C-reactive protein (CRP) is an acute inflammatory protein that increases up to 1,000-fold at sites of infection or inflammation. CRP is produced as a homopentameric protein, termed native CRP (nCRP), ...which can irreversibly dissociate at sites of inflammation and infection into five separate monomers, termed monomeric CRP (mCRP). CRP is synthesized primarily in liver hepatocytes but also by smooth muscle cells, macrophages, endothelial cells, lymphocytes, and adipocytes. Evidence suggests that estrogen in the form of hormone replacement therapy influences CRP levels in the elderly. Having been traditionally utilized as a marker of infection and cardiovascular events, there is now growing evidence that CRP plays important roles in inflammatory processes and host responses to infection including the complement pathway, apoptosis, phagocytosis, nitric oxide (NO) release, and the production of cytokines, particularly interleukin-6 and tumor necrosis factor-α. Unlike more recent publications, the findings of early work on CRP can seem somewhat unclear and at times conflicting since it was often not specified which particular CRP isoform was measured or utilized in experiments and whether responses attributed to nCRP were in fact possibly due to dissociation into mCRP or lipopolysaccharide contamination. In addition, since antibodies for mCRP are not commercially available, few laboratories are able to conduct studies investigating the mCRP isoform. Despite these issues and the fact that most CRP research to date has focused on vascular disorders, there is mounting evidence that CRP isoforms have distinct biological properties, with nCRP often exhibiting more anti-inflammatory activities compared to mCRP. The nCRP isoform activates the classical complement pathway, induces phagocytosis, and promotes apoptosis. On the other hand, mCRP promotes the chemotaxis and recruitment of circulating leukocytes to areas of inflammation and can delay apoptosis. The nCRP and mCRP isoforms work in opposing directions to inhibit and induce NO production, respectively. In terms of pro-inflammatory cytokine production, mCRP increases interleukin-8 and monocyte chemoattractant protein-1 production, whereas nCRP has no detectable effect on their levels. Further studies are needed to expand on these emerging findings and to fully characterize the differential roles that each CRP isoform plays at sites of local inflammation and infection.
Metal–organic framework nanosheets (MONs) have recently emerged as a distinct class of 2D materials with programmable structures that make them useful in diverse applications. In this review, the ...breadth of applications that have so far been investigated are surveyed, thanks to the distinct combination of properties afforded by MONs. How: 1) The high surface areas and readily accessible active sites of MONs mean they have been exploited for a variety of heterogeneous, photo‐, and electro‐catalytic applications; 2) their diverse surface chemistry and wide range of optical and electronic responses have been harnessed for the sensing of small molecules, biological molecules, and ions; 3) MONs tunable optoelectronic properties and nanoscopic dimensions have enabled them to be harnessed in light harvesting and emission, energy storage, and other electronic devices; 4) the anisotropic structure and porous nature of MONs mean they have shown great promise in a variety of gas separation and water purification applications; are discussed. The aim is to draw links between the uses of MONs in these different applications in order to highlight the common opportunities and challenges presented by this promising class of nanomaterials.
Metal–organic framework nanosheets display the high surface area and aspect ratio of 2D materials but possess a modular structure that allows for systematic tuning of their chemical and optoelectronic properties, and the introduction of new surface functionalities. Here, the progress that has so far been made in four key application areas are discussed and common opportunities and challenges are identified.
Fibres from a variety of sources are a common constituent of pig feeds. They provide a means to utilise locally-produced plant materials which are often a by-product of the food or drink industry. ...The value of a high fibre diet in terms of producing satiety has long been recognised. However the addition of fibre can reduce feed intake, which is clearly detrimental during stages of the production cycle when nutrient needs are high, for example in growing piglets and during lactation. More recently, fibre has been found to promote novel benefits to pig production systems, particularly given the reduction in antimicrobial use world-wide, concern for the welfare of animals fed a restricted diet and the need to ensure that such systems are more environmentally friendly. For example, inclusion of dietary fibre can alter the gut microbiota in ways that could reduce the need for antibiotics, while controlled addition of certain fibre types may reduce nitrogen losses into the environment and so reduce the environmental cost of pig production. Of particular potential value is the opportunity to use crude fibre concentrates as 'functional' feed additives to improve young pig growth and welfare. Perhaps the greatest opportunity for the use of high fibre diets is to improve the reproductive efficiency of pigs. Increased dietary fibre before mating improves oocyte maturation, prenatal survival and litter size; providing a consumer-acceptable means of increasing the amount of saleable meat produced per sow. The mechanisms responsible for these beneficial effects remain to be elucidated. However, changes in plasma and follicular fluid concentrations of key hormones and metabolites, as well as effects of the hypothalamic satiety centre on gonadotrophin secretion and epigenetic effects are strong candidates.
is one of the most commonly reported foodborne human bacterial gastrointestinal pathogens.
is the etiological agent of campylobacteriosis, which is generally a self-limited illness and therefore does ...not require treatment. However, when patients are immunocompromised or have other co-morbidities, antimicrobial treatment may be necessary for clinical treatment of campylobacteriosis, macrolides and fluoroquinolones are the drugs of choices. However, the increase in antimicrobial resistance of
to clinically important antibiotics may become insurmountable. Because of the transmission between poultry and humans, the poultry industry must now allocate resources to address the problem by reducing
as well as antimicrobial use, which may reduce resistance. This review will focus on the incidence of antibiotic-resistant
in poultry, the clinical consequences of this resistance, and the mechanisms of antibiotic resistance associated with
.
The connectivity of rocks' porous structure and the presence of fractures influence the transfer of fluids in the Earth's crust. Here, we employed laboratory experiments to measure the influence of ...macro-fractures and effective pressure on the permeability of volcanic rocks with a wide range of initial porosities (1-41 vol. %) comprised of both vesicles and micro-cracks. We used a hand-held permeameter and hydrostatic cell to measure the permeability of intact rock cores at effective pressures up to 30 MPa; we then induced a macro-fracture to each sample using Brazilian tensile tests and measured the permeability of these macro-fractured rocks again. We show that intact rock permeability increases non-linearly with increasing porosity and decreases with increasing effective pressure due to compactional closure of micro-fractures. Imparting a macro-fracture both increases the permeability of rocks and their sensitivity to effective pressure. The magnitude of permeability increase induced by the macro-fracture is more significant for dense rocks. We finally provide a general equation to estimate the permeability of intact and fractured rocks, forming a basis to constrain fluid flow in volcanic and geothermal systems.
Asis book traces the growth of customs and excise, and their integral role in shaping the framework of industrial England; including state power, technical advance, and the evolution of a consumer ...society. Central to this structure was the development of two economies - one legal and one illicit. If there was a unique English pathway of industrialization, it was less a distinct entrepreneurial and techno-centric culture, than one predominantly defined within an institutional framework spearheaded by the excise and a wall of tariffs. This process reached its peak by the end of the 1770s. The structure then quickly started to crumble under the weight of the fiscal-military state, and Pitt's calculated policy of concentrating industrial policy around cotton, potteries, and iron - at the expense of other taxed industries. The breakthrough of the new political economy was the erosion of the illicit economy; the smugglers' free trade now became the state's most powerful weapon in the war against non-legal trade. If at the beginning of the period covered by this book state administration was predominantly deregulated and industry regulated, by the close the reverse was the case. Available in OSO: http://www.oxfordscholarship.com/oso/public/content/history/9780199259212/toc.html
Intrauterine growth restriction (IUGR) occurs both in humans and domestic species. It has a particularly high incidence in pigs, and is a leading cause of neonatal morbidity and mortality as well as ...impaired postnatal growth. A key feature of IUGR is impaired muscle development, resulting in decreased meat quality. Understanding the developmental origins of IUGR, particularly at the molecular level, is important for developing effective strategies to mitigate its economic impact on the pig industry and animal welfare. The aim of this study was to characterise transcriptional profiles in the muscle of growth restricted pig foetuses at different gestational days (GD; gestational length ~ 115 days), focusing on selected genes (related to development, tissue injury and metabolism) that were previously identified as dysregulated in muscle of GD90 fetuses. Muscle samples were collected from the lightest foetus (L) and the sex-matched foetus with weight closest to the litter average (AW) from each of 22 Landrace x Large White litters corresponding to GD45 (n = 6), GD60 (n = 8) or GD90 (n = 8), followed by analyses, using RT-PCR and protein immunohistochemistry, of selected gene targets. Expression of the developmental genes, MYOD, RET and ACTN3 were markedly lower, whereas MSTN expression was higher, in the muscle of L relative to AW littermates beginning on GD45. Levels of all tissue injury-associated transcripts analysed (F5, PLG, KNG1, SELL, CCL16) were increased in L muscle on GD60 and, most prominently, on GD90. Among genes involved in metabolic regulation, KLB was expressed at higher levels in L than AW littermates beginning on GD60, whereas both IGFBP1 and AHSG were higher in L littermates on GD90 but only in males. Furthermore, the expression of genes specifically involved in lipid, hexose sugar or iron metabolism increased or, in the case of UCP3, decreased in L littermates on GD60 (UCP3, APOB, ALDOB) or GD90 (PNPLA3, TF), albeit in the case of ALDOB this only involved females. In conclusion, marked dysregulation of genes with critical roles in development in L foetuses can be observed from GD45, whereas for a majority of transcripts associated with tissue injury and metabolism differences between L and AW foetuses were apparent by GD60 or only at GD90, thus identifying different developmental windows for different types of adaptive responses to IUGR in the muscle of porcine foetuses.
Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we ...present a “blank slate” culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept that the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (<1 kPa) or breast tumour tissue (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases.
•We propose an optimised self-assembling peptide gel for defined 3D cell culture.•Peptide gels support growth of multiple cell types, including stromal co-culture.•Gels allow independent control of matrix stiffness and ECM functionalisation.•Stiffness, ECM and stromal cells affect growth of breast cancer progression models.•We show proof-of-concept utilising peptide gels to build disease-relevant models.
Impaired wound healing states lead to substantial morbidity and cost with treatment resulting in an expenditure of billions of dollars per annum in the US alone. Both chronic wounds and impaired ...acute wounds are characterized by excessive inflammation, enhanced proteolysis, and reduced matrix deposition. These confounding factors are exacerbated in the elderly, in part, as we report here, related to increased local and systemic tumor necrosis factor‐alpha (TNF‐α) levels. Moreover, we have used a secretory leukocyte protease inhibitor (SLPI) null mouse model of severely impaired wound healing and excessive inflammation, comparable to age‐related delayed human healing, to demonstrate that topical application of anti‐TNF‐α neutralizing antibodies blunts leukocyte recruitment and NFκB activation, alters the balance between M1 and M2 macrophages, and accelerates wound healing. Following antagonism of TNF‐α, matrix synthesis is enhanced, associated with suppression of both inflammatory parameters and NFκB binding activity. Our data suggest that inhibiting TNF‐α is a critical event in reversing the severely impaired healing response associated with the absence of SLPI, and may be applicable to prophylaxis and/or treatment of impaired wound healing states in humans.
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