggest that in MODY1, liver and pancreas development is perturbed early on, contributing to altered hepatic proteins and β cell defects in patients
Novel approaches to predict the effect of single nucleotide polymorphisms on protein function using machine learning tools
EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Synthesis, Characterisationand Study Of Biological Application Of Simple Mixed Ligand Complexes Of Nickel (II) With morpholine dithiocarbamate and Amines Such as Ethylene Diamine, Diethylenetriamine and Triethylenetetramine
ABSTRACT Simple mixed ligand complexes of nickel(II) with morpholinedithiocarbamate and aminessuch asethylene diamine(en),diethylenetriamine(dien), and triethylenetetramine(trien) have been synthesized and characterized by elemental and thermal analysis, IR, UV-Vis and ESRspectral studies, and magnetic susceptibility studies.Antibacterial, and Antifungal and activities have also been carried out on these complexes. All the complexes have shown reasonable activity
A Novel Dendritic Drug Carrier and a Process for Preparing the Same
The invention is directed towards the synthesis and evaluation of release profile from a novel class of PAMAM dendrimers that can emerge as a potential drug carrier for various drug delivery applications
Carcinoma Lung Infiltrating into Left Atrium: A Case of Transvenous Extension
Cardiac metastasis lung malignancy can metastasise to heart. We herein present one such case
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Prolonged aPTT Relative to Anti-Xa Is Associated with Increased 30-Day Mortality in Hospitalized Patients Treated with Unfractionated Heparin
Abstract Abstract 1248 BACKGROUND: Historically, unfractionated heparin (UFH) has been monitored using the aPTT, a global measurement of the ability of the heparin-antithrombin complex to inactivate the relevant clotting factors. However, the aPTT response to heparin depends on patient variables and reagent and instrument factors. Anti-Xa activity is routinely used to calibrate aPTT for heparin therapy nomograms, and some institutions use anti-Xa activity directly in heparin dosing nomograms. In general, there is a lack of data correlating these methods of measuring heparin effect in patients and outcome data validating any particular approach. We sought to determine the concordance of aPTT and anti-Xa measurements and its impact on patient outcomes in adult hospitalized patients treated with UFH. METHODS: All simultaneously drawn aPTT and anti-Xa values from patients 18 years and older receiving UFH while hospitalized at Stanford between February 2009 and August 2009 were extracted from Stanford's patient database. We created an aPTT/anti-Xa reference curve using normal pooled plasma with heparin added at increasing concentrations from 0.05 u/mL to 1.0 u/mL, with simultaneous measurement of aPTT and anti-Xa activity. We designed a polynomial fit correlating aPTT and anti-Xa activity with a 99% confidence limit. We then grouped paired aPTT/anti-Xa values into one of three groups according to whether the paired values fell within or outside of the correlation area: 1) aPTT anti-Xa: discordant pairs, with high aPTT to anti-Xa value, and 3) aPTT= anti-Xa: concordant pairs, with aPTT and anti-Xa values within the correlation area. In addition, each aPTT/anti-Xa data pair which had an INR from the same date was categorized as associated with either a low (= 1.5) INR. Because individual patients could have data pairs that fell into multiple groups, we further narrowed the aPTT > anti-Xa and aPTT= anti-Xa groups into patient subgroups to assess outcomes, wherein each patient had data pairs only in one group. RESULTS: A total of 2321 paired values from 539 patients were studied. Data pairs were frequently discordant: 413 (18%) data pairs were in the aPTT anti-Xa group, and 937 (40%) were in the aPTT=anti-Xa group.1337 of 2321 (58%) aPTT/anti-Xa data pairs had an INR value from the same date. The aPTT>anti-Xa group had the highest proportion of data pairs associated with an INR >= 1.5 (68%, see Figure, p anti-Xa and aPTT=anti-Xa patient subgroups. The 30-day mortality was 19 of 87 (21%) in the aPTT > anti-Xa patient group, higher than in the aPTT=anti-Xa group (6 out of 112, 5%) (p anti-Xa on heparin alone had the highest 30-day mortality (16 of 39, 41%), compared to a 30-day mortality of 6% (3 of 48) for aPTT > anti-Xa patients who were on both heparin and warfarin (p 0.05), nor was the 30-day mortality significantly different between those in the aPTT>anti-Xa on heparin and warfarin (3 of 48, 6%) compared to those in the aPTT=anti-Xa on heparin and warfarin (1 of 23, 4%, p>0.05). DISCUSSION: Simultaneously measured aPTT and anti-Xa values in a large cohort of hospitalized adult patients treated with UFH were discordant the majority of the time. The most common discordant pattern was a high aPTT to anti-Xa value. This group was associated with an INR >= 1.5 68% of the time, indicating that a baseline prolongation of the PT is associated with an increased sensitivity of the aPTT to UFH. Increased sensitivity to heparin as demonstrated by an aPTT > anti-Xa in the absence of warfarin appeared to be an indicator of poor health with significantly higher 30-day mortality from underlying disease conditions. Further study is needed to determine whether the aPTT or anti-Xa should preferentially be used in heparin dosing nomograms when the values are discrepant. Disclosures: No relevant conflicts of interest to declare