Are Binary Copper Sulfides/Selenides Really New and Promising Thermoelectric Materials?

Copper sulfides and copper selenides have recently been reported as new and promising low‐cost and environmentally friendly thermoelectric materials. Here, it is shown that these materials have actually been studied for more than 190 years and the absence of commercial thermoelectric modules based on them stems from some major intrinsic issues related to these chalcogenides. Further development of these semiconductors will require addressing and solving these problems before large scale utilization can be considered.     

Carbohydrate Sequence of the Prostate Cancer-associated Antigen F77 Assigned by a Mucin O-Glycome Designer Array

Monoclonal antibody F77 was previously raised against human prostate cancer cells and has been shown to recognize a carbohydrate antigen, but the carbohydrate sequence of the antigen was elusive. Here, we make multifaceted approaches to characterize F77 antigen, including binding analyses with the glycolipid extract of the prostate cancer cell line PC3, microarrays with sequence-defined glycan probes, and designer arrays from the O-glycome of an antigen-positive mucin, in conjunction with mass spectrometry. Our results reveal F77 antigen to be expressed on blood group H on a 6-linked branch of a poly-N-acetyllactosamine backbone. We show that mAb F77 can also bind to blood group A and B analogs but with lower intensities. We propose that the close association of F77 antigen with prostate cancers is a consequence of increased blood group H expression together with up-regulated branching enzymes. This is in contrast to other epithelial cancers that have up-regulated branching enzymes but diminished expression of H antigen. With knowledge of the structure and prevalence of F77 antigen in prostate cancer, the way is open to explore rationally its application as a biomarker to detect F77-positive circulating prostate cancer-derived glycoproteins and tumor cells.     

Nucleotide selection by the Y-family DNA polymerase Dpo4 involves template translocation and misalignment

Y-family DNA polymerases play a crucial role in translesion DNA synthesis. Here, we have characterized the binding kinetics and conformational dynamics of the Y-family polymerase Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) using single-molecule fluorescence. We find that in the absence of dNTPs, the binary complex shuttles between two different conformations within ∼1 s. These data are consistent with prior crystal structures in which the nucleotide binding site is either occupied by the terminal base pair (preinsertion conformation) or empty following Dpo4 translocation by 1 base pair (insertion conformation). Most interestingly, on dNTP binding, only the insertion conformation is observed and the correct dNTP stabilizes this complex compared with the binary complex, whereas incorrect dNTPs destabilize it. However, if the n+1 template base is complementary to the incoming dNTP, a structure consistent with a misaligned template conformation is observed, in which the template base at the n position loops out. This structure provides evidence for a Dpo4 mutagenesis pathway involving a transient misalignment mechanism.     

Shock Wave Application to Cell Cultures

Shock waves nowadays are well known for their regenerative effects. Basic research findings showed that shock waves do cause a biological stimulus to target cells or tissue without any subsequent damage. Therefore, in vitro experiments are of increasing interest. Various methods of applying shock waves onto cell cultures have been described. In general, all existing models focus on how to best apply shock waves onto cells.However, this question remains: What happens to the waves after passing the cell culture? The difference of the acoustic impedance of the cell culture medium and the ambient air is that high, that more than 99% of shock waves get reflected! We therefore developed a model that mainly consists of a Plexiglas built container that allows the waves to propagate in water after passing the cell culture. This avoids cavitation effects as well as reflection of the waves that would otherwise disturb upcoming ones. With this model we are able to mimic in vivo conditions and thereby gain more and more knowledge about how the physical stimulus of shock waves gets translated into a biological cell signal (“mechanotransduction").     

Angiotensin converting enzyme gene polymorphism is associated with severity of coronary artery disease in men with high total cholesterol levels

This study examines whether renin-angiotensin-aldosterone system gene polymorphisms: ACE (encoding for angiotensin converting enzyme) c.2306-117_404 I/D, AGTR1 (encoding for angiotensin II type-1 receptor) c.1080*86A>C and CYP11B2 (encoding for aldosterone synthase) c.-344C>T are associated with the extension of coronary atherosclerosis in a group of 647 patients who underwent elective coronary angiography. The extension of CAD was evaluated using the Gensini score. The polymorphisms were determined by PCR and RFLP assays. The associations between genotypes and the extent of coronary atherosclerosis were tested by the Kruskal-Wallis test, followed by pairwise comparisons using Wilcoxon test. The population has been divided into groups defined by: sex, smoking habit, past myocardial infarction, BMI (>, ≤ 25), age (>, ≤ 55), diabetes mellitus, level of total cholesterol (>, ≤ 200 mg/dl), LDL cholesterol (>, ≤ 130 mg/dl), HDL cholesterol (>, ≤ 40 mg/dl), triglycerides (>, ≤ 150 mg/dl). Significant associations between the ACE c.2306-117_404 I/D polymorphism and the Gensini score in men with high total cholesterol levels (P_{Kruskal-Wallis} = 0.008; P_adjusted = 0.009), high level of LDL cholesterol (P_{Kruskal-Wallis} = 0.016; P_adjusted = 0.028) and low level of HDL cholesterol (P_{Kruskal-Wallis} = 0.04; P_adjusted = 0.055) have been found. No association between the AGTR1 c.1080*86A>C and CYP11B2 c.-344C>T and the Gensini score has been found. These results suggest that men who carry ACE c.2306-117_404 DD genotype and have high total cholesterol, high LDL cholesterol and low HDL cholesterol levels may be predisposed to the development of more severe CAD.     

Suppression of peeling during the release of O-glycans by hydrazinolysis

The analysis of O-glycans is essential for better understanding their functions in biological processes. Although many techniques for O-glycan release have been developed, the hydrazinolysis release method is the best for producing O-glycans with free reducing termini in high yield. This release technique allows the glycans to be labeled with a fluorophore and analyzed by fluorescence detection. Under the hydrazinolysis release conditions, a side reaction is observed and causes the loss of monosaccharides from the reducing terminus of the glycans (known as peeling). Using bovine fetuin (because it contains the sialylated O-glycans most commonly found on biopharmaceuticals) and bovine submaxillary gland mucin (BSM), here we demonstrate that peeling can be greatly reduced when the sample is buffer exchanged prior to hydrazinolysis with solutions of either 0.1% trifluoroacetic acid (TFA) or low-molarity (100, 50, 20, and 5 mM) ethylenediaminetetraacetic acid (EDTA). The addition of calcium chloride to fetuin resulted in an increase in peeling, whereas subsequent washing with EDTA abolished this effect, suggesting a role of calcium and possibly other cations in causing peeling. The presented technique for sample preparation prior to hydrazinolysis greatly reduces the level of undesirable cleavage products in O-glycan analysis and increases the robustness of the method.     

Tissue engineering: revolution and challenge in auricular cartilage reconstruction

External ear reconstruction for congenital deformity such as microtia or following trauma remains one of the greatest challenges for reconstructive plastic surgeons. The problems faced in reconstructing the intricate ear framework are highly complex. A durable, inert material that is resistant to scar contracture is required. To date, no material, autologous or prosthetic, is available that perfectly mimics the shapely elastic cartilage found in the ear. Current procedure involves autologous costal cartilage that is sculpted to create a framework for the overlying soft tissues. However, this is associated with donor-site morbidity, and few surgeons worldwide are skilled in the techniques required to obtain excellent results. Various alloplastic materials have therefore been used as a framework. However, a degree of immunogenicity and infection and extrusion are inevitable, and results are often disappointing. Tissue-engineered cartilage is an alternative approach but, despite significant progress in this area, many problems remain. These need to be addressed before routine clinical application will become possible. The current tissue-engineered options are fragile and inflexible. The next generation of auricular cartilage engineering is promising, with smart materials to enhance cell growth and integration, and the application of stem cells in a clinical setting. More recently, the authors' team designed the world's first entirely synthetic trachea composed of a novel nanocomposite material seeded with the patient's own stem cells. This was successfully transplanted in a patient at the Karolinska Hospital in Sweden and may translate into a tissue-engineered auricle in the future.     

Role of actin C-terminus in regulation of striated muscle thin filament

In striated muscle, regulation of actin-myosin interactions depends on a series of conformational changes within the thin filament that result in a shifting of the tropomyosin-troponin complex between distinct locations on actin. The major factors activating the filament are Ca²⁺ and strongly bound myosin heads. Many lines of evidence also point to an active role of actin in the regulation. Involvement of the actin C-terminus in binding of tropomyosin-troponin in different activation states and the regulation of actin-myosin interactions were examined using actin modified by proteolytic removal of three C-terminal amino acids. Actin C-terminal modification has no effect on the binding of tropomyosin or tropomyosin-troponin + Ca²⁺, but it reduces tropomyosin-troponin affinity in the absence of Ca²⁺. In contrast, myosin S1 induces binding of tropomyosin to truncated actin more readily than to native actin. The rate of actin-activated myosin S1 ATPase activity is reduced by actin truncation both in the absence and presence of tropomyosin. The Ca²⁺-dependent regulation of the ATPase activity is preserved. Without Ca²⁺ the ATPase activity is fully inhibited, but in the presence of Ca²⁺ the activation does not reach the level observed for native actin. The results suggest that through long-range allosteric interactions the actin C-terminus participates in the thin filament regulation.     

Hippocampal neurogenesis and neuroinflammation after cranial irradiation with (56)Fe particles

Exposure to heavy-ion radiation is considered a potential health risk in long-term space travel. In the central nervous system (CNS), loss of critical cellular components may lead to performance decrements that could ultimately compromise mission goals and long-term quality of life. Hippocampal-dependent cognitive impairments occur after exposure to ionizing radiation, and while the pathogenesis of this effect is not yet clear, it may involve the production of newly born neurons (neurogenesis) in the hippocampal dentate gyrus. We irradiated mice with 0.5-4 Gy of (56)Fe ions and 2 months later quantified neurogenesis and numbers of activated microglia as a measure of neuroinflammation in the dentate gyrus. Results showed that there were few changes after 0.5 Gy, but that there was a dose-related decrease in hippocampal neurogenesis and a dose-related increase in numbers of newly born activated microglia from 0.5-4.0 Gy. While those findings were similar to what was reported after X irradiation, there were also some differences, particularly in the response of newly born glia. Overall, this study showed that hippocampal neurogenesis was sensitive to relatively low doses of (56)Fe particles, and that those effects were associated with neuroinflammation. Whether these changes will result in functional impairments or if/how they can be managed are topics for further investigation.     

Prognostic significance of nuclear and cytoplasmic expression of metallothioneins as related to proliferative activity in squamous cell carcinomas of oral cavity

Metallothioneins (MT) are low molecular weight proteins with high metal and cystein contents. This study was designed to test the hypothesis that cytoplasmic and nuclear MT expression are of prognostic importance in patients with squamous cell carcinomas of the oral cavity, treated by surgery with subsequent radiotherapy. The second aim of the study was to test the potential correlation between the nuclear and cytoplasmic MT expressions as compared to expression of proliferation markers and other clinicopathological variables. Material and Methods: The studies were performed on tumor samples from 50 patients with diagnosis of squamous cell carcinoma of the oral cavity floor or of oral part of the tongue. All the patients were subjected to radical surgery, accompanied by removal of lymph nodes and post-operative radiotherapy. Results: No significant correlation could be detected between percentage and intensity of MT expression on one hand and proportions of cells with Mcm-2 (minichromosome maintenance protein 2), Ki-67 expressions, nor the grade of malignancy (G) on the other. A significantly shorter survival was detected among patients with tumors of MT expression rated 9 or 12 according to the Remmele scale and among patients with a high percentage (> 50%) of nuclear MT staining. In mulivariate analyses, only OTT (Overall Treatment Time), lymph node involvement and high expression of Mcm-2 were found to be independent risk factors for decreased patient's survival. Conclusion: This is relevant evidence that MT overexpression could be related to worse prognosis in patients with oral cancer. We have found no relationship between MT expression and proliferative activity.