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Title:
Financing Diabetes Care in the U.S. Health System: Payment Innovations for Addressing the Medical and Social Determinants of Health
Authors:
Saulsberry, Loren; Peek, Monica
Abstract:
Review innovations in health care financing promoting health system investments in addressing medical and social determinants of health (SDH) for patients with diabetes.
Published:
November 20, 2019
Title:
Ketogenic diet activates protective γδ T cell responses against influenza virus infection
Authors:
Goldberg, Emily L.; Molony, Ryan D.; Kudo, Eriko; Sidorov, Sviatoslav; Kong, Yong; Dixit, Vishwa Deep; Iwasaki, Akiko
Abstract:
Influenza A virus (IAV) infection–associated morbidity and mortality are a key global health care concern, necessitating the identification of new therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing antiviral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet because neither feeding mice a high-fat, high-carbohydrate diet nor providing chemical ketone body substrate that bypasses hepatic ketogenesis protected against infection. Therefore, KD-mediated immune-metabolic integration represents a viable avenue toward preventing or alleviating influenza disease.
Published:
November 15, 2019
Title:
Chimpanzee fibroblasts exhibit greater adherence and migratory phenotypes than human fibroblasts
Authors:
Zintel, Trisha M.; Ducey, Delaney; Babbitt, Courtney C.
Abstract:
Background and objectives: Intercellular signaling facilitated by cell adhesion is vital for many biological processes, such as embryonic development as well as disease states (e.g. metastasis of cancerous cells) and consequently represents a potential mechanism by which functional differences among primates may have evolved. Methodology: Previous work has identified that gene expression differences in cell adhesion pathways exist between humans and chimpanzees. Here, we used a comparative cell biology approach to assay interspecies differences in cell adhesion phenotypes in order to better understand the basic biological differences between species epithelial cells that may underly the organism-level differences we see in wound healing and cancer. We used skin fibroblast cell lines from humans and chimpanzees (two individuals per species) to assay cell adhesion and migration. We then utilized published RNA-Seq data from the same cell lines exposed to a cancer / wound-healing mimic to determine what gene expression changes may be corresponding to altered cellular adhesion dynamics between species. Results: The functional adhesion and migration assays revealed that chimpanzee fibroblasts adhered sooner and remained adherent for significantly longer and move into a wound at faster rate than human fibroblasts. The gene expression data suggest that the enhanced adhesive properties of chimpanzee fibroblasts may be due to chimpanzee fibroblasts exhibiting significantly higher expression of cell and focal adhesion molecule genes than human cells, both during a wound healing assay and at rest. Conclusions and implications: Chimpanzee fibroblasts exhibit stronger adhesion and greater cell migration than human fibroblasts. This may be due to divergent gene expression of focal adhesion and cell adhesion molecules, such as integrins, laminins, and cadherins, as well as ECM proteins like collagens. This is one of few studies demonstrating that these divergences in gene expression between closely related species can manifest in fundamental differences in cell biology. Our results provide better insight into species-specific cell biology phenotypes and how they may influence more complex traits, such as cancer metastasis and wound healing.
Published:
November 13, 2019
Title:
Publications | Joanna Lambert
Authors:
Abstract:
Published:
November 7, 2019
Title:
Can the emerging field of immunometabolism provide insights into neuroinflammation?
Authors:
Lynch, Marina A.
Abstract:
In the past few years it has become increasingly clear that an understanding of the interaction between metabolism and immune function can provide an insight into cellular responses to challenges. Significant progress has been made in terms of how macrophages are metabolically re-programmed in response to inflammatory stimuli but, to date, little emphasis has been placed on evaluating equivalent changes in microglia. The need to make progress is driven by the fact that, while microglial activation and the cell’s ability to adopt an inflammatory phenotype is necessary to fulfil the neuroprotective function of the cell, persistent activation of microglia and the associated neuroinflammation is at the heart of several neurodegenerative diseases. Understanding the metabolic changes that accompany microglial responses may broaden our perspective on how dysfunction might arise and be tempered. This review will evaluate the current literature that addresses the interplay between inflammation and metabolic reprogramming in microglia, reflecting on the parallels that exist with macrophages. It will consider the changes that take place with age including those that have been reported in neurons and astrocytes with the development of non-invasive imaging techniques, and reflect on the literature that is currently available relating to metabolic reprogramming of microglia with age and in neurodegeneration. Finally it will consider the possibility that manipulating microglial metabolism may provide a valuable approach to modulating neuroinflammation.
Published:
November 6, 2019
Title:
Achieving Healthy and Sustainable Diets: A Review of the Results of Recent Mathematical Optimization Studies
Authors:
Wilson, Nick; Cleghorn, Christine L.; Cobiac, Linda J.; Mizdrak, Anja; Nghiem, Nhung
Abstract:
ABSTRACT. Climate protection and other environmental concerns render it critical that diets and agriculture systems become more sustainable. Mathematical optim
Published:
November 1, 2019
Title:
Dietary intake in cystic fibrosis and its role in glucose metabolism
Authors:
Armaghanian, Natasha; Atkinson, Fiona; Taylor, Nicole; Kench, Andrea; Brand-Miller, Jennie; Markovic, Tania; Steinbeck, Kate
Abstract:
Background: Dietary intervention in cystic fibrosis (CF) has historically focused on high-energy diets to address malnutrition, with little attention on diet quality. With increased survival, CF complications such as impaired glucose tolerance (IGT) and cystic fibrosis related diabetes (CFRD) have increased in prevalence. In the absence of consensus on the management of IGT, the role of dietary intake, specifically carbohydrate quality, requires consideration. Aims: The aims of this study were to: 1) determine nutritional quality of dietary intake at an adult CF clinic and compare this to the Australian Dietary Guidelines 2) explore relationships between dietary intake, including glycaemic index (GI) and glycaemic load (GL), and glucose response variables using continuous glucose monitoring (CGM). Methods: Adults attending a Sydney hospital were recruited to undergo CGM for five-seven days and record dietary intake using a food record over the CGM period. The relationship between variables of dietary intake, including GI and GL and variables of glycaemic response, including mean amplitude of glycaemic excursions (MAGE), percentage of time in hyperglycaemic and euglycaemic range, were determined. Results: Eighteen participants completed the study with 87 full days of dietary and CGM data. Dietary intake was higher than recommendations in the Australian Dietary Guidelines in relation to grains and protein foods and only slightly higher in saturated fat. Bivariate correlations showed dietary GI was significantly positively associated with percentage of time in hyperglycaemic range. Dietary GL was significantly associated with SD, MAGE and percentage of time in euglycaemic range on CGM. Results remained significant when controlled for energy intake in partial correlation analyses. Conclusions: This study suggests GI and GL may be important dietary factors influencing glucose metabolism in CF. Further studies exploring low GI or GL diets as a dietary intervention in CF are the next step.
Published:
November 1, 2019
Title:
Effect of Escalating Financial Incentive Rewards on Maintenance of Weight Loss: A Randomized Clinical Trial
Authors:
Yancy, William S.; Shaw, Pamela A.; Reale, Catherine; Hilbert, Victoria; Yan, Jiali; Zhu, Jingsan; Troxel, Andrea B.; Foster, Gary D.; Volpp, Kevin G.
Abstract:
Importance: Identifying effective strategies for treating obesity is a public health priority. Objective: To test an escalating lottery-based incentive tied to daily self-weighing for weight loss maintenance. Design, Setting, and Participants: This 2-phase, 2-arm randomized clinical trial enrolled participants aged 30 to 80 years with an initial body mass index (calculated as weight in kilograms divided by height in meters squared) of 30.0 to 45.0 who lost at least 5 kg during 4 to 6 months in a national online weight management program. Study investigators and outcomes assessors were blinded to participant groups. Data were collected and analyzed from May 23, 2016, through November 13, 2017, based on intention to treat. Interventions: All participants were advised to weigh themselves daily, with a goal of 6 or more days per week, and received text messaging feedback on their performance. Incentive group participants were eligible for a lottery-based incentive worth an expected value of $3.98 in week 1 that escalated by $0.43 each week they achieved their self-weighing goal during months 1 to 6 (phase 1), followed by no incentives during months 7 to 12 (phase 2). Main Outcomes and Measures: The primary outcome was weight change at the end of phase 1. Secondary outcomes included weight change at the end of phase 2 and changes in self-reported physical activity and eating behaviors. Results: A total of 258 participants (128 in the incentive group and 130 in the control group) had a mean (SD) age of 48.0 (10.5) years and mean (SD) body mass index of 32.1 (3.9); 225 (87.2%) were women; 235 (91.1%) were white; and 102 (39.5%) had an annual income of at least $100 000. Weight measurement was transmitted by 250 participants (96.9%) at 6 months and 227 (88.0%) at 12 months. The percentage of weeks that incentive and control participants achieved a mean self-weighing of at least 6 times was 85.3% vs 75.8%, respectively (P = .002) in phase 1 and 37.7% vs 50.2%, respectively (P = .009) in phase 2. Mean weight changes at the end of phase 1 were -1.1 (95% CI, -2.1 to -0.1) kg in the incentive group and -1.9 (95% CI, -2.9 to -0.8) kg in the control group, with a mean difference of 0.7 (95% CI, -0.7 to 2.2) kg (P = .30 for comparison). At the end of phase 2, mean weight changes were 0.2 (95% CI, -1.2 to 1.7) kg in the incentive group and -0.6 (95% CI, -2.0 to 0.8) kg in the control group, with a mean difference of 0.8 (95% CI, -1.2 to 2.8) kg (P = .41 for comparison). Conclusions and Relevance: Compared with an active control condition of weekly messages, escalating lottery-based incentives transiently increased rates of self-weighing but did not significantly enhance weight loss maintenance. Trial Registration: ClinicalTrials.gov identifier: NCT01900392.
Published:
November 1, 2019
Title:
Going beyond the potential equifinality problems: A response to Saladié and Rodríguez-Hidalgo (2019)
Authors:
Rosell Ardèvol, Jordi; Blasco, Ruth; Arilla, Maite; Fernández-Jalvo, Yolanda
Abstract:
Actualistic studies have been commonly used as valid analogies in taphonomic research and, as the growing body of data demonstrate, have proved to be highly informative to explain the formation of terrestrial vertebrate fossil faunas. In Rosell et al. (2019), we conducted an experimental study with free-ranging brown bears (Ursus arctos arctos) with the aim of modeling their behavior and characterizing the bone damage caused on large, medium and small sized ungulate carcasses. The purpose of the study was to highlight the equifinality processes observed experimentally based on the assumption that “some carnivores show physical and dental characteristics that could lead to bone modifications potentially like those generated by humans” (Rosell et al., 2019, p.67). In the case of bears, their “bunodont dentition and plantigrade locomotion –the latter allows them to frequently release and use their claws as ‘hands’”– have led to the production of peeling and tooth marks that show important similarities with those generated during the feeding activities of humans and chimpanzees (Pan troglodytes), although anecdotally also made by other taphonomic agents. Saladié and Rodríguez-Hidalgo (2019) interpret our study as an attempt to invalidate their inferences about human tooth marks from the TD6.2 level of Gran Dolina (Sierra de Atapuerca, Burgos, Spain), even though we do not make any archaeological application. We also clearly maintain that ours is an initial and merely descriptive study that aims to raise awareness of the existence of taphonomic equifinality phenomena between bears and humans. The present work intends, therefore, to respond to their criticisms about the contexts in which humans and bears produce peeling as well as about the methodology used for assessing the tooth mark measurements. We have tried to read positively the Saladié and Rodríguez-Hidalgo's (2019) paper in order to make progress in the main challenge of finding elements and features that allow us to discriminate bone alterations potentially attributable to more than one taphonomic agent.
Published:
November 1, 2019
Title:
Role of non-macrophage cell-derived HMGB1 in oxaliplatin-induced peripheral neuropathy and its prevention by the thrombin/thrombomodulin system in rodents: negative impact of anticoagulants
Authors:
Tsubota, Maho; Fukuda, Ryotaro; Hayashi, Yusuke; Miyazaki, Takaya; Ueda, Shin; Yamashita, Rika; Koike, Nene; Sekiguchi, Fumiko; Wake, Hidenori; Wakatsuki, Shuji; Ujiie, Yuka; Araki, Toshiyuki; Nishibori, Masahiro; Kawabata, Atsufumi
Abstract:
Macrophage-derived high mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) protein, plays a key role in the development of chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel in rodents. Endothelial thrombomodulin (TM) promotes thrombin-induced degradation of HMGB1, and TMα, a recombinant human soluble TM, abolishes peripheral HMGB1-induced allodynia in mice. We thus examined whether HMGB1, particularly derived from macrophages, contributes to oxaliplatin-induced neuropathy in mice and analyzed the anti-neuropathic activity of the TM/thrombin system.
Published:
October 30, 2019
Title:
TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection
Authors:
Marcken, Marine de; Dhaliwal, Khushwant; Danielsen, Ann Caroline; Gautron, Anne Sophie; Dominguez-Villar, Margarita
Abstract:
TLRing the antiviral response Monocytes are critical orchestrators of immunity that both sense pathogens and produce cytokines. When comparing a range of RNA viruses, de Marcken et al. found that the human monocyte response to infection was virus specific and influenced by Toll-like receptor 7 (TLR7) and TLR8, which sense single-stranded RNA. Whereas TLR8 signaling stimulated monocytes to express type I interferon and cytokines involved in CD4+ T helper 1 (TH1) cell differentiation, TLR7 signaling promoted production of cytokines involved in TH17 cell differentiation. Only TLR7 activated monocyte Ca2+ flux, which suppressed antiviral interferon production. Thus, these receptors activate distinct pathways in monocytes, which can tailor the immune response to viral infection. Human blood CD14+ monocytes are bone marrow–derived white blood cells that sense and respond to pathogens. Although innate immune activation by RNA viruses preferentially occurs through intracellular RIG-I–like receptors, other nucleic acid recognition receptors, such as Toll-like receptors (TLRs), play a role in finely programming the final outcome of virus infection. Here, we dissected how human monocytes respond to infection with either Coxsackie (CV), encephalomyocarditis (EMCV), influenza A (IAV), measles (MV), Sendai (SV), or vesicular stomatitis (VSV) virus. We found that in monocytes, type I interferon (IFN) and cytokine responses to infection were RNA virus specific and differentially involved TLR7 and TLR8, which sense single-stranded RNA. These TLRs activated distinct signaling cascades in monocytes, which correlated with differences in the production of cytokines involved in the polarization of CD4+ T helper cells. Furthermore, we found that TLR7 signaling specifically increased expression of the transcription factor FOSL1, which reduced IL-27 and TNFα production by monocytes. TLR7, but not TLR8, activation of monocytes also stimulated Ca2+ flux that prevented type I IFN responses. Our work demonstrates that in human monocytes, TLR7 and TLR8 triggered different signaling pathways that contribute to distinct phenotypes during RNA virus infection. In addition, we defined individual targets within these pathways that promoted specific T helper and antiviral responses. Differences in TLR7 and TLR8 signaling program virus-specific responses of human monocytes to infection. Differences in TLR7 and TLR8 signaling program virus-specific responses of human monocytes to infection.
Published:
October 29, 2019
Title:
Sediment Cores from White Pond, South Carolina, contain a Platinum Anomaly, Pyrogenic Carbon Peak, and Coprophilous Spore Decline at 12.8 ka
Authors:
Moore, Christopher R.; Brooks, Mark J.; Goodyear, Albert C.; Ferguson, Terry A.; Perrotti, Angelina G.; Mitra, Siddhartha; Listecki, Ashlyn M.; King, Bailey C.; Mallinson, David J.; Lane, Chad S.; Kapp, Joshua D.; West, Allen; Carlson, David L.; Wolbach, Wendy S.; Them, Theodore R.; Harris, M. Scott; Pyne-O’Donnell, Sean
Abstract:
A widespread platinum (Pt) anomaly was recently documented in Greenland ice and 11 North American sedimentary sequences at the onset of the Younger Dryas (YD) event (~12,800 cal yr BP), consistent with the YD Impact Hypothesis. We report high-resolution analyses of a 1-meter section of a lake core from White Pond, South Carolina, USA. After developing a Bayesian age-depth model that brackets the late Pleistocene through early Holocene, we analyzed and quantified the following: (1) Pt and palladium (Pd) abundance, (2) geochemistry of 58 elements, (3) coprophilous spores, (4) sedimentary organic matter (OC and sedaDNA), (5) stable isotopes of C (δ13C) and N (δ15N), (6) soot, (7) aciniform carbon, (8) cryptotephra, (9) mercury (Hg), and (10) magnetic susceptibility. We identified large Pt and Pt/Pd anomalies within a 2-cm section dated to the YD onset (12,785 ± 58 cal yr BP). These anomalies precede a decline in coprophilous spores and correlate with an abrupt peak in soot and C/OC ratios, indicative of large-scale regional biomass burning. We also observed a relatively large excursion in δ15N values, indicating rapid climatic and environmental/hydrological changes at the YD onset. Our results are consistent with the YD Impact Hypothesis and impact-related environmental and ecological changes.
Published:
October 22, 2019
Title:
#Bipolar disorder increases the risk of #ParkinsonDisease by over 300%. Mental or metabolic?https://ja.ma/32rFi13
Authors:
MD, Chris Palmer
Abstract:
Published:
October 20, 2019
Title:
Tumor-associated macrophages: an accomplice in solid tumor progression
Authors:
Chen, Yibing; Song, Yucen; Du, Wei; Gong, Longlong; Chang, Haocai; Zou, Zhengzhi
Abstract:
In many solid tumor types, tumor-associated macrophages (TAMs) are important components of the tumor microenvironment (TME). Moreover, TAMs infiltration is strongly associated with poor survival in solid tumor patients. In this review, we describe the origins of TAMs and their polarization state dictated by the TME. We also specifically focus on the role of TAMs in promoting tumor growth, enhancing cancer cells resistance to chemotherapy and radiotherapy, promoting tumor angiogenesis, inducing tumor migration and invasion and metastasis, activating immunosuppression. In addition, we discuss TAMs can be used as therapeutic targets of solid tumor in clinics. The therapeutic strategies include clearing macrophages and inhibiting the activation of TAMs, promoting macrophage phagocytic activity, limiting monocyte recruitment and other targeted TAMs therapies.
Published:
October 20, 2019
Title:
Clinical/Translational Aspects of Advanced Glycation End-Products
Authors:
Zeng, Chang; Li, Yuanyuan; Ma, Jingzhi; Niu, Lina; Tay, Franklin R.
Abstract:
Advanced glycation end-products (AGEs) have been implicated in chronic hyperglycemia and age-related diseases. Endogenous AGEs produced by humans generate oxidative stress and activation of inflammatory signaling pathways via AGE-specific receptors. The present review summarizes current knowledge on the pathogenic role of AGEs in chronic noncommunicable diseases. Although correlations exist between glycation and the pathogenesis of these diseases, uncertainties remain in light of recurrent intervention failures of apparently promising animal models to be translated into clinically useful anti-AGE strategies. Future intervention of AGEs or their receptors should embrace more carefully executed clinical trials. Nevertheless, suppressing symptoms via lifetime drug application is unlikely to eliminate the burden of chronic diseases unless deep-rooted lifestyle issues that cause these diseases are simultaneously addressed.
Published:
October 6, 2019
Title:
Combined dental wear and cementum analyses in ungulates reveal the seasonality of Neanderthal occupations in Covalejos Cave (Northern Iberia)
Authors:
Sánchez-Hernández, Carlos; Gourichon, Lionel; Pubert, Eric; Rendu, William; Montes-Barquín, Ramón; Rivals, Florent
Abstract:
We propose for the first time the use of the combination of two high-resolution techniques, dental wear (meso- and microwear) and dental cementum analyses, to gain a better understanding of Neanderthal subsistence strategies and occupational patterns. Dental wear analysis provides information not only on ungulate palaeodiet and palaeoenvironments but also on hunting time and seasons. Dental cementum analysis allows the accurate determination of the age and season at death of a prey. Our study has focused on the Cantabrian region and has applied both methods to investigate the Mousterian faunal assemblages in Covalejos Cave. Identification of the ungulate palaeodiet reveals information on the environmental conditions of the studied region. Moreover, it may facilitate observation on the evolution of both palaeodiet and palaeoenvironment throughout the site sequence. Results show a general stability in the palaeoenvironmental conditions and in the ungulate palaeodiet throughout the Mousterian sequence; this finding may be attributed to the role of the area as a climate refuge, and slight differences in levels 8, 7 and 4 suggest long- or short-term but repeated Neanderthal occupations at different seasons in the annual cycle.
Published:
October 4, 2019
Title:
Detection and quantification of nitric oxide–derived oxidants in biological systems
Authors:
Möller, Matías N.; Rios, Natalia; Trujillo, Madia; Radi, Rafael; Denicola, Ana; Alvarez, Beatriz
Abstract:
The free radical nitric oxide (NO•) exerts biological effects through the direct and reversible interaction with specific targets (e.g. soluble guanylate cyclase) or through the generation of secondary species, many of which can oxidize, nitrosate or nitrate biomolecules. The NO•-derived reactive species are typically short-lived, and their preferential fates depend on kinetic and compartmentalization aspects. Their detection and quantification are technically challenging. In general, the strategies employed are based either on the detection of relatively stable end products or on the use of synthetic probes, and they are not always selective for a particular species. In this study, we describe the biologically relevant characteristics of the reactive species formed downstream from NO•, and we discuss the approaches currently available for the analysis of NO•, nitrogen dioxide (NO2•), dinitrogen trioxide (N2O3), nitroxyl (HNO), and peroxynitrite (ONOO−/ONOOH), as well as peroxynitrite-derived hydroxyl (HO•) and carbonate anion (CO3•−) radicals. We also discuss the biological origins of and analytical tools for detecting nitrite (NO2−), nitrate (NO3−), nitrosyl–metal complexes, S-nitrosothiols, and 3-nitrotyrosine. Moreover, we highlight state–of–the–art methods, alert readers to caveats of widely used techniques, and encourage retirement of approaches that have been supplanted by more reliable and selective tools for detecting and measuring NO•-derived oxidants. We emphasize that the use of appropriate analytical methods needs to be strongly grounded in a chemical and biochemical understanding of the species and mechanistic pathways involved.
Published:
October 4, 2019
Title:
A flexible high content imaging assay for profiling macrophage efferocytosis
Authors:
Clark, Roger; Usselmann, Laura; Brown, Martin R.; Goeppert, Anne U.; Corrigan, Adam
Abstract:
Macrophages are a diverse population of cells originating from the myeloid lineage, which form an important component of the innate immune system, helping to regulate immune response through secretion of pro/anti-inflammatory cytokines. However they also have an important homeostatic role – helping to remove cellular debris and apoptotic cells from the body (a phagocytic process known as efferocytosis). Here we describe a robust 384 well microplate based imaging assay, using apoptotic target cells for the specific quantification of efferocytosis in human primary monocyte derived macrophages. The methodology described allows for the assay to run in either fixed end-point or live-cell format (the former offering multiple morphological and intensity-based readouts, whilst the latter opens the possibility for future expansion of the methodology to encompass kinetic profiling). Within the methodology described we couple high content image acquisition (on the Cell Voyager 7000S) with multi-parametric image analysis - using Perkin Elmer Columbus combined with GeneData Screener.
Published:
October 1, 2019
Title:
Bone marrow storage and delayed consumption at Middle Pleistocene Qesem Cave, Israel (420 to 200 ka)
Authors:
Blasco, R.; Rosell, J.; Arilla, M.; Margalida, A.; Villalba, D.; Gopher, A.; Barkai, R.
Abstract:
Bone marrow and grease constitute an important source of nutrition and have attracted the attention of human groups since prehistoric times. Marrow consumption has been linked to immediate consumption following the procurement and removal of soft tissues. Here, we present the earliest evidence for storage and delayed consumption of bone marrow at Qesem Cave, Israel (~420 to 200 ka). By using experimental series controlling exposure time and environmental parameters, combined with chemical analyses, we evaluated bone marrow preservation. The combination of archaeological and experimental results allowed us to isolate specific marks linked to dry skin removal and determine a low rate of marrow fat degradation of up to 9 weeks of exposure. This is the earliest evidence of such previously unidentified behavior, and it offers insights into the socio-economy of the human groups who lived at Qesem and may mark a threshold to new modes of Palaeolithic human adaptation. Paleolithic cave dwellers in Israel consumed “canned food” some 400,000 years ago, demonstrating advanced planning skills. Paleolithic cave dwellers in Israel consumed “canned food” some 400,000 years ago, demonstrating advanced planning skills.
Published:
October 1, 2019
Title:
Development of human limb muscles based on whole-mount immunostaining and the links between ontogeny and evolution
Authors:
Diogo, Rui; Siomava, Natalia; Gitton, Yorick
Abstract:
We provide the first detailed ontogenetic analysis of human limb muscles using whole-mount immunostaining. We compare our observations with the few earlier studies that have focused on the development of these muscles, and with data available on limb evolution, variations and pathologies. Our study confirms the transient presence of several atavistic muscles-present in our ancestors but normally absent from the adult human-during normal embryonic human development, and reveals the existence of others not previously described in human embryos. These atavistic muscles are found both as rare variations in the adult population and as anomalies in human congenital malformations, reinforcing the idea that such variations/anomalies can be related to delayed or arrested development. We further show that there is a striking difference in the developmental order of muscle appearance in the upper versus lower limbs, reinforcing the idea that the similarity between various distal upper versus lower limb muscles of tetrapod adults may be derived.
Published:
October 1, 2019
Title:
Mammoth hunting strategies during the Late Gravettian in Central Europe as determined from case studies of Milovice I (Czech Republic) and Krak ow Spadzista (Poland)
Authors:
Wilczyński, Jarosław; Wojtal, Piotr; Oliva, Martin; Sobczyk, Krzysztof; Haynes, Gary; Klimowicz, Janis; Lengyel, György
Abstract:
Download here: https://authors.elsevier.com/c/1ZpsA-4PRtyV6 ************************************************************************* This paper compares lithic and faunal assemblages from Milovice (Czech Republic) and Krak ow Spadzista (Poland) archaeological sites, with the aim of reconstructing temporal variations and patterning in Gravettian hunting of Mammuthus primigenius (woolly mammoth) in Central Europe. Milovice I was occupied ~1 ky earlier than Krak ow Spadzista, and is contemporaneous with Willendorf-Kostienkan sites. It is dated between 30.1 and 29.2 ka cal BP, overlapping the end of the GS 5.1 stadial in the Greenland ice core paleoclimatic record; the site was formed during cold climatic conditions. Radio-carbon dates from Krak ow Spadzista indicate the site was occupied between 28.6 and 27 ka cal BP, spanning periods of significant climate instability through the GI 4 interstadial, GS 4 stadial, and the short interstadial GI 3. The two sites have fundamental differences in armature tool kits, such as raw materials and tool sizes. The hunter-gatherers at both sites had a mammoth-hunting focus, although they used different sized lithic weapon tips for hunting and thus probably had different strategies for procuring prey. The mammoth mortality profiles are significantly different at the two sites. At Milovice I, mid-life adults dominate the profile, while juveniles greatly dominate at Krak ow Spadzista. We suggest that climatically mediated differences in mammoth migratory behavior, feeding behavior, population sizes, and demography influenced Gravettian people to manufacture and use different sizes of projectile points and to significantly increase the number of tool types during the most climatically unstable periods ; these changes reflected tactical changes in Late Gravettian subsistence hunting in East-Central Europe.
Published:
October 1, 2019
Title:
Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Cohort Studies
Authors:
Zeraatkar, Dena; Han, Mi Ah; Guyatt, Gordon H.; Vernooij, Robin W.M.; El Dib, Regina; Cheung, Kevin; Milio, Kirolos; Zworth, Max; Bartoszko, Jessica J.; Valli, Claudia; Rabassa, Montserrat; Lee, Yung; Zajac, Joanna; Prokop-Dorner, Anna; Lo, Calvin; Bala, Malgorzata M.; Alonso-Coello, Pablo; Hanna, Steven E.; Johnston, Bradley C.
Abstract:
Published:
October 1, 2019
Title:
Role of LpL (Lipoprotein Lipase) in Macrophage Polarization In Vitro and In Vivo
Authors:
Chang Hye Rim; Josefs Tatjana; Scerbo Diego; Gumaste Namrata; Hu Yunying; Huggins Lesley-Ann; Barett Tessa J.; Chiang Stephanie S.; Grossman Jennifer; Bagdasarov Svetlana; Fisher Edward A.; Goldberg Ira J.
Abstract:
Objective:Fatty acid uptake and oxidation characterize the metabolism of alternatively activated macrophage polarization in vitro, but the in vivo biology is less clear. We assessed the roles of LpL (lipoprotein lipase)-mediated lipid uptake in macrophage polarization in vitro and in several important tissues in vivo.Approach and Results:We created mice with both global and myeloid-cell specific LpL deficiency. LpL deficiency in the presence of VLDL (very low-density lipoproteins) altered gene expression of bone marrow–derived macrophages and led to reduced lipid uptake but an increase in some anti- and some proinflammatory markers. However, LpL deficiency did not alter lipid accumulation or gene expression in circulating monocytes nor did it change the ratio of Ly6Chigh/Ly6Clow. In adipose tissue, less macrophage lipid accumulation was found with global but not myeloid-specific LpL deficiency. Neither deletion affected the expression of inflammatory genes. Global LpL deficiency also reduced the numbers of elicited peritoneal macrophages. Finally, we assessed gene expression in macrophages from atherosclerotic lesions during regression; LpL deficiency did not affect the polarity of plaque macrophages.Conclusions:The phenotypic changes observed in macrophages upon deletion of Lpl in vitro is not mimicked in tissue macrophages.
Published:
October 1, 2019
Title:
Tubular GM-CSF Promotes Late MCP-1/CCR2-Mediated Fibrosis and Inflammation after Ischemia/Reperfusion Injury
Authors:
Xu, Leyuan; Sharkey, Diana; Cantley, Lloyd G.
Abstract:
Visual Abstract 
Download figureOpen in new tabDownload powerpoint Background After bilateral kidney ischemia/reperfusion injury (IRI), monocytes infiltrate the kidney and differentiate into proinflammatory macrophages in response to the initial kidney damage, and then transition to a form that promotes kidney repair. In the setting of unilateral IRI (U-IRI), however, we have previously shown that macrophages persist beyond the time of repair and may promote fibrosis. Methods Macrophage homing/survival signals were determined at 14 days after injury in mice subjected to U-IRI and in vitro using coculture of macrophages and tubular cells. Mice genetically engineered to lack Ccr2 and wild-type mice were treated ±CCR2 antagonist RS102895 and subjected to U-IRI to quantify macrophage accumulation, kidney fibrosis, and inflammation 14 and 30 days after the injury. Results Failure to resolve tubular injury after U-IRI results in sustained expression of granulocyte-macrophage colony-stimulating factor by renal tubular cells, which directly stimulates expression of monocyte chemoattractant protein-1 (Mcp-1) by macrophages. Analysis of CD45+ immune cells isolated from wild-type kidneys 14 days after U-IRI reveals high-level expression of the MCP-1 receptor Ccr2. In mice lacking Ccr2 and wild-type mice treated with RS102895, the numbers of macrophages, dendritic cells, and T cell decreased following U-IRI, as did the expression of profibrotic growth factors and proimflammatory cytokines. This results in a reduction in extracellular matrix and kidney injury markers. Conclusions GM-CSF–induced MCP-1/CCR2 signaling plays an important role in the cross-talk between injured tubular cells and infiltrating immune cells and myofibroblasts, and promotes sustained inflammation and tubular injury with progressive interstitial fibrosis in the late stages of U-IRI.
Download figureOpen in new tabDownload powerpoint Background After bilateral kidney ischemia/reperfusion injury (IRI), monocytes infiltrate the kidney and differentiate into proinflammatory macrophages in response to the initial kidney damage, and then transition to a form that promotes kidney repair. In the setting of unilateral IRI (U-IRI), however, we have previously shown that macrophages persist beyond the time of repair and may promote fibrosis. Methods Macrophage homing/survival signals were determined at 14 days after injury in mice subjected to U-IRI and in vitro using coculture of macrophages and tubular cells. Mice genetically engineered to lack Ccr2 and wild-type mice were treated ±CCR2 antagonist RS102895 and subjected to U-IRI to quantify macrophage accumulation, kidney fibrosis, and inflammation 14 and 30 days after the injury. Results Failure to resolve tubular injury after U-IRI results in sustained expression of granulocyte-macrophage colony-stimulating factor by renal tubular cells, which directly stimulates expression of monocyte chemoattractant protein-1 (Mcp-1) by macrophages. Analysis of CD45+ immune cells isolated from wild-type kidneys 14 days after U-IRI reveals high-level expression of the MCP-1 receptor Ccr2. In mice lacking Ccr2 and wild-type mice treated with RS102895, the numbers of macrophages, dendritic cells, and T cell decreased following U-IRI, as did the expression of profibrotic growth factors and proimflammatory cytokines. This results in a reduction in extracellular matrix and kidney injury markers. Conclusions GM-CSF–induced MCP-1/CCR2 signaling plays an important role in the cross-talk between injured tubular cells and infiltrating immune cells and myofibroblasts, and promotes sustained inflammation and tubular injury with progressive interstitial fibrosis in the late stages of U-IRI.Published:
October 1, 2019
Title:
Human enhancement: Genetic Engineering and Evolution
Authors:
Almeida, Mara; Diogo, Rui
Abstract:
Genetic engineering opens new possibilities for biomedical enhancement requiring ethical, societal and practical considerations to evaluate its implications for human biology, human evolution, and our natural environment. In this Commentary, we consider human enhancement, and in particular, we explore genetic enhancement in an evolutionary context. In summarizing key open questions, we highlight the importance of acknowledging multiple effects (pleiotropy) and complex epigenetic interactions between genotype, phenotype, and ecology, and the need to consider the unit of impact not only to the human body but also to human populations and their natural environment (systems biology). We also propose that a practicable distinction between 'therapy' and 'enhancement' may need to be drawn and effectively implemented in future regulations. Overall, we suggest that it is essential for ethical, philosophical and policy discussions on human enhancement to consider the empirical evidence provided by evolutionary biology, developmental biology, and other disciplines. Lay Summary This Commentary explores genetic enhancement in an evolutionary context. We highlight the multiple effects associated with germline heritable genetic intervention, the need to consider the unit of impact to human populations and their natural environment, and propose that a practicable distinction between 'therapy' and 'enhancement' is needed.
Published:
September 29, 2019
Title:
Human enhancement: Genetic engineering and evolution
Authors:
Almeida, Mara; Diogo, Rui
Abstract:
Genetic engineering opens new possibilities for biomedical enhancement requiring ethical, societal and practical considerations to evaluate its implications for human biology, human evolution and our natural environment. In this Commentary, we consider human enhancement, and in particular, we explore genetic enhancement in an evolutionary context. In summarizing key open questions, we highlight the importance of acknowledging multiple effects (pleiotropy) and complex epigenetic interactions among genotype, phenotype and ecology, and the need to consider the unit of impact not only to the human body but also to human populations and their natural environment (systems biology). We also propose that a practicable distinction between 'therapy' and 'enhancement' may need to be drawn and effectively implemented in future regulations. Overall, we suggest that it is essential for ethical, philosophical and policy discussions on human enhancement to consider the empirical evidence provided by evolutionary biology, developmental biology and other disciplines. Lay Summary: This Commentary explores genetic enhancement in an evolutionary context. We highlight the multiple effects associated with germline heritable genetic intervention, the need to consider the unit of impact to human populations and their natural environment, and propose that a practicable distinction between 'therapy' and 'enhancement' is needed.
Published:
September 28, 2019
Title:
Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double‐blind, placebo‐controlled, multicenter trial: The MASTERS trial
Authors:
Walton, R. Grace; Dungan, Cory M.; Long, Douglas E.; Tuggle, S. Craig; Kosmac, Kate; Peck, Bailey D.; Bush, Heather M.; Villasante Tezanos, Alejandro G.; McGwin, Gerald; Windham, Samuel T.; Ovalle, Fernando; Bamman, Marcas M.; Kern, Philip A.; Peterson, Charlotte A.
Abstract:
Published:
September 26, 2019
Title:
HMGB1–C1q complexes regulate macrophage function by switching between leukotriene and specialized proresolving mediator biosynthesis
Authors:
Liu, Tianye; Xiang, Alec; Peng, Travis; Doran, Amanda C.; Tracey, Kevin J.; Barnes, Betsy J.; Tabas, Ira; Son, Myoungsun; Diamond, Betty
Abstract:
Macrophage polarization is critical to inflammation and resolution of inflammation. We previously showed that high-mobility group box 1 (HMGB1) can engage receptor for advanced glycation end product (RAGE) to direct monocytes to a proinflammatory phenotype characterized by production of type 1 IFN and proinflammatory cytokines. In contrast, HMGB1 plus C1q form a tetramolecular complex cross-linking RAGE and LAIR-1 and directing monocytes to an antiinflammatory phenotype. Lipid mediators, as well as cytokines, help establish a milieu favoring either inflammation or resolution of inflammation. This study focuses on the induction of lipid mediators by HMGB1 and HMGB1 plus C1q and their regulation of IRF5, a transcription factor critical for the induction and maintenance of proinflammatory macrophages. Here, we show that HMGB1 induces leukotriene production through a RAGE-dependent pathway, while HMGB1 plus C1q induces specialized proresolving lipid mediators lipoxin A4, resolvin D1, and resolvin D2 through a RAGE- and LAIR-1–dependent pathway. Leukotriene exposure contributes to induction of IRF5 in a positive-feedback loop. In contrast, resolvins (at 20 nM) block IRF5 induction and prevent the differentiation of inflammatory macrophages. Finally, we have generated a molecular mimic of HMGB1 plus C1q, which cross-links RAGE and LAIR-1 and polarizes monocytes to an antiinflammatory phenotype. These findings may provide a mechanism to control nonresolving inflammation in many pathologic conditions.
Published:
September 25, 2019
Title:
Colonic Microbiota and Metabolites Response to Different Dietary Protein Sources in a Piglet Model
Authors:
Li, Rui; Chang, Ling; Hou, Gaifeng; Song, Zehe; Fan, Zhiyong; He, Xi; Hou, De-Xing
Abstract:
Dietary protein sources have the potential to affect the colon microbiome of piglets that will subsequently have a large impact on metabolic capabilities and hindgut health. This study explored the effects of different protein sources on the growth performance, diarrhea rate, apparent ileal digestibility (AID) of crude protein (CP), colonic mucin chemotypes, colonic microbiome, and microbial metabolites of piglets. Twenty-four piglets were randomly divided into four groups that received isoenergetic and isonitrogenous diets containing either Palbio 50 RD (P50), Soyppt-50% (S50), concentrated degossypolized cottonseed protein (CDCP), or fish meal (FM) as the sole protein source. The experimental diets did not affect the estimated daily gain (EDG), but P50 increased fecal score compared with S50 and CDCP. CDCP increased, but P50 reduced AID of CP in comparison to FM and S50. S50 and CDCP increased the amount of mixed neutral-acidic mucins relative to P50. Venn analysis identified unique OTUs in the P50 (13), CDCP (74), FM (39), and S50 (31) groups. The protein sources did not change the colonic bacterial richness or diversity. High Escherichia abundance in the P50 and FM, great abundant of Lactobacillus in the CDCP, and high Gemmiger abundance in the S50 were found. The CDCP tended to elevate valeric acid and branched chain fatty acid (BCFA) concentrations compared with the other diets. The P50 and FM groups had greater ammonia nitrogen and methylamine contents than the S50 and CDCP groups. There was a positive correlation between the Escherichia and ammonia nitrogen, the Lactobacillus and short chain fatty acid (SCFA), and a negative correlation between the Gemmige and BCFA. These findings suggested short-term feeding of different protein sources did not affect the piglets' growth, but P50 increased the diarrhea rate. Potential pathogenic bacteria and detrimental metabolites appeared in the colons of piglets fed P50 and FM, whereas, beneficial effects were conferred upon piglets fed CDCP and S50, thus indicating that available plant proteins (cotton seed, soy) added to the diets of piglets enhanced colon health by reducing protein fermentation.
Published:
September 24, 2019
Title:
Feathers and food: Human-bird interactions at Middle Pleistocene Qesem Cave, Israel
Authors:
Blasco, Ruth; Rosell Ardèvol, Jordi; Anchez-Marco, Antonio; Gopher, Avi; Barkai, Ran
Abstract:
The presence of fast-moving small game in the Paleolithic archaeological faunal record has long been considered a key variable to assess fundamental aspects of human behavior and subsistence. Birds occupy a prominent place in this debate not only due to their small size and to the difficulties in capturing them (essentially due to their ability to fly and their elusiveness), but also due to their possible role in the symbolic array in regard to non-nutritional elements (feathers, talons, etc.) and as reflectors of complex humaneworld relationships. In this study, we attempt to contribute to this topic by presenting taphonomical data of bird specimens from Qesem Cave (Israel), dated between 420 and 200 ka. Human-induced damage, including cut marks, peeling and human gnawing, has been identified on wing bones of Cygnus sp., Columba sp., Corvus ruficollis and Sturnus sp. Our evidence suggests that avian exploitation was not limited to food onlydeither to complement the human diet or as occasional food itemdbut also presumably for the use of feathers. While the consumption of birds as a dietary source seems to be evident as early as the Early Pleistocene, the non-alimentary use of inedible elements, such as feathers and talons, appears to be a practice from the Middle Paleolithic onwards. We argue that the combined nutritional and symbolic use of birds is one characteristic of the new mode of adaptation practiced already by the late Lower Paleolithic Acheulo-Yabrudian hominins in the Levant starting 400 ka. The Qesem findings point to the possible emergence of new cognitive and behavioral skills, which are followed in later periods in the Old World. Finally, we discuss the possible ontological and cosmological significance of humanebird interactions to illuminate our hypothesis regarding the emergence of a new perception of human relationships with the world as an integral part of the new Acheulo-Yabrudian mode of adaptation.
Published:
September 20, 2019
Title:
Targeting receptors of advanced glycation end products (RAGE): Preventing diabetes induced cancer and diabetic complications
Authors:
Chhipa, Abu Sufiyan; Borse, Swapnil P.; Baksi, Ruma; Lalotra, Sunali; Nivsarkar, Manish
Abstract:
Cancer and diabetes are the two major disorders that affect a large proportion of the world’s population. Results from multiple epidemiological studies have concluded that diabetes and cancer are linked, and diabetic patients live at much higher risks of developing cancer and diabetic complications at the later phase of disease. Inflammation is the central pathway that mediates both diabetic complications as well as cancer. Receptor of advanced glycation end products (RAGE) is a non-specific multi-ligand pattern recognition receptor that induces the inflammatory responses by binding with multiple ligands. RAGE and its ligands are upregulated in diabetes, inflammation and cancer. Advanced glycation end products (AGEs), high mobility group box protein-1 (HMGB1) and S100 proteins are the major RAGE ligands that contribute to these consequences and an increased release of RAGE ligands during diabetic conditions can be a possible mechanism leading to diabetic complications and cancer. Moreover, further release of RAGE ligands from cancer cells can be a possible mechanism behind the worsening of diabetic complications in diabetic cancer patients. Inhibition of RAGE signaling can prevent diabetic complications and cancer in diabetic patients and can be helpful in the management of worsening diabetic complications and cancer in diabetic cancer patients. Curcumin, Quercetin and Withaferin A are known to inhibit multiple molecular pathways that are involved in RAGE signaling. The combined effects of these molecules can be explored to achieve the complete inhibition of RAGE signaling in diabetic patients.
Published:
September 19, 2019
Title:
Simple propagation method for resident macrophages by co-culture and subculture, and their isolation from various organs
Authors:
Ogawa, Kazushige; Tsurutani, Mayu; Hashimoto, Aya; Soeda, Miharu
Abstract:
Resident macrophages (Mø) originating from yolk sac Mø and/or foetal monocytes colonise tissues/organs during embryonic development. They persist into adulthood by self-renewal at a steady state, independent of adult monocyte inputs, except for those in the intestines and dermis. Thus, many resident Mø can be propagated in vitro under optimal conditions; however, there are no specific in vitro culture methods available for the propagation of resident Mø from diverse tissues/organs.
Published:
September 18, 2019
Title:
Tumor-derived TGF-β inhibits mitochondrial respiration to suppress IFN-γ production by human CD4+ T cells
Authors:
Dimeloe, Sarah; Gubser, Patrick; Loeliger, Jordan; Frick, Corina; Develioglu, Leyla; Fischer, Marco; Marquardsen, Florian; Bantug, Glenn R.; Thommen, Daniela; Lecoultre, Yannic; Zippelius, Alfred; Langenkamp, Anja; Hess, Christoph
Abstract:
Suppressing antitumor immunity The cytokine TGF-β has both immune-suppressive and tumor-suppressive functions; thus, a better understanding of the cell-type specificity of the effects of TGF-β might improve therapeutic strategies that target it. Dimeloe et al. found that TGF-β from tumor effusions suppressed the antitumor activity of CD4+ T cells by inhibiting their production of the inflammatory cytokine IFN-γ. The effects of TGF-β were mediated by Smad proteins in the mitochondria, rather than in the nucleus, and led to decreased mitochondrial respiration. Indeed, direct inhibition of a mitochondrial electron transport chain complex in CD4+ T cells was sufficient to inhibit IFN-γ production. Thus, these data suggest that TGF-β targets T cell metabolism to suppress antitumor immunity. Transforming growth factor–β (TGF-β) is produced by tumors, and increased amounts of this cytokine in the tumor microenvironment and serum are associated with poor patient survival. TGF-β–mediated suppression of antitumor T cell responses contributes to tumor growth and survival. However, TGF-β also has tumor-suppressive activity; thus, dissecting cell type–specific molecular effects may inform therapeutic strategies targeting this cytokine. Here, using human peripheral and tumor-associated lymphocytes, we investigated how tumor-derived TGF-β suppresses a key antitumor function of CD4+ T cells, interferon-γ (IFN-γ) production. Suppression required the expression and phosphorylation of Smad proteins in the TGF-β signaling pathway, but not their nuclear translocation, and depended on oxygen availability, suggesting a metabolic basis for these effects. Smad proteins were detected in the mitochondria of CD4+ T cells, where they were phosphorylated upon treatment with TGF-β. Phosphorylated Smad proteins were also detected in the mitochondria of isolated tumor-associated lymphocytes. TGF-β substantially impaired the ATP-coupled respiration of CD4+ T cells and specifically inhibited mitochondrial complex V (ATP synthase) activity. Last, inhibition of ATP synthase alone was sufficient to impair IFN-γ production by CD4+ T cells. These results, which have implications for human antitumor immunity, suggest that TGF-β targets T cell metabolism directly, thus diminishing T cell function through metabolic paralysis. The mitochondrial activity and antitumor function of human helper T cells are suppressed by a tumor-derived cytokine. The mitochondrial activity and antitumor function of human helper T cells are suppressed by a tumor-derived cytokine.
Published:
September 17, 2019
Title:
Unraveling the association of fecal microbiota and oxidative stress with stillbirth rate of sows
Authors:
Wang, Hao; Hu, Chengjun; Cheng, Chuanhui; Cui, Jiajie; Ji, Yongcheng; Hao, Xiangyu; Li, Qiqi; Ren, Wenkai; Deng, Baichuan; Yin, Yulong; Deng, Jinping; Tan, Chengquan
Abstract:
Previous studies have shown that the composition and function of gut microbiota possibly contribute to the oxidative stress and host metabolism of sows. However, a functional link between gut bacteria with oxidative stress and stillbirth rate of sows remain unclear. To address this issue, the reproductive performance, oxidative stress and gut microbiota of sows with high (H) and low (L) stillbirth rate were analyzed. Results showed that, compared with the H group, the L group had a shorter farrowing duration as well as higher concentration of serum total antioxidant capacity and hydroxyl radical scavenging capacity. For the gut microbiota composition of the tested sows, 6 genera differed between the two groups, 7 genera were correlative with stillbirth rate, and 2 genera were correlated with farrowing duration. The relative abundance of Lachnospiraceae_UCG-001, Marvinbryantia and Ruminococcaceae_UCG-004 were negatively correlated with antioxidant capacity, but positively correlated with the stillbirth rate of sows. Furthermore, the microbiota functions in the polyketide sugar unit biosynthesis and nitrotoluene degradation were found to be different between the two groups through the phylotypic investigation of communities by reconstruction of unobserved states. Collectively, gut microbiota and their functions vary between sows with high or low stillbirth rate, while stillbirth rate and farrowing duration are significantly correlated with the gut microbiota composition and oxidative stress status of sows.
Published:
September 15, 2019
Title:
Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and WNT-pathway-related markers of bowel cancer risk
Authors:
Malcomson, Fiona C.; Willis, Naomi D.; McCallum, Iain; Xie, Long; Kelly, Seamus; Bradburn, David Michael; Belshaw, Nigel J.; Johnson, Ian T.; Mathers, John C.
Abstract:
Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman's rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P =0·039) and WNT11 (P =0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P =0·042), WNT11 (P =0·012) and c-MYC (P =0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3β), catenin β1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.
Published:
September 14, 2019
Title:
Glycemic Index and Insulinemic Index of Foods: An Interlaboratory Study Using the ISO 2010 Method
Authors:
Wolever; Meynier, Alexandra; Jenkins; Brand-Miller, Jennie; Atkinson, Fiona; Gendre; Leuillet; Cazaubiel; Housez, Beatrice; Vinoy, Sophie
Abstract:
An official method for determining food glycemic index (GI) was published by the Organization for International Standardization (ISO) in 2010, but its performance has not been assessed. Therefore, we aimed to determine the intra- and inter-laboratory variation of food GI values measured using the 2010 ISO method. Three laboratories (Australia, Canada and France) determined the GI and insulinemic-index (II) of six foods in groups of 13–15 participants using the 2010 ISO method and intra- and inter-laboratory Standard Deviations (SDs) were calculated. Overall mean food GIs varied from 47 to 86 (p < 0.0001) with no significant difference among labs (p = 0.57) and no food × laboratory interaction (p = 0.20). Within-laboratory SD was similar among foods (range, 17.8–22.5; p = 0.49) but varied among laboratories (range 17.5–23.1; p = 0.047). Between-laboratory SD of mean food GI values ranged from 1.6 to 6.7 (mean, 5.1). Mean glucose and insulin responses varied among foods (p < 0.001) with insulin (p = 0.0037), but not glucose (p = 0.054), varying significantly among labs. Mean II varied among foods (p
Published:
September 13, 2019
Title:
Did our species evolve in subdivided populations across Africa, and Why does it matter?
Authors:
Scerri, Eleanor; Thomas, Mark; Manica, Andrea; Gunz, Philipp; Stock, Jay; Stringer, Christopher; Grove, Matt; Groucutt, Huw; Timmermann, Axel; Rightmire, G.; d’Errico, Francesco; Tryon, Christian; Drake, Nick; Brooks, Alison; Dennell, Robin; Henn, Brenna; Lee-Thorp, Julia; Demenocal, Peter; Chikhi, Lounès
Abstract:
Published:
September 12, 2019
Title:
Asaronic Acid Attenuates Macrophage Activation toward M1 Phenotype through Inhibition of NF-κB Pathway and JAK-STAT Signaling in Glucose-Loaded Murine Macrophages
Authors:
Oh, Hyeongjoo; Park, Sin-Hye; Kang, Min-Kyung; Kim, Yun-Ho; Lee, Eun-Jung; Kim, Dong Yeon; Kim, Soo-Il; Oh, SuYeon; Lim, Soon Sung; Kang, Young-Hee
Abstract:
Macrophage polarization has been implicated in the pathogenesis of obesity and type 2 diabetes, which are recognized as chronic proinflammatory diseases. This study investigated that high level of glucose, similar to lipopolysaccharide (LPS), activated macrophages toward M1 phenotypes and 1–20 μM asaronic acid (AA) counteracted diabetic macrophage activation. AA reduced the LPS-promoted secretion of proinflammatory interleukin (IL)-6 and monocyte chemoattractant protein-1. The LPS markedly elevated the macrophage induction of the M1 markers of Toll-like receptor 4 (TLR4), CD36, and CD68, which was attenuated by AA. Also, the LPS significantly enhanced the nuclear factor (NF)-κB transactivation, signal transducers, and activators of transcription 1 (STAT1)/STAT3 activation and suppressor of cytokine signaling 3 (SOCS3) induction in macrophages. However, AA highly suppressed the aforementioned effects of LPS. Glucose-stimulated macrophages expressed advanced glycation end products (AGEs) and receptor for AGE (RAGE). Administration of 20 μM AA to macrophages partly but significantly attenuated such effects (1.65 ± 0.12 vs 0.95 ± 0.25 times glucose control for AGE; 2.33 ± 0.31 vs 1.40 ± 0.22 times glucose control for RAGE). Furthermore, glucose enhanced the macrophage induction of TLR4 and inducible nitric oxide synthase and IL-6 production, while it demoted the production of anti-inflammatory arginase-1 and IL-10. In contrast, AA reversed the induction of these markers in glucose-loaded macrophages. AA dose-dependently and significantly encumbered NF-κB transactivation, Janus kinase 2 (JAK2) and STAT1/STAT3 activation, and SOCS3 induction upregulated in glucose-supplemented macrophages. These results demonstrated for the first time that AA may limit diabetic macrophage activation toward the M1 phenotype through the inhibition of TLR4-/IL-6-mediated NF-κB/JAK2-STAT signaling entailing AGE–RAGE interaction.
Published:
September 11, 2019
Title:
Ecology of a widespread large omnivore, Homo sapiens, and its impacts on ecosystem processes
Authors:
Root‐Bernstein, Meredith; Ladle, Richard
Abstract:
Discussions of defaunation and taxon substitution have concentrated on megafaunal herbivores and carnivores, but mainly overlooked the particular ecological importance of megafaunal omnivores. In particular, the Homo spp. have been almost completely ignored in this context, despite the extinction of all but one hominin species present since the Plio‐Pleistocene. Large omnivores have a particular set of ecological functions reflecting their foraging flexibility and the varied disturbances they create, functions that may maintain ecosystem stability and resilience. Here, we put the ecology of Homo sapiens in the context of comparative interspecific ecological roles and impacts, focusing on the large omnivore guild, as well as comparative intraspecific variation, focusing on hunter‐gatherers.We provide an overview of the functional traits of H. sapiens, which can be used to spontaneously provide the functions for currently ecologically extinct or endangered ecosystem processes. We consider the negative impacts of variations in H. sapiens phenotypic strategies, its possible status as an invasive species, and the potential to take advantage of its learning capacities to decouple negative and positive impacts.We provide examples of how practices related to foraging, transhumance, and hunting could contribute to rewilding‐inspired programs either drawing on hunter‐gatherer baselines of H. sapiens, or as proxies for extinct or threatened large omnivores. We propose that a greater focus on intraspecific ecological variation and interspecific comparative ecology of H. sapiens can provide new avenues for conservation and ecological research. , The ecology of humans is usually considered separately and often using different concepts to those used for other species. We propose an ecological approach to humans based on the joint consideration of intraspecific variation and interspecific comparison. We look at inter‐ and intraspecific variation and similarity in ecological roles of hunter‐gatherer humans, other hominins, and other large omnivores.
Published:
September 11, 2019
Title:
Quorum Sensing by Monocyte-Derived Populations
Authors:
Postat, Jérémy; Bousso, Philippe
Abstract:
Quorum sensing is a type of cellular communication that was first described in bacteria, consisting of gene expression regulation in response to changes in cell-population density. Bacteria synthesize and secrete diffusive molecules called autoinducers, which concentration varies accordingly with cell density and can be detected by the producing cells themselves. Once autoinducer concentration reaches a critical threshold, all bacteria within the autoinducer-rich environment react by modifying their genetic expression and adopt a coordinated behavior (e.g., biofilm formation, virulence factor expression, or swarming motility). Recent advances highlight the possibility that such type of communication is not restricted to bacteria, but can exist among other cell types, including immune cells and more specifically monocyte-derived cells (). For such cells, quorum sensing mechanisms may not only regulate their population size and synchronize their behavior at homeostasis but also alter their activity and function in unexpected ways during immune reactions. Although the nature of immune autoinducers and cellular mechanisms remains to be fully characterized, quorum sensing mechanisms in the immune system challenge our traditional conception of immune cell interactions and likely represent an important mode of communication at homeostasis or during an immune response. In this mini-review, we briefly present the prototypic features of quorum sensing in bacteria and discuss the existing evidence for quorum sensing within the immune system. Mainly, we review quorum sensing mechanisms among monocyte-derived cells, such as the regulation of inflammation by the density of monocyte-derived cells that produce nitric oxide and discuss the relevance of such models in the context of immune-related pathologies.
Published:
September 11, 2019
Title:
Carbohydrate-restricted Diet and Exercise Increase Brain-derived Neurotrophic Factor and Cognitive Function: A Randomized Crossover Trial
Authors:
Gyorkos, Amy; Baker, Mark H.; Miutz, Lauren N.; Lown, Deborah A.; Jones, Michael A.; Houghton-Rahrig, Lori D.; A, Gyorkos; H, Baker M.; N, Miutz L.; A, Lown D.; A, Jones M.; D, Houghton-Rahrig L.
Abstract:
Introduction Metabolic syndrome (MetS) has been recognized as one of the most important clinical challenges and global health issues of today. Growing evidence suggests that mechanisms of energy metabolism may also play a key role in mediating aspects of cognitive function. Brain-derived neurotrophic factor (BDNF) is one such factor well known for its critical role in neuronal plasticity, including memory and learning, and more recently metabolic processes. BDNF levels have been shown separately to be dependent on diet and exercise programming. Purpose The purpose of this study was to investigate the effect of diet and exercise on BDNF levels and cognitive functioning with any metabolic association in individuals characterized with MetS. Methods Twelve subjects with MetS followed a randomized crossover design with two four-week interventions, including a carbohydrate (CHO)-restricted Paleolithic-based diet (CRPD; <50gCHO) with sedentary activity (CRPD-Sed) and CRPD with high intensity interval training (HIIT; CRPD-Sed), separated by a four-week washout period. The HIIT exercise consisted of 10 x 60 s cycling intervals interspersed with 60 s of active recovery 3 day/week for four-week. Serum BDNF was detected and quantified via enzyme-linked immunosorbent assay (ELISA). Cognitive executive function (Stroop Test) and self-perceived cognitive symptoms and function (MOS-CFS) were quantified. A two-way analysis of variance with repeated measures was performed with post-hoc analysis using simple effects analysis with a Bonferroni adjustment. The level of statistical significance was established a priori as P < 0.05. Results Compared to baseline, CRPD-Sed and CRPD-Ex improved variables for cognitive function, including increased peripheral serum BDNF levels (20% and 38%), psychomotor speed and cognitive flexibility (-14%, -14%), and self-perceived cognitive symptoms and functioning (+8%, +16%), respectively. BDNF inversely correlated with %body fat (r = -0.35, P < 0.05), fasting glucose (r = -0.64, P < 0.05), triglycerides (r = -0.55, P < 0.05), and insulin sensitivity (r = -0.25, P < 0.05). Conclusion This study shows the short-term beneficial effects of carbohydrate-restricted diet on serum BDNF and executive function in those individuals characterized with MetS. We have shown that the addition of exercise can further improve neuroprotection and cognitive function beyond the results of diet alone.
Published:
September 9, 2019
Title:
Sex at Dusk, Sex at Dawn, Selfish Genes: How Old-Dated Evolutionary Ideas Are Used to Defend Fallacious Misogynistic Views on Sex Evolution
Authors:
Diogo, Rui
Abstract:
Ryan and Jetha's 2010 book "Sex at Dawn" caused a huge controversy within the academic community, with several papers, commentaries, and even a whole book, "Sex at Dusk: lifting the shiny wrapping from Sex at Dawn" published in 2012 by Saxon, being written to attack it. However, when one reads the so-called 'scientific' publications that were produced after, and as a reaction to, Sex at Dawn, one can see that the major controversy is not really about monogamy vs polygamy, as the general public tends to think, but about our 'sexual nature' being mainly polygynous (1 male having several females) as argued in Sex at Dusk, vs multimale-multifemale (each female and each male having various partners of the other sex) as argued in Sex at Dawn. In other words, both models assume that it is mainly part of our 'human nature' to have a male copulating with several females: what hit the nerve of people, with the publication of Sex at Dawn, is mainly its idea that it is also part of our 'nature' to have a female having the sexual drive/desire to copulate with various males. What is particularly interesting is that Saxon published Sex at Dusk mainly as if it were an analysis of the evolution of sex in humans based on 'accurate', 'deep knowledge' of evolutionary biology, an idea often accepted in the few book reviews published about this book, which considered the book to be a 'scientific rebuttal' of the 'pseudo-science' of Sex at Dawn. However, despite the crucial importance of the subjects debated in these books for discussions on human evolution, and the huge repercussion of these debates for the media and broader public, puzzlingly no publication has examined so far, in detail, if the 'evolutionary framework' followed in Sex at Dusk is truly a reflection of a 'deep knowledge' of current evolutionary ideas. In this paper I will show that a careful analysis of Sex at Dusk shows that the book instead uses old-dated, extremist adaptationist 'selfish genes' evolutionary ideas that were popular 5 decades ago but that have been more and more discarded since then. In fact, Sex at Dusk has nothing new or progressive: it is just one more repetition of misogynistic narratives/just-so stories that have been strongly contradicted by empirical data in the last decades. That is, Sex at Dusk-written exclusively to attack Sex at Dawn, a book precisely aimed to put in question such old-dated, misogynistic tales-just confirms the premonition made in works such as Ackerman's Natural History of Love: that due to a powerful combination of strong biases and the use of antiquated fallacious evolutionary ideas, such narratives will in fact likely not "change very soon".
Published:
September 7, 2019
Title:
High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense
Authors:
Silvares, Raquel Rangel; Pereira, Evelyn Nunes Goulart da Silva; Flores, Edgar Eduardo Ilaquita; Rodrigues, Karine Lino; Silva, Adriana Ribeiro; Gonçalves-de-Albuquerque, Cassiano Felipe; Daliry, Anissa
Abstract:
High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense
Published:
September 6, 2019
Title:
Tregs in fibrosis: To know your enemy, you must become your enemy
Authors:
Bal, Suzanne M.; Stadhouders, Ralph
Abstract:
T helper 2–skewed regulatory T cells in the skin use GATA3 to suppress local profibrotic type 2 cytokine production. See the related Research Article by Kalekar et al. T helper 2–skewed regulatory T cells in the skin use GATA3 to suppress local profibrotic type 2 cytokine production. See the related Research Article by Kalekar et al. T helper 2–skewed regulatory T cells in the skin use GATA3 to suppress local profibrotic type 2 cytokine production. See the related Research Article by Kalekar et al.
Published:
September 6, 2019
Title:
Open letter to Professor Loren Cordain about Ketogenic and Paleolithic Diet(s)
Authors:
Tóth, Csaba; Dabóczi, Andrea; Clemens, Zsofia
Abstract:
One should only grab a pen or, in this case, a keyboard and write an open letter if they want to make a clear and meaningful point. Competence in the subject is an advantage. We hope we meet both criteria. First of all, please let us express our appreciation for your work in the field of human nutrition science. We particularly appreciate your work as we have learned a lot from you. We are convinced that the changes your work has triggered will result in a considerable shift in nutrition science and help return to a reasonable and healthy diet which conforms to human evolution, or at least it will help with its scientific and exact description. As you suggest, there must be a single, optimal diet for all Homo Sapiens: an authentic Paleolithic Diet. We are writing this open letter because we want to respond to the recent criticism you expressed regarding Ketogenic Diets. We chose to publish an open letter, because thus we can inform laypeople about a professional debate which may be of public interest. You are a distinguished professional in the field of nutrition science and recently have expressed opinions on Ketogenic Diets, which have reached a wide range of people.
Published:
September 5, 2019
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