DISSECTION OF STRESS RESPONSE NETWORKS REGULATING MULTIPLE STRESSES IN RICE

Important food crops like rice are constantly exposed to various stresses that can have devastating effect on their survival and productivity. Being sessile, these highly evolved organisms have developed elaborate molecular machineries to sense a mixture of stress signals and elicit a precise response to minimize the damage. However, recent discoveries revealed that the interplay of these stress regulatory and signaling molecules is highly complex and remains largely unknown. In this work, we conducted large scale analysis of differential gene expression using advanced computational methods to dissect regulation of stress response which is at the heart of all molecular changes leading to the observed phenotypic susceptibility. One of the most important stress conditions in terms of loss of productivity is drought. We performed genomic and proteomic analysis of epigenetic and miRNA mechanisms in regulation of drought responsive genes in rice and found subsets of genes with striking properties. Overexpressed genesets included higher number of epigenetic marks, miRNA targets and transcription factors which regulate drought tolerance. On the other hand, underexpressed genesets were poor in above features but were rich in number of metabolic genes with multiple co-expression partners contributing majorly towards drought resistance. Identification and characterization of the patterns exhibited by differentially expressed genes hold key to uncover the synergistic and antagonistic components of the cross talk between stress response mechanisms. We performed meta-analysis on drought and bacterial stresses in rice and Arabidopsis, and identified hundreds of shared genes. We found high level of conservation of gene expression between these stresses. Weighted co-expression network analysis detected two tight clusters of genes made up of master transcription factors and signaling genes showing strikingly opposite expression status. To comprehensively identify the shared stress responsive genes between multiple abiotic and biotic stresses in rice, we performed meta-analyses of microarray studies from seven different abiotic and six biotic stresses separately and found more than thirteen hundred shared stress responsive genes. Various machine learning techniques utilizing these genes classified the stresses into two major classes' namely abiotic and biotic stresses and multiple classes of individual stresses with high accuracy and identified the top genes showing distinct patterns of expression. Functional enrichment and co-expression network analysis revealed the different roles of plant hormones, transcription factors in conserved and non-conserved genesets in regulation of stress response.

Thalamic stimulation for tremor. Subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect

The aim of this study was to investigate the impact of unilateral deep brain stimulation (DBS) of the ventrointermediate (Vim) thalamic nucleus on neuropsychological functioning comparing stimulation-on with stimulation-off conditions. Nine patients [five patients with Parkinson's Disease (PD), two patients with essential tremor (ET) and 2 patients with multiple sclerosis (MS)] underwent comprehensive neuropsychological testing for cognitive functions, including general mental impairment, aphasia, agnosia, executive and constructional abilities, learning, memory, cognitive processing speed and attention as well as depression. The neuropsychological assessments were performed at least 6 months postoperatively (mean 9 months). Testing in the stimulation-on and stimulation-off condition was obtained within a period of 3 to 4 weeks. Unilateral DBS resulted in improvement of tremor in all patients. There were no significant differences between the stimulation-on and the stimulation-off condition with the exception of a decrement of word-recall in the short delay free-recall subtest of the Rey Auditory-Verbal Learning Test (RAVLT). Subgroup analysis indicated that the impairment in word-recall was related to left-sided thalamic stimulation. Our study confirms that chronic unilateral DBS is a safe method with regard to cognitive function. The subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect.

Effect of discharge desynchronization on the size of motor evoked potentials: an analysis

OBJECTIVE: Motor evoked potentials (MEPs) after transcranial magnetic brain stimulation (TMS) are smaller than CMAPs after peripheral nerve stimulation, because desynchronization of the TMS-induced motor neurone discharges occurs (i.e. MEP desynchronization). This desynchronization effect can be eliminated by use of the triple stimulation technique (TST; Brain 121 (1998) 437). The objective of this paper is to study the effect of discharge desynchronization on MEPs by comparing the size of MEP and TST responses. METHODS: MEP and TST responses were obtained in 10 healthy subjects during isometric contractions of the abductor digiti minimi, during voluntary background contractions between 0% and 20% of maximal force, and using 3 different stimulus intensities. Additional data from other normals and from multiple sclerosis (MS) patients were obtained from previous studies. RESULTS: MEPs were smaller than TST responses in all subjects and under all stimulating conditions, confirming the marked influence of desynchronization on MEPs. There was a linear relation between the amplitudes of MEPs vs. TST responses, independent of the degree of voluntary contraction and stimulus intensity. The slope of the regression equation was 0.66 on average, indicating that desynchronization reduced the MEP amplitude on average by one third, with marked inter-individual variations. A similar average proportion was found in MS patients. CONCLUSIONS: The MEP size reduction induced by desynchronization is not influenced by the intensity of TMS and by the level of facilitatory voluntary background contractions. It is similar in healthy subjects and in MS patients, in whom increased desynchronization of central conduction was previously suggested to occur. Thus, the MEP size reduction observed may not parallel the actual amount of desynchronization.

RESILIENT WOMEN, METISTIC SCIENTISTS: A MULTIPLE CASE STUDY OF HOW WOMEN NEGOTIATE THEIR SITUATEDNESS IN SCIENCE FIELDS

The concept of feminist metistic resilience postulates that the voiceless, the marginalized and the minority in societies employ strategies in order to turn tables in their favor. This study presents a qualitative analysis of how women, considered to be the minority, negotiate their situatedness in science fields in order to effect change in their lives or that of the society and why they become successful. By “situatedness,” I refer to the everyday life of women as they live and encounter people, society and culture, especially, the life of women who have transcended the culturally stipulated role of women and are excelling in a male dominated field. The study, in different dimensions, conceptualizes the reason for the fewer number of women in science; looks at how scientific methods and practices inhibit the development of women in science; and, finally, interrogates the question of objectivity in science. It becomes apparent, through feminist metistic resilience, that women become successful when they accept conventional practices in scientific arrangements and structures. They accept the practices by embracing and not questioning structures and arrangements that have shaped the field of science and by shifting shapes and assuming different forms in order to adapt to conditions they encounter. Apart from adapting and shape shifting, the women also become successful through environmental and social influences. My analysis suggests that more women can be encouraged to pursue science when women practicing science begin to question structures and arrangements that have shaped the practice of science over the centuries. The overall findings of the research provide implications for policy makers, educators and feminist researchers.

The effect of demand, tank parameters, and pumping stations on energy use in municipal drinking water distribution systems

Two of the indicators of the UN Millennium Development Goals ensuring environmental sustainability are energy use and per capita carbon dioxide emissions. The increasing urbanization and increasing world population may require increased energy use in order to transport enough safe drinking water to communities. In addition, the increase in water use would result in increased energy consumption, thereby resulting in increased green-house gas emissions that promote global climate change. The study of multiple Municipal Drinking Water Distribution Systems (MDWDSs) that relates various MDWDS aspects--system components and properties--to energy use is strongly desirable. The understanding of the relationship between system aspects and energy use aids in energy-efficient design. In this study, components of a MDWDS, and/or the characteristics associated with the component are termed as MDWDS aspects (hereafter--system aspects). There are many aspects of MDWDSs that affect the energy usage. Three system aspects (1) system-wide water demand, (2) storage tank parameters, and (3) pumping stations were analyzed in this study. The study involved seven MDWDSs to understand the relationship between the above-mentioned system aspects in relation with energy use. A MDWDSs model, EPANET 2.0, was utilized to analyze the seven systems. Six of the systems were real and one was a hypothetical system. The study presented here is unique in its statistical approach using seven municipal water distribution systems. The first system aspect studied was system-wide water demand. The analysis involved analyzing seven systems for the variation of water demand and its impact on energy use. To quantify the effects of water use reduction on energy use in a municipal water distribution system, the seven systems were modeled and the energy usage quantified for various amounts of water conservation. It was found that the effect of water conservation on energy use was linear for all seven systems and that all the average values of all the systems' energy use plotted on the same line with a high R 2 value. From this relationship, it can be ascertained that a 20% reduction in water demand results in approximately a 13% savings in energy use for all seven systems analyzed. This figure might hold true for many similar systems that are dominated by pumping and not gravity driven. The second system aspect analyzed was storage tank(s) parameters. Various tank parameters: (1) tank maximum water levels, (2) tank elevation, and (3) tank diameter were considered in this part of the study. MDWDSs use a significant amount of electrical energy for the pumping of water from low elevations (usually a source) to higher ones (usually storage tanks). The use of electrical energy has an effect on pollution emissions and, therefore, potential global climate change as well. Various values of these tank parameters were modeled on seven MDWDSs of various sizes using a network solver and the energy usage recorded. It was found that when averaged over all seven analyzed systems (1) the reduction of maximum tank water level by 50% results in a 2% energy reduction, (2) energy use for a change in tank elevation is system specific, and (2) a reduction of tank diameter of 50% results in approximately a 7% energy savings. The third system aspect analyzed in this study was pumping station parameters. A pumping station consists of one or more pumps. The seven systems were analyzed to understand the effect of the variation of pump horsepower and the number of booster stations on energy use. It was found that adding booster stations could save energy depending upon the system characteristics. For systems with flat topography, a single main pumping station was found to use less energy. In systems with a higher-elevation neighborhood, however, one or more booster pumps with a reduced main pumping station capacity used less energy. The energy savings for the seven systems was dependent on the number of boosters and ranged from 5% to 66% for the analyzed five systems with higher elevation neighborhoods (S3, S4, S5, S6, and S7). No energy savings was realized for the remaining two flat topography systems, S1, and S2. The present study analyzed and established the relationship between various system aspects and energy use in seven MDWDSs. This aids in estimating the amount of energy savings in MDWDSs. This energy savings would ultimately help reduce Greenhouse gases (GHGs) emissions including per capita CO 2 emissions thereby potentially lowering the global climate change effect. This will in turn contribute to meeting the MDG of ensuring environmental sustainability.

Effect of urinary tract infection on reservoir function in patients with ileal bladder substitute

PURPOSE: We determined the functional consequences of urinary tract infection in patients with an ileal bladder substitute in terms of urinary continence, post-void residual and urinary retention. MATERIALS AND METHODS: A total of 48 patients with culture documented urinary tract infection (single organism, 10(5) or greater cfu) were retrospectively evaluated before, during and after the infection for changes in continence, post-void residual and urinary retention as well as for resolution of symptomatology after appropriate antibiotic therapy. RESULTS: Of the 48 patients 40 had a single infection while the remaining 8 had multiple urinary tract infection episodes. During daytime 27 of the 44 patients with previously good daytime continence experienced deterioration in their baseline voiding status while infected. Of the 40 patients who were previously continent at night 20 had incontinence while infected. There were 15 patients with documented post-void residual and urinary retention developed in 4 during the urinary tract infection. All patients returned to baseline continence status and reservoir function after appropriate antibiotic treatment based on objective and subjective assessments. CONCLUSIONS: Urinary tract infection may cause urinary incontinence in patients with ileal bladder substitutes. Therefore, when there are complaints of de novo urinary incontinence, a finding of post-void residual or an acute presentation of urinary retention, a urinary tract infection should be excluded. When the urinary tract infection is appropriately treated urinary continence and reservoir function return to their baseline status.

Dermatophagoides farinae-specific immunotherapy in atopic dogs with hypersensitivity to multiple allergens: a randomised, double blind, placebo-controlled study

A randomised, placebo-controlled, double blind study was conducted on 25 dogs that had atopic dermatitis, together with skin test reactivity and elevated serum IgE to Dermatophagoides farinae (Df) and at least one additional allergen. Dogs were treated with either a Df-restricted immunotherapy solution (n=14) or a placebo (n=11) and evaluated 6 weeks and 3, 5, 7 and 9 months after the initiation of treatment using a clinical scoring system (SASSAD) and pruritus analogue scale scores. The Df-restricted solution and the placebo had an equal effect on both pruritus and the skin manifestations (P>0.05). The results of this study indicate that in dogs with atopic dermatitis based on hypersensitivity to environmental allergens in addition to D. farinae, Df-restricted immunotherapy is insufficient to control the disease. Consequently, a solution for allergen-specific immunotherapy should remain customised.

Effect of tin-chloride pretreatment on bond strength of two adhesive systems to dentin

OBJECTIVES: To determine the effect on resin composite-to-dentin bond strength of incorporation of an acidic tin-chloride pretreatment in two adhesive systems. MATERIALS AND METHODS: Human molars were ground to expose mid-coronal dentin. For microtensile bond strength (μTBS) testing, dentin was treated with Optibond FL or Clearfil SE according to one of six protocols (n = 22/group). Group 1: Phosphoric acid etching, Optibond FL Prime, Optibond FL Adhesive (manufacturer's instructions; control); Group 2: Tin-chloride pretreatment, Optibond FL Prime, Optibond FL Adhesive; Group 3: Phosphoric acid etching, tin-chloride pretreatment, Optibond FL Prime, Optibond FL Adhesive; Group 4: Clearfil SE Primer, Clearfil SE Bond (manufacturer's instructions; control); Group 5: Phosphoric acid etching, Clearfil SE Primer, Clearfil SE Bond; and Group 6: Tin-chloride pretreatment, Clearfil SE Primer, Clearfil SE Bond. The molars were then built up with resin composite (Clearfil Majesty Esthetic). After storage (1 week, 100  % humidity, 37 °C) the μTBS was measured and failure mode was determined. Additionally, pretreated dentin surfaces were evaluated using SEM and EDX. The μTBS results were analyzed statistically by a Welch Two Sample t-test and a Kruskal-Wallis test followed by exact Wilcoxon rank sum tests with Bonferroni-Holm adjustment for multiple testing (α = 0.05). RESULTS: When Optibond FL was used, partial or total replacement of phosphoric acid with tin-chloride decreased μTBS significantly. In contrast, when Clearfil SE was used, inclusion of a tin-chloride pretreatment in the adhesive procedure increased μTBS significantly. CONCLUSIONS: Tin-chloride pretreatment had a beneficial influence on the bond promoting capacity of the MDP-containing adhesive system Clearfil SE.

Impact of different breathing protocols on multiple-breath washout outcomes in children

BACKGROUND To standardize multiple-breath washout (MBW) measurements, 1L tidal volume (VT) protocols were suggested. The effect on MBW derived ventilation inhomogeneity (VI) indices is unclear. METHODS We compared VI indices from free breathing MBW at baseline to 1L VT MBW performed in triplicates in 35 children (20 with CF). Mean (range) age was 12.8 (7.0-16.7) years, weight 42 (20-64) kg and height 151 (117-170) cm. RESULTS Baseline lung clearance index (LCI) increased from mean (SD) 11.0 (2.2) to 13.0 (2.6), p=0.011, in CF and from 6.8 (0.5) to 7.7 (1.4), p=0.004, in controls. Moment ratio and Scond similarly increased. While change in VI indices was heterogeneous in individuals, decrease in functional residual capacity was most strongly associated with LCI increase. CONCLUSION MBW protocols strongly influence measures of VI. The 1L VT MBW protocol leads to overestimation of VI and is not recommended in children.

Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6)). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval.

The effect of body mass index on therapeutic response to bacterial vaginosis in pregnancy.

Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multicenter trials of therapy for BV and TRICHOMONAS VAGINALIS. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and > or = 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect of BMI on BV persistence at follow-up, adjusting for potential confounders. No association was identified between BMI and BV rate at follow-up ( P = 0.21). BMI was associated with maternal age, smoking, marital status, and black race. Compared with women with BMI of < 25, adjusted odds ratio (OR) of BV at follow-up were BMI 25 to 29.9: OR, 0.66, 95% CI 0.43 to 1.02; BMI > or = 30: OR, 0.83, 95% CI 0.54 to 1.26. We concluded that the persistence of BV after treatment was not related to BMI.

The effect of body mass index on therapeutic response to bacterial vaginosis in pregnancy.

Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multicenter trials of therapy for BV and TRICHOMONAS VAGINALIS. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and > or = 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect of BMI on BV persistence at follow-up, adjusting for potential confounders. No association was identified between BMI and BV rate at follow-up ( P = 0.21). BMI was associated with maternal age, smoking, marital status, and black race. Compared with women with BMI of < 25, adjusted odds ratio (OR) of BV at follow-up were BMI 25 to 29.9: OR, 0.66, 95% CI 0.43 to 1.02; BMI > or = 30: OR, 0.83, 95% CI 0.54 to 1.26. We concluded that the persistence of BV after treatment was not related to BMI.

Magma-Driven Multiple Dike Propagation and Fracture Toughness of Crustal Rocks

Dike swarms consisting of tens to thousands of subparallel dikes are commonly observed at Earth's surface, raising the possibility of simultaneous propagation of two or more dikes at various stages of a swarm's development. The behavior of multiple propagating dikes differs from that of a single dike owing to the interacting stress fields associated with each dike. We analyze an array of parallel, periodically spaced dikes that grow simultaneously from an overpressured source into a semi-infinite, linear elastic host rock. To simplify the analysis, we assume steady state (constant velocity) magma flow and dike propagation. We use a perturbation method to analyze the coupled, nonlinear problem of multiple dike propagation and magma transport. The stress intensity factor at the dike tips and the opening displacements of the dike surfaces are calculated. The numerical results show that dike spacing has a profound effect on the behavior of dike propagation. The stress intensity factors at the tips of parallel dikes decrease with a decrease in dike spacing and are significantly smaller than that for a single dike with the same length. The reduced stress intensity factor indicates that, compared to a single dike, propagation of parallel dikes is more likely to be arrested under otherwise the same conditions. It also implies that fracture toughness of the host rock in a high confining pressure environment may not be as high as inferred from the propagation of a single dike. Our numerical results suggest fracture toughness values on the order of 100 MPa root m. The opening displacements for parallel dikes are smaller than that for a single dike, which results in higher magma pressure gradients in parallel dikes and lower flux of magma transport.

Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis

BACKGROUND Brain-derived neurotrophic factor (BDNF) blocks activation of caspase-3, reduces translocation of apoptosis-inducing factor (AIF), attenuates excitotoxicity of glutamate, and increases antioxidant enzyme activities. The mechanisms of neuroprotection suggest that BDNF may be beneficial in bacterial meningitis. METHODS To assess a potentially beneficial effect of adjuvant treatment with BDNF in bacterial meningitis, 11-day-old infant rats with experimental meningitis due to Streptococcus pneumoniae or group B streptococci (GBS) were randomly assigned to receive intracisternal injections with either BDNF (3 mg/kg) or equal volumes (10 mu L) of saline. Twenty-two hours after infection, brains were analyzed, by histomorphometrical examination, for the extent of cortical and hippocampal neuronal injury. RESULTS Compared with treatment with saline, treatment with BDNF significantly reduced the extent of 3 distinct forms of brain cell injury in this disease model: cortical necrosis in meningitis due to GBS (median, 0.0% [range, 0.0%-33.7%] vs. 21.3% [range, 0.0%-55.3%]; P<.03), caspase-3-dependent cell death in meningitis due to S. pneumoniae (median score, 0.33 [range, 0.0-1.0] vs. 1.10 [0.10-1.56]; P<.05), and caspase-3-independent hippocampal cell death in meningitis due to GBS (median score, 0 [range, 0-2] vs. 0.88 [range, 0-3.25]; P<.02). The last form of injury was associated with nuclear translocation of AIF. CONCLUSION BDNF efficiently reduces multiple forms of neuronal injury in bacterial meningitis and may hold promise as adjunctive therapy for this disease.

Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis

Matrix metalloproteinases (MMPs) are a family of Zn2+-dependent endopeptidases targeting extracellular matrix (ECM) compounds as well as a number of other proteins. Their proteolytic activity acts as an effector mechanism of tissue remodeling in physiologic and pathologic conditions, and as modulator of inflammation. In the context of neuro-inflammatory diseases, MMPs have been implicated in processes such as (a) blood-brain barrier (BBB) and blood-nerve barrier opening, (b) invasion of neural tissue by blood-derived immune cells, (c) shedding of cytokines and cytokine receptors, and (d) direct cellular damage in diseases of the peripheral and central nervous system. This review focuses on the role of MMPs in multiple sclerosis (MS) and bacterial meningitis (BM), two neuro-inflammatory diseases where current therapeutic approaches are insufficient to prevent severe disability in the majority of patients. Inhibition of enzymatic activity may prevent MMP-mediated neuronal damage due to an overactive or deviated immune response in both diseases. Downregulation of MMP release may be the molecular basis for the beneficial effect of IFN-beta and steroids in MS. Instead, synthetic MMP inhibitors offer the possibility to shut off enzymatic activity of already activated MMPs. In animal models of MS and BM, they efficiently attenuated clinical disease symptoms and prevented brain damage due to excessive metalloproteinase activity. However, the required target profile for the therapeutic use of this novel group of compounds in human disease is not yet sufficiently defined and may be different depending on the type and stage of disease. Currently available MMP inhibitors show little target-specificity within the MMP family and may lead to side-effects due to interference with physiological functions of MMPs. Results from human MS and BM indicate that only a restricted number of MMPs specific for each disease is up-regulated. MMP inhibitors with selective target profiles offer the possibility of a more efficient therapy of MS and BM and may enter clinical trials in the near future.