De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

Women in Public Relations (1982-2019)

Purpose This paper aims to analyse the current literature on women in public relations to establish trends and areas of inquiry in the literature and identify research gaps for future research. Design/methodology/approach A total of 223 articles have been empirically analysed using thematic analysis to identify trends in the existing literature. The data has been coded and analysed per decade (1982–1989, 1990–1999, 2000–2009, 2010–2019). The articles have been identified by searching major journals in the field of public relations and communications, as well as snowballing from identified articles. Findings The results show that the majority of academic articles have been produced by using lived experiences of women working in the public relations industry and thus reflect the professional situation of female public relations employees. The results show that the position of women has reached a full circle in four decades of research and returned to the discriminatory work environment. Finally, the results show that a liberal feminist perspective has an advantage in the literature since the majority of works have been produced in the United States; however, there is an increase in authors calling for the use of socialist and radical feminism. Originality/value The paper provides a comprehensive literature review of works published in the field. The paper takes an empirical approach to the analysis rather than the descriptive one, which helped in identifying major trends in the research and identified a research gap for future inquiries

Sea-ice dynamics in an Arctic coastal polynya during the past 6500 years

The production of high-salinity brines during sea-ice freezing in circum-arctic coastal polynyas is thought to be part of northern deep water formation as it supplies additional dense waters to the Atlantic meridional overturning circulation system. To better predict the effect of possible future summer ice-free conditions in the Arctic Ocean on global climate, it is important to improve our understanding of how climate change has affected sea-ice and brine formation, and thus finally dense water formation during the past. Here, we show temporal coherence between sea-ice conditions in a key Arctic polynya (Storfjorden, Svalbard) and patterns of deep water convection in the neighbouring Nordic Seas over the last 6500 years. A period of frequent sea-ice melting and freezing between 6.5 and 2.8 ka BP coincided with enhanced deep water renewal in the Nordic Seas. Near-permanent sea-ice cover and low brine rejection after 2.8 ka BP likely reduced the overflow of high-salinity shelf waters, concomitant with a gradual slow down of deep water convection in the Nordic Seas, which occurred along with a regional expansion in sea-ice and surface water freshening. The Storfjorden polynya sea-ice factory restarted at ~0.5 ka BP, coincident with renewed deep water penetration to the Arctic and climate amelioration over Svalbard. The identified synergy between Arctic polynya sea-ice conditions and deep water convection during the present interglacial is an indication of the potential consequences for ocean ventilation during states with permanent sea-ice cover or future Arctic ice-free conditions

The influence of sea ice cover and Atlantic water advection on annual particle export north of Svalbard

The Arctic Ocean north of Svalbard has recently experienced large sea ice losses and the increasing prominence of Atlantic water (AW) advection. To investigate the impact of these ongoing changes on annual particle export, two moorings with sequential sediment traps were deployed in ice‐free and seasonally ice‐covered waters on the shelf north (NSv) and east (ESv) of Svalbard, collecting sinking particles nearly continuously from October 2017 to October 2018. Vertical export of particulate organic carbon (POC), total particulate matter (TPM), planktonic protists, chlorophyll a, and zooplankton fecal pellets were measured, and swimmers were quantified and identified. Combined with sensor data from the moorings, these time‐series measurements provided a first assessment of the factors influencing particle export in this region of the Arctic Ocean. Higher annual TPM and POC fluxes at the ice‐free NSv site were primarily driven by the advection of AW, higher grazing by large copepods, and a wind‐induced mixing event during winter. Higher diatom fluxes were observed during spring in the presence of sea ice at the ESv site. Along with sea ice cover, regional differences in AW advection and the seasonal presence of grazers played a prominent role in the biological carbon pump along the continental shelf off Svalbard

Responses in Arctic marine carbon cycle processes: conceptual scenarios & implications for ecosystem.

The Arctic Ocean is one of the fastest changing oceans, plays an important role in global carbon cycling and yet is a particularly challenging ocean to study. Hence, observations tend to be relatively sparse in both space and time. How the Arctic functions, geophysically, but also ecologically, can have significant consequences for the internal cycling of carbon, and subsequently influence carbon export, atmospheric CO2 uptake and food chain productivity. Here we assess the major carbon pools and associated processes, specifically summarizing the current knowledge of each of these processes in terms of data availability and ranges of rates and values for four geophysical Arctic Ocean domains originally described by Carmack & Wassmann (2006): inflow shelves, which are Pacific-influenced and Atlantic-influenced; interior, river-influenced shelves; and central basins. We attempt to bring together knowledge of the carbon cycle with the ecosystem within each of these different geophysical settings, in order to provide specialist information in a holistic context. We assess the current state of models and how they can be improved and/or used to provide assessments of the current and future functioning when observational data are limited or sparse. In doing so, we highlight potential links in the physical oceanographic regime, primary production and the flow of carbon within the ecosystem that will change in the future. Finally, we are able to highlight priority areas for research, taking a holistic pan-Arctic approach

Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes.

PURPOSE: Several clinical phenotypes including fetal hydrops, central conducting lymphatic anomaly or capillary malformations with arteriovenous malformations 2 (CM-AVM2) have been associated with EPHB4 (Ephrin type B receptor 4) variants, demanding new approaches for deciphering pathogenesis of novel variants of uncertain significance (VUS) identified in EPHB4, and for the identification of differentiated disease mechanisms at the molecular level. METHODS: Ten index cases with various phenotypes, either fetal hydrops, CM-AVM2, or peripheral lower limb lymphedema, whose distinct clinical phenotypes are described in detail in this study, presented with a variant in EPHB4. In vitro functional studies were performed to confirm pathogenicity. RESULTS: Pathogenicity was demonstrated for six of the seven novel EPHB4 VUS investigated. A heterogeneity of molecular disease mechanisms was identified, from loss of protein production or aberrant subcellular localization to total reduction of the phosphorylation capability of the receptor. There was some phenotype-genotype correlation; however, previously unreported intrafamilial overlapping phenotypes such as lymphatic-related fetal hydrops (LRFH) and CM-AVM2 in the same family were observed. CONCLUSION: This study highlights the usefulness of protein expression and subcellular localization studies to predict EPHB4 variant pathogenesis. Our accurate clinical phenotyping expands our interpretation of the Janus-faced spectrum of EPHB4-related disorders, introducing the discovery of cases with overlapping phenotypes

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (−6.6%, 95% CI −18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601

Assessment of bone ingrowth potential of biomimetic hydroxyapatite and brushite coated porous E-beam structures

The bone ingrowth potential of biomimetic hydroxyapatite and brushite coatings applied on porous E-beam structure was examined in goats and compared to a similar uncoated porous structure and a conventional titanium plasma spray coating. Specimens were implanted in the iliac crest of goats for a period of 3 (4 goats) or 15 weeks (8 goats). Mechanical implant fixation generated by bone ingrowth was analyzed by a push out test. Histomorphometry was performed to assess the bone ingrowth depth and bone implant contact. The uncoated and hydroxyapatite-coated cubic structure had significantly higher mechanical strength at the interface compared to the Ti plasma spray coating at 15 weeks of implantation. Bone ingrowth depth was significantly larger for the hydroxyapatite- and brushite-coated structures compared to the uncoated structure. In conclusion, the porous E-beam surface structure showed higher bone ingrowth potential compared to a conventional implant surface after 15 weeks of implantation. Addition of a calcium phosphate coating to the E-beam structure enhanced bone ingrowth significantly. Furthermore, the calcium phosphate coating appears to work as an accelerator for bone ingrowth

Inverse correlation between PDGFC expression and lymphocyte infiltration in human papillary thyroid carcinomas

<p>Abstract</p> <p>Background</p> <p>Members of the PDGF family have been suggested as potential biomarkers for papillary thyroid carcinomas (PTC). However, it is known that both expression and stimulatory effect of PDGF ligands can be affected by inflammatory cytokines. We have performed a microarray study in a collection of PTCs, of which about half the biopsies contained tumour-infiltrating lymphocytes or thyroiditis. To investigate the expression level of PDGF ligands and receptors in PTC we measured the relative mRNA expression of all members of the PDGF family by qRT-PCR in 10 classical PTC, eight clinically aggressive PTC, and five non-neoplastic thyroid specimens, and integrated qRT-PCR data with microarray data to enable us to link PDGF-associated gene expression profiles into networks based on recognized interactions. Finally, we investigated potential influence on PDGF mRNA levels by the presence of tumour-infiltrating lymphocytes.</p> <p>Methods</p> <p>qRT-PCR was performed on <it>PDGFA</it>, <it>PDGFB</it>, <it>PDGFC</it>, <it>PDGFD</it>, <it>PDGFRA PDGFRB </it>and a selection of lymphocyte specific mRNA transcripts. Semiquantitative assessment of tumour-infiltrating lymphocytes was performed on the adjacent part of the biopsy used for RNA extraction for all biopsies, while direct quantitation by qRT-PCR of lymphocyte-specific mRNA transcripts were performed on RNA also subjected to expression analysis. Relative expression values of PDGF family members were combined with a cDNA microarray dataset and analyzed based on clinical findings and PDGF expression patterns. Ingenuity Pathway Analysis (IPA) was used to elucidate potential molecular interactions and networks.</p> <p>Results</p> <p>PDGF family members were differentially regulated at the mRNA level in PTC as compared to normal thyroid specimens. Expression of <it>PDGFA </it>(p = 0.003), <it>PDGFB </it>(p = 0.01) and <it>PDGFC </it>(p = 0.006) were significantly up-regulated in PTCs compared to non-neoplastic thyroid tissue. In addition, expression of <it>PDGFC </it>was significantly up-regulated in classical PTCs as compared to clinically aggressive PTCs (p = 0.006), and <it>PDGFRB </it>were significantly up-regulated in clinically aggressive PTCs (p = 0.01) as compared to non-neoplastic tissue. Semiquantitative assessment of lymphocytes correlated well with quantitation of lymphocyte-specific gene expression. Further more, by combining TaqMan and microarray data we found a strong inverse correlation between <it>PDGFC </it>expression and the expression of lymphocyte specific mRNAs.</p> <p>Conclusion</p> <p>At the mRNA level, several members of the PDGF family are differentially expressed in PTCs as compared to normal thyroid tissue. Of these, only the <it>PDGFC </it>mRNA expression level initially seemed to distinguish classical PTCs from the more aggressive PTCs. However, further investigation showed that <it>PDGFC </it>expression level correlated inversely to the expression of several lymphocyte specific genes, and to the presence of lymphocytes in the biopsies. Thus, we find that <it>PDGFC </it>mRNA expression were down-regulated in biopsies containing infiltrated lymphocytes or thyroiditis. No other PDGF family member could be linked to lymphocyte specific gene expression in our collection of PTCs biopsies.</p