scholarly journals Nanoparticle elasticity regulates phagocytosis and cancer cell uptake

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz4316 ◽  
Author(s):  
Yue Hui ◽  
Xin Yi ◽  
David Wibowo ◽  
Guangze Yang ◽  
Anton P. J. Middelberg ◽  
...  

The ability of cells to sense external mechanical cues is essential for their adaptation to the surrounding microenvironment. However, how nanoparticle mechanical properties affect cell-nanoparticle interactions remains largely unknown. Here, we synthesized a library of silica nanocapsules (SNCs) with a wide range of elasticity (Young’s modulus ranging from 560 kPa to 1.18 GPa), demonstrating the impact of SNC elasticity on SNC interactions with cells. Transmission electron microscopy revealed that the stiff SNCs remained spherical during cellular uptake. The soft SNCs, however, were deformed by forces originating from the specific ligand-receptor interaction and membrane wrapping, which reduced their cellular binding and endocytosis rate. This work demonstrates the crucial role of the elasticity of nanoparticles in modulating their macrophage uptake and receptor-mediated cancer cell uptake, which may shed light on the design of drug delivery vectors with higher efficiency.

Author(s):  
Donald Bloxham

Against majority opinion within his profession, Donald Bloxham argues that it is legitimate, often unavoidable, and frequently important for historians to make value judgements about the past. History and Morality draws on a wide range of historical examples, and its author’s insights as a practising historian. Examining concepts like impartiality, neutrality, contextualization, and the use and abuse of the idea of the past as a foreign country, Bloxham’s book investigates how the discipline has got to the point where what is preached can be so inconsistent with what is practised. It illuminates how far tacit moral judgements infuse works of history, and how strange those histories would look if the judgements were removed. Bloxham argues that rather than trying to eradicate all judgemental elements from their work historians need to think more consistently about how, and with what justification, they make the judgements that they do. The importance of all this lies not just in the responsibilities that historians bear towards the past—responsibilities to take historical actors on those actors’ own terms and to portray the impact of those actors’ deeds—but also in the role of history as a source of identity, pride, and shame in the present. The account of moral thought in History and Morality has ramifications far beyond the activities of vocational historians.


2018 ◽  
Vol 18 (16) ◽  
pp. 12105-12121 ◽  
Author(s):  
Thomas Fauchez ◽  
Steven Platnick ◽  
Tamás Várnai ◽  
Kerry Meyer ◽  
Céline Cornet ◽  
...  

Abstract. In a context of global climate change, the understanding of the radiative role of clouds is crucial. On average, ice clouds such as cirrus have a significant positive radiative effect, but under some conditions the effect may be negative. However, many uncertainties remain regarding the role of ice clouds on Earth's radiative budget and in a changing climate. Global satellite observations are particularly well suited to monitoring clouds, retrieving their characteristics and inferring their radiative impact. To retrieve ice cloud properties (optical thickness and ice crystal effective size), current operational algorithms assume that each pixel of the observed scene is plane-parallel and homogeneous, and that there is no radiative connection between neighboring pixels. Yet these retrieval assumptions are far from accurate, as real radiative transfer is 3-D. This leads to the plane-parallel and homogeneous bias (PPHB) plus the independent pixel approximation bias (IPAB), which impacts both the estimation of top-of-the-atmosphere (TOA) radiation and the retrievals. An important factor that determines the impact of these assumptions is the sensor spatial resolution. High-spatial-resolution pixels can better represent cloud variability (low PPHB), but the radiative path through the cloud can involve many pixels (high IPAB). In contrast, low-spatial-resolution pixels poorly represent the cloud variability (high PPHB), but the radiation is better contained within the pixel field of view (low IPAB). In addition, the solar and viewing geometry (as well as cloud optical properties) can modulate the magnitude of the PPHB and IPAB. In this, Part II of our study, we simulate TOA 0.86 and 2.13 µm solar reflectances over a cirrus uncinus scene produced by the 3DCLOUD model. Then, 3-D radiative transfer simulations are performed with the 3DMCPOL code at spatial resolutions ranging from 50 m to 10 km, for 12 viewing geometries and nine solar geometries. It is found that, for simulated nadir observations taken at resolution higher than 2.5 km, horizontal radiation transport (HRT) dominates biases between 3-D and 1-D reflectance calculations, but these biases are mitigated by the side illumination and shadowing effects for off-zenith solar geometries. At resolutions coarser than 2.5 km, PPHB dominates. For off-nadir observations at resolutions higher than 2.5 km, the effect that we call THEAB (tilted and homogeneous extinction approximation bias) due to the oblique line of sight passing through many cloud columns contributes to a large increase of the reflectances, but 3-D radiative effects such as shadowing and side illumination for oblique Sun are also important. At resolutions coarser than 2.5 km, the PPHB is again the dominant effect. The magnitude and resolution dependence of PPHB and IPAB is very different for visible, near-infrared and shortwave infrared channels compared with the thermal infrared channels discussed in Part I of this study. The contrast of 3-D radiative effects between solar and thermal infrared channels may be a significant issue for retrieval techniques that simultaneously use radiative measurements across a wide range of solar reflectance and infrared wavelengths.


Reproduction ◽  
2018 ◽  
Vol 155 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Da Li ◽  
Yue You ◽  
Fang-Fang Bi ◽  
Tie-Ning Zhang ◽  
Jiao Jiao ◽  
...  

The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased. In addition, the ratio of LC3-II/LC3-I was markedly elevated in human PCOS ovarian tissue compared with normal ovarian tissue. Real-time PCR arrays indicated that 7 and 34 autophagy-related genes were down- and up-regulated in human PCOS , Signal-Net, and regression analysis suggested that there are a wide range of interactions among these 41 genes, and a potential network based on EGFR, ERBB2, FOXO1, MAPK1, NFKB1, IGF1, TP53 and MAPK9 may be responsible for autophagy activation in PCOS. Systematic functional analysis of 41 differential autophagy-related genes indicated that these genes are highly involved in specific cellular processes such as response to stress and stimulus, and are linked to four significant pathways, including the insulin, ERBB, mTOR signaling pathways and protein processing in the endoplasmic reticulum. This study provides evidence for a potential role of autophagy disorders in PCOS in which autophagy may be an important molecular event in the pathogenesis of PCOS.


Author(s):  
Ana-Maria Pascal

This chapter explores the moral aspects of commercial deals that allegedly democratic governments enter into with foreign investors. These are discussed against a twofold theoretical background – where the philosophical ideal of public ethics based on truth and transparency meets business ethics theories. The Kantian ethics of duty proves to be the key link between these, as particularly relevant for cases where the impact on a wide range of stakeholders is considerable. The main case under consideration is the controversial USD $2 billion Romanian mining project at Rosia Montana, which highlights the need for accountability mentioned above and lends itself well to a multi-fold business ethics analysis. The role of the civil society in effectively stopping the project is a good illustration of the stakeholder theory. The chapter concludes with the thesis that a high degree of socio-political responsibility may be best achieved when trying to combine principle-based and utilitarian thinking.


2020 ◽  
Vol 56 (1) ◽  
pp. 8-16
Author(s):  
Natalia A Osna ◽  
Murali Ganesan ◽  
Devanshi Seth ◽  
Todd A Wyatt ◽  
Srivatsan Kidambi ◽  
...  

Abstract Chronic and excessive alcohol abuse cause direct and indirect detrimental effects on a wide range of body organs and systems and accounts for ~4% of deaths worldwide. Many factors influence the harmful effects of alcohol. This concise review presents newer insights into the role of select second hits in influencing the progression of alcohol-induced organ damage by synergistically acting to generate a more dramatic downstream biological defect. This review specifically addresses on how a lifestyle factor of high fat intake exacerbates alcoholic liver injury and its progression. This review also provides the mechanistic insights into how increasing matrix stiffness during liver injury promotes alcohol-induced fibrogenesis. It also discusses how hepatotropic viral (HCV, HBV) infections as well as HIV (which is traditionally not known to be hepatotropic), are potentiated by alcohol exposure to promote hepatotoxicity and fibrosis progression. Finally, this review highlights the impact of reactive aldehydes generated during alcohol and cigarette smoke coexposure impair innate antimicrobial defense and increased susceptibility to infections. This review was inspired by the symposium held at the 17th Congress of the European Society for Biomedical research on Alcoholism in Lille, France entitled ‘Second hits in alcohol-related organ damage’.


2020 ◽  
pp. 146978742090820 ◽  
Author(s):  
Naomi Winstone ◽  
Kieran Balloo ◽  
Karen Gravett ◽  
Daniel Jacobs ◽  
Harry Keen

Students’ engagement in extra-curricular activities can play a significant role in their development of a student identity, as well as leading to a greater sense of belonging and wellbeing. However, individual characteristics such as sociability may influence the likelihood of students engaging in extra-curricular activities. We collected mixed mode data from two online surveys to explore students’ perceptions of the impact of engagement in extra-curricular activities on their experience at university, as well as the mediating role of engagement in extra-curricular activities in the relationships between extraversion and wellbeing and sense of belonging to the University. Our data demonstrate that extraversion is positively associated with both belonging and wellbeing, and that engagement in extra-curricular activities also mediates these relationships. Our qualitative data uncover further nuances in engagement with extra-curricular activities; while many perceived outcomes are positive, some students express regret at opportunities missed, and find it challenging to balance extra-curricular activities and their studies. Taken together, these findings indicate that not all students stand to benefit equally from engagement in extra-curricular activities. Providing a range of opportunities that are accessible to a wide range of students may promote equity in participation in extra-curricular activities.


1994 ◽  
Vol 36 (2) ◽  
pp. 285-298 ◽  
Author(s):  
Louise Thornthwaite

While conciliation and arbitration tribunals have been at the forefront of Austral ian research on industrial relations institutions, numerous specialist tribunals enforcing individual workers' rights in employment have been virtually hidden from view. This paper examines the role of two such tribunals in New South Wales, the Government and Related Employees' Appeal Tribunal and the Equal Opportu nity Tribunal. It argues that although their most direct and public role is to resolve individuals' grievances, equally significant is the contribution of these agencies to the detailed regulation of employment relations and hence the increasing sophisti cation of labour management in public sector organizations since the late 1970s, and the institutionalization of management prerogatives and conflicts over an increasingly wide range of employment decisions.


Author(s):  
Hosea Tokwe

In most countries, the introduction of computer technology in schools has seen the role of school libraries transformed. Adoption of new technologies are now seen to be enhancing school libraries’ ability to perform their mission, vision and role, that is, providing learners access to a wide range of reading material to enable them to acquire knowledge as well as ability to read books online. This paper will address the impact computer technology is having on rural school learners at Katsande Primary School. It will explain how embracing of computer technology has influenced learners concerning achieving quality education. 


2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Alexander B. Smith ◽  
Joshua Soto Ocana ◽  
Joseph P. Zackular

ABSTRACT Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium that infects the human gastrointestinal tract, causing a wide range of disorders that vary in severity from mild diarrhea to toxic megacolon and/or death. Over the past decade, incidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically in both the pediatric and adult populations. The factors driving this rapidly evolving epidemiology remain largely unknown but are likely due in part to previously unappreciated host, microbiota, and environmental factors. In this review, we will cover the risks and challenges of CDI in adult and pediatric populations and examine asymptomatic colonization in infants. We will also discuss the emerging role of diet, pharmaceutical drugs, and pathogen-microbiota interactions in C. difficile pathogenesis, as well as the impact of host-microbiota interactions in the manifestation of C. difficile-associated disease. Finally, we highlight new areas of research and novel strategies that may shed light on this complex infection and provide insights into the future of microbiota-based therapeutics for CDI.


2019 ◽  
Vol 683 (1) ◽  
pp. 130-148 ◽  
Author(s):  
Rebecca Zwick

In this article, I review the role of college admissions tests in the United States and consider the fairness issues surrounding their use. The two main tests are the SAT, first administered in 1926, and the ACT, first given in 1959. Scores on these tests have been shown to contribute to the prediction of college performance, but their role in the admissions process varies widely across colleges. Although test scores are consistently listed as one of the most important admissions factors in national surveys of postsecondary institutions, an increasing number of schools have adopted “test-optional” policies. At these institutions, test score requirements are seen as a barrier to campus diversity because of the large performance gaps among ethnic and socioeconomic groups. Fortunately, the decentralized higher education system in the United States can accommodate a wide range of admissions policies. It is essential, however, that the impact of admissions policy changes be studied and that the resource implications of these changes be thoroughly considered.


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