RECQL5 helicase: Connections to DNA recombination and RNA polymerase II transcription

The RecQ family of helicases are traditionally viewed as recombination factors, important for maintaining genome stability. RECQL5 is unique among these proteins in being associated with RNA polymerase II, the enzyme responsible for transcribing all protein-encoding genes in eukaryotes. Here, we describe the possible implications of recent studies and discuss models for RECQL5 function.     

Effects of Taurine on Nitric Oxide and 3-Nitrotyrosine Levels in Spleen During Endotoxemia

Taurine (2-aminoethanesulfonic acid) is a free sulfur-containing β-amino acid which has antioxidant, antiinflammatory and detoxificant properties. In the present study, the role of endotoxemia on peroxynitrite formation via 3-nitrotyrosine (3-NT) detection, and the possible antioxidant effect of taurine in lipopolysaccharide (LPS)-treated guinea pigs were aimed. 40 adult male guinea pigs were divided into four groups; control, endotoxemia, taurine and taurine+endotoxemia. Animals were administered taurine (300 mg/kg), LPS (4 mg/kg) or taurine plus LPS intraperitoneally. After 6 h of incubation, when highest blood levels of taurine and endotoxin were attained, the animals were sacrificed and spleen samples were collected. The amounts of 3-nitrotyrosine and taurine were measured by HPLC, and reactive nitrogen oxide species (NOx) which are stable end products of nitric oxide was measured spectrophotometrically in spleen tissues. LPS administration significantly decreased the concentration of taurine whilst increased levels of 3-NT and NOx compared with control group. It was determined that taurine treatment decreased the levels of 3-nitrotyrosine and NOx in taurine+endotoxemia group. The group in which taurine was administered alone, contradiction to well-known antioxidant effect, taurine caused elevated concentration of 3-NT and NOx. This data suggest that taurine protects spleen against oxidative damage in endotoxemic conditions. However, the effect of taurine is different when it is administered alone. In conclusion, taurine may act as an antioxidant during endotoxemia, and as a prooxidant in healthy subjects at this dose.     

A public genome-scale lentiviral expression library of human ORFs

Functional characterization of the human genome requires tools for systematically modulating gene expression in both loss-of-function and gain-of-function experiments. We describe the production of a sequence-confirmed, clonal collection of over 16,100 human open-reading frames (ORFs) encoded in a versatile Gateway vector system. Using this ORFeome resource, we created a genome-scale expression collection in a lentiviral vector, thereby enabling both targeted experiments and high-throughput screens in diverse cell types.     

Physically crosslinked nanocomposites from silicate-crosslinked PEO: mechanical properties and osteogenic differentiation of human mesenchymal stem cells

The mechanical and biological properties of silicate-crosslinked PEO nanocomposites are studied. A strong correlation is observed between silicate concentration and mechanical properties. In vitro cell culture studies reveal that an increase in silicate concentration enhances the attachment and proliferation of human mesenchymal stem cells significantly. An upregulation in the expression of osteocalcin on nanocomposites compared to the tissue culture polystyrene control is observed. Together, these results suggest that silicate-based nanocomposites are bioactive and have the potential to be used in a range of biotechnological and biomedical applications such as injectable matrices, biomedical coatings, drug delivery, and regenerative medicine.     

Brow suspension,a minimally invasive technique in facial rejuvenation

People tend to prefer noninvasive or minimally invasive methods of facial rejuvenation, especially when it involves their face, which is the hallmark of a person's identity and impossible to hide. It is widely known that brow ptosis gives the face a "tired look" and also accentuates deformities of the upper eyelid. Most people who are interested in facial rejuvenation may not accept even a minor surgery, such as an endoscopic surgery. The senior author has developed a minimally invasive method of suspending the brow at a higher position. In this technique, there is neither surgical dissection nor a surgical incision except for four stab incisions and suture insertion, which is why we refer to it as a nonsurgical brow suspension. It is done under local anesthesia, and the brows are fixed in the position that they assume when the patient is supine. In the past 6 years, we performed 387 brow suspensions on 324 female and 63 male patients. The youngest patient was 19 years old, and the oldest was 74 years old. A retrospective chart review was done. These 387 cases were reviewed by comparison of preoperative and postoperative photographs. This approach was not only used for patients who were not interested in surgical rejuvenation but was also combined with lipofilling, laser resurfacing, and/or upper blepharoplasty. This technique is useful for correcting postsurgical brow asymmetry. We present this technique as an adjunct to the established techniques of facial rejuvenation. Despite the high patient acceptance and technical ease, it is not a replacement for the established techniques of facial rejuvenation.     

Elastic deformation of mineralized collagen fibrils: an equivalent inclusion based composite model

Mineralized collagen fibrils are the basic building blocks of bone tissue at the supramolecular level. Several disease states, manipulation of the expression of specific proteins involved in biomineralization, and treatment with different agents alter the extent of mineralization as well as the morphology of mineral crystals which in turn affect the mechanical function of bone tissue. An experimental assessment of mineralized fibers' mechanical properties is challenged by their small size, leaving analytical and computational models as a viable alternative for investigation of the fibril-level mechanical properties. In the current study the variation of the elastic stiffness tensor of mineralized collagen fibrils with changing mineral volume fraction and mineral aspect ratios was predicted via a micromechanical model. The partitioning of applied stresses between mineral and collagen phases is also predicted for normal and shear loading of fibrils. Model predictions resulted in transversely isotropic collagen fibrils in which the modulus along the longer axis of the fibril was the greatest. All the elastic moduli increased with increasing mineral volume fraction whereas Poisson's ratios decreased with the exception of v12 (=v21). The partitioning of applied stresses were such that the stresses acting on mineral crystals were about 1.5, 15, and 3 times greater than collagen stresses when fibrils were loaded transversely, longitudinally, and in shear, respectively. In the overall the predictions were such that: (a) greatest modulus along longer axis; (b) the greatest mineral/collagen stress ratio along the longer axis of collagen fibers (i.e., greatest relief of stresses acting on collagen); and (c) minimal lateral contraction when fibers are loaded along the longer axis. Overall, the pattern of mineralization as put forth in this model predicts a superior mechanical function along the longer axis of collagen fibers, the direction which is more likely to experience greater stresses.     

Microcracks colocalize within highly mineralized regions of cortical bone tissue

While much work has been performed to quantify the extent of bone damage, its effects on the mechanical integrity of the tissue and its biological impact, the set of factors which gives forth to microdamage are nebulous, particularly the compositional properties local to microdamage. In this context, the current study tested the hypothesis that microcracks initiate within more mineralized regions of bone. Cortical bone specimens were taken from human male donors aged 31, 38, 53, 64, 71, and 84 years at the mid femoral diaphysis in a plane parallel to the osteonal orientation. The mineralization was assessed in a spatially resolved manner using Raman microspectroscopy. Arrays of measurements were taken over the entire area (i.e. global scans) of each sample followed by measurements in the vicinity of microcracks (i.e. local scans). Histograms of mineralization were constructed for global and local scans to determine whether the mineralization of damaged loci differed from the mean overall mineralization. Statistical analysis of this data revealed that the mean mineralization of damaged loci was significantly greater (P < 0.05) than the overall mineralization for each donor, indicating that there exists a highly-mineralized 'brittle volume' in bone. The presence of this damage prone 'brittle volume' has future implications for the assessment of fracture susceptibility.     

Radiation interaction parameters for blood samples of breast cancer patients: an MCNP study

Radiation and Environmental Biophysics - The main goal of this study was to determine radiation interaction parameters such as mass attenuation coefficients, effective atomic numbers, and effective...     

Transgelin: a new gene involved in LDL endocytosis identified by a genome-wide CRISPR-Cas9 screen

A significant proportion of patients with elevated LDL and a clinical presentation of familial hypercholesterolemia do not carry known genetic mutations associated with hypercholesterolemia, such as defects in the LDL receptor. To identify new genes involved in the cellular uptake of LDL, we developed a novel whole-genome clustered regularly interspaced short palindromic repeat-Cas9 KO screen in HepG2 cells. We identified transgelin (TAGLN), an actin-binding protein, as a potentially new gene involved in LDL endocytosis. In silico validation demonstrated that genetically predicted differences in expression of TAGLN in human populations were significantly associated with elevated plasma lipids (triglycerides, total cholesterol, and LDL-C) in the Global Lipids Genetics Consortium and lipid-related phenotypes in the UK Biobank. In biochemical studies, TAGLN-KO HepG2 cells showed a reduction in cellular LDL uptake, as measured by flow cytometry. In confocal microscopy imaging, TAGLN-KO cells had disrupted actin filaments as well as an accumulation of LDL receptor on their surface because of decreased receptor internalization. Furthermore, TAGLN-KO cells exhibited a reduction in total and free cholesterol content, activation of SREBP2, and a compensatory increase in cholesterol biosynthesis. TAGLN deficiency also disrupted the uptake of VLDL and transferrin, other known cargoes for receptors that depend upon clathrin-mediated endocytosis. Our data suggest that TAGLN is a novel factor involved in the actin-dependent phase of clathrin-mediated endocytosis of LDL. The identification of novel genes involved in the endocytic uptake of LDL may improve the diagnosis of hypercholesterolemia and provide future therapeutic targets for the prevention of cardiovascular disease.