Timing of Sleep and Its Relationship with the Endogenous Melatonin Rhythm

While much research has investigated the effects of exogenous melatonin on sleep, less is known about the relationship between the timing of the endogenous melatonin rhythm and the sleep–wake cycle. Significant inter-individual variability in the phase relationship between sleep and melatonin rhythms has been reported although the extent to which the variability reflects intrinsic and/or environmental differences is unknown. We examined the effects of different sleeping schedules on the time of dim light melatonin onset (DLMO) in 28 young, healthy adults. Participants chose to maintain either an early (22:30–06:30 h) or a late (00:30–08:30 h) sleep schedule for at least 3 weeks prior to an overnight laboratory visit. Saliva samples were collected under dim light (<2 lux) and controlled posture conditions to determine salivary DLMO. The 2-h difference between groups in the enforced sleep–wake schedule was associated with a concomitant 1.75-h delay in DLMO. The mean phase relationship between sleep onset and DLMO remained constant (~2 h). The variance in DLMO time, however, was greater in the late group (range 4.5 h) compared to the early group (range 2.4 h) perhaps due to greater effect of environmental influences in delayed sleep types or greater intrinsic instability in their circadian system. The findings contribute to our understanding of individual differences in the human circadian clock and have important implications for the diagnosis and treatment of circadian rhythm sleep disorders, in particular if a greater normative range for phase angle of entrainment occurs in individuals with later sleep–wake schedules

Reduced adipose tissue oxygenation in human obesity evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response

OBJECTIVE-Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation. RESEARCH DESIGN AND METHODS-Oxygen partial pressure (AT pO 2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay. RESULTS-AT pO 2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO 2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO 2 was negatively correlated with percent body fat (R =-0.50, P \u3c 0.05). Compared with lean subjects, overweight/ obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator-activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO 2 (P \u3c 0.05). Of clinical importance, AT pO 2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R =-0.58, R =-0.79, P \u3c 0.05), suggesting that lower AT pO 2 could drive AT inflammation in obesity. CONCLUSIONS-Adipose tissue rarefaction might lie upstream of both low AT pO 2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity. © 2009 by the American Diabetes Association

Complement in reproductive white adipose tissue characterizes the obese preeclamptic-like BPH/5 mouse prior to and during pregnancy

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Preeclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by abnormal placental development with an unknown etiology. To better understand which women will develop PE, a number of maternal risk factors have been identified, including obesity. Visceral white adipose tissue (WAT) contains inflammatory mediators that may contribute to PE. To explore this, we utilized the blood pressure high (BPH)/5 mouse model of superimposed PE that spontaneously recapitulates the maternal PE syndrome. We hypothesized that BPH/5 visceralWAT adjacent to the female reproductive tract (reproductiveWAT) is a source of complement factors that contribute to the inflammatory milieu and angiogenic imbalance at the maternal-fetal interface in this model and in preeclamptic women. To test our hypothesis, we calorie-restricted BPH/5 females for two weeks prior to pregnancy and the first seven days of pregnancy, which attenuated complement component 3 (C3) but not complement factor B, nor complement factor D, (adipsin) in the reproductiveWAT or the implantation site in BPH/5. Furthermore, calorie restriction during pregnancy restored vascular endothelial and placental growth factor mRNA levels in the BPH/5 implantation site. These data show maternal reproductive WAT may be a source of increased C3 during pregnancy, which is increased at the maternal-fetal interface in preeclamptic BPH/5 mice. It also suggests that calorie restriction could regulate inflammatory mediators thought to contribute to placental dysfunction in PE. Future studies are necessary to examine the e_ect of calorie restriction on C3 throughout pregnancy and the role of maternal obesity in PE

2005 AAPP Monograph Series

The African American Professors Program (AAPP) at the University of South Carolina is proud to publish the fifth edition of its annual monograph series. The program recognizes the significance of offering its scholars avenue to engage actively in research and publish papers related thereto. Parallel with the publication of their refereed manuscripts is the opportunity to gain visibility among scholars throughout institutions worldwide. Scholars who have contributed manuscripts for this monograph are to be commended for adding this additional responsibility to their academic workload. Writing across disciplines adds to the intellectual diversity of these papers. From neophytes, relatively speaking, to an array of very experienced individuals, the chapters have been researched and comprehensively written. Founded in 1997 through the Department of Educational Leadership and Policies in the College of Education, AAPP was designed to address the underrepresentation of African American professors on college and university campuses. Its mission is to expand the pool of these professors in critical academic and research areas. Sponsored by the University of South Carolina, the W. K. Kellogg Foundation, and the South Carolina General Assembly, the program recruits doctoral students for disciplines in which African Americans currently are underrepresented among faculty in higher education. The continuation of this monograph series is seen as responding to a window of opportunity to be sensitive to an academic expectation of graduates as they pursue career placement and, at the same time, one that allows for the dissemination of AAPP products to a broader community. The importance of this monograph series has been voiced by one of our 2002 AAPP graduates, Dr. Shundele LaTjuan Dogan, a recent Administrative Fellow at Harvard University and now a Program Officer for the Southern Education Foundation, Atlanta, Georgia. Dr. Dogan wrote: One thing in particular that I want to thank you for is having the African American Professors Program scholars publish articles for the monograph. I have to admit that writing the articles seemed like extra work at the time. However, in my recent interview process, organizations have asked me for samples of my writing. Including an article from a published monograph helped to make my portfolio much more impressive. You were \u27right on target\u27 in having us do the monograph series. (MPP 2003 Monograph, p. xi) The African American Professors Program offers this 2005 publication as a contribution to its readership and hopes that you will be inspired by this select group of manuscripts. John McFadden, Ph.D. The Benjamin Elijah Mays Professor Director, African American Professors Program University of South Carolinahttps://scholarcommons.sc.edu/mcfadden_monographs/1007/thumbnail.jp

Genomic and transcriptomic variation defines the chromosome-scale assembly of Haemonchus contortus, a model gastrointestinal worm

International audienceHaemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Here, we report using PacBio long-read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome for the MHco3(ISE).N1 isolate. We show a remarkable pattern of conservation of chromosome content with Caenorhabditis elegans, but almost no conservation of gene order. Short and long-read transcriptome sequencing allowed us to define coordinated transcriptional regulation throughout the parasite’s life cycle and refine our understanding of cis- and trans-splicing. Finally, we provide a comprehensive picture of chromosome-wide genetic diversity both within a single isolate and globally. These data provide a high-quality comparison for understanding the evolution and genomics of Caenorhabditis and other nematodes and extend the experimental tractability of this model parasitic nematode in understanding helminth biology, drug discovery and vaccine development, as well as important adaptive traits such as drug resistance

ST2 and IL-33 in Pregnancy and Pre-Eclampsia

Normal pregnancy is associated with a mild systemic inflammatory response and an immune bias towards type 2 cytokine production, whereas pre-eclampsia is characterized by a more intense inflammatory response, associated with endothelial dysfunction and a type 1 cytokine dominance. Interleukin (IL)-33 is a newly described member of the IL-1 family, which binds its receptor ST2L to induce type 2 cytokines. A soluble variant of ST2 (sST2) acts as a decoy receptor to regulate the activity of IL-33. In this study circulating IL-33 and sST2 were measured in each trimester of normal pregnancy and in women with pre-eclampsia. While IL-33 did not change throughout normal pregnancy, or between non-pregnant, normal pregnant or pre-eclamptic women, sST2 was significantly altered. sST2 was increased in the third trimester of normal pregnancy (p<0.001) and was further increased in pre-eclampsia (p<0.001). This increase was seen prior to the onset of disease (p<0.01). Pre-eclampsia is a disease caused by placental derived factors, and we show that IL-33 and ST2 can be detected in lysates from both normal and pre-eclampsia placentas. ST2, but not IL-33, was identified on the syncytiotrophoblast layer, whereas IL-33 was expressed on perivascular tissue. In an in vitro placental perfusion model, sST2 was secreted by the placenta into the ‘maternal’ eluate, and placental explants treated with pro-inflammatory cytokines or subjected to hypoxia/reperfusion injury release more sST2, suggesting the origin of at least some of the increased amounts of circulating sST2 in pre-eclamptic women is the placenta. These results suggest that sST2 may play a significant role in pregnancies complicated by pre-eclampsia and increased sST2 could contribute to the type 1 bias seen in this disorder

Practice change in chronic conditions care: an appraisal of theories

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Management of chronic conditions can be complex and burdensome for patients and complex and costly for health systems. Outcomes could be improved and costs reduced if proven clinical interventions were better implemented, but the complexity of chronic care services appears to make clinical change particularly challenging. Explicit use of theories may improve the success of clinical change in this area of care provision. Whilst theories to support implementation of practice change are apparent in the broad healthcare arena, the most applicable theories for the complexities of practice change in chronic care have not yet been identified. Methods We developed criteria to review the usefulness of change implementation theories for informing chronic care management and applied them to an existing list of theories used more widely in healthcare. Results Criteria related to the following characteristics of chronic care: breadth of the field; multi-disciplinarity; micro, meso and macro program levels; need for field-specific research on implementation requirements; and need for measurement. Six theories met the criteria to the greatest extent: the Consolidate Framework for Implementation Research; Normalization Process Theory and its extension General Theory of Implementation; two versions of the Promoting Action on Research Implementation in Health Services framework and Sticky Knowledge. None fully met all criteria. Involvement of several care provision organizations and groups, involvement of patients and carers, and policy level change are not well covered by most theories. However, adaptation may be possible to include multiple groups including patients and carers, and separate theories may be needed on policy change. Ways of qualitatively assessing theory constructs are available but quantitative measures are currently partial and under development for all theories. Conclusions Theoretical bases are available to structure clinical change research in chronic condition care. Theories will however need to be adapted and supplemented to account for the particular features of care in this field, particularly in relation to involvement of multiple organizations and groups, including patients, and in relation to policy influence. Quantitative measurement of theory constructs may present difficulties

SNP Discovery and Chromosome Anchoring Provide the First Physically-Anchored Hexaploid Oat Map and Reveal Synteny with Model Species

A physically anchored consensus map is foundational to modern genomics research; however, construction of such a map in oat (Avena sativa L., 2n = 6x = 42) has been hindered by the size and complexity of the genome, the scarcity of robust molecular markers, and the lack of aneuploid stocks. Resources developed in this study include a modified SNP discovery method for complex genomes, a diverse set of oat SNP markers, and a novel chromosome-deficient SNP anchoring strategy. These resources were applied to build the first complete, physically-anchored consensus map of hexaploid oat. Approximately 11,000 high-confidence in silico SNPs were discovered based on nine million inter-varietal sequence reads of genomic and cDNA origin. GoldenGate genotyping of 3,072 SNP assays yielded 1,311 robust markers, of which 985 were mapped in 390 recombinant-inbred lines from six bi-parental mapping populations ranging in size from 49 to 97 progeny. The consensus map included 985 SNPs and 68 previously-published markers, resolving 21 linkage groups with a total map distance of 1,838.8 cM. Consensus linkage groups were assigned to 21 chromosomes using SNP deletion analysis of chromosome-deficient monosomic hybrid stocks. Alignments with sequenced genomes of rice and Brachypodium provide evidence for extensive conservation of genomic regions, and renewed encouragement for orthology-based genomic discovery in this important hexaploid species. These results also provide a framework for high-resolution genetic analysis in oat, and a model for marker development and map construction in other species with complex genomes and limited resources

Human total, basal and activity energy expenditures are independent of ambient environmental temperature

Acknowledgments The DLW database, which can be found at https://www.dlwdatabase.org, is hosted by the International Atomic Energy Agency (IAEA) and generously supported by Taiyo Nippon Sanso and SERCON . We are grateful to the IAEA and these companies for their support. XYZ was supported by the Chinese Academy of Sciences (grant CAS 153E11KYSB20190045 to J.R.S.), and the database was also supported by the US National Science Foundation (grant BCS-1824466 to H.P.). The funders played no role in the content of this manuscript.Peer reviewedPublisher PD