Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function

The mammary gland is unique in its requirement to develop in close association with a depot of adipose tissue that is commonly referred to as the mammary fat pad. As discussed throughout this issue, the mammary fat pad represents a complex stromal microenvironment that includes a variety of cell types. In this article we focus on adipocytes as local regulators of epithelial cell growth and their function during lactation. Several important considerations arise from such a discussion. There is a clear and close interrelationship between different stromal tissue types within the mammary fat pad and its adipocytes. Furthermore, these relationships are both stage- and species-dependent, although many questions remain unanswered regarding their roles in these different states. Several lines of evidence also suggest that adipocytes within the mammary fat pad may function differently from those in other fat depots. Finally, past and future technologies present a variety of opportunities to model these complexities in order to more precisely delineate the many potential functions of adipocytes within the mammary glands. A thorough understanding of the role for this cell type in the mammary glands could present numerous opportunities to modify both breast cancer risk and lactation performance

Enhancement of Cell Membrane Invaginations, Vesiculation and Uptake of Macromolecules by Protonation of the Cell Surface

The different pathways of endocytosis share an initial step involving local inward curvature of the cell’s lipid bilayer. It has been shown that to generate membrane curvature, proteins or lipids enforce transversal asymmetry of the plasma membrane. Thus it emerges as a general phenomenon that transversal membrane asymmetry is the common required element for the formation of membrane curvature. The present study demonstrates that elevating proton concentration at the cell surface stimulates the formation of membrane invaginations and vesiculation accompanied by efficient uptake of macromolecules (Dextran-FITC, 70 kD), relative to the constitutive one. The insensitivity of proton induced uptake to inhibiting treatments and agents of the known endocytic pathways suggests the entry of macromolecules to proceeds via a yet undefined route. This is in line with the fact that neither ATP depletion, nor the lowering of temperature, abolishes the uptake process. In addition, fusion mechanism such as associated with low pH uptake of toxins and viral proteins can be disregarded by employing the polysaccharide dextran as the uptake molecule. The proton induced uptake increases linearly in the extracellular pH range of 6.5 to 4.5, and possesses a steep increase at the range of 4> pH>3, reaching a plateau at pH≤3. The kinetics of the uptake implies that the induced vesicles release their content to the cytosol and undergo rapid recycling to the plasma membrane. We suggest that protonation of the cell’s surface induces local charge asymmetries across the cell membrane bilayer, inducing inward curvature of the cell membrane and consequent vesiculation and uptake

Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis

Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies

Update of complications and functional outcome of the ileo-pouch anal anastomosis: overview of evidence and meta-analysis of 96 observational studies

Item does not contain fulltextOBJECTIVE: The objective of this study is to provide a comprehensive update of the outcome of the ileo-pouch anal anastomosis (IPAA). DATA SOURCES: An extensive search in PubMed, EMBASE, and The Cochrane Library was conducted. STUDY SELECTION AND DATA EXTRACTION: All studies published after 2000 reporting on complications or functional outcome after a primary open IPAA procedure for UC or FAP were selected. Study characteristics, functional outcome, and complications were extracted. DATA SYNTHESIS: A review with similar methodology conducted 10 years earlier was used to evaluate developments in outcome over time. Pooled estimates were compared using a random-effects logistic meta-analyzing technique. Analyses focusing on the effect of time of study conductance, centralization, and variation in surgical techniques were performed. RESULTS: Fifty-three studies including 14,966 patients were included. Pooled rates of pouch failure and pelvic sepsis were 4.3% (95% CI, 3.5-6.3) and 7.5% (95% CI 6.1-9.1), respectively. Compared to studies published before 2000, a reduction of 2.5% was observed in the pouch failure rate (p = 0.0038). Analysis on the effect of the time of study conductance confirmed a decline in pouch failure. Functional outcome remained stable over time, with a 24-h defecation frequency of 5.9 (95% CI, 5.0-6.9). Technical surgery aspects did not have an important effect on outcome. CONCLUSION: This review provides up to date outcome estimates of the IPAA procedure that can be useful as reference values for practice and research. It is also shows a reduction in pouch failure over time.1 juli 201

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health

GWTC-2.1: Deep extended catalog of compact binary coalescences observed by LIGO and Virgo during the first half of the third observing run

The second Gravitational-Wave Transient Catalog, GWTC-2, reported on 39 compact binary coalescences observed by the Advanced LIGO and Advanced Virgo detectors between 1 April 2019 15 ∶ 00 UTC and 1 October 2019 15 ∶ 00 UTC. Here, we present GWTC-2.1, which reports on a deeper list of candidate events observed over the same period. We analyze the final version of the strain data over this period with improved calibration and better subtraction of excess noise, which has been publicly released. We employ three matched-filter search pipelines for candidate identification, and estimate the probability of astrophysical origin for each candidate event. While GWTC-2 used a false alarm rate threshold of 2 per year, we include in GWTC-2.1, 1201 candidates that pass a false alarm rate threshold of 2 per day. We calculate the source properties of a subset of 44 high-significance candidates that have a probability of astrophysical origin greater than 0.5. Of these candidates, 36 have been reported in GWTC-2. We also calculate updated source properties for all binary black hole events previously reported in GWTC-1. If the eight additional high-significance candidates presented here are astrophysical, the mass range of events that are unambiguously identified as binary black holes (both objects ≥ 3 M⊙ ) is increased compared to GWTC-2, with total masses from ∼ 14 M ⊙ for GW190924_021846 to ∼ 182 M⊙ for GW190426_190642. Source properties calculated using our default prior suggest that the primary components of two new candidate events (GW190403_051519 and GW190426_190642) fall in the mass gap predicted by pair-instability supernova theory. We also expand the population of binaries with significantly asymmetric mass ratios reported in GWTC-2 by an additional two events (the mass ratio is less than 0.65 and 0.44 at 90% probability for GW190403_051519 and GW190917_114630 respectively), and find that two of the eight new events have effective inspiral spins χeff > 0 (at 90% credibility), while no binary is consistent with χeff < 0 at the same significance. We provide updated estimates for rates of binary black hole and binary neutron star coalescence in the local Universe

All-sky, all-frequency directional search for persistent gravitational waves from Advanced LIGO’s and Advanced Virgo’s first three observing runs

We present the first results from an all-sky all-frequency (ASAF) search for an anisotropic stochastic gravitational-wave background using the data from the first three observing runs of the Advanced LIGO and Advanced Virgo detectors. Upper limit maps on broadband anisotropies of a persistent stochastic background were published for all observing runs of the LIGO-Virgo detectors. However, a broadband analysis is likely to miss narrowband signals as the signal-to-noise ratio of a narrowband signal can be significantly reduced when combined with detector output from other frequencies. Data folding and the computationally efficient analysis pipeline, {\tt PyStoch}, enable us to perform the radiometer map-making at every frequency bin. We perform the search at 3072 {\tt{HEALPix}} equal area pixels uniformly tiling the sky and in every frequency bin of width $1/32$~Hz in the range $20-1726$~Hz, except for bins that are likely to contain instrumental artefacts and hence are notched. We do not find any statistically significant evidence for the existence of narrowband gravitational-wave signals in the analyzed frequency bins. Therefore, we place $95\%$ confidence upper limits on the gravitational-wave strain for each pixel-frequency pair, the limits are in the range $(0.030 - 9.6) \times10^{-24}$. In addition, we outline a method to identify candidate pixel-frequency pairs that could be followed up by a more sensitive (and potentially computationally expensive) search, e.g., a matched-filtering-based analysis, to look for fainter nearly monochromatic coherent signals. The ASAF analysis is inherently independent of models describing any spectral or spatial distribution of power. We demonstrate that the ASAF results can be appropriately combined over frequencies and sky directions to successfully recover the broadband directional and isotropic results

Reconstructing the Neanderthal brain using computational anatomy

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/