Degree Of Structural Alterations Research Articles

Quantitative analysis of nanoscale intranuclear structural alterations in hippocampal cells in chronic alcoholism via transmission electron microscopy imaging

Chronic alcoholism is known to alter the morphology of the hippocampus, an important region of cognitive function in the brain. Therefore, to understand the effect of chronic alcoholism on hippocampal neural cells, we employed a mouse model of chronic alcoholism and quantified intranuclear nanoscale structural alterations in these cells. Transmission electron microscopy (TEM) images of hippocampal neurons were obtained, and the degree of structural alteration in terms of mass density fluctuation was determined using the light-localization properties of optical media generated from TEM imaging. The results, which were obtained at length scales ranging from ~30 to 200 nm, show that 10–12 week-old mice fed a Lieber–DeCarli liquid (alcoholic) diet had a higher degree of structural alteration than control mice fed a normal diet without alcohol. The degree of structural alteration became significantly distinguishable at a sample length of ~100 nm, which is the typical length scale of the building blocks of cells, such as DNA, RNA, proteins and lipids. Interestingly, different degrees of structural alteration at such length scales suggest possible structural rearrangement of chromatin inside the nuclei in chronic alcoholism.

Differential scanning calorimetric examination of pathologic scar tissues of human skin

Keloid and hypertrophic scarring is a dermal fibroproliferative disorder characterized by increased fibroblast proliferation and excessive production of collagen. Excess scar formation occurs after dermal injury as a result of abnormal wound healing. Keloid formation has been ascribed to altered growth factor regulation, aberrant collagen turnover, genetics, immune dysfunction, sebum reaction, and altered mechanics. No single hypothesis adequately explains keloid formation. The thermal denaturations of pathologic human skin scar tissues were monitored by a SETARAM Micro DSC-II calorimeter. All the experiments were performed between 0 and 100 °C. The heating rate was 0.3 K min−1. DSC scans clearly demonstrated significant differences between the different types and conditions of samples (intact skin: T m = 54.8 °C and ΔH cal = 4.5 J g−1; normal scar: T m = 53.8 °C and ΔH cal = 4.2 J g−1; hypertrophic scar: T m = 54.2 °C and ΔH cal = 2.4 J g−1; keloid: T m = 52.9 °C and ΔH cal = 8.3 J g−1). The heat capacity change between native and denatured states of samples increased with the degree of structural alterations indicating significant water loosing. These observations could be explained with the structural alterations caused by the biochemical processes. With our investigations, we could demonstrate that DSC is a useful and well-applicable method for the investigation of collagen tissue of the human keloid and hypertrophic scar tissues. Our results may be of clinical relevance in the future, i.e., in the diagnosis of the two different pathologic scar formations, or in the choice of the optimal therapy of the disease.

Structure of Triplex DNA in the Gas Phase

Extensive (more than 90 microseconds) molecular dynamics simulations complemented with ion-mobility mass spectrometry experiments have been used to characterize the conformational ensemble of DNA triplexes in the gas phase. Our results suggest that the ensemble of DNA triplex structures in the gas phase is well-defined over the experimental time scale, with the three strands tightly bound, and for the most abundant charge states it samples conformations only slightly more compact than the solution structure. The degree of structural alteration is however very significant, mimicking that found in duplex and much larger than that suggested for G-quadruplexes. Our data strongly supports that the gas phase triplex maintains an excellent memory of the solution structure, well-preserved helicity, and a significant number of native contacts. Once again, a linear, flexible, and charged polymer as DNA surprises us for its ability to retain three-dimensional structure in the absence of solvent. Results argue against the generally assumed roles of the different physical interactions (solvent screening of phosphate repulsion, hydrophobic effect, and solvation of accessible polar groups) in modulating the stability of DNA structures.

Changes of lignin phenols and neutral sugars in different soil types of a high-elevation forest ecosystem 25 years after forest dieback

Long-term effects of forest disturbance 25 yr ago on lignin and non-cellulosic polysaccharide pools in an unmanaged high-elevation Norway spruce ( Picea abies L. [Karst.]) forest were investigated by comparing three dieback sites with three adjacent control sites with non-infested spruce on identical soils. Samples were taken from the forest floor and the mineral soil; one Ah horizon sample per site was physically fractionated into density and particle size fractions. Additionally, changes in the above- and belowground input of lignin and non-cellulosic polysaccharides after forest dieback were quantified. Lignin and its degree of structural alteration in plant and soil samples were assessed by CuO oxidation and subsequent analysis of the lignin phenols. Non-cellulosic polysaccharides were determined after hydrolysis with trifluoroacetic acid (TFA), derivatisation of their neutral sugar monomers by reduction to alditols, and subsequent acetylation. The total plant-derived input of lignin and non-cellulosic polysaccharides to the soil was similar for the dieback and the control sites. The chemical composition of the input has changed considerably after forest dieback, as shown by significantly higher syringyl/vanillyl (S/V) ratios and significantly lower (galactose+mannose)/(arabinose+xylose) (GM/AX) ratios. This indicates a changed plant input and a higher contribution of microbial sugars. Contents of lignin phenols in the forest floor and coarse particle size fractions of the A horizons were significantly smaller at the dieback sites ( p<0.01). Moreover, larger acid-to-aldehyde ratios of vanillyl units (Ac/Al) v indicated an increased degree of lignin phenol alteration. Also contents of neutral sugars were significantly ( p<0.01) smaller in the forest floor, but not in the A horizons of the dieback sites. The GM/AX mass ratios as well as the (rhamnose+fucose)/(arabinose+xylose) (RF/AX) ratios in the forest floor and coarse particle size fractions of the mineral topsoil were significantly ( p<0.01) larger after forest dieback, indicating a larger relative contribution of microbial sugars. In general, the lignin phenol and neutral sugar pools of all three soil types exhibited similar response patterns to the changed site conditions. Our results demonstrate that the lignin and neutral sugar pools of humic topsoil horizons are highly sensitive to forest disturbances. However, the two compounds show different patterns in the mineral soil, with the major neutral sugar pool being stabilized against changes whereas the lignin phenol pool decreases significantly.

Rock-strength and physical properties of Norites of the Merensky and Bastard Units, western Bushveld Complex

Platinum mining in the Bushveld Complex has expanded greatly over the last decade with many operations planned for, or already at depths greater than 1000 m. Mine infrastructures, rock fragmentation properties, rock failures and safety issues are important aspects of deeper mining operations and require an understanding of controls and properties which influence rock strength. This study, which includes rock classification of both fresh and altered material, chemical compositions, fabrics and structure, was carried out to investigate mainly the noritic rocks in the vicinity of the Merensky reef in the western Bushveld Complex. Uniaxial compressive strength (UCS) and tensile strength (TS) are shown to be broadly dependent on rock type, and strongly dependent on the degree of structural alteration as reflected by the Rock Quality Designation (RQD). In addition, there is an unexpectedly strong correlation between UCS values and both normative quartz and Zr contents of the whole rock. Both of these compositional parameters relate to the entrapment of a late-stage liquid which when solidified acted as cement and influenced the propagation of fractures under conditions of failure. Micrographic observations indicate that interstitial quartz, even in relatively small amounts, is effective in arresting fracture propagation. Relatively small variations in the quartz content could therefore significantly affect the rock strength of the norites. Other possible controls on rock strength include the relative development of foliation fabric, the distribution of crystal sizes, and the way that the rocks have annealed at high temperature.

Contribution of lignin and polysaccharides to the refractory carbon pool in C-depleted arable soils

We assessed the contribution of polysaccharides and lignin, major components of plant residues, to the refractory pool of soil organic carbon (SOC) in arable soils. Soil samples from two contrasting treatment types of European long-term agroecosystem experiments, i.e. conventionally managed (fertilized) and C-depleted plots, enriched in refractory compounds, were compared. Bulk samples from eight experimental sites and particle-size fractions of two of the sites were investigated. The CuO oxidation technique was used as a relative measure of lignin and its degree of structural alteration. The contents and composition of polysaccharides were determined following hydrolysis with trifluoroacetic acid (TFA). For the bulk samples, the amount of lignin phenols declined more than the total OC in the course of C-depletion. The contribution of lignin phenols to total OC was thus lower in the C-depleted versus the fertilized plots. A greater lignin biodegradation was found in the bulk samples of the depleted plots compared with the fertilized plots. The analysis of size fractions revealed lower OC-normalized contents of lignin phenols and a higher degree of lignin alteration in fractions <63 μm of the depleted versus the fertilized plots. These findings indicate that lignin does not accumulate within the refractory C pool of arable soils. The refractory SOC pool shows a lower contribution of lignin as compared with more labile fractions of SOC. If lignin-derived carbon is present in the stable pool it has been extensively modified so that it can no longer be identified as phenolic CuO oxidation products. OC-normalized contents of polysaccharides (neutral sugars and galacturonic acid) were similar in bulk samples of the C-depleted and fertilized plots. The contrasting treatments showed similar polysaccharide contents especially in separates <6 μm. The separates <6 μm in the C-depleted plots retained between 50 and 100% of the polysaccharide amounts in the fertilized plots. The mass ratio of (galactose+mannose)-to-(arabinose+xylose) (GM/AX) was higher in bulk samples of the C-depleted versus the fertilized plots, indicating a higher relative contribution of microbial sugars. Within a particular soil, the fine separates were those with the highest GM/AX ratio. These results indicate that the refractory C pool has a similar proportion of polysaccharides as the labile C pool, but refractory polysaccharides are mainly associated with fine separates and show a dominant contribution of microbial sugars. Our results provide evidence that polysaccharides, mainly those of microbial origin, are stabilized over the long-term within fine separates of arable soils. In contrast, CuO lignin is associated mainly with the coarse fractions and does not contribute to the refractory C pool.

Primary Macular Amyloidosis: An Ultrastructural Approach to Diagnosis

Seven cases of primary macular amyloidosis were studied on skin biopsies. The Congo red stain was positive only in three cases, whereas the ultrastructural observation allowed for the detection of amyloid deposits in all biopsies. Fibrillary degeneration of basal keratynocytes was occasionally observed, and regressive changes of keratynocytes and dermal nerve bundles presumably related to the intensity of the scratch trauma were detected in one case. In six biopsies mast cell profiles exhibiting various degrees of degranulation were detected in the dermis. Melanosome aggregates were also observed consistently in dermal macrophages and occasionally in Schwann cells. A variable degree of structural alteration was observed in dermal unmyelinated nerve fibers. Even if the intimate mechanism of amyloid deposition was not explained by the ultrastructural study, this approach is a useful instrument in the differential diagnosis of cutaneous macular hyperpigmented lesions.

Adrenergic nervous system and left ventricular mass in primary hypertension.

A link between the activity of the adrenergic nervous system and left ventricular hypertrophy has frequently been found in hypertensives. In 16 patients with untreated primary hypertension of mild to moderate degree, we have evaluated the possible correlations between echocardiographic left ventricular mass (LVMe) and sympathetic nervous system activity, using pressor response to exogenous noradrenaline infusion, measurement of 24-h catecholamine urinary excretion and pressure response to ergometric exercise. Pressor response to noradrenaline infusion was significantly related to echocardiographic measures of left ventricular hypertrophy (correlation coefficients were: -0.60 for LVMe; -0.51 for septal thickness (ST); -0.51 for posterior wall thickness). Left ventricular mass was also related to systolic blood pressure measured during ergometric exercise (correlation coefficients were: 0.52 with LVM index, 0.51 with LVMe and 0.61 with ST). Arterial wall hypertrophy has been identified as being responsible for the vascular hyperreactivity in hypertension. A likely explanation of our findings is that the degree of left ventricular hypertrophy is associated with the degree of structural alterations of the resistance vessels and that the vascular impairment is responsible for the increased pressure response to noradrenaline.

Interaction of xenobiotics with reproductive endocrine functions in a protogynous teleost, Monopterus albus

The effects of sublethal concentrations of three xenobiotics, cadmium, malathion and 3-methylcholanthrene (3-MC) on pituitary-thyroid-liver-ovary axis were studied in a protogynous teleost, Monopterus albus. After one week of exposure the gonadosomatic index (GSI) of pollutant-exposed fish was significantly reduced but the hepatosomatic index (HSI) of some fish was higher than the control. Disintegration of the histological structure of thyroid, liver and ovary was a common feature of exposed fish; however, the degree of structural alteration was different in different tissues for different pollutants. Plasma levels of both testosterone and estradiol and also phosphoprotein (vitellogenin) were significantly reduced following exposure to cadmium, malathion and 3-MC. Thyroid was differently affected by these treatments. Cadmium and 3-MC have significantly elevated triiodothyronine (T 3) and thyroxine (T 4) levels in both plasma and thyroid, however, the T 3 T 4 ratio was high only in thyroid. In comparison, malathion has significantly increased T 3 and T 4 levels and T 3 T 4 ratio in both plasma and thyroid. In in vivo as well as in vitro studies, exposure to cadmium and 3-MC resulted in significant elevation of thyroid peroxidase activity. This study provides evidence that these pollutants interfere with the endocrine system, resulting in hormonal imbalance which may be due to an impairment of either the synthesis or the secretion of these hormones, and thereby significantly affect the reproductive physiology of this species.

Corticosteroid Therapy in Central Stromal Keratitis

Use of adrenal corticosteroids in central corneal inflammatory disease has been heat­ edly discussed during the past 15 years. Kaufman and Thomas have recom­ mended topical corticosteroid therapy (com­ bined with IUDR) for disciform lesions in herpetic keratitis, while Thygeson has cau­ tioned that they may encourage virus prolif­ eration and lead to catastrophic events. Theo­ dore believes that some cases of deep stromal herpes cannot be controlled without corti­ costeroids. DeVoe has emphasized that corticosteroid therapy in herpes simplex kera­ titis should not be condemned on the basis of rabbit experiments. Corticosteroids may be used guard­ edly' in herpes zoster keratitis; they probably should be avoided in central bacterial ulcers. However, corticosteroids are the treatment of choice' in allergic cor­ neal disease. The general consensus indicates that the use of corticosteroids depends upon the etiologic agent involved rather than the degree of structural alteration. Specific therapy is always preferable but, when it is not successful, nonspecific (corticosteroid) therapy may be used. Following extensive experimental evalua­ tion of the mechanisms of inflammatory reac­ tivity in the rabbit and guinea pig cornea,