bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPLEMENTING ENTANGLEMENT SWAPPING WITH A THERMAL CAVITY
Authors: HE ZHI , LONG CHAO-YUN , QIN SHUI-JIE , WEI GAO-FENG
Published: January 2008

We proposed a scheme to implement the entanglement swapping based on cavity QED. Using this scheme, we can obtain the entanglement swapping with the success probability of 100% for a two atoms system and a three atoms system respectively, and the entanglement swapping is insensitive to both the cavity decay and thermal field.
ON THE NON-EXISTENCE OF A UNIVERSAL HADAMARD GATE
Authors: PARASHAR PREETI
Published: January 2008

We establish the non-existence of a universal Hadamard gate for an arbitrary qubit, by considering two different principles; namely, no-superluminal signalling and non-increase of entanglement under LOCC. It is also shown that these principles are not violated if and only if the qubit states belong to the special ensemble obtained recently. We then extend the non-existence of the Hadamard operation to a multi-qubit system. In higher dimensions, the analog of the Hadamard gate is the quantum Fourier transform. We show that it is not possible to design this gate for an arbitrary qudit.
LPS induces the TNF-α-mediated downregulation of rat liver aquaporin-8: role in sepsis-associated cholestasis
Authors: Lehmann Guillermo L. , Carreras Flavia I. , Soria Leandro R. , Gradilone Sergio A. , Marinelli Raúl A.
Published: January 2008

Although bacterial lipopolysaccharides (LPS) are known to cause cholestasis in sepsis, the molecular mechanisms accounting for this effect are only partially known. Because aquaporin-8 (AQP8) seems to facilitate the canalicular osmotic water movement during hepatocyte bile formation, we studied its gene and functional expression in LPS-induced cholestasis. By subcellular fractionation and immunoblotting analysis, we found that 34-kDa AQP8 was significantly decreased by 70% in plasma (canalicular) and intracellular (vesicular) liver membranes. However, expression and subcellular localization of hepatocyte sinusoidal AQP9 were unaffected. Immunohistochemistry for liver AQPs confirmed these observations. Osmotic water permeability ( Pf) of canalicular membranes, measured by stopped-flow spectrophotometry, was significantly reduced (65 ± 1 vs. 49 ± 1 μm/s) by LPS, consistent with defective canalicular AQP8 functional expression. By Northern blot analysis, we found that 1.5-kb AQP8 mRNA expression was increased by 80%, suggesting a posttranscriptional mechanism of protein reduction. The tumor necrosis factor-α (TNF-α) receptor fusion protein TNFp75:Fc prevented the LPS-induced impairment of AQP8 expression and bile flow, suggesting the cytokine TNF-α as a major mediator of LPS effect. Accordingly, studies in hepatocyte primary cultures indicated that recombinant TNF-α downregulated AQP8. The effect of TNF-α was prevented by the lysosomal protease inhibitors leupeptin or chloroquine or by the proteasome inhibitors MG132 or lactacystin, suggesting a cytokine-induced AQP8 proteolysis. In conclusion, our data suggest that LPS induces the TNF-α-mediated posttranscriptional downregulation of AQP8 functional expression in hepatocytes, a mechanism potentially relevant to the molecular pathogenesis of sepsis-associated cholestasis.
Effects of vasoconstriction and vasodilatation on LV and segmental circulatory energetics
Authors: Wang Jiun-Jr , Shrive Nigel G. , Parker Kim H. , Tyberg John V.
Published: January 2008

Although the hydraulic work generated by the left ventricle (LV) is not disputed, how the work was dissipated through the systemic circulation is still subject to interpretation. Recently, we proposed that the systemic circulation should be considered as waves and a reservoir system (Wk). By combining the arterial and venous reservoirs, the systemic vascular resistance can be viewed as a series of resistors, which in sequence are the large-artery resistance, arterial reservoir resistance, the microcirculatory resistance, venous reservoir resistance, and large-vein resistance, and propelling blood through these resistance elements represents resistive losses. We then studied the changes in the fraction of the work consumed by each element when infusing methoxamine (MTX), a vasoconstrictor, and sodium nitroprusside (NP), a vasodilator. Results show that, under control condition, ∼50% of the LV stroke work was dissipated through arterial reservoir resistance (NP, ∼36%; MTX, ∼27%), another ∼25% was dissipated by the microcirculation (NP, ∼20%; MTX, ∼66%), and ∼20% of work by the large-artery resistances (NP, ∼37%; MTX, ∼6%). The energy dissipated by the venous resistances was small and had limited variation with NP and MTX, where the large-vein and venous reservoir resistances shared ∼1 and ∼3% of LV stroke work, respectively. Approximately 60% of LV stroke work is stored as the potential energy during systole under control, and the ratio decreases to ∼45% with NP and ∼80% with MTX.
Coughing May Lead to Spontaneous Chylothorax and Chylous Ascites
Authors: Adas Gokhan , Karatepe Oguzhan , Battal Muharrem , Dogan Yasar , Karyagar Savas , Kutlu Asım
Published: January 2008

Chylous ascites is a rare form of ascites resulting from the accumulation of lymph in the abdominal cavity. It is due to an interruption in the lymphatic system. Surgical management is indicated in cases of recurrence or failure after conservative treatment. We report a case of spontaneous chylous peritonitis after chylothorax, which is a rare clinical event. The primary reason was unclear and the outcome of medical and surgical treatment was successful.
Measurement of the ‘Shoulder-Umbilical’ Distance for Insertion of Umbilical Catheters in Newborn Babies: Questionnaire Study
Authors: Lopriore Enrico , Verheij Gerdina H. , Walther Frans J.
Published: January 2008

Approximately 40 years ago, Dr. Peter Dunn introduced a simple method to determine the insertion length of umbilical catheters in neonates, by using the ‘shoulder-umbilical’ (S-U) length. Since then, various studies have reported a high rate of malposition of umbilical catheters. One of the possible reasons is that the method used to determine the S-U length varies among paediatric professionals. We performed a questionnaire study among 101 paediatric professionals in the Netherlands and found that the method used by the participants to measure the S-U length was highly inconsistent. Placement of an umbilical venous catheter in a too deep position may lead to potentially life-threatening complications. Therefore, uniformity in measurement is paramount for clinical and teaching purposes. Paediatric professionals using Dunn’s definition to place umbilical catheters should adhere more strictly to the original description of the measurement of the S-U length.
The Level of Awareness of Stroke Risk Factors and Symptoms in the Gulf Cooperation Council Countries: Gulf Cooperation Council Stroke Awareness Study
Authors: Kamran S. , Bener A.B. , Deleu D. , Khoja W. , Jumma M. , Al Shubali A. , Inshashi J. , Sharouqi I. , Al Khabouri J.
Published: January 2008

Objective: To assess the knowledge of stroke in the general public in the Gulf Cooperation Council (GCC) countries. Background: The Arabian Gulf is a rapidly developing part of the world with major changes in the lifestyle that can increase the risk of stroke. To design effective stroke treatment and prevention strategies, an assessment of the public knowledge of stroke is required. Methods: A cross-sectional community-based survey was conducted at primary health care centers (PHCs), in urban and semi-urban areas, of the GCC countries (Qatar, Saudi Arabia, Kuwait, Bahrain, the United Arab Emirates, Oman) on the level of stroke awareness in the general public. Health care workers completed 3,750 face-to-face interviews. Results: 1,089 (29.0%) were familiar with the term ‘stroke’, and 29.3% considered the age group 30–50 at the highest risk for stroke. The commonest risk factors identified were hypertension (23.1%) and smoking (27.3%). People who did not know the term stroke had a higher incidence of diabetes, hypertension, and had more than one risk factor (p < 0.05). The most frequently identified stroke symptoms were weakness (23%) and speech problems (21.7%). Of those who recognized stroke, blockage of blood vessels was identified as the commonest cause of stroke (22%) followed by tension/worrying (20%). Doctors and nurses were regarded as the best source of stroke information (70%). In the univariate comparison, younger age (p < 0.001), higher level of education (p < 0.001), and female gender (p = 0.008) better predicted stroke recognition. In a multivariate logistic regression analysis, the level of education, monthly income and smoking were independent variables predicting stroke knowledge. Conclusion: The majority of the patients had not even heard the term stroke. Stroke knowledge was poorest among the groups that were at the highest risk for stroke. Stroke education has to focus on the high-risk groups, particularly the younger population. The health care workers at the PHCs and hospitals will need instructions on providing stroke information to the public. The level of knowledge of stroke risk factors and symptoms emphasizes the need for stroke education efforts in the community.
Pharmacological Properties of SD-282 – An α-Isoform Selective Inhibitor for p38 MAP Kinase
Authors: Koppelman Bruce , Webb Heather K. , Medicherla Satyanarayana , Almirez Ramona , Feng Ying , Chavez Jose Carlos , Mao Cheng Ping , Nguyen Aaron , Liu Yu-Wang , Kapoun Ann M. , Muiru Gladys , Huang Yuanying Anne , Dugar Sundeep , Mavunkel Babu J. , Lim Don W. , Chakravarty Sarvajit , Luedtke Gregory , Protter Andrew A. , Higgins Linda S.
Published: January 2008

The effects of small-molecule p38 inhibitors in numerous models of different disease states have been published, including those of SD-282, an indole-5-carboxamide inhibitor. The aim of the present study was to evaluate the pharmacological activity of SD-282 on cytokine production in vitro as well as in 2 in vivo models of inflammation in order to illuminate the role of this particular inhibitor in diverse disease states. The results presented here provide further characterization of SD-282 and provide a context in which to interpret the activity of this p38 inhibitor in models of arthritis, pain, myocardial injury, sepsis and asthma; all of which have an inflammatory component. SD-282 represents a valuable tool to elucidate the role of p38 MAP kinase in multiple models of inflammation.
The Scavenger Receptor Class B Type I Adaptor Protein PDZK1 Maintains Endothelial Monolayer Integrity
Authors: Zhu Weifei , Saddar Sonika , Seetharam Divya , Chambliss Ken L. , Longoria Christopher , Silver David L. , Yuhanna Ivan S. , Shaul Philip W. , Mineo Chieko
Published: January 2008

Circulating levels of high-density lipoprotein (HDL) cholesterol are inversely related to the risk of cardiovascular disease, and HDL and the HDL receptor scavenger receptor class B type I (SR-BI) initiate signaling in endothelium through src that promotes endothelial NO synthase activity and cell migration. Such signaling requires the C-terminal PDZ-interacting domain of SR-BI. Here we show that the PDZ domain–containing protein PDZK1 is expressed in endothelium and required for HDL activation of endothelial NO synthase and cell migration; in contrast, endothelial cell responses to other stimuli, including vascular endothelial growth factor, are PDZK1-independent. Coimmunoprecipitation experiments reveal that Src interacts with SR-BI, and this process is PDZK1-independent. PDZK1 also does not regulate SR-BI abundance or plasma membrane localization in endothelium or HDL binding or cholesterol efflux. Alternatively, PDZK1 is required for HDL/SR-BI to induce Src phosphorylation. Paralleling the in vitro findings, carotid artery reendothelialization following perivascular electric injury is absent in PDZK1
−/−
mice, and this phenotype persists in PDZK1
−/−
mice with genetic reconstitution of PDZK1 expression in liver, where PDZK1 modifies SR-BI abundance. Thus, PDZK1 is uniquely required for HDL/SR-BI signaling in endothelium, and through these mechanisms, it is critically involved in the maintenance of endothelial monolayer integrity.
Non–Cell-Autonomous Roles for the Planar Cell Polarity Gene Vangl2 in Development of the Coronary Circulation
Authors: Phillips Helen M. , Hildreth Victoria , Peat Jonathan D. , Murdoch Jennifer N. , Kobayashi Kazuto , Chaudhry Bill , Henderson Deborah J.
Published: January 2008

Establishment of cellular polarity is essential for the development of many tissues. In this study, we describe defects in the formation of the coronary vasculature in the loop-tail (
Lp
) mutant in which the planar cell polarity (PCP) gene,
Vangl2
, is disrupted. Although Vangl2 is expressed exclusively in the myocardial cells of the developing heart, the coronary vessels do not develop an intact smooth muscle layer, and there are enlarged, ectopic vessels on the surface of the heart. Reduced fibronectin deposition in the subepicardial space is associated with limited migration of epicardially derived cells (EPDCs) into the ventricular myocardium and likely contributes to these defects. Analysis of cardiomyocytes shows that the actin cytoskeleton is disrupted and the cytoarchitecture of the ventricular myocardium is abnormal in
Lp/Lp
hearts. Moreover, activation of RhoA/Rho kinase signaling is disrupted in these cells. Conditional inhibition of myocardial Rho kinase activity disrupts the organization of the cardiomyocytes and formation of the coronary vessels to produce the same spectrum of defects as seen in
Lp
. These data suggest that Vangl2 and Rho kinase act cell autonomously in the myocardium to regulate the organization of cardiomyocytes but also have non–cell-autonomous effects on the formation of the coronary vasculature.
Factor Xa Binding to Annexin 2 Mediates Signal Transduction via Protease-Activated Receptor 1
Authors: Bhattacharjee Gourab , Ahamed Jasimuddin , Pawlinski Rafal , Liu Cheng , Mackman Nigel , Ruf Wolfram , Edgington Thomas S.
Published: January 2008

The serine protease zymogen factor X is converted to its catalytically active form factor Xa by the binary complex of factor VIIa bound to its cell surface receptor tissue factor (TF) or by the intrinsic Xase complex, which consists of active factors VIII (VIIIa), IX (IXa), factor X, and Ca
2+
. Factor Xa has procoagulant activity by conversion of prothrombin to thrombin and also induces signal transduction, either alone or in the ternary TF:VIIa:factor Xa coagulation initiation complex. Factor Xa cleaves and activates protease activated receptor (PAR)1 or -2, but factor Xa signaling efficiency varies among cell types. We show here that annexin 2 acts as a receptor for factor Xa on the surface of human umbilical vein endothelial cells and that annexin 2 facilitates factor Xa activation of PAR-1 but does not enhance coagulant function of factor Xa. Overexpression of TF abolishes annexin 2 dependence on factor Xa signaling and diminishes binding to cell surface annexin 2, whereas selectively abolishing TF promotes the annexin 2/factor Xa interaction. We propose that annexin 2 serves to regulate factor Xa signaling specifically in the absence of cell surface TF and may thus play physiological or pathological roles when factor Xa is generated in a TF-depleted environment.
Preferred Involvement of the Basal Ganglia After Lenticulostriate Infarction as a Possible Indicator of Different Gray and White Matter Vulnerability
Authors: Nagakane Yoshinari , Yamada Kei , Ohara Tomoyuki , Yoshikawa Kenji , Kuriyama Nagato , Takayasu Natsuko , Kasai Takashi , Yuki Natsuko , Nishimura Tsunehiko , Mizuno Toshiki , Nakagawa Masanori
Published: January 2008

Background and Purpose—

Symptomatic progression is frequently observed in lacunar infarcts. The exact mechanisms of this phenomenon have not yet been clarified.

Summary of Cases—

We report 2 patients with lenticulostriate artery infarcts that presented with skip lesions that were restricted to gray matter. One of the patients subsequently developed symptomatic deterioration; the other experienced no further neurological events.

Conclusions—

A possible mechanism of differential vulnerability to ischemia of gray and white matter is considered. White matter may have a longer therapeutic time window for neuroprotective treatment than gray matter.
Rapid Identification of High-Risk Transient Ischemic Attacks
Authors: Sciolla Rossella , Melis Fabio
Published: January 2008

Background and Purpose—

A 6-point score, based on age, blood pressure, clinical features, and duration (ABCD), was shown to effectively stratify the short-term risk of stroke after a transient ischemic attack (TIA). Prospective validation in different populations of patients should precede its widespread use. Whether adding computed tomography (CT) scan findings to the score would improve its performance deserves exploring. We aimed to validate the ABCD score in a prospective cohort of patients accessing Emergency Departments within 24 hours of a TIA in an area of northern Italy and to acquire preliminary data on CT-based refinement.

Methods—

During a 6-month period, all TIA patients accessing the Emergency Departments of 13 Piemonte and Valle d’Aosta hospitals were prospectively enrolled and stratified according to the 6-point ABCD score and to a 7-point score (ABCDI, where I=imaging) incorporating CT findings.

Results—

Of 274 patients, stroke occurred in 10 (3.6%) within 7 days and in 15 (5.5%) within 30 days. The ABCD score was predictive of stroke risk at both 7 and 30 days (odds ratio for every point of the score=2.55 at 7 days and 2.62 at 30 days;
P
for linear trend across the ABCD score levels=0.018 at 7 days and 0.0017 at 30 days). CT scan findings further increased prediction (odds ratio for every point of the score=2.68 at 7 days and 2.89 at 30 days;
P
for linear trend across the ABCDI score levels=0.0043 at 7 days and 0.0003 at 30 days).

Conclusions—

The ABCD score confirmed its prognostic value in this prospective cohort. CT results could further improve prediction.
Domain of Aspectual Interpretation
Authors: MacDonald Jonathan E.
Published: January 2008

Thompson (2006) argues for a syntactic account of telicity in which DPs and PPs check a [bounded] feature at an AspP projection above vP to create a telic predicate. I provide evidence for an AspP projection between vP and VP and argue that AspP and everything AspP dominates defines a domain of aspectual interpretation, a syntactic space within which elements must be located in order to affect the telicity of a predicate. I provide data showing that elements above AspP cannot affect aspectual interpretation. These data pose a serious problem for Thompson's account.
Observing Surf-Zone Dispersion with Drifters
Authors: Spydell Matthew , Feddersen Falk , Guza R. T. , Schmidt W. E.
Published: January 2008

Surf-zone dispersion is studied using drifter observations collected within about 200 m of the shoreline (at depths of less than about 5 m) on a beach with approximately alongshore uniform bathymetry and waves. There were about 70 individual drifter releases, each 10–20 min in duration, on two consecutive days. On the first day, the sea-swell significant wave height Hs was equal to 0.5 m and mean alongshore currents |υ| were moderate (<0.1 m s−1). On the second day, the obliquely incident waves were larger, with Hs equal to 1.4 m, and at some surf-zone locations |υ| was greater than 0.5 m s−1. The one-particle diffusivity was larger, with larger waves and stronger currents. On both days, the one-particle diffusivity tensor is nonisotropic and time-dependent. The major axis is initially parallel to the cross-shore direction, but after a few wave periods it is aligned with the alongshore direction. In both the along- and cross-shore directions, the asymptotic diffusivity is reached sooner within, rather than seaward of, the surf zone. Two-particle statistics indicate that relative dispersion grows like D2(t) ∼ t3/2 and that the relative diffusivity is scale-dependent as μ ∼ l2/3, with l being the particle separation. The observed scalings differ from 2D inertial-subrange scalings [D2(t) ∼ t3 and μ ∼ l4/3]. Separations have a non-Gaussian self-similar distribution that is independent of time. The two-particle statistics are consistent with a nonconstant-coefficient diffusion equation for the separation probability density functions. The dispersion is explained by neither irrotational surface gravity waves nor shear dispersion. The observations imply the existence of a 2D eddy field with 5–50-m length scales, the source of which is speculated to be alongshore gradients in breaking-wave height associated with finite crest lengths.
Long Barotropic Waves Generated by a Storm Crossing Topography
Authors: Vennell Ross
Published: January 2008

Storms crossing topography are shown to radiate long surface gravity waves. The waves are transients generated by changes in the depth-dependent amplitude of the atmospherically forced pressure wave beneath a storm. This generation mechanism for long waves, known as “meteorological tsunamis” or rissaga, does not appear to have been previously discussed. The transients have periods equal to the passage time of the storm, of order 30 min for small fast-moving storms. A 1D model is used to give the amplitudes of the transient waves generated by a small fast-moving storm crossing a topographic step on to a continental shelf and across a ridge. Large transients are generated by storms whose translation speed is subcritical in deep water and supercritical in shallow water, that is, faster than the shallow-water wave speed. Surprisingly, when the depth difference between the deep water and the continental shelf is large, a gentle transition from deep to shallow water over 10 storm widths only slightly reduces the amplitudes of the transients. The influence of a finite-width shelf on the enhancement of coastal storm surge is also discussed. A 2D numerical model illustrates the topographic transients generated by sub- and supercritical storms moving across a ridge. Topographic transients are suggested as a source of energy for seiches on shelves and within embayments. The energy may come from a storm crossing the adjacent continental slope and possibly from distant open-ocean storms crossing multiple ridges and seamounts.
Primitive erythropoiesis and megakaryopoiesis in the yolk sac are independent of c-myb
Authors: Tober Joanna , McGrath Kathleen E. , Palis James
Published: January 2008

Hematopoiesis initiates within the yolk sac of mammalian embryos in overlapping primitive and definitive waves, each containing erythroid and megakaryocyte progenitors. c-myb–null mouse fetuses lack definitive erythrocytes but contain primitive erythroblasts and hepatic megakaryocytes. However, it is unclear if c-myb–null embryos harbor definitive erythroid or any megakaryocyte progenitors. We determined that c-myb was not expressed in primitive erythroid precursors and that c-myb–null embryos had normal primitive erythroid and megakaryocyte progenitor numbers and kinetics between embryonic day (E) 7.0 and E9.0. While primitive hematopoiesis is c-myb–independent, no definitive erythroid potential was detected in c-myb–null embryos, confirming that definitive erythropoiesis, beginning at E8.25 in the yolk sac, is completely c-myb–dependent. In contrast, reduced numbers of megakaryocyte progenitors with restricted proliferative capacity persist in E10.5 yolk sac and E11.5 liver. Despite this impaired megakaryocyte potential, c-myb–null fetuses had normal platelet numbers at E12.5 but became thrombocytopenic by E15.5, suggesting that c-myb is required for sustained thrombopoiesis.
Extending pathways based on gene lists using InterPro domain signatures
Authors: Hahne Florian , Mehrle Alexander , Arlt Dorit , Poustka Annemarie , Wiemann Stefan , Beissbarth Tim
Published: January 2008

Background

High-throughput technologies like functional screens and gene expression analysis produce extended lists of candidate genes. Gene-Set Enrichment Analysis is a commonly used and well established technique to test for the statistically significant over-representation of particular pathways. A shortcoming of this method is however, that most genes that are investigated in the experiments have very sparse functional or pathway annotation and therefore cannot be the target of such an analysis. The approach presented here aims to assign lists of genes with limited annotation to previously described functional gene collections or pathways. This works by comparing InterPro domain signatures of the candidate gene lists with domain signatures of gene sets derived from known classifications, e.g. KEGG pathways.

Results

In order to validate our approach, we designed a simulation study. Based on all pathways available in the KEGG database, we create test gene lists by randomly selecting pathway genes, removing these genes from the known pathways and adding variable amounts of noise in the form of genes not annotated to the pathway. We show that we can recover pathway memberships based on the simulated gene lists with high accuracy. We further demonstrate the applicability of our approach on a biological example.

Conclusion

Results based on simulation and data analysis show that domain based pathway enrichment analysis is a very sensitive method to test for enrichment of pathways in sparsely annotated lists of genes. An R based software package domainsignatures, to routinely perform this analysis on the results of high-throughput screening, is available via Bioconductor.
MacroH2A1 knockdown effects on the Peg3 imprinted domain
Authors: Choo Jung Ha , Kim Jeong Do , Kim Joomyeong
Published: January 2008

Background

MacroH2A1 is a histone variant that is closely associated with the repressed regions of chromosomes. A recent study revealed that this histone variant is highly enriched in the inactive alleles of Imprinting Control Regions (ICRs).

Results

The current study investigates the potential roles of macroH2A1 in genomic imprinting by lowering the cellular levels of the macroH2A1 protein. RNAi-based macroH2A1 knockdown experiments in Neuro2A cells changed the expression levels of a subset of genes, including Peg3 and Usp29 of the Peg3 domain. The expression of these genes was down-regulated, rather than up-regulated, in response to reduced protein levels of the potential repressor macroH2A1. This down-regulation was not accompanied with changes in the DNA methylation status of the Peg3 domain.

Conclusion

MacroH2A1 may not function as a transcriptional repressor for this domain, but that macroH2A1 may participate in the heterochromatin formation with functions yet to be discovered.
Single nucleotide polymorphisms (SNPs) are highly conserved in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques
Authors: Street Summer L , Kyes Randall C , Grant Richard , Ferguson Betsy
Published: January 2008

Background

Macaca fascicularis (cynomolgus or longtail macaques) is the most commonly used non-human primate in biomedical research. Little is known about the genomic variation in cynomolgus macaques or how the sequence variants compare to those of the well-studied related species, Macaca mulatta (rhesus macaque). Previously we identified single nucleotide polymorphisms (SNPs) in portions of 94 rhesus macaque genes and reported that Indian and Chinese rhesus had largely different SNPs. Here we identify SNPs from some of the same genomic regions of cynomolgus macaques (from Indochina, Indonesia, Mauritius and the Philippines) and compare them to the SNPs found in rhesus.

Results

We sequenced a portion of 10 genes in 20 cynomolgus macaques. We identified 69 SNPs in these regions, compared with 71 SNPs found in the same genomic regions of 20 Indian and Chinese rhesus macaques. Thirty six (52%) of the M. fascicularis SNPs were overlapping in both species. The majority (70%) of the SNPs found in both Chinese and Indian rhesus macaque populations were also present in M. fascicularis. Of the SNPs previously found in a single rhesus population, 38% (Indian) and 44% (Chinese) were also identified in cynomolgus macaques. In an alternative approach, we genotyped 100 cynomolgus DNAs using a rhesus macaque SNP array representing 53 genes and found that 51% (29/57) of the rhesus SNPs were present in M. fascicularis. Comparisons of SNP profiles from cynomolgus macaques imported from breeding centers in China (where M. fascicularis are not native) showed they were similar to those from Indochina.

Conclusion

This study demonstrates a surprisingly high conservation of SNPs between M. fascicularis and M. mulatta, suggesting that the relationship of these two species is closer than that suggested by morphological and mitochondrial DNA analysis alone. These findings indicate that SNP discovery efforts in either species will generate useful resources for both macaque species. Identification of SNPs that are unique to regional populations of cynomolgus macaques indicates that location-specific SNPs could be used to distinguish monkeys of uncertain origin. As an example, cynomolgus macaques obtained from 2 different breeding centers in China were shown to have Indochinese ancestry.
Humoral response to HspX and GlcB to previous and recent infection by Mycobacterium tuberculosis
Authors: Rabahi Marcelo Fouad , Junqueira-Kipnis Ana Paula , dos Reis Michelle Cristina Guerreiro , Oelemann Walter , Conde Marcus Barreto
Published: January 2008

Background

Tuberculosis (TB) remains a major world health problem. Around 2 billions of people are infected by Mycobacterium tuberculosis, the causal agent of this disease. This fact accounts for a third of the total world population and it is expected that 9 million people will become infected each year. Only approximately 10% of the infected people will develop disease. However, health care workers (HCW) are continually exposed to the bacilli at endemic sites presenting increased chance of becoming sick. The objective of this work was to identify LTBI (latent tuberculosis infection) among all asymptomatic HCW of a Brazilian Central Hospital, in a three year follow up, and evaluate the humoral response among HCW with previous and recent LTBI to recombinant HspX and GlcB from M. tuberculosis.

Methods

Four hundred and thirty seven HCW were screened and classified into three different groups according to tuberculin skin test (TST) status: uninfected, previous LTBI and recent LTBI. ELISA test were performed to determine the humoral immune response to HspX and GlcB.

Results

The levels of IgG and IgM against the HspX and GlcB antigens were the same among HCW with recent and previous LTBI, as well as among non infected HCW. However, the IgM levels to HspX was significantly higher among HCW with recent LTBI (OD = 1.52 ± 0.40) than among the uninfected (OD = 1.09 ± 0.50) or subjects with previous LTBI (OD = 0.96 ± 0.51) (p < 0.001).

Conclusion

IgG and IgM humoral responses to GlcB antigens were similar amongst all studied groups; nevertheless IgM levels against HspX were higher among the recent LTBI/HCW.
A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails
Authors: Tang Shaohua , Xu Qiyu , Xu Xueqin , Du Jicheng , Yang Xuemei , Jiang Yusheng , Wang Xiaoqin , Speck Nancy , Huang Taosheng
Published: January 2008

Background

Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD.

Methods

Here, a large Chinese family with CCD and hyperplastic nails was recruited. The clinical features displayed a significant intrafamilial variation. We sequenced the coding region of the RUNX2 gene for the mutation and phenotype analysis.

Results

The family carries a c.T407C (p.L136P) mutation in the DNA- and CBFβ-binding Runt domain of RUNX2. Based on the crystal structure, we predict this novel missense mutation is likely to disrupt DNA binding by RUNX2, and at least locally affect the Runt domain structure.

Conclusion

A novel missense mutation was identified in a large Chinese family with CCD with hyperplastic nails. This report further extends the mutation spectrum and clinical features of CCD. The identification of this mutation will facilitate prenatal diagnosis and preimplantation genetic diagnosis.
Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma
Authors: Tian Ze , Si Jianyong , Chang Qi , Zhou Liang , Chen Shilin , Xiao Peigen , Wu Erxi
Published: January 2008

Background

Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of Cimicifuga dahurica showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of C. dahurica and therefore might eventually be useful in the prevention or treatment of Hepatoma.

Methods

The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H22 hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA in vivo.

Results

The IC50 values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G0/G1 cell cycle arrest at lower concentration (25 μg/ml), and triggered G2/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H22 tumor in a dose-dependent manner.

Conclusion

TGA may potentially find use as a new therapy for the treatment of hepatoma.
Lumbar position sense and the risk of low back injuries in college athletes: a prospective cohort study
Authors: Silfies Sheri P , Cholewicki Jacek , Reeves N Peter , Greene Hunter S
Published: January 2008

Background

Impaired proprioception in the lumbar spine has often been reported in people with low back pain. However, no prospective studies exist to assert the cause and effect of this association. We hypothesized that athletes with a history of low back injury (LBI) would demonstrate poorer lumbar position sense (PS) than athletes without a history of LBI, and that this deficit would be a risk factor for future LBI.

Methods

This was a prospective cohort study with 2–3 year follow-up. Lumbar spine PS in the transverse plane was evaluated in 292 athletes using three tests: 1) passive and 2) active trunk repositioning, and 3) motion perception threshold. Mean absolute (accuracy) and variable (precision) errors were computed.

Results

There were no significant differences in the repositioning errors or motion perception threshold between athletes with and without a history of LBI or between those who did and did not get injured during the follow-up. Active trunk repositioning resulted in smaller errors than passive repositioning (1.6°± 0.8°) versus 2.1°± 1.0°) and 1.7°± 0.8°) versus 2.3°± 1.1°) for the absolute and relative errors, respectively).

Conclusion

Poor trunk PS in transverse plane is not associated with LBI in athletes, nor does it appear that poor trunk PS predisposes athletes to LBI.
Effectiveness of low-dose doxycycline (LDD) on clinical symptoms of Sjögren's Syndrome: a randomized, double-blind, placebo controlled cross-over study
Authors: Seitsalo Hubertus , Niemelä Raija K , Marinescu-Gava Magdalena , Vuotila Tuija , Tjäderhane Leo , Salo Tuula
Published: January 2008

Background

Matrix metalloproteinases (MMPs) are proteolytic enzymes that may contribute to tissue destruction in Sjögren's syndrome (SS). Low-dose doxycycline (LDD) inhibits MMPs. We evaluated the efficacy of LDD for the subjective symptoms in primary SS patients.

This was a randomized, double blind, placebo controlled cross-over study. 22 patients were randomly assigned to receive either 20 mg LDD or matching placebo twice a day for 10 weeks. The first medication period was followed by 10-week washout period, after which the patient received either LDD or placebo, depending on the first drug received, followed by the second washout period. Stimulated saliva flow rates and pH were measured before and after one and ten weeks of each medication and after washout periods. VAS scale was used to assess the effect of LDD and placebo on following six subjective symptoms: xerostomia; xerophtalmia; difficulty of swallowing; myalgia; arthralgia; and fatigue. The effect was evaluated for each medication and washout period separately.

Results

Overall, the effects of medications on subjective symptoms were minor. Wilcoxon test demonstrated increased fatigue with LDD during medication (p < 0.05). The differences may, however, reflect normal fluctuation of symptoms in SS patients.

Conclusion

LDD may not be useful in reducing the primary SS symptoms.
Biotin deficiency up-regulates TNF-α production in murine macrophages
Authors: Kuroishi Toshinobu , Endo Yasuo , Muramoto Koji , Sugawara Shunji
Published: January 2008

Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze an indispensable cellular metabolism. Although significant decreases in serum biotin levels have been reported in patients with chronic inflammatory diseases, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin deficiency on TNF-α production. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. Serum biotin levels were significantly lower in biotin-deficient mice than biotin-sufficient mice. After i.v. administration of LPS, serum TNF-α levels were significantly higher in biotin-deficient mice than biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in a biotin-sufficient or -deficient medium for 4 weeks. Cell proliferation and biotinylation of intracellular proteins were decreased significantly in biotin-deficient cells compared with biotin-sufficient cells. Significantly higher production and mRNA expression of TNF-α were detected in biotin-deficient J774.1 cells than biotin-sufficient cells in response to LPS and even without LPS stimulation. Intracellular TNF-α expression was inhibited by actinomycin D, indicating that biotin deficiency up-regulates TNF-α production at the transcriptional level. However, the expression levels of TNF receptors, CD14, and TLR4/myeloid differentiation protein 2 complex were similar between biotin-sufficient and -deficient cells. No differences were detected in the activities of the NF-κB family or AP-1. The TNF-α induction by biotin deficiency was down-regulated by biotin supplementation in vitro and in vivo. These results indicate that biotin deficiency may up-regulate TNF-α production or that biotin excess down-regulates TNF-α production, suggesting that biotin status may influence inflammatory diseases.
Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression
Authors: Larmonier Nicolas , Cantrell Jessica , LaCasse Collin , Li Gang , Janikashvili Nona , Situ Elaine , Sepassi Marjan , Andreansky Samita , Katsanis Emmanuel
Published: January 2008

CD4+CD25+ regulatory T lymphocytes (Tregs) critically contribute to the mechanisms of cancer-induced tolerance. These cells suppress anti-tumoral CD8+ and CD4+ T lymphocytes and can also restrain the function of APCs. We have previously documented the immunostimulatory effects of a chaperone-rich cell lysate (CRCL) anti-cancer vaccine. Tumor-derived CRCL induces tumor immunity in vivo, partly by promoting dendritic cell (DC) and macrophage activation. In the current study, we evaluated the effects of CD4+CD25+forkhead box P3+ Tregs isolated from mice bearing 12B1 bcr-abl+ leukemia on DC and macrophages that had been activated by 12B1-derived CRCL. CRCL-activated DC and macrophages resisted Treg suppression, as the production of proinflammatory cytokines, the activation of transcription factor NF-κB, and their immunostimulatory potential was unaffected by Tregs. Our results thus highlight CRCL as a powerful adjuvant endowed with the capacity to overcome tumor-induced Treg-inhibitory effects on APCs.
Gelatinases mediate neutrophil recruitment in vivo: evidence for stimulus specificity and a critical role in collagen IV remodeling
Authors: Reichel Christoph A , Rehberg Markus , Bihari Peter , Moser Christian M , Linder Stefan , Khandoga Andrej , Krombach Fritz
Published: January 2008

In the present study, the role of gelatinases [matrix metalloproteinase-2 and -9 (MMP-2 and -9)] for leukocyte rolling, adherence, and transmigration was analyzed in the mouse cremaster muscle under different inflammatory conditions including ischemia-reperfusion (I/R) and stimulation with MIP-1α or platelet-activating factor (PAF). Using zymography, we detected a significant elevation of MMP-9 activity in response to the stimuli applied, and MMP-2 expression was not altered. However, treatment with a specific MMP-2/-9 inhibitor significantly abrogated elevated MMP-9 activity. As observed by intravital microscopy, all inflammatory conditions induced a significant increase in numbers of adherent and transmigrated leukocytes (>80% Ly-6G+ neutrophils). Blockade of gelatinases significantly diminished I/R- and MIP-1α-induced leukocyte adherence and subsequent transmigration, and upon stimulation with PAF, gelatinase inhibition had no effect on leukocyte adherence but selectively reduced leukocyte transmigration. Concomitantly, we observed an increase in microvascular permeability after I/R and upon stimulation with MIP-1α or PAF, which was almost completely abolished in the inhibitor-treated groups. Using immunofluorescence staining and confocal microscopy, discontinuous expression of collagen IV, a major substrate of gelatinases within the perivascular basement membrane (BM), was detected in postcapillary venules. Analysis of intensity profiles demonstrated regions of low fluorescence intensity, whose size was enlarged significantly after I/R and upon stimulation with MIP-1α or PAF as compared with unstimulated controls. However, this enlargement was abolished significantly after inhibition of gelatinases, respectively. In conclusion, these data demonstrate that gelatinases strictly regulate microvascular permeability and BM remodeling during the early inflammatory response, whereas concomitant leukocyte recruitment is mediated by these proteases in a stimulus-specific manner.
Catch-Up Growth after Hypothyroidism Is Caused by Delayed Growth Plate Senescence
Authors: Marino Rose , Hegde Anita , Barnes Kevin M. , Schrier Lenneke , Emons Joyce A. , Nilsson Ola , Baron Jeffrey
Published: January 2008

Catch-up growth is defined as a linear growth rate greater than expected for age after a period of growth inhibition. We hypothesized that catch-up growth occurs because growth-inhibiting conditions conserve the limited proliferative capacity of growth plate chondrocytes, thus slowing the normal process of growth plate senescence. When the growth-inhibiting condition resolves, the growth plates are less senescent and therefore grow more rapidly than normal for age. To test this hypothesis, we administered propylthiouracil to newborn rats for 8 wk to induce hypothyroidism and then stopped the propylthiouracil to allow catch-up growth. In untreated controls, the growth plates underwent progressive, senescent changes in multiple functional and structural characteristics. We also identified genes that showed large changes in mRNA expression in growth plate and used these changes as molecular markers of senescence. In treated animals, after stopping propylthiouracil, these functional, structural, and molecular senescent changes were delayed, compared with controls. This delayed senescence included a delayed decline in longitudinal growth rate, resulting in catch-up growth. The findings demonstrate that growth inhibition due to hypothyroidism slows the developmental program of growth plate senescence, including the normal decline in the rate of longitudinal bone growth, thus accounting for catch-up growth.
Effect of Estrogen on the Expression of Luteinizing Hormone-Human Chorionic Gonadotropin Receptor Messenger Ribonucleic Acid in Cultured Rat Granulosa Cells
Authors: Ikeda Sadatomo , Nakamura Kazuto , Kogure Kayoko , Omori Yuki , Yamashita Soichi , Kubota Kazuko , Mizutani Tetsuya , Miyamoto Kaoru , Minegishi Takashi
Published: January 2008

Estrogen has been considered to enhance FSH actions in the ovary, including the induction of the LH receptor (LHR). In this study, we elucidated the mechanism underlying the effect of estrogen on the induction of LHR by FSH in rat granulosa cells. Estradiol clearly enhanced the FSH-induced LHR mRNA increase in a time- and dose-dependent manner, with a maximum increase of approximately 3.5-fold at 72 h, compared with the level of LHR mRNA solely induced by FSH. We then investigated whether the effect of estrogen on LHR mRNA was due to increased transcription and/or altered mRNA stability. A luciferase assay with the plasmid containing the LHR 5′-flanking region did not show that estradiol increased the promoter activity induced by FSH. In contrast, the decay curves for LHR mRNA showed a significant increase in half-life with FSH and estradiol, suggesting that the increased stability of LHR mRNA is at least responsible for the regulation of LHR mRNA by estrogen. Recently mevalonate kinase (Mvk) was identified as a trans-factor that binds to LHR mRNA and alters LHR mRNA stability in the ovary. We found that estradiol, with FSH, decreased Mvk mRNA levels in rat granulosa cell culture, resulting in up-regulation of LHR mRNA that was inversely correlated to Mvk mRNA expression. Furthermore, the augmentation of FSH-induced LHR expression in the presence of estrogen was erased with the overexpression of Mvk by transient transfection. Taken together, these data indicate that LHR mRNA is up-regulated due to increased stability when estrogen negatively controls Mvk.
The Ca2+-Binding Capacity of Epidermal Furin Is Disrupted by H2O2-Mediated Oxidation in Vitiligo
Authors: Spencer J. D. , Gibbons N. C. J. , Böhm M. , Schallreuter K. U.
Published: January 2008

The Ca2+-dependent precursor convertase furin is abundantly expressed in epidermal keratinocytes and melanocytes. In this context, it is noteworthy that proopiomelanocortin (POMC) cleavage is also processed by furin, leading to ACTH, β-lipotropin, and β-endorphin. All prohormone convertases including furin are regulated by Ca2+. Because numerous epidermal peptides and enzymes are affected by H2O2-mediated oxidation, including the POMC-derived peptides α-MSH and β-endorphin as shown in the epidermis of patients with vitiligo, we here asked the question of whether furin could also be a possible target for this oxidation mechanism by using immunofluorescence, RT-PCR, Western blotting, Ca2+-binding studies, and computer modeling. Our results demonstrate significantly decreased in situ immunoreactivity of furin in the epidermis of patients with progressive vitiligo (n = 10), suggesting H2O2-mediated oxidation. This was confirmed by 45Ca2+-binding studies with human recombinant furin identifying the loss of one Ca2+-binding site from the enzyme after oxidation with H2O2. Computer simulation supported alteration of one of the two Ca2+-binding sites on furin. Taken together, our results implicate that the Ca2+-dependent proteolytic activity of this convertase is targeted by H2O2, which in turn could contribute to the reduced epidermal expression of the POMC-derived peptides α-MSH and β-endorphin as documented earlier in patients with vitiligo.