BODIL: a molecular modeling environment for structure-function analysis and drug design

BODIL is a molecular modeling environment geared to help the user to quickly identify key features of proteins critical to molecular recognition, especially (1) in drug discovery applications, and (2) to understand the structural basis for function. The program incorporates state-of-the-art graphics, sequence and structural alignment methods, among other capabilities needed in modern structure–function–drug target research. BODIL has a flexible design that allows on-the-fly incorporation of new modules, has intelligent memory management, and fast multi-view graphics. A beta version of BODIL and an accompanying tutorial are available at http://www.abo.fi/fak/mnf/bkf/research/johnson/bodil.html     

Parents' satisfaction with medical and social assistance provided to children with Down syndrome: experience in Estonia

OBJECTIVE: Parents of children with mental or physical disabilities have been assumed to live more stressful lives than other parents, and people with Down syndrome (DS) may get second-rate care because of their diagnosis. The aim of this work is to investigate the extent of parents' satisfaction with medical and social services in Estonia provided for the DS individuals and their families. METHODS: From 1999 to 2001, fifty-nine DS families answered questionnaires in which we inquired about their satisfaction with medical and social assistance. RESULTS: We found that satisfaction with the quality of the information about DS is low, and most of the parents are not satisfied with the social benefits and rehabilitation options. CONCLUSIONS: The DS families need more medical information about this syndrome.The medical staff has to learn more about how to deliver bad news and how to support parents. More work needs to be done in the area of rehabilitation options and social assistance.     

Space-resolved thermal properties of thermoplastics reinforced with carbon nanotubes

Composites comprising biobased poly(lactic acid) (PLA) and polyethylene (Bio-PE) were reinforced with multi-walled carbon nanotubes (MWCNTs). These nanocomposites were analyzed using space-resolved thermal analysis (TA) integrated with atomic force microscopy. The deflection temperature, which indicates thermal-induced expansion and thermal transitions of the composite, was monitored by nanoscale TA (nanoTA) utilizing the displacement of a cantilever in contact with the material. Results were compared to bulk electrical, mechanical and thermal properties. Electrical conductivity was detected at lower MWCNT loadings for PLA than for Bio-PE (at 2.5 vs. 5 mass%). Maximal electrical conductivity of 27 S m^?1 for PLA and 0.7 S m^?1 for Bio-PE-based samples was reached at 10 mass% MWCNT loading. Tensile behavior combined with thermogravimetric analysis indicated strong MWCNT–Bio-PE interactions, in contrast to PLA. The glass transition and melting temperature measured by differential scanning calorimetry (DSC) were not changed by the increase in MWCNT loading. Increased deflection temperature was registered by bulk heat deflection measurements on Bio-PE, but not for PLA. The thermal transitions obtained by nanoTA at the nanoscale were in the same temperature range as the first transitions observed upon temperature ramp in DSC (e.g., glass transition and melt temperatures of PLA and Bio-PE, respectively). Remarkably, thermal expansion was detected by nanoTA for PLA- and Bio-PE-based composites below electrical percolation threshold as well as an increase in PLA softening temperature. Space-resolved nanothermal analysis revealed thermal phenomena that are otherwise overlooked when bulk methods are applied.     

Isotopic Indications of Late Pleistocene and Holocene Paleoenvironmental Changes at Boodie Cave Archaeological Site,Barrow Island,Western Australia

This paper presents the first application of mammal tooth enamel carbonate stable isotope analysis for the purpose of investigating late Pleistocene–early Holocene environmental change in an Australian archaeological context. Stable carbon (δ¹³C) and oxygen (δ¹⁸O) isotope ratios were analyzed from archaeological and modern spectacled hare wallaby (Lagorchestes conspicillatus) and hill kangaroo (Osphranter robustus) tooth enamel carbonates from Boodie Cave on Barrow Island in Western Australia. δ¹⁸O results track the dynamic paleoecological history at Boodie Cave including a clear shift towards increasing aridity preceding the onset of the Last Glacial Maximum and a period of increased humidity in the early to mid-Holocene. Enamel δ¹³C reflects divergent species feeding ecology and may imply a long-term shift toward increasing diversity in vegetation structure. This study contributes new data to the carbonate-isotope record for Australian fauna and demonstrates the significant potential of stable isotope based ecological investigations for tracking paleoenvironment change to inter-strata resolution.     

Determination of beef tallow in lard through a multidimensional off-line non-aqueous reversed phase-argentation LC method coupled to mass spectrometry

The presence of tallow in lard is not easy to determine, due to the similarity of the composition of these two animal fats, which differ mainly in the distribution of fatty acids (FA) in the three positions of the glycerol molecule. The determination of the composition of the triacylglycerol (TAG) fraction of lard, tallow, and their mixtures was investigated by HPLC in combination with atmospheric pressure chemical ionization mass spectrometry (APCI-MS). The presence of tallow in lard was determined through the study of the sn-POP/sn-PPO ratio by multidimensional HPLC. The off-line bidimensional system was attained through the coupling of non-aqueous reversed phase (NARP)-HPLC and silver ion (Ag)-HPLC. The primary column eluate was fractionated and the fraction containing POP/PPO isomers was injected onto the secondary column, allowing the separation of positional isomers, unresolved in the first dimension. Peak assignment was carried out by combining retention data with APCI-MS spectral information. The fatty acid distribution along the glycerol backbone, determined by Ag-HPLC, was confirmed through diglyceride ion ratios derived from APCI-MS analysis. Method validation was carried out in preliminary applications on standard TAGs. The analytical results obtained show that even a 5% addition of tallow to lard modifies the distribution of positional isomers.     

Improved Fire Retardancy of Cellulose Fibres via Deposition of Nitrogen-Modified Biopolyphenols

Driven by concerns over the health and environmental impacts of currently used fire retardants (FRs), recent years have seen strong demand for alternative safer and sustainable bio-based FRs. In this paper, we evaluated the potential of nitrogen-modified biopolyphenols as FRs for cellulosic natural fibres that could be used in low-density cellulose insulations. We describe the preparation and characterisation of nitrogen-modified lignin and tannin containing over 10% nitrogen as well as the treatment of cellulose pulp fibres with combinations of lignin or tannin and adsorption-enhancing retention aids. Combining lignin or tannin with a mixture of commercial bio-based flocculant (cationised tannin) and anionic retention chemical allowed for a nearly fourfold increase in lignin adsorption onto cellulosic pulp. The nitrogen-modified biopolyphenols showed significant improvement in heat release parameters in micro-scale combustion calorimetry (MCC) testing compared with their unmodified counterparts. Moreover, the adsorption of nitrogen-modified lignin or tannin onto cellulose fibres decreased the maximum heat release rate and total heat release compared with cellulose reference by 15–23%. A further positive finding was that the temperature at the peak heat release rate did not change. These results show the potential of nitrogen-modified biopolyphenols to improve fire-retarding properties of cellulosic products.     

Chemical profiles of birch and alder bark by ambient mass spectrometry

Desorption atmospheric pressure photoionization (DAPPI) is an ambient mass spectrometry (MS) technique that allows the analysis of both polar and nonpolar compounds directly from the surfaces of various sample types. Here, DAPPI was used to study the chemical profiles in different parts of birch and alder tree barks. Four distinct fractions of Betula pendula (silver birch) bark were collected from three different developmental stages of the stem, after which the chemical profiles of the different tissue types were measured. Of special interest were triterpenoids, a class of important defensive substances, which are found in the bark of the silver birch. Additionally, the chemical profiles of lenticels and the surrounding surfaces in the phellem of B. pendula (silver birch), Alnus glutinosa (black alder), and Alnus incana (gray alder) were screened with DAPPI. Another ambient MS technique, laser ablation atmospheric pressure photoionization (LAAPPI), was further used for the mass spectrometry imaging of lenticels on the B. pendula phellem. All the studied birch bark fractions showed individual chemical profiles in DAPPI. The mass spectra from the young apical stem and the transition zone resembled each other more than the mature stem. Instead, the phellem was found to contain a high amount of triterpenoids in all the developmental stages of the stem. The most intense peaks in the DAPPI mass spectra of the birch bark fractions were those of betulin and lupeol. Betulinic and betulonic acid peaks were intense as well, and these compounds were detected especially in the lenticels of the tree samples.

Graphical abstract

     

Feasibility of SU-8-based capillary electrophoresis-electrospray ionization mass spectrometry microfluidic chips for the analysis of human cell lysates

Monolithically integrated, polymer (SU-8) microchips comprising an electrophoretic separation unit, a sheath flow interface and an ESI emitter were developed to improve the speed and throughput of proteomics analyses. Validation of the microchip method was performed based on peptide mass fingerprinting and single peptide sequencing of selected protein standards. Rapid, yet reliable identification of four biologically important proteins (cytochrome C, β-lactoglobulin, ovalbumin and BSA) confirmed the applicability of the SU-8 microchips to ambitious proteomic applications and allowed their use in the analysis of human muscle cell lysates. The characteristic tryptic peptides were easily separated with plate numbers approaching 10(6), and with peak widths at half height as low as 0.6 s. The on-chip sheath flow interface was also exploited to the introduction of an internal mass calibrant along with the sheath liquid which enabled accurate mass measurements by high-resolution Q-TOF MS. Additionally, peptide structural characterization and protein identification based on MS/MS fragmentation data of a single tryptic peptide was obtained using an ion trap instrument. Protein sequence coverages exceeding 50% were routinely obtained without any pretreatment of the proteolytic samples and a typical total analysis time from sampling to detection was well below ten minutes. In conclusion, monolithically integrated, dead-volume-free, SU-8 microchips proved to be a promising platform for fast and reliable analysis of complex proteomic samples. Good analytical performance of the microchips was shown by performing both peptide mass fingerprinting of complex cell lysates and protein identification based on single peptide sequencing.     

Novel water-soluble quaternary piperazine derivatives of chitosan: synthesis and characterization

Novel synthesis methods for the preparation of quaternary piperazine derivatives of chitosan were developed. Quaternary ammonium moiety can be selectively inserted into either one or both of the piperazine nitrogens, yielding structurally uniform chitosan derivative structures. Water-soluble end products were thoroughly characterized with FT-IR, 1H NMR, 13C NMR and 2D 1H-13C HSQC NMR. The molecular weights of the end products were determined by GPC with triple detection.