160 research outputs found
Cognitive Impairment and Magnetic Resonance Imaging Correlates in Primary Progressive Multiple Sclerosis
Objectives: To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data.
Materials and methods: In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes.
Results: We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=-.516 [BVMT-R DR, P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests.
Conclusion: Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction.info:eu-repo/semantics/publishedVersio
Surfactant protein D modulates HIV infection of both T-cells and dendritic cells
Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo
Cognitive impairment and magnetic resonance imaging correlates in primary progressive multiple sclerosis
Objectives: To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data. Materials and methods: In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes. Results: We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=−.516 [BVMT-R DR,
P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests. Conclusion: Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction
Assessment of Surfactant Protein A (SP-A) dependent agglutination
Background: Monomers of the collectin surfactant associated protein-A (SP-A) are arranged in trimers and higher oligomers. The state of oligomerization differs between individuals and likely affects SP-A's functional properties. SP-A can form aggregates together with other SP-A molecules. Here we report and assess a test system for the aggregate forming properties of SP-A in serum and broncho-alveolar lavage samples. Methods: Anti-SP-A antibodies fixed to latex beads bound SP-A at its N-terminal end and allowed the interaction with other SP-A molecules in a given sample by their C-terminal carbohydrate recognition domain (CRD) to agglutinate the beads to aggregates, which were quantified by light microscopy. Results: SP-A aggregation was dependent on its concentration, the presence of calcium, and was dose-dependently inhibited by mannose. Unaffected by the presence of SP-D no aggregation was observed in absence of SP-A. The more complex the oligomeric structure of SP-A present in a particular sample, the better was its capability to induce aggregation at a given total concentration of SP-A. SP-A in serum agglutinated independently of the pulmonary disease; in contrast SP-A in lung lavage fluid was clearly inferior in patients with chronic bronchitis and particularly with cystic fibrosis compared to controls. Conclusions: The functional status of SP-A with respect to its aggregating properties in serum and lavage samples can be easily assessed. SP-A in lung lavage fluid in patients with severe neutrophilic bronchitis was inferior
Performance of Anaerobic Co‑digestion of Pig Slurry with Pineapple (Ananas comosus) Bio‑waste Residues
Agro-food industries produce large amounts of bio-waste, challenging innovative valorisation strategies in the framework of
circular economy principles. Anaerobic digestion technology is an interesting route to stabilise organic matter and produce
biogas as a renewable energy source. This paper aimed to study the optimal performance conditions for anaerobic co-digestion
(AcoD) of pig slurry with pineapple (Ananas comosus) peel bio-waste. The anaerobic digestion (AD) trials were performed
at lab scale, in a continuous stirred reactor, for 16 days’ hydraulic retention time in mesophilic conditions (37 ± 1 °C). Three
hydraulic retention time were performed, one for the reference scenario (
T0) and two for AcoD trials (
T1, T2).
Feeding mixtures
(20:80; v:v) of pineapple peel liquor and pig slurry, with an OLR of 1.46 ± 0.04 g TVS L−
1
reactor day−
1 were used during
AD/AcoD trials, presenting high values for soluble chemical oxygen demand and C/N ratio. This operational conditions
highlight bioenergy recovery up to 0.58 L CH4
g TVSadded
−1, in comparison with that obtained with pig slurry substrate (0.31
L CH4
g VSadded
−1). The AD performance showed a total volatile solids and chemical oxygen demand removal efficiency of
23% to 47% and 26% to 48%, comparing T0
with the average of T1
and T2,
respectively. The digester stability, evaluated by
specific energetic loading rate, was below the limit (0.4 day−1) throughout the trials. Pig slurry co-digestion with pineapple
peel liquor seems to be a promising approach for potential bioenergy recovery.info:eu-repo/semantics/publishedVersio
Inhibiting mycobacterial tryptophan synthase by targeting the inter-subunit interface
Drug discovery efforts against the pathogen Mycobacterium tuberculosis (Mtb) have been advanced through phenotypic screens of extensive compound libraries. Such a screen revealed sulfolane 1 and indoline-5-sulfonamides 2 and 3 as potent inhibitors of mycobacterial growth. Optimization in the sulfolane series led to compound 4, which has proven activity in an in vivo murine model of Mtb infection. Here we identify the target and mode of inhibition of these compounds based on whole genome sequencing of spontaneous resistant mutants, which identified mutations locating to the essential α- and β-subunits of tryptophan synthase. Over-expression studies confirmed tryptophan synthase as the biological target. Biochemical techniques probed the mechanism of inhibition, revealing the mutant enzyme complex incurs a fitness cost but does not prevent inhibitor binding. Mapping of the resistance conferring mutations onto a low-resolution crystal structure of Mtb tryptophan synthase showed they locate to the interface between the α- and β-subunits. The discovery of anti-tubercular agents inhibiting tryptophan synthase highlights the therapeutic potential of this enzyme and draws attention to the prospect of other amino acid biosynthetic pathways as future Mtb drug targets
Relationships Linking Amplification Level to Gene Over-Expression in Gliomas
Background: Gene amplification is thought to promote over-expression of genes favouring tumour development. Because amplified regions are usually megabase-long, amplification often concerns numerous syntenic or non-syntenic genes, among which only a subset is over-expressed. The rationale for these differences remains poorly understood. Methodology/Principal Finding: To address this question, we used quantitative RT-PCR to determine the expression level of a series of co-amplified genes in five xenografted and one fresh human gliomas. These gliomas were chosen because we have previously characterised in detail the genetic content of their amplicons. In all the cases, the amplified sequences lie on extra-chromosomal DNA molecules, as commonly observed in gliomas. We show here that genes transcribed in nonamplified gliomas are over-expressed when amplified, roughly in proportion to their copy number, while non-expressed genes remain inactive. When specific antibodies were available, we also compared protein expression in amplified and nonamplified tumours. We found that protein accumulation barely correlates with the level of mRNA expression in some of these tumours. Conclusions/Significance: Here we show that the tissue-specific pattern of gene expression is maintained upon amplification in gliomas. Our study relies on a single type of tumour and a limited number of cases. However, it strongly suggests that, even when amplified, genes that are normally silent in a given cell type play no role in tumour progression
Fast X-Ray Fluorescence Microtomography of Hydrated Biological Samples
Metals and metalloids play a key role in plant and other biological systems as some of them are essential to living organisms and all can be toxic at high concentrations. It is therefore important to understand how they are accumulated, complexed and transported within plants. In situ imaging of metal distribution at physiological relevant concentrations in highly hydrated biological systems is technically challenging. In the case of roots, this is mainly due to the possibility of artifacts arising during sample preparation such as cross sectioning. Synchrotron x-ray fluorescence microtomography has been used to obtain virtual cross sections of elemental distributions. However, traditionally this technique requires long data acquisition times. This has prohibited its application to highly hydrated biological samples which suffer both radiation damage and dehydration during extended analysis. However, recent advances in fast detectors coupled with powerful data acquisition approaches and suitable sample preparation methods can circumvent this problem. We demonstrate the heightened potential of this technique by imaging the distribution of nickel and zinc in hydrated plant roots. Although 3D tomography was still impeded by radiation damage, we successfully collected 2D tomograms of hydrated plant roots exposed to environmentally relevant metal concentrations for short periods of time. To our knowledge, this is the first published example of the possibilities offered by a new generation of fast fluorescence detectors to investigate metal and metalloid distribution in radiation-sensitive, biological samples
Genetic Co-Occurrence Network across Sequenced Microbes
The phenotype of any organism on earth is, in large part, the consequence of
interplay between numerous gene products encoded in the genome, and such
interplay between gene products affects the evolutionary fate of the genome
itself through the resulting phenotype. In this regard, contemporary genomes
can be used as molecular records that reveal associations of various genes
working in their natural lifestyles. By analyzing thousands of orthologs across
~600 bacterial species, we constructed a map of gene-gene co-occurrence across
much of the sequenced biome. If genes preferentially co-occur in the same
organisms, they were called herein correlogs; in the opposite case, called
anti-correlogs. To quantify correlogy and anti-correlogy, we alleviated the
contribution of indirect correlations between genes by adapting ideas developed
for reverse engineering of transcriptional regulatory networks. Resultant
correlogous associations are highly enriched for physically interacting
proteins and for co-expressed transcripts, clearly differentiating a subgroup
of functionally-obligatory protein interactions from conditional or transient
interactions. Other biochemical and phylogenetic properties were also found to
be reflected in correlogous and anti-correlogous relationships. Additionally,
our study elucidates the global organization of the gene association map, in
which various modules of correlogous genes are strikingly interconnected by
anti-correlogous crosstalk between the modules. We then demonstrate the
effectiveness of such associations along different domains of life and
environmental microbial communities. These phylogenetic profiling approaches
infer functional coupling of genes regardless of mechanistic details, and may
be useful to guide exogenous gene import in synthetic biology.Comment: Supporting information is available at PLoS Computational Biolog
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