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BackgroundMitochondrial dysfunction has been implicated in sarcopenia. P-31 magnetic resonance spectroscopy (MRS) enables non-invasive measurement of adenosine triphosphate (ATP) synthesis rates to probe mitochondrial function. Here, we assessed muscle energetics in older sarcopenic and non-sarcopenic men and compared with muscle biopsy-derived markers of mitochondrial function. MethodsTwenty Chinese men with sarcopenia (SARC, age = 73.1 +/- 4.1 years) and 19 healthy aged and sex-matched controls (CON, age = 70.3 +/- 4.2 years) underwent assessment of strength, physical performance, and magnetic resonance imaging. Concentrations of phosphocreatine (PCr), ATP and inorganic phosphate (Pi) as well as muscle pH were measured at rest and during an interleaved rest-exercise protocol to probe muscle mitochondrial function. Results were compared to biopsy-derived mitochondrial complex activity and expression to understand underlying metabolic perturbations. ResultsDespite matched muscle contractile power (strength/cross-sectional area), the ATP contractile cost was higher in SARC compared with CON (low-intensity exercise: 1.06 +/- 0.59 vs. 0.57 +/- 0.22, moderate: 0.93 +/- 0.43 vs. 0.58 +/- 0.68, high: 0.70 +/- 0.57 vs. 0.43 +/- 0.51 mmol L-1 min(-1) bar(-1) cm(-2), P = 0.003

Background and purpose: Various blood biomarkers reflecting brain amyloid-β (Aβ) load have recently been proposed with promising results. However, to date, no comparative study amongst blood biomarkers has been reported. Our objective was to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort. Methods: Using the same cohort (n = 68), the performances of the single-molecule array (Simoa) Aβ40, Aβ42, Aβ42/Aβ40 and the amplified plasmonic exosome (APEX) Aβ42 blood biomarkers were compared using amyloid positron emission tomography (PET) as the reference standard. The extent to which these blood tests can reduce the recruitment cost of clinical trials was also determined by identifying amyloid positive (Aβ+) participants. Results: Compared to Simoa biomarkers, APEX-Aβ42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity 100%, specificity 93.3%, area under the curve 0.995). When utilized for clinical trial recruitment, our simulation showed that pre-screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX-Aβ42 and 48.6% for Simoa-Aβ42/Aβ40) compared to the situation where only PET imaging is used. Moreover, with 100% sensitivity, APEX-Aβ42 pre-screening does not increase the required number of initial participants. Conclusions: With its high diagnostic performance, APEX is an ideal candidate for Aβ+ subject identification, monitoring and primary care screening, and could efficiently enrich clinical trials with Aβ+ participants whilst halving recruitment costs. (Less)

Osteoblast commitment and differentiation are controlled by multiple growth factors including members of the Notch signaling pathway. JAGGED1 is a cell surface ligand of the Notch pathway that is necessary for murine bone formation. The delivery of JAGGED1 to induce bone formation is complicated by its need to be presented in a bound form to allow for proper Notch receptor signaling. In this study, we investigate whether the sustained release of JAGGED1 stimulates human mesenchymal cells to commit to osteoblast cell fate using polyethylene glycol malemeide (PEG-MAL) hydrogel delivery system. Our data demonstrated that PEG-MAL hydrogel constructs are stable in culture for at least three weeks and maintain human mesenchymal cell viability with little cytotoxicity in vitro. JAGGED1 loaded on PEG-MAL hydrogel (JAGGED1-PEG-MAL) showed continuous release from the gel for up to three weeks, with induction of Notch signaling using a CHO cell line with a Notch1 reporter construct, and qPCR gene expression analysis in vitro. Importantly, JAGGED1-PEG-MAL hydrogel induced mesenchymal cells towards osteogenic differentiation based on increased Alkaline phosphatase activity and osteoblast genes expression including RUNX2, ALP, COL1, and BSP. These results thus indicated that JAGGED1 delivery in vitro using PEG-MAL hydrogel induced osteoblast commitment, suggesting that this may be a viable in vivo approach to bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 552-560, 2018.

Here we present the isotopic concentrations of He, Ne, Ar, Kr, and Xe for the three Martian meteorites, namely Grove Mountains 99027 (GRV 99027), Northwest Africa 7906 (NWA 7906), and Northwest Africa 7907 (NWA 7907). The cosmic ray exposure (CRE) age for GRV 99027 of 5.7 ± 0.4 Ma (1δ) is consistent with CRE ages for other poikilitic basaltic shergottites and suggests that all were ejected in a single event ~5.6 Ma ago. After correcting for an estimated variable sodium concentration, the CRE ages for NWA 7906 and NWA 7907 of 5.4 ± 0.4 and 4.9 ± 0.4 Ma (1r), respectively, are in good agreement with the CRE age of ~5 Ma favored by Cartwright et al. (2014) for NWA 7034. The data, therefore, support the conclusion that all three basaltic regolith breccias are paired. The ⁴⁰Ar gas retention age for NWA 7907 of ~1.3 Ga is in accord with Cartwright et al. (2014). For NWA 7906, we were unable to determine a ⁴⁰Ar gas retention age. The ⁴He gas retention ages for NWA 7906 and 7907 are in the range of 200 Ma and are much shorter than the ⁴⁰Ar gas retention age of NWA 7907, indicating that about 86–88% of the radiogenic ⁴He has been lost. The Kr and Xe isotopic concentrations in GRV 99027 are composed almost exclusively of Martian interior (MI) gases, while for NWA 7906 and NWA 7907, they indicate gases from the MI, elementally fractionated air, and possibly Martian atmosphere.

Purpose: In vivo ³¹P MRS magnetization transfer (MT) provides a direct measure of neuronal activity at the metabolic level. This work aims to use functional ³¹P MRS-MT to investigate the change in cerebral ATP metabolic rates in healthy adults upon repeated visual stimuli. Methods: A magnetization saturation transfer sequence with narrowband selective saturation of γ-ATP was developed for ³¹P MT experiments at 3 T. Results: Using progressive saturation of γ-ATP, the intrinsic T1 relaxation times of phosphocreatine (PCr) and inorganic phosphate (Pi) at 3 T were measured to be 5.1±0.8 s and 3.0±1.4 s, respectively. Using steady-state saturation of γ-ATP, a significant 24±14% and 11±7% increase in the forward creatine kinase (CK) pseudo-first-order reaction rate constant, k₁, was observed upon visual stimulation in the first and second cycles respectively of a paradigm consisting of 10min-rest followed by 10min-stimulation, with the measured baseline k₁ being 0.35±0.04 s⁻¹. No significant changes in forward ATP synthase (ATPase) reaction rate, PCr/γ- ATP, Pi/γ-ATP, and NAD(H)/γ-ATP ratios, or intracellular pH were detected upon stimulation. Conclusion: This work demonstrates the potential of studying cerebral bioenergetics using functional ³¹P MRS-MT to determine the change in the forward CK reaction rate at 3 T.

There is considerable interest in manipulating the behavior of dietary emulsions in the human stomach as a means of altering satiating properties of fatty foods. However assessing this using intubation markedly disturbs normal gastric motility so a non-invasive imaging approach has a strong rationale. Two 20% sunflower oil-in-water fat emulsions test meals with different droplet sizes (termed Fine and Coarse) and intragastric behaviors were used to demonstrate, for the first time, the feasibility of carrying out magnetic resonance spectroscopy (MRS) measurements of fat emulsions fat fraction, in vivo, in the gastric lumen of six healthy volunteers. Magnetic resonance imaging (MRI) confirmed that as expected the fine emulsion remained mostly homogeneously distributed inside the stomach over the course of 3 h but the Coarse quickly creamed showing an upper layer much richer in fat. The MRS measurements showed that the Coarse emulsion had an upper layer of high lipid/water ratio compared to the lower layer. The fine emulsion fat fraction values remained stable throughout the study with no difference between upper and lower layers. It is therefore possible to quantify in vivo, in the gastric lumen, the intragastric fat fraction of oil-in-water fat emulsions using non invasive MRS techniques. Practical applications: This study shows that it is possible to quantify in vivo, in the gastric lumen, the intragastric fat fraction of oil-in-water fat emulsions using non invasive magnetic resonance spectroscopy techniques. These measurements can help improve understanding of intragastric distribution of fat, its relation to satiety, can improve the relevance of in vitro/in vivo models of fat digestion, and will ultimately aid the design of foods with desired health promoting characteristics and check their performance in vivo. Two 20% sunflower oil-in-water fat emulsions test meals with different droplet sizes and intragastric behaviours are used to demonstrate, for the first time, the feasibility of carrying out magnetic resonance spectroscopy (MRS) measurements of fat emulsions fat fraction, in vivo, in the gastric lumen of six healthy volunteers.

The measurement of tissue lipid and glycogen contents and the establishment of normal levels of variability are important when assessing changes caused by pathology or treatment. We measured hepatic and skeletal muscle lipid and glycogen levels using 1H and 13C MRS at 3 T in groups of subjects with and without type 2 diabetes. Within-visit reproducibility, due to repositioning and instrument errors was determined from repeat measurements made over 1 h. Natural variability was assessed from separate measurements made on three occasions over 1 month. Hepatic lipid content was greater in subjects with diabetes relative to healthy subjects (p = 0.03), whereas levels of hepatic and skeletal muscle glycogen, and of intra- and extra-myocellular lipid, were similar. The single-session reproducibility values (coefficient of variation, CV) for hepatic lipid content were 12% and 7% in groups of subjects with and without diabetes, respectively. The variability of hepatic lipid content over 1 month was greater than the reproducibility, with CV = 22% (p = 0.08) and CV = 44% (p = 0.004) in subjects with and without diabetes, respectively. Similarly, levels of variation in basal hepatic glycogen concentrations (subjects with diabetes, CV = 38%; healthy volunteers, CV = 35%) were significantly larger than single-session reproducibility values (CV = 17%, p = 0.02 and CV = 13%, p = 0.05, respectively), indicating substantial biological changes in basal concentrations over 1 month. There was a decreasing correlation in measurements of both hepatic lipid and glycogen content with increasing time between scans. Levels of variability in intra- and extra-myocellular lipid in the soleus muscle, and glycogen concentrations in the gastrocnemius muscle, tended to be larger than expected from single-session reproducibility, although these did not reach significance. Copyright © 2013 John Wiley & Sons, Ltd.

Arguably, Alzheimer’s disease (AD) is a multifactorial syndrome, rather than single disease, arising from a complex array of neurochemical factors. Numerous studies on the molecular pathogenesis of AD implicate a diversity of factors ranging from neurotoxic peptides (β-amyloid) to inflammatory processes (interleukins), but all culminating in a common neuropathology. This diversity of molecular causation is an impediment to the design of effective therapies for AD. To address this design problem, we sought to identify a single, common motif (a “common receptor”) shared by multiple structurally and functionally diverse proteins implicated in AD. This search revealed the presence of a common BBXB peptide motif and upon refinement, an AXBBXB motif; these regions can be exploited for the design of a “promiscuous drug” that exploits a “one-drug-multiple-receptors” therapeutic strategy for AD.

We managed two pregnancies in a woman with congenital afibrinogenemia with increasing amounts of cryoprecipitate to achieve a pre-infusion fibrinogen level of 60 mg/dL. The first pregnancy resulted in placental abruption at 36 weeks, in spite of recent cryoprecipitate infusion. Both placentas showed infarction. Post-partum ovarian and renal vein thromboses complicated the second pregnancy. Mean FVIII (344%) and vWF Antigen (323%) were elevated prior to cryoprecipitate infusion, with mean post-infusion levels of 367% and 363%. The clearance of fibrinogen after cryoprecipitate infusion increased during the course of pregnancy. A paradoxical prothrombotic state with embolization may play a role in the observed complications of pregnancy.

The localization of a hybrid protein composed of swallow and Green Fluorescent Protein (GFP) during Drosophila oogenesis is reported. I constructed a hybrid gene with GFP inserted into an internal position of swallow. This gene was integrated into the Drosophila genome and provides full swallow+ function, as assayed by the complete rescue of strong swallow mutants. Swallow-GFP is localized at all points along the oocyte cortex from vitellogenic stages of oogenesis through the end of oogenesis. Higher concentrations of swallow-GFP are present at the anterior oocyte cortex than at the lateral and posterior oocyte cortices at Stages 10 and 11, when bicoid and htsN4 mRNA transport from nurse cells and localization in the oocyte are most active. At Stage 9 and at Stages 12-14 swallow-GFP is equally distributed at the anterior, lateral, and posterior oocyte cortices. The position of swallow-GFP in vitellogenic stages is identical to the position of endogenous swallow protein determined by indirect immunofluorescence using an anti-swallow antibody. At the oocyte cortex, swallow-GFP is present in particulate structures that lie within or just internal to the dense cortical actin meshwork. These particles show little or no movement, suggesting that they are attached to or embedded in the oocyte cortex. These observations are most easily interpreted in the context of mRNA anchoring or microtubule organizing functions for the swallow protein.

The ratios of stable isotopes 18 O/ 16 O and 13 C/ 12 C. in sagittal otolith carbonate from two tropical demersal teleosts, red emperot Lutjanus sebae and Rankin cod Epmephelis multimototus. from several locations in northern Western Australia, differed between sites. On a broad scale. fish from the foat locations. Shark Bay, Ningaloo, Pilbara, and Broome had stable isotope values that were sufliciently different to indicate separate stocks, and it is appropriate to manage these populations of the two species independently in these areas. On a smaller scale, there may be limited mixing of these species between the Pilbara trawl fishery and the trap and line fisheries operating out of Onslow and Broome. Values of stable oxygen isotopes were strongly related to sea surface temperature, although there were some sites in shallow water where low values of stable oxygen isotopes indicated that fish were living in warm water. The use of stable oxygen and carbon isotope values as a valuable, cost effective method of determining the degree of miving of fish stocks.

Summary Vegetative lipoxygenases (VLXs) in soybean are hypothesized to function in nitrogen storage and partitioning. Isoform-specific antibodies for four of the five known VLX isoenzymes were used to investigate the influence of source-sink status on protein levels, as well as to analyze the tissue and subcellular localization of the different isoforms. VLXD responded most strongly to sink limitation, although the levels of VLXA, B and C increased as well. After sink limitation, VLXD and the vegetative storage protein, VSPα, accumulated in the vacuoles of bundle sheath and paraveinal mesophyll cells, while VLXA, B and C localized to the cytosol of these cells. All five known VLX isoenzymes were active with both linoleic and linolenic acid substrates after expression in Escherichia coli. The strong upregulation of VLXD levels after sink limitation as well as the localization of this isoform to the vacuoles of paraveinal mesophyll and bundle sheath cells (where VSPs are found) strongly suggest that VLXD should be considered as a major storage protein in soybean leaves. Furthermore, since VLXA, B and C also accumulate in sink-limited soybean leaves, are located in the cytosol of paraveinal mesophyll cells and are active at pH values typically found in this compartment, their activities may well contribute to lipid metabolism in this tissue. This multi-gene family is thus ideally poised to play a pivotal role in the balance of N deposition relative to lipid-based storage, defense or signaling, by modulating contribu- tions to these processes in the transient storage cells of the paraveinal mesophyll.

A de novo apparently balanced translocation involving chromosomes 8 and 20 was found in a 14-year-old boy with minor anomalies, mild skeletal abnormalities and ambiguous external genitalia including perineoscrotal hypospadias, rudimentary fused labioscrotal folds, bilateral cryptorchidism, and small penis. The karyotype was 46,XY, t(8;20)(q22.3-23;p13). No signs of other conditions known to be associated with structural anomalies of either chromosome 8 or 20 were present and incomplete masculinisation of the external genitalia appears to be the main component of the phenotype. Clinical and biological studies showed apparently normal testicular function in utero and after birth. Examinations excluded 5{alpha}-reductase deficiency or a block in any enzymatic steps of testosterone, glucocorticoid and mineralocorticoid biosynthesis. Coding sequences of the sex-determining gene (SRY) and androgen receptor gene (AR) were found to be identical to those of a normal male excluding their role in the cause of the present condition. Since several other reports describe the association of hypospadias and hypertelorism with deletions or translocations involving 8q, we suggest that a locus necessary for male sex differentiation is located at distal 8q. 24 refs., 3 figs.

Tax Increment Financing (TIF) is a popular yet controversial tool that allows local governments to use property tax revenue to fund the public costs of economic development. Since TIF gives one local government the power to affect the tax bases of the overlapping jurisdictions, there is uncertainty and argument on the part of government officials and taxpayers as to who really finances the program. To evaluate the alternative contentions, this paper presents a general methodology that identifies which taxpayers in which locations fund the TIF's expenditures, and sets forward the conditions under which such a local economic development policy can be beneficial to taxpayers. The paper applies the model to study the TIF program currently active in downtown Des Moines, Iowa. The evidence indicates that the taxpayers in the entire metropolitan area subsidized the downtown activities in the early years, but now pay lower property tax rates due to the city's TIF-financed urban revitalization program.

Optically driven surface reactions are attracting an increasing level of attention in the physical chemistry community. Not only have there been recent advances in establishing the viability of laser driven surface reactions, but there has also been an increased awareness of the need to understand the underlying reaction mechanisms. The necessity of accounting for energy-transfer processes that occur on the femtosecond time scale is now apparent. In this review the experimental and theoretical basis of current understanding is surveyed, and the prospective areas of advancement are considered. 142 refs., 8 figs.

Pregnant and progesterone-treated, ovariectomized ewes accumulate secretory products in the uterus that are immunosuppressive in mitogen-stimulated and mixed lymphocyte sheep cell cultures. In this study, uterine secretions from pregnant (Preg-UTM) and progesterone-treated, ovariectomized (P-UTM) ewes were equally effective in suppressing 3H-Tdr incorporation in mouse spleen cells stimulated with PHA. P-UTM inhibited PHA-stimulated, purified T-cells and separated L3T4+ and Lyt2+ T-cell subpopulations more than Preg-UTM, however. Both fluids were slightly inhibitory to conA-stimulated mouse spleen cells, enriched T-cells, and Lyt2+ T-cells but neither inhibited L3T4+ T-cells. For LPS-stimulated cells, P-UTM caused more suppression than Preg-UTM of enriched B-cells; however, suppression was similar for the two fluids on unseparated splenic cells. In antigen-stimulated mouse spleen cell cultures, both fluids inhibited antibody-forming cell responses to sheep erythrocytes, a thymus-dependent antigen, but neither suppressed antibody-forming cell responses to TNP-Ficoll, a thymus-independent antigen. These data indicate that uterine secretions in the ewe produced under the influence of progesterone or pregnancy contain immunoregulatory molecule(s) which modulate the activity of both homologous sheep and unrelated mouse lymphocytes. These studies establish the mouse as a useful in vivo model for studying the biological actions of these molecules.

The load-bearing capabilities of short-fiber reinforced thermoplastics composites can be evaluated, in principle, by the methods known to be satisfactory for unreinforced thermoplastics, but in practice the cost of a comprehensive evaluation of a composite would be prohibitive because of the anisotropy of the properties and its variation from point to point. For the same reasons the properties measured on a specimen cut from a molding may have little relevance to its overall performance. This paper describes recent experiments that could lead to a radical change in testing strategy. Instead of the classical method in which standard specimens cut from moldings are assumed to provide the various stiffness coefficients needed for anisotropic stress analysis, simple moldings such as discs or plaques are tested directly. The sacrifice of precision in the measurements and the loss of rigor in the definition of the measured quantities is more than compensated for by a gain in the general utility of the data and the substantial reduction in the cost of evaluations. The mechanical properties of shortfiber thermoplastics composites are particularly sensitive to mold geometry and the new methods of testing enable the effects to be assessed readily, whereas the information generated by the classical method is virtually indecipherable in that context. Examples are given in the paper.

Poly(Vinyl chloride) is the basic material for a huge number of products which are fabricated using very many different techniques. Established processing techniques continue to be improved, leading to additional benefits in process efficiency and product quality. New processes are also being introduced which are intended to increase the efficiency of material usage and to open up new application areas. These include: molecular orientation, foaming, and cross-linking. Developments are also occurring in the use of PVC in conjunction with other materials as micro- or macro-composites. Processing techniques include coextrusion and lamination. Many processing methods are likely to benefit from the microelectronics revolution in process control and monitoring.

The rotational‐, spin‐, and lambda doublet‐state distributions for nitric oxide (NO) formed in the CO2 laser multiphoton dissociation of methyl nitrite, CH3ONO, in a pulsed molecular beam are reported. Upon methyl nitrite photolysis by temporal square wave infrared laser pulses at 983 cm−1 of 50 ns duration and 800 MW/cm2 intensity, the low‐lying rotational levels of the nitric oxide fragments formed in the 2Π1/2 (F1) and 2Π3/2 (F2) spin‐orbit states exhibited Boltzmann‐like population distributions, characterizable by the rotational temperatures TR (F1)=400±10 K and TR (F2)=530±100 K; the integrated populations for J

A simple analytical solution of the equations which govern the formation, collisional relaxation, and mass transport rates of species produced in radially symmetric laser‐induced processes is given. These equations are specifically applied to the CO2 laser‐induced dissociations of CF2HCl and C2F3Cl dilute in argon. The concentration of the vibrational ground state of the CF2 radical product was probed as a function of time and pressure both during and after the photolyzing laser pulse by the laser‐excited fluorescence technique. From these measurements, the vibrational relaxation rate of ? CF2 in argon was determined to be kVT=2.0×10−15 cm3 sec−1 and its diffusion coefficient was found to be D=90 cm2 Torr sec−1 in argon.

The CFCl radical has been produced in the gas phase by both IR multiphoton photolysis of C2F3Cl and He metastable reaction with C2F3Cl. Single vibronic level fluorescence and excitation spectra taken of this species have yielded sufficient information to determine certain vibronic constants. The excited state was found to have an origin of T0=25 283±5 cm−1 with vibrational frequencies: ω2′=394±3 cm−1 and ω3′=739±5 cm−1. In the ground state, the vibrational frequencies were found to be: ω3″=118±10 cm−1, ω2″=448±6 cm−1, and ω3″=750±6 cm−1. The rotational structure of the vibronic bands is similar to those of band transitions of a near prolate top, and the electronic transition has been tentatively identified as ? 1A″←? 1A′ by analogy to similar CF2 transitions. The radiative lifetime of the excited state, τr=700±10 nsec, was found to be independent of the rovibronic excitation frequency. The change in the major rotational constant was found to be A′−A″=1.8±0.2 cm−1.