Serum amyloid A inhibits RANKL-induced osteoclast formation

When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellular domain. SAA also restrained the fusion of osteoclast precursors by blocking intracellular ATP release. This inhibitory response of SAA is not mediated by the well-known SAA receptors (formyl peptide receptor 2, Toll-like receptor 2 (TLR2) or TLR4). These findings provide insight into a novel inhibitory role of SAA in osteoclastogenesis and suggest that SAA is an important endogenous modulator that regulates bone homeostasis.open

Whole genome resequencing of black Angus and Holstein cattle for SNP and CNV discovery

Background: One of the goals of livestock genomics research is to identify the genetic differences responsible for variation in phenotypic traits, particularly those of economic importance. Characterizing the genetic variation in livestock species is an important step towards linking genes or genomic regions with phenotypes. The completion of the bovine genome sequence and recent advances in DNA sequencing technology allow for in-depth characterization of the genetic variations present in cattle. Here we describe the whole-genome resequencing of two Bos taurus bulls from distinct breeds for the purpose of identifying and annotating novel forms of genetic variation in cattle.Results: The genomes of a Black Angus bull and a Holstein bull were sequenced to 22-fold and 19-fold coverage, respectively, using the ABI SOLiD system. Comparisons of the sequences with the Btau4.0 reference assembly yielded 7 million single nucleotide polymorphisms (SNPs), 24% of which were identified in both animals. Of the total SNPs found in Holstein, Black Angus, and in both animals, 81%, 81%, and 75% respectively are novel. In-depth annotations of the data identified more than 16 thousand distinct non-synonymous SNPs (85% novel) between the two datasets. Alignments between the SNP-altered proteins and orthologues from numerous species indicate that many of the SNPs alter well-conserved amino acids. Several SNPs predicted to create or remove stop codons were also found. A comparison between the sequencing SNPs and genotyping results from the BovineHD high-density genotyping chip indicates a detection rate of 91% for homozygous SNPs and 81% for heterozygous SNPs. The false positive rate is estimated to be about 2% for both the Black Angus and Holstein SNP sets, based on follow-up genotyping of 422 and 427 SNPs, respectively. Comparisons of read depth between the two bulls along the reference assembly identified 790 putative copy-number variations (CNVs). Ten randomly selected CNVs, five genic and five non-genic, were successfully validated using quantitative real-time PCR. The CNVs are enriched for immune system genes and include genes that may contribute to lactation capacity. The majority of the CNVs (69%) were detected as regions with higher abundance in the Holstein bull.Conclusions: Substantial genetic differences exist between the Black Angus and Holstein animals sequenced in this work and the Hereford reference sequence, and some of this variation is predicted to affect evolutionarily conserved amino acids or gene copy number. The deeply annotated SNPs and CNVs identified in this resequencing study can serve as useful genetic tools, and as candidates in searches for phenotype-altering DNA differences

Biomimetic transferable surface for a real time control over wettability and photoerasable writing with water drop lens

We demonstrate a transferable device that can turn wettability of surfaces to sticky or slippy, as per requirement. It is composed of polymeric yarn with a fibrous structure, which can be lifted and placed on any surface to render it the unique wettability properties. We introduce Polyvinylidenefluoride (PVDF) random fiber as biomimetic rose petal surface. When it is decorated with PVDF nanofibers yarns, the random mesh transform from rose petal sticky state into grass leaf slippy state. When it is placed on sticky, hydrophilic metal coin, it converts the surface of the coin to super hydrophobic. Adjustments in the yarn system, like interyarn spacing, can be done in real time to influence its wettability, which is a unique feature. Next, we load the polymer with a photochromic compound for chemical restructuring. It affects the sliding angle of water drop and makes the fibers optically active. We also demonstrate a “water droplets lens” concept that enables erasable writing on photochromic rose petal sticky fibrous surface. The droplet on a highly hydrophobic surface acts as a ball lens to concentrate light onto a hot spot; thereby we demonstrate UV light writing with water lenses and visible light erasing

The economic burden of musculoskeletal disease in Korea: A cross sectional study

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal diseases are becoming increasingly important due to population aging. However, studies on the economic burden of musculoskeletal disease in Korea are scarce. Therefore, we conducted a population-based study to measure the economic burden of musculoskeletal disease in Korea using nationally representative data.</p> <p>Methods</p> <p>This study used a variety of data sources such as national health insurance statistics, the Korea Health Panel study and cause of death reports generated by the Korea National Statistical Office to estimate the economic burden of musculoskeletal disease. The total cost of musculoskeletal disease was estimated as the sum of direct medical care costs, direct non-medical care costs, and indirect costs. Direct medical care costs are composed of the costs paid by the insurer and patients, over the counter drugs costs, and other costs such as medical equipment costs. Direct non-medical costs are composed of transportation and caregiver costs. Indirect costs are the sum of the costs associated with premature death and the costs due to productivity loss. Age, sex, and disease specific costs were estimated.</p> <p>Results</p> <p>Among the musculoskeletal diseases, the highest costs are associated with other dorsopathies, followed by disc disorder and arthrosis. The direct medical and direct non-medical costs of all musculoskeletal diseases were $4.18 billion and$338 million in 2008, respectively. Among the indirect costs, those due to productivity loss were $2.28 billion and costs due to premature death were$79 million. The proportions of the total costs incurred by male and female patients were 33.8% and 66.2%, respectively, and the cost due to the female adult aged 20-64 years old was highest. The total economic cost of musculoskeletal disease was $6.89 billion, which represents 0.7% of the Korean gross domestic product.</p> <p>Conclusions</p> <p>The economic burden of musculoskeletal disease in Korea is substantial. As the Korean population continues to age, the economic burden of musculoskeletal disease will continue to increase. Policy measures aimed at controlling the cost of musculoskeletal disease are therefore required.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Human U87 Astrocytoma Cell Invasion Induced by Interaction of βig-h3 with Integrin α5β1 Involves Calpain-2

It is known that βig-h3 is involved in the invasive process of many types of tumors, but its mechanism in glioma cells has not been fully clarified. Using immunofluorescent double-staining and confocal imaging analysis, and co-immunoprecipitation assays, we found that βig-h3 co-localized with integrin α5β1 in U87 cells. We sought to elucidate the function of this interaction by performing cell invasion assays and gelatin zymography experiments. We found that siRNA knockdowns of βig-h3 and calpain-2 impaired cell invasion and MMP secretion. Moreover, βig-h3, integrins and calpain-2 are known to be regulated by Ca2+, and they are also involved in tumor cell invasion. Therefore, we further investigated if calpain-2 was relevant to βig-h3-integrin α5β1 interaction to affect U87 cell invasion. Our data showed that βig-h3 co-localized with integrin α5β1 to enhance the invasion of U87 cells, and that calpain-2, is involved in this process, acting as a downstream molecule

Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians

<p>Abstract</p> <p>Background</p> <p><it>CYP2C9 </it>and <it>VKORC1 </it>are two major genetic factors associated with inter-individual variability in warfarin dose. Additionally, genes in the warfarin metabolism pathway have also been associated with dose variance. We analyzed Single Nucleotide Polymorphisms (SNPs) in these genes to identify genetic factors that might confer warfarin sensitivity in Indonesian patients.</p> <p>Methods</p> <p>Direct sequencing method was used to identify SNPs in <it>CYP2C9, VKORC1, CYP4F2, EPHX1, PROC </it>and <it>GGCX </it>genes in warfarin-treated patients. Multiple linear regressions were performed to model the relationship warfarin daily dose requirement with genetic and non-genetic variables measured and used to develop a novel algorithm for warfarin dosing.</p> <p>Results</p> <p>From the 40 SNPs analyzed, <it>CYP2C9 </it>rs17847036 and <it>VKORC1 </it>rs9923231 showed significant association with warfarin sensitivity. In our study population, no significant correlation could be detected between <it>CYP2C9*3, CYP2C9C</it>-65 (rs9332127), <it>CYP4F2 </it>rs2108622, <it>GGCX </it>rs12714145, <it>EPHX1 </it>rs4653436 and <it>PROC </it>rs1799809 with warfarin sensitivity.</p> <p>Conclusions</p> <p><it>VKORC1 </it>rs9923231 AA and <it>CYP2C9 </it>rs17847036 GG genotypes were associated with low dosage requirements of most patients (2.05 ± 0.77 mg/day and 2.09 ± 0.70 mg/day, respectively). <it>CYP2C9 </it>and <it>VKORC1 </it>genetic variants as well as non-genetic factors such as age, body weight and body height account for 15.4% of variance in warfarin dose among our study population. Additional analysis of this combination could allow for personalized warfarin treatment in ethnic Indonesians.</p

Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer

International audienc

Metastatic lymph node in gastric cancer; Is it a real distant metastasis?

<p>Abstract</p> <p>Background</p> <p>Currently, the TNM staging system is a widely accepted method for assessing the prognosis of the disease and planning therapeutic strategies for cancer. Of the TNM system, the extent of lymph node involvement is the most important independent prognostic factor for gastric cancer. The aim of our study is to evaluate the survival and prognosis of gastric cancer patients with LN#12 or #13 involvement only and to assess the impact of anatomic regions of primary gastric tumor on survival in this particular subset of patients.</p> <p>Methods</p> <p>Among data of 1,008 stage IV gastric cancer patients who received curative R0 gastrectomy, a total of 79 patients with LN#12 (n = 68) and/or #13 (n = 11) were identified. All patients performed gastrectomy with D2 or D3 lymph node dissection.</p> <p>Results</p> <p>In 79 patients with LN#12/13 involvement, the estimated one-, three- and five-year survival rate was 77.2%, 41.8% and 26.6% respectively. When we compared the patients with LN#12/13 involvement to those without involvement, there was no significant difference in OS (21.0 months vs. 25.0 months, respectively; P = 0.140). However, OS was significantly longer in patients with LN#12/13 involvement only than in those with M1 lymph node involvement (14.3 months; P = 0.001). There was a significant difference in survival according to anatomic locations of the primary tumor (lower to mid-body vs. high body or whole stomach): 26.5 vs. 9.2 months (P = 0.009). In Cox proportional hazard analysis, only N stage (p = 0.002) had significance to predict poor survival.</p> <p>Conclusion</p> <p>In this study we found that curatively resected gastric cancer patients with pathologic involvement of LN #12 and/or LN #13 had favorable survival outcome, especially those with primary tumor location of mid-body to antrum. Prospective analysis of survival in gastric cancer patients with L N#12 or #13 metastasis is warranted especially with regards to primary tumor location.</p

Thienoisoindigo-Based Semiconductor Nanowires Assembled with 2-Bromobenzaldehyde via Both Halogen and Chalcogen Bonding

We fabricated nanowires of a conjugated oligomer and applied them to organic field-effect transistors (OFETs). The supramolecular assemblies of a thienoisoindigo-based small molecular organic semiconductor (TIIG-Bz) were prepared by co-precipitation with 2-bromobenzaldehyde (2-BBA) via a combination of halogen bonding (XB) between the bromide in 2-BBA and electron-donor groups in TIIG-Bz, and chalcogen bonding (CB) between the aldehyde in 2-BBA and sulfur in TIIG-Bz. It was found that 2-BBA could be incorporated into the conjugated planes of TIIG-Bz via XB and CB pairs, thereby increasing the pi - pi stacking area between the conjugated planes. As a result, the driving force for one-dimensional growth of the supramolecular assemblies via pi - pi stacking was significantly enhanced. TIIG-Bz/2-BBA nanowires were used to fabricate OFETs, showing significantly enhanced charge transfer mobility compared to OFETs based on pure TIIG-Bz thin films and nanowires, which demonstrates the benefit of nanowire fabrication using 2-BB