Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition

The recognition of sialic acids by two strains of minute virus of mice (MVM), MVMp (prototype) and MVMi (immunosuppressive), is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA) capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM). Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3′SIA-LN) and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3′SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3′SIA-LeX identified in a previous glycan microarray screen

A meta-analysis of the prevalence of Low Anterior Resection Syndrome and systematic review of risk factors

Aim: To summarize the reported prevalence and causative factors of Low Anterior Resection Syndrome (LARS) from studies using the LARS score. Methods: A systematic literature search was conducted using Pubmed, Ovid Medline and the Cochrane database. Searches were performed using a combination of MeSH (medical subject headings) terms and key terms. Studies that were included used the LARS score as their primary collection tool. Studies were excluded if initial surgery was not for malignancy, or if the majority of LARS scores were from patients less than 1 year post initial surgery or closure of diverting stoma. Eligible studies were assessed with a validated quality assessment tool prior to performing a meta-analysis with quality effects model. Meta-analysis was conducted with prevalence estimates that had been transformed using the double arcsine method. Results: Following the initial search and implementation of inclusion and exclusion criteria 11 studies were deemed suitable for meta-analysis. Meta-analysis found the estimated prevalence of major LARS was 41% (95% CI 34 -48). Where possible outlier studies were excluded, the prevalence was 42% (95%CI 35-48). Radiotherapy and tumour height were the most consistently assessed variables, both showing a consistent negative effect on bowel function. Defunctioning ileostomy was found to have a statically significant negative impact on bowel function in 4 of 11 studies. The majority of reported data has been produced by groups in Denmark and the United Kingdom with limited numbers provided by other locations. Available data is heterogenous with some variables having limited numbers, making meta-analysis of certain variables impossible. Conclusions: There is significant prevalence of Low Anterior Resection Syndrome following oncological rectal resection. A low anastomotic height or history of radiotherapy are major risk factors

Angiopoietin-2 attenuates angiotensin II-induced aortic aneurysm and atherosclerosis in apolipoprotein E-deficient mice

Angiogenesis and inflammation are implicated in aortic aneurysm and atherosclerosis and regulated by angiopoietin-2 (Angpt2). The effect of Angpt2 administration on experimental aortic aneurysm and atherosclerosis was examined. Six-month-old male apolipoprotein E deficient (ApoE⁻/⁻) mice were infused with angiotensin II (AngII) and administered subcutaneous human Fc-protein (control) or recombinant Angpt2 (rAngpt2) over 14 days. Administration of rAngpt2 significantly inhibited AngII-induced aortic dilatation and rupture of the suprarenal aorta (SRA), and development of atherosclerosis within the aortic arch. These effects were blood pressure and plasma lipoprotein independent and associated with Tie2 activation and down-regulation of monocyte chemotactic protein-1 (MCP-1) within the SRA. Plasma concentrations of MCP-1 and interleukin-6 were significantly lower in mice receiving rAngpt2. Immunostaining for the monocyte/macrophage marker MOMA-2 and the angiogenesis marker CD31 within the SRA were less in mice receiving rAngpt2 than controls. The percentage of inflammatory (Ly6Cʰⁱ) monocytes within the bone marrow was increased while that in peripheral blood was decreased by rAngpt2 administration. In conclusion, administration of rAngpt2 attenuated angiotensin II-induced aortic aneurysm and atherosclerosis in ApoE⁻/⁻ mice associated with reduced aortic inflammation and angiogenesis. Up-regulation of Angpt2 may have potential therapeutic value in patients with aortic aneurysm and atherosclerosis

Molecular and Epigenetic Mechanisms Underlying Cognitive and Adaptive Responses to Stress

Consolidation of contextual memories after a stressful encounter is essential for the survival of an organism and in allowing a more appropriate response to be elicited should the perceived threat reoccur. Recent evidence has explored the complex role that epigenetic mechanisms play in the formation of such memories, and the underlying signaling pathways are becoming more apparent. The glucocorticoid receptor (GR) has been shown to play a key role in these events having both genomic and non-genomic actions in the brain. GR has been shown to interact with the extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) signaling pathway which, in concert, drives epigenetic modifications and chromatin remodeling, resulting in gene induction and memory consolidation. Evidence indicates that stressful events can have an effect on the offspring in utero, and that epigenetic marks altered early in life may persist into adulthood. A new and controversial area of research, however, suggests that epigenetic modifications could be inherited through the germline, a concept known as transgenerational epigenetics. This review explores the role that epigenetic processes play in the central nervous system, specifically in the consolidation of stress-induced memories, the concept of transgenerational epigenetic inheritance, and the potential role of epigenetics in revolutionizing the treatment of stress-related disorders through the emerging field of pharmacoepigenetics and personalized medical treatment

How large are the level sets of the Takagi function?

Let T be Takagi's continuous but nowhere-differentiable function. This paper considers the size of the level sets of T both from a probabilistic point of view and from the perspective of Baire category. We first give more elementary proofs of three recently published results. The first, due to Z. Buczolich, states that almost all level sets (with respect to Lebesgue measure on the range of T) are finite. The second, due to J. Lagarias and Z. Maddock, states that the average number of points in a level set is infinite. The third result, also due to Lagarias and Maddock, states that the average number of local level sets contained in a level set is 3/2. In the second part of the paper it is shown that, in contrast to the above results, the set of ordinates y with uncountably infinite level sets is residual, and a fairly explicit description of this set is given. The paper also gives a negative answer to a question of Lagarias and Maddock by showing that most level sets (in the sense of Baire category) contain infinitely many local level sets, and that a continuum of level sets even contain uncountably many local level sets. Finally, several of the main results are extended to a version of T with arbitrary signs in the summands.Comment: Added a new Section 5 with generalization of the main results; some new and corrected proofs of the old material; 29 pages, 3 figure

Governors and directors: Competing models of corporate governance

Why do we use the term ‘corporate governance’ rather than ‘corporate direction’? Early British joint stock companies were normally managed by a single ‘governor’. The ‘court of governors’ or ‘board of directors’ emerged slowly as the ruling body for companies. By the nineteenth century, however, companies were typically run by directors while not-for-profit entities such as hospitals, schools and charitable bodies had governors. The nineteenth century saw steady refinement of the roles of company directors, often in response to corporate scandals, with a gradual change from the notion of the director as a ‘representative shareholder’ to the directors being seen collectively as ‘representatives of the shareholders’. Governors in not-for-profit entities, however, were regarded as having broader responsibilities. The term ‘governance’ itself suggests that corporate boards should be studied as ‘political’ entities rather than merely through economic lenses such as agency theory

Biomass burning fuel consumption rates: a field measurement database

Landscape fires show large variability in the amount of biomass or fuel consumed per unit area burned. Fuel consumption (FC) depends on the biomass available to burn and the fraction of the biomass that is actually combusted, and can be combined with estimates of area burned to assess emissions. While burned area can be detected from space and estimates are becoming more reliable due to improved algorithms and sensors, FC is usually modeled or taken selectively from the literature. We compiled the peerreviewed literature on FC for various biomes and fuel categories to understand FC and its variability better, and to provide a database that can be used to constrain biogeochemical models with fire modules. We compiled in total 77 studies covering 11 biomes including savanna (15 studies, average FC of 4.6 t DM (dry matter) ha 1 with a standard deviation of 2.2),tropical forest (n = 19, FC = 126 +/- 77),temperate forest (n = 12, FC = 58 +/- 72),boreal forest (n = 16, FC = 35 +/- 24),pasture (n = 4, FC = 28 +/- 9.3),shifting cultivation (n = 2, FC = 23, with a range of 4.0-43),crop residue (n = 4, FC = 6.5 +/- 9.0),chaparral (n = 3, FC = 27 +/- 19),tropical peatland (n = 4, FC = 314 +/- 196),boreal peatland (n = 2, FC = 42 [42-43]),and tundra (n = 1, FC = 40). Within biomes the regional variability in the number of measurements was sometimes large, with e. g. only three measurement locations in boreal Russia and 35 sites in North America. Substantial regional differences in FC were found within the defined biomes: for example, FC of temperate pine forests in the USA was 37% lower than Australian forests dominated by eucalypt trees. Besides showing the differences between biomes, FC estimates were also grouped into different fuel classes. Our results highlight the large variability in FC, not only between biomes but also within biomes and fuel classes. This implies that substantial uncertainties are associated with using biome-averaged values to represent FC for whole biomes. Comparing the compiled FC values with co-located Global Fire Emissions Database version 3 (GFED3) FC indicates that modeling studies that aim to represent variability in FC also within biomes, still require improvements as they have difficulty in representing the dynamics governing FC

United in Separation? Lozi Secessionism in Zambia and Namibia

Secessionism perseveres as a complex political phenomenon in Africa, yet often a more in-depth analysis is overshadowed by the aspirational simplicity of pursuing a new state. Using historical and contemporary approaches, this edited volume offers the most exhaustive collection of empirical studies of African secessionism to date. The respected expert contributors put salient and lesser known cases into comparative perspective, covering Biafra, Katanga, Eritrea and South Sudan alongside Barotseland, Cabinda, and the Comoros, among others. Suggesting that African secessionism can be understood through the categories of aspiration, grievance, performance, and disenchantment, the book's analytical framework promises to be a building block for future studies of the topic

Chronic testicular Chlamydia muridarum infection impairs mouse fertility and offspring development

With approximately 131 million new genital tract infections occurring each year, Chlamydia is the most common sexually transmitted bacterial pathogen worldwide. Male and female infections occur at similar rates and both cause serious pathological sequelae. Despite this, the impact of chlamydial infection on male fertility has long been debated, and the effects of paternal chlamydial infection on offspring development are unknown. Using a male mouse chronic infection model, we show that chlamydial infection persists in the testes, adversely affecting the testicular environment. Infection increased leukocyte infiltration, disrupted the blood:testis barrier and reduced spermiogenic cell numbers and seminiferous tubule volume. Sperm from infected mice had decreased motility, increased abnormal morphology, decreased zona-binding capacity, and increased DNA damage. Serum anti-sperm antibodies were also increased. When both acutely and chronically infected male mice were bred with healthy female mice, 16.7% of pups displayed developmental abnormalities. Female offspring of chronically infected sires had smaller reproductive tracts than offspring of noninfected sires. The male pups of infected sires displayed delayed testicular development, with abnormalities in sperm vitality, motility, and sperm-oocyte binding evident at sexual maturity. These data suggest that chronic testicular Chlamydia infection can contribute to male infertility, which may have an intergenerational impact on sperm quality