Association between blood cadmium level and bone mineral density reduction modified by renal function in young and middle-aged men

The association between cadmium exposure and bone mineral density (BMD) has not been well studied in young and middle-aged men. This study examined the relationship between the level of blood Cd (BCd) and BMD in a young to middle-aged representative male population while considering renal function. Using data from the 4th Korea National Health and Nutrition Examination Survey, 2008–2009, 1275 adult men aged 20–64 years were analyzed. BCd was measured by atomic absorption spectrophotometry and renal function was assessed by the estimated glomerular filtration rate (eGFR) with CKD-EPI formula. The risk of lower bone density was increased according to the increase in BCd levels after adjusting for eGFR and covariates, in which a significant interaction between BCd and eGFR existed. Significant negative associations between BCd and BMD were found: beta (p-value) were −0.03 (0.02), −0.04 (0.004) and −0.03 (0.04) in total femur, lumbar spine and femoral neck, respectively, which were limited to the people with eGFR ≤ lower 25%. Although, a causal relationship could not be determined because of a cross-sectional design in the present study, the results suggest low level Cd toxicity to bone via low eGFR and that measures to reduce environmental Cd exposure may be helpful to prevent bone loss in men.     

Identifying high value areas for conservation: Accounting for connections among terrestrial,freshwater, and marine habitats in a tropical island system

Functional ecosystems depend on biotic and abiotic connections among different environmental realms, including terrestrial, freshwater, and marine habitats. Accounting for such connections is increasingly recognized as critical for conservation of ecosystems, especially given growing understanding of the way in which anthropogenic landscape disturbances can degrade both freshwater and marine habitats. This need may be paramount in conservation planning for tropical island ecosystems, as habitats across realms are often in close proximity, and because endemic organisms utilize multiple habitats to complete life histories. In this study, we used Marxan analysis to develop conservation planning scenarios across the five largest islands of Hawaii, in one instance accounting for and in another excluding habitat connectivity between inland and coastal habitats. Native vegetation, perennial streams, and areas of biological significance along the coast were used as conservation targets in analysis. Cost, or the amount of effort required for conservation, was estimated using an index that integrated degree and intensity of anthropogenic landscape disturbances. Our results showed that when connectivity is accounted for among terrestrial, freshwater, and marine habitats, areas identified as having high conservation value are substantially different compared to results when connectivity across realms is not considered. We also showed that the trade-off of planning conservation across realms was minimal and that cross-realm planning had the unexpected benefit of selecting areas with less habitat degradation, suggesting less effort for conservation. Our cross-realm planning approach considers biophysical interactions and complexity within and across ecosystems, as well as anthropogenic factors that may influence habitats outside of their physical boundaries, and we recommend implementing similar approaches to achieve integrated conservation efforts.     

Glycochenodeoxycholate promotes the metastasis of gallbladder cancer cells by inducing epithelial to mesenchymal transition via activation of SOCS3/JAK2/STAT3 signaling pathway

The incidence of gallbladder cancer (GBC) is relatively rare but a high degree of malignancy. The migration and invasion potential of GBC severely affects the prognosis of patients with GBC. Glycochenodeoxycholate (GCDC) is one of the most important components in GBC-associated microenvironment. However, the role of GCDC in the metastatic feature of GBC cells is not fully understood. First, the results of this study found that GCDC could effectively enhance the metastasis of GBC cells. Furthermore, GCDC could lead to the enhancement of epithelial to mesenchymal transition (EMT) phenotype in GBC cells, which is concerned to be an important mechanism of tumor metastasis. Further studies showed that GCDC treatment induced the upregulation of matrix metalloproteinase-3 (MMP3), MMP9, and SOCS3/JAK2/p-STAT3 signal pathway in GBC cells, which could regulate the level of EMT. Beside that, we also found the positive expression of farnesoid X receptor (FXR) in GBC cells and inhibition of FXR could significantly block the effect of GCDC on the metastasis of GBC cells. These results indicated that GCDC promoted GBC cells metastasis by enhancing the level of EMT and inhibition of FXR could significantly block the effect of GCDC. On one hand, FXR might be an indicator for predicting the metastasis of patient with GBC. On the other hand, FXR might serve as a potential antimetastasis target in GBC therapy.     

Statistical Evaluation of the Effect of Gemfibrosil,a Cholesterol Reducing Drug,on Some Biochemical Coronary Heart Disease Risk Variables

The evaluation is based on the clinic trial with gemfibrosil (“Gevilon”, Parke-Davis) carried out in a group of 48 patients, to whom the drug was administered in the single dose of 900 mg daily during the period of 3 months. In this paper we show the results of the treatment on five biochemical Coronary Heart Disease (CHD) risk variables: Cholesterol (CHOL), High Density Lipoprotein (HDL), Triglyccrides (TGL), Uric Acid (UA) and Glucose (GL). We are concerned with a statistical model allowing to predict which and how large changes in the considered variable can be expected in a patient taking the drug. This is done considering the “regression to the mean” effect.     

An improved approach to evaluate car sharing options

We develop an improved approach to evaluate car sharing options under uncertain environments with the combination of Fuzzy Analytic Hierarchy Process (F-AHP) and Fuzzy Technique for Order Preference by Similarity to Ideal Solution (F-TOPSIS), which consists of three steps. In the first step, we propose a SCUMN (Specific, Comprehensive, Understandable, Measurable, and Neutral) methodology to identify appropriate indicators and obtain a final list of 24 indicators according to their relevance to car sharing options. In the second step, we determine the weight of each indicator with F-AHP and conduct consistency check of the comparison matrix of selected indicators. In the third step, comparison of different options is performed with selected indicators and F-TOPSIS. A case study is provided to validate the proposed approach. Twenty-four indicators are identified to evaluate five different car sharing options and rank them according to their closeness coefficients in decreasing order. And thirty-one sensitivity analysis experiments are conducted to figure out the influence of indicators on decision making. The experimental results show that the proposed approach is capable of evaluating car sharing options with uncertainty and vagueness. F-AHP is able to determine the weight for each selected indicator and F-TOPSIS demonstrates its advantage in comparing potential options.     

Microsecond Dynamics During the Binding-induced Folding of an Intrinsically Disordered Protein

Tau is an intrinsically disordered protein implicated in many neurodegenerative diseases. The repeat domain fragment of tau, tau-K18, is known to undergo a disorder to order transition in the presence of lipid micelles and vesicles, in which helices form in each of the repeat domains. Here, the mechanism of helical structure formation, induced by a phospholipid mimetic, sodium dodecyl sulfate (SDS) at sub-micellar concentrations, has been studied using multiple biophysical probes. A study of the conformational dynamics of the disordered state, using photoinduced electron transfer coupled to fluorescence correlation spectroscopy (PET-FCS) has indicated the presence of an intermediate state, I, in equilibrium with the unfolded state, U. The cooperative binding of the ligand (L), SDS, to I has been shown to induce the formation of a compact, helical intermediate (IL₅) within the dead time (∼37 µs) of a continuous flow mixer. Quantitative analysis of the PET-FCS data and the ensemble microsecond kinetic data, suggests that the mechanism of induction of helical structure can be described by a U ↔ I ↔ IL₅ ↔ FL₅ mechanism, in which the final helical state, FL₅, forms from IL₅ with a time constant of 50–200 µs. Finally, it has been shown that the helical conformation is an aggregation-competent state that can directly form amyloid fibrils.     

Interaction between the light quality and flowering time pathways in Arabidopsis

Flowering in Arabidopsis is accelerated by a reduced ratio of red light to far-red light (R/FR), which indicates the proximity of competitive vegetation. By exploiting the natural genetic variation in flowering time responses to low R/FR, we obtained further insight into the complex pathways that fine-tune the transition to flowering in Arabidopsis. The Bla-6 ecotype does not flower significantly earlier in response to low R/FR, but is still able to display other features of shade avoidance, suggesting branching of low R/FR signalling. Here we show that the muted flowering response of Bla-6 is due to high levels of the floral repressor FLOWERING LOCUS C (FLC), conferred by a combination of functional FLC and FRIGIDA ( FRI ) alleles with a 'weak' FY allele. The Bla-6 FY allele encodes a protein with a corrupted WW binding domain, and we provide evidence that this locus plays a key role in the natural variation in light quality-induced flowering in Arabidopsis. In Bla-6, FLC blocks promotion to flowering by reduced R/FR by inhibiting expression of the floral integrator FLOWERING LOCUS T ( FT ) in a dose-dependent manner. Reduction of FLC removes this obstruction, and Bla6 plants then exhibit strong induction of FT and flower early in response to a low R/FR signal. This paper illustrates the intricate interaction of environmental signals and genetic factors to regulate flowering in Arabidopsis.     

The role of the basal hypothalamus in the regulation of reproductive behavior in the lizard, Anolis carolinensis: lesion studies

Bilateral radiofrequency lesions in the anterior and posterior basal hypothalamus decreased courtship and agonistic behaviors in both intact, sexually active, and castrated, androgen treated male Anolis carolinensis. Intact males receiving lesions in the anterior basal hypothalamus had atrophied testes, aspermia, and decreased epithelial cell height of the renal sex segment. Lesions of the posterior basal hypothalamus had no effect on testicular activity or the development of accessory organs. All animals demonstrating behavioral changes had lesion destruction in the ventromedial nucleus and the accompanying periventricular system. It is concluded that the basal hypothalamus in male A. carolinensis is involved both in the regulation of reproductive behavior and pituitary function.     

Proton nmr spectroscopy of high-spin ferrous cytochrome P-450 models

Alkyl mercaptide complexes of both synthetic and natural-derivative iron(II) porphyrins have been characterized in DMSO solution by proton nmr spectroscopy. A single mercaptide ligand binds to form a high-spin iron(II) complex as determined by solution magnetic measurements and the nmr isotropic shift pattern. Ligand exchange is slow on the nmr time scale unlike corresponding 2-methyl imidazole exchange rates which are very rapid. Further comparison of mercaptide and 2-methyl imidazole adducts reveals a downfield bias in isotropic shift values for the mercaptide species, which may be explained by different signs in the dipolar shift term for the two complexes. This apparent magnetic anisotropy of the mercaptide complex is in the same direction, although smaller, than that observed for bacterial cytochrome P-450. Isotropic shift values of at least 250 ppm for methylene resonances of the coordinated mercaptide support a very efficient unpaired spin delocalization for this axial ligand.     

Chronic caffeine consumption increases the number of brain adenosine receptors

Caffeine, a potent central stimulant, is known to competitively inhibit the specific binding of both adenosine and benzodiazepine receptor ligands to brain membranes in vitro. In mice receiving a diet containing non-toxic doses of caffeine (200 or 400 mg/kg diet) for periods up to 40 days, a dose-related increase in the number of binding sites for [3H]-CHA and [3H] DPX was observed in whole brain membranes without modifications of the receptors' affinity. Furthermore, a transitory increase in the number of [3H]-DZP binding sites was observed. These preliminary data seem to confirm the involvement of the adenosine receptors in the mode of action of caffeine and may be relevant to the development of both tolerance and dependence to some of the central effects of this compound.