Membrane protein alterations in rodent erythrocytes and synaptosomes due to aging and hyperoxia

AbstractWe have applied the technique of electron paramagnetic resonance (EPR) protein-specific spin labeling to the study of membrane protein alterations occurring during age and exposure to isobaric hyperoxia. Cortical synaptosomes and erythrocyte membranes (ghosts) were isolated from young rodents (Fisher 344 rats or mongolian gerbils, 3–4 months of age) and aged rodents (age 22–27 months for rats, greater than 15 months for gerbils). Membrane proteins were spin labeled with the thiol-specific spin label MAL-6 (2,2,6,6,-tetramethyl-4-maleimido-piperdin-1-oxyl). The relevant EPR spectral parameter of MAL-6 labeled membranes, the W/S ratio, decreased significantly with age of animal in both synaptosomes and ghosts (P < 0.001). As a paradigm for accelerated oxidative stress, young and aged gerbils were exposed to an atmosphere of 90–100% O2 for 0–48 h. In both young and aged gerbils, the W/S ratio decreased significantly with hyperoxic stress (P < 0.003). The W/S ratio of synaptosomes isolated from aged gerbils decreased continually from 0–48 h hyperoxia, whereas the W/S ratio of synaptosomes from young animals demonstrated a pronounced rebound effect from 24–48 h. The results are discussed with reference to membrane protein oxidation in aging

Towards real-time classification of astronomical transients

Exploration of time domain is now a vibrant area of research in astronomy, driven by the advent of digital synoptic sky surveys. While panoramic surveys can detect variable or transient events, typically some follow-up observations are needed; for short-lived phenomena, a rapid response is essential. Ability to automatically classify and prioritize transient events for follow-up studies becomes critical as the data rates increase. We have been developing such methods using the data streams from the Palomar-Quest survey, the Catalina Sky Survey and others, using the VOEventNet framework. The goal is to automatically classify transient events, using the new measurements, combined with archival data (previous and multi-wavelength measurements), and contextual information (e.g., Galactic or ecliptic latitude, presence of a possible host galaxy nearby, etc.); and to iterate them dynamically as the follow-up data come in (e.g., light curves or colors). We have been investigating Bayesian methodologies for classification, as well as discriminated follow-up to optimize the use of available resources, including Naive Bayesian approach, and the non-parametric Gaussian process regression. We will also be deploying variants of the traditional machine learning techniques such as Neural Nets and Support Vector Machines on datasets of reliably classified transients as they build up

Development of a Novel Biological Intervertebral Disc Scaffold

Back pain is a major public health issue in our society, and is strongly correlated with the degeneration of intervertebral discs (IVDs). Current therapies are conservative or surgical, and no attempt to regenerate the IVD. The first goal of our project is to create a fully decellularized bovine caudal IVD to be used as a scaffold on which to seed adult human stem cells in an attempt to engineer a healthy, replacement IVD for patients suffering from IVD degeneration and lower back pain. The goal of decellularization is to eliminate DNA content while retaining glycosaminoglycan (GAG) content. Eliminating DNA content will prevent a foreign body response by the host\u27s immune system once the IVD is implanted. GAG is responsible for forming interfibrillar bridges with collagen fibrils and thus assisting in resisting compressive and tensile forces. By retaining GAG content in our decellularized IVDs we will maintain structural integrity of the extracellular matrix. The IVDs closest to the base of the bovine tail were targeted, because they are similar in size and biochemistry to the human IVD. We use a mix of conventional methods including freeze thaw, sonication and agitation in a solution of sodium dodecyl sulfate (SDS) and ethylene diamine tetraacetic acid (EDTA). After decellularization, half of each IVD was placed in a tissue cassette and put formalin in preparation for histological analysis, and the other half was frozen prior to biochemical analysis (DMMB and PicoGreen assay). Our results thus far are promising in eliminating DNA content but show we have a large room for improvement in retaining GAG content

Only Yes Means Yes: Sexual Coercion in Rural Adolescent Relationships

Purpose Sexual consent is important to healthy relationships; however, sexual coercion is common. We examine modifiable risk and protective factors for sexual coercion among high school students in a rural community. Methods We surveyed 10th graders (N = 442) in a rural, Midwestern, low-to-middle income county before receiving an evidence-based sex education program. Sexual coercion was a single item, “has anyone you were dating or going out with forced you to do sexual things that you did not want to do?” We examined associations between sexual coercion and demographics, risk behaviors, sexual self-efficacy, controlling relationship behaviors, parent communication, and adverse childhood experiences. Results Approximately 22% of females and 8% of males reported experiencing sexual coercion at least once in their lifetime. Gender differences emerged in associated risk and protective factors, including sexual sex efficacy, controlling relationship behaviors, parent–adolescent communication about sex, and adverse childhood experiences. Conclusions Sexual coercion is common among adolescents in rural communities. Prevention interventions should target modifiable risk and protective factors

The Lagrange and Markov spectra from the dynamical point of view

This text grew out of my lecture notes for a 4-hours minicourse delivered on October 17 \& 19, 2016 during the research school "Applications of Ergodic Theory in Number Theory" -- an activity related to the Jean-Molet Chair project of Mariusz Lema\'nczyk and S\'ebastien Ferenczi -- realized at CIRM, Marseille, France. The subject of this text is the same of my minicourse, namely, the structure of the so-called Lagrange and Markov spectra (with an special emphasis on a recent theorem of C. G. Moreira).Comment: 27 pages, 6 figures. Survey articl

ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy in borderline-resected pancreatic cancer

Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise RT modality to intensify the irradiation effect for cancer involving upper abdominal structures and organs, generally delivered with electrons (IOERT). Unresectable, borderline and resectable disease categories benefit from dose-escalated chemoradiation strategies in the context of active systemic therapy and potential radical surgery. Prolonged preoperative treatment may act as a filter for selecting patients with occult resistant metastatic disease. Encouraging survival rates have been documented in patients treated with preoperative chemoradiation followed by radical surgery and IOERT (>20 months median survival, >35% survival at 3 years). Intensive preoperative treatment, including induction chemotherapy followed by chemoradiation and an IOERT boost, appears to prolong long-term survival within the subset of patients who remain relapse-free for>2 years (>30 months median survival; >40% survival at 3 years). Improvement of local control through higher RT doses has an impact on the survival of patients with a lower tendency towards disease spread. IOERT is a well-accepted approach in the clinical scenario (maturity and reproducibility of results), and extremely accurate in terms of dose-deposition characteristics and normal tissue sparing. The technique can be adapted to systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend use of IOERT in cases of close surgical margins and residual disease. We hereby report the ESTRO/ACROP recommendations for performing IOERT in borderline-resectable pancreatic cancer