Development of a cell population migration assay

Cellular migration is central to many physiological and pathological processes, from wound healing and the immune response to cancer cell invasion. Many in-vitro assays have been developed to study these processes and can be classified by the nature of the assay, for example migration of single cells or entire populations, as well as migration on a planar surface or through a 3D structure. This work concerns the development of an assay to study the migration of whole populations of cells across a deformable planar substratum, which may be coated in adsorbed adhesion molecules. The technique detailed below was developed from the Teflon fence assay

Sustainability through Resilience. The very essence of the Wine Industry

Abstract= -Purpose: The current environment surrounding the wine industry is extremely volatile. This paper, therefore, examines how Old World wine producers use marketing and supply chain management to sustain their business in the current business environment. -Design/methodology/approach: Seventeen employees from ten Italian wine producers were interviewed using a grounded theory approach to determine how they are dealing with the current economic conditions and competitive landscape. -Findings: Leaders of successful Italian wineries, those large and small who achieve sustainability in the face of intense competitive pressures, engage in detailed assessments of the marketplace and adopt specific and focused strategies to become resilient. Two discovered in this study include (1) focusing what it means \u201cto be Italian\u201d as in culture and history and (2) adapting to the marketplace and innovating. - Practical implications: The research offers prescriptive marketing strategy for wine producers to become and/or remain sustainable

Role of prolactin, growth hormone and insulin-like growth factor 1 in mammary gland involution in the dairy cow.

Bovine mammary involution, an important process for subsequent lactations, is characterized by loss of epithelial cells by apoptosis, but its hormonal regulation is still not well defined. Prolactin (PRL) and growth hormone (GH) play a specific role on rat mammary gland apoptosis, through insulin-like growth factor 1 (IGF-1) and the IGF binding protein (IGFBP) system. The purpose of our investigation was to determine the possible role of PRL, GH, and IGF-1 on cell survival and on IGFBP-5 expression in the bovine mammary gland. Mammary gland explants were cultured in the presence of cortisol, 17beta-estradiol, progesterone, insulin, PRL, GH, and IGF-1 and with the same treatment but without PRL, GH or IGF-1, respectively. After 24 h of culture, we determined the level of apoptosis through evaluation of DNA laddering in the oligonucleosomal fraction and examined IGFBP-5 messenger RNA (mRNA) expression. The results show a high level of DNA laddering and an increase in IGFBP-5 mRNA content in mammary explants cultured in the absence of PRL, GH, or IGF-I with respect to explants treated with all hormones. Moreover, explants cultured in presence of PRL, GH, or IGF-I show a low level of DNA laddering and IGFBP-5 expression with respect to explants cultured without any hormones. These data demonstrate a relationship between levels of apoptosis and IGFBP-5 mRNA expression in the bovine mammary gland and confirm the involvement of this binding protein programmed cell death and its relationship with the main lactogenic hormones

Increasing alkyl chain length in a series of layered metal–organic frameworks aids ultrasonic exfoliation to form nanosheets

Metal–organic framework nanosheets (MONs) are attracting increasing attention as a diverse class of two-dimensional materials derived from metal–organic frameworks (MOFs). The principles behind the design of layered MOFs that can readily be exfoliated to form nanosheets, however, remain poorly understood. Here we systematically investigate an isoreticular series of layered MOFs functionalized with alkoxy substituents in order to understand the effect of substituent alkyl chain length on the structure and properties of the resulting nanosheets. A series of 2,5-alkoxybenzene-1,4-dicarboxylate ligands (O2CC6H2(OR)2CO2, R = methyl–pentyl, 1–5, respectively) was used to synthesize copper paddle-wheel MOFs. Rietveld and Pawley fitting of powder diffraction patterns for compounds Cu(3–5)(DMF) showed they adopt an isoreticular series with two-dimensional connectivity in which the interlayer distance increases from 8.68 Å (R = propyl) to 10.03 Å (R = pentyl). Adsorption of CO2 by the MOFs was found to increase from 27.2 to 40.2 cm3 g–1 with increasing chain length, which we attribute to the increasing accessible volume associated with increasing unit-cell volume. Ultrasound was used to exfoliate the layered MOFs to form MONs, with shorter alkyl chains resulting in higher concentrations of exfoliated material in suspension. The average height of MONs was investigated by AFM and found to decrease from 35 ± 26 to 20 ± 12 nm with increasing chain length, with the thinnest MONs observed being only 5 nm, corresponding to five framework layers. These results indicate that careful choice of ligand functionalities can be used to tune nanosheet structure and properties, enabling optimization for a variety of applications

Using grounded theory for theory building in operations management research:a study on inter-firm relationship governance

Purpose – Qualitative theory building approaches, such as grounded theory method (GTM), are still not very widespread and rigorously applied in operations management (OM) research. Yet it is agreed that more systematic observation of current industrial phenomena is necessary to help managers deal with their problems. The purpose of this paper is to provide an example to help guide other researchers on using GTM for theory building in OM research. Design/methodology/approach – A GTM study in the German automotive industry consisting of 31 interviews is followed by a validation stage comprising a survey (110 responses) and a focus group. Findings – The result is an example of conducting GTM research in OM, illustrated by the development of the novel collaborative enterprise governance framework for inter-firm relationship governance in the German automotive industry. Research limitations/implications – GTM is appropriate for qualitative theory building research, but the resultant theories need further testing. Research is necessary to identify the transferability of the collaborative enterprise governance concept to other industries than automotive, to other organisational areas than R&D and to product and service settings that are less complex and innovative. Practical implications – The paper helps researchers make more informed use of GTM when engaging in qualitative theory building research in OM. Originality/value – There is a lack of explicit and well-informed use of GTM in OM research because of poor understanding. This paper addresses this deficiency. The collaborative enterprise governance framework is a significant contribution in an area of growing importance within OM

A cell cycle model for somitogenesis: mathematical formulation and numerical simulation

After many years of research, the mechanisms that generate a periodic pattern of repeated elements (somites) along the length of the embryonic body axis is still one of the major unresolved problems in developmental biology. Here we present a mathematical formulation of the cell cycle model for somitogenesis proposed in Development105 (1989), 119–130. Somite precursor cells in the node are asynchronous, and therefore, as a population, generate continuously pre-somite cells which enter the segmental plate. The model makes the hypothesis that there exists a time window within the cell cycle, making up one-seventh of the cycle, which gates the pre-somite cells so that they make somites discretely, seven per cycle. We show that the model can indeed account for the spatiotemporal patterning of somite formation during normal development as well as the periodic abnormalities produced by heat shock treatment. We also relate the model to recent molecular data on the process of somite formation

Emerging role of insulin with incretin therapies for management of type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a progressive disease warranting intensification of treatment, as beta-cell function declines over time. Current treatment algorithms recommend metformin as the first-line agent, while advocating the addition of either basal-bolus or premixed insulin as the final level of intervention. Incretin therapy, including incretin mimetics or enhancers, are the latest group of drugs available for treatment of T2DM. These agents act through the incretin axis, are currently recommended as add-on agents either as second-or third-line treatment, without concurrent use of insulin. Given the novel role of incretin therapy in terms of reducing postprandial hyperglycemia, and favorable effects on weight with reduced incidence of hypoglycemia, we explore alternative options for incretin therapy in T2DM management. Furthermore, as some evidence alludes to incretins potentially increasing betacell mass and altering disease progression, we propose introducing these agents earlier in the treatment algorithm. In addition, we suggest the concurrent use of incretins with insulin, given the favorable effects especially in relation to weight gain

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362