A one-step procedure to probe the viscoelastic properties of cells by Atomic Force Microscopy

The increasingly recognised importance of viscoelastic properties of cells in pathological conditions requires rapid development of advanced cell microrheology technologies. Here, we present a novel Atomic Force Microscopy (AFM)-microrheology (AFM2) method for measuring the viscoelastic properties in living cells, over a wide range of continuous frequencies (0.005 Hz ~ 200 Hz), from a simple stress-relaxation nanoindentation. Experimental data were directly analysed without the need for pre-conceived viscoelastic models. We show the method had an excellent agreement with conventional oscillatory bulk-rheology measurements in gels, opening a new avenue for viscoelastic characterisation of soft matter using minute quantity of materials (or cells). Using this capability, we investigate the viscoelastic responses of cells in association with cancer cell invasive activity modulated by two important molecular regulators (i.e. mutation of the p53 gene and Rho kinase activity). The analysis of elastic (G′(ω)) and viscous (G″(ω)) moduli of living cells has led to the discovery of a characteristic transitions of the loss tangent (G″(ω)/G′(ω)) in the low frequency range (0.005 Hz ~ 0.1 Hz) that is indicative of the capability for cell restructuring of F-actin network. Our method is ready to be implemented in conventional AFMs, providing a simple yet powerful tool for measuring the viscoelastic properties of living cells

Development Strategies for Animal Medical Therapeutics

The process of developing a new therapeutic is long, expensive, and risky. Current small animal models are often poor representations of human disease, contributing to the high rate of failure in human trials. Outbred dogs can be excellent models for researching human disease. Clinical trials in dogs are inexpensive and efficient compared with human trials. Advaxis, a clinical-stage biotechnology company developing cancer immunotherapies, provides one case study on how trials in dogs can help advance trials in humans

Does kindness always pay? The influence of recipient affection and generosity on young children's allocation decisions in a resource distribution task

The aim of the current study was to determine whether the level of generosity shown by 3- to 8-year-old children (N = 136; M age = 69 months) in a resource distribution task would vary according to whether the recipient had previously displayed kind (affection and generosity) and/or non-kind (non-affection and non-generosity) behavior towards a third party. We first asked whether donor children would show higher levels of generosity towards an affectionate than a non-affectionate recipient (condition 1), and a generous than a non-generous recipient (condition 2), before pitting the two forms of recipient kindness directly against each other (condition 3). Last, we asked whether donations to generous recipients would decrease if the recipient simultaneously displayed non-kind behavior through a lack of affection (condition 4). Here we show that children allocated a greater share of the available resource to generous and affectionate recipients than non-generous and non-affectionate recipients respectively. However, when asked to divide resources between a generous and an affectionate recipient, or two recipients who had each displayed a combination of kind and non-kind behavior, children allocated each recipient an equal share of the resource. These findings suggest that children donate selectively based on previous information regarding recipient generosity and affection, however when both forms of kindness are pitted directly against each other, children strive for equality, suggesting that kindness engenders donor generosity irrespective of the form of kindness previously displayed

Expression of RUNX1 correlates with poor patient prognosis in triple negative breast cancer

The RUNX1 transcription factor is widely recognised for its tumour suppressor effects in leukaemia. Recently a putative link to breast cancer has started to emerge, however the function of RUNX1 in breast cancer is still unknown. To investigate if RUNX1 expression was important to clinical outcome in primary breast tumours a tissue microarray (TMA) containing biopsies from 483 patients with primary operable invasive ductal breast cancer was stained by immunohistochemistry. RUNX1 was associated with progesterone receptor (PR)-positive tumours (P<0.05), more tumour CD4+(P<0.05) and CD8+(P<0.01) T-lymphocytic infiltrate, increased tumour CD138+plasma cell (P<0.01) and more CD68+macrophage infiltrate (P<0.001). RUNX1 expression did not influence outcome of oestrogen receptor (ER)-positive or HER2-positive disease, however on univariate analysis a high RUNX1 protein was significantly associated with poorer cancer-specific survival in patients with ER-negative (P<0.05) and with triple negative (TN) invasive breast cancer (P<0.05). Furthermore, multivariate Cox regression analysis of cancer-specific survival showed a trend towards significance in ER-negative patients (P<0.1) and was significant in triple negative patients (P<0.05). Of relevance, triple negative breast cancer currently lacks good biomarkers and patients with this subtype do not benefit from the option of targeted therapy unlike patients with ER-positive or HER2-positive disease. Using multivariate analysis RUNX1 was identified as an independent prognostic marker in the triple negative subgroup. Overall, our study identifies RUNX1 as a new prognostic indicator correlating with poor prognosis specifically in the triple negative subtype of human breast cancer

The Development of CERVIS: Cervical cancer Early Response Visual Identification System

The goal of CERVIS is to make a substantial, positive impact in the cervical cancer diagnostic space through the development of a minimally invasive, cost effective solution that enables women in low-resource settings to test for cervical cancer on a frugal and effective platform. In the developed world, there are a variety of options that can aid in early detection, including pap smears. However, due to the high cost and laboratory requirements that accompany this procedure, women in low-resource settings rarely have access to this preventative care or regular screenings for cervical cancer. Using new research about the changes in the vaginal microbiome, we aim to create a frugal, visual diagnostic screening tool for early stage cervical cancer as an alternative to the existing expensive, invasive, and clinic-dependent methods. Outcomes will be measured by partnering with a Kenyan NGO to collect data from several clinics

Dynamic Computable General Equilibrium Simulations in Support of Quantitative Foresight Modeling to Inform the CGIAR Research Portfolio

In the context of the project Quantitative Foresight Modeling to Inform the CGIAR Research Portfolio, IFPRI’s International Model for Policy Analysis of Agricultural Commodities and Trade (IMPACT) was linked to the global dynamic computable general equilibrium model, GLOBE-Energy. This linkage is documented here to provide a detailed account of the methodological approach. GLOBE’s role within the analytical framework of the project is to assess the macroeconomic income and welfare effects associated with the alternative pathways for agricultural productivity under the different scenarios and to feed the simulated aggregate income time paths back to IMPACT

Searching for black holes in subways.

Abstract Current mobile agent algorithms for mapping faults in computer networks assume that the network is static. However, for large classes of highly dynamic networks (e.g., wireless mobile ad hoc networks, sensor networks, vehicular networks), the topology changes as a function of time. These networks, called delay-tolerant, challenged, opportunistic, etc., have never been investigated with regard to locating faults. We consider a subclass of these networks modelled on an urban subway system. We examine the problem of creating a map of such a subway. More precisely, we study the problem of a team of asynchronous computational entities (the mapping agents) determining the location of black holes in a highly dynamic graph, whose edges are defined by the asynchronous movements of mobile entities (the subway carriers). We determine necessary conditions for the problem to be solvable. We then present and analyze a solution protocol; we show that our algorithm solves the fault mapping problem in subway networks with the minimum number of agents possible, k = γ + 1, where γ is the number of carrier stops at black holes. The number of carrier moves between stations required by the algorithm in the worst case is , where n C is the number of subway trains, and l R is the length of the subway route with the most stops. We establish lower bounds showing that this bound is tight. Thus, our protocol is both agent-optimal and move-optimal

The Microbe Directory: An Annotated, Searchable Inventory of Microbes\u27 Characteristics

The Microbe Directory is a collective research effort to profile and annotate more than 7,500 unique microbial species from the MetaPhlAn2 database that includes bacteria, archaea, viruses, fungi, and protozoa. By collecting and summarizing data on various microbes\u27 characteristics, the project comprises a database that can be used downstream of large-scale metagenomic taxonomic analyses, allowing one to interpret and explore their taxonomic classifications to have a deeper understanding of the microbial ecosystem they are studying. Such characteristics include, but are not limited to: optimal pH, optimal temperature, Gram stain, biofilm-formation, spore-formation, antimicrobial resistance, and COGEM class risk rating. The database has been manually curated by trained student-researchers from Weill Cornell Medicine and CUNY-Hunter College, and its analysis remains an ongoing effort with open-source capabilities so others can contribute. Available in SQL, JSON, and CSV (i.e. Excel) formats, the Microbe Directory can be queried for the aforementioned parameters by a microorganism\u27s taxonomy. In addition to the raw database, The Microbe Directory has an online counterpart ( https://microbe.directory/) that provides a user-friendly interface for storage, retrieval, and analysis into which other microbial database projects could be incorporated. The Microbe Directory was primarily designed to serve as a resource for researchers conducting metagenomic analyses, but its online web interface should also prove useful to any individual who wishes to learn more about any particular microbe

Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb

BackgroundThe bat has strikingly divergent forelimbs (long digits supporting wing membranes) and hindlimbs (short, typically free digits) due to the distinct requirements of both aerial and terrestrial locomotion. During embryonic development, the morphology of the bat forelimb deviates dramatically from the mouse and chick, offering an alternative paradigm for identifying genes that play an important role in limb patterning.ResultsUsing transcriptome analysis of developing Natal long-fingered bat (Miniopterus natalensis) fore- and hindlimbs, we demonstrate that the transcription factor Meis2 has a significantly higher expression in bat forelimb autopods compared to hindlimbs. Validation by reverse transcriptase and quantitative polymerase chain reaction (RT-qPCR) and whole mount in situ hybridisation shows that Meis2, conventionally known as a marker of the early proximal limb bud, is upregulated in the bat forelimb autopod from CS16. Meis2 expression is localised to the expanding interdigital webbing and the membranes linking the wing to the hindlimb and tail. In mice, Meis2 is also expressed in the interdigital region prior to tissue regression. This interdigital Meis2 expression is not activated by retinoic acid (RA) signalling as it is present in the retained interdigital tissue of Rdh10trex/trex mice, which lack RA. Additionally, genes encoding RA-synthesising enzymes, Rdh10 and Aldh1a2, and the RA nuclear receptor Rarβ are robustly expressed in bat fore- and hindlimb interdigital tissues indicating that the mechanism that retains interdigital tissue in bats also occurs independently of RA signalling.ConclusionsMammalian interdigital Meis2 expression, and upregulation in the interdigital webbing of bat wings, suggests an important role for Meis2 in autopod development. Interdigital Meis2 expression is RA-independent, and retention of interdigital webbing in bat wings is not due to the suppression of RA-induced cell death. Rather, RA signalling may play a role in the thinning (rather than complete loss) of the interdigital tissue in the bat forelimb, while Meis2 may interact with other factors during both bat and mouse autopod development to maintain a pool of interdigital cells that contribute to digit patterning and growth.Electronic supplementary materialThe online version of this article (doi:10.1186/s13227-015-0001-y) contains supplementary material, which is available to authorized users