Hyalohyphomycosis caused byPaecilomyces variotii: a case report,animal pathogenicity and ‘in vitro’ sensitivity

A case of cutaneous infection in a 25-year-old male caused byPaecilomyces variotii is described. Animal pathogenicity studies with normal and cortisone-treated mice revealed the predeliction ofP. variotii for skin and liver in both normal and cortisone-treated mice and for lungs and heart only in immunosuppressed mice. 5-fluorocytosine gave the best MIC value forP. variotii in vitro. This report documents for the first time thatP. variotii causes cutaneous infection.     

Molecular docking and dynamic simulations of benzimidazoles with beta-tubulins

It is of interest to document the molecular docking and dynamic simulations of benzimidazoles with beta-tubulins in the context of anthelmintic activity. We document the compound BI-02 (2-(3,4-dimethyl phenyl)-1H-1,3-benzimidazole (BI-02) with optimal bindig features compared to the standard molecule albendazole (7.0 Kcal/mol) with binding energy -8.50 Kcal/mol and _PIC₅₀ value 583.62 nM.     

A revised indirect estimate of mutation rates in Amerindians

We have previously raised the possibility that the mutation rate resulting in rare electrophoretic variants is higher in tribal/tropical-dwelling/nonindustrialized societies than in civilized/temperate-dwelling/industrialized societies. Here, we report the results of examining 11 additional proteins for the occurrence of rare electrophoretic variants in 10 Amerindian tribes, for a total of 8,968 determinations and a total of 17,648 locus tests. When these data are combined with the results of all our previous similar studies of Amerindians, a total of 272,298 polypeptides, the products of 43 different loci, have been examined for the occurrence of rare electrophoretic variants. On the assumption that these variants are maintained by mutation pressure and are essentially neutral in their phenotypic effects, we have calculated by three different approaches that it requires an average mutation rate of 1.3 X 10(-5)/locus per generation to maintain the observed variant frequency. Concurrently, we are reporting elsewhere that a direct estimate of the mutation rate resulting in electromorphs in various studies of civilized industrialized populations is 0.3 X 10(-5)/locus per generation. Although this difference appears to have statistical significance, the nonquantifiable uncertainties to both approaches are such that our enthusiasm for a true difference in mutation rates between the two types of populations has diminished. However, even the lower of these estimates, when corrected for all the types of genetic variation that electrophoresis does not detect, implies total locus and gametic mutation rates well above those which in the past have dominated genetic thinking.     

Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism

Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1±0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80±0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine.     

Cutaneous phaeohyphomycosis caused byPhialophora richardsiae and the effect of topical clotrimazole in its treatment

A 15 year-old girl and her 50-year-old mother from Jabalpur, India, were found to have phaeohyphomycotic skin lesions due toPhialophora richardsiae. Among the antimycotics testedin vitro, clotrimazole was found to be most active. Topical application of clotrimazole cream cured the lesions completely.     

A simple method to separate base population and segregation effects in genomic relationship matrices

Background

Genomic selection and estimation of genomic breeding values (GBV) are widely used in cattle and plant breeding. Several studies have attempted to detect population subdivision by investigating the structure of the genomic relationship matrix G. However, the question of how these effects influence GBV estimation using genomic best linear unbiased prediction (GBLUP) has received little attention.

Methods

We propose a simple method to decompose G into two independent covariance matrices, one describing the covariance that results from systematic differences in allele frequencies between groups at the pedigree base (G_A^*) and the other describing genomic relationships (G_S) corrected for these differences. Using this decomposition and F_st statistics, we examined whether observed genetic distances between genotyped subgroups within populations resulted from the heterogeneous genetic structure present at the base of the pedigree and/or from breed divergence. Using this decomposition, we tested three models in a forward prediction validation scenario on six traits using Brown Swiss and dual-purpose Fleckvieh cattle data. Model 0 (M0) used both components and is equivalent to the model using the standard G-matrix. Model 1 (M1) used G_S only and model 2 (M2), an extension of M1, included a fixed genetic group effect. Moreover, we analyzed the matrix of contributions of each base group (Q) and estimated the effects and prediction errors of each base group using M0 and M1.

Results

The proposed decomposition of G helped to examine the relative importance of the effects of base groups and segregation in a given population. We found significant differences between the effects of base groups for each breed. In forward prediction, differences between models in terms of validation reliability of estimated direct genomic values were small but predictive power was consistently lowest for M1. The relative advantage of M0 or M2 in prediction depended on breed, trait and genetic composition of the validation group. Our approach presents a general analogy with the use of genetic groups in conventional animal models and provides proof that standard GBLUP using G yields solutions equivalent to M0, where base groups are considered as correlated random effects within the additive genetic variance assigned to the genetic base.     

Molecular simulation of Tyr105 phosphorylated pyruvate kinase M2 to understand its structure and dynamics

Microstructure of dibenzo-18-crown-6 (DB18C6) and DB18C6/Li⁺ complex in different solvents (water, methanol, chloroform, and nitrobenzene) have been analyzed using radial distribution function (RDF), coordination number (CN), and orientation profiles, in order to identify the role of solvents on complexation of DB18C6 with Li⁺, using molecular dynamics (MD) simulations. In contrast to aqueous solution of LiCl, no clear solvation pattern is found around Li⁺ in the presence of DB18C6. The effect of DB18C6 has been visualized in terms of reduction in peak height and shift in peak positions of g_Li-Ow. The appearance of damped oscillations in velocity autocorrelation function (VACF) of complexed Li⁺ described the high frequency motion to a “rattling” of the ion in the cage of DB18C6. The solvent-complex interaction is found to be higher for water and methanol due to hydrogen bond (HB) interactions with DB18C6. However, the stability of DB18C6/Li⁺ complex is found to be almost similar for each solvent due to weak complex-solvent interactions. Further, Li⁺ complex of DB18C6 at the liquid/liquid interface of two immiscible solvents confirm the high interfacial activity of DB18C6 and DB18C6/Li⁺ complex. The complexed Li⁺ shows higher affinity for water than organic solvents; still they remain at the interface rather than migrating toward water due to higher surface tension of water as compared to organic solvents. These simulation results shed light on the role of counter-ions and spatial orientation of species in pure and hybrid solvents in the complexation of DB18C6 with Li⁺. Graphical Abstract

DB18C6/Li⁺ complex in pure solvents (water, methanol, chloroform, and nitrobenzene) and water/nitrobenzene interface     

Iron uptake and transport by the carboxymycobactin-mycobactin siderophore machinery of Mycobacterium tuberculosis is dependent on the iron-regulated protein HupB

BioMetals - Iron-starved Mycobacterium tuberculosis utilises the carboxymycobactin-mycobactin siderophore machinery to acquire iron. These two siderophores have high affinity for ferric iron and...     

Reference genes for quantitative reverse transcription-polymerase chain reaction expression studies in wild and cultivated peanut

Background

Molecular genetic studies on rare tumour entities, such as bone tumours, often require the use of decalcified, formalin-fixed, paraffin-embedded tissue (dFFPE) samples. Regardless of which decalcification procedure is used, this introduces a vast breakdown of DNA that precludes the possibility of further molecular genetic testing. We set out to establish a robust protocol that would overcome these intrinsic hurdles for bone tumour research.

Findings

The goal of our study was to establish a protocol, using a modified DNA isolation procedure and quality controls, to select decalcified samples suitable for array-CGH testing. Archival paraffin blocks were obtained from 9 different pathology departments throughout Europe, using different fixation, embedding and decalcification procedures, in order to preclude a bias for certain lab protocols. Isolated DNA samples were subjected to direct chemical labelling and enzymatic labelling systems and were hybridised on a high resolution oligonucleotide chip containing 44,000 reporter elements. Genomic alterations (gains and losses) were readily detected in most of the samples analysed. For example, both homozygous deletions of 0.6 Mb and high level of amplifications of 0.7 Mb were identified.

Conclusions

We established a robust protocol for molecular genetic testing of dFFPE derived DNA, irrespective of fixation, decalcification or sample type used. This approach may greatly facilitate further genetic testing on rare tumour entities where archival decalcified, formalin fixed samples are the only source.     

Stereo-selectivity of human serum albumin to enantiomeric and isoelectronic pollutants dissected by spectroscopy, calorimetry and bioinformatics

1-naphthol (1N), 2-naphthol (2N) and 8-quinolinol (8H) are general water pollutants. 1N and 2N are the configurational enantiomers and 8H is isoelectronic to 1N and 2N. These pollutants when ingested are transported in the blood by proteins like human serum albumin (HSA). Binding of these pollutants to HSA has been explored to elucidate the specific selectivity of molecular recognition by this multiligand binding protein. The association constants (K(b)) of these pollutants to HSA were moderate (10(4)-10(5) M(-1)). The proximity of the ligands to HSA is also revealed by their average binding distance, r, which is estimated to be in the range of 4.39-5.37 nm. The binding free energy (ΔG) in each case remains effectively the same for each site because of enthalpy-entropy compensation (EEC). The difference observed between ΔC(p) (exp) and ΔC(p) (calc) are suggested to be caused by binding-induced flexibility changes in the HSA. Efforts are also made to elaborate the differences observed in binding isotherms obtained through multiple approaches of calorimetry, spectroscopy and bioinformatics. We suggest that difference in dissociation constants of pollutants by calorimetry, spectroscopic and computational approaches could correspond to occurrence of different set of populations of pollutants having different molecular characteristics in ground state and excited state. Furthermore, our observation of enhanced binding of pollutants (2N and 8H) in the presence of hemin signifies that ligands like hemin may enhance the storage period of these pollutants in blood that may even facilitate the ill effects of these pollutants.