Differential, Stage Dependent Detection of Peptidylarginine Deiminases and Protein Deimination in Lewy Body Diseases-Findings from a Pilot Study

Over 10 million people worldwide live with Parkinson's disease (PD) and 4% of affected people are diagnosed before the age of 50. Research on early PD-related pathways is therefore of considerable importance. Peptidylarginine deiminases (PADs) are a family of calcium-activated enzymes that, through post-translational deimination of arginine to citrulline, contribute to changes in protein function, including in pathological processes. Recent studies have highlighted roles for PADs in a range of neurological disorders including PD, but overall, investigations on PADs in Lewy body disease (LBD), including PD, are still scarce. Hence, the current pilot study aimed at performing an immunohistochemistry screen of post-mortem human brain sections from Braak stages 4-6 from PD patients, as well as patients with incidental LBD (ILBD). We assessed differences in PAD isozyme detection (assessing all five PADs), in total protein deimina-tion/citrullination and histone H3 deimination-which is an indicator of epigenetic changes and extracellular trap formation (ETosis), which can elicit immune responses and has involvement in pathogenic conditions. The findings of our pilot study indicate that PADs and deimination are increased in cingulate cortex and hippocampus, particularly in earlier stages of the disease. PAD2 and PAD3 were the most strongly upregulated PAD isozymes, with some elevation also observed for PAD1, while PAD4 and PAD6 increase was less marked in PD brains. Total protein deimination and histone H3 deimination were furthermore increased in PD brains, with a considerable increase at earlier Braak stages, compared with controls. Our findings point to a significant contribution of PADs, which may further aid early disease biomarker discovery, in PD and other LBDs

Temporal Analysis of Activity Patterns of Editors in Collaborative Mapping Project of OpenStreetMap

In the recent years Wikis have become an attractive platform for social studies of the human behaviour. Containing millions records of edits across the globe, collaborative systems such as Wikipedia have allowed researchers to gain a better understanding of editors participation and their activity patterns. However, contributions made to Geo-wikis_wiki-based collaborative mapping projects_ differ from systems such as Wikipedia in a fundamental way due to spatial dimension of the content that limits the contributors to a set of those who posses local knowledge about a specific area and therefore cross-platform studies and comparisons are required to build a comprehensive image of online open collaboration phenomena. In this work, we study the temporal behavioural pattern of OpenStreetMap editors, a successful example of geo-wiki, for two European capital cities. We categorise different type of temporal patterns and report on the historical trend within a period of 7 years of the project age. We also draw a comparison with the previously observed editing activity patterns of Wikipedia.Comment: Submitte

Detection of Multi-drug Resistant \u3cem\u3eEscherichia coli\u3c/em\u3e in the Urban Waterways of Milwaukee, WI

Urban waterways represent a natural reservoir of antibiotic resistance which may provide a source of transferable genetic elements to human commensal bacteria and pathogens. The objective of this study was to evaluate antibiotic resistance of Escherichia coli isolated from the urban waterways of Milwaukee, WI compared to those from Milwaukee sewage and a clinical setting in Milwaukee. Antibiotics covering 10 different families were utilized to determine the phenotypic antibiotic resistance for all 259 E. coli isolates. All obtained isolates were determined to be multi-drug resistant. The E. coli isolates were also screened for the presence of the genetic determinants of resistance including ermB (macrolide resistance), tet(M) (tetracycline resistance), and β-lactamases (blaOXA, blaSHV, and blaPSE). E. coli from urban waterways showed a greater incidence of antibiotic resistance to 8 of 17 antibiotics tested compared to human derived sources. These E. coli isolates also demonstrated a greater incidence of resistance to higher numbers of antibiotics compared to the human derived isolates. The urban waterways demonstrated a greater abundance of isolates with co-occurrence of antibiotic resistance than human derived sources. When screened for five different antibiotic resistance genes conferring macrolide, tetracycline, and β-lactam resistance, clinical E. coli isolates were more likely to harbor ermB and blaOXA than isolates from urban waterway. These results indicate that Milwaukee’s urban waterways may select or allow for a greater incidence of multiple antibiotic resistance organisms and likely harbor a different antibiotic resistance gene pool than clinical sources. The implications of this study are significant to understanding the presence of resistance in urban freshwater environments by supporting the idea that sediment from urban waterways serves as a reservoir of antibiotic resistance

Asperger’s Syndrome in a Clinical Sample: Reasons for Referral and Comorbidity

Asperger’s Syndrome (AS) is an autism spectrum disorder without mental retardation and language delay. AS often remains unrecognized until these children fail to adapt to school or kindergarten. The comorbid psychiatric disorders, achieving clinical significance, were considered as another pathway to diagnosis. This study is aimed to elucidate the reasons for referral, the frequency and the kinds of comorbidities in a clinical sample of consecutive cases of children and adolescents with AS. To this objective, clinical records of children and adolescents, who have received a DSM-IV diagnosis of AS after multidisciplinary assessment in a given time period were reviewed. After excluding 3 cases due to insufficient information, 24 cases of children and adolescents with Asperger’s Syndrome (23 boys and one girl) were identified. The mean age at the time of assessment and receiving diagnosis was 9.6 yrs. (age range 4 to 17 years). In twenty-one (87%) of the cases the reason for referral was an episode of disorganized behavior following an attempt to enrollthe child at school or kindergarten, and more rare referral occurred within the significant school transition period. In the remaining 3 cases, the reason for referral was a comorbid condition. Comorbid conditions identified at the moment of assessment include: ADHD documented in 4 cases, tics in 3 cases, obsessive-compulsive behaviors in 4 cases, Stereotypic Movement Disorder or Trichotilomania in 4 of the cases. Within the clinical sample, a priori expected to include relatively severe cases, a higher frequency of comorbidity was found as compared to the rates in the general population. Adjustment reactions and comorbidities occasioned the refer

Transient growth in Taylor-Couette flow

Transient growth due to non-normality is investigated for the Taylor-Couette problem with counter-rotating cylinders as a function of aspect ratio eta and Reynolds number Re. For all Re < 500, transient growth is enhanced by curvature, i.e. is greater for eta < 1 than for eta = 1, the plane Couette limit. For fixed Re < 130 it is found that the greatest transient growth is achieved for eta between the Taylor-Couette linear stability boundary, if it exists, and one, while for Re > 130 the greatest transient growth is achieved for eta on the linear stability boundary. Transient growth is shown to be approximately 20% higher near the linear stability boundary at Re = 310, eta = 0.986 than at Re = 310, eta = 1, near the threshold observed for transition in plane Couette flow. The energy in the optimal inputs is primarily meridional; that in the optimal outputs is primarily azimuthal. Pseudospectra are calculated for two contrasting cases. For large curvature, eta = 0.5, the pseudospectra adhere more closely to the spectrum than in a narrow gap case, eta = 0.99

Practical Stability in terms of Two Measures for Impulsive Differential Equations with “Supremum”

The object of investigations is a system of impulsive differential equations with “supremum.” These equations are not widely studied yet, and at the same time they are adequate mathematical model of many real world processes in which the present state depends significantly on its maximal value on a past time interval. Practical stability for a nonlinear system of impulsive differential equations with “supremum” is defined and studied. It is applied Razumikhin method with piecewise continuous scalar Lyapunov functions and comparison results for scalar impulsive differential equations. To unify a variety of stability concepts and to offer a general framework for the investigation of the stability theory, the notion of stability in terms of two measures has been applied to both the given system and the comparison scalar equation. An example illustrates the usefulness of the obtained sufficient conditions

Selenium Biotransformations in an Engineered Aquatic Ecosystem for Bioremediation of Agricultural Wastewater via Brine Shrimp Production

An engineered aquatic ecosystem was specifically designed to bioremediate selenium (Se), occurring as oxidized inorganic selenate from hypersalinized agricultural drainage water while producing brine shrimp enriched in organic Se and omega-3 and omega-6 fatty acids for use in value added nutraceutical food supplements. Selenate was successfully bioremediated by microalgal metabolism into organic Se (seleno-amino acids) and partially removed via gaseous volatile Se formation. Furthermore, filterfeeding brine shrimp that accumulated this organic Se were removed by net harvest. Thriving in this engineered pond system, brine shrimp (Artemia franciscana Kellogg) and brine fly (Ephydridae sp.) have major ecological relevance as important food sources for large populations of waterfowl, breeding, and migratory shore birds. This aquatic ecosystem was an ideal model for study because it mimics trophic interactions in a Se polluted wetland. Inorganic selenate in drainage water was metabolized differently in microalgae, bacteria, and diatoms where it was accumulated and reduced into various inorganic forms (selenite, selenide, or elemental Se) or partially incorporated into organic Se mainly as selenomethionine. Brine shrimp and brine fly larva then bioaccumulated Se from ingesting aquatic microorganisms and further metabolized Se predominately into organic Se forms. Importantly, adult brine flies, which hatched from aquatic larva, bioaccumulated the highest Se concentrations of all organisms tested

Endogenous transforming growth factor β1 suppresses inflammation and promotes survival in adult CNS

Transforming growth factor β1 (TGFβ1) is a pleiotropic cytokine with potent neurotrophic and immunosuppressive properties that is upregulated after injury, but also expressed in the normal nervous system. In the current study, we examined the regulation of TGFβ1 and the effects of TGFβ1 deletion on cellular response in the uninjured adult brain and in the injured and regenerating facial motor nucleus. To avoid lethal autoimmune inflammation within 3 weeks after birth in TGFβ1-deficient mice, this study was performed on a T- and B-cell-deficient RAG2-/- background. Compared with wild-type siblings, homozygous deletion of TGFβ1 resulted in an extensive inflammatory response in otherwise uninjured brain parenchyma. Astrocytes increased in GFAP and CD44 immunoreactivity; microglia showed proliferative activity, expression of phagocytosis-associated markers [αXβ2, B7.2, and MHC1 (major histocompatibility complex type 1)], and reduced branching. Ultrastructural analysis revealed focal blockade of axonal transport, perinodal damming of axonal organelles, focal demyelination, and myelin debris in granule-rich, phagocytic microglia. After facial axotomy, absence of TGFβ1 led to a fourfold increase in neuronal cell death (52 vs 13%), decreased central axonal sprouting, and significant delay in functional recovery. It also interfered with the microglial response, resulting in a diminished expression of early activation markers [ICAM1 (intercellular adhesion molecule 1), α6β1, and αMβ2] and reduced proliferation. In line with axonal and glial findings in the otherwise uninjured CNS, absence of endogenous TGFβ1 also caused an ∼10% reduction in the number of normal motoneurons, pointing to an ongoing and potent trophic role of this anti-inflammatory cytokine in the normal as well as in the injured brain. Copyright © 2007 Society for Neuroscience

A mathematical model and inversion procedure for Magneto-Acousto-Electric Tomography (MAET)

Magneto-Acousto-Electric Tomography (MAET), also known as the Lorentz force or Hall effect tomography, is a novel hybrid modality designed to be a high-resolution alternative to the unstable Electrical Impedance Tomography. In the present paper we analyze existing mathematical models of this method, and propose a general procedure for solving the inverse problem associated with MAET. It consists in applying to the data one of the algorithms of Thermo-Acoustic tomography, followed by solving the Neumann problem for the Laplace equation and the Poisson equation. For the particular case when the region of interest is a cube, we present an explicit series solution resulting in a fast reconstruction algorithm. As we show, both analytically and numerically, MAET is a stable technique yilelding high-resolution images even in the presence of significant noise in the data

Quasilinearization of the Initial Value Problem for Difference Equations with “Maxima”

The object of investigation of the paper is a special type of difference equations containing the maximum value of the unknown function over a past time interval. These equations are adequate models of real processes which present state depends significantly on their maximal value over a past time interval. An algorithm based on the quasilinearization method is suggested to solve approximately the initial value problem for the given difference equation. Every successive approximation of the unknown solution is the unique solution of an appropriately constructed initial value problem for a linear difference equation with “maxima,” and a formula for its explicit form is given. Also, each approximation is a lower/upper solution of the given mixed problem. It is proved the quadratic convergence of the successive approximations. The suggested algorithm is realized as a computer program, and it is applied to an example, illustrating the advantages of the suggested scheme