Publications by authors named "H Judah"

3 Publications

  • Page 1 of 1

Cell-free DNA testing of maternal blood in screening for trisomies in twin pregnancy: cohort study at 10-14 weeks and updated meta-analysis.

Ultrasound Obstet Gynecol 2021 Apr 10. Epub 2021 Apr 10.

Harris Birthright Research Centre of Fetal Medicine, King's College Hospital, London, UK.

Objective: To expand the limited knowledge on cell-free (cf)DNA analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancies by updating the data from the Fetal Medicine Foundation (FMF) on prospective first trimester screening and those arising from systematic review of the literature.

Methods: The FMF data were derived from prospective screening for trisomies 21, 18 and 13 in twin pregnancies at 10 -14 weeks' gestation using the Harmony® prenatal test of Roche/Ariosa Diagnostics, Inc. Search of Medline, Embase, CENTRAL (The Cochrane Library), ClinicalTrials.gov and ICTRP (World Health Organization) was carried out to identify all peer-reviewed publications on clinical validation or implementation of maternal cfDNA testing for trisomies 21, 18 and 13 in twin pregnancies, irrespective of gestational age at testing, in which data on pregnancy outcome were provided for more than 85% of the study population. Meta-analysis was then performed using the FMF data and data from the studies identified by the literature search. This review was registered in PROSPERO international database for systematic reviews RESULTS: In the FMF study, cfDNA testing was carried out in 1442 twin pregnancies and a result was obtained, after first or second sampling, in 1367 (94.8%) cases. In 93.1% (1272/1367) cases there was prenatal or postnatal karyotyping or the birth of phenotypically normal babies; 95 cases were excluded from further analysis either because the pregnancies ended in termination, miscarriage or stillbirth with no known karyotype (n=56) or there was loss to follow up (n=39). In the 1272 pregnancies included in the study there were 20 cases with trisomy 21, 10 with trisomy 18, 2 with trisomy 13 and 1240 without trisomy 21, 18 or 13. The cfDNA test classified correctly 19 (95.0%) of the 20 cases of trisomy 21, 9 (90.0%) of 10 of trisomy 18, 1 (50.0%) of 2 of trisomy 13 and 1235 (99.6%) of 1240 cases without any of the three trisomies. The literature search identified 12 relevant studies, excluding our papers because their data are included in the current study. In the combined total of our study and the 12 studies identified by the literature search there were 137 trisomy 21 and 7507 non-trisomy 21 twin pregnancies; the pooled weighted detection rate (DR) and false positive rate (FPR) were 99.0% (95% CI 92.0, 99.9%) and 0.02% (95% CI 0.001, 0.43%), respectively. In the combined total of 50 cases of trisomy 18 and 6840 non-trisomy 18 pregnancies the pooled weighted DR and FPR were 92.8% (95% CI 77.6, 98.0%) and 0.01% (95% CI 0.00, 0.44%), respectively. In the combined total of 11 cases of trisomy 13 and 6290 non-trisomy 13 pregnancies the pooled weighted DR and FPR were 94.7% (95% CI 9.14, 99.97%) and 0.10% (95% CI 0.03., 0.39%), respectively.

Conclusions: In twin pregnancies the reported DR of trisomy 21 by cfDNA testing is high, but lower than in singleton pregnancies, whereas the FPR appears to be equally low. The number of cases of trisomy 18 and more so trisomy 13 is too small for accurate assessment of the predictive performance of the cfDNA test. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/uog.23648DOI Listing
April 2021

Influence of Buffers, Ionic Strength, and pH on the Volume Phase Transition Behavior of Acrylamide-Based Nanogels.

Polymers (Basel) 2020 Nov 4;12(11). Epub 2020 Nov 4.

Department of Chemistry, SBCS, Queen Mary University of London, Mile End Road, London E1 4NS, UK.

The use of covalently crosslinked nanogels for applications in biology and medicine is dependent on their properties and characteristics, which often change because of the biological media involved. Understanding the role of salts, ionic strength and pH in altering specific properties is key to progress in this area. We studied the effect of both chemical structure and media environment on the thermoresponsive behavior of nanogels. A small library of methylenebisacrylamide (MBA) crosslinked nanogels were prepared using -isopropylacrylamide (NIPAM) or -propylacrylamide (NPAM), in combination with functional monomers -hydroxyethylacrylamide (HEAM) and -acryloyl-l-proline (APrOH). The thermoresponsive properties of nanogels were evaluated in phosphate buffer, tris-acetate buffer and Ringer HEPES, with varying concentrations and ionic strengths. The presence of ions facilitates the phase separation of nanogels, and this "salting-out" effect strongly depends on the electrolyte concentration as well as the specificity of individual anions, e.g., their positions in the Hofmeister series. A subtle change in the chemical structure of the side chain of the monomer from NIPAM to NPAM leads to a reduction of the volume phase transition temperature (VPTT) value by ~10 °C. The addition of hydrophilic comonomers such as HEAM, on the other hand, causes a ~20 °C shift in VPTT to higher values. The data highlight the significant role played by the chemical structure of the monomers used, with hydrophobicity and rigidity closely interlinked in determining thermoresponsive behavior. Furthermore, the volume phase transition temperature (VPTT) of nanogels copolymerized with ionizable APrOH comonomer can be tailored by changes in the pH of buffer solutions. This temperature-controlled phase transition is driven by intricate interplay involving the entropy of mixing, electrostatic interactions, conformational transitions, and structural rigidity. These results highlight the importance of understanding the physiochemical properties and behavior of covalently crosslinked nanogels in a biological environment prior to their applications in life-science, such as temperature/pH-triggered drug delivery systems.
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http://dx.doi.org/10.3390/polym12112590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694245PMC
November 2020

Three Cdk1 sites in the kinesin-5 Cin8 catalytic domain coordinate motor localization and activity during anaphase.

Cell Mol Life Sci 2017 09 28;74(18):3395-3412. Epub 2017 Apr 28.

Department of Chemistry and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, PO Box 653, 84105, Beer-Sheva, Israel.

The bipolar kinesin-5 motors perform essential functions in mitotic spindle dynamics. We previously demonstrated that phosphorylation of at least one of the Cdk1 sites in the catalytic domain of the Saccharomyces cerevisiae kinesin-5 Cin8 (S277, T285, S493) regulates its localization to the anaphase spindle. The contribution of these three sites to phospho-regulation of Cin8, as well as the timing of such contributions, remains unknown. Here, we examined the function and spindle localization of phospho-deficient (serine/threonine to alanine) and phospho-mimic (serine/threonine to aspartic acid) Cin8 mutants. In vitro, the three Cdk1 sites undergo phosphorylation by Clb2-Cdk1. In cells, phosphorylation of Cin8 affects two aspects of its localization to the anaphase spindle, translocation from the spindle-pole bodies (SPBs) region to spindle microtubules (MTs) and the midzone, and detachment from the mitotic spindle. We found that phosphorylation of S277 is essential for the translocation of Cin8 from SPBs to spindle MTs and the subsequent detachment from the spindle. Phosphorylation of T285 mainly affects the detachment of Cin8 from spindle MTs during anaphase, while phosphorylation at S493 affects both the translocation of Cin8 from SPBs to the spindle and detachment from the spindle. Only S493 phosphorylation affected the anaphase spindle elongation rate. We conclude that each phosphorylation site plays a unique role in regulating Cin8 functions and postulate a model in which the timing and extent of phosphorylation of the three sites orchestrates the anaphase function of Cin8.
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http://dx.doi.org/10.1007/s00018-017-2523-zDOI Listing
September 2017