Anatomical localization of progenitor cells in human breast tissue reveals enrichment of uncommitted cells within immature lobules

Introduction: Lineage tracing studies in mice have revealed the localization and existence of lineage-restricted mammary epithelial progenitor cells that functionally contribute to expansive growth during puberty and differentiation during pregnancy. However, extensive anatomical differences between mouse and human mammary tissues preclude the direct translation of rodent findings to the human breast. Therefore, here we characterize the mammary progenitor cell hierarchy and identify the anatomic location of progenitor cells within human breast tissues. Methods: Mammary epithelial cells (MECs) were isolated from disease-free reduction mammoplasty tissues and assayed for stem/progenitor activity in vitro and in vivo. MECs were sorted and evaluated for growth on collagen and expression of lineages markers. Breast lobules were microdissected and individually characterized based on lineage markers and steroid receptor expression to identify the anatomic location of progenitor cells. Spanning-tree progression analysis of density-normalized events (SPADE) was used to identify the cellular hierarchy of MECs within lobules from high-dimensional cytometry data. Results: Integrating multiple assays for progenitor activity, we identified the presence of luminal alveolar and basal ductal progenitors. Further, we show that Type I lobules of the human breast were the least mature, demonstrating an unrestricted pattern of expression of luminal and basal lineage markers. Consistent with this, SPADE analysis revealed that immature lobules were enriched for basal progenitor cells, while mature lobules consisted of increased hierarchal complexity of cells within the luminal lineages. Conclusions: These results reveal underlying differences in the human breast epithelial hierarchy and suggest that with increasing glandular maturity, the epithelial hierarchy also becomes more complex. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0453-3) contains supplementary material, which is available to authorized users

TiO2/Cu2O all-oxide heterojunction solar cells produced by spray pyrolysis

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Late Pleistocene prey mobility in southwestern France and its implications for reconstructing Neandertal ranging behaviors

We thank Sarah Barakat for consultation. We also thank Jenni Henecke, Jen Everhart, Carol Lee, Charisse Carver, and Hope Williams for assistance with 87Sr/86Sr sample preparation. Access to the Metal Geochemistry Center at Yale University was kindly granted by Noah Planavsky, and Dan Asael assisted with 87Sr/86Sr measurement there. Jiuyuan Wang provided important advice on 87Sr/86Sr data correction, and Alice Knaf shared insights into sample elution. We would also like to thank Curtis Marean, Kim Hill, David Strait, Caley Orr, and Ben Schoville for advice and comments on the manuscript. Two anonymous reviewers provided helpful comments that improved the quality of the manuscript. Finally, we thank the late Harold Dibble for access to the Roc de Marsal collections. CRediT authorship contribution statement Jamie Hodgkins: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing. Alex Bertacchi: Formal analysis, Methodology, Visualization, Writing – review & editing. Kelly J. Knudson: Conceptualization, Methodology, Writing – review & editing. Troy Rasbury: Conceptualization, Methodology, Writing – review & editing. Julia I. Giblin: Methodology, Resources. Gwyneth Gordon: Conceptualization, Methodology, Writing – review & editing. Ariel Anbar: Resources. Alain Turq: Resources. Dennis Sandgathe: Resources, Writing – review & editing. Hannah M. Keller: Visualization, Writing – review & editing. Kate Britton: Conceptualization, Methodology, Writing – review & editing. Shannon P. McPherron: Conceptualization, Methodology, Writing – review & editing.Peer reviewe

Family-centred music therapy with preterm infants and their parents in the Neonatal Intensive Care Unit (NICU) in Colombia – A mixed-methods study

This article reports a mixed-methods study of Music Therapy (MT) with preterm infants and their parents in a neonatal intensive care unit (NICU) in Colombia. The aim was to find out whether live MT during kangaroo care had an effect on the physiological outcomes of the neonates and would help parents to decrease their anxiety levels and improve parent–infant bonding. The participants were 36 medically stable neonates born between the 28th and 34th week of gestation and their parents. The quantitative data collection included heart rate, oxygen saturation, weight gain, length of hospitalization and re-hospitalization rate. The assessment measures for anxiety and bonding were the State-Trait Anxiety Inventory (STAI) and the Mother-to-Infant-Bonding Scale (MIBS). Thematic analysis was used to analyse the qualitative data collected with semi-structured interviews and questionnaires. The quantitative results showed statistically significant improvements in maternal state-anxiety (p = .007) and in the babies weight gain per day during the intervention period (p = .036). Positive trends were found regarding the babies’ length of hospitalization and re-hospitalization rate. Both parents improved their scores with the MIBS, but this was not statistically significant. The qualitative analysis showed that MT was important for parental well-being, for bonding and for fostering the development of the neonates. Interacting musically with their babies helped parents to experience feelings of connectedness and to distract themselves from their difficulties and from the noisy hospital environment

Navigating Mealtimes to Meet Public Health Mandates in Long-Term Care During COVID-19: Staff Perspectives

Context: Mealtimes in long-term care (LTC) settings play a pivotal role in the daily lives of residents. The COVID-19 pandemic and the required precautionary infection control mandates influenced many aspects of resident care within LTC homes, including mealtimes. Limited research has been conducted on how mealtimes in LTC were affected during the pandemic from staff perspectives. Objective: To understand the experiences of LTC staff on providing mealtimes during the pandemic. Methods: Semi-structured telephone interviews were conducted with 22 staff involved with mealtimes between February and April 2021. Transcripts were analysed using interpretive description. Findings: Three themes emerged from the analysis: (1) recognizing the influence of homes’ contextual factors. Home size, availability of resources, staffing levels and resident care needs influenced mealtime practices during the pandemic; (2) perceiving a compromised mealtime experience for residents and staff. Staff were frustrated and described residents as being dissatisfied with mealtime and pandemic-initiated practices as they were task-focused and socially isolating and (3) prioritizing mealtimes while trying to stay afloat. An ‘all hands-on deck’ approach, maintaining connections and being adaptive were strategies identified to mitigate the negative impact of the mandates on mealtimes during the pandemic. Limitations: Perspectives were primarily from nutrition and food service personnel. Implications: Overly restrictive public health measures resulted in mealtime practices that prioritized tasks and safety over residents’ quality of life. Learning from this pandemic experience, homes can protect the relational mealtime experience for residents by fostering teamwork, open and frequent communication and being flexible and adaptive

Influence of alternating temperature preculture on cryopreservation results for potato shoot tips

Cryopreservation is the most suitable long-term storage method for genetic resources of vegetatively maintained crops like potato. In the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) the DMSO droplet method is applied, and so far more than 1000 accessions are cryopreserved with an average regeneration rate of 58%. New experiments with four potato accessions using alternating temperatures (22/8°C day/night temperature, 8 h photoperiod, 7 d) prior to cryopreservation showed improved regeneration. The influence of this preculture on the shoot tips was studied for two wild, frost resistant species Solanum acaule and S. demissum and for two cultivated, frost sensitive potatoes S. tuberosum ‘Désirée’ and ‘King Edward’. Comparison of liquid and solid media after cryopreservation showed improved regeneration on solid media with higher regeneration percentages, less callus formation and better plantlet structure. In comparative analyses biochemical factors like soluble sugars, starch, and amino acid concentrations were measured. Shoot tips after constant and after alternating temperature preculture were analyzed. Total concentrations of soluble sugars (glucose, fructose, and sucrose) were higher for all accessions after the alternating temperature preculture, which could be the reason for improved cryopreservation results

Imaging Transient Blood Vessel Fusion Events in Zebrafish by Correlative Volume Electron Microscopy

The study of biological processes has become increasingly reliant on obtaining high-resolution spatial and temporal data through imaging techniques. As researchers demand molecular resolution of cellular events in the context of whole organisms, correlation of non-invasive live-organism imaging with electron microscopy in complex three-dimensional samples becomes critical. The developing blood vessels of vertebrates form a highly complex network which cannot be imaged at high resolution using traditional methods. Here we show that the point of fusion between growing blood vessels of transgenic zebrafish, identified in live confocal microscopy, can subsequently be traced through the structure of the organism using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) and Serial Block Face/Scanning Electron Microscopy (SBF/SEM). The resulting data give unprecedented microanatomical detail of the zebrafish and, for the first time, allow visualization of the ultrastructure of a time-limited biological event within the context of a whole organism

Complementary regulation of four Eucalyptus CBF genes under various cold conditions

CBF transcription factors play central roles in the control of freezing tolerance in plants. The isolation of two additional CBF genes, EguCBF1c and EguCBF1d, from E. gunnii, one of the cold-hardiest Eucalyptus species, is described. While the EguCBF1D protein sequence is very similar to the previously characterized EguCBF1A and EguCBF1B sequences, EguCBF1C is more distinctive, in particular in the AP2-DBD (AP2-DNA binding domain). The expression analysis of the four genes by RT-qPCR reveals that none of them is specific to one stress but they are all preferentially induced by cold, except for the EguCBF1c gene which is more responsive to salt. The calculation of the transcript copy number enables the quantification of constitutive CBF gene expression. This basal level, significant for the four genes, greatly influences the final EguCBF1 transcript level in the cold. A cold shock at 4 °C, as well as a progressive freezing which mimics a natural frost episode, trigger a fast and strong response of the EguCBF1 genes, while growth at acclimating temperatures results in a lower but more durable induction. The differential expression of the four EguCBF1 genes under these cold regimes suggests that there is a complementary regulation. The high accumulation of the CBF transcript, observed in response to the different types of cold conditions, might be a key for the winter survival of this evergreen broad-leaved tree

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Multiple Sclerosis: MicroRNA Expression Profiles Accurately Differentiate Patients with Relapsing-Remitting Disease from Healthy Controls

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs) are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS) and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA) platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS