IFN-gamma is associated with risk of Schistosoma japonicum infection in China.

Before the start of the schistosomiasis transmission season, 129 villagers resident on a Schistosoma japonicum-endemic island in Poyang Lake, Jiangxi Province, 64 of whom were stool-positive for S. japonicum eggs by the Kato method and 65 negative, were treated with praziquantel. Forty-five days later the 93 subjects who presented for follow-up were all stool-negative. Blood samples were collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and soluble egg antigen (SEA) stimulated IL-4, IL-5 and IFN-gamma production in whole-blood cultures were measured by ELISA. All the subjects were interviewed nine times during the subsequent transmission season to estimate the intensity of their contact with potentially infective snail habitats, and the subjects were all re-screened for S. japonicum by the Kato method at the end of the transmission season. Fourteen subjects were found to be infected at that time. There was some indication that the risk of infection might be associated with gender (with females being at higher risk) and with the intensity of water contact, and there was evidence that levels of SEA-induced IFN-gamma production were associated with reduced risk of infection

Secondary resonances of co-orbital motions

The size distribution of the stability region around the Lagrangian point L4 is investigated in the elliptic restricted three-body problem as the function of the mass parameter and the orbital eccentricity of the primaries. It is shown that there are minimum zones in the size distribution of the stability regions, and these zones are connected with secondary resonances between the frequencies of librational motions around L4. The results can be applied to hypothetical Trojan planets for predicting values of the mass parameter and the eccentricity for which such objects can be expected or their existence is less probable.Comment: 9 pages, 7 figures, accepted for publication in MNRA

Epidermal growth factor mediates spermatogonial proliferation in newt testis

The complex processes of spermatogenesis are regulated by various factors. The aim of the current study is to determine the effect of epidermal growth factor (EGF) on spermatogonial proliferation and clarify the mechanism causing the proliferation in newt testis. In the organ culture, EGF stimulated spermatogonial proliferation, but not their differentiation into spermatocytes. cDNA cloning identified 3 members of the EGF receptors, ErbB1, ErbB2, and ErbB4, in the testis. RT-PCR showed that all the receptors cloned were expressed in both Sertoli and germ cells at the spermatogonial stage. In the organ cultures with inhibitors for the EGF receptors, mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K), the EGF-induced spermatogonial proliferation was suppressed. Furthermore, when the organ culture was exposed to EGF, the expressions of stem cell factor (SCF), immunoglobulin-like domain containing neuregulin1 (Ig-NRG1), and ErbB4 mRNA were increased. These results suggested that, since the spermatogonia are sequestered within cysts by the blood-testis barrier consisted of Sertoli cells, EGF possibly mediates spermatogonial proliferation in an endocrine manner through the receptors including ErbB1, ErbB2, and ErbB4 expressed on Sertoli cells via activation of MAPK cascade or/and PI3K cascade by elevating the expressions of SCF, Ig-NRG1, and ErbB4

Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells

IL-2 is the primary growth factor for promoting survival and proliferation of activated T cells that occurs following engagement of the Janus Kinase (JAK)1-3/and Signal Transducer and Activator of Transcription (STAT) 5 signaling pathway. STAT5 has two isoforms: STAT5A and STAT5B ( commonly referred to as STAT5) which, in T cells, play redundant roles transcribing cell cycle and survival genes. As such, inhibition of STAT5 by a variety of mechanisms can rapidly induce apoptosis in certain lymphoid tumor cells, suggesting that it and its target genes represent therapeutic targets to control certain lymphoid diseases. To search for these molecules we aligned IL-2 regulated genes detected by Affymetrix gene expression microarrays with the STAT5 cistrome identified by chip-on-ChIP analysis in an IL-2-dependent human leukemia cell line, Kit225. Select overlapping genes were then validated using qRT(2)PCR medium-throughput arrays in human PHA-activated PBMCs. Of 19 putative genes, one key regulator of T cell receptor signaling, PDE4B, was identified as a novel target, which was readily up-regulated at the protein level (3 h) in IL-2 stimulated, activated human PBMCs. Surprisingly, only purified CD8+ primary T-cells expressed PDE4B, but not CD4+ cells. Moreover, PDE4B was found to be highly expressed in CD4+ lymphoid cancer cells, which suggests that it may represent a physiological role unique to the CD8+ and lymphoid cancer cells and thus might represent a target for pharmaceutical intervention for certain lymphoid diseases

Possible Beneficial Effect of Exercise, by Reducing Oxidative Stress, on the Incidence of Preeclampsia

We hypothesize that regular exercise enhances antioxidative enzymes in pregnant women, which reduce oxidative stress and, thus, the incidence of preeclampsia. Oxidative stress with enhanced lipid peroxide formation could lead to endothelial dysfunction in preeclampsia. Other conditions, such as increased transferrin saturation and decreased iron-binding capacity, directly and indirectly promote the process of oxidative stress and subsequent endothelial dysfunction. Exercise increases oxidative metabolism and produces a prooxidant environment. This acidic environment during exercise (at or beyond anaerobic threshold) promotes oxygen release from hemoglobin and increases in PO2 in tissues, as well as releases iron from transferrin. When exercise is repeated regularly, the body promptly adjusts so that oxidative stress is eliminated or reduced. The body's adaptations to a regular exercise habit seem to have an antioxidant effect. In humans, training effects have been identified with an enhanced activity of antioxidative enzymes. Another concerted adaptation that regular exercise brings to women's bodies is resistance against production of prooxidants by increasing the number of mitochondria. Equally important is a training effect that decreases susceptibility to lipid peroxidation. Evidence suggests that physically active women are less likely to develop preeclampsia. In theory, intracellular and extracellular conditions resulting from regular exercise should counteract the enhancement of oxidative stress, thus interfering with the process leading to endothelial dysfunction. This position paper describes a hypothesis and includes a brief review of exercise physiology and biochemical research in preeclampsia. Unlike other preventive treatments, such as aspirin or calcium supplements, a regular exercise habit leads to a positive and healthy lifestyle without concern of side effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63167/1/152460901317193558.pd

?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

New Bending Algorithm for Field-Driven Molecular Dynamics

A field-driven bending method is introduced in this paper according to the coordinate transformation between straight and curved coordinates. This novel method can incorporate with the periodic boundary conditions in analysis along axial, bending, and transverse directions. For the case of small bending, the bending strain can be compatible with the beam theory. Consequently, it can be regarded as a generalized SLLOD algorithm. In this work, the bulk copper beam under bending is analyzed first by the novel bending method. The bending stress estimated here is well consistent to the results predicted by the beam theory. Moreover, a hollow nanowire is also analyzed. The zigzag traces of atomic stress and the corresponding 422 common neighbor type can be observed near the inner surface of the hollow nanowire, which values are increased with an increase of time. It can be seen that the novel bending method with periodic boundary condition along axial direction can provide a more physical significance than the traditional method with fixed boundary condition

Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Mediates Neuronal Aβ42 Uptake and Lysosomal Trafficking

Alzheimer's disease (AD) is characterized by the presence of early intraneuronal deposits of amyloid-beta 42 (Abeta42) that precede extracellular amyloid deposition in vulnerable brain regions. It has been hypothesized that endosomal/lysosomal dysfunction might be associated with the pathological accumulation of intracellular Abeta42 in the brain. Our previous findings suggest that the LDL receptor-related protein 1 (LRP1), a major receptor for apolipoprotein E, facilitates intraneuronal Abeta42 accumulation in mouse brain. However, direct evidence of neuronal endocytosis of Abeta42 through LRP1 is lacking.Here we show that LRP1 endocytic function is required for neuronal Abeta42 uptake. Overexpression of a functional LRP1 minireceptor, mLRP4, increases Abeta42 uptake and accumulation in neuronal lysosomes. Conversely, knockdown of LRP1 expression significantly decreases neuronal Abeta42 uptake. Disruptions of LRP1 endocytic function by either clathrin knockdown or by removal of its cytoplasmic tail decreased both uptake and accumulation of Abeta42 in neurons. Finally, we show that LRP1-mediated neuronal accumulation of Abeta42 is associated with increased cellular toxicity.These results demonstrate that LRP1 endocytic function plays an important role in the uptake and accumulation of Abeta42 in neuronal lysosomes. These findings emphasize the central function of LRP1 in neuronal Abeta metabolism

Effect of a Dipeptidyl Peptidase-IV Inhibitor, Des-Fluoro-Sitagliptin, on Neointimal Formation after Balloon Injury in Rats

Background: Recently, it has been suggested that enhancement of incretin effect improves cardiac function. We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms. Methods and Findings: Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group). Sitagliptin or normal saline were given orally from 1 week before to 2 weeks after carotid injury. After 3 weeks of treatment, sitagliptin treatment caused a significant and dose-dependent reduction in intima-media ratio (IMR) in obese diabetic rats. This effect was accompanied by improved glucose homeostasis, decreased circulating levels of high-sensitivity C-reactive protein (hsCRP) and increased adiponectin level. Moreover, decreased IMR was correlated significantly with reduced hsCRP, tumor necrosis factor-$\alpha$ and monocyte chemoattractant protein-1 levels and plasminogen activator inhibitor-1 activity. In vitro evidence with vascular smooth muscle cells (VSMCs) demonstrated that proliferation and migration were decreased significantly after sitagliptin treatment. In addition, sitagliptin increased caspase-3 activity and decreased monocyte adhesion and NFκB activation in VSMCs. Conclusions: Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes