Monitoring techniques for the manufacture of tapered optical fibers

The use of a range of optical techniques to monitor the process of fabricating optical fiber tapers is investigated. Thermal imaging was used to optimize the alignment of the optical system; the transmission spectrum of the fiber was monitored to confirm that the tapers had the required optical properties and the strain induced in the fiber during tapering was monitored using in-line optical fiber Bragg gratings. Tapers were fabricated with diameters down to 5 μm and with waist lengths of 20 mm using single-mode SMF-28 fiber

Cytoplasmic Redox Imbalance in the Thioredoxin System Activates Hsf1 and Results in Hyperaccumulation of the Sequestrase Hsp42 With Misfolded Proteins

Cells employ multiple systems to maintain homeostasis when experiencing environmental stress. For example, the folding of nascent polypeptides is exquisitely sensitive to proteotoxic stressors including heat, pH, and oxidative stress, and is safeguarded by a network of protein chaperones that concentrate potentially toxic misfolded proteins into transient assemblies to promote folding or degradation. The redox environment itself is buffered by both cytosolic and organellar thioredoxin and glutathione pathways. How these systems are linked is poorly understood. Here, we determine that specific disruption of the cytosolic thioredoxin system resulted in constitutive activation of the heat shock response in Saccharomyces cerevisiae and accumulation of the sequestrase Hsp42 into an exaggerated and persistent juxtanuclear quality control (JUNQ) compartment. Terminally misfolded proteins also accumulated in this compartment in thioredoxin reductase (TRR1)-deficient cells, despite apparently normal formation and dissolution of transient cytoplasmic quality control (CytoQ) bodies during heat shock. Notably, cells lacking TRR1 and HSP42 exhibited severe synthetic slow growth exacerbated by oxidative stress, signifying a critical role for Hsp42 under redox-challenged conditions. Finally, we demonstrated that Hsp42 localization patterns in trr1∆ cells mimic those observed in chronically aging and glucose-starved cells, linking nutrient depletion and redox imbalance with management of misfolded proteins via a process of long-term sequestration

Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli

Human skin equivalents (HSEs) are an increasingly popular research tool due to limitations associated with animal testing for dermatological research. They recapitulate many aspects of skin structure and function, however, many only contain two basic cell types to model dermal and epidermal compartments, which limits their application. We describe advances in the field skin tissue modeling to produce a construct containing sensory-like neurons that is responsive to known noxious stimuli. Through incorporation of mammalian sensory-like neurons, we were able to recapitulate aspects of the neuroinflammatory response including secretion of substance P and a range of pro-inflammatory cytokines in response to a well-characterized neurosensitizing agent: capsaicin. We observed that neuronal cell bodies reside in the upper dermal compartment with neurites extending toward the keratinocytes of the stratum basale where they exist in close proximity to one another. These data suggest that we are able to model aspects of the neuroinflammatory response that occurs during exposure to dermatological stimuli including therapeutics and cosmetics. We propose that this skin construct can be considered a platform technology with a wide range of applications including screening of actives, therapeutics, modeling of inflammatory skin diseases, and fundamental approaches to probe underlying cell and molecular mechanisms

Links that speak: The global language network and its association with global fame

International audienceLanguages vary enormously in global importance because of historical, demographic, political, and technological forces. However , beyond simple measures of population and economic power, there has been no rigorous quantitative way to define the global influence of languages. Here we use the structure of the networks connecting multilingual speakers and translated texts, as expressed in book translations, multiple language editions of Wikipedia, and Twitter, to provide a concept of language importance that goes beyond simple economic or demographic measures. We find that the structure of these three global language networks (GLNs) is centered on English as a global hub and around a handful of intermediate hub languages, which include Spanish, German, French, Russian, Portuguese, and Chinese. We validate the measure of a language's centrality in the three GLNs by showing that it exhibits a strong correlation with two independent measures of the number of famous people born in the countries associated with that language. These results suggest that the position of a language in the GLN contributes to the visibility of its speakers and the global popularity of the cultural content they produce. networks | languages | culture | digital humanities | fam

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

Application of single molecule technology to rapidly map long DNA and study the conformation of stretched DNA

Herein we describe the first application of direct linear analysis (DLA) to the mapping of a bacterial artificial chromosome (BAC), specifically the 185.1 kb-long BAC 12M9. DLA is a single molecule mapping technology, based on microfluidic elongation and interrogation of individual DNA molecules, sequence-specifically tagged with bisPNAs. A DNA map with S/N ratio sufficiently high to detect all major binding sites was obtained using only 200 molecule traces. A new method was developed to extract an oriented map from an averaged map that included a mixture of head-first and tail-first DNA traces. In addition, we applied DLA to study the conformation and tagging of highly stretched DNA. Optimal conditions for promoting sequence-specific binding of bisPNA to an 8 bp target site were elucidated using DLA, which proved superior to electromobility shift assays. DLA was highly reproducible with a hybridized tag position localized with an accuracy of ±0.7 µm or ±2.1 kb demonstrating its utility for rapid mapping of large DNA at the single molecule level. Within this accuracy, DNA molecules, stretched to at least 85% of their contour length, were stretched uniformly, so that the map expressed in relative coordinates, was the same regardless of the molecule extension

Overview of the Large-Scale Biosphere–Atmosphere Experiment in Amazonia Data Model Intercomparison Project (LBA-DMIP)

A fundamental question connecting terrestrial ecology and global climate change is the sensitivity of key terrestrial biomes to climatic variability and change. The Amazon region is such a key biome: it contains unparalleled biological diversity, a globally significant store of organic carbon, and it is a potent engine driving global cycles of water and energy. The importance of understanding how land surface dynamics of the Amazon region respond to climatic variability and change is widely appreciated, but despite significant recent advances, large gaps in our understanding remain. Understanding of energy and carbon exchange between terrestrial ecosystems and the atmosphere can be improved through direct observations and experiments, as well as through modeling activities. Land surface/ecosystem models have become important tools for extrapolating local observations and understanding to much larger terrestrial regions. They are also valuable tools to test hypothesis on ecosystem functioning. Funded by NASA under the auspices of the LBA (the Large-Scale Biosphere–Atmosphere Experiment in Amazonia), the LBA Data Model Intercomparison Project (LBA-DMIP) uses a comprehensive data set from an observational network of flux towers across the Amazon, and an ecosystem modeling community engaged in ongoing studies using a suite of different land surface and terrestrial ecosystem models to understand Amazon forest function. Here an overview of this project is presented accompanied by a description of the measurement sites, data, models and protocol

Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators

Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on differential single-cell gene expression analysis of mesenchymal osteolineage cells close to and further removed from hematopoietic stem/progenitor cells to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. Amongst the genes which were preferentially expressed in proximal cells, we functionally examined three secreted or cell surface molecules not previously connected to HSPC biology: the secreted RNase Angiogenin, the cytokine IL18 and the adhesion molecule Embigin and discovered that all of these factors are HSPC quiescence regulators. Our proximity-based differential single cell approach therefore reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance understanding of microenvironmental regulation of stem cell function

International variations and sex disparities in the treatment of peripheral arterial occlusive disease : a report from VASCUNET and the International Consortium Of Vascular Registries

Objective: The aim of this study was to determine sex specific differences in the invasive treatment of symptomatic peripheral arterial occlusive disease (PAOD) between member states participating in the VASCUNET and International Consortium of Vascular Registries.Methods: Data on open surgical revascularisation and peripheral vascular intervention (PVI) of symptomatic PAOD from 2010 to 2017 were collected from population based administrative and registry data from 11 countries. Differences in age, sex, indication, and invasive treatment modality were analysed.Results: Data from 11 countries covering 671 million inhabitants and 1 164 497 hospitalisations (40% women, mean age 72 years, 49% with intermittent claudication, 54% treated with PVI) in Europe (including Russia), North America, Australia, and New Zealand were included. Patient selection and treatment modality varied widely for the proportion of female patients (23% in Portugal and 46% in Sweden), the proportion of patients with claudication (6% in Italy and 69% in Russia), patients’ mean age (70 years in the USA and 76 years in Italy), the proportion of octogenarians (8% in Russia and 33% in Sweden), and the proportion of PVI (24% in Russia and 88% in Italy). Numerous differences between females and males were observed in regard to patient age (72 vs. 70 years), the proportion of octogenarians (28% vs. 15%), proportion of patients with claudication (45% vs. 51%), proportion of PVI (57% vs. 51%), and length of hospital stay (7 days vs. 6 days).Conclusion: Remarkable differences regarding the proportion of peripheral vascular interventions, patients with claudication, and octogenarians were seen across countries and sexes. Future studies should address the underlying reasons for this, including the impact of national societal guidelines, reimbursement, and differences in health maintenance.peer-reviewe

The impact of growth promoters on muscle growth and the potential consequences for meat quality

To meet the demands of increased global meat consumption, animal production systems will have to become more efficient, or at least maintain the current efficiency utilizing feed ingredients that are not also used for human consumption. Use of growth promoters is a potential option for increasing production animal feed efficiency and increased muscle growth. The objective of this manuscript is to describe the mechanisms by which the growth promoters, beta-adrenergic agonists and growth hormone, mediate their effects, with specific consideration of the aspects which have implications for meat quality.The work described in this manuscript was supported by a BBSRC LINK Zoetis grant, number BB/J005320/1, as well as a BBSRC CASE PhD studentship awarded to David Brown and Krystal Hemmings and a PhD scholarship awarded to Molebeledi HD Mareko by the Botswana College of Agricultur