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إدارة الأزمات في زمن الأوبئة : مقالات لـ 56 عالما في الإدارة
يضم هذا الكتاب خلاصة تجارب وعصارة أفكار 56 عالما، هم من أبرز علماء الإدارة في الصين، وقد حملوا على عاتقهم مسؤولية قيادة المؤسسات الصينية لسنوات عديدة، وهو كتاب مرجعي لكل المؤسسات على المستوى العالمي والتي إن حدث لها ضرر في فترات الأزمات أو الأوبئة، فلن يتوقف هذا الضرر عند ملاكها أو المنتفعين منها، بل سيمتد أثره إلى قطاعات عريضة من العمالة، وسيضرب القوة الإنتاجية ولا سيما الصادرات والواردات وغيرها من الموارد. ومن ثم فهم محاربون على الخطوط الأولى، مثلهم مثل الأطباء في أزمة انتشار فيروس كورونا المستجد، وإن كان مجال تخصص كل مختلفا منهم عن الآخر، ففريق منهم ينقذ حياة الناس، بينما الفريق الآخر ينقذ أقواتهم. ولغة الكتاب لغة سهلة وبسيطة، تنطلق أفكاره من مواقف عامة وليست من مواقف خاصة محددة، ومن هنا تعد أفكاره صالحة للتطبيق على المؤسسات الصغيرة والمتوسطة في كل مكان، والتي أصبح لزاما عليها أن تلجأ للابتكار والإبداع إن أرادت الاستمرار على قيد الحياة، وبات عليها أن تبحث وسط ركام الأزمة عن الإيجابيات التي يمكن أن تهب لها حياة جديدة وسبلا مبتكرة للخلاص.
Book
Monocyte progenitors give rise to multinucleated giant cells
The immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche.
Multinucleated giant cells characterize granuloma formation in mycobacterial infections. Here the authors identify monocyte precursors with distinct immunological and metabolic properties as a source of the granuloma multinucleated giant cell compartment.
Journal Article
Classical Activation of Macrophages Leads to Lipid Droplet Formation Without de novo Fatty Acid Synthesis
Altered lipid metabolism in macrophages is associated with various important inflammatory conditions. Although lipid metabolism is an important target for therapeutic intervention, the metabolic requirement involved in lipid accumulation during pro-inflammatory activation of macrophages remains incompletely characterized. We show here that macrophage activation with IFNγ results in increased aerobic glycolysis, iNOS-dependent inhibition of respiration, and accumulation of triacylglycerol. Surprisingly, metabolite tracing with
C-labeled glucose revealed that the glucose contributed to the glycerol groups in triacylglycerol (TAG), rather than to
synthesis of fatty acids. This is in stark contrast to the otherwise similar metabolism of cancer cells, and previous results obtained in activated macrophages and dendritic cells. Our results establish a novel metabolic pathway whereby glucose provides glycerol to the headgroup of TAG during classical macrophage activation.
Journal Article
Lipidomics and genomics of Mycobacterium tuberculosis reveal lineage‐specific trends in mycolic acid biosynthesis
Mycolic acids (MAs) are α‐alkyl, β‐hydroxy long‐chain fatty acids found in abundance in the cell envelope of the Mycobacterium tuberculosis complex (MTBC). MAs form an efficient permeability barrier, modulate host innate immune responses, and are the targets of several anti‐tuberculosis drugs. Using mass spectrometry, we measured the relative abundance of 80 MA species across 36 clinical isolates of MTBC covering four major phylogenetic lineages. We found significant variations in the MA patterns between different MTBC strains and lineages. MA patterns of “ancient” lineages contrasted those from “modern” lineages, with a lower representation of alpha‐mycolates among Lineage 6 strains and an inversion of the methoxy: keto‐mycolates ratio in Lineage 1 strains. By interrogating the whole genome sequences of these MTBC strains, we identified relevant single‐nucleotide polymorphisms that may sustain the lineage‐specific MA patterns. Our results show that the strain genetic background influences MA metabolism and suggests that strain diversity should be considered in the development of new anti‐tuberculosis drugs that target MA synthesis. Mycolic acids are involved in Mycobacterium tuberculosis pathogenicity and its metabolism is targeted by several current anti‐tuberculosis drugs. Functional single‐nucleotide polymorphisms support our observation that phylogenetic lineages of Mycobacterium tuberculosis complex MTBC differ in their mycolic acid content. Inherent mycolic acid metabolism differences may account for lineage‐specific variability in drug sensitivity and resistance development propensity.
Journal Article
Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries
Trypanosomatids are parasitic protozoa which cause a spectrum of diseases, including trypanosomiasis and leishmaniasis, affecting millions of humans and animals worldwide. The surface of most protozoan parasites is heavily decorated with lipids and lipid-anchored molecules, forming protective barriers and acting as virulence factors during infection. Sphingolipids (SP) are major components of eukaryotic biomembranes, which play important roles in structural integrity, energy homeostasis and signaling. However, the precise chemical composition of SP in pathogens as well as their biochemical pathways and functions remain poorly characterized. Here, we present the first system-scale analyses of SP found in a panel of 7 trypanosomatids, including
Leishmania donovani
,
Trypanosoma brucei
and
Trypanosoma cruzi
. We characterized the structure of aminoethylphosphonate-containing ceramides, which are found exclusively in stercorarian
Trypanosoma
. Employing the sensitive and semi-quantitative sphingolipidomics approach that we developed, we report the detection of over 300 molecular species of SP, and identified unique metabolic signatures which serve as discriminants of the pathogens based on their taxonomy and lifecycle stages. The deep sphingolipidome presented here is an important biochemical and technological resource for future works to dissect SP metabolism and functions in these medically and agriculturally relevant systems.
Journal Article
Metabolic Versatility of Mycobacterium tuberculosis during Infection and Dormancy
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a highly successful intracellular pathogen with the ability to withstand harsh conditions and reside long-term within its host. In the dormant and persistent states, the bacterium tunes its metabolism and is able to resist the actions of antibiotics. One of the main strategies Mtb adopts is through its metabolic versatility—it is able to cometabolize a variety of essential nutrients and direct these nutrients simultaneously to multiple metabolic pathways to facilitate the infection of the host. Mtb further undergo extensive remodeling of its metabolic pathways in response to stress and dormancy. In recent years, advancement in systems biology and its applications have contributed substantially to a more coherent view on the intricate metabolic networks of Mtb. With a more refined appreciation of the roles of metabolism in mycobacterial infection and drug resistance, and the success of drugs targeting metabolism, there is growing interest in further development of anti-TB therapies that target metabolism, including lipid metabolism and oxidative phosphorylation. Here, we will review current knowledge revolving around the versatility of Mtb in remodeling its metabolism during infection and dormancy, with a focus on central carbon metabolism and lipid metabolism.
Journal Article
Macrophage–Bacteria Interactions—A Lipid-Centric Relationship
Macrophages are professional phagocytes at the front line of immune defenses against foreign bodies and microbial pathogens. Various bacteria, which are responsible for deadly diseases including tuberculosis and salmonellosis, are capable of hijacking this important immune cell type and thrive intracellularly, either in the cytoplasm or in specialized vacuoles. Tight regulation of cellular metabolism is critical in shaping the macrophage polarization states and immune functions. Lipids, besides being the bulk component of biological membranes, serve as energy sources as well as signaling molecules during infection and inflammation. With the advent of systems-scale analyses of genes, transcripts, proteins, and metabolites, in combination with classical biology, it is increasingly evident that macrophages undergo extensive lipid remodeling during activation and infection. Each bacterium species has evolved its own tactics to manipulate host metabolism toward its own advantage. Furthermore, modulation of host lipid metabolism affects disease susceptibility and outcome of infections, highlighting the critical roles of lipids in infectious diseases. Here, we will review the emerging roles of lipids in the complex host-pathogen relationship and discuss recent methodologies employed to probe these versatile metabolites during the infection process. An improved understanding of the lipid-centric nature of infections can lead to the identification of the Achilles' heel of the pathogens and host-directed targets for therapeutic interventions. Currently, lipid-moderating drugs are clinically available for a range of non-communicable diseases, which we anticipate can potentially be tapped into for various infections.
Journal Article
microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data
microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms’ role in ecology and human health.
microbeMASST is a tool to associate known and unknown metabolites to microbial producers leveraging untargeted metabolomics data.
Journal Article
The Health for Life in Singapore (HELIOS) Study: delivering precision medicine research for Asian populations
Asian people are under-represented in population-based, clinical, and genomic research. To address this gap, we have initiated the Health for Life in Singapore (HELIOS) longitudinal cohort study, comprising comprehensive behavioural, phenotypic, and genomic measurements from 10,004 Asian men and women of Chinese, Indian or Malay background. Phenotyping has been carried out using validated approaches, that are internationally interoperable. Health record linkage enriches both baseline phenotyping and evaluation of prospective outcomes. The integrated multi-omics data include whole-genome and RNA sequencing, quantification of DNA methylation, and metabolomic profiling. Our data reveal extensive lifestyle, physiological, genomic, and molecular diversity between the distinct Asian ethnic groups, and the biological interconnectivity between functional layers. This includes characterisation of divergent patterns of genome regulation between Asian individuals, that correlate with differences in educational attainment, dietary quality, and adiposity, and which overlap transcription factors and DNA methylation sites linked to the development of diabetes and other chronic diseases. Our unique HELIOS Asian Precision Medicine cohort study represents a state-of-the-art platform to enable biomedical researchers to understand the aetiology and pathogenesis of diverse disease outcomes in Asia, and to generate insights that have the potential to improve health outcomes for Asian populations globally.
With rich, multi-layered baseline data and long-term follow-up through linkage, the HELIOS Study provides a resource to investigate the behavioural, environmental, genomic, and molecular factors impacting health in Asian populations.
Journal Article
A lipidomics roadmap: from basic research to societal challenges
Lipidomics, a rapidly evolving discipline at the interface of biology and analytical chemistry, seeks to comprehensively characterize the lipid composition of biological systems. Driven by advances in mass spectrometry, chromatography and computational analysis, lipidomics has enabled the high-resolution mapping of lipid networks and their functional dynamics across molecular, cellular and organismal scales. In biomedical research, lipidomics is emerging as a powerful platform for biomarker discovery, enabling early diagnosis, prognosis, and therapeutic monitoring of cancer, metabolic, and neurodegenerative diseases. The field is also reshaping drug discovery by uncovering lipid-mediated pathways, identifying novel therapeutic targets, and refining assessments of drug efficacy and safety. Beyond medicine, lipidomic analyses are redefining food and nutrition science by elucidating how dietary lipids influence metabolic health and disease risk. In parallel, environmental and ecological lipidomics are emerging as powerful frameworks for assessing ecosystem health, tracking the impact of pollutants and exploring the biological consequences of climate change. Such approaches are also informing the discovery of sustainable lipid resources and the development of novel biotechnological and agricultural innovations. With its rapidly expanding analytical repertoire and cross-disciplinary relevance, lipidomics is poised to make substantial contributions to both fundamental biology and applied science. This Perspective aims to synthesise the current state of the field, delineate major analytical and conceptual challenges, and outline future directions for translating lipidomic knowledge into tangible societal and environmental benefits.
Lipidomics, a rapidly evolving field at the interface of biology and analytical chemistry, enables comprehensive analysis of lipids in biological systems. This Perspective outlines advances, challenges, and future directions, highlighting applications of lipidomics in basic and translational science.
Journal Article