Tomato spotted wilt virus benefits a non-vector arthropod, Tetranychus urticae, by modulating different plant responses in tomato.
The interaction between plant viruses and non-vector arthropod herbivores is poorly understood. However, there is accumulating evidence that plant viruses can impact fitness of non-vector herbivores. In this study, we used oligonucleotide microarrays, phytohormone, and total free amino acid analyses to characterize the molecular mechanisms underlying the interaction between Tomato spotted wilt virus (TSWV) and a non-vector arthropod, twospotted spider mite (Tetranychusurticae), on tomato plants, Solanumlycopersicum. Twospotted spider mites showed increased preference for and fecundity on TSWV-infected plants compared to mock-inoculated plants. Transcriptome profiles of TSWV-infected plants indicated significant up-regulation of salicylic acid (SA)-related genes, but no apparent down-regulation of jasmonic acid (JA)-related genes which could potentially confer induced resistance against TSM. This suggests that there was no antagonistic crosstalk between the signaling pathways to influence the interaction between TSWV and spider mites. In fact, SA- and JA-related genes were up-regulated when plants were challenged with both TSWV and the herbivore. TSWV infection resulted in down-regulation of cell wall-related genes and photosynthesis-associated genes, which may contribute to host plant susceptibility. There was a three-fold increase in total free amino acid content in virus-infected plants compared to mock-inoculated plants. Total free amino acid content is critical for arthropod nutrition and may, in part, explain the apparent positive indirect effect of TSWV on spider mites. Taken together, these data suggest that the mechanism(s) of increased host suitability of TSWV-infected plants to non-vector herbivores is complex and likely involves several plant biochemical processes.


Effect of low-level radiation on the death of male germ cells.
Hormetic and adaptive responses induced by low-level radiation in hematopoietic and immune systems have been observed, as shown by stimulatory effects on cell growth and resistance to subsequent radiation-induced cytogenetic damage. However, in terms of cell death by apoptosis, the effects of low-level radiation are controversial: Some studies showed decreased apoptosis in response to low-level radiation while others showed increased apoptosis. This controversy may be related to the radiation doses or dose rates and also, more importantly, to the cell types. Testes are one of the most radiosensitive organs. The loss of male germ cells after exposure to ionizing radiation has been attributed to apoptosis. In the present study, the effects of low-level radiation at doses up to 200 mGy on mouse male germ cells in terms of apoptosis and the expression of apoptosis-related proteins were examined at different times after whole-body exposure of mice to low-level radiation. In addition, the effect of pre-exposure to low-level radiation on subsequent cell death induced by high doses of radiation was examined to explore the possibility of low-level radiation-induced adaptive response. The results showed that low-level radiation in the dose range of 25-200 mGy induced significant increases in apoptosis in both spermatogonia and spermatocytes, with the maximal effect at 75 mGy. The increased apoptosis is most likely associated with Trp53 protein expression. Furthermore, 75 mGy low-level radiation given pre-irradiation led to an adaptive response of seminiferous germ cells to subsequent high-level radiation-induced apoptosis. These results suggest that low-level radiation induces increased apoptosis in male germ cells but also induces a significant adaptive response that decreases cell death after a subsequent high-dose irradiation.


Short-term HFD does not alter lipolytic function of adipocytes.
A short bout of high fat diet (HFD) impairs glucose tolerance and hepatic insulin sensitivity. We recently identified adipose tissue inflammation and resulting dysfunctional adipose tissue-liver cross-talk as an early event in the development of HFD-induced hepatic insulin resistance. In particular, reducing white adipose tissue (WAT) inflammation by adipocyte-specific depletion of Fas/CD95 protected mice from developing hepatic insulin resistance but not hepatic steatosis. Herein, we expanded our previous work and determined the impact of four days of HFD on lipolytic activity of isolated adipocytes. Compared with chow-fed mice, the degree of basal and isoproterenol-stimulated free fatty acid (FFA) and glycerol release was similar in HFD-fed animals. Moreover, insulin's ability to suppress lipolysis remained intact, suggesting retained insulin sensitivity. Despite unaltered lipolysis, circulating FFA concentrations were greatly increased in non-fasted HFD-fed mice. In conclusion, a short-term HFD challenge does not affect lipolytic function of adipocytes. The observed increase of circulating FFA levels in randomly fed animals may rather be the result of increased dietary fat supply.


Reduction of postprocedure microemboli following retrospective quality assessment and practice improvement measures for carotid angioplasty and stenting.
We have previously demonstrated a 70% incidence of microemboli on diffusion weighted magnetic resonance imaging (DW-MRI) following carotid angioplasty and stenting (CAS). The purpose of this study is to compare the incidence of microemboli in two distinct time periods when procedural modifications were implemented into a CAS program. Following a retrospective quality review of our CAS cohort (n = 27) from November 2004 through April 2006 (period 1), we enrolled patients (n = 20) from May 2006 through February 2008 (period 2) undergoing CAS into a prospective cohort that included obtaining pre- and postprocedure DW-MRI exams. Procedural modifications during period 2 included the preferential use of closed-cell systems (60% vs 0% in period 1), early heparinization at the initiation of arterial access, and elimination of an arch angiogram. The hospital records of these 47 patients were reviewed; symptoms, comorbidities, lesion characteristics, periprocedural information, and postoperative outcomes were collected. The incidence and location of acute, postprocedural microemboli were determined using DW-MRIs. Twenty (74%) CAS patients from period 1 and seven (35%) patients from period 2 demonstrated acute microemboli on postprocedural DW-MRI (P = .02). The mean number of microemboli in period 1 was 4.1 +/- 5.3 vs 1.5 +/- 2.7 during period 2 (P = .04). Two of the 27 patients (7.4%) during period 1 experienced temporary neurologic changes that resolved within 36 hours. None of the patients during period 2 exhibited any neurologic changes. Patient demographics, comorbidities, and presenting symptoms were similar between the two groups except for smoking prevalence, female presence, and obesity (BMI > 30). Period 2 patients when compared with period 1 had more technically challenging anatomy with more calcified lesions (68% vs 27%), longer lesions (15.9 mm vs 8.2 mm), and higher incidence of ulceration (55% vs 27%) (all P < .04). Despite successful performance of 47 consecutive CAS procedures without permanent neurologic sequelae, significant reductions in periprocedural embolic events as identified via DW-MRI lesions may be achieved through implementation of quality improvement measures identified through continuous outcome analysis. The long-term neurologic benefits associated with reduced subclinical neurologic events remains to be determined.


Exploration of external light trapping for photovoltaic modules.
The reflection of incident sunlight by photovoltaic modules prevents them from reaching their theoretical energy conversion limit. We explore the effectiveness of a universal external light trap that can tackle this reflection loss. A unique feature of external light traps is their capability to simultaneously recycle various broadband sources of reflection on the module level, such as the reflection from the metal front grid, the front interfaces, the reflective backside of the cell, and the white back sheet. The reflected light is recycled in the space between the solar cell and a mirror above the solar cell. A concentrator funnels the light into this cage through a small aperture in the mirror. As a proof-of-principle experiment, a significant reflectance reduction of a bare crystalline silicon (c-Si) photodiode is demonstrated. In contrast to conventional light trapping methods, external light trapping does not induce any damage to the active solar cell material. Moreover, this is a universally applicable technology that enables the use of thin and planar solar cells of superior electrical quality that were so far hindered by limited optical absorption. We considered several trap designs and identified fabrication issues. A series of prototype millimeter-scale external metal light traps were milled and applied on an untextured c-Si photodiode, which is used as a model for future thin solar cells. We determined the concentrator transmittance and analyzed the effect of both the concentration factor and cage height on the absorptance and spatial intensity distribution on the surface of the solar cell. This relatively simple and comprehensive light management solution can be a promising candidate for highly efficient solar modules using thin c-Si solar cells.


Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype-phenotype associations.
Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype-phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL-negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplications (e.g. 1q12-->1q32 in PV, 1q21-32-->1q32-44 in post-PV MF or PMF), deletions (e.g. 1p13-36-->pter in PV or PMF, 1q21 in PMF) and unbalanced translocations involving chromosome 6, such as der(6)t(1;6)(q21-25;p21.3-23), and other partner chromosomes involving 1q10/1p11 and 1q21-25 breakpoints. Although occasionally seen in chronic phase MPN, unbalanced 1;7 translocations, e.g. der(1;7)(q10;p10), are usually seen in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and post-MPN AML/MDS. These observations suggest that certain chromosome 1 regions, especially 1q21-1q32 and 1p11-13, might harbor oncogenes or tumor suppressor genes that are pathogenetically relevant to both chronic and advanced phases of MPN.


Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients.
HIV infection leads to decreases in the number of CD4 T lymphocytes and an increased risk for opportunistic infections and neoplasms. The administration of intermittent cycles of IL-2 to HIV-infected patients can lead to profound increases (often greater than 100%) in CD4 cell number and percentage. Using in vivo labeling with 2H-glucose and BrdU, we have been able to demonstrate that, although therapy with IL-2 leads to high levels of proliferation of CD4 as well as CD8 lymphocytes, it is a remarkable preferential increase in survival of CD4 cells (with half-lives that can exceed 3 years) that is critical to the sustained expansion of these cells. This increased survival was time-dependent: the median half-life, as determined by semiempirical modeling, of labeled CD4 cells in 6 patients increased from 1.7 weeks following an early IL-2 cycle to 28.7 weeks following a later cycle, while CD8 cells showed no change in the median half-life. Examination of lymphocyte subsets demonstrated that phenotypically naive (CD27+CD45RO-) as well as central memory (CD27+CD45RO+) CD4 cells were preferentially expanded, suggesting that IL-2 can help maintain cells important for host defense against new antigens as well as for long-term memory to opportunistic pathogens.


[Feministic research means that all research is political].
The article is a review of different trends and epistemologies in women's studies/feminist research within the field of medicine. In the beginning of the 1980s, women's studies entered the field of medicine in the Nordic countries. They are now a part of the feminist research that has been established within most sciences both nationally and internationally. The gender power relation and its impact on health--first of all women's, but in extension also men's--has been in focus. Moreover, science itself, its limits and possibilities, and the kind of knowledge it produces, is discussed. In this respect, feminist theory of science is a useful tool.


[Bioethics and nutrition in adult patients with cancer in palliative care].
Cancer constitutes a major group of chronic diseases and is the second leading cause of death in the developed countries. Palliative care proposes to offer comprehensive support to control symptoms and improve quality of life for patients and their families. Nutrition is an important tool in palliative care, helping patients with their physical, psychological, and social issues and promoting comfort and quality of life. However, in the context of palliative care, nutritional support rarely achieves its role of fully recovering and assuring nutritional status. At this point, the nutritionist must consider the individual patient's needs, preferences, and eating habits, which are essential both for controlling symptoms and assuring satisfaction and comfort. The impossibility of conventionally applying established management and the development of a new perception of the patient often raise dilemmas for professional nutritionists.


The effect of HIV coinfection on hepatitis C: A review.
Many Hepatitis C (HCV) infected patients are coinfected with HIV. As HIV-directed anti-viral therapy has delayed HIV progression and mortality, pathologic consequences of HCV infection are occurring at an increased rate. In this review, a case presentation delineating the clinical course of an HIV/HCV coinfected patient at our institution is presented. The pathobiology, interrelation of HCV and HIV infection in coinfected patients is discussed as well as the effect of treatment in this unique patient population. The interaction of HIV and HCV coinfection is complex. It is clear that HIV infection negatively affects the natural history of HCV, while HIV-directed therapy may enhance immunologic response and exacerbate hepatocellular injury induced by HCV. Further studies assessing the effect of anti-HIV and anti-HCV-directed therapy on the clinical course of HCV/HIV coinfected patients is warranted.


Social determinants and their unequal distribution: clarifying policy understandings.
Public health policy in older industrialized societies is being reconfigured to improve population health and to address inequalities in the social distribution of health. The concept of social determinants is central to these policies, with tackling the social influences on health seen as a way to reduce health inequalities. But the social factors promoting and undermining the health of individuals and populations should not be confused with the social processes underlying their unequal distribution. This distinction is important because, despite better health and improvement in health determinants, social disparities persist. The article argues that more emphasis on social inequalities is required for a determinants-oriented approach to be able to inform policies to address health inequalities.


Obesity and the neurocognitive basis of food reward and the control of intake.
With the rising prevalence of obesity, hedonic eating has become an important theme in obesity research. Hedonic eating is thought to be that driven by the reward of food consumption and not metabolic need, and this has focused attention on the brain reward system and how its dysregulation may cause overeating and obesity. Here, we begin by examining the brain reward system and the evidence for its dysregulation in human obesity. We then consider the issue of how individuals are able to control their hedonic eating in the present obesogenic environment and compare 2 contrasting perspectives on the control of hedonic eating, specifically, enhanced control of intake via higher cognitive control and loss of control over intake as captured by the food addiction model. We conclude by considering what these perspectives offer in terms of directions for future research and for potential interventions to improve control over food intake at the population and the individual levels.


Is the apparent rise in cancer mortality in the elderly real? Analysis of changes in certification and coding of cause of death in England and Wales, 1970-1990.
The effect of changes in recording and coding of cause of death on trends in cancer mortality in England and Wales in persons aged 45 and over during 1970-1990 is reviewed. During this period, all-cancer mortality rates increased only at ages over 75 in males and over 55 in females. Rises in cancer mortality were largely due to increases in cancer of lung, prostate and unspecified site in men, and of lung, breast and unspecified site in women. Death coding and certification artefacts were much larger in older persons. In those aged 75-84, a change in the position of recording cancer on the death certificate could potentially account for 46% of the recorded increase in prostate-cancer mortality and 28% of the increase in breast-cancer mortality. The decrease in recorded mortality from ill-defined terminal events was far greater than the increase in cancer mortality in this age group. The rise in all-cancer mortality in the elderly was partly due to an increase in lung-cancer mortality, and data artefacts explained a large proportion of the increase in the other common specified cancers in those aged 75-84. The use of routine mortality statistics to chart progress against cancer lacks validity at older ages because of imprecision in certification of cause of death.


Rationale for control of anthropogenic nitrogen and phosphorus to reduce eutrophication of inland waters.
Concentrations of phosphorus and nitrogen in surface waters are being regulated in the United States and European Union. Human activity has raised the concentrations of these nutrients, leading to eutrophication of inland waters, which causes nuisance growth of algae and other aquatic plants. Control of phosphorus often has had the highest priority because of its presumed leading role in limiting development of aquatic plant biomass. Experimental evidence shows, however, that nitrogen is equally likely to limit growth of algae and aquatic plants in inland waters, and that additions of both nutrients cause substantially more algal growth than either added alone. A dual control strategy for N and P will reduce transport of anthropogenic nitrogen through drainage networks to aquatic ecosystems that may be nitrogen limited. Control of total phosphorus in effluents is feasible and is increasingly being required by regulations. The control strategy for nitrogen in effluents is more difficult, but could be made more feasible by recognition that a substantial portion of dissolved organic nitrogen is not bioavailable; regulation should focus on bioavailable N (nitrate, ammonium, and some dissolved organic nitrogen) rather than total N. Regulation of both N and P also is essential for nonpoint sources.


Two-dimensional concurrent HMQC-COSY as an approach for small molecule chemical shift assignment and compound identification.
Chemical shift assignment is the first step toward the structure elucidation of natural products and other chemical compounds. We propose here the use of 2D concurrent HMQC-COSY as an experiment for rapid chemical shift assignment of small molecules. This experiment provides well-dispersed (1)H-(13)C peak patterns that are distinctive for different functional groups plus (1)H-(1)H COSY connectivities that serve to identify adjacent groups. The COSY diagonal peaks, which are phased to be absorptive, resemble (1)H-(13)C HMQC cross peaks. We demonstrate the applicability of this experiment for rapidly and unambiguously establishing correlations between different functional groups through the analysis of the spectrum of a metabolite (jasmonic acid) dissolved in CDCl(3). In addition, we show that the experiment can be used to assign spectra of compounds in a mixture of metabolites in D(2)O.


Cellular responses to attaching and effacing bacteria: activation and implication of the innate immune system.
During the last decade, research on attaching-effacing (A/E) bacteria/host cell interactions has revealed much of the molecular basis of colonization and lesion formation. The colonic mucosa represents the first line of defense against these pathogens, and its integrity is required to avoid translocation of bacteria or bacterial soluble factors into the infected host. Therefore, the cellular immune response to A/E pathogens plays an important role in bacterial pathogenesis since it can clear the bacteria or modulate the inflammatory processes. Data obtained from infected patients demonstrate a correlation between the production of pro-inflammatory cytokines and the severity of the disease. In vitro studies of infected epithelial cells have clearly elucidated A/E bacteria-induced host signal transduction events. However, the identification of the bacterial factors responsible for cellular activation remains a subject of controversy. Experimental studies with knock-out mice infected with Citrobacter rodentium, a rodent A/E pathogen, indicate that innate immunity is an essential component of pathogenesis. This review summarizes in vivo and in vitro evidence for the induction and potential role of the innate immune system during infection with A/E bacteria.


The Effects of Botulinum Toxin Injections on Spasticity and Motor Performance in Chronic Stroke with Spastic Hemiplegia.
Spastic muscles are weak muscles. It is known that muscle weakness is linked to poor motor performance. Botulinum neurotoxin (BoNT) injections are considered as the first-line treatment for focal spasticity. The purpose of this study was to quantitatively investigate the effects of BoNT injections on force control of spastic biceps brachii muscles in stroke survivors. Ten stroke survivors with spastic hemiplegia (51.7 ± 11.5 yrs; 5 men) who received 100 units of incobotulinumtoxinA or onabotulinumtoxinA to the biceps brachii muscles participated in this study. Spasticity assessment (Modified Ashworth Scale (MAS) and reflex torque) and muscle strength of elbow flexors, as well as motor performance assessment (force variability of submaximal elbow flexion) were performed within one week before (pre-injection) and 3~4 weeks (3-wk) after BoNT injections. As expected, BoNT injections reduced the MAS score and reflex torque, and elbow flexor strength on the spastic paretic side. However, motor performance remained within similar level before and after injections. There was no change in muscle strength or motor performance on the contralateral arm after BoNT injections. The results of this study provide evidence that BoNT injections can reduce spasticity and muscle strength, while motor performance of the weakened spastic muscle remains unchanged.


Nail Psoriasis: An Updated Review and Expert Opinion on Available Treatments, Including Biologics.
Nail psoriasis affects 50-79% of patients with skin psoriasis and up to 80% of patients with psoriatic arthritis, and can also represent a negative prognostic factor in individuals with plaque psoriasis. Treatments for nail psoriasis are limited, as nails are often difficult to treat with topical therapies alone, and relapse is common. Among different systemic agents, secukinumab, a fully human monoclonal antibody targeting interleukin (IL)-17A, is the only antibody supported by a trial specifically conducted in patients with nail psoriasis (the TRANSFIGURE trial) and has the longest follow-up available to date. In this setting, secukinumab is characterized by the highest efficacy at week 16. This review analysed the different therapeutic options for nail psoriasis, focusing on new treatments that have shown promising results in this field.


Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer.
Accurate diagnosis of histological type is important for therapy selection in lung cancer. Immunohistochemical (IHC) and histochemical stains are often used to complement morphology for definite diagnosis and are incorporated in the WHO classification. Our main aim was to compare different mucin stains and assess their value in relation to common IHC analyses in lung cancer diagnostics. Using tissue microarrays from 657 surgically treated primary lung cancers, we evaluated the mucin stains periodic acid-Schiff with diastase (PASD), alcian blue-periodic acid-Schiff (ABPAS) and mucicarmine, and compared with the IHC markers p40, p63, cytokeratin 5, thyroid transcription factor 1 (TTF-1), napsin A and cytokeratin 7. Ten or more cytoplasmic mucin inclusions in a tissue microarray core were seen in 51%, 48% and 31% of the 416 adenocarcinomas and 3%, 4% and 0.5% of the 194 squamous cell carcinomas with PASD, ABPAS and mucicarmine, respectively. Diagnostic pitfalls, such as entrapped benign epithelium, apoptotic/necrotic cells and glycogen, partly differed for the mucin stains. TTF-1 and napsin A IHC stainings had similar specificity but better sensitivity for adenocarcinoma than the mucin stains, but addition of PASD or ABPAS identified more tumors as adenocarcinomas (n = 8 and n = 10, respectively) than napsin A (n = 1) in cases with solid growth that were negative for TTF-1 and p40. We conclude that PASD and ABPAS have similar diagnostic performance and that these markers are of value in poorly differentiated cases. However, morphology and TTF-1 and p40 IHC staining is sufficient for correct diagnosis in most non-small cell lung cancers.


Voltammetric Behaviour of Sulfamethoxazole on Electropolymerized-Molecularly Imprinted Overoxidized Polypyrrole.
In this work, preparation of a molecularly imprinted polymer (MIP) film and its recognition properties for sulfamethoxazolewere investigated. The overoxidized polypyrrole (OPPy) film was prepared by the cyclic voltammetric deposition of pyrrole (Py) in the presence of supporting electrolyte (tetrabutylammonium perchlorate-TBAP) with and without a template molecule (sulfamethoxazole) on a pencil graphite electrode (PGE). The voltammetric behaviour of sulfamethoxazole on imprinted and non-imprinted (NIP) films was investigated by differential pulse voltammetry (DPV) in Britton-Robinson (BR) buffer solutions prepared in different ratio of acetonitrile-water binary mixture, between the pH 1.5 and 7.0. The effect of the acetonitrile-water ratio and pH, monomer and template concentrations, electropolymerization cycles on the performance of the MIP electrode was investigated and optimized. The MIP electrode exhibited the best reproducibility and highest sensitivity. The results showed that changing acetonitrile-water ratio and pH of BR buffer solution changes the oxidation peak current values. The highest anodic signal of sulfamethoxazole was obtained in BR buffer solution prepared in 50% (v/v) acetonitrile-water at pH 2.5. The calibration curve for sulfamethoxazole at MIP electrode has linear region for a concentration range of 25.10-3 to 0.75 mM (R²=0.9993). The detection limit of sulfamethoxazole was found as 3.59.10-4 mM (S/N=3). The same method was also applied to determination of sulfamethoxazole in commercial pharmaceutical samples. Method precision (RSD87%) were satisfactory. The proposed method is simple and quick. The polypyrrole (PPy) electrodes have low response time, good mechanical stability and are disposable simple to construct.


Dopamine Transporter Amino and Carboxyl Termini Synergistically Contribute to Substrate and Inhibitor Affinities.
Extracellular dopamine and serotonin concentrations are determined by the presynaptic dopamine (DAT) and serotonin (SERT) transporters, respectively. Numerous studies have investigated the DAT and SERT structural elements contributing to inhibitor and substrate binding. To date, crystallographic studies have focused on conserved transmembrane domains, where multiple substrate binding and translocation features are conserved. However, it is unknown what, if any, role the highly divergent intracellular N and C termini contribute to these processes. Here, we used chimeric proteins to test whether DAT and SERT N and C termini contribute to transporter substrate and inhibitor affinities. Replacing the DAT N terminus with that of SERT had no effect on DA transport Vmax but significantly decreased DAT substrate affinities for DA and amphetamine. Similar losses in uptake inhibition were observed for small DAT inhibitors, whereas substituting the DAT C terminus with that of SERT affected neither substrate nor inhibitor affinities. In contrast, the N-terminal substitution was completely tolerated by the larger DAT inhibitors, which exhibited no loss in apparent affinity. Remarkably, all affinity losses were rescued in DAT chimeras encoding both SERT N and C termini. The sensitivity to amino-terminal substitution was specific for DAT, because replacing the SERT N and/or C termini affected neither substrate nor inhibitor affinities. Taken together, these findings provide compelling experimental evidence that DAT N and C termini synergistically contribute to substrate and inhibitor affinities.


The effect of radiation on the permeability of human saphenous vein to 17 beta-oestradiol.
Radiation therapy is an effective way of treating many forms of cancer, however, there are some indications that it may facilitate the development of metastasis. The question arises whether radiation therapy during cancer treatment might result in an alteration of the permeability of the tissues being treated. This alteration in the permeability might lead to metastatic cells escaping from the irradiated tissue, leading to the spread of cancer to other sites in the body. Because of the above implication, we determined the diffusion kinetics of a radioactive marker, 17 beta-oestradiol, through human saphenous vein before and after a single half hour exposure to 60 Gy of 60Co gamma-irradiation. Six clinically healthy saphenous vein specimens (mean patient age +/- standard deviation 57 +/- 13 years; age range 41-77 years) were obtained during cardiac surgery. In vitro flux rates of 17 beta-oestradiol were determined through use of a flow-through diffusion apparatus immediately after irradiation for a period of 24 hours. No statistically significant differences could be demonstrated for the flux rates of 17 beta-oestradiol through the non-irradiated and 60 Gy irradiated saphenous vein tissue. These findings strongly suggest that irradiation at 2 Gy/min and a total dose of 60 Gy would not alter the permeability of the venous wall. We have demonstrated that the in vitro flow-through diffusion method is capable of measuring permeability aspects of endothelial cell layers in saphenous vein biopsies under conditions resembling clinical reality.


The APC network regulates the removal of mutated cells from colonic crypts.
Self-renewal is essential for multicellular organisms but carries the risk of somatic mutations that can lead to cancer, which is particularly critical for rapidly renewing tissues in a highly mutagenic environment such as the intestinal epithelium. Using computational modeling and in vivo experimentation, we have analyzed how adenomatous polyposis coli (APC) mutations and β-catenin aberrations affect the maintenance of mutant cells in colonic crypts. The increasing abundance of APC along the crypt axis forms a gradient of cellular adhesion that causes more proliferative cells to accelerate their movement toward the top of the crypt, where they are shed into the lumen. Thus, the normal crypt can efficiently eliminate β-catenin mutant cells, whereas APC mutations favor retention. Together, the molecular design of the APC/β-catenin signaling network integrates cell proliferation and migration dynamics to translate intracellular signal processing and protein gradients along the crypt into intercellular interactions and whole-crypt physiological or pathological behavior.


Molecular genetics of human hypertension.
For the past decade, hypertension research has shifted strongly in the direction of molecular genetics. The success stories are the monogenic hypertensive syndromes. Classic linkage analyses has located the responsible genes for glucocorticoid-remediable aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess. The genes have been cloned and their function elucidated. Other monogenic syndromes are currently being intensively studied. However, in the area of primary hypertension, the successes have relied on the candidate gene approach. Allelic variants in the genes for angiotensinogen, alpha-adducin, beta2-adrenergic receptor, the G-protein beta3-subunit and the T594M mutation in the beta-subunit of the epithelial sodium channel have been identified; however, the importance of these allelic variants to primary hypertension as a whole, is not yet clear. A variant in the angiotensin-converting enzyme gene could not, initially, be convincingly associated with hypertension, but more recent analyses suggest an influence of the deletion allele on blood pressure in men, but apparently not in women. In all likelihood we are dealing with many genes with small effects. Affected sibling pair linkage analyses will probably not be successful in identifying the loci of these genes. To find new genes, novel approaches will be necessary, including searching for quantitative trait loci linked to blood pressure in normotensive persons, haplotype sharing methodology in trios and family units, the use of better study designs, and the investigation of isolated populations. Finally, rethinking the phenotype 'hypertension' and its intermediates must also receive priority.


[Outcome of pregnancy in patients exposed in utero to diethylstilbestrol. Survey by the National College of French Gynecologists and Obstetricians].
This study analyses the outcome of 110 pregnancies that occurred in 57 patients who were exposed to DES (DiEthylStilboestrol) during their fetal life. The quantities of Distilbene that were received in the first trimester of the pregnancy were the same in France and in the United States. The obstetrical complications of exposure in utero to DES were identically the same in France and in the United States. Of particular note is the high level of extra-uterine pregnancies (15%) and of 1st and 2nd trimester miscarriages (42%). Only 41% of the population exposed to DES delivered a live baby. It is estimated that 80,000 women were exposed to it in France. Exposure in utero to DES has given rise to a public health problem.


[Blood transfusion in pediatric patients and strategies to decrease it: a reevaluation.].
Several approaches and techniques are used in adult patients to decrease or prevent both blood loss and homologous blood transfusion during surgical procedures where massive blood losses are expected. While these blood-sparing strategies are widely used in adults, they are mostly neglected in children. Perhaps in pediatric patients, these blood-sparing techniques may not be as effective as in adults and technical limitations, as the small size of patients could limit its advantages. In the following review, blood-sparing techniques established for adults are described and their applicability in pediatric patients discussed. Blood-sparing strategies developed for adult patients aiming at decreasing or even preventing homologous blood transfusion when massive blood losses are expected, are presented through a bibliographic review. Since all known methods were developed for adult patients, an action line was drawn for the reevaluation of these methods, techniques and drugs to be used in pediatric patients. It has become once more clear that solutions for adult patients may not be as effective for pediatric patients. Intraoperative blood-sparing techniques and consequent decrease in the need for homologous blood are effective for adult patients but are by far more invasive, complicated, and some of them ineffective in pediatric patients, especially those under two years of age.


Lens differentiation is controlled by the balance between PDGF and FGF signaling.
How multiple receptor tyrosine kinases coordinate cell fate determination is yet to be elucidated. We show here that the receptor for platelet-derived growth factor (PDGF) signaling recruits the p85 subunit of Phosphoinositide 3-kinase (PI3K) to regulate mammalian lens development. Activation of PI3K signaling not only prevents B-cell lymphoma 2 (BCL2)-Associated X (Bax)- and BCL2 Antagonist/Killer (Bak)-mediated apoptosis but also promotes Notch signaling to prevent premature cell differentiation. Reducing PI3K activity destabilizes the Notch intracellular domain, while the constitutive activation of Notch reverses the PI3K deficiency phenotype. In contrast, fibroblast growth factor receptors (FGFRs) recruit Fibroblast Growth Factor Receptor Substrate 2 (Frs2) and Rous sarcoma oncogene (Src) Homology Phosphatase 2 (Shp2) to activate Mitogen-Activated Protein Kinase (MAPK) signaling, which induces the Notch ligand Jagged 1 (Jag1) and promotes cell differentiation. Inactivation of Shp2 restored the proper timing of differentiation in the p85 mutant lens, demonstrating the antagonistic interaction between FGF-induced MAPK and PDGF-induced PI3K signaling. By selective activation of PI3K and MAPK, PDGF and FGF cooperate with and oppose each other to balance progenitor cell maintenance and differentiation.


Micelle-like architecture of the monomer ensemble of Alzheimer's amyloid-β peptide in aqueous solution and its implications for Aβ aggregation.
Aggregation of amyloid-β (Aβ) peptide, a 39- to 43-residue fragment of the amyloid precursor protein, is associated with Alzheimer's disease, the most common form of dementia in the elderly population. Several experimental studies have tried to characterize the atomic details of amyloid fibrils, which are the final product of Aβ aggregation. Much less is known about species forming during the early stages of aggregation, in particular about the monomeric state of the Aβ peptide that may be viewed as the product of the very first step in the hypothesized amyloid cascade. Here, the equilibrium ensembles of monomeric Aβ alloforms Aβ(1-40) and Aβ(1-42) are investigated by Monte Carlo simulations using an atomistic force field and implicit solvent model that have been shown previously to correctly reproduce the ensemble properties of other intrinsically disordered polypeptides. Our simulation results indicate that at physiological temperatures, both alloforms of Aβ assume a largely collapsed globular structure. Conformations feature a fluid hydrophobic core formed, on average, by contacts both within and between the two segments comprising residues 12-21 and 24-40/42, respectively. Furthermore, the 11 N-terminal residues are completely unstructured, and all charged side chains, in particular those of Glu22 and Asp23, remain exposed to solvent. Taken together, these observations indicate a micelle-like† architecture at the monomer level whose implications for oligomerization, as well as fibril formation and elongation, are discussed. We establish quantitatively the intrinsic disorder of Aβ and find the propensity to form regular secondary structure to be low but sequence specific. In the presence of a global and unspecific bias for backbone conformations to populate the β-basin, the β-sheet propensity along the sequence is consistent with the arrangement of the monomer within the fibril, as derived from solid-state NMR data. These observations indicate that the primary sequence partially encodes fibril structure, but that fibril elongation must be thought of as a templated assembly step.


A New Rice Disease, Black Sheath Spot, Caused by Curvularia fallax in China.
In July 2011, we observed a new rice disease, black sheath spot, on tillering rice plants in Huayuan County, Hunan Province, China. Field surveys indicated that this disease covered a ~1,000-ha paddy field, mainly on Y series 2-line hybrid rice cultivars, especially Y Liangyou 7 and Y Liangyou 302, in hills of which 10 to 70% infection was observed (average of 45%), causing estimated damages up to $1.2 million (US). The diseased rice plants were cultivated with standard practices. Weather, flooding, herbicide damage, and fertilizer application did not appear to account for the symptoms. Typical symptoms of the disease included elliptical spots, about 10 × 5 mm, dark brown to black and with a diffuse yellow-brown margin. The leaf blades with diseased sheaths became yellow and blighted. After 7 days of growth on PDA, groups of cylindrical and branched stromata scattered over dark green colony. Conidia averaged 30.4 × l2.5 μm and contained five cells with three dark central cells. The morphology of spores was consistent with that of C. fallax (1). We inoculated 8-cm healthy rice sheath segments with culture disk of an isolate HNAH001. Sheath segments were divided into four groups: I) disks on wounded sheath surfaces; II) disks on non-wounded sheath surfaces; III) disks between the leaf sheath and stem, and IV) a sterilized water control. The segments were maintained in moist, covered plates in a 25°C incubator after inoculation. After another 24 h, circular brown lesions, less than 10 mm long, appeared on all inoculated segments in treatments I,II, and III. Treatment I induced the most serious symptoms. No lesions developed on control segments. For further verification of pathogenicity, we sprayed a spore suspension of HNHY001 on healthy rice plants at the boot stage. Black spots reappeared on the sheaths after 5 days. No lesions appeared on the stems or the leaf blades of inoculated rice plants. We recovered HNHY001 from the spots on inoculated plants and completed all steps of Koch's postulates. For molecular identification of the fungus, DNA was extracted from mycelia and used as a template for PCR with a primer pair of ITS 5 and ITS 4 targeting the rDNA-ITS. The sequence of the PCR product (Accession No. JQ360963) had 100% identity with rDNA-ITS of Cochliobolus geniculatus (teleomorphic state of C. geniculata) and C. affinis in GenBank after a BLAST search and clustered with them after a phylogenetic analysis. There was no sequence of C. fallax on the BLAST list because ITS sequence of C. fallax had not yet been submitted to any nucleotide databank. Hosokawa et al. concluded that C. fallax and C. affinis are synonyms for C. geniculata (2), which is supported by our results from BLAST and phylogenetic analysis. In view of its relative straight conidia and branching stromata, we suggest that the causal agent of black sheath spot of rice be C. fallax. Although Curvularia spp. were reported as pathogens responsible for black kernel of rice, there is no report of sheath spot of rice caused by Curvularia (3). To our knowledge, this is the first report of a rice sheath disease caused by C. fallax. It seems likely the disease exists in areas beyond Huayuan County. Further field inspection and molecular identification are necessary. References: (1) K. B. Boedijn. Bull. Jard. Bot. Buitenzorg, ser. 3 13:129, 1933. (2) M. Hosokawa et al. Mycoscience 44:227, 2003. (3) S. H. Ou. Page 317 in: Rice Diseases, 2nd Edition, Commonwealth Mycological Institute, Kew, UK, 1985.


Acute dependence on, but not tolerance to, heroin and morphine as measured by respiratory effects in rhesus monkeys.
Acute dependence on and tolerance to heroin and morphine were assessed in rhesus monkeys using measures of respiration. Respiratory frequency (f) and minute volume (V(e)) were measured in monkeys breathing air or 5% CO(2) in air using a pressure-displacement plethysmograph. Cumulative doses of naltrexone (0.0001-1.0 mg/kg, i.m) did not alter these parameters in untreated monkeys. Twenty-four hours after a cumulative dose of heroin (1 mg/kg, i.m.), naltrexone produced an increase in both f and V(e) when monkeys were breathing air or 5% CO(2). Following 1 to 3 days of treatment with heroin (0.5 mg/kg/day, i.m.) or morphine (16 mg/kg/day, i.m.), naltrexone produced an increase in f and V(e) that was related to the dose of naltrexone and the number of days of agonist administration. Two days following termination of heroin administration, naltrexone-induced respiratory stimulation declined and had disappeared completely by the fifth day. In tolerance studies, heroin (0.032-0.5 mg/kg, i.m.) and morphine (1-16 mg/kg, i. m.) were injected cumulatively each day for three consecutive days. These drugs suppressed f and V(e) to nearly the same extent on day 3 as they had on day 1 of administration. These results suggest that dependence to morphine and heroin can be measured under conditions of acute 1 to 3 day administration conditions in primates using f and V(e) as reliable and quantitative indicators of opioid withdrawal. Under these conditions, tolerance does not occur.


PlasMapper: a web server for drawing and auto-annotating plasmid maps.
PlasMapper is a comprehensive web server that automatically generates and annotates high-quality circular plasmid maps. Taking only the plasmid/vector DNA sequence as input, PlasMapper uses sequence pattern matching and BLAST alignment to automatically identify and label common promoters, terminators, cloning sites, restriction sites, reporter genes, affinity tags, selectable marker genes, replication origins and open reading frames. PlasMapper then presents the identified features in textual form and as high-resolution, multicolored graphical output. The appearance and contents of the output can be customized in numerous ways using several supplied options. Further, PlasMapper images can be rendered in both rasterized (PNG and JPG) and vector graphics (SVG) formats to accommodate a variety of user needs or preferences. The images and textual output are of sufficient quality that they may be used directly in publications or presentations. The PlasMapper web server is freely accessible at http://wishart.biology.ualberta.ca/PlasMapper.


The Synthetic Phenotype of ΔbamB ΔbamE Double Mutants Results from a Lethal Jamming of the Bam Complex by the Lipoprotein RcsF.
The selective permeability of the Gram-negative outer membrane (OM) is maintained by integral β-barrel outer membrane proteins (OMPs). The heteropentomeric β-barrel assembly machine (Bam) folds and inserts OMPs into the OM. Coordination of the essential proteins BamA and BamD is critical for OMP assembly and therefore the viability of the cell. The role of the nonessential lipoproteins BamBCE has yet to be characterized; however, genetic evidence suggests that they have nonoverlapping roles in OMP assembly. In this work, we quantify changes of the proteome in the conditional lethal ΔbamB ΔbamE double mutant. We show that cells lacking BamB and BamE have a global OMP defect that is a result of a lethal obstruction of an assembly-competent Bam complex by the lipoprotein RcsF. RcsF is a stress-sensing lipoprotein that is threaded through the lumen of abundant β-barrel OMPs by the Bam complex to expose the amino terminus on the cell surface. We demonstrate that simply removing this lipoprotein corrects the severe OMP assembly defect of the double mutant nearly as efficiently as a previously isolated suppressor mutation in bamA We propose that BamB and BamE play crucial, nonoverlapping roles to coordinate the activities of BamA and BamD during OMP biogenesis.IMPORTANCE Protein assembly into lipid bilayers is an essential process that ensures the viability of diverse organisms. In Gram-negative bacteria, the heteropentomeric β-barrel assembly machine (Bam) folds and inserts proteins into the outer membrane. Due to its essentiality, outer membrane protein (OMP) assembly by the Bam complex is an attractive target for antibiotic development. Here, we show that the conditional lethal phenotype of a mutant lacking two of the three nonessential lipoproteins, BamB and BamE, is caused by lethal jamming of the stripped-down Bam complex by a normally surface-exposed lipoprotein, RcsF. The heterotrimeric Bam complex (BamA, BamD, BamC) is nearly as efficient as the wild-type complex in OMP assembly if RcsF is removed. Our study highlights the importance of BamB and BamE in regulating the interaction between BamA and BamD and expands our understanding of the role of the Bam complex in outer membrane biogenesis.


Factors associated with attitudes towards intimate partner violence against women: a comparative analysis of 17 sub-Saharan countries.
Violence against women, especially by intimate partners, is a serious public health problem that is associated with physical, reproductive and mental health consequences. Even though most societies proscribe violence against women, the reality is that violations against women's rights are often sanctioned under the garb of cultural practices and norms, or through misinterpretation of religious tenets. We utilised data from 17 Demographic and Health Surveys (DHS) conducted between 2003 and 2007 in sub-Saharan Africa to assess the net effects of socio-demographic factors on men's and women's attitudes toward intimate partner violence against women (IPVAW) using multiple logistic regression models estimated by likelihood ratio test. IPVAW was widely accepted under certain circumstances by men and women in all the countries studied. Women were more likely to justify IPVAW than men. "Neglecting the children" was the most common reason agreed to by both women and men for justifying IPVAW followed by "going out without informing husband" and "arguing back with the husband". Increasing wealth status, education attainment, urbanization, access to media, and joint decision making were associated with decreased odds of justifying IPVAW in most countries. In most Sub-Saharan African countries studied where IPVAW is widely accepted as a response to women's transgressing gender norms, men find less justification for the practice than do women. The present study suggests that proactive efforts are needed to change these norms, such as promotion of higher education and socio-demographic development. The magnitude and direction of factors associated with attitudes towards IPVAW varies widely across the countries, thus suggesting the significance of capitalizing on need-adapted interventions tailored to fit conditions in each country.


Alarmins from corneal epithelial cells upregulate CCL11 and VCAM-1 in corneal fibroblasts.
Severe ocular allergic diseases are characterized by pronounced conjunctival inflammation triggered by T helper 2 (Th2) cells and corneal epithelial damage induced by eosinophils. To examine the role of alarmins released by damaged corneal epithelial cells in tissue eosinophilia, we investigated the effects of a supernatant derived from necrotic human corneal epithelial (HCE) cells on expression of the chemokine CCL11 (eotaxin) and the adhesion molecule VCAM-1 in human corneal fibroblasts. An alarmin preparation was obtained as the material released from HCE cells after three cycles of freezing and thawing. CCL11 released into culture medium and cell surface expression of VCAM-1 were measured with enzyme-linked immunosorbent assays, and the amounts of CCL11 and VCAM-1 mRNAs were quantitated by reverse transcription and real-time polymerase chain reaction analysis. Signaling by the transcription factor NF-κB was evaluated by immunoblot and immunofluorescence analyses. The combination of the necrotic HCE cell supernatant and either interleukin (IL)-4 or IL-13 induced synergistic increases in CCL11 release, VCAM-1 expression, and the abundance of CCL11 and VCAM-1 mRNAs in corneal fibroblasts. The necrotic HCE cell supernatant also induced NF-κB activation in corneal fibroblasts, whereas an inhibitor of NF-κB and IL-1 receptor antagonist each attenuated CCL11 release induced by the alarmin preparation and either IL-4 or IL-13. Alarmins including IL-1 released from necrotic corneal epithelial cells cooperate with Th2 cytokines to induce CCL11 production and VCAM-1 expression in corneal fibroblasts, and may thereby play an important role in tissue eosinophilia associated with ocular allergic diseases.


Pharmacokinetics and pharmacodynamics of dichloroacetate in children with lactic acidosis due to severe malaria.
Lactic acidosis frequently complicates severe malaria in African children, and is a strong independent predictor of mortality. We tested the hypothesis that sodium dichloroacetate (DCA), an activator of pyruvate dehydrogenase, rapidly reduces hyperlactataemia in this patient population. Eighteen children with severe malaria and capillary plasma lactate > or = 5 mM were randomized to receive either intramuscular quinine plus a single 50 mg/kg intravenous infusion of DCA in saline, or quinine plus intravenous saline alone. Two patients in each treatment group died following randomization. Thirty minutes after treatment, the mean plasma lactate was 28% below pretreatment baseline values in the DCA group, but was unchanged in the placebo group. Throughout the first 4 h after treatment, mean plasma lactate in the DCA-treated patients was significantly less than that in controls (p = 0.003). Thereafter, mean plasma lactate declined in both groups and was < 2 mM 10 h after treatment. DCA was well tolerated and did not alter quinine pharmacokinetics. A single intravenous dose of DCA rapidly improved lactic acidosis in African children with severe malaria, suggesting that DCA may be a useful adjunct in the initial treatment of these patients, and may increase their chance of survival by improving a major complication of their illness.


Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras.
Giant cell arteritis (GCA) is a vasculitic syndrome that preferentially affects medium and large-sized arteries. Glucocorticoid therapy resolves clinical symptoms within hours to days, but therapy has to be continued over several years to prevent disease relapses. It is not known whether and how glucocorticoids affect the function of the inflammatory infiltrate or why the disease persists subclinically despite chronic treatment. GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo. Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of IL-2, IL-1beta, and IL-6 mRNA, and by the diminished expression of inducible NO synthase. In contrast, synthesis of IFN-gamma mRNA was only slightly decreased, and expression of TGF-beta1 was unaffected. These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB in the xenotransplanted tissue. Dose-response experiments suggested that steroid doses currently used in clinical medicine are suboptimal in repressing NFkappaB-mediated cytokine production in the inflammatory lesions. Chronic steroid therapy was able to deplete the T cell products IL-2 and IFN-gamma, whereas the activation of tissue-infiltrating macrophages was only partially affected. IL-1beta transcription was abrogated; in contrast, TGF-beta1 mRNA synthesis was steroid resistant. The persistence of TGF-beta1-transcribing macrophages, despite paralysis of T cell function, may provide an explanation for the chronicity of the disease, and may identify a novel therapeutic target in this inflammatory vasculopathy.


Is there a trend of decreasing prevalence of TMD-related symptoms with ageing among the elderly?
Older adults have not been studied as much as younger ones regarding prevalence of TMD-related symptoms. The aim was to assess the prevalence of TMD-related symptoms in two population samples, 70 and 80 years old. Identical questionnaires were in 2012 sent to all subjects born in 1932 and 1942 living in two Swedish counties. The response rate was 70.1%, resulting in samples of 5697 70- and 2922 80-year-old subjects. The questionnaire comprised 53 questions. Answers to questions on problems regarding TMD-related symptoms and awareness of bruxism were analysed. Twelve per cent of the women and 7% of the men in the 70-year-old group reported some, rather great or severe problems regarding TMD pain. In the 80-year-olds the prevalence was 8% and 7%, respectively. Subjects who had problems with TMJ sounds reported difficulty to open the jaw wide 6-times and TMJ pain 10-13-times more frequently than subjects without such problems. Changes of taste and awareness of bruxism were the only variables significantly associated with TMD symptoms in both age groups. Number of teeth was not significantly associated with any of the TMD-related symptoms. Most of the elderly subjects had no severe problems with TMD-related symptoms, but 12% of the 70-year-old women reported some, rather great or severe problems. The marked gender difference at age 70 had disappeared in the 80-year-old group. The prevalence was lower among the 80- compared with the 70-year-old subjects of both sexes. The results support the comorbidity between TMD-related symptoms and general health problems.


Impact of skull density ratio on efficacy and safety of magnetic resonance-guided focused ultrasound treatment of essential tremor.
Skull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs. In 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria. Of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups. MRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.


Comparison of rapid methods for detection of Giardia spp. and Cryptosporidium spp. (oo)cysts using transportable instrumentation in a field deployment.
Reliable, sensitive, quantitative, and mobile rapid screening methods for pathogenic organisms are not yet readily available, but would provide a great benefit to humanitarian intervention units in disaster situations. We compared three different methods (immunofluorescent microscopy, IFM; flow cytometry, FCM; polymerase chain reaction, PCR) for the rapid and quantitative detection of Giardia lamblia and Cryptosporidium parvum (oo)cysts in a field campaign. For this we deployed our mobile instrumentation and sampled canal water and vegetables during a 2 week field study in Thailand. For purification and concentrations of (oo)cysts, we used filtration and immunomagnetic separation. We were able to detect considerably high oo(cysts) concentrations (ranges: 15-855 and 0-240 oo(cysts)/liter for Giardia and Cryptosporidium, respectively) in 85 to 300 min, with FCM being fastest, followed by PCR, and IFM being slowest due to the long analysis time per sample. FCM and IFM performed consistently well, whereas PCR reactions often failed. The recovery, established by FCM, was around 30% for Giardia and 13% for Cryptosporidium (oo)cysts. It was possible to track (oo)cysts from the wastewater further downstream to irrigation waters and confirm contamination of salads and water vegetables. We believe that rapid detection, in particular FCM-based methods, can substantially help in disaster management and outbreak prevention.


Comparison of Micropore Distribution in Cell Walls of Softwood and Hardwood Xylem.
The porosity of wood cell walls is of interest for both understanding xylem functionality and from a wood materials perspective. The movement of water in xylem generally occurs through the macroporous networks formed in softwood by bordered pits and in hardwood by the intervessel pits and open conduits created by vessels and perforation plates. In some situations, such as cavitated xylem, water can only move through the micropores that occur in lignified tracheid and fiber cell walls; however, these micropore networks are poorly understood. Here, we used molecular microscopy analysis of radiata pine (Pinus radiata) and red beech (Nothofagus fusca) to determine the distribution of micropores in the secondary walls and middle lamellae of tracheids and fibers in relation to cell wall composition. Using two different types of probe, we identified a greater porosity of secondary cell walls and a reduced porosity of the middle lamella. Areas of reduced porosity were observed in the outer regions of the secondary cell wall of both tracheids and fibers that appear unrelated to lignification or the distribution of cellulose, mannan, and xylan. Hardwood fiber cell walls were less lignified than those of softwood tracheids and showed greater accessibility to porosity probes. Vessel cell walls were comparable to those of fibers in terms of both porosity and lignification. Lignification is probably the primary determinant of cell wall porosity in xylem. The highly lignified middle lamella, and lumen surface, act as a barrier to probe movement and, therefore, water movement in both softwood and hardwood.


C11-acetate and F-18 FDG PET for men with prostate cancer bone metastases: relative findings and response to therapy.
This study tested the feasibility of C11-acetate (acetate) positron emission tomography (PET) imaging to assess response to therapy in men with bone metastatic prostate cancer and compared results for disease detection and response evaluation with F-18 fluorodeoxyglucose (FDG) PET. Men with ≥3 prostate cancer bone metastases identified by Tc-99m methylene diphosphonate (MDP) bone scintigraphy and/or computed tomography were enrolled in a prospective study of serial acetate and FDG PET imaging. Patients were imaged before and 6 to 12 weeks after initial androgen deprivation therapy for new metastatic prostate cancer or first-line chemotherapy with docetaxel for castration-resistant prostate cancer. Qualitative assessment and changes in the tumor:normal uptake ratio were used to assess response by both acetate and FDG PET. In addition, the detection of bone metastases pretherapy was compared for acetate and FDG PET. A total of 8 patients with documented bone metastases were imaged, of which 6 were imaged both pre- and post-therapy. Acetate PET detected bone metastases in all 8 patients, whereas FDG PET detected lesions in 6 of the 7 imaged patients. Acetate PET generally detected more metastases with a higher tumor:normal uptake ratio. Qualitative and quantitative assessments of post-treatment response correlated with composite clinical designations of response, stable disease, or progression in 6 of 6 and 5 of 6 by acetate and 4 of 5 and 3 of 5 by FDG PET, respectively. In this pilot study, results indicate that acetate PET holds promise for response assessment of prostate cancer bone metastases and is complementary to FDG PET in bone metastasis detection.


Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight.
Changes in whole body energy levels are closely linked to alterations in body weight and bone mass. Here, we show that hypothalamic signals contribute to the regulation of bone mass in a manner consistent with the central perception of energy status. Mice lacking neuropeptide Y (NPY), a well-known orexigenic factor whose hypothalamic expression is increased in fasting, have significantly increased bone mass in association with enhanced osteoblast activity and elevated expression of bone osteogenic transcription factors, Runx2 and Osterix. In contrast, wild type and NPY knockout (NPY (-/-)) mice in which NPY is specifically over expressed in the hypothalamus (AAV-NPY+) show a significant reduction in bone mass despite developing an obese phenotype. The AAV-NPY+ induced loss of bone mass is consistent with models known to mimic the central effects of fasting, which also show increased hypothalamic NPY levels. Thus these data indicate that, in addition to well characterized responses to body mass, skeletal tissue also responds to the perception of nutritional status by the hypothalamus independently of body weight. In addition, the reduction in bone mass by AAV NPY+ administration does not completely correct the high bone mass phenotype of NPY (-/-) mice, indicating the possibility that peripheral NPY may also be an important regulator of bone mass. Indeed, we demonstrate the expression of NPY specifically in osteoblasts. In conclusion, these data identifies NPY as a critical integrator of bone homeostatic signals; increasing bone mass during times of obesity when hypothalamic NPY expression levels are low and reducing bone formation to conserve energy under 'starving' conditions, when hypothalamic NPY expression levels are high.


Early complications in spine surgery and relation to preoperative diagnosis: a single-center prospective study.
The reported incidence of complications in spine surgery varies widely. Variable study methodologies may open differing avenues for potential bias, and unclear definitions of perioperative complication make analysis of the literature challenging. Although numerous studies have examined the morbidity associated with specific procedures or diagnoses, no prospective analysis has evaluated the impact of preoperative diagnosis on overall early morbidity in spine surgery. To accurately assess perioperative morbidity in patients undergoing spine surgery, a prospective analysis of all patients who underwent spine surgery by the neurosurgical service at a large tertiary care center over a 6-month period was conducted. The correlation between preoperative diagnosis and the incidence of postoperative complications was assessed. Data were prospectively collected on 248 consecutive patients undergoing spine surgery performed by the neurosurgical service at the Thomas Jefferson University Hospital from May to December 2008. A standardized definition of minor and major complications was applied to all adverse events occurring within 30 days of surgery. Data on diagnosis, complications, and length of stay were retrospectively assessed using stepwise multivariate analysis. Patients were analyzed by preoperative diagnosis (neoplasm, infection, degenerative disease, trauma) and level of surgery (cervical or thoracolumbar). Total early complication incidence was 53.2%, with a minor complication incidence of 46.4% and a major complication incidence of 21.3%. Preoperative diagnosis correlated only with the occurrence of minor complications in the overall cohort (p = 0.02). In patients undergoing surgery of the thoracolumbar spine, preoperative diagnosis correlated with presence of a complication and the number of complications (p = 0.003). Within this group, patients with preoperative diagnoses of infection and neoplasm were more often affected by isolated and multiple complications (p = 0.05 and p = 0.02, respectively). Surgeries across the cervicothoracic and thoracolumbar junctions were associated with higher incidences of overall complication than cervical or lumbar surgery alone (p = 0.04 and p = 0.03, respectively). Median length of stay was 5 days for patients without a complication. Length of stay was significantly greater for patients with a minor complication (10 days, p < 0.0001) and even greater for patients with a major complication (14 days, p < 0.0001). The incidence of complications found in this prospective analysis is higher than that reported in previous studies. This association may be due to a greater accuracy of record-keeping, absence of recall bias via prospective data collection, high complexity of pathology and surgical approaches, or application of a more liberal definition of what constitutes a complication. Further large-scale prospective studies using clear definitions of complication are necessary to ascertain the true incidence of early postoperative complications in spine surgery.


Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer.
Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins. We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium. After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10(-4)); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R(2) = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers. Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women. Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.


Deliberate self-harm patients of no fixed abode: a study of characteristics and subsequent deaths in patients presenting to a general hospital.
International studies report high rates of deliberate self-harm (DSH) and suicide in the homeless. Little is known about DSH among homeless people in the UK and their subsequent risk of death from suicide and non-suicidal causes. We have carried out a study of no fixed abode (NFA) patients using data collected through the Oxford Monitoring System for Attempted Suicide. We describe the demographic and clinical characteristics of NFA DSH patients and the findings of a mortality follow-up study of a cohort of these patients. Between July 1988 and December 2002, 10,346 persons presented following 17,352 DSH episodes. Of these persons, 374 (3.6%) were of NFA. Compared with domiciled DSH patients, NFA patients were more likely to be male, single, unemployed, to have been a recent victim of violence and violent towards others, to have a criminal record and to have a personality disorder. More NFA patients faced problems with drugs and alcohol, social isolation, finances, the law and housing and had received psychiatric treatment within the previous 12 months. Substantially more NFA patients had a past history of DSH and re-presented with a further episode of DSH within 12 months. In the cohort of DSH patients who presented between January 1978 and December 1997 and who were followed up until December 2000, mortality from probable suicide and from all causes was approximately double that of domiciled patients. NFA DSH patients are a vulnerable group of patients at high risk of DSH repetition and with increased mortality from all causes. Good liaison between medical and psychiatric services is important. Specialist services may need to be developed to meet the particular needs of this patient group.


The feasibility of a training course for clubfoot treatment in Africa: A mixed methods study.
There is no available training programme with standard elements for health workers treating clubfoot in Africa. Standardised training with continued mentorship has the potential to improve management of clubfoot. We aimed to evaluate the feasibility of such a training programme among clubfoot providers in Africa, and assess implications for training effectiveness and scale up. We used participatory research with trainers from 18 countries in Africa over two years to devise, pilot and refine a 2-day basic and a 2-day advanced clubfoot treatment course. (The Africa Clubfoot Training or 'ACT' Course.) The pilots involved training 113 participants. Mixed methods (both qualitative and quantitative) were used for evaluation. We describe and synthesise the results using the eight elements proposed by Bowen et al (2010) to assess feasibility. All participants completed feedback questionnaires, and interviews were conducted with a subset of participants. We undertook a narrative description of themes raised in the participant questionnaires and interviews. Descriptive statistics were used to compare pre- and post-course scores for confidence and knowledge. 113 participants completed pre and post-course measures (response rate = 100%). Mean participant confidence increased from 64% (95%CI: 59-69%) to 88% (95%CI: 86-91%) post course. Mean participant knowledge increased from 55% (95%CI: 51-60%) to 78% (95%CI: 76-81%) post course. No difference was found in mean for either subscale of cadre or sex. The qualitative analysis generated themes under four domains: 'practical learning in groups', 'interactive learning', 'relationship with the trainer' and 'ongoing supervision and mentorship'. The Africa Clubfoot Training package to teach health care workers to manage clubfoot is likely to be feasible in Africa. Future work should evaluate its impact on short and long term treatment outcomes and a process evaluation of implementation is required.


Effect of post etching cleansing on surface microstructure, surface topography, and microshear bond strength of lithium disilicate.
This study assessed the effect of postetch cleansing on the surface microstructure, surface topography, and microshear bond strength (μSBS) of lithium disilicate and the resin cement. In Vitro analytical study. Fifteen discs (10 mm diameter and 2 mm thickness) were fabricated from highly translucent lithium disilicate IPS Emax 2 ceramic (Ivoclar Vivadent, Schaan, Liechtenstein). Four resin cement (RelyX Ultimate, 3M ESPE) cylinders (0.9 mm diameter and 4 mm high) were placed on each ceramic disc (total n = 60). The samples were divided into three groups based on the surface treatment of the ceramic discs (20 resin cement cylinders on 5 discs in each group). Group I (HF) (control) etched with 9.6% HF with no postetch cleansing, Group II (HFP) etched with 9.6% HF for 20 s followed by rinsing with water and postetching cleansing with 37% phosphoric acid, and Group III (HFPU) etched with 9.6% HF followed by active application of 37% phosphoric acid followed by postetch cleansing in ultrasonic bath for 5 min. μSBS of resin cement to ceramic surfaces was tested following a standard protocol. Surface roughness was evaluated using an atomic force microscope. Surface topography and elemental analysis were analyzed using SEM/EDX. Mode of failure was also assessed. The data were analysed using one way analysis of variance and post hoc tukeys test. The μSBS were found to be highest for Group III (HFPU), followed by Group II (HFP) followed by Group I (HF) and were statistically significant. There was a difference in the surface topography and surface microstructure between the three groups. Mode of failure was predominantly adhesive. The μSBS, surface topography, and surface microstructure were found to be superior in the groups, in which postetch cleansing was done as compared to the control in which no postetch cleansing was done.


Observation and origin of self-organized textures in agates.
One of the most impressive manifestations of spontaneous pattern generation in natural materials is iris agate, which contains submicrometer concentric striations that may cycle several thousand times within an individual specimen. Analysis by secondary ion mass spectroscopy and transmission electron microscopy identified the iris texture as alternating layers of fine-grained, highly defective chalcedony and coarse-grained low-defect quartz. This oscillatory zonation in defect concentration may be ascribed to Ostwald-Liesegang crystallization cycles from silica-rich fluids that are variably polymeric and monomeric. Periodic changes in defect concentration and grain size also are observed with wavelengths of hundreds of micrometers and of centimeters, so that agates reveal textural self-similarity over three length scales.


A cardiac arrhythmia syndrome caused by loss of ankyrin-B function.
220-kDa ankyrin-B is required for coordinated assembly of Na/Ca exchanger, Na/K ATPase, and inositol trisphosphate (InsP(3)) receptor at transverse-tubule/sarcoplasmic reticulum sites in cardiomyocytes. A loss-of-function mutation of ankyrin-B identified in an extended kindred causes a dominantly inherited cardiac arrhythmia, initially described as type 4 long QT syndrome. Here we report the identification of eight unrelated probands harboring ankyrin-B loss-of-function mutations, including four previously undescribed mutations, whose clinical features distinguish the cardiac phenotype associated with loss of ankyrin-B activity from classic long QT syndromes. Humans with ankyrin-B mutations display varying degrees of cardiac dysfunction including bradycardia, sinus arrhythmia, idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, and risk of sudden death. However, a prolonged rate-corrected QT interval was not a consistent feature, indicating that ankyrin-B dysfunction represents a clinical entity distinct from classic long QT syndromes. The mutations are localized in the ankyrin-B regulatory domain, which distinguishes function of ankyrin-B from ankyrin-G in cardiomyocytes. All mutations abolish ability of ankyrin-B to restore abnormal Ca(2+) dynamics and abnormal localization and expression of Na/Ca exchanger, Na/K ATPase, and InsP(3)R in ankyrin-B(+/-) cardiomyocytes. This study, considered together with the first description of ankyrin-B mutation associated with cardiac dysfunction, supports a previously undescribed paradigm for human disease due to abnormal coordination of multiple functionally related ion channels and transporters, in this case the Na/K ATPase, Na/Ca exchanger, and InsP(3) receptor.


Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) increases vascular permeability: impaired permeability and angiogenesis in eNOS-deficient mice.
Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) is emerging as an important regulator of vascular pathophysiology. Here, we demonstrate a novel role of RANKL as a vascular permeability factor and a critical role of endothelial nitric oxide synthase (eNOS) in RANKL-induced endothelial function. RANKL increased the vascular permeability and leukocyte infiltration in vivo and caused the breakdown of the blood-retinal barrier in wild-type mice but not in eNOS-deficient mice. In vitro, it increased endothelial permeability and reduced VE-cadherin-facilitated endothelial cell-cell junctions in a NO-dependent manner. RANKL also led to the activation of Akt and eNOS and to NO production in endothelial cells (ECs). These effects were suppressed by the inhibition of TRAF6, phosphoinositide 3'-kinase (PI3K), Akt, or NOS by genetic or pharmacologic means. Inhibition of the TRAF6-mediated NO pathway reduced EC migration and capillary-like tube formation in response to RANKL. Moreover, the effects of RANKL on ECs sprouting from the aorta, and neovessel formation in both the mouse Matrigel plug assay and corneal micropocket assay, were impaired in eNOS-deficient mice. These results demonstrate that RANKL promotes vascular permeability and angiogenesis by stimulating eNOS by a TRAF6-PI3K-Akt-dependent mechanism. These properties may be relevant to the pathogenesis of angiogenesis-dependent and inflammatory vascular diseases.


Comparative analysis of absorbance calculations for integrated optical waveguide configurations by use of the ray optics model and the electromagnetic wave theory.
Focusing on the use of planar waveguides as platforms for highly sensitive attenuated total reflection spectroscopy of organic thin films, we extend the ray optics model to provide absorbance expressions for the case of dichroic layers immobilized on the waveguide surface. Straightforward expressions are derived for the limiting case of weakly absorbing, anisotropically oriented molecules in the waveguide-cladding region. The second major focus is on the accuracy of the ray optics model. This model assumes that the introduction of absorbing species, either in the bulk cladding or as an adlayer on the waveguide surface, only causes a small perturbation to the original waveguide-mode profile. We investigate the accuracy of this assumption and the conditions under which it is valid. A comparison to an exact calculation by use of the electromagnetic wave theory is implemented, and the discrepancy of the ray optics model is determined for various waveguide configurations. We find that in typical situations in which waveguide-absorbance measurements are used to study organic thin films (k(l)/n(l) <or= (-1), h/lambda approximately (-2)) the discrepancy between the ray optics and the exact calculations is only a few percent (2-3%).


Breastfeeding and Childhood Wheeze: Age-Specific Analyses and Longitudinal Wheezing Phenotypes as Complementary Approaches to the Analysis of Cohort Data.
Systematic reviews suggest that breastfeeding is associated with a lower risk of asthma, although marked heterogeneity exists. Using UK Millennium Cohort Study data (n = 10,126 children, born 2000-2002), we examined the association between breastfeeding duration and wheezing in the previous year, first for each age group separately (ages 9 months, 3 years, 5 years, 7 years, and 11 years) and then in terms of a longitudinal wheezing phenotype: "early transient" (wheezing any time up to age 5 years but not thereafter), "late onset" (any time from age 7 years but not beforehand), and "persistent" (any time up to age 5 years and any time from age 7 years). The association between breastfeeding and wheeze varied by age (2-sided P for interaction = 0.0003). For example, breastfeeding for 6-9 months was associated with lower odds of wheezing at ages 9 months, 3 years, and 5 years but less so at ages 7 years and 11 years (adjusted odds ratios = 0.73, 0.78, 0.79, 0.84, 1.06, respectively). There was a strong dose-response relationship for breastfeeding per month and early transient wheeze (adjusted odds ratio for linear trend = 0.961, 95% confidence interval: 0.942, 0.980) but no clear trend for late-onset or persistent wheeze. Our results identified heterogeneity in the association between breastfeeding and wheezing according to age at wheezing and wheezing phenotype.


Crossed fiber optic Bessel beams for curvilinear optofluidic transport of dielectric particles.
Due to its unique non-diffracting and self-reconstructing nature, Bessel beams have been successfully adopted to trap multiple particles along the beam's axial direction. However, prior bulk-optic based Bessel beams have a fundamental form-factor limitation for in situ, in-vitro, and in-vivo applications. Here we present a novel implementation of Fourier optics along a single strand of hybrid optical fiber in a monolithic manner that can generate pseudo Bessel beam arrays in two-dimensional space. We successfully demonstrate unique optofluidic transport of the trapped dielectric particles along a curvilinear optical route by multiplexing the fiber optic pseudo Bessel beams. The proposed technique can form a new building block to realize reconfigurable optofluidic transportation of particulates that can break the limitations of both prior bulk-optic Bessel beam generation techniques and conventional microfluidic channels.


Outcome of psychological treatments of pathological gambling: a review and meta-analysis.
To investigate the short- and long-term effect of psychological treatments of pathological gambling and factors relating to treatment outcome. This study provides a quantitative meta-analytical review of psychotherapeutic treatments of pathological gambling. Studies were identified by computer search in the PsycINFO and Medline databases covering the period from 1966 to 2004, as well as from relevant reference lists. The target problem was pathological gambling, the treatment was psychological, the study was published in English and outcomes directly pertaining to gambling were employed. Single case studies, studies where elimination of gambling not was the priority and studies with insufficient statistical information were excluded from the present meta-analysis. A total of 37 outcome studies, published or reported between 1968 and 2004, were identified. Of these 15 were excluded, thus 22 studies were included, involving 1434 subjects. The grand mean age was 40.1 years. The overall proportion of men was 71.5%. The included studies were coded for outcome measures of pathological gambling. For each condition, means and standard deviations for gambling-related outcome measures, all based upon self-reports or therapist ratings, were compiled at three points in time: baseline, post-treatment and the last follow-up reported. Effect sizes represent the difference between the mean score in a treatment condition and a control condition or the difference between mean scores at separated points in time for one group, expressed in terms of standard deviation units. At post-treatment the analysis indicated that psychological treatments were more effective than no treatment, yielding an overall effect size of 2.01 (P < 0.01). At follow-up (averaging 17.0 months) the corresponding effect size was 1.59 (P < 0.01). A multiple regression analysis showed that the magnitude of effect sizes at post-treatment were lower in studies including patients with a formal diagnosis of pathological gambling only, compared to studies not employing such inclusion criteria. Effect sizes were also higher in randomized controlled trials compared to not randomized controlled trials, higher in within subjects designs compared to between subjects designs and also positively related to number of therapy sessions. No mediator variables were significantly related to the magnitude of the effect sizes at follow-up. Psychological interventions for pathological gamble seem to be yield very favourable short- and long-term outcomes.


Aging of microplastics promotes their ingestion by marine zooplankton.
Microplastics (<5 mm) are ubiquitous in the marine environment and are ingested by zooplankton with possible negative effects on survival, feeding, and fecundity. The majority of laboratory studies has used new and pristine microplastics to test their impacts, while aging processes such as weathering and biofouling alter the characteristics of plastic particles in the marine environment. We investigated zooplankton ingestion of polystyrene beads (15 and 30 μm) and fragments (≤30 μm), and tested the hypothesis that microplastics previously exposed to marine conditions (aged) are ingested at higher rates than pristine microplastics. Polystyrene beads were aged by soaking in natural local seawater for three weeks. Three zooplankton taxa ingested microplastics, excluding the copepod Pseudocalanus spp., but the proportions of individuals ingesting plastic and the number of particles ingested were taxon and life stage specific and dependent on plastic size. All stages of Calanus finmarchicus ingested polystyrene fragments. Aged microbeads were preferred over pristine ones by females of Acartia longiremis as well as juvenile copepodites CV and adults of Calanus finmarchicus. The preference for aged microplastics may be attributed to the formation of a biofilm. Such a coating, made up of natural microbes, may contain similar prey as the copepods feed on in the water column and secrete chemical exudates that aid chemodetection and thus increase the attractiveness of the particles as food items. Much of the ingested plastic was, however, egested within a short time period (2-4 h) and the survival of adult Calanus females was not affected in an 11-day exposure. Negative effects of microplastics ingestion were thus limited. Our findings emphasize, however, that aging plays an important role in the transformation of microplastics at sea and ingestion by grazers, and should thus be considered in future microplastics ingestion studies and estimates of microplastics transfer into the marine food web.


Evolution of mitotic spindle behavior during the first asymmetric embryonic division of nematodes.
Asymmetric cell division is essential to generate cellular diversity. In many animal cells, the cleavage plane lies perpendicular to the mitotic spindle, and it is the spindle positioning that dictates the size of the daughter cells. Although some properties of spindle positioning are conserved between distantly related model species and different cell types, little is known of the evolutionary robustness of the mechanisms underlying this event. We recorded the first embryonic division of 42 species of nematodes closely related to Caenorhabditis elegans, which is an excellent model system to study the biophysical properties of asymmetric spindle positioning. Our recordings, corresponding to 128 strains from 27 Caenorhabditis and 15 non-Caenorhabditis species (accessible at http://www.ens-lyon.fr/LBMC/NematodeCell/videos/), constitute a powerful collection of subcellular phenotypes to study the evolution of various cellular processes across species. In the present work, we analyzed our collection to the study of asymmetric spindle positioning. Although all the strains underwent an asymmetric first cell division, they exhibited large intra- and inter-species variations in the degree of cell asymmetry and in several parameters controlling spindle movement, including spindle oscillation, elongation, and displacement. Notably, these parameters changed frequently during evolution with no apparent directionality in the species phylogeny, with the exception of spindle transverse oscillations, which were an evolutionary innovation at the base of the Caenorhabditis genus. These changes were also unrelated to evolutionary variations in embryo size. Importantly, spindle elongation, displacement, and oscillation each evolved independently. This finding contrasts starkly with expectations based on C. elegans studies and reveals previously unrecognized evolutionary changes in spindle mechanics. Collectively, these data demonstrate that, while the essential process of asymmetric cell division has been conserved over the course of nematode evolution, the underlying spindle movement parameters can combine in various ways. Like other developmental processes, asymmetric cell division is subject to system drift.


First Report of Rhizoctonia solani AG4 HG-II Infecting Potato Stems in Idaho.
The fungus Rhizoctonia solani is the causal agent of stem canker and black scurf of potato (Solanum tuberosum). R. solani is a species complex consisting of 13 anastomosis groups (AGs) designated AG1 to 13 (2, 3). Stems of potato (cv. Russet Norkotah) with brown lesions were recovered from one field in Kimberley, Idaho, in August 2011. Using previously described methods (3), R. solani was recovered from the symptomatic stems and one representative isolate (J15) was selected for further characterization. Sequencing of the rDNA ITS region of isolate J15 was undertaken as previously described (3) and the resulting rDNA ITS sequence (HE667745) was 99% identical to sequences of other AG4 HG-II isolates in GenBank (AF354072 and AF354074). Pathogenicity of the isolate was determined by conducting the following experiment. Mini-tubers of cv. Santé were planted individually in 1-liter pots containing John Innes Number 3 compost (John Innes Manufacturers Association, Reading, UK). Pots were either inoculated with J15, an isolate of AG3-PT (Rs08), or were not inoculated. Each treatment was replicated four times. Inoculum consisted of five 10-mm-diameter potato dextrose agar plugs, fully colonized by the appropriate isolate, placed in the compost approximately 40 mm above each seed tuber. Pots were held in a controlled environment room at 21°C with 50% relative humidity and watered as required. After 21 days, plants were assessed for disease. No symptoms of the disease were present in non-inoculated plants. In the Rs08 (AG3-PT) inoculated plants, all stems displayed large brown lesions and 20% of the stems had been killed. No stem death was observed in J15 (AG4 HG-II) inoculated plants. However, brown lesions were observed in three of the four J15 (AG4 HG-II) inoculated plants. These lesions were less severe than in plants inoculated with the Rs08(AG3-PT) inoculated plants and were present in 40% of the main stems. In the J15 (AG4 HG-II) inoculated pots, R. solani AG4 HG-II was reisolated from the five symptomatic stems, thereby satisfying Koch's postulates. To our knowledge, this is the first report of AG4 HG-II causing disease on potatoes in Idaho. AG4 has been isolated from potato previously from North Dakota, although the subgroup was not identified (1). The only previous report where AG4 HG-II was specifically determined to cause disease on potato was in Finland, but the isolate could not be maintained and Koch's postulates were not completed (3). The present study shows that AG4 HG-II can cause stem disease in potatoes, although disease does not develop as severely or as consistently as for AG3-PT. However, as demonstrated with isolates of AG2-1 and AG5, even mild stem infection can reduce tuber yield by as much as 12% (4). AG4 HG-II is a pathogen of sugar beet in Idaho, which was grown previously in this field. This history may have contributed to high levels of soilborne inoculum required to produce disease on potato. References: (1) N. C. Gudmestad et al. Page 247 in: J. Vos et al. eds. Effects of Crop Rotation on Potato Production in the Temperate Zones. Kluwer, Dordrecht, Netherlands, 1989. (2) M. J. Lehtonen et al. Agric. Food Sci. 18:223, 2009. (3) J. W. Woodhall et al. Plant Pathol. 56:286, 2007. (4) J. W. Woodhall et al. Plant Pathol. 57:897, 2008.


Comparing Surface and Intramuscular Electromyography for Simultaneous and Proportional Control Based on a Musculoskeletal Model: A Pilot Study.
Simultaneous and proportional control (SPC) of neural-machine interfaces uses magnitudes of smoothed electromyograms (EMG) as control inputs. Though surface EMG (sEMG) electrodes are common for clinical neural-machine interfaces, intramuscular EMG (iEMG) electrodes may be indicated in some circumstances (e.g., for controlling many degrees of freedom). However, differences in signal characteristics between sEMG and iEMG may influence SPC performance. We conducted a pilot study to determine the effect of electrode type (sEMG and iEMG) on real-time task performance with SPC based on a novel 2-degree-of-freedom EMG-driven musculoskeletal model of the wrist and hand. Four able-bodied subjects and one transradial amputee performed a virtual posture matching task with either sEMG or iEMG. There was a trend of better task performance with sEMG than iEMG for both able-bodied and amputee subjects, though the difference was not statistically significant. Thus, while iEMG may permit targeted recording of EMG, its signal characteristics may not be as ideal for SPC as those of sEMG. The tradeoff between recording specificity and signal characteristics is an important consideration for development and clinical implementation of SPC for neural-machine interfaces.


Mental simulation and meaning in life.
Mental simulation, the process of self-projection into alternate temporal, spatial, social, or hypothetical realities is a distinctively human capacity. Numerous lines of research also suggest that the tendency for mental simulation is associated with enhanced meaning. The present research tests this association specifically examining the relationship between two forms of simulation (temporal and spatial) and meaning in life. Study 1 uses neuroimaging to demonstrate that enhanced connectivity in the medial temporal lobe network, a subnetwork of the brain's default network implicated in prospection and retrospection, correlates with self-reported meaning in life. Study 2 demonstrates that experimentally inducing people to think about the past or future versus the present enhances self-reported meaning in life, through the generation of more meaningful events. Study 3 demonstrates that experimentally inducing people to think specifically versus generally about the past or future enhances self-reported meaning in life. Study 4 turns to spatial simulation to demonstrate that experimentally inducing people to think specifically about an alternate spatial location (from the present location) increases meaning derived from this simulation compared to thinking generally about another location or specifically about one's present location. Study 5 demonstrates that experimentally inducing people to think about an alternate spatial location versus one's present location enhances meaning in life, through meaning derived from this simulation. Study 6 demonstrates that simply asking people to imagine completing a measure of meaning in life in an alternate location compared with asking them to do so in their present location enhances reports of meaning. This research sheds light on an important determinant of meaning in life and suggests that undirected mental simulation benefits psychological well-being.