When to consult a geneticist specialising in gestational trophoblastic disease

Background: Gestational trophoblastic disease comprises hydatidiform moles and a rare group of malignancies that derive from trophoblasts. Although there are typical morphological features that may distinguish hydatidiform moles from non-molar products of conception, such features are not always present, especially at early stages of pregnancy. Furthermore, mosaic/chimeric pregnancies and twin pregnancies make pathological diagnosis challenging while trophoblastic tumours can also pose diagnostic problems in terms of their gestational or non-gestational origin. Objectives: To show that ancillary genetic testing can be used to aid diagnosis and clinical management of GTD. Methods: Each author identified cases where genetic testing, including short tandem repeat (STR) genotyping, ploidy analysis, next generation sequencing and immunostaining for p57, the product of the imprinted gene CDKN1C, facilitated accurate diagnosis and improved patient management. Representative cases were chosen to illustrate the value of ancillary genetic testing in different scenarios. Outcome: Genetic analysis of placental tissue can aid in determining the risk of developing gestational trophoblastic neoplasia, facilitating discrimination between low risk triploid (partial) and high risk androgenetic (complete) moles, discriminating between a hydatidiform mole twinned with a normal conceptus and a triploid conception and identification of androgenetic/biparental diploid mosaicism. STR genotyping of placental tissue and targeted gene sequencing of patients can identify women with an inherited predisposition to recurrent molar pregnancies. Genotyping can distinguish gestational from non-gestational trophoblastic tumours using tissue or circulating tumour DNA, and can also identify the causative pregnancy which is the key prognostic factor for placental site and epithelioid trophoblastic tumours. Conclusions and Outlook: STR genotyping and P57 immunostaining have been invaluable to the management of gestational trophoblastic disease in many situations. The use of next generation sequencing and of liquid biopsies are opening up new pathways for GTD diagnostics. Development of these techniques has the potential to identify novel biomarkers of GTD and further refine diagnosis

Low CO/CO₂ ratios of comet 67P measured at the Abydos landing site by the <i>Ptolemy</i> mass spectrometer

Comets are generally considered to contain the best-preserved material from the beginning of our planetary system, although the mechanism of their formation and subsequent evolution are still poorly understood. Here we report the direct in situ measurement of H2O, CO, and CO2 by the Ptolemy mass spectrometer onboard the Philae lander, part of the European Space Agency’s Rosetta mission, at the Abydos site of the Jupiter-family comet 67P/Churyumov-Gerasimenko. A CO/CO2 ratio of around 0.07 ± 0.04 is found at the surface of the comet, a value substantially lower than the one measured by ROSINA in the coma. Such a major difference is a potential indication of heterogeneity of the nucleus and not of changes in the CO/CO2 ratio of the coma with radial distance

Sponge-Inspired Dibromohemibastadin Prevents and Disrupts Bacterial Biofilms without Toxicity

Since the banning of several families of compounds in antifouling (AF) coatings, the search for environmentally friendly AF compounds has intensified. Natural sources of AF compounds have been identified in marine organisms and can be used to create analogues in laboratory. In a previous study, we identified that dibromohemibastadin-1 (DBHB) is a promising AF molecule, leading to the inhibition of the activity of phenoloxidase, an enzyme involved in the attachment of mussels to surfaces. This paper describes the activity of the DBHB on biofilm formation and its detachment and on bacterial adhesion and communication: quorum sensing. DBHB has an anti-biofilm activity without affecting adhesion of marine and terrestrial bacteria at a dose of 10 µM. Moreover, DBHB activity on quorum sensing (QS) is demonstrated at doses of 8 and 16 µM. The activity of DBHB on QS is compared to kojic acid, a quorum sensing inhibitor already described. This compound is a promising environmentally friendly molecule potentially useful for the inhibition of microfouling

Itinerant-Electron Magnet of the Pyrochlore Lattice: Indium-Doped YMn2Zn20

We report on a ternary intermetallic compound, "YMn2Zn20", comprising a pyrochlore lattice made of Mn atoms. A series of In-doped single crystals undergo no magnetic long-range order down to 0.4 K, in spite of the fact that the Mn atom carries a local magnetic moment at high temperatures, showing Curie-Weiss magnetism. However, In-rich crystals exhibit spin-glass transitions at approximately 10 K due to a disorder arising from the substitution, while, with decreasing In content, the spin-glass transition temperature is reduced to 1 K. Then, heat capacity divided by temperature approaches a large value of 280 mJ K-2 mol-1, suggesting a significantly large mass enhancement for conduction electrons. This heavy-fermion-like behavior is not induced by the Kondo effect as in ordinary f-electron compounds, but by an alternative mechanism related to the geometrical frustration on the pyrochlore lattice, as in (Y,Sc)Mn2 and LiV2O4, which may allow spin entropy to survive down to low temperatures and to couple with conduction electrons.Comment: 5 pages, 4 figures, J. Phys. Soc. Jpn., in pres

Gambian cultural beliefs, attitudes and discourse on reproductive health and mortality: Implications for data collection in surveys from the interviewer's perspective.

BACKGROUND: A community's cultural beliefs, attitudes and discourse can affect their responses in surveys. Knowledge of these cultural factors and how to comply with them or adjust for them during data collection can improve data quality. OBJECTIVE: This study describes implications of features of Gambian culture related to women's reproductive health, and mortality, when collecting data in surveys. METHODS: 13 in-depth interviews of female interviewers and a focus group discussion among male interviewers were conducted in two rural health and demographic surveillance systems as well as three key informant interviews in three regions in The Gambia. RESULTS: From the fieldworker's viewpoint, questions relating to reproduction were best asked by women as culturally pregnancies should be concealed, and menstruation is considered a sensitive topic. Gambians were reluctant to speak about decedents and the Fula did not like to be counted, potentially affecting estimation of mortality. Asking about siblings proved problematic among the Fula and Serahule communities. Proposals made to overcome these challenges were that culturally-appropriate metaphors and symbols should be used to discuss sensitive matters and to enumerating births/deaths singly instead of collecting summary totals, which had threatening connotations. This was as opposed to training interviewers to ask standardised and precise verbatim questions. CONTRIBUTION: This paper presents indigenous Gambian solutions by fieldworkers to culturally sensitive topics when collecting pregnancy outcomes and mortality data in demographic and health surveys. For researchers collecting maternal mortality data, it highlights the potential shortcomings of the sibling history methodology

Kondo Effects and Multipolar Order in the cubic PrTr2Al20 (Tr=Ti, V)

Our single crystal study reveals that PrTr2Al20 (Tr = Ti and V) provides the first examples of a cubic {\Gamma}3 nonmagnetic ground doublet system that shows the Kondo effect including a -ln T dependent resistivity. The {\Gamma}3 quadrupolar moments in PrV2Al20 induce anomalous metallic behavior through hybridization with conduction electrons, such as T^{1/2} dependent resistivity and susceptibility below ~ 20 K down to its ordering temperature T_O = 0.6 K. In PrTi2Al20, however, quadrupoles are well-localized and exhibit an order at T_O = 2.0 K. Stronger Kondo coupling in PrV2Al20 than in PrTi2Al20 suppresses quadrupolar ordering, and instead promotes hybridization between the {\Gamma}3 doublet and conduction electrons, leading to most likely the quadrupolar Kondo effect.Comment: 12 pages, 4 figure

How much laser power can propagate through fusion plasma?

Propagation of intense laser beams is crucial for inertial confinement fusion, which requires precise beam control to achieve the compression and heating necessary to ignite the fusion reaction. The National Ignition Facility (NIF), where fusion will be attempted, is now under construction. Control of intense beam propagation may be ruined by laser beam self-focusing. We have identified the maximum laser beam power that can propagate through fusion plasma without significant self-focusing and have found excellent agreement with recent experimental data, and suggest a way to increase that maximum by appropriate choice of plasma composition with implication for NIF designs. Our theory also leads to the prediction of anti-correlation between beam spray and backscatter and suggests the indirect control of backscatter through manipulation of plasma ionization state or acoustic damping.Comment: 15 pages, 4 figures, submitted to Plasma Physics and Controlled Fusio

Dynamin 2 mutations in Charcot-Marie-Tooth neuropathy highlight the importance of clathrin-mediated endocytosis in myelination

Mutations in dynamin 2 (DNM2) lead to dominant intermediate Charcot-Marie-Tooth neuropathy type B, while a different set of DNM2 mutations cause autosomal dominant centronuclear myopathy. In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy. We used tissue derived from Dnm2-deficient mice to establish an appropriate peripheral nerve model and found that dominant intermediate Charcot-Marie-Tooth neuropathy type B-associated dynamin 2 mutants, but not autosomal dominant centronuclear myopathy mutants, impaired myelination. In contrast to autosomal dominant centronuclear myopathy mutants, Schwann cells and neurons from the peripheral nervous system expressing dominant intermediate Charcot-Marie-Tooth neuropathy mutants showed defects in clathrin-mediated endocytosis. We demonstrate that, as a consequence, protein surface levels are altered in Schwann cells. Furthermore, we discovered that myelination is strictly dependent on Dnm2 and clathrin-mediated endocytosis function. Thus, we propose that altered endocytosis is a major contributing factor to the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type

Hydrogen Bonding Between Ions of Like Charge in Ionic Liquids Characterized by NMR Deuteron Quadrupole Coupling Constants—Comparison with Salt Bridges and Molecular Systems

We present deuteron quadrupole coupling constants (DQCC) for hydroxyl-functionalized ionic liquids (ILs) in the crystalline or glassy states characterizing two types of hydrogen bonding: The regular Coulomb-enhanced hydrogen bonds between cation and anion (c–a), and the unusual hydrogen bonds between cation and cation (c–c), which are present despite repulsive Coulomb forces. We measure these sensitive probes of hydrogen bonding by means of solid-state NMR spectroscopy. The DQCCs of (c–a) ion pairs and (c–c) H-bonds are compared to those of salt bridges in supramolecular complexes and those present in molecular liquids. At low temperatures, the (c–c) species successfully compete with the (c–a) ion pairs and dominate the cluster populations. Equilibrium constants obtained from molecular-dynamics (MD) simulations show van't Hoff behavior with small transition enthalpies between the differently H-bonded species. We show that cationic-cluster formation prevents these ILs from crystallizing. With cooling, the (c–c) hydrogen bonds persist, resulting in supercooling and glass formation. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Proposal of a consensus set of hypervariable mycobacterial interspersed repetitive-unit-variable-number tandem-repeat loci for subtyping of mycobacterium tuberculosis Beijing isolates

Mycobacterium tuberculosis Beijing strains represent targets of special importance for molecular surveillance of tuberculosis (TB), especially because they are associated with spread of multidrug resistance in some world regions. Standard 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing lacks resolution power for accurately discriminating closely related clones that often compose Beijing strain populations. Therefore, we evaluated a set of 7 additional, hypervariable MIRU-VNTR loci for better resolution and tracing of such strains, using a collection of 535 Beijing isolates from six world regions where these strains are known to be prevalent. The typeability and interlaboratory reproducibility of these hypervariable loci were lower than those of the 24 standard loci. Three loci (2163a, 3155, and 3336) were excluded because of their redundant variability and/or more frequent noninterpretable results compared to the 4 other markers. The use of the remaining 4-locus set (1982, 3232, 3820, and 4120) increased the number of types by 52% (from 223 to 340) and reduced the clustering rate from 58.3 to 36.6%, when combined with the use of the standard 24-locus set. Known major clonal complexes/24-locus-based clusters were all subdivided, although the degree of subdivision varied depending on the complex. Only five single-locus variations were detected among the hypervariable loci of an additional panel of 92 isolates, representing 15 years of clonal spread of a single Beijing strain in a geographically restricted setting. On this calibrated basis, we propose this 4-locus set as a consensus for subtyping Beijing clonal complexes and clusters, after standard typing