RNAi-mediated COPS3 gene silencing inhibits metastasis of osteogenic sarcoma cells

Metastatic disease is the primary cause of mortality among patients with osteogenic sarcoma (OGS). In this study, we aimed to identify the relationship of COPS3 gene expression to metastasis. Immunohistochemical staining for COPS3 was performed on 65 OGS samples (37 without and 28 with metastatic disease); 18.9% (7/37) of specimens from patients with no metastasis and 57.1% (16/28) of specimens from patients with metastasis showed intense staining of COPS3. Comparison of COPS3 expression between a poorly metastatic osteosarcoma cell line (SAOS-2) and highly metastatic osteosarcoma cell line (HOS) showed stronger expression of COPS3 in HOS cells. Inhibiting COPS3 function by siRNA resulted in reduced proliferation and migration of HOS cells. Inhibition of COPS3 gene downregulated expression of the MAPK signaling pathway, which has an important role in metastasis of OGS. Our results suggested that overexpression of the COPS3 gene might have important roles in metastasis of osteosarcoma cells

Stretchable and wearable colorimetric patches based on thermoresponsive plasmonic microgels embedded in a hydrogel film

Stimuli-responsive colorimetric sensors are promising for various industrial and medical applications due to the capability of simple, fast, and inexpensive visualization of external stimuli. Here we demonstrate a thermoresponsive, smart colorimetric patch based on a thermoresponsive plasmonic microgel embedded in a stretchable hydrogel film. To achieve a fast and efficient thermoresponsive color change, raspberry-shaped plasmonic microgels were fabricated by decorating gold nanoparticles (AuNPs) on poly(N-isopropylacrylamide) (PNIPAM) microgels, which exhibit reversible and strain-insensitive color shifts (between red and grayish violet) in response to a temperature change. The smart colorimetric patch containing a plasmonic microgels exhibits a significant extinction peak shift (176 nm) in a short time (1 s), with a temperature-sensing resolution of 0.2 degrees C. Moreover, the transition temperature of the plasmonic microgel can be finely tuned by additives and comonomers, so that the exquisite temperature visualization can be conducted over a wide temperature range of 25-40 degrees C by assembling plasmonic microgel films with different transition temperatures into an array patch. For proof-of-concept demonstrations, a freestanding smart colorimetric patch was utilized as a spatial temperature scanner and a colorimetric thermometer for a thermoresponsive actuator, which is potentially applicable in smart, wearable sensors and soft robotics

Computed tomography segmental calcium score (SCS) to predict stenosis severity of calcified coronary lesions

To estimate the probability of ≥50 % coronary stenoses based on computed tomography (CT) segmental calcium score (SCS) and clinical factors. The Institutional Review Board approved the study. A training sample of 201 patients underwent CT calcium scoring and conventional coronary angiography (CCA). All patients consented to undergo CT before CCA after being informed of the additional radiation dose. SCS and calcification morphology were assessed in individual coronary segments. We explored the predictive value of patient’s symptoms, clinical history, SCS and calcification morphology. We developed a prediction model in the training sample based on these variables then tested it in an independent test sample. The odds ratio (OR) for ≥50 % coronary stenosis was 1.8-fold greater (p = 0.006) in patients with typical chest pain, twofold (p = 0.014) greater in patients with acute coronary syndromes, twofold greater (p < 0.001) in patients with prior myocardial infarction. Spotty calcifications had an OR for ≥50 % stenosis 2.3-fold (p < 0.001) greater than the absence of calcifications, wide calcifications 2.7-fold (p < 0.001) greater, diffuse calcifications 4.6-fold (p < 0.001) greater. In middle segments, each unit of SCS had an OR 1.2-fold (p < 0.001) greater than in distal segments; in proximal segments the OR was 1.1-fold greater (p = 0.021). The ROC curve area of the prediction model was 0.795 (0.95 confidence interval 0.602–0.843). Validation in a test sample of 201 independent patients showed consistent diagnostic performance. In conjunction with calcification morphology, anatomical location, patient’s symptoms and clinical history, SCS can be helpful to estimate the probability of ≥50 % coronary stenosis

Identification of Genes Directly Involved in Shell Formation and Their Functions in Pearl Oyster, Pinctada fucata

Mollusk shell formation is a fascinating aspect of biomineralization research. Shell matrix proteins play crucial roles in the control of calcium carbonate crystallization during shell formation in the pearl oyster, Pinctada fucata. Characterization of biomineralization-related genes during larval development could enhance our understanding of shell formation. Genes involved in shell biomineralization were isolated by constructing three suppression subtractive hybridization (SSH) libraries that represented genes expressed at key points during larval shell formation. A total of 2,923 ESTs from these libraries were sequenced and gave 990 unigenes. Unigenes coding for secreted proteins and proteins with tandem-arranged repeat units were screened in the three SSH libraries. A set of sequences coding for genes involved in shell formation was obtained. RT-PCR and in situ hybridization assays were carried out on five genes to investigate their spatial expression in several tissues, especially the mantle tissue. They all showed a different expression pattern from known biomineralization-related genes. Inhibition of the five genes by RNA interference resulted in different defects of the nacreous layer, indicating that they all were involved in aragonite crystallization. Intriguingly, one gene (UD_Cluster94.seq.Singlet1) was restricted to the ‘aragonitic line’. The current data has yielded for the first time, to our knowledge, a suite of biomineralization-related genes active during the developmental stages of P.fucata, five of which were responsible for nacreous layer formation. This provides a useful starting point for isolating new genes involved in shell formation. The effects of genes on the formation of the ‘aragonitic line’, and other areas of the nacreous layer, suggests a different control mechanism for aragonite crystallization initiation from that of mature aragonite growth

The Staphylococcus aureus Response to Unsaturated Long Chain Free Fatty Acids: Survival Mechanisms and Virulence Implications

Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the σB and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids

Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults.

BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults. METHODS: We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity). FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0·01 kg/m2 per decade; 95% credible interval -0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (-0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50-1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to 5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8% (6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6) among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese. INTERPRETATION: The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults. FUNDING: Wellcome Trust, AstraZeneca Young Health Programme

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

Observation of a New Excited Beauty Strange Baryon Decaying to Ξb- π+π-

The Ξb-π+π- invariant mass spectrum is investigated with an event sample of proton-proton collisions at s=13 TeV, collected by the CMS experiment at the LHC in 2016-2018 and corresponding to an integrated luminosity of 140 fb-1. The ground state Ξb- is reconstructed via its decays to J/ψΞ- and J/ψΛK-. A narrow resonance, labeled Ξb(6100)-, is observed at a Ξb-π+π- invariant mass of 6100.3±0.2(stat)±0.1(syst)±0.6(Ξb-) MeV, where the last uncertainty reflects the precision of the Ξb- baryon mass. The upper limit on the Ξb(6100)- natural width is determined to be 1.9 MeV at 95% confidence level. The low Ξb(6100)- signal yield observed in data does not allow a measurement of the quantum numbers of the new state. However, following analogies with the established excited Ξc baryon states, the new Ξb(6100)- resonance and its decay sequence are consistent with the orbitally excited Ξb- baryon, with spin and parity quantum numbers JP=3/2-