bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation
Authors: Morrissey James H. , Choi Sharon H. , Smith Stephanie A.
Published: April 2012

Inorganic polyphosphate is widespread in biology and exhibits striking prohemostatic, prothrombotic, and proinflammatory effects in vivo. Long-chain polyphosphate (of the size present in infectious microorganisms) is a potent, natural pathophysiologic activator of the contact pathway of blood clotting. Medium-chain polyphosphate (of the size secreted from activated human platelets) accelerates factor V activation, completely abrogates the anticoagulant function of tissue factor pathway inhibitor, enhances fibrin clot structure, and greatly accelerates factor XI activation by thrombin. Polyphosphate may have utility as a hemostatic agent, whereas antagonists of polyphosphate may function as novel antithrombotic/anti-inflammatory agents. The detailed molecular mechanisms by which polyphosphate modulates blood clotting reactions remain to be elucidated.
Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis
Authors: Zarychanski Ryan , Schulz Vincent P. , Houston Brett L. , Maksimova Yelena , Houston Donald S. , Smith Brian , Rinehart Jesse , Gallagher Patrick G.
Published: April 2012

Hereditary xerocytosis (HX, MIM 194380) is an autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. Copy number analyses, linkage studies, and exome sequencing were used to identify novel mutations affecting PIEZO1, encoded by the FAM38A gene, in 2 multigenerational HX kindreds. Segregation analyses confirmed transmission of the PIEZO1 mutations and cosegregation with the disease phenotype in all affected persons in both kindreds. All patients were heterozygous for FAM38A mutations, except for 3 patients predicted to be homozygous by clinical and physiologic studies who were also homozygous at the DNA level. The FAM38A mutations were both in residues highly conserved across species and within members of the Piezo family of proteins. PIEZO proteins are the recently identified pore-forming subunits of channels that mediate mechanotransduction in mammalian cells. FAM38A transcripts were identified in human erythroid cell mRNA, and discovery proteomics identified PIEZO1 peptides in human erythrocyte membranes. These findings, the first report of mutation in a mammalian mechanosensory transduction channel-associated with genetic disease, suggest that PIEZO proteins play an important role in maintaining erythrocyte volume homeostasis.
Statistical properties of interval mapping methods on quantitative trait loci location: impact on QTL/eQTL analyses
Authors: Wang Xiaoqiang , Gilbert Hélène , Moreno Carole , Filangi Olivier , Elsen Jean-Michel , Le Roy Pascale
Published: April 2012

Background

Quantitative trait loci (QTL) detection on a huge amount of phenotypes, like eQTL detection on transcriptomic data, can be dramatically impaired by the statistical properties of interval mapping methods. One of these major outcomes is the high number of QTL detected at marker locations. The present study aims at identifying and specifying the sources of this bias, in particular in the case of analysis of data issued from outbred populations. Analytical developments were carried out in a backcross situation in order to specify the bias and to propose an algorithm to control it. The outbred population context was studied through simulated data sets in a wide range of situations.

The likelihood ratio test was firstly analyzed under the "one QTL" hypothesis in a backcross population. Designs of sib families were then simulated and analyzed using the QTL Map software. On the basis of the theoretical results in backcross, parameters such as the population size, the density of the genetic map, the QTL effect and the true location of the QTL, were taken into account under the "no QTL" and the "one QTL" hypotheses. A combination of two non parametric tests - the Kolmogorov-Smirnov test and the Mann-Whitney-Wilcoxon test - was used in order to identify the parameters that affected the bias and to specify how much they influenced the estimation of QTL location.

Results

A theoretical expression of the bias of the estimated QTL location was obtained for a backcross type population. We demonstrated a common source of bias under the "no QTL" and the "one QTL" hypotheses and qualified the possible influence of several parameters. Simulation studies confirmed that the bias exists in outbred populations under both the hypotheses of "no QTL" and "one QTL" on a linkage group. The QTL location was systematically closer to marker locations than expected, particularly in the case of low QTL effect, small population size or low density of markers, i.e. designs with low power. Practical recommendations for experimental designs for QTL detection in outbred populations are given on the basis of this bias quantification. Furthermore, an original algorithm is proposed to adjust the location of a QTL, obtained with interval mapping, which co located with a marker.

Conclusions

Therefore, one should be attentive when one QTL is mapped at the location of one marker, especially under low power conditions.
Aestivation and hypoxia-related events share common silent neuron trafficking processes
Authors: Giusi Giuseppina , Zizza Merylin , Facciolo Rosa Maria , Chew Shit Fun , Ip Yuen Kwong , Canonaco Marcello
Published: April 2012

Background

The availability of oxygen is a limiting factor for neuronal survival since low levels account not only for the impairment of physiological activities such as sleep-wake cycle, but above all for ischemic-like neurodegenerative disorders. In an attempt to improve our knowledge concerning the type of molecular mechanisms operating during stressful states like those of hypoxic conditions, attention was focused on eventual transcriptional alterations of some key AMPAergic silent neuronal receptor subtypes (GluR1 and GluR2) along with HSPs and HIF-1α during either a normoxic or a hypoxic aestivation of a typical aquatic aestivator, i.e. the lungfish (Protopterus annectens).

Results

The identification of partial nucleotide fragments codifying for both AMPA receptor subtypes inProtopterus annectensdisplayed a putative high degree of similarity to that of not only fish but also to those of amphibians, birds and mammals. qPCR andin situhybridization supplied a very high (p < 0.001) reduction of GluR1 mRNA expression in diencephalic areas after 6 months of aerial normoxic aestivation (6mAE). Concomitantly, high (p < 0.01) levels of HSP70 mRNAs in hypothalamic, mesencephalic and cerebellar areas of both 6mAE and after 6 months of mud hypoxic aestivation (6mMUD) were detected together with evident apoptotic signals. Surprisingly, very high levels of GluR2 mRNAs were instead detected in thalamic along with mesencephalic areas after 6 days of normoxic (6dAE) and hypoxic (6dMUD) aestivation. Moreover, even short- and long-term hypoxic states featured high levels of HIF-1α and HSP27 transcripts in the different brain regions of the lungfish.

Conclusions

The distinct transcriptional variations of silent neurons expressing GluR1/2 and HSPs tend to corroborate these factors as determining elements for the physiological success of normoxic and hypoxic aestivation. A distinct switching among these AMPA receptor subtypes during aestivation highlights new potential adaptive strategies operating in key brain regions of the lungfish in relation to oxygen availability. This functional relationship might have therapeutic bearings for hypoxia-related dysfunctions, above all in view of recently identified silent neuron-dependent motor activity ameliorations in mammals.
Gastric cancer cell supernatant causes apoptosis and fibrosis in the peritoneal tissues and results in an environment favorable to peritoneal metastases, in vitro and in vivo
Authors: Na Di , Lv Zhi-Dong , Liu Fu-Nan , Xu Yan , Jiang Cheng-Gang , Sun Zhe , Miao Zhi-Feng , Li Feng , Xu Hui-Mian
Published: April 2012

Background

In this study, we examined effects of soluble factors released by gastric cancer cells on peritoneal mesothelial cells in vitro and in vivo.

Methods

HMrSV5, a human peritoneal mesothelial cell line, was incubated with supernatants from gastric cancer cells. Morphological changes of HMrSV5 cells were observed. Apoptosis of HMrSV5 cells was observed under a transmission electron microscope and quantitatively determined by MTT assay and flow cytometry. Expressions of apoptosis-related proteins (caspase-3, caspase-8, Bax, bcl-2) were immunochemically evaluated.

Results

Conspicuous morphological changes indicating apoptosis were observed in HMrSV5 cells 24 h after treatment with the supernatants of gastric cancer cells. In vivo, peritoneal tissues treated with gastric cancer cell supernatant were substantially thickened and contained extensive fibrosis.

Conclusions

These findings demonstrate that supernatants of gastric cancer cells can induce apoptosis and fibrosis in HMrSV5 human peritoneal mesothelial cells through supernatants in the early peritoneal metastasis, in a time-dependent manner, and indicate that soluble factors in the peritoneal cavity affect the morphology and function of mesothelial cells so that the resulting environment can become favorable to peritoneal metastases.
Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice
Authors: Zheng Liu , Weilun Zhang , Minghong Jiang , Yaxi Zhang , Shilian Liu , Yanxin Liu , Dexian Zheng
Published: April 2012

Background

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy.

Methods

Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity.

Results

The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline.

Conclusion

These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.
Reduced lung function is independently associated with increased risk of type 2 diabetes in Korean men
Authors: Kwon Chang-Hee , Rhee Eun-Jung , Song Jae-Uk , Kim Jung-Tae , Kwag Hyon Joo , Sung Ki-Chul
Published: April 2012

Background

Reduced lung function is associated with incident insulin resistance and diabetes. The aim of this study was to assess the relationship between lung function and incident type 2 diabetes in Korean men.

Methods

This study included 9,220 men (mean age: 41.4 years) without type 2 diabetes at baseline who were followed for five years. Subjects were divided into four groups according to baseline forced vital capacity (FVC) (% predicted) and forced expiratory volume in one second (FEV1) (% predicted) quartiles. The incidence of type 2 diabetes at follow-up was compared according to FVC and FEV1 quartiles.

Results

The overall incidence of type 2 diabetes was 2.2%. Reduced lung function was significantly associated with the incidence of type 2 diabetes after adjusting for age, BMI, education, smoking, exercise, alcohol, and HOMA-IR. Both FVC and FEV1 were negatively associated with type 2 diabetes (P < 0.05). In non-obese subjects with BMI < 25, the lowest quartile of FVC and FEV1 had a significantly higher odds ratio for type 2 diabetes compared with the highest quartile after adjusting for age and BMI (2.15 [95% CI 1.02-4.57] and 2.19 [95% CI 1.09-4.42]).

Conclusions

Reduced lung function is independently associated with the incidence of type 2 diabetes in Korean men.
Proteomic profiling of the rat hypothalamus
Authors: Pedroso Amanda P , Watanabe Regina L H , Albuquerque Kelse T , Telles Mônica M , Andrade Maria C C , Perez Juliana D , Sakata Maísa M , Lima Mariana L , Estadella Debora , Nascimento Cláudia M O , Oyama Lila M , Rosa José C , Casarini Dulce E , Ribeiro Eliane B
Published: April 2012

Background

The hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE) profile of rat hypothalamus proteins.

Results

As a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D) gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development.

Conclusion

The present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis.
Treatment of adult MPSI mouse brains with IDUA-expressing mesenchymal stem cells decreases GAG deposition and improves exploratory behavior
Authors: da Silva Flávia Helena , Pereira Vanessa Gonçalves , Yasumura Eduardo G , Tenório Lígia Zacchi , de Carvalho Leonardo Pinto , Lisboa Bianca Cristina Garcia , Matsumoto Priscila Keiko , Stilhano Roberta Sessa , Samoto Vivian Y , Calegare Bruno Frederico Aguilar , Brandão Letícia de Campos , D’Almeida Vânia , Filippo Thaís RM , Porcionatto Marimélia , Toma Leny , Nader Helena Bonciani , Valero Valderez Bastos , Camassola Melissa , Nardi Nance Beyer , Han Sang Won
Published: April 2012

Background

Mucopolysaccharidosis type I (MPSI) is caused by a deficiency in alpha-L iduronidase (IDUA), which leads to lysosomal accumulation of the glycosaminoglycans (GAGs) dermatan and heparan sulfate. While the currently available therapies have good systemic effects, they only minimally affect the neurodegenerative process. Based on the neuroprotective and tissue regenerative properties of mesenchymal stem cells (MSCs), we hypothesized that the administration of MSCs transduced with a murine leukemia virus (MLV) vector expressing IDUA to IDUA KO mouse brains could reduce GAG deposition in the brain and, as a result, improve neurofunctionality, as measured by exploratory activity.

Methods

MSCs infected with an MLV vector encoding IDUA were injected into the left ventricle of the brain of 12- or 25-month-old IDUA KO mice. The behavior of the treated mice in the elevated plus maze and open field tests was observed for 1 to 2 months. Following these observations, the brains were removed for biochemical and histological analyses.

Results

After 1 or 2 months of observation, the presence of the transgene in the brain tissue of almost all of the treated mice was confirmed using PCR, and a significant reduction in GAG deposition was observed. This reduction was directly reflected in an improvement in exploratory activity in the open field and the elevated plus maze tests. Despite these behavioral improvements and the reduction in GAG deposition, IDUA activity was undetectable in these samples. Overall, these results indicate that while the initial level of IDUA was not sustainable for a month, it was enough to reduce and maintain low GAG deposition and improve the exploratory activity for months.

Conclusions

These data show that gene therapy, via the direct injection of IDUA-expressing MSCs into the brain, is an effective way to treat neurodegeneration in MPSI mice.
Molecular xenomonitoring of Dirofilaria immitis and Dirofilaria repens in mosquitoes from north-eastern Italy by real-time PCR coupled with melting curve analysis
Authors: Latrofa Maria Stefania , Montarsi Fabrizio , Ciocchetta Silvia , Annoscia Giada , Dantas-Torres Filipe , Ravagnan Silvia , Capelli Gioia , Otranto Domenico
Published: April 2012

Background

Dirofilaria immitis and Dirofilaria repens are transmitted by bloodsucking culicid mosquitoes belonging to Culex, Aedes, Ochlerotatus, Anopheles and Mansonia genera.

The detection of filarioids in mosquitoes for assessing distribution of vectors and/or of pathogens in a given area (also known as “xenomonitoring”), when based on individual dissection of wild-caught female mosquitoes is time consuming and hardly applicable in large epidemiological surveys.

Our study aimed to evaluate the recently developed duplex real-time PCR for screening large number of culicids and to assess their positivity for D. immitis and D. repens in an area where both species are endemic.

Methods

A duplex real-time PCR was used to detect and differentiate D. immitis and D. repens in mosquitoes collected in six provinces of the Veneto region using 43 carbon dioxide-baited traps under the frame of an entomological surveillance program to monitor the vectors of West Nile disease. From early May till October 2010, unfed female mosquitoes (n = 40,892) were captured in 20 selected sites.

Results

Mosquitoes identified as Culex pipiens, Ochlerotatus caspius, Aedes vexans and Culex modestus were grouped into 995 pools according to species, day and site of collection (from minimum of 1 to maximum of 57). Out of 955 pools, 23 (2.41 %) scored positive for Dirofilaria spp. of which, 21 (2.2 %) for D. immitis and two (0.21 %) for D. repens. An overall Estimated Rate of Infection (ERI) of 0.06 % was recorded, being higher in Och. caspius and Ae. vexans (i.e., 0.18 % and 0.14 %, respectively). At least one mosquito pool was positive for Dirofilaria spp. in each province with the highest ERI recorded in Vicenza and Padova provinces (i.e., 0.42% and 0.16 %, respectively). Mosquitoes collected in all provinces were positive for D. immitis whereas, only two (i.e., Padova and Rovigo) provinces scored positive for D. repens. All mosquito species, except for Cx. modestus, were positive for D. immitis, whereas D. repens was only found in Cx. pipiens.

Conclusions

The results suggest that both Dirofilaria species are endemic and may occur in sympatry in the examined area. The molecular approach herein used represents a powerful tool for surveillance programs of D. immitis and D. repens in the culicid vectors towards a better understanding of the epidemiology of the infections they cause and their seasonal transmission patterns.
Using angiogenic factors and their soluble receptors to predict organ dysfunction in patients with disseminated intravascular coagulation associated with severe trauma
Authors: Wada Takeshi , Jesmin Subrina , Gando Satoshi , Sultana Sayeeda N , Zaedi Sohel , Yokota Hiroyuki
Published: April 2012

Introduction

Disseminated intravascular coagulation (DIC) is characterized by the concomitant activation of coagulofibrinolytic disorders and systemic inflammation associated with endothelial dysfunction-induced microvascular permeability. Angiogenic factors, including vascular endothelial growth factor (VEGF), angiopoietin (Ang), and their receptors, play crucial roles in angiogenesis and microvascular permeability. The aim of the study was to assess the relationship between angiogenic factors, their soluble receptors and organ dysfunction associated with DIC after severe trauma.

Materials and methods

A total of 57 patients with severe trauma were divided into two subgroups; 30 DIC patients and 27 non-DIC patients. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC and the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. The serum levels of angiogenic factors were measured at the time of admission (Day 1), Day 3 and Day 5. This study compared levels of these angiogenic factors between the two DIC groups, and evaluated their predictive value for organ dysfunction.

Results

DIC patients, especially those with ISTH DIC, showed higher Sequential Organ Failure Assessment (SOFA) scores and lactate levels. There were lower levels of VEGF, Ang1 and the soluble Tie2 in the ISTH DIC patients than the non-DIC patients. The levels of soluble VEGF receptor-1 (sVEGFR1), Ang2 and the Ang2/Ang1 ratio in the ISTH DIC patients were higher than in non-DIC patients. The relationship between the presence of massive transfusion and angiogenic factors indicated the same results. The levels of sVEGFR1, Ang2 and the Ang2/Ang1 ratio correlated with the SOFA scores. In particular, sVEGFR1 and Ang2 were independent predictors of an increase in the SOFA score. The lactate levels independently predicted increases in the levels of sVEGFR1 and Ang2. The decrease in the platelet counts also independently predicted the increase in Ang2 levels in DIC patients.

Conclusions

Angiogenic factors and their soluble receptors, particularly sVEGFR1 and Ang2, are considered to play pivotal roles in the development of organ dysfunction in DIC associated with severe trauma. DIC-induced tissue hypoxia and platelet consumption may play crucial roles in inducing sVEGFR1 and Ang2, and in determining the prognosis of the severity of organ dysfunction.
Integration of hydraulically induced microseismic event locations with active seismic attributes: A North Texas Barnett Shale case study
Authors: Refunjol Xavier E. , Keranen Katie M. , Le Calvez Joël H. , Marfurt Kurt J.
Published: April 2012

Hydraulic fractures are delineated by induced microseismic event distributions and typically propagate perpendicular to the regional minimum stress direction. However, at a smaller scale, varying mineralogical composition and existing fault and fracture networks can influence developing fracture networks. We integrated microseismic event locations with seismic attributes from multichannel seismic reflection data, including inversion results for impedance and Lamé parameters, and seismic curvature attributes. We found that microseismic event locations consistently correlate to zones of low seismic impedance and low [Formula: see text] and [Formula: see text] values, describing characteristic material properties of fracture-prone zones within the North Texas Lower and Upper Barnett Shale. Additionally, event locations showed a weak correlation with anticlinal structures as defined by volumetric curvature attributes. We suggest that the low impedance, low [Formula: see text] and [Formula: see text] zones were related to the boundary between calcite-filled fractures and the host rock.
Rapid 1D/3D inversion of shallow resistivity multipole data: Examples in archaeological prospection
Authors: Brinon Claire , Simon François-Xavier , Tabbagh Alain
Published: April 2012

Fifteen years ago, the introduction of mobile multipole arrays led to substantial improvements in shallow electric prospection because it allowed information related to the vertical distribution of ground resistivity, in complement to the horizontal pattern of the detected features, to be extracted. However, to make full use of this wealth of information, further progress is needed to extend the qualitative interpretation of data to a more quantitative evaluation of the explored terrain. To that intent, we developed a two-step process: In the first step, a 1D electric model is fitted to the data over the full explored area, and in the second step, using the moment method, localized 3D interpretation is applied to limited areas, for which the characteristics of a given feature require closer scrutiny. After a first test with synthetic data generated using the surface integral 3D modeling method, this process was applied to three different archaeological sites and one test site, for both handheld pole-pole array systems and a multipole continuous electric profiling mechanically pulled system. At the test site, the characteristics of a known wall were accurately recovered. At the Duntzenheim site, the thickness and width of the archaeological remains determined by 3D interpretation corresponded to the features observed through excavation. At the other two sites, 3D interpretation made it possible to establish that the conductive features extend across the full extent of the superficial resistive second layers.
Impact of a Bladder Cancer Diagnosis on Smoking Behavior
Authors: Bassett Jeffrey C. , Gore John L. , Chi Amanda C. , Kwan Lorna , McCarthy William , Chamie Karim , Saigal Christopher S.
Published: April 2012

Purpose

Bladder cancer is the second most common tobacco-related malignancy. A new bladder cancer diagnosis may be an opportunity to imprint smoking cessation. Little is known about the impact of a diagnosis of bladder cancer on patterns of tobacco use and smoking cessation among patients with incident bladder cancer.

Patients and Methods

A simple random sample of noninvasive bladder cancer survivors diagnosed in 2006 was obtained from the California Cancer Registry. Respondents completed a survey on history of tobacco use, beliefs regarding bladder cancer risk factors, and physician influence on tobacco cessation. Respondents were compared by smoking status. Those respondents smoking at diagnosis were compared with general population controls obtained from the California Tobacco Survey to determine the impact of a diagnosis of bladder cancer on patterns of tobacco use.

Results

The response rate was 70% (344 of 492 eligible participants). Most respondents (74%) had a history of cigarette use. Seventeen percent of all respondents were smoking at diagnosis. Smokers with a new diagnosis of bladder cancer were almost five times as likely to quit smoking as smokers in the general population (48% v 10%, respectively; P < .001). The bladder cancer diagnosis and the advice of the urologist were the reasons cited most often for cessation. Respondents were more likely to endorse smoking as a risk factor for bladder cancer when the urologist was the source of their understanding.

Conclusion

The diagnosis of bladder cancer is an opportunity for smoking cessation. Urologists can play an integral role in affecting the patterns of tobacco use of those newly diagnosed.
Both asymmetric mitotic segregation and cell-to-cell invasion are required for stable germline transmission of Wolbachia in filarial nematodes
Authors: Landmann Frédéric , Bain Odile , Martin Coralie , Uni Shigehiko , Taylor Mark J. , Sullivan William
Published: April 2012

Parasitic filarial nematodes that belong to the Onchocercidae family live in mutualism with Wolbachia endosymbionts. We developed whole-mount techniques to follow the segregation patterns of Wolbachia through the somatic and germline lineages of four filarial species. These studies reveal multiple evolutionarily conserved mechanisms that are required for Wolbachia localization to the germline. During the initial embryonic divisions, Wolbachia segregate asymmetrically such that they concentrate in the posteriorly localized P2 blastomere, a precursor to the adult germline and hypodermal lineages. Surprisingly, in the next division they are excluded from the germline precursor lineage. Rather, they preferentially segregate to the C blastomere, a source of posterior hypodermal cells. Localization to the germline is accomplished by a distinct mechanism in which Wolbachia invade first the somatic gonadal cells close to the ovarian distal tip cell, the nematode stem cell niche, from the hypodermis. This tropism is associated with a cortical F-actin disruption, suggesting an active engulfment. Significantly, germline invasion occurs only in females, explaining the lack of Wolbachia in the male germline. Once in the syncytial environment of the ovaries, Wolbachia rely on the rachis to multiply and disperse into the germ cells. The utilization of cell-to-cell invasion for germline colonization may indicate an ancestral mode of horizontal transfer that preceded the acquisition of the mutualism.
Comparative efficacy and safety of intravenous ferric carboxymaltose (Ferinject) and iron(III) hydroxide dextran (Cosmofer) in pregnancy
Authors: Myers B , Myers O , Moore J
Published: April 2012

Background

Iron-deficiency anaemia is common in pregnancy, with well-described maternal morbidities. When oral iron therapy has failed, intravenous (IV) preparations are considered. Ferric carboxymaltose (ferinject) is a new IV preparation which can be given quickly. There are no published data on Ferinject use in pregnancy. This study analyses historical data from women given Cosmofer, compared with those given Ferinject in pregnancy, to assess comparative efficacy and safety.

Methods

Pregnant women treated with Cosmofer and Ferinject, were identified from pharmacy records. Records for all cases were reviewed and those which fulfilled inclusion criteria selected. The inclusion criteria included: symptomatic iron-deficient anaemia unresponsive to oral iron; age ≥18; second to third trimester; full blood count taken at least once at two, four and/or six weeks post-infusion. Data were collected on the pre-treatment Hb, ferritin, and same data collected at two, four and six weeks after the infusion. Side-effects or adverse reactions were noted for both the Cosmofer and Ferinject patients.

Results

Results were obtained for 92 women (44 received Ferinject and 48 Cosmofer). Pre-infusion Hb and ferritin levels were comparable in the two groups. At two weeks, the mean Hb rise in the Ferinject group was 1.73 g/dL and 1.34 g/dL in the Cosmofer group. At four weeks, the total rise in Hb was 2.57 g/dL Ferinject, 2.34 g/dL Cosmofer. At six weeks the rise was 3.01 g/dL and 3.2 g/dL respectively. No serious adverse events were reported in either group.

Conclusion

Both preparations appear effective and safe, with low risk of serious adverse effects and side-effects.
Hyperglycosylated Human Chorionic Gonadotropin in Serum of Testicular Cancer Patients
Authors: Lempiäinen Anna , Hotakainen Kristina , Blomqvist Carl , Alfthan Henrik , Stenman Ulf-Håkan
Published: April 2012

BACKGROUND

Hyperglycosylated human chorionic gonadotropin (hCG-h) contains larger and more complex carbohydrate chains than regular human chorionic gonadotropin (hCG). hCG-h is thought to be the major form of hCG produced by testicular cancers and it has been suggested to play a key role in tumor invasion, but studies on hCG-h in testicular cancer are limited. We studied whether serum hCG is hyperglycosylated, and whether measurement of hCG-h in serum offers clinical value in the management of testicular cancer.

METHODS

We determined the serum concentrations of hCG-h, hCG, and the free β subunit of hCG (hCGβ) by time-resolved immunofluorometric assays in 176 serum samples (preoperative n = 67, relapse n = 20, follow-up n = 89) obtained from 84 testicular cancer patients. We analyzed the association between preoperative serum concentrations of hCG, hCG-h, and hCGβ with known prognostic factors and progression-free survival time.

RESULTS

A major proportion of hCG was hyperglycosylated preoperatively, at relapse, and shortly after treatment. The serum concentrations of hCG-h and hCG correlated strongly with each other and had similar diagnostic value. The preoperative serum concentration of hCG-h correlated with prognostic factors and outcome in the same way as hCG. Increased preoperative hCGβ concentration predicted shorter progression-free survival.

CONCLUSIONS

Most of the hCG expressed by testicular cancers is hyperglycosylated and therefore it is important that hCG assays used for management of testicular cancer recognize hCG-h.
The Option Value of Innovation
Authors: Thornton Snider Julia , Romley John A. , Vogt William B. , Philipson Tomas J.
Published: April 2012

Standard techniques of cost effectiveness analysis measure a technology’s benefits in terms of expected life years (or quality-adjusted life years) gained at today’s life expectancies. However, this approach ignores the gains which derive from the possibility that a health technology allows an individual to survive long enough to benefit from other technological innovations which raise life expectancy (and quality of life) in the future. Borrowing a term from the finance literature, we refer to this source of value as the “option value” of innovation. We explain where this value comes from and how to calculate it in a variety of standard cost effectiveness analysis contexts. We provide a proof-of-concept using the example of the drug tamoxifen, which delayed the onset of breast cancer for some patients until more effective adjuvant treatment was available. We find that incorporating option value can increase the conventionally estimated value of tamoxifen with better adjuvant treatment by nearly a quarter (from $200,000 to $248,000 for those who initiated tamoxifen in 1999). We expect similar results for other drugs in therapeutic areas of rapid technological advancement.
Tax Morale and Compliance Behavior: First Evidence on a Causal Link
Authors: Halla Martin
Published: April 2012

Recent literature on tax evasion emphasizes the importance of moral considerations to explain compliance behavior. As a consequence scholars aim to identify factors that shape this so-called tax morale. However, the causal link between tax morale and actual compliance behavior is not established yet. Exploiting exogenous variation in tax morale – given by the inherited part of tax morale of American-born from their ancestors country of origin – our Two-Stage Least Square Estimation provides first evidence on a causal effect of tax morale on the size of the underground production.
The Virtual Genetics Lab II: Improvements to a Freely Available Software Simulation of Genetics
Authors: White Brian T.
Published: April 2012

The Virtual Genetics Lab II (VGLII) is an improved version of the highly successful genetics simulation software, the Virtual Genetics Lab (VGL). The software allows students to use the techniques of genetic analysis to design crosses and interpret data to solve realistic genetics problems involving a hypothetical diploid insect. This is a brief outline of the program and its new features; details are available at http://intro.bio.umb.edu/vgl/.
Qualitative Brain MRI at Term and Cognitive Outcomes at 9 Years After Very Preterm Birth
Authors: Iwata Sachiko , Nakamura Tomohiko , Hizume Eriko , Kihara Hideki , Takashima Sachio , Matsuishi Toyojiro , Iwata Osuke
Published: April 2012

OBJECTIVE:

A prospective study was performed to assess the relationship between the appearance of cerebral MRI at term and the cognitive functioning at 9 years old in very preterm born infants.

METHODS:

Seventy-six very preterm born infants (birth weight <1500 g or gestational age ≤32 weeks) obtained cerebral MRI at term-equivalent period, which was assessed by using established composite scores for the white and gray matter; cognitive outcomes at 9 years old were assessed in 60 subjects by using Wechsler Intelligence Scale for Children, Third Edition.

RESULTS:

Mildly low scores on the different IQ indices (<85) were observed in 23.3% (verbal IQ), 41.7% (performance IQ), and 30.0% (full-scale IQ) of the cohort, whereas moderately low scores (<70) were noted in 3.3% (verbal IQ), 11.7% (performance IQ), and 11.7% (full-scale IQ); cerebral palsy was diagnosed in 10.0%, whereas special assistance at school was required in 56.7%. Abnormal white matter appearances predicted mildly low verbal, performance, and full-scale IQs; moderately low performance and full-scale IQs; cerebral palsy; and the requirement for special assistance at school. Abnormal white matter appearances predicted mild cognitive impairment even after the adjustment for known clinical risk factors. In contrast, abnormal gray matter appearances did not predict any of the outcome measures.

CONCLUSIONS:

In a cohort of very preterm born infants, abnormal white matter appearance on term MRI showed consistent associations with cognitive impairments at 9 years old, further supporting the benefit of obtaining term MRI for very preterm born infants.
Decreasing Prevalence of Obesity Among Young Children in Massachusetts From 2004 to 2008
Authors: Wen Xiaozhong , Gillman Matthew W. , Rifas-Shiman Sheryl L. , Sherry Bettylou , Kleinman Ken , Taveras Elsie M.
Published: April 2012

OBJECTIVE:

To examine whether the obesity prevalence is increasing, level, or decreasing among young US children (aged <6 years) in the past decade; and to compare regional data to those of 2 national databases.

METHODS:

We analyzed data from 108 762 well-child visits (36 827 children) at a multisite pediatric practice in eastern Massachusetts during 1999–2008. By using the Centers for Disease Control and Prevention 2000 gender-specific growth charts, we defined obesity as weight-for-length ≥95th percentile for children aged <24 months and BMI ≥95th percentile for children aged 24 to <72 months. By using multivariable logistic regression, we estimated gender-specific obesity trends in 2 separate periods, 1999–2003 and 2004–2008, adjusting for age group, race/ethnicity, health insurance, and practice site.

RESULTS:

From 1999 to 2003, the obesity prevalence was fairly stable among both boys and girls. From 2004 to 2008, the obesity prevalence substantially decreased among both boys and girls. The decline in obesity prevalence during 2004–2008 was more pronounced among children insured by non-Medicaid health plans than among those insured by Medicaid.

CONCLUSIONS:

Among children aged <6 years at this multisite pediatric practice, obesity prevalence decreased during 2004–2008, which is in line with national data showing no increase in prevalence during this time period. The smaller decrease among Medicaid-insured children may portend widening of socioeconomic disparities in childhood obesity.
Parametric Analysis of Cemented Ultrahigh Molecular Weight Polyethylene (UHMWPE) Total Hip Acetabular Cups in a Quasi-Static Loading Model
Authors: Mittlmeier Thomas , Plitza W. , Schmotzer H.
Published: April 2012

Owing to the interest in ever increasing lifetimes for total hip prostheses, possible failure due to aseptic loosening of the acetabular component is an issue that may require increased attention. Mechanical factors, especially the deformation behavior of the material and the stress distribution at the implant-cement and the bone-cement interfaces, presumably play an essential role in total hip failure. Therefore the experimental model of the present work makes use of rosette strain gauge techniques to evaluate the deformation behavior of cemented polyethylene cups under quasi-static loading. Standard tests in UHMWPE beam specimens confirmed that the present method is a reliable tool for strain measurements in the polymer that was tested. On the other hand, the apparent elastic modulus of UHMWPE can be shown to be markedly dependent on the testing method, the geometry, and, owing to the visco-elastic properties, dependent on the strain rate. Thus in the present work a correlation between the measured strain and the ultimate strength was not attempted. Instead a parametric analysis quantifying the influence of the cup thickness and the cement distribution on the strain pattern was performed.
Cascading effect of economic globalization on human risks of scrub typhus and tick‐borne rickettsial diseases
Authors: Kuo Chi-Chien , Huang Jing-Lun , Shu Pei-Yun , Lee Pei-Lung , Kelt Douglas A. , Wang Hsi-Chieh
Published: April 2012

The increase in global travel and trade has facilitated the dissemination of disease vectors. Globalization can also indirectly affect vector‐borne diseases through the liberalization of cross‐border trade, which has far‐reaching, worldwide effects on agricultural practices and may in turn influence vectors through the modification of the ecological landscape. While the cascading effect of economic globalization on vector‐borne diseases, sometimes acting synergistically with regional agricultural policy, could be substantial and have significant economic, agricultural, and public health implications, research into this remains very limited. We evaluated how abandonment of rice paddies in Taiwan after joining the World Trade Organization, along with periodic plowing, an agricultural policy to reduce farm pests in abandoned fields can unexpectedly influence risks to diseases transmitted by ticks and chiggers (larval trombiculid mites), which we collected from their small‐mammal hosts. Sampling was limited to abandoned (fallow) and plowed fields due to the challenge of trapping small mammals in flooded rice paddies. Striped field mice (Apodemus agrarius) are the main hosts for both vectors. They harbored six times more ticks and three times more chiggers in fallow than in plowed plots. The proportion of ticks infected with Rickettsia spp. (etiologic agent of spotted fever) was three times higher in fallow plots, while that of Orientia tsutsugamushi (scrub typhus) in chiggers was similar in both treatments. Fallow plots had more ground cover and higher vegetation than plowed ones. Moreover, ticks and chiggers in both field types were dominated by species known to infest humans. Because ticks and chiggers should exhibit very low survival in flooded rice paddies, we propose that farm abandonment in Taiwan, driven by globalization, may have inadvertently led to increased risks of spotted fever and scrub typhus. However, periodic plowing can unintentionally mitigate vector burdens. Economic globalization can have unexpected consequences on disease risk through modification of the agricultural landscape, but the outcome may also be influenced by agricultural policies, calling for further research on vector‐borne diseases and their control from broader perspectives.
Zinc removal from wastewater by complexation-microfiltration process
Authors: Trivunac Katarina , Sekulic Zoran , Stevanovic Slavica
Published: April 2012

As a result of its wide industrial applications, zinc has become an important
contaminant in aquatic environment since it is a toxic heavy metal and some
of its compounds such as zinc arsenate and zinc cyanide, may be extremely
hazardous. Therefore, there is a growing need for developing simple methods
capable of separating and recovering trace zinc from environmental waters.
Nowadays, the ultra and microfiltration method for trace metals removal from
waters by the addition of water-soluble polymers into the aqueous solutions
has become a significant research area. The choice of watersoluble
macroligands remains important for developing this technology. Sodium
carboxymethyl cellulose (Na-CMC) was selected as complexing agent. The
microfiltration experiments were carried out in stirred dead-end cell. To
separate formed polymer-metal complex Versapor membranes were used. The
concentration of heavy metal ions after microfiltration in aqueous solution
was determined using atomic absorption spectroscopy (AAS). Effects of amount
of complexing agent, pH value, type of anion, ionic strength and operating
pressure on the flux (J) and rejection coefficient (R) were investigated.
Experimental results indicate a considerable influence of the pH, ionic
strength and type of anion on the rejection coefficient, while effect of
amount of complexing agent is relatively insignificant. The Na-CMC used in
the research proved to be very effective, which may be supported by the high
rejection coefficients obtained (99%).
An Analysis of the Medical Expense Deduction Post-O'Donnabhain
Authors: Smith Eric S. , Pace Ryan H.
Published: April 2012

In 2010, the United States Tax Court upheld a taxpayer's deduction for medical expenses arising from gender reassignment surgery. This article discusses the facts of the O'Donnabhain case and the Tax Court's holding in light of relevant legislative history, and finds that a new layer of understanding now exists in the context of deductible plastic surgery: in a post-O'Donnabhain world, mental (not just physical) diseases may be treated through physical alterations to the body and give rise to deductible medical expenses. Based on the Tax Court's opinion, we posit an algorithm for application of what we consider to be a fourth case law-created exception to the disallowance of deductions for cosmetic surgery, which may have application in both LGBT- and non-LGBT-related instances.
Intraurban Near-Water Areas and Their Role in Distribution of Ticks (Acari, Ixodidae) in Megapolis the Example of Kyiv
Authors: Nebogatkin I.
Published: April 2012

Intraurban Near-Water Areas and Their Role in Distribution of Ticks (Acari, Ixodidae) in Megapolis the Example of Kyiv

In 2002-2009, we studied 12 islands within the city of Kyiv, and found four indigenous species of ticks (Dermacentor reticulatus Fabricius, 1794; Ixodes ricinus Linnaeus, 1758; I. apronophorus Schulze, 1924; Rhipicephalus rossicus Jakimov et Kohl-Jakimova, 1911) and one invasive species (Hyalomma marginatum Koch, 1844). For A-E-gradient, established by man's impact degree, we revealed atypical distribution of species: their majority is noted in two pole areas - where the man impact is maximum and minimum. The investigated near-water areas are a kind of survival areas and sources of ixodides diversity in megalopolis.
Electric mine motor thermal models aiding design and setting thermal protections
Authors: Krok R.
Published: April 2012

Electric mine motor thermal models aiding design and setting thermal protections

The paper presents original modified thermal networks for calculations of the temperature field in induction mine motors under steady and transient conditions aiding design and setting thermal protections. They can be used for location of the hottest places in motor elements in order to place in them sensors for temperature measurements. They can be also applied to determining the equivalent thermal constants of windings needed when setting microprocessor thermal protections.