Clinical significance of combined liver function and high-sensitivity C-reactive protein measurement in children with hand-foot-mouth disease.

Hand-foot-mouth disease (HFMD) is a common pediatric disease responsible for the development of rashes or herpes on the hand, foot, and mouth. Severe complications of HFMD include myocarditis, pulmonary edema, aseptic meningoencephalitis, and even death. Therefore, early diagnosis of HFMD is of particular importance. In this study, we determined the clinical value of the combined detection of liver function and high-sensitivity C-reactive protein (hs-CRP) expression in children with HFMD. Three hundred children with HFMD were recruited to this study between July 2013 and July 2015 and divided into the mild and severe HFMD groups (N = 150 per group). The liver function [aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels] and hs-CRP expression were evaluated using standardized tests, and the clinical value of combined detection of these indices (in parallel and serially) was determined. Patients in the severe HFMD group showed significantly higher levels of ALT, AST, ALP, and hs-CRP compared to those in the mild HFMD group (P < 0.05). The hs-CRP and liver function tests had low specificity and sensitivity, respectively. However, parallel combined detection improved the sensitivity and negative predicted value of these indices, whereas serial combined detection improved the specificity and positive predicted value. In conclusion, hs-CRP and liver function play a major role in the diagnosis of HFMD (and identifying its severity), and serial combined detection of these indices enhances the positive predicted value, and could be employed to diagnose severe HFMD at an earlier stage.

Molecular characterization and functional analysis of sheep thyroid transcription factor-1.

Thyroid transcription factor-1 (TTF-1), a member of the Nkx2 family of homeodomain-containing proteins, is involved in binding to and in activating the promoters of several important genes in the thyroid, lungs, and brain, and in regulating expression of these tissue-specific genes. We investigated potential roles of sheep (Ovis aries) TTF-1 in regulating cell fate and organ morphogenesis and in controlling puberty and reproductive capability of females. We amplified and cloned the sheep TTF-1 full-length DNA for the first time, analyzed its functional domains and regions, predicted molecular structure of its homeodomain and DNA-binding sites, and examined its expression in pituitary, brain, thyroid gland, ovary, and hypothalamus. We found that sheep TTF-1 has a high degree of homologous identity with that of other mammals, and it has several important domains including domain N, DNA-binding domain, domain C, TN-domain, domain I, and NK2-SD. The DNA-binding domain of sheep TTF-1 has 10 potential DNA-binding sites and is a novel mammalian homeodomain that shows considerable sequence homology with the corresponding rat homeodomain. Several functional regions in sheep TTF-1 share high sequence identity with rat TTF-1, indicating that these regions may have the same activity as in the rat. Expression of TTF-1 in several specific tissues implies that sheep TTF-1 in involved in sheep sexual development and reproductive capability. These results suggest a role of sheep TTF-1 in enhancing sheep reproduction performance and we propose it as a candidate gene for selection.

Arsenic solubility and distribution in poultry waste and long-term amended soil.

The purpose of this study was to quantify the solubility and distribution of As among solid-phase components in poultry wastes and soils receiving long-term poultry waste applications. Arsenic in the water-soluble, NaOCl-extractable (organically bound), NH(2)OH x HCl-extractable (oxide bound) and residual fractions were quantified in an Upper Coastal Plain soil (Neshoba County, MS) that received annual waste applications. After 25 years, As in the amended soil had a mean of 8.4 mg kg(-1) compared to 2.68 mg kg(-1) for a non-amended soil. Arsenic in the amended soil was mainly in the residual fraction (72% of total), which is generally considered the least bioavailable fraction. Arsenic in poultry waste samples was primarily water-soluble (5.3-25.1 mg kg(-1)), representing 36-75% of the total As. To assess the extent of spatial heterogeneity, total As in a 0.5-ha area within the long-term waste-amended field was quantified. Soil surface samples were taken on 10-m grid points and results for total As appeared negatively skewed and approximated a bimodal distribution. Total As in the amended soil was strongly correlated with Fe oxides, clay and hydroxy interlayered vermiculite concentrations, and negatively correlated with Mehlich III-P, mica and quartz contents.

Water-quality effects of incorporating poultry litter into perennial grassland soils.

Poultry litter provides a rich source of nutrients for perennial forages, but the usual practice of surface-applying litter to pastures can degrade water quality by allowing nutrients to be transported from fields in surface runoff, while much of the NH4-N volatilizes. Incorporating litter into the soil can minimize such problems in tilled systems, but has not been used for perennial forage systems. In this study, we minimized disturbance of the crop, thatch, and soil structure by using a knifing technique to move litter into the root zone. Our objective was to determine effects of poultry litter incorporation on quantity and quality of runoff water. Field plots were constructed on a silt loam soil with well-established bermudagrass [Cynodon dactylon (L.) Pers.] and mixed grass forage. Each plot had 8 to 10% slopes, borders to isolate runoff, and a downslope trough with sampling pit. Poultry litter was applied (5.6 Mg ha(-1)) by one of three methods: surface-applied, incorporated, or surface-applied on soil-aeration cuts. There were six treatment replications and three controls (no litter). Nutrient concentrations and mass losses in runoff from incorporated litter were significantly lower (generally 80-95% less) than in runoff from surface-applied litter. By the second year of treatment, litter-incorporated soils had greater rain infiltration rates, water-holding capacities, and sediment retention than soils receiving surface-applied litter. Litter incorporation also showed a strong tendency to increase forage yield.

Redistribution index and relative binding intensity of heavy metals in salt-amended soils.

Redistribution processes of heavy metals and their binding intensity in salt-amended arid-zone soils were analyzed under saturated, field capacity and wetting-drying cycle moisture regimes. Two newly developed parameters, redistribution index and reduced partitioning parameter, were used to depict the removal/attainment of metal-amended soils from/to the fractional distribution pattern in the native soils and the relative binding intensity of metals in the amended soils, respectively. Metal-amended soils, in forms of salts approached the fractional distribution pattern in the non-amended soils with time. The rates at which the metal-amended arid-zone soils approached the fractional distribution pattern characteristic of the native soil were affected by the nature and loading levels of the metals, soil properties and time. Metals in amended soils at low loading levels approach the fractional distribution pattern characteristic of non-amended soil more rapidly than at high loading levels. The sequences of approach by various metals to the fractional distribution pattern in the native soil are as follows: Cd > Cu > Ni, Zn > Cr. Moisture regime, however, did not considerably affect the metal-amended soils' overall rates of approach to the fractional distribution pattern prevailing in the non-amended soils. The binding intensity of metals in soils was affected by the nature of metal, loading level, soil properties and time. In both non-amended and amended soils, Cr had highest binding intensity, Cd lowest and Cu, Ni and Zn intermediate. The binding intensity decreased with the loading level of the metals and increased with time. The redistribution index and reduced partitioning index can quantitatively and effectively depict the kinetics of redistribution processes of metals and their relatively binding intensity in waste-amended soils.

Accumulation, distribution, and toxicity of copper in sediments of catfish ponds receiving periodic copper sulfate applications.

Copper sulfate (CuSO4) is applied periodically to commercial channel catfish (Ictalurus panctatus) ponds as an algicide or parasiticide. Current understanding of the chemistry of copper in soil-water systems suggests that copper may accumulate in pond sediments, although the forms and potential bioavailability of copper in catfish pond sediments are not known. This study investigated the accumulation and distribution of copper in the sediment of catfish ponds receiving periodic additions of CuSO4.5H2O. All ponds were constructed in Sharkey (very-fine, smectitic, thermic Chromic Epiaquert) soil. Nine 0.40-ha ponds received 59 applications of 2.27 kg CuSO4.5H2O per application per pond over 3 yr; no CuSO4.5H2O applications were made to nine additional ponds. Total Cu concentration in the sediments of CuSO4.5H2O-amended catfish ponds (172.5 mg kg(-1)) was four to five times higher than that in the sediments of nonamended ponds (36.1 mg kg(-1)). Copper accumulated in catfish pond sediments at a rate of 41 microg kg(-1) dry sediment for each 1 kg ha(-1) of CuSO4. 5H2O applied to ponds. Copper in the sediments of amended ponds was mainly in the organic matter-bound (30.7%), carbonate-bound (31.8%), and amorphous iron oxide-bound (22.1%) fractions with a considerable fraction (3.4%; 3 to 8 mg kg(-1)) in soluble and exchangeable fractions. This indicates that Cu accumulates differentially in various fractions, with proportionally greater initial accumulation in potentially bioavailable forms. However, toxicity bioassays with amphipods (Hyallela azteca) and common cattail (Typha latifolia L.) indicated that the effect of exposure to amended or nonamended pond sediments was not different.

G-quadruplexes as targets for drug design.

G-quadruplexes are a family of secondary DNA structures formed in the presence of monovalent cations that consist of four-stranded structures in which Hoogsteen base-pairing stabilizes G-tetrad structures. These structures are proposed to exist in vivo, although direct confirmatory evidence is lacking. Guanine-rich regions of DNA capable of forming G-quadruplex structures are found in a variety of chromosomal regions, including telomeres and promoter regions of DNA. In this review, we describe the design of three separate groups of G-quadruplex-interactive compounds and their interaction with G-quadruplex DNA. Using the first group of compounds (anthraquinones), we describe experiments that provide the proof of concept that a G-quadruplex is required for inhibition of telomerase. Using the second group of compounds (perylenes), we describe the structure of a G-quadruplex-ligand complex and its effect on the dynamics of formation and enzymatic unwinding of the quadruplex. For the third group of compounds (porphyrins), we describe the experiments that relate the biological effects to their interactions with G-quadruplexes.

A model for the T-antigen-induced structural alteration of the SV40 replication origin based upon experiments with specific probes for bent, straight, and unwound DNA.

The T-antigen-induced structural changes of the SV40 replication origin were probed with three DNA-reactive antitumor agents: (+)-CC-1065, bizelesin, and pluramycin. (+)-CC-1065 is an N3 adenine minor groove alkylating agent that selectively reacts with AT-rich DNA sequences with a bent conformation; bizelesin also reacts with the minor groove of AT-rich sequences but is selective for a conformation; bizelesin also reacts with the minor groove of AT-rich sequences but is selective for a straight DNA conformation. Pluramycin is an intercalative guanine alkylator whose reactivity is increased by unwinding and decreased by compression of the minor and/or major grooves of DNA. We show that while binding of T-antigen reduced the ability of (+)-CC-1065 to alkylate the AT tract in the SV40 replication origin, it did not interfere with bizelesin modification of the same sequence. These unexpected results suggest that when T-antigen binds to the SV40 origin the AT tract is in a straight DNA conformation. High-resolution DNase I footprinting experiments indicate that at least three helically in-phase T-antigen binding sites exist in the GC box region located immediately downstream of the AT tract. The binding of T-antigen enhances the reactivity of (+)-CC-1065 to the two 5'-AGTTA(asterisk) (the asterisk indicates the covalent bonding site) drug modification sites in the GC box region, demonstrating that these sites are in a bent conformation. In contrast, T-antigen inhibited the reactivity of pluramycin at sequences within the GC box region that are known not to bind T-antigen. These data, in combination with the DNase I footprinting results, suggest that T-antigen binding induces a conformational change in the DNA that no longer favors pluramycin intercalation. Based on our results, we propose that T-antigen binds tightly to the upstream region of the AT tract of SV40 replication origin forming double hexamers. In the downstream region, binding of T-antigen to the helically in-phase sites in the GC box region induces DNA bending in the opposite direction of the natural AT tract bending, while simultaneously transforming the naturally bent AT tract DNA into a straight conformation.