Chemical Synthesis of 4-Trifluoromethylumbelliferyl-α-d-N-acetylneuraminic Acid Glycoside and Its Use for the Fluorometric Detection of Poorly Expressed Natural and Recombinant Sialidases

When compared to bacterial or viral sialidases, eukaryotic sialidases are expressed at lower levels and frequently show poor specific activities. The identification and characterization of sialidases from eukaryotes have been slowed down due to the limited sensitivity of available sialidase substrates. Therefore, we chemically synthesized a fluorogenic compound, 4-trifluoromethylumbelliferyl-α-d-N-acetylneuraminic acid (CF₃MU-Neu5Ac), and tested its use as a substrate for eight different sialidases, including enzymes from viral, bacterial, and eukaryotic sources. Kinetic analysis revealed CF₃MU-Neu5Ac to be a very sensitive sialidase substrate. Furthermore, this substance proves to be perfectly suitable for thein vivoexamination of sialidases and for the detection of recombinant sialidase by means of expression cloning.     

Autosomal dominant spastic paraplegia with anticipation maps to a 4-cM interval on chromosome 2p21-p24 in a large German family

Autosomal dominant familial spastic paraplegias (AD-FSP) are a group of genetically heterogeneous diseases characterised by a progressive spasticity of the lower limbs. Three loci have already been identified by genetic linkage studies on chromosomes 2p, 14q and 15q. Here we present linkage data from a large German family displaying AD-FSP with anticipation which confirms the existence of the FSP2 locus on chromosome 2p. The recombination events observed in our family define the critical region for the FSP2 gene to be within a 4-cM interval, flanked by markers D2S400 and D2S367. Moreover, clinical data from our family show evidence of anticipation, a phenomenon caused by trinucleotide expansion in several other neurodegenerative diseases. Received: 6 April 1996 / Revised: 22 April 1996     

Latent Class Analysis: Insights about design and analysis of schistosomiasis diagnostic studies

Various global health initiatives are currently advocating the elimination of schistosomiasis within the next decade. Schistosomiasis is a highly debilitating tropical infectious disease with severe burden of morbidity and thus operational research accurately evaluating diagnostics that quantify the epidemic status for guiding effective strategies is essential. Latent class models (LCMs) have been generally considered in epidemiology and in particular in recent schistosomiasis diagnostic studies as a flexible tool for evaluating diagnostics because assessing the true infection status (via a gold standard) is not possible. However, within the biostatistics literature, classical LCM have already been criticised for real-life problems under violation of the conditional independence (CI) assumption and when applied to a small number of diagnostics (i.e. most often 3-5 diagnostic tests). Solutions of relaxing the CI assumption and accounting for zero-inflation, as well as collecting partial gold standard information, have been proposed, offering the potential for more robust model estimates. In the current article, we examined such approaches in the context of schistosomiasis via analysis of two real datasets and extensive simulation studies. Our main conclusions highlighted poor model fit in low prevalence settings and the necessity of collecting partial gold standard information in such settings in order to improve the accuracy and reduce bias of sensitivity and specificity estimates.     

Current progress in Striga management

The Striga, particularly S. he rmonthica, problem has become a major threat to food security, exacerbating hunger and poverty in many African countries. A number of Striga control strategies have been proposed and tested during the past decade, however, further research efforts are still needed to provide sustainable and effective solutions to the Striga problem. In this paper, we provide an update on the recent progress and the approaches used in Striga management, and highlight emerging opportunities for developing new technologies to control this enigmatic parasite.

Advances

• The recently established Striga control technologies, such as push-pull, toothpick, and imidazolinone seed dressing have opened up new opportunities for smallholder farmers to overcome this parasite.
• The development of low-cost and efficient germination stimulants together with an application protocol for rain-fed agriculture has made the suicidal germination strategy a realistic approach.
• Molecular elucidation of strigolactone biosynthesis and perception has led to the development of new chemicals that disrupt the communication between Striga and its hosts.

     

Modification of cellulosic fiber with polyurethane acrylate copolymers. Part I: Physicochemical properties

Polyurethane (PU) prepolymers were prepared by using two different diisocyanates i.e., toluene-2,4-diisocyanate (TDI) and or isophorone diisocyanate (IPDI), and poly (2-methyl-1,3-propylene glutarate), hydroxyl terminated group. PU prepolymer was reacted with 2-hydroxyethylacrylate (HEA) to form vinyl terminated PU prepolymer. Vinyl terminated PU prepolymers were further copolymerized with butyl acrylates (BuA) by emulsion process. The structure of proposed PUACs samples was confirmed by FT-IR, and their physicochemical properties were studied determining solid contents (%), emulsion stability and its appearance, tackiness and film appearance. Their acids and base chemical resistance was also studied and discussed. The synthesized PUACs samples were applied using dip-padding techniques on mill un-desized poly-cotton plain weave fabrics. The results emphasis that PUACs based on toluene-2,4-diisocyanate (TDI) have shown excellent performance against physical and chemical resistance as compared to isophorone diisocyanate (IPDI) based PUACs, however vice versa results were found in some studies.     

Local delivery of simvastatin maintains tooth anchorage during mechanical tooth moving via anti-inflammation property and AMPK/MAPK/NF-kB inhibition

Simvastatin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM). However, previous studies on its bone-specific anabolic and anti-inflammation properties were based on static in vitro and in vivo conditions. AMPK is a stress-activated kinase that protects tissue against serious damage from overloading inflammation. Rat periodontal ligament cells (PDLCs) were subjected to a serial of SMV concentrations to investigate the optimization that promoted osteogenic differentiation. The PDLCs in static and/or tensile culturing conditions then received the proper concentration SMV. Related factors expression was measured by the protein array, real-time PCR and Western blot. The 0.05UM SMV triggered osteogenic differentiation of PDLCs. The inhibition of AMPK activation through a pharmacological approach (Compound C) caused dramatic decrease in osteogenic/angiogenic gene expression and significant increase in inflammatory NF-κB phosphorylation. In contrast, pharmacological activation of AMPK by AICAR significantly inhibited inflammatory factors expression and activated ERK1/2, P38 MAPK phosphorylation. Moreover, AMPK activation induced by SMV delivery significantly attenuated the osteoclastogenesis and decreased the expression of pro-inflammatory TNF-α and NF-κB in a rodent model of OTM. The current studies suggested that SMV could intrigue intrinsic activation of AMPK in PDLCs that promote attenuate the inflammation which occurred under tensile irritation through AMPK/MAPK/NF-kB Inhibition.     

The evolution of Dianthus polylepis complex (Caryophyllaceae) inferred from morphological and nuclear DNA sequence data: one or two species?

Dianthus polylepis complex consists of two already known endemic species, Dianthus polylepis and D. binaludensis, in Khorassan-Kopetdagh floristic province. The taxonomic position of these species has long been debated. The aim of the present study is to shed light on the evolutionary relationships of the members of the complex using morphological and molecular data. In morphological study, firstly, 56 vegetative and floral characters were measured on 33 specimens of the both species. Multivariate analyses were performed on 25 (out of 56) significantly discriminating morphological traits. In molecular study, we sequenced alleles obtained from a region between 2nd and 6th exons of the gene coding for the enzyme dihydroflavonol 4-reductase copy1 (DFR1). Morphological results show that most of a priori identified accessions were not grouped in a posteriori classification. It is difficult to discriminate D. polylepis from D. binaludensis in morphological continuum among the accessions. Results obtained from the molecular data indicated no monophyly for the members of the D. polylepis complex. Consistency between the morphological and molecular results shows that D. polylepis and D. binaludensis were not morphologically and molecularly well differentiated. Therefore, we propose a new combination as D. polylepis subsp. binaludensis.     

Multiply accelerated ReaxFF molecular dynamics: coupling parallel replica dynamics with collective variable hyper dynamics

ABSTRACT

To tackle the time scales required to study complex chemical reactions, methods performing accelerated molecular dynamics are necessary even with the recent advancement in high-performance computing. A number of different acceleration techniques are available. Here we explore potential synergies between two popular acceleration methods – Parallel Replica Dynamics (PRD) and Collective Variable Hyperdynamics (CVHD), by analysing the speedup obtained for the pyrolysis of n-dodecane. We observe that PRD?+?CVHD provides additional speedup to CVHD by reaching the required time scales for the reaction at an earlier wall-clock time. Although some speedup is obtained with the additional replicas, we found that the effectiveness of the inclusion of PRD is depreciated for systems where there is a dramatic increase in reaction rates induced by CVHD. Similar observations were made in the simulation of ethylene-carbonate/Li system, which is inherently more reactive than pyrolysis, indicate that the speedup obtained via the combination of the two acceleration methods can be generalised to most practical chemical systems.