These periods came to include rice farming and the formation of l

These periods came to include rice farming and the formation of large, often fortified villages and towns. With these developments came also the establishment of socially, politically, and economically dominant elites whose wealth and power were attested by their grand living quarters and the rich bronzes, jades, and other manifestations of wealth and high social status. The earliest stage of such highly developed society in north China is traditionally

ascribed to “the Three Dynasties” – Xia, Shang, and Zhou – collectively dated to about 3900–2200 cal BP. The site of Erlitou, on the Middle Yellow River some 300 km east of modern Xi’an and dated to final Longshan Neolithic times, displays the above characteristics ON-01910 nmr and is thought by many to represent China’s legendary Xia period, which came before the dawn of written documentation during the Shang-Zhou period. The following Qin period, marking the accession of China’s first recognized Emperor, Qin Shihuangdi, is dated to 221–206 BC. Qin Shihuangdi was the lord of a Zhou noble family, who achieved his imperial status by fighting and maneuvering his way to political dominance over the other lords of the area (Chang, 1986, Liu, 1996 and Liu and Chen, 2012). Historians and archeologists long saw this Wei/Yellow River nexus as the central

place where Chinese civilization flowered, and from which it spread (Barnes, 1999, Chang, 1986, Liu, 1996 and Liu and Chen, 2012), but more recent research now suggests that socially, economically, and politically complex Chinese polities did not

simply arise in this place and then spread across China as a whole. Instead, the two great river valley zones of China – the Yellow River in the north and the Yangzi River in the south, together constituting China’s great Central Plain – developed their cultures and histories in parallel fashion and with ample inter-regional communication and interaction. The two regions are now seen Amine dehydrogenase as fundamentally contemporaneous and interactive, which gave rise to elite politico-economic subgroups that intensively engaged peasant labor in agricultural, industrial, and commercial processes that transformed the landscapes on which everyone depended (Liu and Chen, 2012). Since the culture history of the northern zone has been more fully explicated, we use examples from this area to illustrate how radical social and anthropogenic change proceeded on the landscape of China. Both archeological and written records indicate that the broad economic base established in China during the Neolithic came over in time to support many small sociopolitical entities that controlled local agriculture, commerce, and warfare.

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A significant negative correlation was observed between ROC1 and

A significant negative correlation was observed between ROC1 and cyclin D1 expression in the study cases. When ROC1

expression increased, cyclin D1 expression decreased, and vice-versa. Melanomas containing areas of high ROC1 protein expression and low cyclin D1 positivity were observed alongside areas of high cyclin D1 expression and low ROC1 expression, making evident the presence of different cell clones in these lesions, as visualized by light microscopy. The amplification of the CCND1 gene in melanocytic nevi is rare, and so is cyclin D1 expression increase [5] and [29]. Strikingly, one of the melanocytic nevus cases included in this study showed CCND1 amplification and the highest level of cyclin D1 expression of all melanocytic cases studied (51–75%), associated with a decreased ROC1 expression (26–50%). This case of melanocytic nevus LDN-193189 was observed in the genital region of a 20-year-old female. It was characterized by intense junctional

activity and cellularity and by areas with morphologically distinct cells contiguous with each other in the likeness of clones. Interpreting an isolated case is difficult, but one explanation for the partial reduction in ROC1 may be the consumption of this protein for the degradation of the increased cyclin D1 that is found in a lesion in the proliferative stage. In this study, both melanomas with all cells amplified showed cyclin D1 expression in >50% of cells and ROC1 expression in <25% of cells. The Carteolol HCl lower ROC1 expression observed in the amplified melanomas as

compared to the amplified nevus suggests a ROC1 deficiency and not just its consumption for the labeling of the increased cyclin. This assumption is corroborated by the fact that in focally amplified melanomas, no significant ROC1 decrease occurred even when cyclin D1 was increased. It is also confirmed by non-amplified cases that showed increased cyclin D1 expression and a significant ROC1 decrease. The ROC1/cyclin D1 relationship correlated with neoplasia type. In melanocytic nevi, there was a predominance of increased ROC1 expression in relation to cyclin D1 (86.2% of the cases), whereas in melanomas, ROC1 expression was higher than cyclin D1 expression in 45.2% of the cases. The only case of a melanocytic nevus in which cyclin D1 was higher than ROC1 expression showed CCND1 amplification, which is in contrast with the melanomas where the majority of cases showed increased cyclin D1 as compared to ROC1 expression and no gene amplification (85.7%). This fact, and the absence of correlations between ROC1/cyclin D1 and gene amplification observed here, supports the idea of ROC1 deficiency in melanomas as part of the phenomenon responsible for the increase in cyclin D1. The amplification of the CCND1 gene is more common in acral lentiginous melanomas, followed by SSM.

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It is known that cryopreservation

of lymphocytes may have

It is known that cryopreservation

of lymphocytes may have effects on cell surface molecules of T-cells such CCR5 and CD45 RA/RO and may decrease response to infectious diseases and recall antigens [6] in both HIV-infected and non-infected blood click here donors. Furthermore, cryopreservation can modify the ability of T-cells to secrete cytokines. Freezing and thawing cells significantly altered the cytokine secretion of cells [24] and [42]. Cyclical temperature increase during sample storage could have similar effects. In summary, we have investigated the influence of cyclical temperature fluctuations on PBMC health and have demonstrated that small cyclical temperature rises during the storage process in liquid nitrogen induced by sample storage, sorting and removal, leads to decreased cell recovery, cell viability and T-cell functionality. Retrospective sample analysis is commonly used in clinical programs including studies for infectious diseases, malaria, and cancer. In addition, samples from clinical trial will often be allocated and stored in central cryorepositories under low temperature condition in PF-01367338 research buy liquid nitrogen. These studies show the impact of sample storage conditions on the integrity and quality of the cryopreserved

samples and the resulting data analysis. Further investigations will be necessary to determine of the minimal number of temperature fluctuations during the storage process that lead to Buspirone HCl the beginning of the negative biological effects. The knowledge of this critical number of temperature rises could be used as an additional sample quality indicator. Beside the avoidance of temperature fluctuations during the sample storage, the opening of the storage tanks and the resultant temperature rises should be monitored and documented to use this data as a supplemental quality parameter. The authors

thank B. Kemp-Kamke and M. Fuß for their excellent technical assistance, Julia Neubauer for her assistance in the design of the diagrams and Marcella Sarzotti Kelsoe for careful proofreading. This study was generously supported by the Bill & Melinda Gates Foundation (grant number OPP38580_01). “
“Dr. Akira Sakai, a pioneer of plant cryobiology and plant cryopreservation, passed away on October 5, 2012, at the age of 92. Sakai-sensei (in Japan we use a suffix “sensei” for teachers, instructors and professor to show our respect) was born on January 22, 1920, in a town of Aichi, a prefecture located in the central part of Japan. He graduated from the Department of Animal Science, Hokkaido Imperial University (later renamed to Hokkaido University) in 1944.

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, 2009) This dye also exhibited mutagenic activity in the Salmon

, 2009). This dye also exhibited mutagenic activity in the Salmonella/microsome assay with the strains TA98, TA100, YG1041 and YG1042 in the absence of metabolic activation, but after adding the S9 mix, its mutagenicity was decreased (or eliminated). It has been proposed that the P450-dependent metabolism probably generated more stable products, with a Gemcitabine reduced probability of interacting with DNA ( Ferraz et al., 2010). It is therefore important to know the toxicity of both the original dye and its metabolic products, since the effluent

treatment applied by industries does not completely remove the mutagenic compounds, and consequently they can be found in treated water ( Oliveira et al., 2007). Thus the aim of the present study was to investigate the oxidation and reduction products obtained from the azo dye DR1 using the methodologies of HPLC–DAD and GC–MS. It also proposed to evaluate the mutagenic potential of these products using two different methods: the Salmonella/microsome Selleck UMI-77 assay with the strains TA98 and YG1041 in the absence of exogenous metabolic

activation (S9), and the mouse lymphoma assay (MLA). The Salmonella/microsome mutagenicity assay (Salmonella test; Ames test) is a short-term bacterial reverse mutation assay specifically designed to detect a wide range of chemical substances that can produce genetic damage leading to gene mutation ( Mortelmans and Zeiger, 2000). The MLA, using the thymidine kinase (Tk) gene as the target, is the most widely used of the in vitro assays for gene mutation in mammalian cells ( Moore et al., 2003), Cyclic nucleotide phosphodiesterase detecting a broad spectrum of genetic damage, such as gene and chromosomal mutations ( Clements, 2000 and Soriano et al., 2007). The dye DR1 (CAS No. 2872–52-8) was purchased from Sigma (St. Louis, MO, purity > 95%)

(Fig. 1). The metabolic pathways of the dye were investigated using the mimetic system based on oxidation and reduction processes. The oxidation reactions were evaluated using three different techniques, one enzymatic (using an exogenous metabolic system – S9 mixture) and two chemical techniques (spectroelectrochemistry and controlled potential electrolysis). The reduction reactions were carried out by the two techniques used in chemical oxidation. The S9 metabolizing system is widely used in mutagenicity assays (mainly the Salmonella/microsome mutagenicity assay) in order to mimic the oxidation reactions that take place via cytochrome P450. These reactions are extremely important in toxicology, because they may generate more or less toxic products, i.e. bioactivation and detoxification, respectively. Considering this, the role of the cytochrome P450 isoenzymes in the chromophore group of this dye was monitored spectrophotometrically in the present study, promoting the reaction between DR1 and S9, as described below.

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The large size of the pooled database enabled more precise estima

The large size of the pooled database enabled more precise estimates of association than previous studies, particularly in stratified analyses, spline TSA HDAC clinical trial models, and assessment of interaction. Second, although pooling and harmonization of data is a substantial undertaking and requires expertise, time, and resources, individual patient data allows for many benefits over meta-analysis of published estimates, including building consistent models across studies, studying novel questions including interaction, and using novel methods of analysis such as splines. Third, the availability of 2 control groups

for comparison, that is, population-based and GERD, allows us to postulate where risk factors might be active in the pathogenesis of Barrett’s esophagus. This is important because it is feasible that a significant proportion of the population-based control group might unknowingly have Barrett’s esophagus,63 although such misclassification would bias results toward the null. Limitations of this analysis include the moderate-to-high levels of heterogeneity for some analyses. Although constituents of tobacco smoke have

changed over time,64 the studies included in this analysis Trametinib molecular weight recruited incident cases and controls during a similar period (1997–2006). Regardless, constituents of tobacco smoke are likely to have differed geographically as is population susceptibility to genotoxic exposures. The unexplained pentoxifylline heterogeneity does warrant a cautious interpretation of summary estimates, although associations were largely consistent in a majority of studies included, and similar summary estimates with low heterogeneity were estimated when the study that was the source of the most heterogeneity was omitted from analysis. Another limitation is the possibility of recall bias, given the case-control design of the included studies, although the intensity and duration of smoking are usually recalled relatively reliably.65 Lastly, we did not adjust for dietary

variables in this analysis; although previous studies suggest that diet has minimal effects on relationships between smoking and Barrett’s esophagus, there remains the possibility of residual confounding through diet and other exposures. In conclusion, cigarette smoking is a risk factor for Barrett’s esophagus, with adjusted ORs for multiple measures of association in the 1.5 to 2 range. The association appears to strengthen with increased exposure to cigarette smoking until approximately 20 pack-years, where it begins to plateau. If smoking is a causative agent of Barrett’s esophagus, it is an attractive modifiable risk factor, especially in high-risk groups such as elderly, obese males with GERD symptoms.

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, 1999), pancreas (Askari et al , 2005), breast (Cakir et al , 20

, 1999), pancreas (Askari et al., 2005), breast (Cakir et al., 2002), and gastric (Shin et al., 2007) cancers, all of which are adenocarcinomas. Studies investigating the influence of catecholamines on human HNSCC

cell proliferation, as in our case, are still scarce. Liu et al. (2008) have demonstrated that epinephrine stimulates esophageal squamous cell carcinoma cell proliferation. This effect occurred via β-AR-dependent transactivation of the extracellular signal-regulated kinase/cyclooxygenase-2 pathway. Recently, Shang et al. (2009) have reported that the OSCC cell line TCa8113 expresses β2-AR and presents NE-induced proliferation, an effect that was also inhibited by propranolol. However, the authors presented no data concerning the expression of the β1-receptor subtype.

Here, constitutive expression of both β1- and β2-ARs in the three studied OSCC cell lines has been demonstrated. selleck chemical Collectively, Carfilzomib purchase the results obtained by us and by Shang et al. (2009) provide evidence that catecholamines such as NE may play an important role in the progression of oral cancer. Effects of cortisol on IL-6 expression differ according to the hormone dose. At different times, cortisol at a concentration compatible with physiological stress levels in humans (10 nM) enhanced IL-6 expression in SCC9, SCC15, and SCC25 cells, but these results were not significant. In contrast, cortisol concentrations closer to pharmacological levels (1000 nM) promoted reduction in IL-6 expression at all analyzed time points in SCC9 and SCC15 cells. These data suggest the possibility

of cortisol have a dual role on IL-6 expression in OSCC cell, in which doses that simulate physiological stress levels (e.g., 10 nM) could have a proinflammatory effect, while pharmacological doses inhibit the proinflammatory cytokine IL-6. Inhibitory effects of glucocorticoids on the expression of cytokines such as IL-6 and IL-8 have been reported previously (Hasan et 3-mercaptopyruvate sulfurtransferase al., 2003 and Yano et al., 2006). Nevertheless, in these studies the cortisol was generally tested at pharmacological concentrations (1000 nM or more). Lutgendorf et al. (2003) also found different effects of cortisol on VEGF in ovarian carcinoma cells, depending on the hormone dose. In line with our results on IL-6, pharmacological doses of cortisol inhibited VEGF secretion, while cortisol simulating physiological stress levels (10 nM) induced significant increase in VEGF. Although some types of non-steroidal anti-inflammatory drugs (NSAIDs) cause antiproliferative effects and induce apoptosis in HNSCC cell lines (Thurnher et al., 2001 and Pelzmann et al., 2004), it seems that the effects of glucocorticoids on the growth of these cells are not as clear. For example, previous experiments with a high dose of hydrocortisone (3000 nM) did not reveal relevant effects on the HNSCC cell proliferation rate (Thurnher et al., 2001).

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(2011) Fish, corals, and other invertebrates (Table 2) were coll

(2011). Fish, corals, and other invertebrates (Table 2) were collected from Bantayan Reef, Dumaguete (9° 19′ 56.1″ N, 123° 18′ 38.06″ E) across the SU-IEMS Marine Laboratory. Fish were collected by local fishermen using hand nets and fish traps. Experiments were conducted using four concrete tanks (3 m long × 1 m wide × 0.5 m deep) with

flow-through seawater at ambient conditions (mean temperature = 28 °C, salinity = 33 ppt, pH = 8.3). Half of each coral colony was Alectinib enclosed in a wire cage to ensure that a portion of every coral survived despite feeding activities of newly introduced A. planci ( Fig. 1). Coral fragments and colonies (∼15 cm L × W × H) were arranged in a way that the least preferred species were closest to the seawater inlet and the injected sea stars, while the most preferred species were farthest ( Pratchett, 2007). Fish and mobile invertebrates were also placed in the tanks. Eight sea stars GSK126 were separated in pairs and one A. planci was injected

with 10 ml oxgall (8 g l−1), oxgall (4 g l−1), peptone (20 g l−1), and TCBS (44 g l−1) at day 1 and the remaining one at day 4. All starfish were placed near the seawater inlet of Tanks 1–4, respectively. Interaction between all the animals in the tank was recorded for 4 h in the morning and 4 h in the afternoon using a GoPro Hero 2 HD video camera. Signs of disease such as darkened coloration to the skin and fins, erythema, changes to the eyes such as distension and cloudiness, periorbital swelling, haemorrhagic septicaemia and mortality were monitored every 8 h for 12 days. Mortality rates Cell press were highest in individuals injected

with bile derivatives (bile salts, oxgall) and TCBS, while mortality rates in peptones were moderate and only increased when concentrations were raised to 10–20× the standard concentration based on manufacturer formulation of TCBS (Fig. 2). Severity of clinical signs, mentioned hereafter, will range from low (i.e. localized to site of injection) to high (i.e. spread to more than 50% of the sea star). At the TCBS standard concentration of 10 g l−1, there was 0% mortality up to 48 h using Oxoid brand and only one 1 out of 10 A. planci died using Himedi brand. Most A. planci showed localized loss of turgor, matting, and mucus secretion. At half the TCBS standard concentration (5 g l−1), 50% of the sea stars showed loss of turgor and swelling after 8 h, but all recovered after 48 h and there was 0% mortality. At twice (20 g l−1) the TCBS standard concentration, 4 out of 10 exhibited localized tissue necrosis and 2 out of 10 sea stars showed medium severity necrosis at 8 h. After 24 h, 6 out of 10 showed medium severity necrosis and 1 out of 10 with localized necrosis.

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Patients hospitalized in Asia,4 in Europe and the United Kingdom,

Patients hospitalized in Asia,4 in Europe and the United Kingdom,1 and 43 and in North44 and South America45 were at higher risk of dying if malnourished. Costs were also higher when extra care and longer stays were needed to treat health complications, as supported by studies from Singapore,

Brazil, and The Netherlands (Table 1). The traditional recommendations of nutrition screening, assessment, and intervention are sometimes overlooked or inadequate. In a European-wide survey of hospital nutrition care (1217 units, 325 selleck screening library hospitals, 25 countries, >21,000 patients), only half of the units reported routine use of nutrition screening.51 Even when energy intake was assessed and an energy goal was specified, about half of the patients consumed less than their energy goal; or they self-reported inadequate food intake.8 and 51 According to the British Nutrition Foundation, more than 60% of hospital patients experienced a decline in nutritional status during their stay in the hospital.12 Nutrition guidelines worldwide advise nutritional intervention for patients who cannot meet nutrient needs with a diet of regular food. Nutrition interventions, including oral nutrition supplements RGFP966 molecular weight (ONS) and enteral and parenteral nutrition, had significant clinical and economic

benefits across patient groups and in different settings, as shown by results of randomized, Tolmetin controlled trials (RCTs), prospective studies, and meta-analyses. Health benefits of nutrition intervention include improved nutrition status, muscle mass, strength, or performance; fewer health complications; improved quality of life; and reduced risk of mortality (Table 2).23, 24, 25, 52, 53, 54, 55, 56 and 57 Economic benefits include reduced length of stay, fewer hospital readmissions,

and lowered cost of care (Table 3).24, 26, 55, 58, 59 and 60 To provide best-practice nutrition care, it is essential that caregivers appreciate the current definition of malnutrition. Malnutrition has been newly defined as 3 clinical syndromes, which are characterized by underlying illness or injury and varying degrees of inflammation.61 The three syndromes are (1) starvation-related malnutrition, a form of malnutrition without inflammation; (2) chronic disease-related malnutrition, which is nutritional inadequacy associated with chronic conditions that impose sustained inflammation of a mild-to-moderate degree; and (3) acute disease- or injury-related malnutrition, which is undernutrition related to conditions that elicit marked inflammatory responses. Many chronic conditions (such as kidney disease, cancer, heart failure, or rheumatoid arthritis) have inflammation as a disease component, thus increasing the risk of malnutrition, 62 and 63 even among patients who are overweight or obese.

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g , Hasumi and Suginohara,

g., Hasumi and Suginohara, 1999, Jayne and St. Laurent, 2001 and Friedrich et al., 2011). The majority of these studies are concerned about effects of vertical mixing in the deep ocean. Several studies have begun to explore how regional changes in κbκb impact the upper, tropical ocean. It has been recognized that, below the mixed layer and within the region in which κbκb is changed, the response of the stratification (temperature or density) is qualitatively consistent with changes

generated locally by the anomalous, vertical diffusive flux (e.g., Richards et al., 2009 and Jochum, 2009). Anomalies generated by such local processes are then propagated to other regions by advection, diffusion, or wave radiation. In particular, it has been suggested that off-equatorial effects of diffusion are propagated to the equator by the Pacific Subtropical Cells (STCs; McCreary and Lu, 1994) through advection in the main pycnocline (e.g., Jochum, 2009, Tatebe and Hasumi, 2010 and Manucharyan et al., 2011). The equatorial stratification anomalies due to local and remote κbκb changes Bortezomib affect the climate state and

variability such as ENSO in atmosphere–ocean coupled models (Meehl et al., 2001, Richards et al., 2009, Jochum, 2009, Manucharyan et al., 2011 and Sasaki et al., 2013; Kim et al., in preparation). In this paper, we continue the effort to understand impacts of spatially-varying Vildagliptin vertical diffusion in the tropical Pacific. Our goal is to understand the basic processes by which the ocean responds both locally and remotely to changes in κbκb in different regions. For one thing, this knowledge allows the identification of regions where vertical mixing has the greatest impact on important aspects of the ocean state, such as tropical sea surface temperature (SST). For another, it will help in the development of new κbκb parameterizations, by allowing researchers to understand better how the parameterization will impact the ocean state. We consider κbκb anomalies

that are depth independent, the simplest choice when not dealing with particular mixing processes. (We will consider the impact of depth-dependent κbκb anomalies in a companion study; see the discussion at the end of Section 4.) Our approach is to obtain a set of OGCM solutions in which κbκb is increased from a standard value κ0κ0 to κ0+δκb(x,y)κ0+δκb(x,y) in spatially distinct subregions of the tropical Pacific, to assess the impact of those changes, and to diagnose the processes that cause them. A particular focus is on how δκbδκb affects the equatorial temperature structure, because the mean climate and its variability are known to be sensitive to that structure.

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Our results also suggest that investigating neuropsychiatric adve

Our results also suggest that investigating neuropsychiatric adverse effects that may develop or persist years after the therapy termination is as important as detecting these adverse effects during the antiviral therapy. Finally, prospective pharmacogenetic

studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-α-induced depression; and the search for other candidate genes that may fill the gaps in prediction of this substance-induced affective disorder must continue. The authors do not have any actual or potential conflict of interest, including any financial, personal, or other relationships with other people or organizations, selleck within three years of beginning the work submitted that could inappropriately influence, or be perceived to influence, their work. Amanda Galvão-de Almeida is supported by the National Council of Technological and Scientific Development (CNPq): 471592/2008-0; 142262/2008-0. Ângela Miranda-Scippa is recipient of the CNPq fellowship. We thank Dr. Susana Carolina Batista-Neves, Dr. selleck compound Luiz Guilherme Lyra, Dr. Nelma Pereira de Santana, Dr. Mateus Fiúza, Dr. Nádia Caldas, Dr. Maria Isabel Schinoni, Dr. Helma Cotrim, Dr. Marcelo Portugal de Souza, Dr. Antônio Ricardo Andrade, Dr. Ana Cristina

Siqueira Landim, Dr. Lourianne Nascimento Cavalcante, Dr. Aloma Conceição Campeche, Dr. Edison Parise, Dr. Delvone Almeida, Dr. Ana Thereza Gomes, and the 2008–2010 Gastroenterology residents for clinical and

technical assistance. “
“Humans and animals are constantly exposed to the risk of infection by bacterial and viral pathogens, and sub-clinical, low grade infections are reported to account for up to 35% of all general practitioner consultations in the UK (Fleming et al., 2002). These infections can initiate a set of immune, physiological, metabolic, and behavioural responses, characterised by fever, reduced activity, reduced appetite, impaired cognitive function, anxiety and depression (Hart, 1988), also known as sickness behaviour. These behavioural changes are believed to be largely triggered Terminal deoxynucleotidyl transferase by pro-inflammatory mediators that are produced by activated immune cells (Konsman et al., 2002) or by COX-2 mediated prostaglandin (PG) production in endothelial cells (Yamagata et al., 2001). More specifically, it is believed that the pro-inflammatory cytokines IL-1β (Bluthe et al., 2000a), IL-6 (Bluthe et al., 2000b and Cartmell et al., 2000) and TNF-α (Bluthe et al., 2000a) have a pivotal role in the onset of LPS-induced behavioural symptoms. These cytokines communicate with the brain by different mechanisms (Ek et al., 1998 and Konsman et al., 2000), each resulting in de novo expression of cytokines within CNS tissues and widespread activation of resident immune-competent cells within the brain, the microglia.

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