Faint dwarfs as a test of DM models: WDM vs. CDM

We use high resolution Hydro$+$N-Body cosmological simulations to compare the assembly and evolution of a small field dwarf (stellar mass ~ 10$^{6-7}$ M$\odot$, total mass 10$^{10}$ M$\odot$ in $\Lambda$ dominated CDM and 2keV WDM cosmologies. We find that star formation (SF) in the WDM model is reduced and delayed by 1-2 Gyr relative to the CDM model, independently of the details of SF and feedback. Independent of the DM model, but proportionally to the SF efficiency, gas outflows lower the central mass density through `dynamical heating', such that all realizations have circular velocities $<$ 20kms at 500$~$pc, in agreement with local kinematic constraints. As a result of dynamical heating, older stars are less centrally concentrated than younger stars, similar to stellar population gradients observed in nearby dwarf galaxies. Introducing an important diagnostic of SF and feedback models, we translate our simulations into artificial color-magnitude diagrams and star formation histories in order to directly compare to available observations. The simulated galaxies formed most of their stars in many $\sim$10 Myr long bursts. The CDM galaxy has a global SFH, HI abundance and Fe/H and alpha-elements distribution well matched to current observations of dwarf galaxies. These results highlight the importance of directly including `baryon physics' in simulations when 1) comparing predictions of galaxy formation models with the kinematics and number density of local dwarf galaxies and 2) differentiating between CDM and non-standard models with different DM or power spectra.Comment: 13 pages including Appendix on Color Magnitude Diagrams. Accepted by MNRAS. Added one plot and details on ChaNGa implementation. Reduced number of citations after editorial reques

Arranging Small Molecules with Subnanometer Precision on DNA Origami Substrates for the Single‐Molecule Investigation of Protein–Ligand Interactions

DNA origami nanostructures are versatile substrates for the single‐molecule investigation of biomolecular interactions as they enable the display of molecular species in complex arrangements. Herein, the fundamental limitations of this approach are explored by displaying pairs of small‐molecule ligands of the protein trypsin on DNA origami substrates and adjusting their ligand–ligand spacing with subnanometer precision. Bidentate binding of trypsin to the ligand pairs is investigated by atomic force microscopy (AFM), microscale thermophoresis (MST), and molecular dynamics simulations. Bidentate trypsin binding is strongly affected by the distance of the ligand pairs and the accessibility of the protein's binding pockets. MST cannot resolve the differences in bidentate trypsin binding because of the nonspecific binding of trypsin to the DNA origami substrates, rendering the AFM‐based single‐molecule detection of binding events superior to ensemble measurements. Finally, even monodentate binding to a single ligand may be affected by subnanometer variations in its position, highlighting the importance of local microenvironments that vary even over molecular distances. While this single‐molecule approach can provide viable information on the effects of ligand arrangements on bidentate protein binding, in‐depth investigations into the nature of local microenvironments will be required to exploit its full potential

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

Bestial boredom: a biological perspective on animal boredom and suggestions for its scientific investigation

Boredom is likely to have adaptive value in motivating exploration and learning, and many animals may possess the basic neurological mechanisms to support it. Chronic inescapable boredom can be extremely aversive, and understimulation can harm neural, cognitive and behavioural flexibility. Wild and domesticated animals are at particular risk in captivity, which is often spatially and temporally monotonous. Yet biological research into boredom has barely begun, despite having important implications for animal welfare, the evolution of motivation and cognition, and for human dysfunction at individual and societal levels. Here I aim to facilitate hypotheses about how monotony affects behaviour and physiology, so that boredom can be objectively studied by ethologists and other scientists. I cover valence (pleasantness) and arousal (wakefulness) qualities of boredom, because both can be measured, and I suggest boredom includes suboptimal arousal and aversion to monotony. Because the suboptimal arousal during boredom is aversive, individuals will resist low arousal. Thus, behavioural indicators of boredom will, seemingly paradoxically, include signs of increasing drowsiness, alongside bouts of restlessness, avoidance and sensation-seeking behaviour. Valence and arousal are not, however, sufficient to fully describe boredom. For example, human boredom is further characterized by a perception that time ‘drags’, and this effect of monotony on time perception can too be behaviourally assayed in animals. Sleep disruption and some abnormal behaviour may also be caused by boredom. Ethological research into this emotional phenomenon will deepen understanding of its causes, development, function and evolution, and will enable evidence-based interventions to mitigate human and animal boredom

Fusarium and mycotoxin spectra in Swiss barley are affected by various cropping techniques

Fusarium head blight is one of the most important cereal diseases worldwide. Cereals differ in terms of the main occurring Fusarium species and the infection is influenced by various factors, such as weather and cropping measures. Little is known about Fusarium species in barley in Switzerland, hence harvest samples from growers were collected in 2013 and 2014, along with information on respective cropping factors. The incidence of different Fusarium species was obtained by using a seed health test and mycotoxins were quantified by LC-MS/MS. With these techniques, the most dominant species, F. graminearum, and the most prominent mycotoxin, deoxynivalenol (DON), were identified. Between the three main Swiss cropping systems, Organic, Extenso and Proof of ecological performance, we observed differences with the lowest incidence and toxin accumulation in organically cultivated barley. Hence, we hypothesise that this finding was based on an array of growing techniques within a given cropping system. We observed that barley samples from fields with maize as previous crop had a substantially higher F. graminearum incidence and elevated DON accumulation compared with other previous crops. Furthermore, the use of reduced tillage led to a higher disease incidence and toxin content compared with samples from ploughed fields. Further factors increasing Fusarium infection were high nitrogen fertilisation as well as the application of fungicides and growth regulators. Results from the current study can be used to develop optimised cropping systems that reduce the risks of mycotoxin contamination

Pervasive and strong effects of plants on soil chemistry: a meta-analysis of individual plant ‘Zinke’ effects

Plant species leave a chemical signature in the soils below them, generating fine-scale spatial variation that drives ecological processes. Since the publication of a seminal paper on plant-mediated soil heterogeneity by Paul Zinke in 1962, a robust literature has developed examining effects of individual plants on their local environments (individual plant effects). Here, we synthesize this work using meta-analysis to show that plant effects are strong and pervasive across ecosystems on six continents. Overall, soil properties beneath individual plants differ from those of neighbours by an average of 41%. Although the magnitudes of individual plant effects exhibit weak relationships with climate and latitude, they are significantly stronger in deserts and tundra than forests, and weaker in intensively managed ecosystems. The ubiquitous effects of plant individuals and species on local soil properties imply that individual plant effects have a role in plant–soil feedbacks, linking individual plants with biogeochemical processes at the ecosystem scale

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

Epigenetic Reprogramming of Lineage-Committed Human Mammary Epithelial Cells Requires DNMT3A and Loss of DOT1L

Summary Organogenesis and tissue development occur through sequential stepwise processes leading to increased lineage restriction and loss of pluripotency. An exception to this appears in the adult human breast, where rare variant epithelial cells exhibit pluripotency and multilineage differentiation potential when removed from the signals of their native microenvironment. This phenomenon provides a unique opportunity to study mechanisms that lead to cellular reprogramming and lineage plasticity in real time. Here, we show that primary human mammary epithelial cells (HMECs) lose expression of differentiated mammary epithelial markers in a manner dependent on paracrine factors and epigenetic regulation. Furthermore, we demonstrate that HMEC reprogramming is dependent on gene silencing by the DNA methyltransferase DNMT3A and loss of histone transcriptional marks following downregulation of the methyltransferase DOT1L. These results demonstrate that lineage commitment in adult tissues is context dependent and highlight the plasticity of somatic cells when removed from their native tissue microenvironment