Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems.

Gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), graft-versus-host disease (GVHD), and inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are common human gastrointestinal diseases that share inflammation as a key driver for their development. A general outcome resulting from these chronic inflammatory conditions is increased oxidative stress. Oxidative stress is caused by the generation of reactive oxygen and nitrogen species that are part of the normal inflammatory response, but are also capable of damaging cellular DNA, protein, and organelles. Damage to DNA can include DNA strand breaks, point mutations due to DNA adducts, as well as alterations in methylation patterns leading to activation of oncogenes or inactivation of tumor suppressors. There are a number of significant long-term consequences associated with chronic oxidative stress, most notably cancer. Infiltrating immune cells and stromal components of tissue including fibroblasts contribute to dynamic changes occurring in tissue related to disease development. Immune cells can potentiate oxidative stress, and fibroblasts have the capacity to contribute to advanced growth and proliferation of the epithelium and any resultant cancers. Disease models for GERD, BE, GVHD, and ulcerative colitis based on three-dimensional human cell and tissue culture systems that recapitulate in vivo growth and differentiation in inflammatory-associated microphysiological environments would enhance our understanding of disease progression and improve our ability to test for disease-prevention strategies. The development of physiologically relevant, human cell-based culture systems is therefore a major focus of our research. These novel models will be of enormous value, allowing us to test hypotheses and advance our understanding of these disorders, and will have a translational impact allowing us to more rapidly develop therapeutic and chemopreventive agents. In summary, this work to develop advanced human cell-based models of inflammatory conditions will greatly improve our ability to study, prevent, and treat GERD, BE, GVHD, and inflammatory bowel disease. The work will also foster the development of novel therapeutic and preventive strategies that will improve patient care for these important clinical conditions

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring for these patients. These guidelines continue to endorse screening of high-risk patients for BE; however, routine screening is limited to men with reflux symptoms and multiple other risk factors. Acknowledging recent data on the low risk of malignant progression in patients with nondysplastic BE, endoscopic surveillance intervals are attenuated in this population; patients with nondysplastic BE should undergo endoscopic surveillance no more frequently than every 3-5 years. Neither routine use of biomarker panels nor advanced endoscopic imaging techniques (beyond high-definition endoscopy) is recommended at this time. Endoscopic ablative therapy is recommended for patients with BE and high-grade dysplasia, as well as T1a esophageal adenocarcinoma. Based on recent level 1 evidence, endoscopic ablative therapy is also recommended for patients with BE and low-grade dysplasia, although endoscopic surveillance continues to be an acceptable alternative. Given the relatively common recurrence of BE after ablation, we suggest postablation endoscopic surveillance intervals. Although many of the recommendations provided are based on weak evidence or expert opinion, this document provides a pragmatic framework for the care of the patient with BE

Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2016

Standards are essential to the advancement of science and technology. In systems and synthetic biology, numerous standards and associated tools have been developed over the last 16 years. This special issue of the Journal of Integrative Bioinformatics aims to support the exchange, distribution and archiving of these standards, as well as to provide centralised and easily citable access to them

Spin Dependent Fragmentation Functions for Heavy Flavor Baryons and Single Heavy Hyperon Polarization

Spin dependent fragmentation functions for heavy flavor quarks to fragment into heavy baryons are calculated in a quark-diquark model. The production of intermediate spin 1/2 and 3/2 excited states is explicity included. $\Lambda_b$ , $\Lambda_c$ and $\Xi_c$ production rate and polarization at LEP energies are calculated and, where possible, compared with experiment. A different approach, also relying on a heavy quark-diquark model, is proposed for the small momentum transfer inclusive production of polarized heavy flavor hyperons. The predicted $\Lambda_c$ polarization is roughly in agreement with experiment.Comment: LaTeX2e 11 pages with 4 PostScript figures. To be published in Proceedings of the International Workshop ``Symmetries and spin'', Praha-SPIN-200

Social Preferences and the Efficiency of Bilateral Exchange

Under what conditions do social preferences, such as altruism or a concern for fair outcomes, generate efficient trade? I analyze theoretically a simple bilateral exchange game: Each player sequentially takes an action that reduces his own material payoff but increases the other player’s. Each player’s preferences may depend on both his/her own material payoff and the other player’s. I identify necessary conditions and sufficient conditions on the players’ preferences for the outcome of their interaction to be Pareto efficient. The results have implications for interpreting the rotten kid theorem, gift exchange in the laboratory, and gift exchange in the field

Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors

Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe−/− mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4+ T cells, generated CD4+, CD8+, T regulatory (Treg) effector and central memory cells, converted naive CD4+ T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe−/−Ltbr−/− and to a similar extent in aged Apoe−/−Ltbrfl/flTagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs

Comparison of different wheelchair seating on thermoregulation and perceptual responses in thermoneutral and hot conditions in children

We examined the effects of 4 different wheelchair seatings on physiological and perceptual measures in 21 healthy, pre-pubertal children (9 ± 2 years). Participants were able-bodied and did not regularly use a wheelchair. Participants sat for 2 h in Neutral (∼22.5 °C, ∼40%RH) and Hot (∼35 °C, ∼37%RH) conditions. Four seating technologies were: standard incontinent cover and cushion (SEAT1); standard incontinent cover with new cushion (SEAT2) were tested in Neutral and Hot; new non-incontinent cover with new cushion (SEAT3); new incontinent cover and new cushion (SEAT4) were tested in Neutral only. Measurements included skin blood flow (SkBF), sweating rate (SR) and leg skin temperature (TlegB) on the bottom of the leg (i.e. skin-seat interface), heart rate (HR), mean skin temperature, tympanic temperature, thermal comfort, and thermal sensation. During Neutral, SkBF and TlegB were lower (∼50% and ∼1 °C, respectively) and SR higher (∼0.5 mg cm−2·min−1) (p  0.05). During Hot, HR and temperatures were higher than in Neutral but there were no differences (p > 0.05) between SEATs. New cover and cushion improved thermoregulatory responses during Neutral but not Hot. An impermeable incontinent cover negated improvements from cushion design. Seat cover appears more important than seat cushion during typical room conditions

Skin blood flow responses to acetylcholine and local heating at rest and 60%V O2max, and associated nitric oxide contribution, in boys vs. girl

To determine sex-related differences in the skin-blood-flow (SkBF) response to exercise, local heating, and acetylcholine (ACh) in children. Additionally, the contribution of nitric oxide (NO) was examined. Methods: Forearm SkBF during local heating (44˚C), ACh iontophoresis, and exercise (30 min cycling, 60% OV 2max) was assessed, using Laser-Doppler fluxmetry, in 12 boys and 12 girls (7–13 yrs old), with and without NO synthase inhibition, using Nω-nitro-L-arginine methyl ester (L-NAME) iontophoresis. Results: Local-heating-induced and ACh-induced SkBF increase were not different between boys and girls (Local heating: 1445±900% and 1432±582% of baseline, , p=.57; ACh: 673±434% and 558±405% of baseline, respectively, p=0.18). Exercise-induced increase in SkBF was greater in boys than girls (528±290 and 374±192% of baseline, respectively, p=0.03). L-NAME blunted the SkBF response to ACh and during exercise (p<0.001), with no difference between sexes. Summary: SkBF responses to ACh and local heat stimuli were similar in boys and girls, while the increase in SkBF during exercise was greater in boys. The apparent role of NO was not different between boys and girls. It is suggested that the greater SkBF response in the boys during exercise is related to greater relative heat production and dissipation needs during this exercise intensity. The response to body-size-related workload should be further examined

Sequencing of 15 622 Gene-bearing BACs Clarifies the Gene-dense Regions of the Barley Genome

Barley (Hordeum vulgare L.) possesses a large and highly repetitive genome of 5.1 Gb that has hindered the development of a complete sequence. In 2012, the International Barley Sequencing Consortium released a resource integrating whole-genome shotgun sequences with a physical and genetic framework. However, because only 6278 bacterial artificial chromosome (BACs) in the physical map were sequenced, fine structure was limited. To gain access to the gene-containing portion of the barley genome at high resolution, we identified and sequenced 15 622 BACs representing the minimal tiling path of 72 052 physical-mapped gene-bearing BACs. This generated ~1.7 Gb of genomic sequence containing an estimated 2/3 of all Morex barley genes. Exploration of these sequenced BACs revealed that although distal ends of chromosomes contain most of the gene-enriched BACs and are characterized by high recombination rates, there are also gene-dense regions with suppressed recombination. We made use of published map-anchored sequence data from Aegilops tauschii to develop a synteny viewer between barley and the ancestor of the wheat D-genome. Except for some notable inversions, there is a high level of collinearity between the two species. The software HarvEST:Barley provides facile access to BAC sequences and their annotations, along with the barley–Ae. tauschii synteny viewer. These BAC sequences constitute a resource to improve the efficiency of marker development, map-based cloning, and comparative genomics in barley and related crops. Additional knowledge about regions of the barley genome that are gene-dense but low recombination is particularly relevant