Identification and single-cell functional characterization of an endodermally biased pluripotent substate in human embryonic stem cells

Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal. When clonal stem cell colonies were formed from GATA6-positive and GATA6-negative cells, more of those derived from GATA6-positive cells contained spontaneously differentiated endoderm cells than similar colonies derived from the GATA6-negative cells. We characterized these discrete cellular states using single-cell transcriptomic analysis, identifying a potential role for SOX17 in the establishment of the endoderm-biased stem cell state

Comparison of geometrical layouts for a multi-box aerosol model from a single-chamber dispersion study

Models are increasingly used to estimate and pre-emptively calculate the occupational exposure of airborne released particulate matter. Typical two-box models assume instant and fully mixed air volumes, which can potentially cause issues in cases with fast processes, slow air mixing, and/or large volumes. In this study, we present an aerosol dispersion model and validate it by comparing the modelled concentrations with concentrations measured during chamber experiments. We investigated whether a better estimation of concentrations was possible by using different geometrical layouts rather than a typical two-box layout. A one-box, two-box, and two three-box layouts were used. The one box model was found to underestimate the concentrations close to the source, while overestimating the concentrations in the far field. The two-box model layout performed well based on comparisons from the chamber study in systems with a steady source concentration for both slow and fast mixing. The three-box layout was found to better estimate the concentrations and the timing of the peaks for fluctuating concentrations than the one-box or two-box layouts under relatively slow mixing conditions. This finding suggests that industry-relevant scaled volumes should be tested in practice to gain more knowledge about when to use the two-box or the three-box layout schemes for multi-box models

Wainwright’s West Yorkshire: affect and landscape in the television drama of Sally Wainwright

Over the past two decades RED Production Company's key presence in British television drama has been grounded in its regional focus on the North of England. It shares this commitment with Sally Wainwright, whose work with and outside of RED is built around a strong affective engagement with its characters’ experiences. These stories offer intimate explorations of family dynamics and female relationships, situated within and interwoven with the spaces and places of West Yorkshire. From her adaptation of Wuthering Heights in Sparkhouse (BBC, 2002) to her 2016 Christmas biopic of the Brontë sisters To Walk Invisible (BBC, 2016), through Last Tango in Halifax (BBC, 2012–16) and Happy Valley (BBC, 2014–) these are distinctly regional narratives whose female-led familial melodrama, psychodrama and romance are embedded within and return to the landscapes of the region, spaces which blend the stolid and torrid. Wide and spectacular aerial shots follow cars that track through the green and brown expanses between the Harrogate and Halifax families of the elderly couple in Last Tango, the beauty of the Calder Valley pens in the stark bleakness that is foundational to Happy Valley, and the Brontë sisters stride across heathered hills and are silhouetted against grey skies in To Walk Invisible. This article explores the visual dynamics of Wainwright's work and her engagement with the landscapes of the region in both her writing and direction, evoking their numerous literary and cultural connotations in her interweaving of West Yorkshire's stark, dynamic beauty with her stories of intimate female affect

Patient-specific factors to differentiate between branchial cleft cysts and CUP syndrome: a 10 year unicenter study

Objectives: Due to its generally-poor prognosis and varied clinical presentation, cervical cancer of unknown primary (CUP) poses particular challenges for clinical and imaging diagnosis. Differential diagnoses of CUP syndrome may also include lateral cervical cysts. When a benign neck cyst is initially suspected, squamous cell carcinoma is often diagnosed after receiving histopathology. Our study investigates the risk factors to differentiate between CUP syndrome and lateral neck cysts (LNC) to possibly improve the prognosis. Methods: Between 2013 and 2023, 244 patients with an initial diagnosis of LNC (n = 121) or CUP (n = 123) were recruited from the Department of Otorhinolaryngology of Heidelberg University Hospital and underwent panendoscopy with lymph node removal. In general, disease- and progression-free survival, prognostic relevant risk factors, and treatment data were recorded and analyzed. Results: The mean age of patients with CUP was significantly higher at 65 ± 13.2 years than that of patients with LNC (41 ± 15.8 years; P = .000). The calculated cutoff value was 50 to 59 years for a 50% chance of CUP syndrome or other malignant neck mass. Alcohol and tobacco consumption were not found to be risk factors. Previous tumor diseases were diagnosed more frequently in patients with CUP than in patients with LNC (P = .045). The 5 year overall survival for patients with CUP was 77.0% and did not differ significantly between the other various tumor entities (P = .423). Conclusions: The consideration of patient-specific factors such as age or synchronous/asynchronous malignancies is crucial in the diagnostic decision-making process. In the age group of 50 to 59 years, there is ~50% probability of diagnosing CUP syndrome with unilateral painless neck swelling. A thorough clinical examination using panendoscopy with at least 1 unilateral tonsillectomy and biopsies from the base of the tongue is essential to detect a possible primarius early and improve the prognosis

Does personality affect premating isolation between locally-adapted populations?

Background: One aspect of premating isolation between diverging, locally-adapted population pairs is female mate choice for resident over alien male phenotypes. Mating preferences often show considerable individual variation, and whether or not certain individuals are more likely to contribute to population interbreeding remains to be studied. In the Poecilia mexicana-species complex different ecotypes have adapted to hydrogen sulfide (H2S)-toxic springs, and females from adjacent non-sulfidic habitats prefer resident over sulfide-adapted males. We asked if consistent individual differences in behavioral tendencies (animal personality) predict the strength and direction of the mate choice component of premating isolation in this system. Results: We characterized focal females for their personality and found behavioral measures of ‘novel object exploration’, ‘boldness’ and ‘activity in an unknown area’ to be highly repeatable. Furthermore, the interaction term between our measures of exploration and boldness affected focal females’ strength of preference (SOP) for the resident male phenotype in dichotomous association preference tests. High exploration tendencies were coupled with stronger SOPs for resident over alien mating partners in bold, but not shy, females. Shy and/or little explorative females had an increased likelihood of preferring the non-resident phenotype and thus, are more likely to contribute to rare population hybridization. When we offered large vs. small conspecific stimulus males instead, less explorative females showed stronger preferences for large male body size. However, this effect disappeared when the size difference between the stimulus males was small. Conclusions: Our results suggest that personality affects female mate choice in a very nuanced fashion. Hence, population differences in the distribution of personality types could be facilitating or impeding reproductive isolation between diverging populations depending on the study system and the male trait(s) upon which females base their mating decisions, respectively

Methylation levels of a novel genetic element, EgNB3 as a candidate biomarker associated with the embryogenic competency of oil palm

The association between DNA methylation status and embryogenic competency in oil palm tissue culture was examined through Representational Difference Analysis (RDA) approach, using methylation-sensitive restriction endonucleases. "Difference Products" (DPs) of RDA derived from palms of similar genetic backgrounds but exhibiting different embryogenesis rates during the regeneration process were isolated. The DPs were sequenced using a pyrosequencing platform. To our knowledge, this is the first study profiling partial HpaII methylation sites in oil palm young leaf tissues which are potentially associated with embryogenic amenability through a genomic subtractive approach. Quantitative real-time PCR analysis demonstrated that the methylation status of a novel fragment, EgNB3, was higher in highly embryogenic leaf explants compared to low embryogenesis rate materials. These differences are likely to be contributed by the 5′-mCCGG-3′ and/or 5′-mCmCGG-3′ methylation patterns. Our data suggest that the differentially methylated site in EgNB3 has potential as a molecular biomarker for the screening of oil palm leaf explants for their embryogenic potentials

Normative data for interpreting the SNOT-22

Objectives: The Sino-Nasal Outcome Test 22 (SNOT-22) is a validated patient-reported outcome instrument to evaluate the health-related quality of life (HRQoL) in patients with chronic rhinosinusitis (CRS). There are no published normative SNOT-22 scores, limiting its interpretation. Methods: Symptom scores from 1,000 SNOT-22 questionnaires were analysed by principal component analysis (PCA) and exploratory factor analyses. Data were derived from a survey with 1,000 healthy Europeans (reference cohort) who were recruited using the Respondi panel for market and social science research. This subsample was quoted to the population distribution of the German Microcensus and selected from a non-probability panel. Results: The overall normative SNOT-22 score can be detected to be 20.2 ± 19.44. Male (18.49 ± 19.15) and older (> 50 years old; 18.3 ± 17.49) participants had overall lower SNOT-22 mean results than females (21.8 ± 19.6) and younger (21.4 ± 20.55) participants, indicating higher levels of satisfaction. PCA proposed two SNOT-22 domains ("physiological well-being" and "psychological well-being"), which explained 65% of the variance. Conclusions: These are the first published (German) normative scores for the SNOT-22 and provide a clinical reference point for the interpretation of data

Long-term outcomes and quality of life following parotidectomy for benign disease

Objective: Parotidectomy worsens quality of life (QoL) in the short-term, but the long-term impact is unknown. In this study, we analysed the long-term effects of parotidectomy on QoL. Methods: In this prospective long-term follow-up study, participants were divided into three groups: short-term (ST) follow-up of six weeks, long-term (LT) follow-up of 13 years and short- and long-term (SLT) follow-up. QoL was assessed using the Parotidectomy Outcome Inventory (POI-8). Parotidectomies were classified based on whether the great auricular nerve (GAN) had been preserved or sacrificed. Results: In total, 164 observations were analysed, 74 in the LT group, 57 in the ST group and 33 in the SLT group. Hypoaesthesia was a major problem and facial palsy was a minor problem. Pain (p < 0.01) and hypoaesthesia (p < 0.001) were significantly lower after 13 years compared with after six weeks, and QoL was higher after 13 years compared with after six weeks (p = 0.04). The disease-specific impairment rate decreased from 70% at short-term follow-up to 30% at long-term follow-up. Removal of the GAN was associated with hypoaesthesia in the ST group (p = 0.028). Conclusions: Hypoaesthesia has a long-term impact on the QoL, and this should be emphasised during preoperative discussions

lincRNAs act in the circuitry controlling pluripotency and differentiation

Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state.Broad InstituteHarvard UniversityNational Human Genome Research Institute (U.S.)Merkin Family Foundation for Stem Cell Researc

Mužjaci ribe Poecilia mexicana ne raspoznaju receptivne ženke bez tjelesnog kontakta

We investigated the preference of Cave molly males to associate with a receptive or a non-receptive female while body contact was prevented but water-borne cues were allowed to reach the male. Both in light and in darkness, males did not prefer the receptive female. Water-borne chemical cues (pheromones) seem to be absent or they are not detected/used by males, respectively.Istraživali smo način na koji mužjak špiljske ribe Poecilia mexicana odabire receptivnu odnosno nereceptivnu ženku, pri čemu je tjelesni kontakt bio onemogućen, ali su čimbenici nošeni vodom mogli doprijeti do mužjaka. Niti na svjetlu niti u tami mužjaci nisu preferirali receptivne ženke. Proizlazi da vodom nošenih tvari (feromona) nema, ili ih mužjaci ne raspoznaju, odnosno ne koriste