Psychiatric disorders and SLC6A4 gene variants: possible effects on alcohol dependence and alzheimer’s disease

Molecular Biology Reports - Serotoninergic system is one of the most important neurotransmission systems investigated in the field of psychiatry. Extensive evidence reveals how alterations of this...     

Regulation of stem cell therapies under attack in Europe: for whom the bell tolls

At the time of writing, the Italian Parliament is debating a new law that would make it legal to practice an unproven stem cell treatment in public hospitals. The treatment, offered by a private non‐medical organization, may not be safe, lacks a rationale, and violates current national laws and European regulations. This case raises multiple concerns, most prominently the urgent need to protect patients who are severely ill, exposed to significant risks, and vulnerable to exploitation. The scientific community must consider the context—social, financial, medical, legal—in which stem cell science is currently situated and the need for stringent regulation. Additional concerns are emerging. These emanate from the novel climate, created within science itself, and stem cell science in particular, by the currently prevailing model of ‘translational medicine’. Only rigorous science and rigorous regulation can ensure translation of science into effective therapies rather than into ineffective market products, and mark, at the same time, the sharp distinction between the striving for new therapies and the deceit of patients.     

1H-NMR Investigation of the Interaction of the Amino Terminal Domain of the LexA Repressor with a Synthetic Half-Operator

Abstract

A synthetic half-operator DNA-duplex, d(GCTACTGTATGT), containing a portion of the proposed recognition sequence (CTGT) of serveral “SOS” genes, has been synthesized. The dodecamer has been characterized through ¹H-NMR spectroscopy. Complete assignment of exchangeable hydrogen bonded imino protons has been acheived by applying 1D NOE techniques and an analysis of the temperature dependence of the chemical shifts. In order to determine the specific role of the CTGT consensus sequence in the overall recognition process, the oligonucleotide duplex has been titrated with the amino terminal DNA binding domain of the LexA repressor. The observation of substantial changes of ¹H-NMR chemical shifts in the imino proton region upon interaction with the protein strongly suggests that the protein binds specifically to the operator DNA. The largest deviations of ¹H-NMR chemical shifts upon protein binding have been observed for protons assigned to the CTGT segment, thus strongly suggesting a direct involvement of this sequence in the binding process. At high potassium chloride concentrations the ¹H-NMR chemical shift deviations are reverted which is consistent with the known drop in the affinity constant of LexA for operator DNA at high salt concentrations.     

Model for the Porphyrin-DNA Binding Site: ENDOR Investigations of Cu-Porphyrins Binding to DNA

Abstract

Proton ENDOR has been observed from frozen solutions (ca. 38K°) of copper meso-(4-N-tetra-methylpyridyl)porphyrin (CuTMpyP(4)) complexed with Salmon sperm DNA in water and D₂O. Lines from exchangeable protons of the DNA bases have been observed in these ENDOR spectra. Analyses of these ENDOR data show that the separations of these DNA protons from the copper atom are between 3.76 and 3.84 A with angles of 19.5 to 22.5 degrees between the Cu-H vectors and the g_z axis. A distant ENDOR response has also been observed from phosphorous nuclei in the DNA backbone. We estimate that the phosphorous atoms producing this ENDOR signal are 7.5–10 Å from the copper center of the porphyrin. These ENDOR data combined with results from an earlier NMR investigation (1) have been used to construct a computer simulated model of the binding site in which the porphyrin is partially intercalated and extends into the major groove of DNA. The two GC base pairs at this site are slightly inequivalent. For each, the G imino proton and one of the C amino protons are at appropriate positions to account for the ENDOR signals arising from exchangeable protons. It is unlikely that this inequivalence would persist at room temperature where dynamic processes would give an apparently symmetric interaction. Although the model accounts for all reported experimental data involving tetracationic porphyrin species which have been suggested to be intercalators, it is not a unique solution.     

Mechanical behavior of bovine nasal cartilage under static and dynamic loading

Abnormal mechanical loading may trigger cartilage degeneration associated with osteoarthritis. Tissue response to load has been the subject of several in vitro studies. However, simple stimuli were often applied, not fully mimicking the complex in vivo conditions. Therefore, a rolling/plowing explant test system (RPETS) was developed to replicate the combined in vivo loading patterns. In this work we investigated the mechanical behavior of bovine nasal septum (BNS) cartilage, selected as tissue approximation for experiments with RPETS, under static and dynamic loading. Biphasic material properties were determined and compared with those of other cartilaginous tissues. Furthermore, dynamic loading in plowing modality was performed to determine dynamic response and experimental results were compared with analytical models and Finite Elements (FE) computations. Results showed that BNS cartilage can be modeled as a biphasic material with Young's modulus E=2.03±0.7 MPa, aggregate modulus H_A=2.35±0.7 MPa, Poisson's ratio ν=0.24±0.07, and constant hydraulic permeability k₀=3.0±1.3×10⁻¹⁵ m⁴ (N s)⁻¹. Furthermore, dynamic analysis showed that plowing induces macroscopic reactions in the tissue, proportionally to the applied loading force. The comparison among analytical, FE analysis and experimental results showed that predicted tangential forces and sample deformation lay in the range of variation of experimental results for one specific experimental condition. In conclusion, mechanical properties of BNS cartilage under both static and dynamic compression were assessed, showing that this tissue behave as a biphasic material and has a viscoelastic response to dynamic forces.     

Sputum analysis: Non‐invasive early lung cancer detection

Lung cancer is the leading cause of cancer‐related deaths over the world, characterized by a very high mortality rate. Molecular technique development tries to focus on early detection of cancers by studying molecular alterations that characterize cancer cells. Worldwide lung cancer research has focused on an ever‐increasing number of molecular elements of carcinogenesis at genetic, epigenetic and protein levels. The non‐invasiveness is the characteristic that all clinical trials on cancer detection should have. Abnormal chest imaging and/or non‐specific symptoms are initial signals of lung cancer that appear in an advanced stage of disease. This fact represents the cause of the low 5‐year survival rate: over 90% of patients dying within 5 years of diagnosis. Since smokers have higher quantity of sputum containing exfoliated cells from the bronchial tree, and the sputum represents the most easily accessible biological fluid and its collection is non‐invasive, analysis of this sample represents a good area of research in early lung cancer diagnosis. Continued cigarette smoking is the cause of chronic obstructive pulmonary disease (COPD), with an estimated attributable risk factor exceeding 80% in smoking affected individuals. Lung cancer is found in 40–70% of patients with COPD, particularly in severe disease, and it is a common cause of death in these patients. A large prospective trial of almost half a million non‐smokers showed as lung cancer is also common in patients with COPD who have never smoked. This review describes issues related to early lung cancer screening using non‐invasive methods. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.