Dietary Protein Content and Digestibility Influences Discrimination of Amino Acid Nitrogen Isotope Values in a Terrestrial Omnivorous Mammal

RATIONALE: Ecologists increasingly determine the δ15N values of amino acids (AA) in animal tissue; source AA typically exhibit minor variation between diet and consumer, while trophic AA have increased δ15N values in consumers. Thus, trophic-source δ15N offsets (i.e., Δ15NT-S) reflect trophic position in a food web. However, even minor variation in δ15Nsource AA values may influence the magnitude of offset that represents a trophic step, known as the trophic discrimination factor (i.e., TDFT-S). Diet digestibility and protein content can influence the δ15N values of bulk animal tissue, but the effects on AA Δ15NT-S and TDFT-S in mammals are unknown. METHODS: We fed captive mice (Mus musculus) either (A) a low-fat, high-fiber diet with low, intermediate, or high protein; or (B) a high-fat, low-fiber diet with low or intermediate protein. Mouse muscle and dietary protein were analyzed for bulk tissue δ15N using elemental analyzer-isotope ratio mass spectrometry (EA-IRMS), and were also hydrolyzed into free AA that were analyzed for δ15N using EA-IRMS. RESULTS: As dietary protein increased, Δ15NConsumer-Diet slightly declined for bulk muscle tissue in both experiments, increased for AA in the low-fat, high-fiber diet (A), and remained the same or decreased for AA in the high-fat, low-fiber diet (B). The effects of dietary protein on Δ15 NT-S and on TDFT-S varied by AA but were consistent between variables. CONCLUSIONS: Diets were less digestible and included more protein in Experiment A than in Experiment B. As a result, the mice in Experiment A probably oxidized more AA, resulting in greater Δ15 NConsumer-Diet values. However, the similar responses of Δ15 NT-S and of TDFT-S to diet variation suggest that if diet samples are available, Δ15 NT-S accurately tracks trophic position. If diet samples are not available, the patterns presented here provide a basis to interpret Δ15 NT-S values The trophic-source offset of Pro-Lys did not vary across diets, and therefore may be more reliable for omnivores than other offsets (e.g., Glu-Phe)

Differing roles of autophagy in HIV-associated neurocognitive impairment and encephalitis with implications for morphine co-exposure

We investigated the role of autophagy in HIV-infected subjects with neurocognitive impairment (NCI) ± HIV encephalitis (HIVE), many of which had a history of polysubstance abuse/dependence, using post-mortem brain tissues to determine whether differences in autophagy related factors may be more associated with NCI or NCI-encephalitis. Using qRT-PCR, we detected significant differences in gene expression levels with SQSTM1, LAMP1 higher in HIV-infected subjects without NCI while ATG5, SQSTM1 were then lower in HIV infection/NCI and ATG7, SQSTM1 being higher in NCI-HIVE. Immunohistochemical labeling of these autophagy associated proteins (also including Beclin 1 and LC3B) in Iba1-positive microglial cells showed generally higher immunoreactivity in the NCI and NCI-HIVE groups with more focal vs. diffuse patterns of expression in the NCI-HIVE group. Furthermore, analysis of microarray data from these same subjects found significantly higher levels of LAMP1 in NCI-HIVE compared to uninfected subjects in the basal ganglia. Finally, we tested the effect of supernatant from HIV-1-infected microglia and HIV-1 Tat protein in combination with morphine on neurons in vitro and found opposing events with both significant inhibition of autophagic flux and reduced dendrite length for morphine and supernatant treatment while Tat and morphine exposure resulted in lower autophagic activity at an earlier time point and higher levels in the later. These results suggest autophagy genes and their corresponding proteins may be differentially regulated at the transcriptional, translational, and post-translational levels in the brain during various stages of the HIV disease and that infected individuals exposed to morphine can experience mixed signaling of autophagic activity which could lead to more severe NCI than those without opioid use

Trinidad Food Producers’ Training Needs for Food Security and Implications for Extension

The purpose of this study was to explore farmers’ knowledge of food security issues in Trinidad. Such information can be used to develop appropriate extension training interventions. Using a Borich (1980) methodology, a total of 300 agricultural producers in Trinidad were surveyed with an instrument that consisted of two parts: (a) personal demographic and farm related questions, and (b) indicators of knowledge and importance of 27 food security issues derived from The National Food Production Action Plan 2012 – 2015. Overall, the top five issues identified by producers were: (a) the incentive program that is focused on outputs; (b) research and development for both livestock and crop farmers; (c) partnerships between public sector agencies, research institutions, and the private sector to provide suitable capacity to deliver all food production programs; (d) postharvest technologies that create employment opportunities, increase returns to farmers, improve food quality, and ensure food safety; and (e) and technology packages (of information) to help farmers improve yield, quality, and availability. All 27 food security issues varied in at least one of the categories assessed: 22 issues varied by location; 18 issues varied by farm type; 5 issues varied by farming status; and 19 issues varied by education level of the farmer. These results can guide extension programming in Trinidad and also be informative for policy makers

Astronaut Health Participant Summary Application

The Longitudinal Study of Astronaut Health (LSAH) Participant Summary software captures data based on a custom information model designed to gather all relevant, discrete medical events for its study participants. This software provides a summarized view of the study participant s entire medical record. The manual collapsing of all the data in a participant s medical record into a summarized form eliminates redundancy, and allows for the capture of entire medical events. The coding tool could be incorporated into commercial electronic medical record software for use in areas like public health surveillance, hospital systems, clinics, and medical research programs

Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation

We previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent HIV-infected brain reservoirs. In the present study and for the first time, the bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear polyethylenimines (PEI) as a gene carrier was investigated in adult mouse brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA delivered intranasally was found in the cytoplasm of neurons and glial cells of the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse immune reaction encountered. Intranasal delivery of the siRNA targeting Beclin1 significantly depleted the target protein expression levels in brain tissues with no evidence of toxicity. Binding of siRNA to PEI-polymer was characterized and confirmed by Raman spectroscopy. These results indicate that the intranasal drug delivery allows for the direct delivery of the PEI-siRNA nano-complex to the central nervous system, which could potentially offer an efficient means of gene silencing-mediated therapy in the HIV-infected brain

Human Fat-Derived Mesenchymal Stem Cells Xenogenically Implanted in a Rat Model Show Enhanced New Bone Formation in Maxillary Alveolar Tooth Defects

Background. Due to restorative concerns, bone regenerative therapies have garnered much attention in the field of human oral/maxillofacial surgery. Current treatments using autologous and allogenic bone grafts suffer from inherent challenges, hence the ideal bone replacement therapy is yet to be found. Establishing a model by which MSCs can be placed in a clinically acceptable bone defect to promote bone healing will prove valuable to oral/maxillofacial surgeons. Methods. Human adipose tissue-derived MSCs were seeded onto Gelfoam® and their viability, proliferation, and osteogenic differentiation was evaluated in vitro. Subsequently, the construct was implanted in a rat maxillary alveolar bone defect to assess in vivo bone healing and regeneration. Results. Human MSCs were adhered, proliferated, and uniformly distributed, and underwent osteogenic differentiation on Gelfoam®, comparable with the tissue culture surface. Data confirmed that Gelfoam® could be used as a scaffold for cell attachment and a delivery vehicle to implant MSCs in vivo. Histomorphometric analyses of bones harvested from rats treated with hMSCs showed statistically significant increase in collagen/early bone formation, with cells positive for osteogenic and angiogenic markers in the defect site. This pattern was visible as early as 4 weeks post treatment. Conclusions. Xenogenically implanted human MSCs have the potential to heal an alveolar tooth defect in rats. Gelfoam®, a commonly used clinical biomaterial, can serve as a scaffold to deliver and maintain MSCs to the defect site. Translating this strategy to preclinical animal models provides hope for bone tissue engineering

Patients with ulcerative colitis who have normalized histology are clinically stable after de-escalation of therapy

We have previously demonstrated that histological normalization in ulcerative colitis (UC) is associated with superior maintenance of remission outcomes. This single-center, retrospective case-control study assessed outcomes after the therapeutic de-escalation in UC patients who have achieved histologic normalization. A total of 111 patients were included, of which 24 underwent de-escalation, and 87 patients without therapeutic changes. The most commonly withdrawn therapy was aminosalicylates (50%), followed by immunomodulators (37.5%), and biologics (12.5%). Fourteen patients remained on therapies after de-escalation, including aminosalicylate (9/14), immunomodulators (3/14), and biologics (3/14), while 10 patients were not on any therapy immediately after withdrawal. Median follow-up was 43 months in the de-escalation group and 47 months in the control. The rates of clinical, endoscopic, and histologic recurrence were not significantly different between the two groups, nor was the proportion of patients who subsequently required additional therapies after withdrawal (P = 0.133). Clinical and endo-histologic recurrence rates were the lowest in patients who withdrew immunomodulators (0% and 14.3%, respectively). We demonstrate the clinical stability of therapeutic withdrawal in UC patients with histologic normalization

Biomanufacturing Organized Collagen-Based Microfibers as a Tissue ENgineered Device (TEND) for Tendon Regeneration

Approximately 800,000 surgical repairs are performed annually in the U.S. for debilitating injuries to ligaments and tendons of the foot, ankle, knee, wrist, elbow and shoulder, presenting a significant healthcare burden. To overcome current treatment shortcomings and advance the treatment of tendon and ligament injuries, we have developed a novel electrospun Tissue ENgineered Device (TEND), comprised of type I collagen and poly(D,L-lactide) (PDLLA) solubilized in a benign solvent, dimethyl sulfoxide (DMSO). TEND fiber alignment, diameter and porosity were engineered to enhance cell infiltration leading to promote tissue integration and functional remodeling while providing biomechanical stability. TEND rapidly adsorbs blood and platelet-rich-plasma (PRP), gradually releases growth factors over two weeks. TEND further supported cellular alignment and upregulation of tenogenic genes from clinically relevant human stem cells within three days of culture. TEND implanted in a rabbit Achilles tendon injury model showed new in situ tissue generation, maturation, and remodeling of dense, regularly oriented connective tissue in vivo. In all, TEND\u27s organized microfibers, biological fluid and cell compatibility, strength and biocompatiblility make significant progress towards clinically translating electrospun collagen-based medical devices for improving the clinical outcomes of tendon injuries

2MASS photometry of edge-on spiral galaxies. I. Sample and general results

A sample of edge-on spiral galaxies aimed at a study of the main structural and photometric parameters of edge-on galaxies both of early and late types is presented. The data were taken from the 2MASS in the J, H and K_s filters. The sample consists of 175 galaxies in the K_s-filter, 169 galaxies in the H-filter and 165 galaxies in the J-filter. We present bulge and disc decompositions of each galaxy image. All galaxies have been modelled with a Sersic bulge and exponential disc with the BUDDA v2.1 package. The main conclusions of our general statistical analysis of the sample are: (1) The distribution of the apparent bulge axis ratio q_b for the subsample with n < 2 can be attributed to triaxial, nearly prolate bulges that are seen from different projections, while n > 2 bulges seem to be oblate spheroids with moderate flattening. (2) For the sample galaxies, the effective radius of the bulge r_{e,b}, the disc scalelength h and the disc scaleheight z_0 are well correlated. However, there is a clear trend for the ratio r_{e,b}/h to increase with n. (3) There is a hint that the fundamental planes of discs, which links only disc parameters and the maximum rotational velocity of gas, are different for galaxies with different bulges. (4) The investigation of the Photometric Plane of sample bulges shows that the plane is not flat and has a prominent curvature towards small values of n. For bulges this fact was not noticed earlier. (5) The clear relation between the flattening of stellar discs h/z_0 and the relative mass of a spherical component, including a dark halo, is confirmed not for bulgeless galaxies but for galaxies with massive bulges. (Abridged)Comment: 20 pages, 13 figures, accepted for publication in MNRA