A mathematical model of blood,cerebrospinal fluid and brain dynamics

Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood, cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating hydrocephalus. The system of differential equations of first principles conservation balances is discretized and solved numerically. Fluid–solid interactions of the brain parenchyma with cerebral blood and CSF are calculated. The model provides the transitions from normal dynamics to the diseased state during the onset of communicating hydrocephalus. Predicted results were compared with physiological data from Cine phase-contrast magnetic resonance imaging to verify the dynamic model. Bolus injections into the CSF are simulated in the model and found to agree with clinical measurements.

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An extracellular polyhydroxybutyrate depolymerase in <Emphasis Type="Italic">Thermus thermophilus</Emphasis> HB8

The thermophilic bacterium Thermus thermophilus HB8 has been characterized as a polyhydroxybutyrate (PHB)-degrading microorganism since it grows efficiently and forms clear zones on agar plates containing PHB as sole carbon source. T. thermophilus extracellular PHB depolymerase was purified to homogeneity using an affinity chromatography protocol. The purified enzyme was estimated to have an apparent molecular mass of 42 kDa. The extracellular PHB depolymerase gene was identified as the TTHA0199 gene product of T. thermophilus HB8. The amino acid sequence of the TTHA0199 gene product shared significant homologies to other carboxylesterases. A catalytic triad was identified consisting of S₁₈₃, E₃₁₀, and H₄₀₅. A pentapeptide sequence (GX₁SX₂G) exists within the molecule, characteristic for PHB depolymerases (lipase box) and for other serine hydrolases. Purified extracellular PHB depolymerase was stable at high temperatures with an optimum activity at pH 8.0. The apparent Km value of the purified enzyme for PHB was 53 μg/ml. As the main product of the enzymic hydrolysis of PHB, the monomer 3-hydroxybutyrate was identified, suggesting that the enzyme acts principally as an exo-type hydrolase.     

Blood reflects tissue oxidative stress depending on biomarker and tissue studied

This study investigated whether selected oxidative stress markers measured in blood adequately reflect redox status in skeletal muscle, heart, and liver. Several markers were determined after implementing two treatments known to affect redox status, namely exercise and allopurinol administration. Xanthine oxidase, thiobarbituric acid-reactive substances (TBARS), protein carbonyls (PC), reduced glutathione (GSH), oxidized glutathione (GSSG), catalase, and total antioxidant capacity were determined in blood, skeletal muscle, heart, and liver. Correlation between blood and tissues in each marker was performed through the Spearman rank correlation coefficient. GSSG in erythrocytes was correlated with all tissues, ranging in the five experimental groups as follows: skeletal muscle r_s = 0.656–0.874, heart r_s = 0.742–0.981, liver r_s = 0.646–0.855. Xanthine oxidase and TBARS measured in blood satisfactorily described the redox status of the heart (0.753–0.964 and 0.705–1.000, respectively) and liver (0.755–0.902 and 0.656–1.000, respectively). Skeletal muscle and heart redox status can be adequately described by PC (0.652–1.000 and 0.656–0.964, respectively), GSH (0.693–1.000 and 0.656–1.000, respectively), and catalase (0.745–1.000 and 0.656–1.000, respectively) measured in blood. In conclusion, this study suggests that a combination of markers measured in blood provides a reliable indication about the redox status in skeletal muscle, heart, and liver.     

Production of polyhydroxyalkanoates from whey by Thermus thermophilus HB8

The thermophilic bacterium Thermus thermophilus HB8 is able to utilize lactose from whey-based media for the biosynthesis of polyhydroxyalkanoates (PHAs) under nitrogen limitation. T. thermophilus can utilize both, glucose and galactose, the products of lactose hydrolysis. When T. thermophilus HB8 was grown in culture media containing 24% (v/v) whey, PHA was accumulated up to 35% (w/w) of its biomass after 24 h of cultivation. The effect of initial phosphate concentration on the PHA production was also investigated. Using an initial phosphate concentration of 50 mM the PHA accumulation was enhanced. Analysis of the produced PHA from T. thermophilous HB8 grown in whey-based media revealed a novel heteropolymer consisting of the short chain length 3-hydroxyvalerate (3HV; 38 mol%) and the medium chain length, 3-hydroxyheptanoate (3HHp; 9.89 mol%), 3-hydroxynanoate (3HN; 16.59 mol%) and 3-hydroxyundecanoate (3HU; 35.42 mol%). Despite the low molecular weight of the produced PHA by T. thermophilus, whey could be an excellent substrate for the production of heteropolymers with unique properties.     

Weeds of change: Cardamine hirsuta as a new model system for studying dissected leaf development

Cardamine hirsuta, a small crucifer closely related to the model organism Arabidopsis thaliana, offers high genetic tractability and has emerged as a powerful system for studying the genetic basis for diversification of plant form. Contrary to A. thaliana, which has simple leaves, C. hirsuta produces dissected leaves divided into individual units called leaflets. Leaflet formation requires activity of Class I KNOTTED1-like homeodomain (KNOX) proteins, which also promote function of the shoot apical meristem (SAM). In C. hirsuta, KNOX genes are expressed in the leaves whereas in A. thaliana their expression is confined to the SAM, and differences in expression arise through cis-regulatory divergence of KNOX regulation. KNOX activity in C. hirsuta leaves delays the transition from proliferative growth to differentiation thus facilitating the generation of lateral growth axes that give rise to leaflets. These axes reflect the sequential generation of cell division foci across the leaf proximodistal axis in response to auxin activity maxima, which are generated by the PINFORMED1 (PIN1) auxin efflux carriers in a process that resembles organogenesis at the SAM. Delimitation of C. hirsuta leaflets also requires the activity of CUP SHAPED COTYLEDON (CUC) genes, which direct formation of organ boundaries at the SAM. These observations show how species-specific deployment of fundamental shoot development networks may have sculpted simple versus dissected leaf forms. These studies also illustrate how extending developmental genetic studies to morphologically divergent relatives of model organisms can greatly help elucidate the mechanisms underlying the evolution of form.     

Divergence Among an International Population of Trichophyton tonsurans Isolates

Trichophyton tonsurans is a widely distributed pathogen that demonstrates a significant degree of genetic and phenetic heterogeneity. To date, the degree of genetic relatedness among geographically segregated isolates has not been explored. This investigation evaluates the extent of genetic variation among an international population of T. tonsurans isolates and examines the relatedness of isolates within and between countries. Molecular strain typing was performed on 198 isolates obtained from 14 countries. A mixed-marker strategy utilizing 27 sequence variations in 13 gene loci was applied to all isolates and cluster analysis was performed to examine the relationship between strains. Phylogenetic analysis was used to corroborate the findings of the cluster analysis with T. equinum strains serving as an out-group. In total, 47 distinct strain types were identified represented by seven clusters and one singleton. There appeared to be a moderate degree of clustering among isolates obtained from North America, Asia and Australia, although European isolates were uniformly distributed among the majority of clusters. The degree of genetic variation observed in this study coupled with the geographic localization would support the argument for allopatric divergence within this species.     

Device Thrombogenicity Emulator (DTE) − Design optimization methodology for cardiovascular devices: A study in two bileaflet MHV designs

Patients who receive prosthetic heart valve (PHV) implants require mandatory anticoagulation medication after implantation due to the thrombogenic potential of the valve. Optimization of PHV designs may facilitate reduction of flow-induced thrombogenicity and reduce or eliminate the need for post-implant anticoagulants. We present a methodology entitled Device Thrombogenicty Emulator (DTE) for optimizing the thrombo-resistance performance of PHV by combining numerical and experimental approaches. Two bileaflet mechanical heart valves (MHV) designs, St. Jude Medical (SJM) and ATS, were investigated by studying the effect of distinct flow phases on platelet activation. Transient turbulent and direct numerical simulations (DNS) were conducted, and stress loading histories experienced by the platelets were calculated along flow trajectories. The numerical simulations indicated distinct design dependent differences between the two valves. The stress loading waveforms extracted from the numerical simulations were programmed into a hemodynamic shearing device (HSD), emulating the flow conditions past the valves in distinct ‘hot-spot’ flow regions that are implicated in MHV thrombogenicity. The resultant platelet activity was measured with a modified prothrombinase assay, and was found to be significantly higher in the SJM valve, mostly during the regurgitation phase. The experimental results were in excellent agreement with the calculated platelet activation potential. This establishes the utility of the DTE methodology for serving as a test bed for evaluating design modifications for achieving better thrombogenic performance for such devices.