CIRCADIAN ENTRAINMENT IN MILITARY PILOTS: TRANSITIONING FROM DAY TO NIGHT FLIGHTS

This study assessed the effectiveness of light exposure in transitioning aviation schedules from days to nights. We hypothesized that a single night of light treatment will delay melatonin onset and improve performance in a simulated flight task. Study participants were military pilots who flew four simulated flights: one baseline daytime flight and three consecutive night flights. Pilots were exposed to four hours of high energy visible (HEV) light (1,000 lux) on the second night but remained in dim light on the first and third nights. Saliva samples for determining melatonin levels were collected every half hour during the three nighttime data collections. Participants also completed questionnaires to include the Bedford Workload Scale and the Karolinska Sleepiness Scale. We tracked each participant’s circadian rhythm using their melatonin onset profiles over the three nights of the study. Pilot performance in a flight simulator was assessed for each of the three data collection sessions using three flight profiles of progressing difficulty. Results showed an average delay in melatonin onset mean of 1.33 hr (SD = .36 hr). Flight performance over the testing period did not show any significant changes. This study showed that light can be used to effectively delay the onset of melatonin, potentially providing a substantive advantage to personnel who must rapidly transition to new work schedules. Further study is recommended before implementing in operational conditions.Lieutenant Commander, United States Coast GuardApproved for public release. Distribution is unlimited

The effect of light on circadian entrainment: Risk mitigation techniques for shifting from day to night flight operations

Prepared for: Assistant Commandant of the Marine CorpsA midair collision in the early morning hours of December 6, 2018 resulted in the tragic deaths of six US Marine Corps aircrew members and the loss of two aircraft, a KC-130 tanker and an F/A-18. The mishap occurred around 2 AM during a routine nighttime air refueling training mission off the coast of Japan. In the investigation that followed, fatigue was identified as a major contributor; the transition from day to night flights was called out as a problem area that continues to plague aviation commands. Subsequent investigations confirmed findings and requested help from the Naval Postgraduate School (NPS) Crew Endurance Team to study the problem and make recommendations for safer transition from day to night flight operations. The study goal was to provide recommendations to the fleet regarding the limitations and best practices for shifting aviators from day to night operations. After reviewing the scientific literature, NPS designed a study to determine the efficacy of high energy visible (HEV) light exposure in shifting the circadian rhythms of study participants. The project was a hybrid study of military aviators who, as graduate students at NPS, continued normal daily schedules but came into the laboratory for 6 to 8 hours on three consecutive evenings. The study attempted to replicate the patterns of aviators who could potentially be required to abruptly shift to night flight operations. Results showed that a single 4-hour exposure of blue-enriched white light (~1000 lux) successfully delayed the circadian phase of all participants an average of 1 hour 19 minutes (range 53 minutes to 1 hour 56 minutes). Melatonin onset was delayed in all participants. This circadian shift is estimated to be a 10-fold increase over what would be achieved without the HEV light. Light was shown to have an alerting effect with participants reporting less sleepiness and reduced subjective workload with improved flight performance. Conclusions from the literature review and our study indicate that circadian entrainment in military operational settings should use light management as the dominant method for shifting the circadian clock. In general, it is expected that higher rates of adaptation (i.e., more rapid entrainment) will occur by aligning and applying multiple synchronization methods simultaneously, i.e., light management combined with strategically timed exercise, meals, melatonin, and caffeine. Based on these conclusions, we developed general recommendations and two circadian synchronization plans for crewmembers switching from day to night operations. One plan shows a schedule that prepares for night operations shifting over multiple days. The other shows a schedule for crewmembers required to shift from abruptly without notice. These plans warrant further development in an operational environment to ensure they can be implemented safely and effectively.Assistant Commandant of the Marine CorpsAssistant Commandant of the Marine CorpsApproved for public release; distribution is unlimite

Cross-talk among gp130 cytokines in adipocytes

The interleukin-6 (IL-6) family of cytokines is a family of structurally and functionally related proteins, including IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1). These proteins are also known as gp130 cytokines because they all share gp130 as a common transducer protein within their functional receptor complexes. Several of these cytokines (LIF, OSM, CNTF, and CT-1) also utilize the LIF receptor (LIFR) as a component of their receptor complex. We have shown that all of these cytokines are capable of activating both the JAK/STAT and p42/44 mitogen-activated protein kinase signaling pathways in 3T3-L1 adipocytes. By performing a variety of preincubation studies and examining the ability of these cytokines to activate STATs, ERKs, and induce transcription of SOCS-3 mRNA, we have also examined the ability of gp130 cytokines to modulate the action of their family members. Our results indicate that a subset of gp130 cytokines, in particular CT-1, LIF, and OSM, has the ability to impair subsequent signaling activity initiated by gp130 cytokines. However, IL-6 and CNTF do not exhibit this cross-talk ability. Moreover, our results indicate that the cross-talk among gp130 cytokines is mediated by the ability of these cytokines to induce ligand-dependent degradation of the LIFR, in a proteasome-independent manner, which coincides with decreased levels of LIFR at the plasma membrane. In summary, our results demonstrate that an inhibitory cross-talk among specific gp130 cytokines in 3T3-L1 adipocytes occurs as a result of specific degradation of LIFR via a lysosome-mediated pathway. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc

The solution structure of a cyclic endothelin antagonist, BQ-123, based on 1H1H and 13H1H three bond oupling constants

AbstractA cyclic pentapeptide endothelin antagonist, cyclo(dTrp-dAsp-Pro-dVal-Leu), recently reported (K. Ishikawa et al., 13th Am. Pept. Symp., Cambridge MA, 1991) has been studied by NMR spectroscopy and molecular modeling. A stable structure has been determined without the use of nuclear Overhauser effects and is based primarily on homonuclear and heteronuclear three bond coupling constants. The 13C-edited TOCSY experiment is demonstrated at natural abundance and ∼30 mM peptide concentrations. Three bond 13C1H coupling constants obtained by this method are shown to reduce the ambiguity in φ angle determination which exists when only interproton coupling constants are used. Three out of four φ angles were determined uniquely by this method and the fourth was reduced to two possible values. The proline φ angle was determined to be −78° based on the 3JHzHα and 3JHzHβ coupling constants. Comparison of amide proton temperature dependence, chemical shifts and vicinal proton coupling constants in a 20% acetonitrile/80% water solvent mixture and in (CD3)2SO indicates that the structure is similar in both solvents

Partners in the Parks: Field Guide to an Experiential Program in the National Parks (1st edition)

When Joan Digby first proposed taking collegiate honors students into our national parks, I jumped at the chance. Within minutes of reading her email, I not only responded with an enthusiastic “Yes!” but went so far as to volunteer the resources of the Southern Utah University Honors Program to get things started. Nestled among 5 national parks in southwestern Utah, I felt our campus would be a natural focal point for the kind of program Joan envisioned. Within weeks we had laid the groundwork for a proof-of-concept pilot project at nearby Bryce Canyon National Park. Little did I know at the time, but I was taking the first steps on a nationwide journey that would introduce me to 11 amazing national parks, some 47 park rangers, and over 100 outstanding college students—with the prospect of these numbers growing annually. The aim of Partners in the Parks (PITP) from its inception has been to introduce, or reintroduce, collegiate honors students to this country: not the transformed environment that we have constructed on its surface but the bedrock world upon which it rests. Like de Toqueville, Jefferson, Thoreau, Emerson, and so many others, we recognized that the unique place that is America cannot be separated from the land upon which it was built. One valuable way to study and understand it, then, is to visit places where the bones of America lie exposed, often without the veneer of civilization, cultivation, or modernization: places protected by the people to preserve for this and future generations, original American landscapes, and important historical landmarks that illustrate and define what America was, is, and can be. PITP takes students deep into America’s national parks. PITP is a see-America-first program. While we recognize the importance of a global perspective in an overall honors education, our goal is to help students see and understand America before or in addition to going abroad. Indeed, for students without the desire or resources to leave the country, PITP offers many of the same kinds of personal development that make study abroad so valuable. In the Field Notes to Chapter 2, “Growing from Within,” Bill Atwill and Kathleen King, share their experience in Acadia National Park, observing how their students demonstrated valuable growth in the same four key areas that researchers of study abroad programs have identified in their alumni: personal discovery, academic commitment, cultural development, and career development. The student writings in this volume, such as Andy Grube’s “soul expanding” talk with Juste Gatari on the rocky coast of Mount Desert Island, aptly illustrate this important facet of the PITP experience. (See the Field Notes to Chapter 5, “Sitting There in Silence.”

Prevention of diabetic nephropathy in Ins2+/−AkitaJ mice by the mitochondria-targeted therapy MitoQ

Mitochondrial production of ROS (reactive oxygen species) is thought to be associated with the cellular damage resulting from chronic exposure to high glucose in long-term diabetic patients. We hypothesized that a mitochondria-targeted antioxidant would prevent kidney damage in the Ins2+/−AkitaJ mouse model (Akita mice) of Type 1 diabetes. To test this we orally administered a mitochondria-targeted ubiquinone (MitoQ) over a 12-week period and assessed tubular and glomerular function. Fibrosis and pro-fibrotic signalling pathways were determined by immunohistochemical analysis, and mitochondria were isolated from the kidney for functional assessment. MitoQ treatment improved tubular and glomerular function in the Ins2+/−AkitaJ mice. MitoQ did not have a significant effect on plasma creatinine levels, but decreased urinary albumin levels to the same level as non-diabetic controls. Consistent with previous studies, renal mitochondrial function showed no significant change between any of the diabetic or wild-type groups. Importantly, interstitial fibrosis and glomerular damage were significantly reduced in the treated animals. The pro-fibrotic transcription factors phospho-Smad2/3 and β-catenin showed a nuclear accumulation in the Ins2+/−AkitaJ mice, which was prevented by MitoQ treatment. These results support the hypothesis that mitochondrially targeted therapies may be beneficial in the treatment of diabetic nephropathy. They also highlight a relatively unexplored aspect of mitochondrial ROS signalling in the control of fibrosis

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead