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1.
The Current Situation of the Tyrolean Iceman.
Zink, AR, Maixner, F
Gerontology. 2019;(6):699-706
Abstract
The Tyrolean Iceman, commonly known as Ötzi, is the world's oldest glacier mummy and one of the best investigated ancient human remains in the world. Since the discovery of the 5,300-year-old Copper Age individual in 1991, in a glacier in the Eastern Italian Alps, a variety of morphological, biochemical, and molecular analyses have been performed that revealed important insights into his origin, his life habits, and the circumstances surrounding his demise. In more recent research, the mummy was subjected to cutting-edge modern research methodologies currently focusing on high-throughput sequence analysis of ancient biomolecules (DNA, proteins, lipids) that are still preserved in the mummified tissues. This application of innovative "-omics" technologies revealed novel insights on the ancestry, disease predisposition, diet, and the presence of pathogens in the glacier mummy. In this review, the most important and actual results of the molecular studies will be highlighted.
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The expanding roles and mechanisms of G protein-mediated presynaptic inhibition.
Zurawski, Z, Yim, YY, Alford, S, Hamm, HE
The Journal of biological chemistry. 2019;(5):1661-1670
Abstract
Throughout the past five decades, tremendous advancements have been made in our understanding of G protein signaling and presynaptic inhibition, many of which were published in the Journal of Biological Chemistry under the tenure of Herb Tabor as Editor-in-Chief. Here, we identify these critical advances, including the formulation of the ternary complex model of G protein-coupled receptor signaling and the discovery of Gβγ as a critical signaling component of the heterotrimeric G protein, along with the nature of presynaptic inhibition and its physiological role. We provide an overview for the discovery and physiological relevance of the two known Gβγ-mediated mechanisms for presynaptic inhibition: first, the action of Gβγ on voltage-gated calcium channels to inhibit calcium influx to the presynaptic active zone and, second, the direct binding of Gβγ to the SNARE complex to displace synaptotagmin downstream of calcium entry, which has been demonstrated to be important in neurons and secretory cells. These two mechanisms act in tandem with each other in a synergistic manner to provide more complete spatiotemporal control over neurotransmitter release.
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3.
Iran in transition.
Danaei, G, Farzadfar, F, Kelishadi, R, Rashidian, A, Rouhani, OM, Ahmadnia, S, Ahmadvand, A, Arabi, M, Ardalan, A, Arhami, M, et al
Lancet (London, England). 2019;(10184):1984-2005
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Abstract
Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries.
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4.
Cytochrome P450 research and The Journal of Biological Chemistry.
Guengerich, FP
The Journal of biological chemistry. 2019;(5):1671-1680
Abstract
In honor of the 100th birthday of Dr. Herbert Tabor, JBC's Editor-in-Chief for 40 years, I will review here JBC's extensive coverage of the field of cytochrome P450 (P450) research. Research on the reactions catalyzed by these enzymes was published in JBC before it was even realized that they were P450s, i.e. they have a "pigment" with an absorption maximum at 450 nm. After the P450 pigment discovery, reported in JBC in 1962, the journal proceeded to publish the methods for measuring P450 activities and many seminal findings. Since then, the P450 field has grown extensively, with significant progress in characterizing these enzymes, including structural features, catalytic mechanisms, regulation, and many other aspects of P450 biochemistry. JBC has been the most influential journal in the P450 field. As with many other research areas, Dr. Tabor deserves a great deal of the credit for significantly advancing this burgeoning and important topic of research.
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Aspergillus fumigatus and Aspergillosis in 2019.
Latgé, JP, Chamilos, G
Clinical microbiology reviews. 2019;(1)
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Abstract
Aspergillus fumigatus is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of A. fumigatus; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against Aspergillus in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of A. fumigatus.
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The 2018 AHA/ACC/Multi-Society Cholesterol guidelines: Looking at past, present and future.
Stone, NJ, Grundy, SM
Progress in cardiovascular diseases. 2019;(5):375-383
Abstract
The authors review more than three decades of progress in providing clinicians and patients with guidance on risk assessment, patient evaluation and cholesterol management. Beginning with the National Cholesterol Education Program's Initial Adult Treatment Panel report, the cholesterol guidelines increasingly reflect the progress made in understanding the benefits of improved lifestyle and nutrition to improve lipid profiles, major risk factors and reduce ASCVD risk. Moreover, they now provide qualitative and quantitative assessment tools to guide appropriate risk reduction LDL-C lowering therapy. Use of the Pooled Cohort Equations to determine Low, Borderline, Intermediate and High 10-year ASCVD risk is now joined by recognition of conditions and biomarkers that enhance ASCVD risk. This personalizes the risk discussion for the patient. An important addition is the selective use of coronary artery calcium (CAC) scoring to reclassify risk in patients at borderline or intermediate risk, but for whom a risk decision regarding statin therapy is uncertain. In secondary prevention, current guidelines provide criteria for determining a "very high" risk group in whom risk is especially high and in whom aggressive LDL-C lowering can be shown to provide increased absolute benefit. Current guidelines provide a comprehensive look at children and adolescents, young adults, elderly, women and issues specific to women through the life course. They provide guidance for those adults at risk due to severe hypercholesterolemia, persistent hypertriglyceridemia after secondary causes have been addressed, those with inflammatory disorders and HIV, those adults with chronic kidney disease, and those affected by issues of race/ethnicity. They conclude with a brief summary of recommendations emphasizing important concepts for providing safety with LDL-C lowering therapy. This combination of best external evidence and clinical expertise from the expert panel should provide a solid foundation for lipid management of patients at risk for or with clinical ASCVD.
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Incidence of antiviral drug resistance markers among human influenza A viruses in the Eastern Mediterranean Region, 2005-2016.
Moasser, E, Moasser, A, Zaraket, H
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2019;:60-66
Abstract
BACKGROUND Two classes of antiviral drugs are available for influenza antiviral therapy: the adamantanes and the neuraminidase inhibitors (NAIs). Due to the emergence of adamantane-resistant variants, the use of these drugs has been largely limited in the world. The NAIs became the drugs of choice for treatment of influenza A infections. However, amino acid substitutions in the NA protein might lead to reduced sensitivity to NAIs. METHODS The frequency and distribution of matrix protein 2 (M2) and neuraminidase (NA) variants which confer resistance to antiviral drugs was investigated in the Eastern Mediterranean Region (EMR) between 2005 and 2016. A total of 314 M2 and 1209 NA protein sequences from influenza A/H1N1, A/H1N1pdm09, A/H3N2, and A/H5N1 available in the public database were analyzed. RESULTS Eighty-six percent of the influenza A viruses detected in the EMR were resistant to adamantanes, among which, H3 strains exhibited the highest (95.32%) level of adamantane resistance. Approximately 98.51% (265/269) of influenza A/H1N1 and H3N2 resistant viruses had the S31N substitution in their M2 sequences. The V27A mutation was the only resistance marker found in A/H5N1 viruses and was detected at a frequency of 7.40% among the investigated viruses. Other resistant mutations L26F, A30T, G34E, and L38F were not detected in any of the variants. We found that 2.81% (n = 34) of the detected NA sequences from influenza A viruses possessed at least one NAI-resistant mutation and the vast majority of resistant viruses 79.41% (27/34) bear the H274Y mutation. The frequency of NAI-resistant viruses was 3.29% (24/729) for the H1N1pdm09, 10.64% (5/47) for the seasonal H1N1, and 4.06% (5/123) for H5N1 viruses. None of the H3N2 viruses analyzed during the study period were resistant to NAIs. CONCLUSION Our study reveals the emergence and spread of antiviral drug resistant influenza A viruses in the EMR and emphasizes the importance of continuous surveillance to maintain the effective use of the current antivirals.
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Chocolate, "Food of the Gods": History, Science, and Human Health.
Montagna, MT, Diella, G, Triggiano, F, Caponio, GR, De Giglio, O, Caggiano, G, Di Ciaula, A, Portincasa, P
International journal of environmental research and public health. 2019;(24)
Abstract
Chocolate is well known for its fine flavor, and its history began in ancient times, when the Maya considered chocolate (a cocoa drink prepared with hot water) the "Food of the Gods". The food industry produces many different types of chocolate: in recent years, dark chocolate, in particular, has gained great popularity. Interest in chocolate has grown, owing to its physiological and potential health effects, such as regulation of blood pressure, insulin levels, vascular functions, oxidation processes, prebiotic effects, glucose homeostasis, and lipid metabolism. However, further translational and epidemiologic studies are needed to confirm available results and to evaluate other possible effects related to the consumption of cocoa and chocolate, verifying in humans the effects hitherto demonstrated only in vitro, and suggesting how best to consume (in terms of dose, mode, and time) chocolate in the daily diet.
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History of the establishment of the Preterm Birth international collaborative (PREBIC).
Hobel, CJ, Dolan, SM, Hindoyan, NA, Zhong, N, Menon, R
Placenta. 2019;:3-20
Abstract
INTRODUCTION The primary aim of PREBIC is to assess the underlying mechanisms and developing strategies for preterm birth (PTB) prevention. MATERIALS AND METHODS We used concept mapping and logic models to track goals. This paper reviews our progress over 13 years using working group activities, research developments, guest speakers, and publications. RESULTS Using interactions between genetics, environment, and behaviors we identified complex interactions between biological systems. PREBIC determined that epidemiology and biomarkers should be an initial focus. In 2005, we initiated presentations by young investigators, yearly satellite meetings, working groups including nutrition and inflammation, assessment of clinical trials, and accepted an invitation by the WHO to begin yearly meetings in Geneva. DISCUSSION PREBIC used epidemiology to identify PTB factors and complex pathways. Candidate genes are associated with the environment, behavior (stress), obesity, inflammation and insulin resistance. Epigenetic changes and production of proteins can be used as biomarkers to define risk. Subsequently, we found risk factors for PTB that were also associated with the risk of cardiovascular disease (CVD) of the mother. Tanz et al. (2017) found that a history of PTB is independently predictive of CVD later in life and suggested that a modest proportion of PTB-CVD association was accounted by CVD risk factors, many of which have been identified in this paper. CONCLUSION Our findings support a relationship between genes, environment, behaviors and risk of CVD in women. The next several years must assess which factors are modifiable early in life and before pregnancy to prevent PTB.
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Mitochondrial DNA, a Powerful Tool to Decipher Ancient Human Civilization from Domestication to Music, and to Uncover Historical Murder Cases.
Merheb, M, Matar, R, Hodeify, R, Siddiqui, SS, Vazhappilly, CG, Marton, J, Azharuddin, S, Al Zouabi, H
Cells. 2019;(5)
Abstract
Mitochondria are unique organelles carrying their own genetic material, independent from that in the nucleus. This review will discuss the nature of mitochondrial DNA (mtDNA) and its levels in the cell, which are the key elements to consider when trying to achieve molecular identification in ancient and degraded samples. mtDNA sequence analysis has been appropriately validated and is a consistent molecular target for the examination of biological evidence encountered in forensic cases-and profiling, in certain conditions-especially for burnt bodies and degraded samples of all types. Exceptional cases and samples will be discussed in this review, such as mtDNA from leather in Beethoven's grand piano, mtDNA in mummies, and solving famous historical criminal cases. In addition, this review will be discussing the use of ancient mtDNA to understand past human diet, to trace historical civilizations and ancient trade routes, and to uncover geographical domestication origins and lineage relationships. In each topic, we will present the power of mtDNA and how, in many cases, no nuclear DNA was left, leaving mitochondrial DNA analysis as a powerful alternative. Exploring this powerful tool further will be extremely useful to modern science and researchers, due to its capabilities in providing us with previously unattainable knowledge.