Myocardial Dysfunction in an Animal Model of Cancer Cachexia

Aims Fatigue is a common occurrence in cancer patients regardless of tumor type or anti-tumor therapies and is an especially problematic symptom in persons with incurable tumor disease. In rodents, tumor-induced fatigue is associated with a progressive loss of skeletal muscle mass and increased expression of biomarkers of muscle protein degradation. The purpose of the present study was to determine if muscle wasting and expression of biomarkers of muscle protein degradation occur in the hearts of tumor-bearing mice, and if these effects of tumor growth are associated with changes in cardiac function. Main methods The colon26 adenocarcinoma cell line was implanted into female CD2F1 mice and skeletal muscle wasting, in vivo heart function, in vitro cardiomyocyte function, and biomarkers of muscle protein degradation were determined. Key findings Expression of biomarkers of protein degradation were increased in both the gastrocnemius and heart muscle of tumor-bearing mice and caused systolic dysfunction in vivo. Cardiomyocyte function was significantly depressed during both cellular contraction and relaxation. Significance These results suggest that heart muscle is directly affected by tumor growth, with myocardial function more severely compromised at the cellular level than what is observed using echocardiography

Vertical distribution of microbial and meiofaunal populations in sediments of a natural coastal hydrocarbon seep

We studied the vertical distribution of microbes and meiofauna in natural hydrocarbon seep sediments to determine if there was a relationship between profiles of benthic trophic structure and the unique biogeochemical conditions present at the seep. Three stations in the Santa Barbara Channel represented a gradient of natural petroleum seepage, from very active, to moderate, to none. Seasonal differences were examined by sampling in the three major oceanographic seasons, upwelling (April), mixed (July), and Davidson (December). Densities of microbes and meiofauna were highest in July, and decreased in winter. All population sizes decreased with increasing depth in the sediment. Harpacticoids and Chl a were practically restricted to the surface sediments. Harpacticoids and Chl a were more dense (number per unit volume or strata of sediment) and abundant (number per unit area of sediment or sum of the strata) at the comparison site than at the seep sites. Density and abundance of nematodes, bacteria cell counts, and bacterial biomass were greater at the station with the most active seepage rates. Bacterial biovolumes appeared constant among sediment depths and stations, but cell biovolumes were larger in July. The data are consistent with the hypothesis that organic enrichment via petroleum utilization is responsible for increased abundances of bacteria and nematodes at the seep. There were strong correlations between densities of harpacticoids and microalgae, and densities of nematodes and bacteria. These links indicate that seeping petroleum might have an enhanced effect on the detrital (bacterial based) food web, but a toxic effect on the grazing (microalgal based) food web

Correlation of Treatment Dose Enoxaparin with Anti-Xa Concentrations in Adult Hemodialysis Inpatients

Enoxaparin, a low-molecular-weight-heparin, is being used in hemodialysis patients despite a lack of guideline or manufacturer dose recommendations. Due to enoxaparin’s renal excretion, the possibility of accumulating anti-Xa concentrations in hemodialysis patients using enoxaparin creates a hemorrhagic risk, calling for more research. The objectives of this study are to determine the correlation between treatment dose enoxaparin use and anti-Xa concentrations within the defined therapeutic range in patients receiving chronic, scheduled hemodialysis to determine the degree of change in anti-Xa concentrations in those cases where a concentration was obtained before and after a specific hemodialysis session, and to determine if there is evidence of enoxaparin accumulation over the course of treatment. This was a retrospective cohort study. Patients that were admitted to Indiana University Health facilities in a two-year period were identified from a Cerner query for inclusion eligibility. Inclusion criteria involved patients that received therapeutic dose enoxaparin based on actual body weight on a once daily basis, maintained a scheduled hemodialysis regimen, and had an anti-Xa concentration obtained after at least one enoxaparin dose. Despite lacking statistical significance, the data collected from this study depicts trends which can be utilized to guide future studies. The results of this study suggest that hemodialysis does not effectively remove enoxaparin

Infrared Transmissometer to Measure the Thickness of NbN Thin Films

We present an optical setup that can be used to characterize the thicknesses of thin NbN films to screen samples for fabrication and to better model the performance of the resulting superconducting nanowire single photon detectors. The infrared transmissometer reported here is easy to use, gives results within minutes and is non-destructive. Thus, the thickness measurement can be easily integrated into the workflow of deposition and characterization. Comparison to a similar visible-wavelength transmissometer is provided.Comment: 6 pages, 8 figure

Temporal variability and the relationship between benthic meiofaunal and microbial populations of a natural coastal petroleum seep

Previous studies of the Isla Vista petroleum seep in the Santa Barbara Channel found much higher abundances of macrofauna and concentrations of adenosine triphosphate (ATP) in sediments near petroleum seepage compared to those from nonseep areas. To further assess the possible effect of petroleum on organisms at the base of benthic food webs, population abundances of meiobenthos and their suspected microbial food (bacteria and diatoms) were measured biweekly for one year at three stations with differing petroleum exposure. Determinations of suspended particulate matter and the abundance and gut contents of juvenile fishes were also made at seep and nonseep stations. Nematodes and bacteria had higher abundances in areas of active petroleum seepage than in areas of moderate seepage (within 20 m) or no seepage (1.4 km away). Bacterial productivity (based on the frequency of dividing cells) was 340% greater in sediments from areas of active seepage compared to those from a nonseep station. Sediments within the seep, but away from active seepage, had rates of bacterial productivity 15 times greater than a nonseep comparison site. Densities of harpacticoid copepods and their probable principal food, diatoms, were not affected by petroleum seepage. Suspended organic matter caught in settling traps was not different between seep and nonseep stations. In addition, there was no evidence that predation pressure by juvenile fish on meiofauna was different between stations. The higher bacterial biomass and productivity in areas of petroleum seepage are consistent with the hypothesis that petroleum carbon is available for assimilation by sediment bacteria. The enhanced level of microbial carbon associated with the petroleum seep is available for consumption by benthic invertebrates and could explain the higher abundances of macrofauna and meiofauna found there

Synthesis of Bioinspired Carbohydrate Amphiphiles that Promote and Inhibit Biofilms

The synthesis and characterization of a new class of bioinspired carbohydrate amphiphiles that modulate Pseudomonas aeruginosa biofilm formation are reported. The carbohydrate head is an enantiopure poly-amido-saccharide (PAS) prepared by a controlled anionic polymerization of β-lactam monomers derived from either glucose or galactose. The supramolecular assemblies formed by PAS amphiphiles are investigated in solution using fluorescence assays and dynamic light scattering. Dried samples are investigated using X-ray, infrared spectroscopy, and transmission electron microscopy. Additionally, the amphiphiles are evaluated for their ability to modulate biofilm formation by the Gram-negative bacterium Pseudomonas aeruginosa. Remarkably, from a library of eight amphiphiles, we identify a structure that promotes biofilm formation and two structures that inhibit biofilm formation. Using biological assays and electron microscopy, we relate the chemical structure of the amphiphiles to the observed activity. Materials that modulate the formation of biofilms by bacteria are important both as research tools for microbiologists to study the process of biofilm formation and for their potential to provide new drug candidates for treating biofilm-associated infections

Prolonged and tunable residence time using reversible covalent kinase inhibitors.

Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo

Universal scaling of the critical temperature for thin films near the superconducting-to-insulating transition

Thin superconducting films form a unique platform for geometrically-confined, strongly-interacting electrons. They allow an inherent competition between disorder and superconductivity, which in turn enables the intriguing superconducting-to-insulator transition and believed to facilitate the comprehension of high-Tc superconductivity. Furthermore, understanding thin film superconductivity is technologically essential e.g. for photo-detectors, and quantum-computers. Consequently, the absence of an established universal relationships between critical temperature ($T_c$), film thickness ($d$) and sheet resistance ($R_s$) hinders both our understanding of the onset of the superconductivity and the development of miniaturised superconducting devices. We report that in thin films, superconductivity scales as $d^.$$T_c(R_s)$. We demonstrated this scaling by analysing the data published over the past 46 years for different materials (and facilitated this database for further analysis). Moreover, we experimentally confirmed the discovered scaling for NbN films, quantified it with a power law, explored its possible origin and demonstrated its usefulness for superconducting film-based devices.Comment: 100 pages, 37 figure