This review presents data on the cellular-molecular mechanisms regulating angiogenesis associated with the vascular endothelium. Existing concepts hold that the control of angiogenesis involves ...activated endothelial cells and their precursors (progenitor cells), which synthesize and release angiogenic molecules with different chemical structures and mechanisms of biological action, but all allowing these cells to control each stage of angiogenesis directly or indirectly. Balanced functioning of the system of molecular stimulators and inhibitors of angiogenesis is particularly important for the brain, as excessive formation of blood vessels, like inadequate development of blood vessels, leads in certain conditions to rapid and irreversible changes in nervous tissue. Post-operative neurorepair cannot occur without adequate reperfusion of the injured part of the brain, which can be supported by timely stimulation of angiogenesis, while intensification of this process in tumors, conversely, has adverse consequences. Tumor growth and metastasis are significantly linked with increases in the level of vascularization of malignant tissue, while blockade of angiogenesis is not infrequently the only productive method of limiting tumor growth. However, we have insufficient knowledge of the mechanisms regulating angiogenesis in the brain at the cellular-molecular level in physiological conditions and pathology, so angiogenic influences do not always produce the expected effect.
First-fourth order pial branches of the median cerebral artery were studied by biomicroscopy in male Wistar rats aged 1 and 12 months. Irrespective of age, CO-mediated mechanisms are involved in the ...regulation of the basal tone of pial vessels of various diameters (more so of arteries with well-developed muscular tunic). Injection of hemin confirmed that endogenous production of CO maintained vasodilatation and this effect was most pronounced in large pial branches of young animals, while zinc protoporphyrin IX blocked this effect in all cases. On the other hand, zinc IX protoporphyrin did not modify NO-mediated reaction caused by injection of L-arginine, while hemin compensated (though not completely) vasoconstriction induced by NO synthase blocker L-NAME. In contrast to NO, the effect of CO on blood vessels was not so rapid and potent, but more lasting. Other targets for CO were arteries with well-developed muscular tunic, while targets for NO were small vessels. The vasomotor effects of both gas transmitters were more pronounced in young animals.
The capillaries containing MMP-2 and its tissue inhibitor TIMP-2 were examined in cerebral cortex and white matter obtained from intact Wistar rats (
n
=5) and the rats with progressing experimental ...renovascular hypertension (
n
=35). In hypertensive rats, the changes in intensity of the immunohistochemical reaction and in the density of capillaries expressing TIMP-2 significantly differed from the corresponding values in MMP-2-positive capillaries, which resulted in pronounced deviation of MMP-2/TIMP-2 index from the control level (especially in cerebral cortex) probably attesting to enhanced risk of complications in cases with arterial hypertension.
The locations of heme oxygenase-2 (HO-2) and heme oxygenase-1 (HO-1) in the walls of 1st- to 4th-order arterial branches in the pia mater were studied in normotensive rats and in animals with induced ...renovascular hypertension (RVH). Immunohistochemical detection of heme oxygenase was performed on 40 Wistar rats. The vasomotor function of carbon monoxide (CO) in 3rd- to 5th-order arteries was found to be associated mainly with the endothelium, while in 1st- and 2nd-order arteries it was associated with myocytes. In normotensive animals, HO-2 was involved in forming CO, while both HO-2 and HO-1 had roles in hypertensive animals. The largest number of vessels expressing HO-1 was seen in week 16 of RVH, when the proportion of vessels positive for HO-2 was minimal, which is consistent with the time at which arterial pressure stabilizes at the new, higher, level.
To study the distribution of MMP-2 and MMP-9 and their inhibitors (TIMP-2 and TIMP-1 respectively) in the brain vascular bed of rats exposed to chronic tobacco smoke.
Localization and expression of ...MMP-2, MMP-9, TIMP-2 and TIMP-1 in the pial branches (I-V order vessels), intracerebral arteries and capillaries of rats exposed to tobacco smoke were studied for 36 weeks. The level of enzymatic activity was assessed by the relative quantity of enzymopositive arteries and amount of fragments per 1 mm
and rate of immunohistochemical reaction. Specific capillary density per mm
of brain tissue and optical density of the immunohistochemical product were calculated.
MMP-2 and TIMP-2 were found in all segments of the arterial course in control animals. In rats exposed to tobacco smoking, the expression of MMP-2 increased only in intracerebral arteries and capillaries while TIMP-2 level decreased. MMP-9 and TIMP-1 were noted only in single vessels, mainly small pial and intracerebral arteries, in intact animals. In rats exposed to tobacco smoke, MMP-9 expression significantly increased in all segments of the arterial course whereas the increase in TIMP-1 was observed mainly in large pial arteries.
In physiological conditions, the dynamic balance between MMP-2 and TIMP-2 maintains basic tissue metabolism. Products of tobacco combustion are inductors of the inducible MMP-9 which promotes morphofunctional changes. The imbalance in MMP-9 - TIMP-1 system causes the degradation of extracellular matrix in different segments of the brain arterial course promoting the development of cerebral dysfunction.
We developed a method to spatially control gene expression following nonviral delivery of DNA. This method includes surface-modifying DNA nanocarriers with heparin to inhibit passive gene transfer in ...both the target and the off-target tissues and using ultrasound-targeted microbubble destruction (UTMD) to selectively activate heparin-inhibited gene transfer at the target site. We observed that the engraftment of heparin onto the surface of cationic liposomes reduced off-target gene expression in the liver, a major site of nanoplex accumulation, by more than 700-fold compared to the nonheparinized PEGylated liposomes. We further observed that tumor-directed UTMD increased gene transfer with heparin-modified nanoplexes by more than 10-fold. This method augmented tumor-to-liver selectivity of gene expression by 4000-fold compared to controls. We conclude that heparinization of DNA nanocarriers in conjunction with localized activation of gene transfer by UTMD may enable greater spatial control over genetic therapy.
We present new observational data on the phenomena of extremely high activity on the Sun and in the heliosphere that took place in October-November 2003. A large variety of solar and heliospheric ...parameters give evidence that the interval under consideration is unique over the entire observation time. Based on these data, comparing them with similar situations in the past and using available theoretical concepts, we discuss possible cause-and-effect connections between the processes observed. The paper includes the first results and conclusions derived by the collaboration "Solar Extreme Events-2003" organized in Russia for detailed investigations of these events. As a result of our consideration, it is beyond question that the physical causes of solar and heliospheric phenomena in October-November 2003 are not exclusively local and do not belong only to the active regions and solar atmosphere above them. The energy reservoirs and driving forces of these processes have a more global nature. In general, they are hidden from an observer, since ultimately their sources lie in the subphotospheric layers of the Sun, where changes that are fast and difficult to predict can sometimes take place (and indeed they do). Solar flares can serve as sufficiently good tracers of these sudden changes and reconstructions on the Sun, although one can still find other diagnostic indicators among the parameters of magnetic fields, motions of matter, and emission characteristics.PUBLICATION ABSTRACT
Proteomics of human milk has been used to identify the comprehensive cargo of proteins involved in immune and cellular function. Very little is known about the effects of gestational diabetes ...mellitus (GDM) on lactation and breast milk components. The objective of the current study was to examine the effect of GDM on the expression of proteins in the whey fraction of human colostrum. Colostrum was collected from women who were diagnosed with (n = 6) or without (n = 12) GDM at weeks 24–28 in pregnancy. Colostral whey was analyzed for protein abundances using high-resolution, high-mass accuracy liquid chromatography tandem mass spectrometry. A total of 601 proteins were identified, of which 260 were quantified using label free spectral counting. Orthogonal partial least-squares discriminant analysis identified 27 proteins that best predict GDM. The power law global error model corrected for multiple testing was used to confirm that 10 of the 27 proteins were also statistically significantly different between women with versus without GDM. The identified changes in protein expression suggest that diabetes mellitus during pregnancy has consequences on human colostral proteins involved in immunity and nutrition.
•Men’s support of women’s empowerment is associated with a negative opinion about female genital mutilation.•Lack of education among men is a factor contributing to support for female genital ...mutilation.•Men’s opinions differed by ethnicity with Afar and Somali respondents more likely to believe FGM should continue.•Access to media, specifically newspapers, shows promise in deterring men from having their daughters experience FGM.
Female genital mutilation (FGM) is considered a human rights violation against women and girls causing serious short and long-term health complications. Despite being a criminal offence in Ethiopia since 2004, the practice continues. Minimal research has been published on factors associated with men’s opinion about FGM in Ethiopia.
The present cross-sectional study used secondary data to identify factors associated with men’s opinions about the practice of FGM.
Secondary data analysis was conducted using data from 8,718 men who responded to the 2016 Ethiopian Demographic and Health Surveys (EDHS). The dependent variable was men’s opinion about FGM. Demographic, socioeconomic, and other characteristics were examined.
Variables associated with men’s support for FGM were lack of education (AOR = 2.91; 95% CI: 1.93, 4.40, p = <0.001), poor wealth index (AOR, 1.76; 95% CI 1.32, 2.35, p = 0.001), ethnically Afar (AOR = 2.50, 95% CI: 1.27, 4.95, p = 0.009) and Somali (AOR = 2.02, 95% CI: 1.15, 3.54, p = 0.015), Muslim religion (AOR = 1.58, 95% CI 1.13, 2.50, p = 0.007), and support for wife beating with at least one justification (AOR = 2.04, 95% CI: 1.66, 2.50, p = <0.001).
Lack of education, poor household wealth index, being Muslim and being a member of the Afar or Somali ethnicity and having a tendency that it is appropriate for a husband to beat his wife, were positively associated support for FGM. These findings suggest that context-specific interventions are needed to eradicate the practice.
The volcanic parent rock (“protolith”) composing the lunar maria is likely to have developed diverse mechanical properties upon emplacement. The abundance of rocks ejected by impacts may be sensitive ...to protolith properties. We investigate the relationship between the possible diversity of mare protoliths and the abundance of rocks excavated and emplaced by impacts employing cumulative size‐frequency distributions (SFDs) of rocky craters in the maria. The SFDs of 15 mare units were calculated through varying degrees of Lunar Reconnaissance Orbiter Diviner‐derived rock abundance within crater ejecta blankets. By inspecting the frequency of high rock abundance craters, we find that the age of a surface does not control an impactor's ability to excavate rocks. Through analysis of SFDs, we find that differences in SFD behavior may act as probes for the mechanical strength of the protolith and the thickness of buried lava flows. Generally, regions with SFDs that have shallower slopes with increasing rockiness may be associated with thick, competent flow types, and regions with SFDs that have unchanging slopes with increasing rockiness may be associated with stacked, thin flows that are possibly more friable. The greater frequency of high rock abundance craters and the converging behavior of SFDs at two units within Mare Humorum and Oceanus Procellarum suggest that the surfaces are underlain by thick, competent lava flows. Finally, SFD slope analysis suggests that secondary impact craters are relatively ineffective at excavating rocks and the SFDs of rocky craters may reflect primary cratering populations.
Plain Language Summary
When ancient lunar lava flows cooled and hardened into rock, they likely developed different properties depending on the conditions of eruption. The variations in these now‐buried volcanic rocks can be probed using impacts, which break up and eject material from the subsurface. Ejected pieces of lava flow can be measured in terms of their abundance, which we use to infer lava flow properties in this study. By inspecting the populations of craters with a high abundance of rocks in their ejecta, we determine that age does not control the frequency of highly rocky craters. Further, we determine the size‐distribution of craters with rocks in their ejecta and find different relationships between the rock‐free crater populations and the rocky crater populations. We find that changes in the rock‐free and rocky crater populations may represent variations in lava flow properties. Finally, secondary impact craters that are formed from high‐velocity debris made by primary impacts are ordinarily difficult to discern from the primary impact population; however, we determine that by inspecting the slightly rockier crater population, secondaries may be filtered out.
Key Points
Rock excavating impact populations are probes of mare protolith properties
Surface age does not control an impactor's ability to excavate rock
The size‐frequency distributions of rocky crater populations exhibit behaviors reflective of substrate competence
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