116 research outputs found
Blame-rebalance fMRI neurofeedback in major depressive disorder: A randomised proof-of-concept trial
Differential expression and sex chromosome association of CHD3/4 and CHD5 during spermatogenesis
ATP-dependent nucleosome remodelers of the CHD family play important roles in chromatin regulation during development and differentiation. The ubiquitously expressed CHD3 and CHD4 proteins are essential for stem cell function and serve to orchestrate gene expression in different developmental settings. By contrast, the closely related CHD5 is predominantly expressed in neural tissue and its role is believed to be restricted to neural differentiation. Indeed, loss of CHD5 contributes to neuroblastoma. In this study, we first demonstrate that CHD5 is a nucleosome-stimulated ATPase. We then compare CHD3/4 and CHD5 expression in mouse brain and show that CHD5 expression is restricted to a subset of cortical and hippocampal neurons whereas CHD3/4 expression is more widespread. We also uncover high levels of CHD5 expression in testis. CHD5 is transiently expressed in differentiating germ cells. Expression is first detected in nuclei of postmeiotic round spermatids, reaches a maximum in stage VIII spermatids and then falls to undetectable levels in stage IX spermatids. Surprisingly, CHD3/4 and CHD5 show complementary expression patterns during spermatogenesis with CHD3/ 4 levels progressively decreasing as CHD5 expression increases. In spermatocytes, CHD3/4 localizes to the pseudoautosomal region, the X centromeric region and then spreads into the XY body chromatin. In postmeiotic cells, CHD5 colocalises with macroH2A1.2 in association with centromeres and part of the Y chromosome. The subnuclear localisations of CHD4 and CHD5 suggest specif
Caring for a sick or injured child during the COVID‐19 pandemic lockdown in 2020 in the UK: An online survey of parents' experiences
Abstract Background During the COVID‐19 pandemic, the first UK lockdown (March to May 2020) witnessed a dramatic reduction in children presenting to primary/emergency care, creating concern that fear of the virus was resulting in children presenting late. Methods An online survey was co‐developed with UK parents to understand the impact of the lockdown on parents' help‐seeking for, and care of, their sick/injured child(ren). The survey was advertised through social media and snowballing to parents whose children had been ill/injured during the lockdown. Analysis used descriptive statistics, SPSSv25 and thematic analysis. Results The survey was fully completed by 198 UK parents. The majority asked for help (144/198): from their family doctor (78), national helplines (48) or an Emergency Department (23). Most reported that their decision‐making had not changed, although how they sought help had changed. A few parents reported that the severity and duration of illness had increased because of uncertainty about and/or difficulty accessing services. Parents did not always report seeking help for symptoms rated red or amber by the Royal College of Paediatrics and Child Health. Parents reported accessing information through the internet or using information that they already had. Parent Contribution This was a collaboration with parents from survey development to dissemination, with two parents being integral members of our research team. Conclusions Our questionnaire was completed by parents who were not deterred from seeking help for their sick or injured children. Even for these parents, the lockdown changes to services created uncertainty about, and barriers to, accessing medical help for their children
Effect of strain on surface diffusion in semiconductor heteroepitaxy
We present a first-principles analysis of the strain renormalization of the
cation diffusivity on the GaAs(001) surface. For the example of
In/GaAs(001)-c(4x4) it is shown that the binding of In is increased when the
substrate lattice is expanded. The diffusion barrier \Delta E(e) has a
non-monotonic strain dependence with a maximum at compressive strain values (e
0) studied.
We discuss the consequences of spatial variations of both the binding energy
and the diffusion barrier of an adatom caused by the strain field around a
heteroepitaxial island. For a simplified geometry, we evaluate the speed of
growth of two coherently strained islands on the GaAs(001) surface and identify
a growth regime where island sizes tend to equalize during growth due to the
strain dependence of surface diffusion.Comment: 10 pages, 8 figures, LaTeX2e, to appear in Phys. Rev. B (2001). Other
related publications can be found at
http://www.rz-berlin.mpg.de/th/paper.htm
The human keratins: biology and pathology
The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family
The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells
BACKGROUND: Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1+/MAGE-A4-), which fail to differentiate to pre-spermatogonia (POU5F1-/MAGE-A4+) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to investigate the role of Gankyrin in progression from gonocyte to pre-invasive GCNIS and subsequent invasive TGCC. METHODS: We determined Gankyrin expression in human fetal testicular tissue (gestational weeks 9-20; n = 38), human adult testicular tissue with active spermatogenesis (n = 9), human testicular tissue with germ cell maturation delay (n = 4), testicular tissue from patients with pre-invasive GCNIS (n = 6), and invasive TGCC including seminoma (n = 6) and teratoma (n = 7). Functional analysis was performed in-vitro by siRNA knock-down of Gankyrin in the NTera2 cells (derived from embryonal carcinoma). RESULTS: Germ cell expression of Gankyrin was restricted to a sub-population of prespermatogonia in human fetal testes. Nuclear Gankyrin was also expressed in GCNIS cells of childhood and adult pre-invasive TGCC patients, and in GCNIS from seminoma and non-seminoma patients. Cytoplasmic expression was observed in seminoma tumour cell
Separated twins or just siblings? A multi-planet system around an M dwarf including a cool sub-Neptune
We report the discovery of two TESS sub-Neptunes orbiting the early M dwarf
TOI-904 (TIC 261257684). Both exoplanets, TOI-904 b and c, were initially
observed in TESS sector 12 with twin sizes of 2.49R and
2.31R, respectively. Through observations in five additional sectors
in the TESS primary mission and the first and second extended missions, the
orbital periods of both planets were measured to be 10.8870.001 and
83.9990.001 days, respectively. Reconnaissance radial velocity
measurements (taken with EULER/CORALIE) and high resolution speckle imaging
with adaptive optics (obtained from SOAR/HRCAM and Gemini South/ZORRO) show no
evidence of an eclipsing binary or a nearby companion, which together with the
low false positive probabilities calculated with the statistical validation
software TRICERATOPS establish the planetary nature of these candidates. The
outer planet, TOI-904 c, is the longest-period M dwarf exoplanet found by TESS,
with an estimated equilibrium temperature of 217K. As the three other validated
planets with comparable host stars and orbital periods were observed by Kepler
around much dimmer stars (J 12), TOI-904 c, orbiting a brighter
star (J 9.6), is the coldest M dwarf planet easily accessible for
atmospheric follow-up. Future mass measurements and transmission spectroscopy
of the similar sized planets in this system could determine whether they are
also similar in density and composition, suggesting a common formation pathway,
or whether they have distinct origins.Comment: 18 pages, 6 figures, Accepted by the Astrophysical Journal Letter
Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study
BACKGROUND: During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. METHODS AND FINDINGS: Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. CONCLUSIONS: Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. TRIAL REGISTRATION: ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258
First-principles calculation of the effect of strain on the diffusion of Ge adatoms on Si and Ge (001) surfaces
First-principles calculations are used to calculate the strain dependencies
of the binding and diffusion-activation energies for Ge adatoms on both Si(001)
and Ge(001) surfaces. Our calculations reveal that the binding and activation
energies on a strained Ge(001) surface increase and decrease, respectively, by
0.21 eV and 0.12 eV per percent compressive strain. For a growth temperature of
600 degrees C, these strain-dependencies give rise to a 16-fold increase in
adatom density and a 5-fold decrease in adatom diffusivity in the region of
compressive strain surrounding a Ge island with a characteristic size of 10 nm.Comment: 4 pages, 4 figure
TOI-199 b: A well-characterized 100-day transiting warm giant planet with TTVs seen from Antarctica
We present the spectroscopic confirmation and precise mass measurement of the
warm giant planet TOI-199 b. This planet was first identified in TESS
photometry and confirmed using ground-based photometry from ASTEP in Antarctica
including a full 6.5h long transit, PEST, Hazelwood, and LCO; space
photometry from NEOSSat; and radial velocities (RVs) from FEROS, HARPS,
CORALIE, and CHIRON. Orbiting a late G-type star, TOI-199\,b has a
period, a mass of
, and a radius of .
It is the first warm exo-Saturn with a precisely determined mass and radius.
The TESS and ASTEP transits show strong transit timing variations, pointing to
the existence of a second planet in the system. The joint analysis of the RVs
and TTVs provides a unique solution for the non-transiting companion TOI-199 c,
which has a period of and an estimated
mass of . This period places it within
the conservative Habitable Zone.Comment: 33 pages, 23 figures. Accepted for publication in A
- …