Perinatal Gram-Positive Bacteria Exposure Elicits Distinct Cytokine Responses In Vitro

During pregnancy, infections caused by the gram-positive bacteria Enterococcus faecalis (E. faecalis), Streptococcus agalacticae (S. agalacticae), and Staphylococcus aureus (S. aureus) are major reasons for preterm labor, neonatal prematurity, meningitis, or sepsis. Here, we propose cytokine responses to bacterial infections by the immature perinatal immune system as central players in the pathogenesis of preterm birth and neonatal sepsis. We aimed to close the gap in knowledge about such cytokine responses by stimulating freshly isolated umbilical blood mononuclear cells (UBMC) with lysates of E. faecalis, S. agalacticae, and S. aureus collected from pregnant women in preterm labor. Bacterial lysates and, principally, S. aureus and S. agalacticae distinctly triggered most of the eleven inflammatory, anti-inflammatory, TH₁/TH₂ cytokines, and chemokines quantified in UBMC culture media. Chemokines depicted the most robust induction. Among them, MIP-1β was further enhanced in UBMC from female compered to male newborn infants. Due to its stability and high levels, we investigated the diagnostic value of IL-8. IL-8 was critically upregulated in cord blood of preterm neonates suffering from infections compared to gestational age-matched controls. Our results provide novel clues about perinatal immunity, underscoring a potential value of IL-8 for the timely detection of infections and suggesting that MIP-1β constitutes an early determinant of sex-specific immunity, which may contribute, e.g., to male’s vulnerability to preterm birth.     

Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.     

The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes

Bone metastasis remains the most frequent and the deadliest complication of prostate cancer (PCa). Mechanisms leading to the homing of tumor cells to bone remain poorly characterized. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well established. Bone is an adipocyte-rich organ since 50 to 70% of the adult bone marrow (BM) volume comprise bone marrow adipocytes (BM-Ads), which are likely to produce chemokines within the bone microenvironment. Using in vitro migration assays, we demonstrated that soluble factors released by human primary BM-Ads are able to support the directed migration of PCa cells in a CCR3-dependent manner. In addition, we showed that CCL7, a chemokine previously involved in the CCR3-dependent migration of PCa cells outside of the prostate gland, is released by human BM-Ads. These effects are amplified by obesity and ageing, two clinical conditions known to promote aggressive and metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone metastasis vs. primary tumors at mRNA levels using Oncomine microarray database. In addition, immunohistochemistry experiments demonstrated overexpression of CCR3 in bone versus visceral metastases. These results underline the potential importance of BM-Ads in the bone metastatic process and imply a CCR3/CCL7 axis whose pharmacological interest needs to be evaluated.     

Chemical-nutritional characterization of the moss Spagnum magellanicum

The goal of the present study was to know the chemical characteristics of the moss Sphagnum magellanicum (S.M.) growing in the southern part of Chile, spreading approximately. in a geographic area of 500.000 Has. Very few antecedents are reported in the literature concerning the functional properties of this resource, with the exception of the water absorption and holding capacity. Many of the industrial or agricultural uses of this moss are strongly related with this characteristic. Looking for other alternatives of utilization, it has been planned its incorporation to staple foods as a source of dietary fiber. But first it is necessary to know its chemical characteristics Representative samples of this material were submitted to different chemical analysis such as proximal analysis, fractional fiber analysis and anti nutrient factors.. Results of those analysis show the high amount of dietary fiber founded in this resource (77%), higher than reported data for other traditional fiber sources such as lupin bran, rice hull, barley hull, oat bran, etc. Finally it is important emphasize the absence of antinutrient factor in this moss, that could make feasible its use for human nutrition.     

A Fluorometric CYP19A1 (Aromatase) Activity Assay in Live Cells

Inhibition of estrogen synthesis is an integral component of the frontline pharmacologic therapy for the treatment of estrogen receptor positive cancers. However, there is currently no direct, high-throughput-ready assay for aromatase (also known as CYP19A1) that can be performed in live cells. Herein we present a cell-based assay that allows for multiplexed assessment of enzyme activity, protein half-life, cell viability, and identification of inhibitors with slow off-rates.     

Visualization and Analysis of Clickstream Data of Online Stores for Understanding Web Merchandising

Clickstreams are visitors' paths through a Web site. Analysis of clickstreams shows how a Web site is navigated and used by its visitors. Clickstream data of online stores contains information useful for understanding the effectiveness of marketing and merchandising efforts, such as how customers find the store, what products they see, and what products they purchase. In this paper, we present an interactive visualization system that provides users with greater abilities to interpret and explore clickstream data of online stores. This system visualizes the effectiveness of Web merchandising from two different points of view by using two different visualization techniques: visualization of sessions by using parallel coordinates and visualization of product performance by using starfield graphs. Furthermore, this system provides facilities for zooming, filtering, color-coding, dynamic querying and data sampling. It also provides summary information along with visualizations, and by maintaining a connection between visualizations and the source database, it dynamically updates the summary information. To demonstrate how the presented visualization system provides capabilities for examining online store clickstreams, we present a series of parallel coordinates and starfield visualizations that display clickstream data from an operating online retail store. A framework for understanding Web merchandising is briefly explained. A set of metrics referred to as micro-conversion rates, which are defined for Web merchandising analysis in our previous work (Lee et al., Electronic Markets, 2000), is also explained and used for the visualizations of online store effectiveness.     

The shield that never was: Societies with single-peaked preferences are more open to manipulation and control

Much work has been devoted, during the past 20 years, to using complexity to protect elections from manipulation and control. Many “complexity shield” results have been obtained—results showing that the attacker’s task can be made NP-hard. Recently there has been much focus on whether such worst-case hardness protections can be bypassed by frequently correct heuristics or by approximations. This paper takes a very different approach: We argue that when electorates follow the canonical political science model of societal preferences the complexity shield never existed in the first place. In particular, we show that for electorates having single-peaked preferences, many existing NP-hardness results on manipulation and control evaporate.     

Patterns of content, contextual, and working memory impairments in schizophrenia and nonamnesic alcoholism.

This study used tests of content memory (item recognition of words and abstract designs), context memory (order recognition of verbal and nonverbal items), and working memory (recognition at a short retention interval) to examine patterns of performance in 27 schizophrenic patients, 52 chronic alcoholic patients, and 66 healthy control participants. When performance was age- and IQ-adjusted the schizophrenia group was significantly impaired in item and order recognition of verbal and nonverbal material; the alcoholic group was impaired only in order recognition for both material types. Item- and order-recognition deficits in the schizophrenia group were greatest at the shortest retention intervals, a pattern previously observed in patients with Parkinson's disease, suggesting a prominence of a working memory deficit in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hemispheric laterality and memory bias for threat in anxiety disorder.

Examined auditory perceptual asymmetries and explicit memory biases for threat in patients with panic disorder and generalized anxiety disorder relative to healthy control Ss. They did not find a greater explicit memory bias for threat in the anxiety patients. However, explicit memory biases for threat were associated with perceptual asymmetry scores; patients with a greater right-ear (left hemisphere) advantage exhibited an explicit memory bias for threat material, whereas patients with a lower right-ear advantage displayed apparent cognitive avoidance of threat material. Memory for threat words was unrelated to perceptual asymmetry in healthy control Ss. These findings suggest that neuropsychological variables may partly determine the degree to which anxiety patients process threatening stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Women, sex roles, and alcohol problems.

Notes that, although the percentage of female social drinkers has risen, female intoxication still elicits more negative response then does male intoxication. The existing research on genetic/biological, psychological, and sociological explanations of alcoholism are examined expressly in light of the female perspective. Female alcoholic behaviors are identified in terms of initial intoxication, association with a stressful event, tendency to drink privately, nature of drinking habits, and tendency to use other drugs. The implications of research for clinical practice are seen to include consideration of related psychological and health problems, the need for adjunctive services, an emphasis on family treatment and restoration of social networks, and the therapist's need to achieve a balance between acceptance of the client and refusal to accept the client's acting-out behavior. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)