Axial prestretch and circumferential distensibility in biomechanics of abdominal aorta

Elastic arteries are significantly prestretched in an axial direction. This property minimises axial deformations during pressure cycle. Ageing-induced changes in arterial biomechanics, among others, are manifested via a marked decrease in the prestretch. Although this fact is well known, little attention has been paid to the effect of decreased prestretch on mechanical response. Our study presents the results of an analytical simulation of the inflation–extension behaviour of the human abdominal aorta treated as nonlinear, anisotropic, prestrained thin-walled as well as thick-walled tube with closed ends. The constitutive parameters and geometries for 17 aortas adopted from the literature were supplemented with initial axial prestretches obtained from the statistics of 365 autopsy measurements. For each aorta, the inflation–extension response was calculated three times, with the expected value of the initial prestretch and with the upper and lower confidence limit of the initial prestretch derived from the statistics. This approach enabled age-related trends to be evaluated bearing in mind the uncertainty in the prestretch. Despite significantly decreased longitudinal prestretch with age, the biomechanical response of human abdominal aorta changes substantially depending on the initial axial stretch was used. In particular, substituting the upper limit of initial prestretch gave mechanical responses which can be characterised by (1) low variation in axial stretch and (2) high circumferential distensibility during pressurisation, in contrast to the responses obtained for their weakly prestretched counterparts. The simulation also suggested the significant effect of the axial prestretch on the variation of axial stress in the pressure cycle. Finally, the obtained results are in accordance with the hypothesis that circumferential-to-axial stiffness ratio is the quantity relatively constant within this cycle.     

Spectrophotometric parameters of conformational states of hemoglobin and its complexes with ligands in the sturgeons

Parameters of carbo-, carboxy-, oxy-, deoxy-, and methemoglobin of the human and four species of sturgeons (sterlet, Russian sturgeon, starred sturgeon, great sturgeon) were analyzed spectrophotometrically. It has been shown that in the absorption spectra of all forms of hemoglobins there is only one Soret γ₁ band due to the prosthetic group of the pigment; the wavelength of this band is undoubtedly associated with the hemoglobin conformation. This permits the use of the band as an indicator parameter to control an initial state of the fish hemoglobin solutions, the analysis of conformational states of the pigment macromolecules, and the study of hemoglobin derivatives (its complexes with ligands).     

Papilio nandina, a probable hybrid between Papilio dardanus and Papilio phorcas

Abstract. Hybrids bred in the laboratory between Papilio dardanus Brown and Papilio phorcas Cramer resulted in male butterflies similar to the two naturally occurring males described as P.nandina Rothschild & Jordan. A single female hybrid insect resembling the female parent was also bred. Male hybrids were also obtained between P.dardanus and P.demodocus/demoleus but not between P.dardanus and P.constantinus .
The phylogenetic relationships of dardanus and phorcas are discussed, and reasons given for preferring the older hypothesis that male-like females are primitive rather than that they represent the most specialized forms. Further information on this point would be forthcoming if backcrosses and F₂ s could be obtained.     

Thio-NADP is not an antagonist of NAADP

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a metabolite of NADP, which can release Ca²⁺ from stores that are distinct from those activated by either cyclic ADP-ribose or inositol 1,4,5-trisphosphate (IP₃). It has previously been suggested that thio-NADP is a specific antagonist of NAADP (Chini et al. [1995]J. Biol. Chem. 270, 3216–3223). Its effects in sea-urchin egg homogenates were investigated. At 50 μM, thio-NADP activates partial Ca²⁺ release and totally inhibits subsequent challenge with a saturating concentration of NAADP. Purification by HPLC eliminates the Ca²⁺ releasing activity of 50 μM thio-NADP and reduces the subsequent inhibition by 73.7±1.3%. The residual inhibitory effect is no more than that exerted by 50 μM of either NADP itself or nicotinic acid adenine dinucleotide (NAAD). These results are confirmed by³²P-NAADP binding studies. Unpurified thio-NADP inhibits the specific³²P-NAADP binding to egg microsomes with an IC₅₀ of 40 μM. After HPLC purification, only 20% inhibition is seen at a concentration as high as 50 μM, similar to the extent of inhibition effected by 40 μM NADP. These results indicate the inhibitory substance in thio-NADP is a contaminant. The partial Ca²⁺ release activity of unpurified thio-NADP suggests the contaminant is NAADP itself. This is supported by the fact that pretreatment with a subthreshold concentration of only 2 nM NAADP totally desensitizes the egg homogenates such that no Ca²⁺ response is seen with saturating NAADP. Estimation from the binding studies shows that a contamination of 0.012% of NAADP in the unpurified thio-NADP samples is sufficient to account for the inhibitory effects. These results indicate thio-NADP is not an antagonist of NAADP.     

Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death

Inclusions composed of α-synuclein (α-syn), i.e., Lewy bodies (LBs) and Lewy neurites (LNs), define synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Here, we demonstrate that preformed fibrils generated from full-length and truncated recombinant α-syn enter primary neurons, probably by adsorptive-mediated endocytosis, and promote recruitment of soluble endogenous α-syn into insoluble PD-like LBs and LNs. Remarkably, endogenous α-syn was sufficient for formation of these aggregates, and overexpression of wild-type or mutant α-syn was not required. LN-like pathology first developed in axons and propagated to form LB-like inclusions in perikarya. Accumulation of pathologic α-syn led to selective decreases in synaptic proteins, progressive impairments in neuronal excitability and connectivity, and, eventually, neuron death. Thus, our data contribute important insights into the etiology and pathogenesis of PD-like α-syn inclusions and their impact on neuronal functions, and they provide a model for discovering therapeutics targeting pathologic α-syn-mediated neurodegeneration.     

Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.     

Acute lead exposure increases arterial pressure: role of the renin-angiotensin system

Background

Chronic lead exposure causes hypertension and cardiovascular disease. Our purpose was to evaluate the effects of acute exposure to lead on arterial pressure and elucidate the early mechanisms involved in the development of lead-induced hypertension.

Methodology/Principal Findings

Wistar rats were treated with lead acetate (i.v. bolus dose of 320 µg/Kg), and systolic arterial pressure, diastolic arterial pressure and heart rate were measured during 120 min. An increase in arterial pressure was found, and potential roles of the renin-angiotensin system, Na⁺,K⁺-ATPase and the autonomic reflexes in this change in the increase of arterial pressure found were evaluated. In anesthetized rats, lead exposure: 1) produced blood lead levels of 37±1.7 µg/dL, which is below the reference blood concentration (60 µg/dL); 2) increased systolic arterial pressure (Ct: 109±3 mmHg vs Pb: 120±4 mmHg); 3) increased ACE activity (27% compared to Ct) and Na⁺,K⁺-ATPase activity (125% compared to Ct); and 4) did not change the protein expression of the α1-subunit of Na⁺,K⁺-ATPase, AT₁ and AT₂. Pre-treatment with an AT₁ receptor blocker (losartan, 10 mg/Kg) or an ACE inhibitor (enalapril, 5 mg/Kg) blocked the lead-induced increase of arterial pressure. However, a ganglionic blockade (hexamethonium, 20 mg/Kg) did not prevent lead''s hypertensive effect.

Conclusion

Acute exposure to lead below the reference blood concentration increases systolic arterial pressure by increasing angiotensin II levels due to ACE activation. These findings offer further evidence that acute exposure to lead can trigger early mechanisms of hypertension development and might be an environmental risk factor for cardiovascular disease.     

Determinants of invasion by single versus multiple plant species in temperate lowland forests

Biological Invasions - Invasions of alien plants pose a serious threat to native biodiversity and ecosystem processes. Forests are considered more resistant to invasion due to limited light...