A novel method to identify and characterise peptide mimotopes of heat shock protein 70-associated antigens

The heat shock protein, Hsp70, has been shown to play an important role in tumour immunity. Vaccination with Hsp70-peptide complexes (Hsp70-PCs), isolated from autologous tumour cells, can induce protective immune responses. We have developed a novel method to identify synthetic mimic peptides of Hsp70-PCs and to test their ability to activate T-cells. Peptides (referred to as "recognisers") that bind to Hsp70-PCs from the human breast carcinoma cell line, MDA-MB-231, were identified by bio-panning a random peptide M13 phage display library. Synthetic recogniser peptides were subsequently used as bait in a reverse bio-panning experiment to identify potential Hsp70-PC mimic peptides. The ability of the recogniser and mimic peptides to prime human lymphocyte responses against tumour cell antigens was tested by stimulating lymphocytes with autologous peptide-loaded monocyte-derived dendritic cells (DCs). Priming and subsequent stimulation with either the recogniser or mimic peptide resulted in interferon-γ (IFN-γ) secretion by the lymphocytes. Furthermore, DCs loaded with Hsp70, Hsp70-PC or the recogniser or the mimic peptide primed the lymphocytes to respond to soluble extracts from breast cells. These results highlight the potential application of synthetic peptide-mimics of Hsp70-PCs, as modulators of the immune response against tumours.     

Analysis of hyperpolarized dynamic C lactate imaging in a transgenic mouse model of prostate cancer

This study investigated the application of an acquisition that selectively excites the [1-¹³C]lactate resonance and allows dynamic tracking of the conversion of ¹³C-lactate from hyperpolarized ¹³C-pyruvate at a high spatial resolution. In order to characterize metabolic processes occurring in a mouse model of prostate cancer, 20 sequential 3D images of ¹³C-lactate were acquired 5 s apart using a pulse sequence that incorporated a spectral–spatial excitation pulse and a flyback echo-planar readout to track the time course of newly converted ¹³C-lactate after injection of prepolarized ¹³C-pyruvate. The maximum lactate signal (MLS), full-width half-maximum (FWHM), time to the peak ¹³C-lactate signal (TTP) and area under the dynamic curve were calculated from the dynamic images of 10 TRAMP mice and two wild-type controls. The regional variation in ¹³C-lactate associated with the injected pyruvate was demonstrated by the peak of the ¹³C-lactate signal occurring earlier in the kidney than in the tumor region. The intensity of the dynamic ¹³C-lactate curves also varied spatially within the tumor, illustrating the heterogeneity in metabolism that was most prominent in more advanced stages of disease development. The MLS was significantly higher in TRAMP mice that had advanced disease.     

Theoretical and numerical analysis of a heat pump model utilizing Dufour effect

A heat pump model utilizing the Dufour effect is proposed, and studied by numerical and theoretical analysis. Numerically, we perform MD simulations of this system and measure the cooling power and the coefficient of performance (COP) as figures of merit. Theoretically, we calculate the cooling power and the COP from the phenomenological equations describing this system by using the linear irreversible thermodynamics and compare the theoretical results with the MD results.     

Noise-induced precursors of tonic-to-bursting transitions in hypothalamic neurons and in a conductance-based model

The dynamics of neurons is characterized by a variety of different spiking patterns in response to external stimuli. One of the most important transitions in neuronal response patterns is the transition from tonic firing to burst discharges, i.e., when the neuronal activity changes from single spikes to the grouping of spikes. An increased number of interspike-interval sequences of specific temporal correlations was detected in anticipation of temperature induced tonic-to-bursting transitions in both, experimental impulse recordings from hypothalamic brain slices and numerical simulations of a stochastic model. Analysis of the modelling data elucidates that the appearance of such patterns can be related to particular system dynamics in the vicinity of the period-doubling bifurcation. It leads to a nonlinear response on de- and hyperpolarizing perturbations introduced by noise. This explains why such particular patterns can be found as reliable precursors of the neurons' transition to burst discharges.     

Percolation and spreading of damage in a simplified Kauffman model

A simplified version of the Kauffman cellular automaton is introduced. As in the usual Kauffman model, there is a transition between a frozen phase and a chaotic phase where damage may spread. We associate the onset of chaos in this model with a percolation transition of certain rules occurring in the model. It seems to be in a different universality class from the usual Kauffman cellular automaton.     

Effects of a reverse shock wave on neutrino oscillations in a new supernova model

It is known that in supernova explosions, there might be a reverse shock wave in addition to the forward shock wave during the explosion phase, when the mass of supernova is in a certain range. In this paper, we propose to add the reverse shock wave to the previous supernova model, in which only the forward shock wave was included,and thus obtain a new model. By analyzing the resonance condition as well as the density jump in the new model and using the Landau-Zener method, an expression for the crossing probability in high density matter(PH) is given.We proceed to study how PH varies with time and with neutrino energy when both the reverse shock wave and the forward shock wave are considered. From comparison with the previous results, where only the effects of the forward shock wave were considered, it is clear that the reverse shock wave brings significant changes to PH.     

Effects of atrazine on female Wistar rats: morphological alterations in ovarian follicles and immunocytochemical labeling of 90 kDa heat shock protein

Fertility in female mammals may be affected by a variety of endocrine disrupters present in the environment. Herbicide atrazine is an example of endocrine disrupter employed in agriculture, which disrupts estrous cyclicity in rats. Aiming to characterize morphologically the effect of low and sublethal doses of atrazine on the ovaries of Wistar rats, in an effort to determine the possible intrafollicular target site through which this herbicide acts adult females were submitted to both subacute and subchronic treatments. Additionally, immunocytochemical labeling of 90 kDa heat shock protein (HSP90) was performed in order to evaluate the role played by this protein in the ovary, under stressed conditions induced by herbicide exposure. The results indicated that atrazine induced impaired folliculogenesis, increased follicular atresia and HSP90 depletion in female rats submitted to subacute treatment, while the subchronic treatment with low dose of atrazine could compromise the reproductive capacity reflected by the presence of multioocytic follicle and stress-inducible HSP90.     

Hall effect on Hartmann flow and heat transfer of a Burgers' fluid

The effect of Hall current on the steady magnetohydrodynamics (MHD) flow of an electrically conducting, incompressible Burgers' fluid between two parallel electrically insulating infinite planes is studied. The MHD flow is generated by applying constant pressure gradient. An external uniform magnetic field normal to the disks is applied. The disks are kept at two different constant temperatures. Exact solutions are obtained for the governing momentum and energy equations. The effects of Hartmann number M, Reynolds number Re, Prandtl number Pr, Eckert number Ec, pressure gradient dp/dx and Hall parameter η are examined.     

Transplanted bone marrow stem cells relocate to infarct penumbra and co-express endogenous proliferative and immature neuronal markers in a mouse model of ischemic cerebral stroke

Background  

Several studies demonstrate that neurogenesis may be induced or activated following vascular insults, which may be important for neuronal regeneration and functional recovery. Understanding the cellular mechanism underlying stroke-associated neurogenesis is of neurobiological as well as neurological/clinical relevance. The present study attempted to explore potential homing and early development of transplanted bone marrow stem cells in mouse forebrain after focal occlusion of the middle cerebral artery, an experimental model of ischemic stroke.     

Implantation of undifferentiated and predifferentiated human neural stem cells in the R6/2 transgenic mouse model of Huntington's disease

ABSTRACT: BACKGROUND: Cell therapy is a potential therapeutic approach for several neurodegenetative disease, including Huntington Disease (HD). To evaluate the putative efficacy of cell therapy in HD, most studies have used excitotoxic animal models with only a few studies having been conducted in genetic animal models. Genetically modified animals should provide a more accurate representation of human HD, as they emulate the genetic basis of its etiology. RESULTS: In this study, we aimed to assess the therapeutic potential of a human striatal neural stem cell line (STROC05) implanted in the R6/2 transgenic mouse model of HD. As DARPP-32 GABAergic output neurons are predominately lost in HD, STROC05 cells were also predifferentiated using purmorphamine, a hedgehog agonist, to yield a greater number of DARPP-32 cells. A bilateral injection of 4.5x105 cells of either undifferentiated or predifferentiated DARPP-32 cells, however, did not affect outcome compared to a vehicle control injection. Both survival and neuronal differentiation remained poor with a mean of only 161 and 81 cells surviving in the undifferentiated and differentiated conditions respectively. Only a few cells expressed the neuronal marker beta-III-tubulin. CONCLUSIONS: Although the rapid brain atrophy and short life-span of the R6/2 model constitute adverse conditions to detect potentially delayed treatment effects, significant technical hurdles, such as poor cell survival and differentiation, were also sub-optimal. Further consideration of these aspects is therefore needed in more enduring transgenic HD models to provide a definite assessment of this cell line's therapeutic relevance. However, a combination of treatments is likely needed to affect outcome in transgenic models of HD.     

Histone deacetyltransferase1 expression in mouse oocyte and their in vitro-fertilized embryo: effect of oocyte vitrification

This study was conducted to investigate the expression of Histone Deacetyltransferase1 (HDAC1) in mouse embryos derived from the vitrified-warmed oocytes. Firstly, the mouse oocytes at metaphaseII (MII) stage were randomly allocated into three groups: A untreated (control), B exposed to vitri?cation solution (VS) without being plunged into liquid nitrogen (toxicity), or C vitri?ed by open-pulled straw (OPS) method (vitri?cation). After warming, they were fertilized in vitro. Fresh oocytes were used as control. Expression of HDAC1 was then examined in MII mouse oocytes and embryos by immunofluorescence with anti-HDAC1 polyclonal antibody and fluorescein isothiocyanate-conjugated goat anti-rabbit IgG. Results showed that after in vitro fertilization (IVF), developmental rates to two-cell embryos (39%), 4-cell embryos (35%), morula (32%) and blastocysts (26%) in cryopreserved oocytes were all significantly lower than those of fresh oocytes (P < 0.01). In addition, HDAC1 expression in the vitrified group was significantly lower (P< 0.05) than that in the control and toxicity groups at all developmental stages except for the blastocyst. Moreover, the vitrified-warmed oocytes showed significantly lower (P < 0.05) HDAC1 expression compared with that of control and toxicity groups. In conclusion, HDAC1 was expressed both in oocytes and in their in vitro-fertilized embryos. This decreased expression of HDAC1 in mouse oocytes and the embryos due to the cryopreservation may have a negative impact on embryo development.     

An effort toward molecular biology of food deprivation induced food hoarding in gonadectomized NMRI mouse model: focus on neural oxidative status

Background

Environmental uncertainty, such as food deprivation, may alter internal milieu of nervous system through various mechanisms. In combination with circumstances of stress or aging, high consumption of unsaturated fatty acids and oxygen can make neural tissues sensitive to oxidative stress (OS). For adult rats, diminished level of gonadal steroid hormones accelerates OS and may result in special behavioral manifestations. This study was aimed to partially answer the question whether OS mediates trade-off between food hoarding and food intake (fat hoarding) in environmental uncertainty (e.g., fluctuations in food resource) within gonadectomized mouse model in the presence of food deprivation-induced food hoarding behavior.

Results

Hoarding behavior was not uniformly expressed in all male mice that exposed to food deprivation. Extended phenotypes including hoarder and non-hoarder mice stored higher and lower amounts of food respectively as compared to that of low-hoarder mice (normal phenotype) after food deprivation. Results showed that neural oxidative status was not changed in the presence of hoarding behavior in gonadectomized mice regardless of tissue type, however, glutathione levels of brain tissues were increased in the presence of hoarding behavior. Decreased superoxide dismutase activity in brain and spinal cord tissues and increased malondialdehyde in brain tissues of gonadectomized mice were also seen.

Conclusions

Although, food deprivation-induced hoarding behavior is a strategic response to food shortage in mice, it did not induce the same amount of hoarding across all colony mates. Hoarding behavior, in this case, is a response to the environmental uncertainty of food shortage, therefore is not an abnormal behavior. Hoarding behavior induced neural OS with regard to an increase in brain glutathione levels but failed to show other markers of neural OS. Decreased superoxide dismutase activity in brain and spinal cord tissues and increased malondialdehyde levels in brain tissues of gonadectomized mice could be a hallmark of debilitated antioxidative defense and more lipid peroxidation due to reduced amount of gonadal steroid hormones during aging.

     

The effect of solution level on calorific and dosimetric results in a 70 kHz tower type sonochemical reactor

In order to design and optimise sonochemical reactors it is important to study the impact of liquid level, or path length, on the standing wave phenomena and the influence this has on temperature increase and OH radical rate of production. In this work, an ultrasonic tower type reactor operating at 70 kHz is investigated with results from variations to liquid levels reported. Calorimetry data was obtained using a modified reactor set up with temperature change monitored at selected points within the chamber. OH radical rate of formation was shown via chemical dosimetry, following the conversion of terephthalic acid (TA) to 2-hydroxyterephthalic acid (HTA). The results obtained have shown that changes in solution depth of a few millimetres significantly impacts on the interaction of the propagated and reflected waveforms with the results of calorific measurements and HTA rates of formation varying by 90% (750 J) and 88% (80 mmol dm(-3) min(-1)) between the operational extremes over the studied depth range.     

Alternans and higher-order rhythms in an ionic model of a sheet of ischemic ventricular muscle

Life-threatening arrhythmias such as ventricular tachycardia and fibrillation often occur during acute myocardial ischemia. During the first few minutes following coronary occlusion, there is a gradual rise in the extracellular concentration of potassium ions ([K(+)](0)) within ischemic tissue. This elevation of [K(+)](0) is one of the main causes of the electrophysiological changes produced by ischemia, and has been implicated in inducing arrhythmias. We investigate an ionic model of a 3 cmx3 cm sheet of normal ventricular myocardium containing an ischemic zone, simulated by elevating [K(+)](0) within a centrally-placed 1 cmx1 cm area of the sheet. As [K(+)](0) is gradually raised within the ischemic zone from the normal value of 5.4 mM, conduction first slows within the ischemic zone and then, at higher [K(+)](0), an arc of block develops within that area. The area distal to the arc of block is activated in a delayed fashion by a retrogradely moving wavefront originating from the distal edge of the ischemic zone. With a further increase in [K(+)](0), the point eventually comes where a very small increase in [K(+)](0) (0.01 mM) results in the abrupt transition from a global period-1 rhythm to a global period-2 rhythm in the sheet. In the peripheral part of the ischemic zone and in the normal area surrounding it, there is an alternation of action potential duration, producing a 2:2 response. Within the core of the ischemic zone, there is an alternation between an action potential and a maintained small-amplitude response ( approximately 30 mV in height). With a further increase of [K(+)](0), the maintained small-amplitude response turns into a decrementing subthreshold response, so that there is 2:1 block in the central part of the ischemic zone. A still further increase of [K(+)](0) leads to a transition in the sheet from a global period-2 to a period-4 rhythm, and then to period-6 and period-8 rhythms, and finally to a complete block of propagation within the ischemic core. When the size of the sheet is increased to 4 cmx4 cm (with a 2 cmx2 cm ischemic area), one observes essentially the same sequence of rhythms, except that the period-6 rhythm is not seen. Very similar sequences of rhythms are seen as [K(+)](0) is increased in the central region (1 or 2 cm long) of a thin strand of tissue (3 or 4 cm long) in which propagation is essentially one-dimensional and in which retrograde propagation does not occur. While reentrant rhythms resembling tachycardia and fibrillation were not encountered in the above simulations, well-known precursors to such rhythms (e.g., delayed activation, arcs of block, two-component upstrokes, retrograde activation, nascent spiral tips, alternans) were seen. We outline how additional modifications to the ischemic model might result in the emergence of reentrant rhythms following alternans. (c) 2000 American Institute of Physics.     

Nonlinear absorption and optical damage threshold of carbon-based nanostructured material embedded in a protein

Physical processes in laser–matter interaction used to be determined by generation of fast electrons resulting from efficient conversion of the absorbed laser radiation. Composite materials offer the possibility to control the absorption by choice of the host material and dopants. Reported here strong absorption of ultrashort laser pulse in a composite carbon-based nanomaterial including single-walled carbon nanotubes (SWCNTs) or multilayer graphene was measured in the intensity range between 10¹² and 10¹⁶ W cm^?2. A protein (lysozyme) was used as the host. The maximum absorption of femtosecond laser pulse has reached 92–96 %. The optical damage thresholds of the coatings were registered at an intensity of (1.1 ± 0.5) × 10¹³ W cm^?2 for the embedded SWCNTs and at (3.4 ± 0.3) × 10¹³ W cm^?2 for the embedded graphene. Encapsulated variant of the dispersed nanomaterial was investigated as well. It was found that supernatant protein in the coating material tends to dominate the absorption process, independently of the embedded nanomaterial. The opposite was observed for the encapsulated material.     

Local effect of electric and magnetic fields on the position of an attached shock in a supersonic diffuser

Effective ways for controlling shock wave configurations by means of external actions are sought. One such way is a local effect of electric and magnetic fields. In this paper, the local effect of external fields is implemented by current localization in a limited region of a diffuser. The experiment is carried out in a diffuser providing the complete internal compression of the gas with a Mach number at the inlet M=4.3. As a working medium, a xenon plasma is used. The plasma flow is formed in a shock tube equipped with an accelerating nozzle. Two ways of current localization are tested. In the first one, the diffuser inlet is a short channel of Faraday generator type. In this case, the ponderomotive force basically decelerates or accelerates the flow depending on the direction of the electric field. In the second way, the current flows through a narrow near-wall region between adjacent electrodes. In this case, the ponderomotive force compresses or expands the gas. In both cases, it is shown that the angle of an attached shock due to MHD interaction can be both decreased and increased. The central problem with the MHD control of shock waves is near-electrode and near-wall phenomena.     

底部局部加热多孔介质自然对流传热的格子Boltzmann模拟

运用格子Boltzmann方法研究了底部局部加热多孔介质方腔的自然对流传热.方腔的上壁面为低温热源,下壁面为局部高温热源,左右壁面为绝热条件.重点分析了高温热源位置a及尺寸b对多孔介质方腔自然对流传热性能的影响,提出了平均Nusselt数Nu和位置a及尺寸b的拟合关系式.研究结果表明:高温热源位置及尺寸对多孔介质方腔内自然对流传热性质的影响很大,且存在最佳高温热源位置(a=4/16)和尺寸(b=0.75),以达到最强的对流换热强度(Nu_(max)≈10.35)和最大的对流换热量(Q_(max)≈5.69).