Protective effect of selenium against mercury-induced toxicity on hematological and biochemical parameters of Oreochromis niloticus

In this study, to identify mercury (Hg) toxicity and whether selenium (Se) has any role in alleviation of this toxicity, it was investigated the changes in hematological and serum biochemical parameters of Oreochromis niloticus. Fish were exposed to 0.01 and 0.1 mg/L Hg and 0.01 mg/L Hg + 0.1 mg/L Se and 0.1 mg/L Hg + 1.0 mg/L Se for 7 and 14 days. The exposure of O. niloticus to Hg alone resulted in decreases in red blood cell, white blood cell, hemoglobin, hematocrit values, and cholinesterase activity while it increased in alanine aminotransferase and aspartate aminotransferase activities and cortisol and glucose levels. Se, in combination with Hg, partially or totally caused an alleviation for the toxic effect of Hg on the above mentioned hematological and biochemical parameters. The results of our study showed that Se has a protective effect against toxicity induced by Hg.     

Introducing metallocene into a triazole peptide conjugate reduces its off-rate and enhances its affinity and antiviral potency for HIV-1 gp120

In this work, we identified a high affinity and potency metallocene-containing triazole peptide conjugate that suppresses the interactions of HIV-1 envelope gp120 at both its CD4 and co-receptor binding sites. The ferrocene-peptide conjugate, HNG-156, was formed by an on-resin copper-catalysed [2+3] cycloaddition reaction. Surface plasmon resonance interaction analysis revealed that, compared to a previously reported phenyl-containing triazole conjugate HNG-105 (105), peptide 156 had a higher direct binding affinity for several subtypes of HIV-1 gp120 due mainly to the decreased dissociation rate of the conjugate-gp120 complex. The ferrocene triazole conjugate bound to gp120 of both clade A (92UG037-08) and clade B (YU-2 and SF162) virus subtypes with nanomolar KD in direct binding and inhibited the binding of gp120 to soluble CD4 and to antibodies that bind to HIV-1YU-2 gp120 at both the CD4 binding site and CD4-induced binding sites. HNG-156 showed a close-to nanomolar IC50 for inhibiting cell infection by HIV-1BaL whole virus. The dual receptor site antagonist activity and potency of HNG-156 make it a promising viral envelope inhibitor lead for developing anti-HIV-1 treatments.     

Assessment of serum thiol/disulfide homeostasis in multiple myeloma patients by a new method

Objectives: The etiology of multiple myeloma (MM) is not exactly known. This study investigated the role of thiol/disulfide homeostasis in the etiopathogenesis of MM.

Methods: Some 50 patients with MM (aged 39–84 years) and 50 sex-matched healthy volunteer controls (aged 50–91 years) participated in this study. Venous blood samples were collected, and levels of native thiols, total thiols, and disulfide were measured.

Results: Native and total thiol levels in the control group were determined to be higher than in the study and patient groups (P<0.001). Disulfide levels were found to be higher in the control group than in the study group and higher in newly diagnosed patients than in outpatients who were undergoing treatment (P=0.002). The ratios of thiol levels were found to be similar in both the study and control groups (P>0.05).

Discussion: The results of the study show that although there was a decrease in the levels of disulfide, native thiol, and total thiol, the balance of thiol/disulfide was maintained. This is the first study to research the homeostasis of dynamic thiol/disulfide from the perspective of the new method that was used. We hope that this study will encourage and facilitate further studies in this area.     

Comparison of the chemical and thermal denaturation of proteins by a two-state transition model

The conformational stabilities of eight proteins in terms of the free energy differences between the native "folded" state of the protein and its "unfolded" state were determined at 298 K by two methods: chemical denaturation at 298 K and extrapolation to 298 K of the thermal denaturation results at high temperature. The proteins were expressed in Escherichia coli from the Haemophilus influenzae and E. coli genes at different levels of expression, covered a molecular mass range from 13 to 37 kg mol(-1) per monomeric unit (some exhibiting unique structural features), and were oligomeric up to four subunits. The free energy differences were determined by application of a two-state transition model to the chemical and thermal denaturation results, ranged from 9.4 to 148 kJ mol(-1) at 298 K, and were found to be within the experimental uncertainties of both methods for all of the proteins. Any contributions from intermediate states detectable from chemical and thermal denaturation differences in the unfolding free energy differences in these proteins are within the experimental uncertainties of both methods.     

Characterization of a spirochaete isolated from a case of bovine digital dermatitis

AIMS: The aim of the study was to characterize a spirochaete isolated from the lesions of a cow with digital dermatitis (DD). METHODS AND RESULTS: The characterization was on the basis of its light and electron microscopic appearance, enzymic profile and DNA sequence analysis of its flagellin and 16S rRNA genes. The spirochaete was 6-8-microm long and 0.2-0.3 microm in diameter, and possessed seven to eight periplasmic flagella, with three to five helical turns. The enzymic profile of the bacterium resembles, but is not identical to that of Treponema brennaborense. Its flagellin gene sequence was identical to that of Treponema phagedenis but distinct from that of an ovine spirochaete. Analysis of a 1477-bp region of the 16S rRNA genes indicated that this is a Treponema species and that it is indistinguishable from some isolates made from cases of bovine DD in the United States. Finally, electron microscopy revealed the presence of myovirus-like bacteriophage particles in all cultures of the treponeme examined. CONCLUSIONS: The spirochaete isolate was identified as a Treponema species closely related to some isolates from the United States (by 16S rDNA) and to T. phagedenis (by flagellin gene sequence) and is associated with bacteriophage particles. SIGNIFICANCE AND IMPACT OF THE STUDY: The fact that the isolates with the same or very similar 16S rDNA sequences have been obtained from cases of bovine DD in cattle in different countries at different times, lends further support to the hypothesis that treponemes play a role in the pathogenesis of this disease.     

Photosynthetic,hydraulic and biomass properties in closely related C3 and C4 species

In plants, most water is absorbed by roots and transported through vascular conduits of xylem which evaporate from leaves during photosynthesis. As photosynthesis and transport processes are interconnected, it was hypothesized that any variation in water transport demand influencing water use efficiency (WUE), such as the evolution of C₄ photosynthesis, should affect xylem structure and function. Several studies have provided evidence for this hypothesis, but none has comprehensively compared photosynthetic, hydraulic and biomass allocation properties between C₃ and C₄ species. In this study, photosynthetic, hydraulic and biomass properties in a closely related C₃ Tarenaya hassleriana and a C₄ Cleome gynandra are compared. Light response curves, measured at 30°C, showed that the C₄ C. gynandra had almost twice greater net assimilation rates than the C₃ T. hassleriana under each increasing irradiation level. On the contrary, transpiration rates and stomatal conductance were around twice as high in the C₃, leading to approximately 3.5 times higher WUE in the C₄ compared with the C₃ species. The C₃ showed about 3.3 times higher hydraulic conductivity, 4.3 times greater specific conductivity and 2.6 times higher leaf‐specific conductivity than the C₄ species. The C₃ produced more vessels per xylem area and larger vessels. All of these differences resulted in different biomass properties, where the C₄ produced more biomass in general and had less root to shoot ratio than the C₃ species. These results are in support of our previous findings that WUE, and any changes that affect WUE, contribute to xylem evolution in plants.     

The neuronal transporter gene SLC6A15 confers risk to major depression

Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors probably contributes to MD. We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a downregulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of?MD. The same polymorphisms also showed associations with alterations in hippocampal volume and neuronal integrity. Thus, decreased SLC6A15 expression, due to genetic or environmental factors, might alter neuronal circuits related to the susceptibility for MD. Our convergent data from human genetics, expression studies, brain imaging, and animal models suggest a pathophysiological mechanism for MD that may be accessible to drug targeting.     

Aberrant expressions of leptin and adiponectin receptor isoforms in chronic myeloid leukemia patients

Background

Leptin and adiponectin receptors mediate the role of leptin in stimulating the growth of leukemic cells and the protective function of adiponectin undertaken in several malignancies such as leukemia. In this study, we investigated the involvement of the expression of leptin and adiponectin receptors in chronic myeloid leukemia (CML) pathogenesis.

Methods

The expression of leptin receptor isoforms, OB-Rt, OB-Ra, and OB-Rb, and the expression of adiponectin receptors, AdipoR1 and AdipoR2, were measured as mRNA levels in two CML cell lines (K562 and Meg-01) and 20 CML patients and 24 healthy controls by using RT-PCR.

Results

OB-Rt and OB-Ra isoforms expression of the leptin receptors were found to be significantly lower in Meg-01 cell lines than K562 cells. All leptin receptors were downregulated in CML patients and more particularly OB-Rb level was found to be undetectably low in normal PBMC as well as in CML patients. AdipoR1 expression level was higher in Meg-01 than in K562, whereas AdipoR2 level was found to be unchanged in both cell lines. Interestingly, while AdipoR1 expression increased in CML patients, AdipoR2 decreased. Moreover, imatinib therapy did not affect both leptin and adiponectin isoform expressions.

Conclusion

While the decrease in leptin receptor levels in CML patients was confirmed, the increase in AdipoR1 levels and relevant decrease in AdipoR2 levels depicted their possible involvement in CML pathogenesis. This suggests different functions of adiponectin receptors in CML development.     

Management of secondary soft-tissue deficits following microsurgical head and neck reconstruction by means of another free flap

Secondary soft-tissue deficits may develop following a microsurgical reconstruction in the head and neck region because of inadequate planning or chronic effects of radiotherapy. Although most cases could be managed with alternative methods, free flaps might be necessary in difficult cases. Herein are described 11 cases of microsurgical head and neck reconstruction in which secondary soft-tissue deficits required transfer of another soft-tissue free flap. All patients had malignant tumors treated with surgical resection, and their defects were reconstructed with free flaps. Seven patients received either preoperative or postoperative adjunctive radiotherapy. These patients gradually developed signs and symptoms of soft-tissue deficiency in the reconstructed area, and a soft-tissue free flap transfer was required for treatment within an average of 21.5 months of their initial reconstruction. Five rectus abdominis, one rectus femoris, one latissimus dorsi, one tensor fasciae latae myocutaneous, one radial forearm, one medial arm, and one dorsalis pedis flap were used for this purpose. All flaps survived completely. The average follow-up time was 32 months. Significant improvement was achieved in all cases, and no further major surgical procedures were required. Secondary soft-tissue deficits that could not be predicted or prevented during the initial microsurgical reconstruction may be treated successfully by a subsequent free soft-tissue transfer in selected cases.