Quantum effects of nuclear motion in three-particle diatomic ions

A high accuracy, non-relativistic wavefunction is used to study nuclear motion in the ground state of three-particle {a+1a+2a-3} electronic and muonic molecular systems without assuming the Born Oppenheimer approximation. Intracule densities and center of mass particle densities show that as the mass ratio mai/ma3, i=1,2, becomes smaller, the localisation of the like-charged particles (nuclei) a1 and a2 decreases. A new coordinate system is used to calculate center of mass particle densities for systems where a1≠a2. It is shown that the nuclear motion is strongly correlated and depends on the relative masses of the nuclei a1 and a2 rather than just their absolute mass. The heavier particle is always more localised and, the lighter the partner mass, the greater the localisation. It is shown, for systems with ma1<ma2, that the ratio of (i) the density maximum and (ii) the full width at half maximum (FWHM) of the radial distribution of each nucleus from the center of mass, is directly proportional to the mass ratio of the nuclei: ma1/ma2 for the former and ma2/ma1 for the latter, thus quantifying a quantum effect of nuclear correlation

LIN28 is selectively expressed by primordial and pre-meiotic germ cells in the human fetal ovary

Germ cell development requires timely transition from primordial germ cell (PGC) self-renewal to meiotic differentiation. This is associated with widespread changes in gene expression, including downregulation of stem cell–associated genes, such as OCT4 and KIT, and upregulation of markers of germ cell differentiation and meiosis, such as VASA, STRA8, and SYCP3. The stem cell–expressed RNA-binding protein Lin28 has recently been demonstrated to be essential for PGC specification in mice, and LIN28 is expressed in human germ cell tumors with phenotypic similarities to human fetal germ cells. We have therefore examined the expression of LIN28 during normal germ cell development in the human fetal ovary, from the PGC stage, through meiosis to the initiation of follicle formation. LIN28 transcript levels were highest when the gonad contained only PGCs, and decreased significantly with increasing gestation, coincident with the onset of germ cell differentiation. Immunohistochemistry revealed LIN28 protein expression to be germ cell–specific at all stages examined. All PGCs expressed LIN28, but at later gestations expression was restricted to a subpopulation of germ cells, which we demonstrate to be primordial and premeiotic germ cells based on immunofluorescent colocalization of LIN28 and OCT4, and absence of overlap with the meiosis marker SYCP3. We also demonstrate the expression of the LIN28 target precursor pri-microRNA transcripts pri-LET7a/f/d and pri-LET-7g in the human fetal ovary, and that expression of these is highest at the PGC stage, mirroring that of LIN28. The spatial and temporal restriction of LIN28 expression and coincident peaks of expression of LIN28 and target pri-microRNAs suggest important roles for this protein in the maintenance of the germline stem cell state and the regulation of microRNA activity in the developing human ovary

Stochastic dynamics of resistive switching: fluctuations lead to optimal particle number

Resistive switching (RS) is one of the foremost candidates for building novel types of non-volatile random access memories. Any practical implementation of such a memory cell calls for a strong miniaturization, at which point fluctuations start playing a role that cannot be neglected. A detailed understanding of switching mechanisms and reliability is essential. For this reason, we formulate a particle model based on the stochastic motion of oxygen vacancies. It allows us to investigate fluctuations in the resistance states of a switch with two active zones. The vacancies' dynamics are governed by a master equation. Upon the application of a voltage pulse, the vacancies travel collectively through the switch. By deriving a generalized Burgers equation we can interpret this collective motion as nonlinear traveling waves, and numerically verify this result. Further, we define binary logical states by means of the underlying vacancy distributions, and establish a framework of writing and reading such memory element with voltage pulses. Considerations about the discriminability of these operations under fluctuations together with the markedness of the RS effect itself lead to the conclusion, that an intermediate vacancy number is optimal for performance

BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2

STUDY QUESTION: Do changes in the expression of bone morphogenetic proteins (BMPs) 2 and 4, and their antagonists Gremlin1 (GREM1) and Gremlin2 (GREM2) during human fetal ovarian development impact on BMP pathway activity and lead to changes in gene expression that may influence the fate and/or function of ovarian somatic cells? STUDY FINDING: BMPs 2 and 4 differentially regulate gene expression in cultured human fetal ovarian somatic cells. Expression of some, but not all BMP target genes is antagonised by GREM1 and GREM2, indicating the existence of a mechanism to fine-tune BMP signal intensity in the ovary. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker of immature ovarian somatic cells, is identified as a novel transcriptional target of BMP4. WHAT IS KNOWN ALREADY: Extensive re-organisation of the germ and somatic cell populations in the feto-neonatal ovary culminates in the formation of primordial follicles, which provide the basis for a female's future fertility. BMP growth factors play important roles at many stages of ovarian development and function. GREM1, an extracellular antagonist of BMP signalling, regulates the timing of primordial follicle formation in the mouse ovary, and mRNA levels of BMP4 decrease while those of BMP2 increase prior to follicle formation in the human fetal ovary. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Expression of genes encoding BMP pathway components, BMP antagonists and markers of ovarian somatic cells were determined by quantitative (q)RT-PCR in human fetal ovaries (from 8 to 21 weeks gestation) and fetal ovary-derived somatic cell cultures. Ovarian expression of GREM1 protein was confirmed by immunoblotting. Primary human fetal ovarian somatic cell cultures were derived from disaggregated ovaries by differential adhesion and cultured in the presence of recombinant human BMP2 or BMP4, with or without the addition of GREM1 or GREM2. MAIN RESULTS AND THE ROLE OF CHANCE: We demonstrate that the expression of BMP antagonists GREM1, GREM2 and CHRD  increases in the lead-up to primordial follicle formation in the human fetal ovary, and that the BMP pathway is active in cultured ovarian somatic cells. This leads to differential changes in the expression of a number of genes, some of which are further modulated by GREM1 and/or GREM2. The positive transcriptional regulation of LGR5 (a marker of less differentiated somatic cells) by BMP4 in vitro suggests that increasing levels of GREM1 and reduced levels of BMP4 as the ovary develops in vivo may act to reduce LGR5 levels and allow pre-granulosa cell differentiation. LIMITATIONS, REASONS FOR CAUTION: While we have demonstrated that markers of different somatic cell types are expressed in the cultured ovarian somatic cells, their proportions may not represent the same cells in the intact ovary which also contains germ cells. WIDER IMPLICATIONS OF THE FINDINGS: This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. LARGE SCALE DATA: Not applicable. STUDY FUNDING/COMPETING INTERESTS: This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare

Colorectal Cancer Screening in Vulnerable Patients

Low-income, low-literacy, limited English–proficient populations have low colorectal cancer (CRC) screening rates and experience poor patient–provider communication and decision-making processes around screening. The purpose of this study was to test the effect of a CRC screening decision aid on screening-related communication and decision making in primary care visits

Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release

The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon‐induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS‐CoV‐2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS‐CoV‐2 viral titres. We investigate the potential viral proteins involved in abrogating tetherin function and find that SARS‐CoV‐2 ORF3a reduces tetherin localisation within biosynthetic organelles where Coronaviruses bud, and increases tetherin localisation to late endocytic organelles via reduced retrograde recycling. We also find that expression of Spike protein causes a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS‐CoV‐2 and highlight the multiple distinct mechanisms by which SARS‐CoV‐2 subverts tetherin function