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Title:
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation
Authors:
Kotler, Eran; Shani, Odem; Goldfeld, Guy; Lotan-Pompan, Maya; Tarcic, Ohad; Gershoni, Anat; Hopf, Thomas A.; Marks, Debora S.; Oren, Moshe; Segal, Eran
Abstract:
Summary The TP53 gene is frequently mutated in human cancer. Research has focused predominantly on six major “hotspot” codons, which account for only ∼30% of cancer-associated p53 mutations. To comprehensively characterize the consequences of the p53 mutation spectrum, we created a synthetically designed library and measured the functional impact of ∼10,000 DNA-binding domain (DBD) p53 variants in human cells in culture and in vivo. Our results highlight the differential outcome of distinct p53 mutations in human patients and elucidate the selective pressure driving p53 conservation throughout evolution. Furthermore, while loss of anti-proliferative functionality largely correlates with the occurrence of cancer-associated p53 mutations, we observe that selective gain-of-function may further favor particular mutants in vivo. Finally, when combined with additional acquired p53 mutations, seemingly neutral TP53 SNPs may modulate phenotypic outcome and, presumably, tumor progression.
Published:
July 5, 2018
Title:
Biomarkers of intake for coffee, tea, and sweetened beverages
Authors:
Rothwell, Joseph A.; Madrid-Gambin, Francisco; Garcia-Aloy, Mar; Andres-Lacueva, Cristina; Logue, Caomhan; Gallagher, Alison M.; Mack, Carina; Kulling, Sabine E.; Gao, Qian; Praticò, Giulia; Dragsted, Lars O.; Scalbert, Augustin
Abstract:
Non-alcoholic beverages are important sources of nutrients and bioactive compounds that may influence human health and increase or decrease the risk of chronic diseases. A wide variety of beverage constituents are absorbed in the gut, found in the systemic circulation and excreted in urine. They may be used as compliance markers in intervention studies or as biomarkers of intake to improve measurements of beverage consumption in cohort studies and reveal new associations with disease outcomes that may have been overlooked when using dietary questionnaires. Here, biomarkers of intake of some major non-alcoholic beverages—coffee, tea, sugar-sweetened beverages, and low-calorie-sweetened beverages—are reviewed. Results from dietary intervention studies and observational studies are reviewed and analyzed, and respective strengths and weaknesses of the various identified biomarkers discussed. A variety of compounds derived from phenolic acids, alkaloids, and terpenes were shown to be associated with coffee intake and trigonelline and cyclo(isoleucylprolyl) showed a particularly high specificity for coffee intake. Epigallocatechin and 4′-O-methylepigallocatechin appear to be the most sensitive and specific biomarkers for green or black tea, while 4-O-methylgallic acid may be used to assess black tea consumption. Intake of sugar-sweetened beverages has been assessed through the measurement of carbon-13 enrichment of whole blood or of blood alanine in North America where sugar from sugarcane or corn is used as a main ingredient. The most useful biomarkers for low-calorie-sweetened beverages are the low-calorie sweeteners themselves. Further studies are needed to validate these biomarkers in larger and independent populations and to further evaluate their specificity, reproducibility over time, and fields of application.
Published:
July 4, 2018
Title:
Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis
Authors:
Sustarsic, Elahu G.; Ma, Tao; Lynes, Matthew D.; Larsen, Michael; Karavaeva, Iuliia; Havelund, Jesper F.; Nielsen, Carsten H.; Jedrychowski, Mark P.; Moreno-Torres, Marta; Lundh, Morten; Plucinska, Kaja; Jespersen, Naja Z.; Grevengoed, Trisha J.; Kramar, Barbara; Peics, Julia; Hansen, Jakob B.; Shamsi, Farnaz; Forss, Isabel; Neess, Ditte; Keipert, Susanne; Wang, Jianing; Stohlmann, Katharina; Brandslund, Ivan; Christensen, Cramer; Jørgensen, Marit E.; Linneberg, Allan; Pedersen, Oluf; Kiebish, Michael A.; Qvortrup, Klaus; Han, Xianlin; Pedersen, Bente Klarlund; Jastroch, Martin; Mandrup, Susanne; Kjær, Andreas; Gygi, Steven P.; Hansen, Torben; Gillum, Matthew P.; Grarup, Niels; Emanuelli, Brice; Nielsen, Søren; Scheele, Camilla; Tseng, Yu-Hua; Færgeman, Nils J.; Gerhart-Hines, Zachary
Abstract:
Published:
July 3, 2018
Title:
For anyone struggling w mental health problems looking for hope and inspiration, Carrie Brown (@carriebrownblog) generously shares her personal story of recovery from bipolar disorder and suicidal ideation using ketogenic diet and supplements @KetoConATXhttps://youtu.be/iGW-J4PBCeU
Authors:
MD, Georgia Ede
Abstract:
Published:
July 3, 2018
Title:
Limitations of alignment-free tools in total RNA-seq quantification
Authors:
Wu, Douglas C.; Yao, Jun; Ho, Kevin S.; Lambowitz, Alan M.; Wilke, Claus O.
Abstract:
BACKGROUND: Alignment-free RNA quantification tools have significantly increased the speed of RNA-seq analysis. However, it is unclear whether these state-of-the-art RNA-seq analysis pipelines can quantify small RNAs as accurately as they do with long RNAs in the context of total RNA quantification. RESULT: We comprehensively tested and compared four RNA-seq pipelines for accuracy of gene quantification and fold-change estimation. We used a novel total RNA benchmarking dataset in which small non-coding RNAs are highly represented along with other long RNAs. The four RNA-seq pipelines consisted of two commonly-used alignment-free pipelines and two variants of alignment-based pipelines. We found that all pipelines showed high accuracy for quantifying the expression of long and highly-abundant genes. However, alignment-free pipelines showed systematically poorer performance in quantifying lowly-abundant and small RNAs. CONCLUSION: We have shown that alignment-free and traditional alignment-based quantification methods perform similarly for common gene targets, such as protein-coding genes. However, we have identified a potential pitfall in analyzing and quantifying lowly-expressed genes and small RNAs with alignment-free pipelines, especially when these small RNAs contain biological variations.
Published:
July 3, 2018
Title:
Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression
Authors:
Gurevich, David B; Severn, Charlotte E; Twomey, Catherine; Greenhough, Alexander; Cash, Jenna; Toye, Ashley M; Mellor, Harry; Martin, Paul
Abstract:
Wound angiogenesis is an integral part of tissue repair and is impaired in many pathologies of healing. Here, we investigate the cellular interactions between innate immune cells and endothelial cells at wounds that drive neoangiogenic sprouting in real time and in vivo. Our studies in mouse and zebrafish wounds indicate that macrophages are drawn to wound blood vessels soon after injury and are intimately associated throughout the repair process and that macrophage ablation results in impaired neoangiogenesis. Macrophages also positively influence wound angiogenesis by driving resolution of anti‐angiogenic wound neutrophils. Experimental manipulation of the wound environment to specifically alter macrophage activation state dramatically influences subsequent blood vessel sprouting, with premature dampening of tumour necrosis factor‐α expression leading to impaired neoangiogenesis. Complementary human tissue culture studies indicate that inflammatory macrophages associate with endothelial cells and are sufficient to drive vessel sprouting via vascular endothelial growth factor signalling. Subsequently, macrophages also play a role in blood vessel regression during the resolution phase of wound repair, and their absence, or shifted activation state, impairs appropriate vessel clearance.
Published:
July 2, 2018
Title:
Nutrigenética, nutrigenómica y dieta mediterránea: una nueva visión para la gastronomía
Authors:
Corella, Dolores; Barragán, Rocío; Ordovás, José M. ª.; Coltell, Óscar; Ordovás, José María
Abstract:
Both nutrigenetics and nutrigenomics are disciplines that form part of what is known as Nutritional Genomics, which, in the widest sense, provides the framework for integrating different omics with food and nutrition sciences. After decades of nutrigenetic and nutrigenomic studies, there is a large enough amount of knowledge to consider its application in so-called precision nutrition. This new discipline seeks to take into account the particular characteristics of the individual in order to provide the best diet for preventing or treating a disease. Omic markers are considered to be of importance to that personalization. There are many foods, nutrients and dietary patterns that have been researched in nutrigenetics and nutrigenomics, including the Mediterranean Diet pattern. Despite heterogeneity in defining the Mediterranean Diet, there are various studies that show that the Mediterranean Diet can interact with the genome, so reducing the risk of disease in the most genetically susceptible individuals. Likewise, several studies have recently been revealing the mechanisms through which the Mediterranean Diet may exercise this protective effect. Understanding genetic susceptibility, epigenetic mechanisms, the influence of the metabolome and other omics in more detail may be important in gastronomy, understood as the practice of selecting, cooking and eating food. This omic influence can not only be found in health-disease phenotypes, but also in food taste and smell perception and preferences for certain dishes. Considering all of these together may contribute to an increase in enjoying and at the same time pursuing healthy eating.
Published:
July 2, 2018
Title:
Evolution of the Human Brain: the key roles of DHA (omega-3 fatty acid) and Δ6-desaturase gene
Authors:
Majou, Didier
Abstract:
The process of hominization involves an increase in brain size. The development of hominids’ cognitive capital up to the emergence of Homo sapiens was due to interactive, iterative, and integrative coevolution, allowing positive selection. Although this depends on many factors, in this position paper we show three categories that stand out: gene mutations, food resources, and cognitive and behavioral stimulation. Australopithecus benefited both from the inactivation of the GULO and uricase genes and from bipedalism causing the cognitive capital of the Homo genus to develop advantageously. This evolution depended on two factors. Firstly, a triggering factor: gradual climate change. Homo started to regularly consume meat in addition to plants and insects. Secondly, a stimulating factor: mutations in the FADS2 gene, which encodes Δ6-desaturase; a key enzyme for the synthesis of DHA and sapienic acid. The polymorphism of this gene appears to have been essential in allowing the Homo genus to adapt to its food, and for its evolution. It provides an undeniable advantage in terms of the productivity of fat synthesis (DHA), and may partly explain positive selection. With the advent of cooking and new mutations producing even more FADS2, the brain reached its maximum size in Homo neanderthalensis, in a food ecosystem that provided favorable quantities of α-Linolenic acid and DHA. However, the Würm glaciation upset this equilibrium, revealing its fragility as regards to the brain and fertility. Homo sapiens, benefiting from new variants of the FADS2 gene, were able to adapt to this harsh environment, whereas Neanderthal man was unable to do so and became extinct.
Published:
July 1, 2018
Title:
Specialized Vacuoles of Myrosin Cells: Chemical Defense Strategy in Brassicales Plants
Authors:
Shirakawa, Makoto; Hara-Nishimura, Ikuko
Abstract:
Plant vacuoles display many versatile functions. Vacuoles in vegetative tissues are generally involved in protein degradation, and are called lytic vacuoles. However, vegetative vacuoles in specialized cells can accumulate large concentrations of proteins, such as those in idioblast myrosin cells along veins in the order Brassicales, which store large amounts of myrosinases (thioglucoside glucohydrolase and thioglucoside glucohydrolase). Myrosinases cleave the bond between sulfur and glucose in sulfur-rich compounds (glucosinolates) to produce toxic compounds (isothiocyanates) when plants are damaged by pests. This defense strategy is called the myrosinase-glucosinolate system. Recent studies identified atypical myrosinases, PENETRATION 2 (PEN2) and PYK10, along with key components for development of myrosin cells. In this review, we discuss three topics in the myrosinase-glucosinolate system. First, we summarize the complexity and importance of the myrosinase-glucosinolate system, including classical myrosinases, atypical myrosinases and the system that counteracts the myrosinase-glucosinolate system. Secondly, we describe molecular machineries underlying myrosin cell development, including specific reporters, cell lineage, cell differentiation and cell fate determination. The master regulators for myrosin cell differentiation, FAMA and SCREAM, are key transcription factors involved in guard cell differentiation. This indicates that myrosin cells and guard cells share similar transcriptional networks. Finally, we hypothesize that the myrosinase-glucosinolate system may have originated in stomata of ancestral Brassicales plants and, after that, plants co-opted this defense strategy into idioblasts near veins at inner tissue layers.
Published:
July 1, 2018
Title:
The Relationship between Immigration Status and Cardiovascular Disease Risk Factors in United States Adults with Diabetes—A 14-Year Study
Authors:
Dawson, Aprill; Garacci, Emma; Ozieh, Mukoso N.; Walker, Rebekah J.; Egede, Leonard E.
Abstract:
Introduction: Chronic diseases such as heart disease, stroke, and type 2 diabetes are common health issues in the U.S. About 9.4% of the U.S. population has diabetes. Research shows there is a relationship between immigration status and prevalence of chronic disease. The aim of this study is to understand the relationship between immigration status and CVD risk factors such as LDL, blood pressure, hemoglobin A1c (HbA1C), and body mass index (BMI). Methods: The study included seven waves of data from the National Health and Nutrition Examination Survey (NHANES) for individuals with diabetes, aged 20 and older between 2001-2014. Survey participants were categorized as foreign-born and U.S. born based on self-report responses. Outcome measures included BMI, blood pressure, LDL, and HbA1C, measured as part of the NHANES procedures. Survey general linear regression methods were used to model each outcome and results were weighted to calculate nationally representative estimates. Results: Approximately, 5,414 individuals (representing 22,788,949 U.S. adults) were included in the study. Twenty-seven percent of the sample were foreign-born representing about 18% of the U.S. population. After controlling for demographics, NHANES waves, access to health care, and years of residence in the U.S. foreign-born individuals had significantly lower BMI (-3.05; p
Published:
July 1, 2018
Title:
The carnivorous feeding behavior of early Homo at HWK EE, Bed II, Olduvai Gorge, Tanzania
Authors:
Pante, Michael C.; Njau, Jackson K.; Hensley-Marschand, Blaire; Keevil, Trevor L.; Martín-Ramos, Carmen; Peters, Renata Franco; de la Torre, Ignacio
Abstract:
The regular consumption of large mammal carcasses, as evidenced by butchery marks on fossils recovered from Early Stone Age archaeological sites, roughly coincides with the appearance of Homo habilis. However, the significance of this niche expansion cannot be appreciated without an understanding of hominin feeding behavior and their ecological interactions with mammalian carnivores. The Olduvai Geochronology and Archaeology Project (OGAP) has recovered a large and well-preserved fossil assemblage from the HWK EE site, which was deposited just prior to the first appearance of Acheulean technology at Olduvai Gorge and likely represents one of the last H. habilis sites at Olduvai. This taphonomic analysis of the larger mammal fossil assemblage excavated from HWK EE shows evidence of multiple occupations over a long period of time, suggesting the site offered resources that were attractive to hominins. There was a water source indicated by the presence of fish, crocodiles, and hippos, and there was possible tree cover in an otherwise open habitat. The site preserves several stratigraphic intervals with large fossil and artifact assemblages within two of these intervals. Feeding traces on bone surfaces suggest hominins at the site obtained substantial amounts of flesh and marrow, particularly from smaller size group 1–2 carcasses, and exploited a wide range of taxa, including megafauna. A strong carnivore signal suggests hominins scavenged much of their animal foods during the two main stratigraphic intervals. In the later interval, lower carnivore tooth mark and hammerstone percussion mark frequencies, in addition to high epiphyseal to shaft fragment ratios, suggest hominins and carnivores did not fully exploit bone marrow and grease, which may have been acquired from nutritionally-stressed animals that died during a dry period at Olduvai. The diversity of fauna that preserve evidence of butchery suggests that the HWK EE hominins were opportunistic in their acquisition of carcass foods.
Published:
July 1, 2018
Title:
Evolution of ARDS biomarkers: Will metabolomics be the answer?
Authors:
Metwaly, Sayed; Cote, Andreanne; Donnelly, Sarah J.; Banoei, Mohammad M.; Mourad, Ahmed I.; Winston, Brent W.
Abstract:
To date, there is no clinically agreed-upon diagnostic test for acute respiratory distress syndrome (ARDS): the condition is still diagnosed on the basis of a constellation of clinical findings, laboratory tests, and radiological images. Development of ARDS biomarkers has been in a state of continuous flux during the past four decades. To address ARDS heterogeneity, several studies have recently focused on subphenotyping the disease on the basis of observable clinical characteristics and associated blood biomarkers. However, the strong correlation between identified biomarkers and ARDS subphenotypes has yet to establish etiology; hence, there is a need for the adoption of other methodologies for studying ARDS. In this review, we will shed light on ARDS metabolomics research in the literature and discuss advances and major obstacles encountered in ARDS metabolomics research. Generally, the ARDS metabolomics studies focused on identification of differentiating metabolites for diagnosing ARDS, but they were performed to different standards in terms of sample size, selection of control cohort, type of specimens collected, and measuring technique utilized. Virtually none of these studies have been properly validated to identify true metabolomics biomarkers of ARDS. Though in their infancy, metabolomics studies exhibit promise to unfold the biological processes underlying ARDS and, in our opinion, have great potential for pushing forward our present understanding of ARDS.
Published:
June 28, 2018
Title:
Similarities and differences in gut microbiome composition correlate with dietary patterns of Indian and Chinese adults
Authors:
Jain, Abhishek; Li, Xin Hui; Chen, Wei Ning
Abstract:
The interaction between diet and gut microbiota, and ultimately their link to health, has turned into the concentration of huge research. However, this relationship still needs to be fully characterized, particularly in case of the Asian population. We compared the fecal bacterial diversity and composition of healthy Indian and Chinese adults, ages 22-35 years, using next-generation sequencing analysis on IlluminaHiSeq 2500 platform. Our analysis revealed unique community structure, dominant Firmicutes, Actinobacteria and underrepresented Bacteroides, of Indian and Chinese gut bacteria. This community structure closely matched with the gut bacterial composition of the Russian population. Therefore, we hypothesized that enrichment of these bacterial clades is supported by high consumption of starch-rich diet such as rice, potato, refined grains. The dominance of genus Bifidobacterium due to carbohydrate-rich diet is another notable feature of this study. Moreover, Indian gut bacteria are significantly represented by Bacteroidetes (p = 0.001) and Prevotella (p = 0.002) in contrast to Chinese, which could be associated with whole grains and plant-based vegetarian diet of Indians. The gut bacterial population of Indian adults were as diverse as Chinese adults (p > 0.1), but significant difference was noticed in gut bacterial composition and relative abundance between two populations (R = 0.625, p
Published:
June 23, 2018
Title:
Investigation of the long-term sustainability of changes in appetite after weight loss
Authors:
Nymo, S.; Coutinho, S. R.; Eknes, P. H.; Vestbostad, I.; Rehfeld, J. F.; Truby, H.; Kulseng, B.; Martins, C.
Abstract:
BACKGROUND/OBJECTIVE: Diet-induced weight loss (WL) leads to a compensatory increase in appetite and changes in the plasma concentration of appetite-regulating hormones are likely to play a role. Whether these changes are transient or sustained remains unclear. This study aimed to assess if changes in subjective and objective appetite markers observed with WL are sustained after 1 year (1Y). SUBJECTS/METHODS: In total 100 (45 males) individuals with obesity (BMI: 37 ± 4 kg/m2, age: 43 ± 10 years) underwent 8 weeks (wks) of a very-low energy diet (VLED), followed by 4 wks refeeding, and a 1Y maintenance program. Fasting/postprandial subjective ratings of hunger, fullness, desire to eat, and prospective food consumption (PFC) were assessed, and plasma concentration of active ghrelin (AG), total peptide YY (PYY), active glucagon-like peptide 1, cholecystokinin (CCK), and insulin measured, at baseline, week 13 (Wk13) and 1Y. RESULTS: At Wk13, 16% WL (-18 ± 1 kg, P < 0.001) was associated with a significant increase in fasting and postprandial hunger ratings (P < 0.01 and P < 0.05, respectively), and postprandial fullness (P < 0.01) combined with a reduction in PFC (P < 0.001). These were accompanied by a significant rise in basal and postprandial AG concentrations (P < 0.001, for both), a reduction in postprandial CCK (P < 0.01) and in basal and postprandial insulin (P < 0.001). At 1Y follow-up, with sustained WL (15%; -16 ± 1 kg, P < 0.001), fasting hunger and postprandial fullness ratings remained increased (P < 0.05 for both), and postprandial PFC reduced (P < 0.001). Basal and postprandial AG remained elevated and insulin reduced (P < 0.001, for all), while postprandial CCK was increased (P < 0.01) and PYY decreased (P
Published:
June 21, 2018
Title:
Hypertension, overweight/obesity, and diabetes among immigrants in the United States: an analysis of the 2010–2016 National Health Interview Survey
Authors:
Commodore-Mensah, Yvonne; Selvin, Elizabeth; Aboagye, Jonathan; Turkson-Ocran, Ruth-Alma; Li, Ximin; Himmelfarb, Cheryl Dennison; Ahima, Rexford S.; Cooper, Lisa A.
Abstract:
Ethnic minority populations in the United States (US) are disproportionately affected by cardiovascular disease (CVD) risk factors, including hypertension, overweight/obesity, and diabetes. The size and diversity of ethnic minority immigrant populations in the US have increased substantially over the past three decades. However, most studies on immigrants in the US are limited to Asians and Hispanics; only a few have examined the prevalence of CVD risk factors across diverse immigrant populations. The prevalence of diagnosed hypertension, overweight/obesity, and diagnosed diabetes was examined and contrasted among a socioeconomically diverse sample of immigrants. It was hypothesized that considerable variability would exist in the prevalence of hypertension, overweight and diabetes.
Published:
June 20, 2018
Title:
The Expensive-Tissue Hypothesis in Vertebrates: Gut Microbiota Effect, a Review
Authors:
Huang, Chun Hua; Yu, Xin; Liao, Wen Bo
Abstract:
The gut microbiota is integral to an organism’s digestive structure and has been shown to play an important role in producing substrates for gluconeogenesis and energy production, vasodilator, and gut motility. Numerous studies have demonstrated that variation in diet types is associated with the abundance and diversity of the gut microbiota, a relationship that plays a significant role in nutrient absorption and affects gut size. The Expensive-Tissue Hypothesis states (ETH) that the metabolic requirement of relatively large brains is offset by a corresponding reduction of the other tissues, such as gut size. However, how the trade-off between gut size and brain size in vertebrates is associated with the gut microbiota through metabolic requirements still remains unexplored. Here, we review research relating to and discuss the potential influence of gut microbiota on the ETH.
Published:
June 17, 2018
Title:
The Expensive-Tissue Hypothesis in Vertebrates: Gut Microbiota Effect, a Review
Authors:
Huang, Chun Hua; Yu, Xin; Liao, Wen Bo
Abstract:
The gut microbiota is integral to an organism’s digestive structure and has been shown to play an important role in producing substrates for gluconeogenesis and energy production, vasodilator, and gut motility. Numerous studies have demonstrated that variation in diet types is associated with the abundance and diversity of the gut microbiota, a relationship that plays a significant role in nutrient absorption and affects gut size. The Expensive-Tissue Hypothesis states (ETH) that the metabolic requirement of relatively large brains is offset by a corresponding reduction of the other tissues, such as gut size. However, how the trade-off between gut size and brain size in vertebrates is associated with the gut microbiota through metabolic requirements still remains unexplored. Here, we review research relating to and discuss the potential influence of gut microbiota on the ETH.
Published:
June 17, 2018
Title:
Vitamin K Research Analysis
Authors:
Frank, Kurtis; Patel, Kamal; Lopez, Gregory; Willis, Bill
Abstract:
Vitamin K is an essential vitamin found in plants or produced from intestinal bacteria. It plays an essential role in bone health and regulates blood clotting.
Published:
June 14, 2018
Title:
High Resolution GC/MS Metabolomics of Non-Human Primate Serum
Authors:
Misra, Biswapriya B.; Bassey, Ekong; Bishop, Andrew C.; Kusel, David T.; Cox, Laura A.; Olivier, Michael
Abstract:
RATIONALE: Metabolomics analyses using gas chromatography mass spectrometry (GC/MS) - based metabolomics are heavily impeded by the lack of high-resolution mass spectrometers and limited spectral libraries to complement the excellent chromatography that GC platforms offer, a challenge that is being addressed with the implementation of high resolution (HR) platforms such as 1D-GC/Orbitrap-MS. METHODS: We used serum samples from a non-human primate (NHP), a baboon (Papio hamadryas), with suitable quality controls to quantify the chemical space using an advanced HR MS platform for confident metabolite identification and robust quantification to assess the suitability of the platform for routine clinical metabolomics research. In a complementary approach, we also analyzed the same serum samples using a two-dimensional gas chromatography time-of-flight mass-spectrometer (2D-GC/ToF-MS) for metabolite identification and quantification following established standard protocols. RESULTS: Overall, the 2D-GC/ToF-MS (~5000 peaks per sample) and 1D-GC/Orbitrap-MS (~500 peaks per sample) analyses enabled identification and quantification of a total of 555 annotated metabolites from the NHP serum with a spectral similarity score Rsim ≥ 900 and S/N ratio of > 25. A common set of 30 metabolites with HMDB and KEGG IDs was quantified in the serum samples by both platforms where 2D-GC/ToF-MS enabled quantification of a total 384 metabolites (118 HMDB IDs) and 1D-GC/Orbitrap-MS analysis quantification of a total 200 metabolites (47 HMDB IDs). Thus, roughly 30–70% of the peaks remain unidentified or un-annotated across both platforms. CONCLUSIONS: Our study provides insights into the benefits and limitations of the use of a higher mass resolution and mass accuracy instrument for untargeted GC/MS-based metabolomics with multi-dimensional chromatography in future studies addressing clinical conditions or exposome studies.
Published:
June 6, 2018
Title:
Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes
Authors:
Sutton, Elizabeth F.; Beyl, Robbie; Early, Kate S.; Cefalu, William T.; Ravussin, Eric; Peterson, Courtney M.
Abstract:
Summary Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5 weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF’s effects are not solely due to weight loss.
Published:
June 5, 2018
Title:
Foods and Supplements Associated with Vitamin B12 Biomarkers among Vegetarian and Non-Vegetarian Participants of the Adventist Health Study-2 (AHS-2) Calibration Study
Authors:
Damayanti, Didit; Jaceldo-Siegl, Karen; Beeson, W. Lawrence; Fraser, Gary; Oda, Keiji; Haddad, Ella H.
Abstract:
To investigate the association between plasma concentration of vitamin B12 and B12 intake from supplements, fortified foods, and animal source foods among vegetarians and non-vegetarians, we conducted a cross-sectional analysis among 728 participants of the Adventist Health Study 2 (AHS-2) calibration study. The median age of participants was 58 years, 65.4% were female, and 50.3% were White. We used six 24 h dietary recalls to measure B12 intake, serum vitamin B12, and holotranscobalamin (holoTC) concentration. B12 supplements had a significantly positive association with plasma B12 among all subjects (p trend < 0.001), especially among vegans and lacto-ovo vegetarians (p trend < 0.001). Among non-users of B12 supplements, B12 intake from milk substitutes was significantly positively associated with holoTC (p trend < 0.004) and serum B12 (p trend < 0.030). In non-vegetarians, holoTC was significantly positively associated with B12 intake from eggs, while serum B12 was significantly positively associated with B12 intake from milk in the upper tertile compared to the lower, and B12 intake from meat in the middle compared to the lower tertile intake (p
Published:
June 4, 2018
Title:
A call for inclusion of work-related diabetes distress in the spectrum of diabetes management: Results from a cross-sectional survey among working people with type 1 diabetes
Authors:
Hansen, Ulla M.; Olesen, Kasper; Browne, Jessica L.; Skinner, Timothy C.; Willaing, Ingrid
Abstract:
Aim Diabetes distress captures a range of emotional responses and reactions to life with diabetes and is considered a part of the experience of managing diabetes and its treatment. Given the importance of the social context of work life for people of working age we set out to explore whether work-related diabetes distress is a distinct and important dimension of diabetes-related emotional distress in working people with type 1 diabetes. Methods A questionnaire with self-reported measures of psychosocial health and well-being at work was completed by 1126 working people with type 1 diabetes from a specialist diabetes clinic in Denmark. Work-related diabetes distress was assessed with two questions about worry and exhaustion related to reconciling work life and diabetes. Diabetes-related emotional distress was assessed with the Problem Areas in Diabetes scale (PAID-5), a short form version of the full PAID scale. We performed inter-item correlation analyses, exploratory factor analysis, and hierarchical multiple regression analyses. Results Inter-item correlations and exploratory factor analysis indicated that work-related diabetes distress was distinct from diabetes-related emotional distress. Further, work-related diabetes distress was found to be a unique contributor to work ability, quality of life, intentional hyperglycaemia at work, and absenteeism, after adjusting for covariates and diabetes-related emotional distress. Conclusions The findings suggest that work-related diabetes distress captures an aspect of distress so far unaccounted for in workers with type 1 diabetes. Further studies are needed to strengthen the conceptual basis of work-related diabetes distress, explore its clinical usefulness and clarify its risk factors.
Published:
June 1, 2018
Title:
Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis.
Authors:
So, Daniel; Whelan, Kevin; Rossi, Megan; Morrison, Mark; Holtmann, Gerald; Kelly, Jaimon T.; Shanahan, Erin R.; Staudacher, Heidi M.; Campbell, Katrina L.
Abstract:
Background: Dysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota, and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation. Objective: A systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults. Design: A systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators. Results: A total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. (standardized mean difference (SMD): 0.64; 95% CI: 0.42, 0.86; P < 0.00001) and Lactobacillus spp. (SMD: 0.22; 0.03, 0.41; P = 0.02) as well as fecal butyrate concentration (SMD: 0.24; 0.00, 0.47; P = 0.05) compared with placebo/low-fiber comparators. Subgroup analysis revealed that fructans and galacto-oligosaccharides led to significantly greater abundance of both Bifidobacterium spp. and Lactobacillus spp. compared with comparators (P
Published:
June 1, 2018
Title:
Trends in the prevalence of type 2 diabetes and its association with mortality rates in Asians vs. Whites: Results from the United States National Health Interview Survey from 2000 to 2014
Authors:
Lee, Jiwon R.; Yeh, Hsin-Chieh
Abstract:
Aims To identify the prevalence and mortality of type 2 diabetes in Asian Americans (Asians) vs. non-Hispanic whites (Whites). Methods We analyzed a nationally representative sample of 237,354 U.S. adults aged ≥30 years using National Health Interview Survey data from 2000 to 2014 to estimate the prevalence and trends of type 2 diabetes. Additionally, 144,638 Asians and Whites represented in surveys from 2000 to 2009 were included in the mortality analysis with follow-up to 2011. Results Type 2 diabetes was higher in Asians than Whites (7.0–11.2 vs. 5.6–8.3%) and increased over time. Prevalence rates increased from 8.1 (2000−2002) to 9.6% (2012–2014) in Asians and from 6.0 (2000–2002) to 7.9% (2012–2014) in Whites (both P
Published:
June 1, 2018
Title:
Corrigendum: The effects of soluble corn fibre and isomaltooligosaccharides on blood glucose, insulin, digestion and fermentation in healthy young males and females
Authors:
Lowery, Ryan P.; Wilson, Jacob M.; Barninger, Andrew; Sharp, Matthew H.; Irvin, Christopher; Stefan, Matthew; Wallace, William A.; Wilson, Gabriel J.; Roberts, Michael D.; Wagner, Ronald
Abstract:
No abstract available.
Published:
May 31, 2018
Title:
Plant use in the Lower and Middle Palaeolithic: Food, medicine, and raw materials
Authors:
Hardy, Karen
Abstract:
The use of plant materials in the manufacture of technological items is likely to be very extensive throughout the Palaeolithic, though only circumstantial evidence survives from the earliest periods. Abstract There is little surviving evidence for plant use in the Lower and Middle Palaeolithic periods yet the evidence there is, clearly indicates the importance of plants in the diet, as medicines and as raw materials. Here, the current evidence for plants is summarised, and the way this can be used to enrich perceptions of the Lower and Middle Palaeolithic are explored. The evidence for plant food fits well with basic nutritional requirements while the presence of medicinal plants correlates with plant-based self-medication by animals. Many plant-based technologies are likely to have developed early in the Palaeolithic. Though investigating this is challenging due to a lack of evidence, the extensive evidence for use of plant materials as tools by chimpanzees provides a broad backdrop. The ecological knowledge carried by all hominins would have provided a safety net when moving into new regions, while varying levels of neophobia would have enabled adaptation to new environments as hominin populations moved and climates changed. Recent plant use among traditional societies in high latitudes shows that even in locations with reduced biodiversity, plant resources can fulfil essential dietary requirements.
Published:
May 29, 2018
Title:
LpA-II:B:C:D:E: a new immunochemically-defined acute phase lipoprotein in humans
Authors:
Bagdade, John D.; Jilma, Bernd; Hudgins, Lisa C.; Alaupovic, Petar; McCurdy, Carrie E.
Abstract:
Previous studies of lipoproteins in patients with sepsis have been performed on density fractions isolated by conventional ultracentrifugation that are heterogeneous and provide no information about the cargo of apoproteins present in the immunochemically distinct subclasses that populate the density classes. Since apoproteins are now known to have important roles in host defense, we have separated these subclasses according to their apoprotein content and characterized their changes during experimental endotoxemia in human volunteers.
Published:
May 28, 2018
Title:
Maternal Circulating Vitamin Status and Colostrum Vitamin Composition in Healthy Lactating Women-A Systematic Approach
Authors:
Y de Vries, Jasmijn; Pundir, Shikha; Mckenzie, Elizabeth; Keijer, Jaap; Kussmann, Martin
Abstract:
Colostrum is the first ingested sole nutritional source for the newborn infant. The vitamin profile of colostrum depends on the maternal vitamin status, which in turn is influenced by diet and lifestyle. Yet, the relationship between maternal vitamin status and colostrum vitamin composition has not been systematically reviewed. This review was conducted with the aim to generate a comprehensive overview on the relationship between maternal serum (plasma) vitamin concentration and corresponding colostrum composition. Three electronic databases, Embase (Ovid), Medline (Ovid), and Cochrane, were systematically searched based on predefined inclusion and exclusion criteria. Finally, a total of 11 eligible publications were included that examined the vitamins A, C, D, E, and K in both biological fluids. Maternal vitamin A, D, E, and K blood levels were unrelated to colostrum content of the respective vitamins, and serum vitamin A was inversely correlated with colostrum vitamin E. Colostrum versus maternal serum vitamins were higher for vitamins A, C, and K, lower for vitamin D, and divergent results were reported for vitamin E levels. Colostrum appears typically enriched in vitamin A, C, and K compared to maternal serum, possibly indicative of active mammary gland transport mechanisms. Inter-individual and inter-study high variability in colostrum's vitamin content endorses its sensitivity to external factors.
Published:
May 28, 2018
Title:
The effect of vegetarian diets on iron status in adults: A systematic review and meta-analysis
Authors:
Haider, Lisa M.; Schwingshackl, Lukas; Hoffmann, Georg; Ekmekcioglu, Cem
Abstract:
BACKGROUND: Vegetarian diets exclude meat, seafood, and products containing these foods. Although the vegetarian lifestyle could lead to a better health status in adults, it may also bear risks for certain nutritional deficiencies. Cross-sectional studies and narrative reviews have shown that the iron status of vegetarians is compromised by the absence of highly bioavailable haem-iron in meatless diets and the inhibiting effect of certain components present in plant foods on non-haem iron bioavailability. METHODS: The databases Pubmed, Scopus, Embase, and Cochrane CentralRegister of Controlled Trials were searched for studies comparing serum ferritin, as the major laboratory parameter for iron status of adult vegetarians with non-vegetarian control groups. A qualitative review was conducted as well as an inverse-variance random-effects meta-analysis to pool available data. In addition the effect of vegetarian diets according to gender was investigated with a subgroup analysis. The results were validated using a sensitivity analysis. RESULTS: A total of 27 cross-sectional studies and three interventional studies were selected for the systematic review. The meta-analysis which combined data of 24 cross-sectional studies showed that adult vegetarians have significantly lower serum ferritin levels than their non-vegetarian controls (-29.71 µg/L, 95% CI [-39.69, -19.73], p < 0.01). Inclusion of semi-vegetarian diets did not change the results considerably (-23.27 µg/L, 95% CI [-29.77, -16.76], p < 0.01). The effects were more pronounced in men (-61.88 µg/L, 95% CI [-85.59, -38.17], p < 0.01) than in both premenopausal women (-17.70 μg/L, 95% CI [-29.80, -5.60], p < 0.01) and all women (-13.50 μg/L, 95% CI [-22.96, -4.04], p
Published:
May 24, 2018
Title:
Understanding Traditional Meat Processing Knowledge among the Borana Pastoralist of Northern Kenya
Authors:
Dabasso, Buke; Roba, Hassan; Makokha, Anselimo
Abstract:
Indigenous knowledge on food preparation is an activity practised in almost all agricultural production system. Amongst the Borana pastoralist of Northern Kenya, milk and meat production are the cornerstone of livelihood, and more often abundance occurs without possibility of immediate consumption, triggering the need to preserve surplus for future consumption. The objective of this paper is to document and understand traditional meat preparation knowledge amongst Borana pastoralist’s women of Northern Kenya.The method of collecting information included in-depth interviews and participant observations to document meat preparation skills and knowledge of Borana people as appertains to traditional food ways. It was observed that methods of traditional meat processing and preparation included different forms of drying, use of heat and storage in fat. Fourteen traditional meat products and seven preservation techniques were documented. Drying and deep frying were the major form of meat preservation. Women skillfully put a lot of effort in all stages of meat preparation to produce an end product that is not only shelf stable but traditional products that are appreciated and nutritious. It was observed that only four of the products are currently in use, an indication of steady decline in meat handling knowledge and preparation.
Published:
May 21, 2018
Title:
Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment
Authors:
Hawk, Mark A.; Schafer, Zachary T.
Abstract:
Nontransformed cells that become detached from the extracellular matrix (ECM) undergo dysregulation of redox homeostasis and cell death. In contrast, cancer cells often acquire the ability to mitigate programmed cell death pathways and recalibrate the redox balance to survive after ECM detachment, facilitating metastatic dissemination. Accordingly, recent studies of the mechanisms by which cancer cells overcome ECM detachment–induced metabolic alterations have focused on mechanisms in redox homeostasis. The insights into these mechanisms may inform the development of therapeutics that manipulate redox homeostasis to eliminate ECM-detached cancer cells. Here, we review how ECM-detached cancer cells balance redox metabolism for survival.
Published:
May 18, 2018
Title:
Macrophage Cytokines Enhance Cell Proliferation of Normal Prostate Epithelial Cells through Activation of ERK and Akt
Authors:
Dang, Tu; Liou, Geou-Yarh
Abstract:
Macrophage infiltrations (inflammation) are associated with prostate disorders such as prostatitis, prostatic hyperplasia and prostate cancer. All prostate disorders have elevated cell proliferation, and are initiated from normal prostate epithelial cells. To date, the mechanism of how macrophages regulate normal prostate epithelial cell proliferation remains largely unknown. Using a 3D co-culture system, we here show that Raw 264.7 macrophages increased cell proliferation of normal prostate epithelial PZ-HPV-7 cells. In addition, these Raw 264.7 macrophages expressed higher levels of Ym1 and CD206. We further identify macrophage-secreted cytokines including CCL3, IL-1ra, osteopontin, M-CSF1 and GDNF as mediators for potentiating PZ-HPV-7 cell proliferation in 3D. All these cytokines differentially activated ERK and Akt. Blockade of both kinases through their inhibitors hindered macrophage-induced cell proliferation of PZ-HPV-7 cells. Hence, our data provide mechanistic insight of how inflammation may contribute to development of prostatic diseases at a very early stage through augment of cell proliferation of normal prostate epithelial cells.
Published:
May 16, 2018
Title:
The Effect of Lean-Seafood and Non-Seafood Diets on Fasting and Postprandial Serum Metabolites and Lipid Species: Results from a Randomized Crossover Intervention Study in Healthy Adults
Authors:
Schmedes, Mette; Balderas, Claudia; Aadland, Eli Kristin; Jacques, Hélène; Lavigne, Charles; Graff, Ingvild Eide; Eng, Øyvin; Holthe, Asle; Mellgren, Gunnar; Young, Jette Feveile; Sundekilde, Ulrik Kræmer; Liaset, Bjørn; Bertram, Hanne Christine
Abstract:
The metabolic effects associated with intake of different dietary protein sources are not well characterized. We aimed to elucidate how two diets that varied in main protein sources affected the fasting and postprandial serum metabolites and lipid species. In a randomized controlled trial with crossover design, healthy adults (n = 20) underwent a 4-week intervention with two balanced diets that varied mainly in protein source (lean-seafood versus non-seafood proteins). Nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry analyses were applied to examine the effects of the two diets on serum metabolites. In the fasting state, the lean-seafood diet period, as opposed to the non-seafood diet period, significantly decreased the serum levels of isoleucine and valine, and during the postprandial state, a decreased level of lactate and increased levels of citrate and trimethylamine N-oxide were observed. The non-seafood diet significantly increased the fasting level of 26 lipid species including ceramides 18:1/14:0 and 18:1/23:0 and lysophosphatidylcholines 20:4 and 22:5, as compared to the lean-seafood diet. Thus, the lean-seafood diet decreased circulating isoleucine and valine levels, whereas the non-seafood diet elevated the levels of certain ceramides, metabolites that are associated with insulin-resistance.
Published:
May 11, 2018
Title:
Exploration of Patient Characteristics and Quality of Life in Patients with Lipoedema Using a Survey
Authors:
Romeijn, Jeroen R. M.; de Rooij, Michette J. M.; Janssen, Loes; Martens, Herm
Abstract:
Introduction Lipoedema is a chronic disorder in which excessive fat distribution occurs predominantly from the waist down, resulting in a disproportion between the lower extremities and upper torso. Lipoedema is often not recognized, while patients experience pain and easy bruising. As a long-term condition, lipoedema has a massive effect on patients’ lives and mental health. The aim of this study is to explore patient characteristics, quality of life, physical complaints and comorbidities in patients with lipoedema. Methods A survey was conducted by email amongst lipoedema patients, consisting of informed consent and multiple questionnaires. The questionnaires included general patient characteristics, physical complaints, comorbidities, RAND-36 and EQ-5D-3L. Participants who responded to a message on the Dutch Lipoedema Association website were recruited. Results All lipoedema patients experience physical complaints, with pain (88.3 %) and easy bruising (85.9 %) as primary complaints. The diagnosis was mostly made by a dermatologist after visiting a mean of 2.8 doctors. Furthermore, mean time from onset until diagnosis was 18 years. Quality of life (59.3) was significantly lower than the Dutch female average (74.9; p < 0.001). Additionally, patients with comorbidities had significant lower quality of life (RAND 54.7, p
Published:
May 10, 2018
Title:
Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk
Authors:
Hlusko, Leslea J.; Carlson, Joshua P.; Chaplin, George; Elias, Scott A.; Hoffecker, John F.; Huffman, Michaela; Jablonski, Nina G.; Monson, Tesla A.; O’Rourke, Dennis H.; Pilloud, Marin A.; Scott, G. Richard
Abstract:
Because of the ubiquitous adaptability of our material culture, some human populations have occupied extreme environments that intensified selection on existing genomic variation. By 32,000 years ago, people were living in Arctic Beringia, and during the Last Glacial Maximum (LGM; 28,000–18,000 y ago), they likely persisted in the Beringian refugium. Such high latitudes provide only very low levels of UV radiation, and can thereby lead to dangerously low levels of biosynthesized vitamin D. The physiological effects of vitamin D deficiency range from reduced dietary absorption of calcium to a compromised immune system and modified adipose tissue function. The ectodysplasin A receptor ( EDAR ) gene has a range of pleiotropic effects, including sweat gland density, incisor shoveling, and mammary gland ductal branching. The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago. The dental pleiotropic effects of this allele suggest an even higher occurrence among indigenous people in the Western Hemisphere before European colonization. We hypothesize that selection on EDAR V370A occurred in the Beringian refugium because it increases mammary ductal branching, and thereby may amplify the transfer of critical nutrients in vitamin D-deficient conditions to infants via mothers’ milk. This hypothesized selective context for EDAR V370A was likely intertwined with selection on the fatty acid desaturase ( FADS ) gene cluster because it is known to modulate lipid profiles transmitted to milk from a vitamin D-rich diet high in omega-3 fatty acids.
Published:
May 8, 2018
Title:
Propranolol sensitizes prostate cancer cells to glucose metabolism inhibition and prevents cancer progression
Authors:
Brohée, Laura; Peulen, Olivier; Nusgens, Betty; Castronovo, Vincent; Thiry, Marc; Colige, Alain C.; Deroanne, Christophe F.
Abstract:
Propranolol, a widely used non-selective beta-adrenergic receptor blocker, was recently shown to display anticancer properties. Its potential to synergize with certain drugs has been also outlined. However, it is necessary to take into account all the properties of propranolol to select a drug that could be efficiently combined with. Propranolol was reported to block the late phase of autophagy. Hence, we hypothesized that in condition enhancing autophagy flux, cancer cells should be especially sensitive to propranolol. 2DG, a glycolysis inhibitor, is an anti-tumor agent having limited effect in monotherapy notably due to induction of pro-survival autophagy. Here, we report that treatment of cancer cells with propranolol in combination with the glycolysis inhibitor 2DG induced a massive accumulation of autophagosome due to autophagy blockade. The propranolol +2DG treatment efficiently prevents prostate cancer cell proliferation, induces cell apoptosis, alters mitochondrial morphology, inhibits mitochondrial bioenergetics and aggravates ER stress in vitro and also suppresses tumor growth in vivo. Our study underlines for the first time the interest to take advantage of the ability of propranolol to inhibit autophagy to design new anti-cancer therapies.
Published:
May 4, 2018
Title:
First anatomical network analysis of fore- and hindlimb musculoskeletal modularity in bonobos, common chimpanzees, and humans
Authors:
Diogo, Rui; Molnar, Julia L.; Rolian, Campbell; Esteve-Altava, Borja
Abstract:
Studies of morphological integration and modularity, and of anatomical complexity in human evolution typically focus on skeletal tissues. Here we provide the first network analysis of the musculoskeletal anatomy of both the fore- and hindlimbs of the two species of chimpanzee and humans. Contra long-accepted ideas, network analysis reveals that the hindlimb displays a pattern opposite to that of the forelimb: Pan big toe is typically seen as more independently mobile, but humans are actually the ones that have a separate module exclusively related to its movements. Different fore- vs hindlimb patterns are also seen for anatomical network complexity (i.e., complexity in the arrangement of bones and muscles). For instance, the human hindlimb is as complex as that of chimpanzees but the human forelimb is less complex than in Pan. Importantly, in contrast to the analysis of morphological integration using morphometric approaches, network analyses do not support the prediction that forelimb and hindlimb are more dissimilar in species with functionally divergent limbs such as bipedal humans.
Published:
May 2, 2018
Title:
First anatomical network analysis of fore- and hindlimb musculoskeletal modularity in bonobos, common chimpanzees, and humans
Authors:
Diogo, Rui; Molnar, Julia; Rolian, Campbell; Esteve-Altava, Borja
Abstract:
Studies of morphological integration and modularity, and of anatomical complexity in human evolution typically focus on skeletal tissues. Here we provide the first network analysis of the musculoskeletal anatomy of both the fore- and hindlimbs of the two species of chimpanzee and humans. Contra long-accepted ideas, network analysis reveals that the hindlimb displays a pattern opposite to that of the forelimb: Pan big toe is typically seen as more independently mobile, but humans are actually the ones that have a separate module exclusively related to its movements. Different fore- vs hindlimb patterns are also seen for anatomical network complexity (i.e., complexity in the arrangement of bones and muscles). For instance, the human hindlimb is as complex as that of chimpanzees but the human forelimb is less complex than in Pan. Importantly, in contrast to the analysis of morphological integration using morphometric approaches, network analyses do not support the prediction that forelimb and hindlimb are more dissimilar in species with functionally divergent limbs such as bipedal humans.
Published:
May 2, 2018
Title:
Supplementary Material 1
Authors:
Diogo, Rui; Molnar, Julia; Rolian, Campbell; Esteve-Altava, Borja
Abstract:
Published:
May 2, 2018
Title:
Supplementary Material 2
Authors:
Diogo, Rui; Molnar, Julia; Rolian, Campbell; Esteve-Altava, Borja
Abstract:
Published:
May 2, 2018
Title:
3D-3-culture: A tool to unveil macrophage plasticity in the tumour microenvironment
Authors:
Rebelo, Sofia P.; Pinto, Catarina; Martins, Tatiana R.; Harrer, Nathalie; Estrada, Marta F.; Loza-Alvarez, Pablo; Cabeçadas, José; Alves, Paula M.; Gualda, Emilio J.; Sommergruber, Wolfgang; Brito, Catarina
Abstract:
The tumour microenvironment (TME) shapes disease progression and influences therapeutic response. Most aggressive solid tumours have high levels of myeloid cell infiltration, namely tumour associated macrophages (TAM). Recapitulation of the interaction between the different cellular players of the TME, along with the extracellular matrix (ECM), is critical for understanding the mechanisms underlying disease progression. This particularly holds true for prediction of therapeutic response(s) to standard therapies and interrogation of efficacy of TME-targeting agents. In this work, we explored a culture platform based on alginate microencapsulation and stirred culture systems to develop the 3D-3-culture, which entails the co-culture of tumour cell spheroids of non-small cell lung carcinoma (NSCLC), cancer associated fibroblasts (CAF) and monocytes. We demonstrate that the 3D-3-culture recreates an invasive and immunosuppressive TME, with accumulation of cytokines/chemokines (IL4, IL10, IL13, CCL22, CCL24, CXCL1), ECM elements (collagen type I, IV and fibronectin) and matrix metalloproteinases (MMP1/9), supporting cell migration and promoting cell-cell interactions within the alginate microcapsules. Importantly, we show that both the monocytic cell line THP-1 and peripheral blood-derived monocytes infiltrate the tumour tissue and transpolarize into an M2-like macrophage phenotype expressing CD68, CD163 and CD206, resembling the TAM phenotype in NSCLC. The 3D-3-culture was challenged with chemo- and immunotherapeutic agents and the response to therapy was assessed in each cellular component. Specifically, the macrophage phenotype was modulated upon treatment with the CSF1R inhibitor BLZ945, resulting in a decrease of the M2-like macrophages. In conclusion, the crosstalk between the ECM and tumour, stromal and immune cells in microencapsulated 3D-3-culture promotes the activation of monocytes into TAM, mimicking aggressive tumour stages. The 3D-3-culture constitutes a novel tool to study tumour-immune interaction and macrophage plasticity in response to external stimuli, such as chemotherapeutic and immunomodulatory drugs.
Published:
May 1, 2018
Title:
CLINICAL EXPERIENCE AND RESEARCH WITH THE PALEOLITHIC KETOGENIC DIET (PKD) – 2010-2017
Authors:
Tóth, Csaba; Clemens, Zsofia
Abstract:
Published:
May 1, 2018
Title:
First Detailed Anatomical Study of Bonobos Reveals Intra-Specific Variations and Exposes Just-So Stories of Human Evolution, Bipedalism, and Tool Use
Authors:
Diogo, Rui
Abstract:
Just-so stories are prominent in human evolution literature because of our tendency to create simple progressionist narratives about our “special” place in nature, despite the fact that these stories are almost exclusively based on hard tissue data. How can we be so certain about the evolution of human facial communication, bipedalism, tool use, or speech without detailed knowledge of the internal anatomy of for instance, one of the two extant species more closely related to us, the bonobos? Here I show how many of these stories now become obsolete, after such a comprehensive knowledge on the anatomy of bonobos and other primates is finally put together. Each and every muscle that has been long accepted to be “uniquely human” and to provide “crucial singular functional adaptations” for our bipedalism, tool use and/or vocal/facial communication, is actually present as an intra-specific variant or even as normal phenotype in bonobos and/or other apes.
Published:
April 26, 2018
Title:
Oxidative stress, aging, and diseases
Authors:
Liguori, Ilaria; Russo, Gennaro; Curcio, Francesco; Bulli, Giulia; Aran, Luisa; Della-Morte, David; Gargiulo, Gaetano; Testa, Gianluca; Cacciatore, Francesco; Bonaduce, Domenico; Abete, Pasquale
Abstract:
Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer), including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of several diseases, but further investigation is needed to evaluate the real efficacy of these therapeutic interventions. The purpose of this paper is to provide a review of literature on this complex topic of ever increasing interest.
Published:
April 26, 2018
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