Abstract Background and aim Body mass index (BMI) has a U-shaped relationship with mortality among the elderly, in contrast to the general adult population. Skeletal muscle mass may be more ...appropriate than BMI for classifying mortality risk among the elderly. We investigated the relationship between skeletal muscle mass and mortality among elderly Chinese persons. Method and results A total of 1512 elderly from the Nutrition and Health Survey in Taiwanese Elderly (1999–2000) was enrolled, and the survival status was followed using data from the National Death Registry. The skeletal muscle mass index (SMMI) was calculated by dividing skeletal muscle mass by height in meters squared. The Cox proportional hazard model was used to estimate the association between SMMI and mortality. During the follow-up (average time: 7.9 years), one-third elderly died ( n = 506) by any cause and 25% of them was cardiovascular mortality (ICD-9-CM: between 390 and 459). The total mortality and cardiovascular mortality were 4.23 and 1.07 per 100 person-years. Elderly participants with the lowest SMMI had the highest total mortality and cardiovascular mortality among the four quartiles (6.72, 3.76, 3.25 and 3.50 per 100 PY for total mortality; 1.81, 0.76, 0.87, 0.93 for cardiovascular mortality). Those with a low (1st quartile) SMMI had a 2-fold increase in total mortality (1.96; 1.63–2.35) and cardiovascular mortality (2.16; 1.51–3.08) risk compared to those with a normal 2nd, 3rd, or 4th quartile SMMI. Conclusions The threshold relationship between SMMI and mortality is contrast to the reverse J-shaped relationship between BMI and total mortality. Therefore, skeletal muscle mass measurement may be considered with a high priority to identify elderly individuals with a high mortality risk.
Endogenous biomarkers remain at the forefront of early disease detection efforts, but many lack the sensitivities and specificities necessary to influence disease management. Here, we describe a ...cell-based in vivo sensor for highly sensitive early cancer detection. We engineer macrophages to produce a synthetic reporter on adopting an M2 tumor-associated metabolic profile by coupling luciferase expression to activation of the arginase-1 promoter. After adoptive transfer in colorectal and breast mouse tumor models, the engineered macrophages migrated to the tumors and activated arginase-1 so that they could be detected by bioluminescence imaging and luciferase measured in the blood. The macrophage sensor detected tumors as small as 25-50 mm
by blood luciferase measurements, even in the presence of concomitant inflammation, and was more sensitive than clinically used protein and nucleic acid cancer biomarkers. Macrophage sensors also effectively tracked the immunological response in muscle and lung models of inflammation, suggesting the potential utility of this approach in disease states other than cancer.
Recombinant subunit vaccines should contain minimal non-pathogen motifs to reduce potential off-target reactivity. We recently developed a vaccine antigen against respiratory syncytial virus (RSV), ...which comprised the fusion (F) glycoprotein stabilized in its pre-fusion trimeric conformation by "DS-Cav1" mutations and by an appended C-terminal trimerization motif or "foldon" from T4-bacteriophage fibritin. Here we investigate the creation of a cysteine zipper to allow for the removal of the phage foldon, while maintaining the immunogenicity of the parent DS-Cav1+foldon antigen. Constructs without foldon yielded RSV F monomers, and enzymatic removal of the phage foldon from pre-fusion F trimers resulted in their dissociation into monomers. Because the native C terminus of the pre-fusion RSV F ectodomain encompasses a viral trimeric coiled-coil, we explored whether introduction of cysteine residues capable of forming inter-protomer disulfides might allow for stable trimers. Structural modeling indicated the introduced cysteines to form disulfide "rings", with each ring comprising a different set of inward facing residues of the coiled-coil. Three sets of rings could be placed within the native RSV F coiled-coil, and additional rings could be added by duplicating portions of the coiled-coil. High levels of neutralizing activity in mice, equivalent to that of the parent DS-Cav1+foldon antigen, were elicited by a 4-ring stabilized RSV F trimer with no foldon. Structure-based alteration of a viral coiled-coil to create a cysteine zipper thus allows a phage trimerization motif to be removed from a candidate vaccine antigen.
The Jupiter-family comet 103P/Hartley 2 (103P) was the target of the NASA EPOXI mission. In support of this mission, we conducted observations from radio to submillimeter wavelengths of comet 103P in ...the three weeks preceding the spacecraft rendezvous on UT 2010 November 4.58. This time period included the passage at perihelion and the closest approach of the comet to the Earth. Here, we report detections of HCN, H sub(2)CO, CS, and OH and upper limits for HNC and DCN toward 103P using the Arizona Radio Observatory Kitt Peak 12 m telescope (ARO 12 m) and submillimeter telescope (SMT), the James Clerk Maxwell Telescope (JCMT), and the Green Bank Telescope (GBT). The water production rate, Q sub(H2O) = (0.67-1.07) x 10 super(28) s super(-1), was determined from the GBT OH data. From the average abundance ratios of HCN and H sub(2)CO relative to water (0.13 + or - 0.03% and 0.14 + or - 0.03%, respectively), we conclude that H sub(2)CO is depleted and HCN is normal with respect to typically observed cometary mixing ratios. However, the abundance ratio of HCN with water shows a large diversity with time. Using the JCMT data, we measured an upper limit for the DCN/HCN ratio <0.01. Consecutive observations of ortho-H sub(2)CO and para-H sub(2)CO on November 2 (from data obtained at the JCMT) allowed us to derive an ortho:para ratio (OPR) of approximately 2.12 + or - 0.59 (1sigma), corresponding to T sub(spin) > 8 K (2sigma).
The interactions that lead to the emergence of superconductivity in iron-based materials remain a subject of debate. It has been suggested that electron-electron correlations enhance electron-phonon ...coupling in iron selenide (FeSe) and related pnictides, but direct experimental verification has been lacking. Here we show that the electron-phonon coupling strength in FeSe can be quantified by combining two time-domain experiments into a “coherent lock-in” measurement in the terahertz regime. X-ray diffraction tracks the light-induced femtosecond coherent lattice motion at a single phonon frequency, and photoemission monitors the subsequent coherent changes in the electronic band structure.Comparison with theory reveals a strong enhancement of the coupling strength in FeSe owing to correlation effects. Given that the electron-phonon coupling affects superconductivity exponentially, this enhancement highlights the importance of the cooperative interplay between electron-electron and electron-phonon interactions.
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