To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
The chapter explains why the EU has so far failed to intervene in private fisheries governance. The chapter starts with comparing private governance schemes since the 1990s. It then analyses EU policy discussions until late 2017, showing that until very recently all involved stakeholders agreed that the fragmentation of the private governance market needed to be addressed. Differences of opinion on the desirability of publicly supporting product differentiation, however, have continued to exist. While most stakeholders consider the costs such differentiation would impose on European producers too high and therefore support procedural regulation, the European Parliament has consistently favored both standards and procedural regulations in the form of an EU-level certification and eco-labeling scheme. Attempts to create a policy failed in 2008–2009 when a legislative proposal for procedural regulation was abandoned, and in 2013 when the discussion was integrated in the reform of the Common Fisheries Policy. A 2016 report on feasible policy options, moreover, questioned the fragmentation of the private governance market, casting further doubt on the likelihood of public intervention.
This article argues that the concept of comity plays an important role in making transnational things work – the global market, hyper-politicised situations, the proliferation of international courts and tribunals, and legal harmonisation and coordination across borders. The idea is that comity might not contribute much to the construction of a clean theoretical edifice, one that agrees with binary, Cartesian, logical thinking. True. It might even undermine such a construction. But it helps to just make things work. This indeed is why comity was developed in the first place – that is, to make sovereignty work in the face of the pragmatic transnationalism that characterises so much of real-world life. The article starts with sovereignty – a nice and clean idea in theory that required comity to work well in practice – and then proceeds with a discussion of how comity helps the operations of the transnational things just mentioned.
In July 2019, Secretary of State Mike Pompeo launched a Commission on Unalienable Rights, charged with a reexamination of the scope and nature of human rights–based claims. From his statements, it seems that Pompeo hopes the commission will substantiate—by appeal to the U.S. Declaration of Independence and to natural law theory—three key conservative ideas: (1) that there is too much human rights proliferation, and once we get things right, social and economic rights as well as gender emancipation and reproductive rights will no longer register as human rights; (2) that religious liberties should be strengthened under the human rights umbrella; and (3) that the unalienable rights that should guide American foreign policy neither need nor benefit from any international oversight. I aim to show that despite Pompeo's framing, the Declaration of Independence, per se, is of no help with any of this, whereas evoking natural law is only helpful in ways that reveal its own limitations as a foundation for both human rights and foreign policy in our interconnected age.
Forming a line of linkage and transition between national orders and the international order, regional structures influence, and are influenced by, these orders. Regional structures that accommodate sub-components of geopolitical, geo-economic and geo-cultural lines are sometimes unifying, sometimes divisive, but always dynamic in terms of their order-forming mission. While this dynamism plays a seminal role in the formation of order when appraised with an inclusive approach, it can also lay the ground for regional chaos in conditions of exclusionary polarization.
The seventh chapter of the book discusses the possibility and conditions of an inclusive regional governance under the light of lessons from recent regional initiatives of Turkey (Platform for Neighbors of Iraq, Syria-Israeli Peace talks and Tehran Agreement) and recommends the following principles of stability: shared destiny/common security, high level political dialogue, economic interdependence and cultural pluralism and co-existence.
The abnormal expression of lncRNAs and miRNAs has been found in the placentas of patients with preeclampsia (PE). Therefore, we determined the role of lncRNA FOXD2-AS1/miR-3127 in trophoblast cells. The expression of lncRNA FOXD2-AS1 was detected by qRT-PCR. The proliferation, migration and invasion ability of trophoblast cells were evaluated using CCK-8, wound healing and transwell assays. The target gene of lncRNA FOXD2-AS1 was determined by StarBase and luciferase reporter assays. Western blotting was used to analyze the expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). The results showed that FOXD2-AS1 affected trophoblast cell viability in vitro, while the expression of miR-3127 was decreased. FOXD2-AS1 silencing decreased the promotion effects on trophoblast cell induced by miR-3127 inhibition. In addition, FOXD2-AS1 and miR-3127 presented the same effect on MMP2 and MMP9 levels. lncRNA FOXD2-AS1 modulated trophoblast cell proliferation, invasion and migration through downregulating miR-3127 expression. Therefore, lncRNA FOXD2-AS1 could act as a latent therapeutic marker in preeclampsia.
This chapter is concerned with exploring the mutually constitutive character of the international law of nuclear weapons, and the Cold War and post–Cold War environs in which that law was to be developed. In one direction it is argued that a consensual treaty-based system of law-making prevailed during the Cold War, which shifted to a system of Security Council legislation in the post-Cold War era, and that this reflected a parallel shift from a multipolar to a unipolar geopolitics. In another direction, however, it is also argued that the international law of nuclear weaponry also contributed to the production of its own political environs by both legitimating the possession of nuclear weaponry and controlling its spread.
We propose and analyse an age-structured model for within-host HIV virus dynamics which is incorporated with both virus-to-cell and cell-to-cell infection routes, and proliferations of both uninfected and infected cells in the form of logistic growth. The model turns out to be a hybrid system with two differential-integral equations and one first-order partial differential equation. We perform some rigorous analyses for the considered model. Among the interesting dynamical behaviours of the model is the occurrence of backward bifurcation in terms of the basic reproduction number R0 at R0 = 1, which raises new challenges for effective infection control. We also discuss the cause of such a backward bifurcation, based on our analytical results.
The present study was performed on antigen-presenting cells (APCs) of Theileria annulata transformed dendritic cells (TaDCs) and monocyte-derived dendritic cells (MoDCs) to compare differences in antigen presentation and stimulation of T lymphocyte proliferation. Antigen presentation for T lymphocyte proliferation was analysed by flow cytometry. Additionally, the level of mRNA transcription of small GTPases of the Rab family expressed in the TaDC cell line was analysed by quantitative real-time polymerase chain reaction (Q-RT-PCR). The endocytosis rate of TaDCs was significantly (P < 0.01) lower than in MoDCs. In contrast, when T lymphocytes were co-cultured with TaDC-APCs T cell proliferation was similar, while co-culture with MoDC-APC stimulated proliferation of CD4+ cells to a greater degree than CD8+ cells. However, the efficacy of TaDC-APCs to stimulate T lymphocytes dropped as the number of passages of TaDC-APC increased. Likewise, the transcription level of Rab family genes also significantly (P > 0.001) declined with progressive passages (>50) of the TaDC cell line. We conclude that initially the TaDC cell line efficiently presents antigen to stimulate T lymphocyte proliferation to produce a cellular immune response against the presented antigen.
Annexin A2 (ANXA2) is reported to be associated with cancer development. To investigate the roles ANXA2 plays during the development of cancer, the RNAi method was used to inhibit the ANXA2 expression in caco2 (human colorectal cancer cell line) and SMMC7721 (human hepatocarcinoma cell line) cells. The results showed that when the expression of ANXA2 was efficiently inhibited, the growth and motility of both cell lines were significantly decreased, and the development of the motility relevant microstructures, such as pseudopodia, filopodia, and the polymerization of microfilaments and microtubules were obviously inhibited. The cancer cell apoptosis was enhanced without obvious significance. The possible regulating pathway in the process was also predicted and discussed. Our results suggested that ANXA2 plays important roles in maintaining the malignancy of colorectal and hepatic cancer by enhancing the cell proliferation, motility, and development of the motility associated microstructures of cancer cells based on a possible complicated signal pathway.
To modify the non-porous surface membrane of a tissue-engineered laryngeal scaffold to allow effective cell entry.
The mechanical properties, surface topography and chemistry of polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane were characterised. A laser technique introduced surface perforations. Micro computed tomography generated porosity data. Scaffolds were seeded with cells, investigated histologically and proliferation studied. Incubation and time effects were assessed.
Laser cutting perforated the polymer, connecting the substructure with the ex-scaffold environment and increasing porosity (porous, non-perforated = 87.9 per cent; porous, laser-perforated at intensities 3 = 96.4 per cent and 6 = 89.5 per cent). Cellular studies confirmed improved cell viability. Histology showed cells adherent to the scaffold surface and cells within perforations, and indicated that cells migrated into the scaffolds. After 15 days of incubation, scanning electron microscopy revealed an 11 per cent reduction in pore diameter, correlating with a decrease in Young's modulus.
Introducing surface perforations presents a viable method of improving polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane as a tissue-engineered scaffold.
This study aimed to set up methodology to monitor parasite-specific T-cell activation in vitro using Eimeria tenella-infected chickens. A sonicated E. tenella sporozoite protein preparation was used for the activation of chicken spleen cell cultures. Proliferation assessed by 3H-thymidin incorporation or blast transformation of T-cells assessed by immunofluorescence labelling and flow cytometry were used as read-outs for activation. Results showed that E. tenella-specific proliferation was detected in cultures of spleen cells collected in a ‘window’ between 8 and 14 days after primary infection. However, due to high variation in proliferative responses between individuals and to high background proliferation, large numbers of observations were needed to obtain significant results. Moreover, the outcome was not improved by increasing the infection dose to chickens or by depletion of T-cell receptor (TCR) γ/δ expressing cells from cultures. An E. tenella-specific blast transformation response was observed for TCRα/β expressing cells within the same ‘window’, confirming the identity of the responding cells as classic T-cells. Thus, it is possible to study the kinetics of E. tenella-specific T-cell responses in vitro. However, more in-depth phenotypic identification of the responding T-cells could improve the methodology.
In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As adipogenesis is a critical factor contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn adipose tissue at the stem-cell level. For in vivo studies, female rats received BPA before and during pregnancy and lactation via drinking water, and offspring were studied for measures of adiposity signals. For in vitro BPA exposure, primary pre-adipocyte cell cultures from healthy newborns were utilized. We studied pre-adipocyte proliferative and differentiation effects of BPA and explored putative signal factors which partly explain adipose responses and underlying epigenetic mechanisms mediated by BPA. Maternal BPA-induced offspring adiposity, hypertrophic adipocytes and increased adipose tissue protein expression of pro-adipogenic and lipogenic factors. Consistent with in vivo data, in vitro BPA exposure induced a dose-dependent increase in pre-adipocyte proliferation and increased adipocyte lipid content. In vivo and in vitro BPA exposure promotes the proliferation and differentiation of adipocytes, contributing to an enhanced capacity for lipid storage. These findings reinforce the marked effects of BPA on adipogenesis and highlight the susceptibility of stem-cell populations during early life with long-term consequence on metabolic homeostasis.
‘Third countries’ are frequently exploited by those involved in networks to transfer proliferation-sensitive technologies, allowing procurement agents to obscure the end user or vendor located in the proliferating state, and to deceive industry, export licensing officials, and intelligence services. While ‘third countries’ frequently feature in illicit transactions, the academic literature exploring the roles played by entities in these jurisdictions is limited. Building on the sanctions busting literature, this article proposes a loose typology considering the ways in which third countries can be exploited by proliferation networks. The typology is illustrated using three cases involving entities based in Malaysia – A. Q. Khan’s nuclear black market network, and Iran and North Korea’s efforts to procure and market WMD-related and military goods. These cases are used to generate insights into proliferators’ selection of ‘third country’ hubs. The article argues that while exploitation of third countries by proliferation networks is a similar, but distinct phenomenon to trade-based sanctions busting, hubs of both activities share characteristics. Furthermore, the article argues that other factors beyond the lax regulatory environment, such as level of development, and personal connections, are often as important in driving the decisions of proliferation networks. The article concludes with implications for nonproliferation policy.
To investigate the effects of soybean isoflavone (SI) on immunity in infectious bursal disease virus (IBDV)-infected broilers, chicks were fed the same basal diet supplemented with 0 (non-infected control), 0 (infected control), 10, 20 or 40 mg/kg SI for 44 days. At 21 days old, chickens were inoculated with bursal infectious dose causing 50% morbidity of the IBDV BC 6/85 strain by the eye-drop and nasal route (except for non-infected controls). Results showed that, over 1–23 days post-infection (dpi), there was a significant interaction between SI supplementation level and time: high-level SI supplementation increased peripheral T lymphocyte proliferation, percentages of CD3+, CD4+ and CD8+ T lymphocytes, CD4+ to CD8+ ratio, serum concentrations of IgA, IgM and IgG, and IBDV antibody titres. Except for serum IgA and IgM, these variables increased over time with far higher values at 23 dpi than earlier. Compared with non-infected controls, IBDV inoculation decreased peripheral T lymphocyte proliferation at 3 dpi, percentages of CD3+, CD4+ and CD8+ T lymphocytes, and serum IgG, IgM concentration at 23 dpi, and increased IBDV antibody titres at 7, 15 and 23 dpi. Supplemental SI quadratically increased peripheral T lymphocyte proliferation, CD4+ to CD8+ ratio and serum IgA concentration at 3 dpi, percentages of CD3+, CD4+ and CD8+ T lymphocytes at 3 and 23 dpi, and serum IgM concentration and IBDV antibody titres at 23 dpi. These results indicate that dietary SI improved cellular and humoral immunity of IBDV-infected birds and may enhance resistance of Yellow-feathered broilers to infectious diseases.
Disarmament and non-proliferation education is a key tool in curbing the spread of nuclear weapons, with a view to their elimination. This article examines the remarkable story of the International School on Disarmament and Research on Conflicts (ISODARCO) on the occasion of its fiftieth anniversary of continuous engagement in educational and training activities. ISODARCO offers a unique forum where nuclear experts from different backgrounds and approaches can meet, debate, and promote action as a transnational knowledge-based network of experts and, equally important, pass on their expertise to the ‘next generation of non-proliferation specialists’. The contribution of this small Italian NGO is indeed noteworthy, highly praised at the national and especially international level, and worth the attention of an audience broader than just non-proliferation and security experts.
This research paper addresses the hypothesis that RagD is a key signalling factor that regulates amino acid (AA) mediated-casein synthesis and cell proliferation in cow mammary epithelial cells (CMECs). The expression of RagD was analysed at different times during pregnancy and lactation in bovine mammary tissue from dairy cows. We showed that expression of RagD at lactation period was higher (P < 0·05) than that at pregnancy period. When CMECs were treated with methionine (Met) or lysine (Lys), expression of RagD, β-casein (CSN2), mTOR and p-mTOR, and cell proliferation were increased. Further, when CMECs were treated to overexpress RagD, expression of CSN2, mTOR and p-mTOR, and cell proliferation were up-regulated. Furthermore, the increase in expression of CSN2, mTOR and p-mTOR, and cell proliferation in response to Met or Lys supply was inhibited by inhibiting RagD, and those effects were reversed in the overexpression model. When CMECs were treated with RagD overexpression together with mTOR inhibition or conversely with RagD inhibition together with mTOR overexpression, results showed that the increase in expression of CSN2 and cell proliferation in response to RagD overexpression was prevented by inhibiting mTOR, and those effects were reversed by overexpressing mTOR. The interaction of RagD with subunit proteins of mTORC1 was analysed, and the result showed that RagD interacted with Raptor. CMECs were treated with Raptor inhibition, and the result showed that the increase in expression of mTOR and p-mTOR in response to RagD overexpression was inhibited by inhibiting Raptor.
In conclusion, our study showed that RagD is an important activation factor of mTORC1 in CMECs, activating AA-mediated casein synthesis and cell proliferation, potentially acting via Raptor.
Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.