Cutting the Gordian Knot: Phylogenetic and ecological diversification of the Mesalina brevirostris species complex (Squamata,Lacertidae)

Mesalina are small lacertid lizards occurring in the Saharo‐Sindian deserts from North Africa to the east of the Iranian plateau. Earlier phylogenetic studies indicated that there are several species complexes within the genus and that thorough taxonomic revisions are needed. In this study, we aim at resolving the phylogeny and taxonomy of the M. brevirostris species complex distributed from the Middle East to the Arabian/Persian Gulf region and Pakistan. We sequenced three mitochondrial and three nuclear gene fragments, and in combination with species delimitation and species‐tree estimation, we infer a time‐calibrated phylogeny of the complex. The results of the genetic analyses support the presence of four clearly delimited species in the complex that diverged approximately between the middle Pliocene and the Pliocene/Pleistocene boundary. Species distribution models of the four species show that the areas of suitable habitat are geographically well delineated and nearly allopatric, and that most of the species have rather divergent environmental niches. Morphological characters also confirm the differences between the species, although sometimes minute. As a result of all these lines of evidence, we revise the taxonomy of the Mesalina brevirostris species complex. We designate a lectotype for Mesalina brevirostris Blanford, 1874; resurrect the available name Eremias bernoullii Schenkel, 1901 from the synonymy of M. brevirostris; elevate M. brevirostris microlepis (Angel, 1936) to species status; and describe Mesalina saudiarabica, a new species from Saudi Arabia.     

Construction of a risk model through the fusion of experimental data and finite element modeling: Application to car crash-induced TBI

This article introduces a new approach for the construction of a risk model for the prediction of Traumatic Brain Injury (TBI) as a result of a car crash. The probability of TBI is assessed through the fusion of an experiment-based logistic regression risk model and a finite element (FE) simulation-based risk model. The proposed approach uses a multilevel framework which includes FE simulations of vehicle crashes with dummy and FE simulations of the human brain. The loading conditions derived from the crash simulations are transferred to the brain model thus allowing the calculation of injury metrics such as the Cumulative Strain Damage Measure (CSDM). The framework is used to propagate uncertainties and obtain probabilities of TBI based on the CSDM injury metric. The risk model from FE simulations is constructed from a support vector machine classifier, adaptive sampling, and Monte-Carlo simulations. An approach to compute the total probability of TBI, which combines the FE-based risk assessment as well as the risk prediction from the experiment-based logistic regression model is proposed. In contrast to previous published work, the proposed methodology includes the uncertainty of explicit parameters such as impact conditions (e.g., velocity, impact angle), and material properties of the brain model. This risk model can provide, for instance, the probability of TBI for a given assumed crash impact velocity.     

Activation of α1A-adrenergic receptor promotes differentiation of rat-1 fibroblasts to a smooth muscle-like phenotype

Background  

Fibroblasts, as connective tissue cells, are able to transform into another cell type including smooth muscle cells. α_1A-adrenergic receptor (α_1A-AR) stimulation in rat-1 fibroblasts is coupled to cAMP production. However, the significance of an increase in cAMP produced by α_1A-AR stimulation on proliferation, hypertrophy and differentiation in these cells is not known.     

Genetic variability of NaCl tolerance in tomato

Cultivation of crops in soils with high salt (NaCl) content can affect plant development. We examined the morphological and physiological mechanisms of salt tolerance in tomato. The responses of 72 accessions of tomato (Solanum lycopersicum) to salinity were compared by measuring shoot and root lengths, and fresh shoot and root weights relative to those of controls (plants grown in normal salt levels). All traits were reduced at the seedling stage when salinity levels were increased. The accession x salinity interaction was significant for all traits. Root length had higher heritability than other traits and was used as a selection criterion to identify salt-tolerant and -non-tolerant accessions. On the basis of root length, accessions LA2661, CLN2498A, CLN1621L, BL1176, 6233, and 17870 were considered to be more tolerant than accessions 17902, LO2875 and LO4360. The degree of salt tolerance was checked by analyzing K+ and Na+ concentrations and K+/Na+ ratio in tissues of plants treated with 10 and 15 dS/m salinity levels. Tolerance of these accessions to salinity was most associated with low accumulation of Na+ and higher K+/Na+ ratios.     

Regulation of expression of fibroblast growth factor 7 in the pig uterus by progesterone and estradiol

Fibroblast growth factor 7 (FGF7) stimulates cell proliferation, differentiation, migration and angiogenesis. The consensus is that FGF7, expressed by mesenchymal cells, binds FGF receptor 2IIIb (FGFR2) on epithelia, thereby mediating epithelial-mesenchymal interactions. The pig uterus is unique in that FGF7 is expressed by the luminal epithelium (LE) and FGFR2 is expressed by the LE, glandular epithelium (GE), and trophectoderm to effect proliferation and differentiated cell functions during conceptus development and implantation. FGF7 expression by the uterine LE of pigs increases between Days 9 and 12 of the estrus cycle and pregnancy, as circulating concentrations of progesterone increase, progesterone receptors (PGR) in the uterine epithelia decrease, and the conceptuses secrete estradiol-17beta (E(2)), for pregnancy recognition. Furthermore, E(2) increases the expression of FGF7 in pig uterine explants. The present study investigates the relationships between progesterone, E(2), and their receptors and the expression of FGF7 in the pig uterus in vivo. Pigs were ovariectomized on Day 4 of the estrus cycle and injected i.m. daily from Day 4 to Day 12 with either corn oil (CO), progesterone (P4), P4 and ZK317,316 (PZK), E(2), P4 and E(2) (PE), or P4 and ZK and E(2) (PZKE). All gilts (n = 5/treatment) were hysterectomized on Day 12. The results suggest that: 1) P4 is permissive to FGF7 expression by down-regulating PGR in LE; 2) P4 stimulates PGR-positive uterine stromal cells to release an unidentified progestamedin that induces FGF7 expression by LE; 3) E(2) and P4 can induce FGF7 when PGR are rendered nonfunctional by ZK; and 4) E(2) from conceptuses interacts via estrogen receptor alpha, but not estrogen receptor beta in LE to induce maximal expression of FGF7 in LE on Day 12 of pregnancy in pigs.     

Multiple-locus variable-number tandem repeat analysis of Salmonella Enteritidis isolates from human and non-human sources using a single multiplex PCR

Simplified multiple-locus variable-number tandem repeat analysis (MLVA) was developed using one-shot multiplex PCR for seven variable-number tandem repeats (VNTR) markers with high diversity capacity. MLVA, phage typing, and PFGE methods were applied on 34 diverse Salmonella Enteritidis isolates from human and non-human sources. MLVA detected allelic variations that helped to classify the S. Enteritidis isolates into more evenly distributed subtypes than other methods. MLVA-based S. Enteritidis clonal groups were largely associated with sources of the isolates. Nei's diversity indices for polymorphism ranged from 0.25 to 0.70 for seven VNTR loci markers. Based on Simpson's and Shannon's diversity indices, MLVA had a higher discriminatory power than pulsed field gel electrophoresis (PFGE), phage typing, or multilocus enzyme electrophoresis. Therefore, MLVA may be used along with PFGE to enhance the effectiveness of the molecular epidemiologic investigation of S. Enteritidis infections.     

A numerical study on hemodynamics in the left coronary bifurcation with normal and hypertension conditions

In this study, a three-dimensional analysis of the non-Newtonian blood flow was carried out in the left coronary bifurcation. The Casson model and hyperelastic and rigid models were used as the constitutive equation for blood flow and vessel wall model, respectively. Physiological conditions were considered first normal and then compliant with hypertension disease with the aim of evaluating hemodynamic parameters and a better understanding of the onset and progression of atherosclerosis plaques in the coronary artery bifurcation. Two-way fluid–structure interaction method applying a fully implicit second-order backward Euler differencing scheme has been used which is performed in the commercial code ANSYS and ANSYS CFX (version 15.0). When artery deformations and blood pressure are associated, arbitrary Lagrangian–Eulerian formulation is employed to calculate the artery domain response using the temporal blood response. As a result of bifurcation, noticeable velocity reduction and backflow formation decrease shear stress and made it oscillatory at the starting point of the LCx branch which caused the shear stress to be less than 1 and 2 Pa in the LCx and the LAD branches, respectively. Oscillatory shear index (OSI) as a hemodynamic parameter represents the increase in residence time and oscillatory wall shear stress. Because of using the ideal 3D geometry and realistic physiological conditions, the values obtained for shear stress are more accurate than the previous studies. Comparing the results of this study with previous clinical investigations shows that the regions with low wall shear stress less than 1.20 Pa and with high OSI value more than 0.3 are in more potential risk to the atherosclerosis plaque development, especially in the posterior after the bifurcation.     

7α-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid reflects the integrity of the blood-brain barrier

There is a continuous flux of the oxysterol 27-hydroxycholesterol (27-OHC) from the circulation across the blood-brain barrier (BBB) into the brain. The major metabolite of 27-OHC in the brain is 7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA). We confirm a recent report describing the presence of this metabolite in cerebrospinal fluid (CSF) at a relatively high concentration. A simple and accurate method was developed for assay of 7-HOCA in CSF based on isotope dilution-mass spectrometry and use of ²H₄-labeled internal standard. The concentration of this metabolite was found to be markedly increased in CSF from patients with a dysfunctional BBB. There was a high correlation between the levels of 7-HOCA in CSF and the CSF/serum albumin ratio. The concentration of 7-HOCA in CSF was not significantly affected by neurodegeneration. Our findings suggest that 7-HOCA could be used as a diagnostic marker for conditions with a dysfunctional BBB.     

Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells

The durable alloantibody responses that develop in organ transplant patients indicate long-lived plasma cell output from T-dependent germinal centers (GCs), but which of the two pathways of CD4 T cell allorecognition is responsible for generating allospecific T follicular helper cells remains unclear. This was addressed by reconstituting T cell-deficient mice with monoclonal populations of TCR-transgenic CD4 T cells that recognized alloantigen only as conformationally intact protein (direct pathway) or only as self-restricted allopeptide (indirect pathway) and then assessing the alloantibody response to a heart graft. Recipients reconstituted with indirect-pathway CD4 T cells developed long-lasting IgG alloantibody responses, with splenic GCs and allospecific bone marrow plasma cells readily detectable 50 d after heart transplantation. Differentiation of the transferred CD4 T cells into T follicular helper cells was confirmed by follicular localization and by acquisition of signature phenotype. In contrast, IgG alloantibody was not detectable in recipient mice reconstituted with direct-pathway CD4 T cells. Neither prolongation of the response by preventing NK cell killing of donor dendritic cells nor prior immunization to develop CD4 T cell memory altered the inability of the direct pathway to provide allospecific B cell help. CD4 T cell help for GC alloantibody responses is provided exclusively via the indirect-allorecognition pathway.     

An Investigation into the Stabilization of Diltiazem HCl Release from Matrices Made from Aged Polyox Powders

Matrices containing PEO fail to provide stable drug release profiles when stored at elevated temperatures for a period of time. The present study aims to stabilize diltiazem HCl release from matrices made from various molecular weights of polyox powders. To this end, various molecular weights of polyox with and without vitamin E (0.25, 0.5 and 1% w/w) were stored at 40°C for 0, 2, 4 and 8 weeks. The aged polyox powders were then mixed with the model drug at a ratio of 1:1 and compressed into tablets. At different time intervals, the aged polyox with vitamin E were taken out of oven and mixed with the drug (1:1 ratio) and compressed into tablets. Dissolution studies showed a significant increase in diltiazem HCl release rate to occur with increased storage time at 40°C ± 1 from tablets made from the aged polyox (no vitamin E). This was as a result of depolymerization of the aged polyox powders as compared to the fresh polyox samples. This was confirmed by differential scanning calorimetry (DSC) which showed a reduction in the melting point of the aged samples. Concentrations of vitamin E as low as 0.25% w/w was able to overcome the quick release of drug from the matrices made from aged polyox powders. DSC traces showed that the melting point of aged polyox samples containing vitamin E remained the same as that of the fresh samples. The presence of vitamin E is essential to stabilize the drug release from polyox matrices containing diltiazem HCl.Key words: depolymerization, drug release kinetics, molecular weight, polyox matrices, thermal behaviour