Investigation of the metabolism of Substance-P at the blood-brain barrier using LC-MS/MS

Please note that this is an author-produced PDF of an article accepted for publication following peer review. The publisher version is available on its site.Substance P (SP) has been associated with pain, depression as well as neurodegenerative diseases. Many of these diverse actions of SP can potentially be attributed to SP metabolites generated at the blood-brain barrier (BBB). In these studies, the metabolism of SP was investigated using an in vitro model of the BBB and LC-MS/MS. Substance P metabolism was found to be non-saturable in the concentration range of 100 nM to 10 μM, with approximately 70% of the peptide remaining intact after 5 hrs. The major metabolites of SP were identified by MS to be 3-11 and 5-11. Two previously unreported metabolites, 5-11 and 6-11 were also found in our studies. Several additional minor SP metabolites including 1-9 and 2-11 were also identified. A profile of the SP metabolites generated by the BBB overtime was obtained. The results from the present study provide us a better understanding of the role of blood-brain barrier in the pharmacology of SP

Population Dynamics Based on Resource Availability & Founding Effects: Live & Computational Models

With the looming global population crisis, it is more important now than ever that students understand what factors influence population dynamics. We present three learning modules with authentic, student-centered investigations that explore rates of population growth and the importance of resources. These interdisciplinary modules integrate biology, mathematics, and computer-literacy concepts aligned with the Next Generation Science Standards. The activities are appropriate for middle and high school science classes and for introductory college-level biology courses. The modules incorporate experimentation, data collection and analysis, drawing conclusions, and application of studied principles to explore factors affecting population dynamics in fruit flies. The variables explored include initial population structure, food availability, and space of the enclosed population. In addition, we present a computational simulation in which students can alter the same variables explored in the live experimental modules to test predictions on the consequences of altering the variables. Free web-based graphing (Joinpoint) and simulation software (NetLogo) allows students to work at home or at school

Comprehensive LESA Mass Spectrometry Imaging of Intact Proteins by Integration of Cylindrical FAIMS

The benefits of high field asymmetric waveform ion mobility spectrometry (FAIMS) for mass spectrometry imaging of intact proteins in thin tissue sections have been demonstrated previously. In those works, a planar FAIMS device coupled with a Thermo Elite mass spectrometer was employed. Here, we have evaluated a newly introduced cylindrical FAIMS device (the FAIMS Pro) coupled with a Thermo Fusion Lumos mass spectrometer for liquid extraction surface analysis mass spectrometry imaging of intact proteins in thin tissue sections from rat testes, kidney, and brain. The method makes use of multiple FAIMS compensation values at each location (pixel) of the imaging array. A total of 975 nonredundant protein species were detected in the testes imaging dataset, 981 in the kidney dataset, and 249 in the brain dataset. These numbers represent a 7-fold (brain) and over 10-fold (testes, kidney) improvement on the numbers of proteins previously detected in LESA FAIMS imaging, and a 10-fold to over 20-fold improvement on the numbers detected without FAIMS on this higher performance mass spectrometer, approaching the same order of magnitude as those obtained in top-down proteomics of cell lines. Nevertheless, high throughput identification within the LESA FAIMS imaging workflow remains a challenge

Intake of Supplemental Deer Pellets Containing Ground Blueberry Juniper by Wild Pigs

Supplemental feeding of cervid species such as white-tailed deer (Odocoileus virginianus; deer) is now a common management practice in the United States. Supplemental feeding can be costly and more expensive when supplements are consumed by non-target species such as wild pigs (Sus scrofa; pigs). From May 13 to June 17, 2015, we evaluated the effects of using ground blueberry juniper (Juniperus ashei) or cottonseed (Gossypium spp.) hulls as a roughage ingredient in a supplemental deer pellet to deter pig consumption at the Texas A&M AgriLife Research Center in San Angelo, Texas, USA. We analyzed dry matter intake, growth performance, in vitro digestibility and fermentation, and blood serum chemistry of pigs using a 2 × 2 factorial study design that included 3 feeding periods. Pigs were assigned to 1 of 4 supplement diets (n = 5 pigs/supplement) or to a commercially available swine diet (BASAL; n = 4 pigs). Animals assigned to supplement diets were also offered BASAL based on percentage of body weight (BW) during each period. Supplement diets differed by roughage source and percentage of roughage: cottonseed hulls 20%, cottonseed hulls 40%, blueberry juniper 20%, or blueberry juniper 40%. During each period, the amount of supplement and BASAL diet offered to animals assigned to a supplement was fed as a percentage of BW; period 1 (day 0 to 17) = 5% supplement diet and 5% BASAL diet, period 2 (day 18 to 26) = 5% supplement diet and 2% BASAL diet, period 3 (day 27 to 34) = 5% supplement diet and 5% BASAL diet. Animals assigned to only BASAL were offered the same amount of feed as a percent of BW as supplement animals during each period. We observed a roughage × period interaction (P = 0.03) for supplement dry matter intake g/day and a roughage × period interaction (P \u3c 0.09) for total dry matter intake as a percentage of BW. No differences were observed within period. No other variables had percent roughage x period differences. Ground blueberry juniper was indigestible by pigs; the in vitro digestibility of dry matter and gross energy was \u3c 1%. Greater blood serum alanine aminotransferase (P= 0.07) in pigs consuming experimental supplement diets suggested the possibility of liver damage. Our findings suggest that there does not appear to be a benefit of using ground juniper as a roughage source to reduce consumption of supplemental deer feed by pigs

Mortality and Readmission After Cervical Fracture from a Fall in Older Adults: Comparison with Hip Fracture Using National Medicare Data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115960/1/jgs13670.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115960/2/jgs13670_am.pd

Metagenomic characterisation of the gut microbiome and effect of complementary feeding on bifidobacterium spp. in Australian infants

Complementary feeding induces dramatic ecological shifts in the infant gut microbiota toward more diverse compositions and functional metabolic capacities, with potential implications for immune and metabolic health. The aim of this study was to examine whether the age at which solid foods are introduced differentially affects the microbiota in predominantly breastfed infants compared with predominantly formula-fed infants. We performed whole-genome shotgun metagenomic sequencing of infant stool samples from a cohort of six-month-old Australian infants enrolled in a nested study within the ORIGINS Project longitudinal birth cohort. Infants born preterm or those who had been administered antibiotics since birth were excluded. The taxonomic composition was highly variable among individuals at this age. Predominantly formula-fed infants exhibited a higher microbiome diversity than predominantly breastfed infants. Among the predominantly breastfed infants, the introduction of solid foods prior to five months of age was associated with higher alpha diversity than solid food introduction after six months of age, primarily due to the loss of Bifidobacterium infantis. In contrast, the age at which solid food was introduced was not associated with the overall change in diversity among predominantly formula-fed infants but was associated with compositional changes in Escherichia abundance. Examining the functional capacity of the microbiota in relation to these changes, we found that the introduction of solid foods after six months of age was associated with elevated one-carbon compound metabolic pathways in both breastfed and formula-fed infants, although the specific metabolic sub-pathways differed, likely reflecting different taxonomic compositions. Our findings suggest that the age of commencement of solid foods influences the gut microbiota composition differently in predominantly breastfed infants than in predominantly formula-fed infants