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Key Points The African trypanosome Trypanosoma brucei is a unicellular pathogen that causes lethal sleeping sickness in humans, which is a devastating and neglected tropical disease that is endemic to vast regions of Africa. T. brucei also infects wild and domestic livestock, which limits sustainable development, and it is thus considered to be both a cause and consequence of poverty. T. brucei has a single flagellum that is present throughout the parasite and its life cycle. The flagellum has conserved and unique features. It emerges from a membrane invagination at the posterior end of the cell and remains attached to the cell body for most of its length. The flagellum contains cytoskeletal structures, which are ensheathed by a specialized flagellar membrane that interfaces with the external environment and that has a protein and lipid composition that is distinct from the rest of the cell surface. The T. brucei flagellum has multiple functions and is essential for parasite motility, viability, transmission and pathogenesis. Flagellum-mediated motility is powered by the axoneme, which is a biological machine that converts dynein motor structural changes into flagellum beating and parasite propulsion. T. brucei motility is crucial for movement through host tissues and provides a surprising immune-evasion mechanism. In addition to motility, the T. brucei flagellum is an important morphogenetic hub that controls cell shape and size, directs organelle segregation and governs cell division. These functions are modulated during developmental transitions of the parasite and are achieved by the direct or indirect physical connections of the flagellum to other cellular elements. The flagellum is a crucial host–pathogen interface that has important roles in parasite transmission and virulence. Flagellar proteins mediate attachment to host tissues, carry out uptake of host growth factors and promote parasite survival by inhibiting host immunity. T. brucei is an excellent model system to study the biology of the highly conserved eukaryotic flagellum and offers valuable insights into how flagella assemble, move and sense the environment. Continued studies of the T.brucei flagellum hold the promise of having a great impact on human health, as human flagella are paramount in human development and physiology. In addition, the flagella of many human pathogens are salient but unexplained structures that await further study. The protozoan parasite Trypanosoma brucei has a single flagellum that is present in all of its different developmental stages. In this Review, Langousis and Hill discuss the structural and functional features of the flagellum and highlight its central role in the virulence and transmission of this important human pathogen. Trypanosoma brucei is a pathogenic unicellular eukaryote that infects humans and other mammals in sub-Saharan Africa. A central feature of trypanosome biology is the single flagellum of the parasite, which is an essential and multifunctional organelle that facilitates cell propulsion, controls cell morphogenesis and directs cytokinesis. Moreover, the flagellar membrane is a specialized subdomain of the cell surface that mediates attachment to host tissues and harbours multiple virulence factors. In this Review, we discuss the structure, assembly and function of the trypanosome flagellum, including canonical roles in cell motility as well as novel and emerging roles in cell morphogenesis and host–parasite interactions.

\"This textbook provides a comprehensive overview of the human-computer interface in clear, non-technical language, making it an ideal introduction for students of both psychology and computer science. Covering the past, present, and future developments in technology and psychology, it combines cutting-edge academic research with engaging illustrations and examples that show students how the material relates to their lives. Topics addressed include: human factors of input devices, and the basics of sensation and perception; memory and cognitive issues of users navigating their way through interfaces; communication via programming languages and natural speech interaction; cyberpathologies such as techno-stress and Internet addiction disorders; and challenges surrounding automation and artificial intelligence. This thoroughly updated second edition features new chapters on virtual reality and cybersecurity; expanded coverage of social media, mobile computing, e-learning, and video games; and end-of-chapter review questions that ensure students have mastered key objectives\"-- Provided by publisher.

Key Points There is increasing evidence that the aberrant activity of numerous members of the Ras superfamily of small GTPases contributes to cancer growth, invasion and metastasis. Unlike the frequent direct mutational activation of the three Ras proteins (which occurs in ∼33% of human cancers), other Ras superfamily GTPases are deregulated by indirect mechanisms, commonly involving the altered expression or activity of their regulatory proteins. Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that control the GDP–GTP cycling of specific members of the Ras superfamily have been shown to contribute to cancer by either promoting or suppressing tumour progression and growth. GEFs and GAPs are deregulated in cancer by somatic mutation, changes in gene expression and through post-translational mechanisms owing to aberrant signalling caused by alterations in upstream oncogene or tumour suppressor function. Although GEFs and GAPs are not considered classically druggable targets, there is growing evidence that supports the feasibility of targeting them. For example, nature has provided examples (such as brefeldin A) that provide proof-of-principle of GEF and GAP druggability. The multi-domain structures of GEFs and GAPs contribute to their regulation by diverse signalling mechanisms and might also identify therapeutic approaches for pharmacological regulation of GEF and GAP activity in cancer. Certain members of the Ras superfamily of small GTPases are commonly deregulated in human cancers, but how can we target them? This Review explores the association of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that regulate GTPases with cancer and discusses whether they can be effectively targeted therapeutically. There is now considerable and increasing evidence for a causal role for aberrant activity of the Ras superfamily of small GTPases in human cancers. These GTPases function as GDP–GTP-regulated binary switches that control many fundamental cellular processes. A common mechanism of GTPase deregulation in cancer is the deregulated expression and/or activity of their regulatory proteins, guanine nucleotide exchange factors (GEFs) that promote formation of the active GTP-bound state and GTPase-activating proteins (GAPs) that return the GTPase to its GDP-bound inactive state. In this Review, we assess the association of GEFs and GAPs with cancer and their druggability for cancer therapeutics.

Background Migrant and refugee populations are disproportionately affected by the housing crises reportedly impacting high-income countries around the globe. However, the health implications of housing inequalities within these communities and contexts remain relatively understudied. This review aimed to synthesise the evidence on housing and health inequalities prevalent among migrant and refugee populations in high-income countries, and to identify the pathways linking housing inequalities and health outcomes. Methods This systematic review employed the Joanna Briggs Institute (JBI) methodology for mixed-methods systematic reviews using a convergent integrated approach to synthesis and integration. Electronic database searches were conducted using Medline (OVID), Web of Science (ISI), Embase (OVID), PsycInfo (OVID), Scopus, and CINAHL (EBSCO), supplemented by grey literature searches on Google Scholar, MedNar, and WHOLIS. Eligible studies included quantitative, qualitative, and mixed methods designs focused on understanding how housing inequalities are associated with physical and mental health outcomes. Results A total of 65 studies published between 1995 and 2024 were included in this review, comprising 38 quantitative and 27 qualitative studies. Substandard housing conditions, such as overcrowding and poor ventilation, were consistently associated with adverse physical and mental health outcomes, including respiratory illnesses and experiences of anxiety and depression. The type of housing tenure also impacted both physical and mental health, specifically living in inadequate rental housing as opposed to self-owned homes, was linked with poorer physical health and increased risk of mental health issues. Similarly, housing insecurity stemming from unstable housing situations and insecure tenancy, as well as neighbourhood conditions such as safety concerns and living in deprived neighbourhoods, led to the exacerbation of both physical and mental health issues. Furthermore, housing affordability challenges and decreased housing satisfaction were linked with poor mental health outcomes such as experiences of depression and psychological distress. Conclusions This review highlights the critical role of housing as a social determinant of health and wellbeing for migrant and refugee populations in high-income countries, along with highlighting the potential pathways through which housing inequalities impact physical and mental health outcomes. Ensuring access to adequate, affordable, and secure housing, while also improving neighbourhood conditions, is essential for improving the health and wellbeing of migrant and refugee populations.

Dialogic theory and engagement hold great potential as frameworks for thinking about how social media can facilitate public discussions about social issues. Of course, having the potential for dialogue is very different than finding actual instances of dialogic engagement. This article explores the philosophical and technical features of dialogue that need to be present for social media to be used dialogically. Through the metaphor of “architecture,” this article reimagines dialogic communication through social media. We introduce four design frameworks including user expectations, engagement, content curation, and sustainment that may facilitate dialogic engagement for fostering social change.

هذا الكتاب هو دراسة للمبادئ التشغيلية التي توجه كل من القرارات الإدارية في مؤسسة الرعاية الصحية الأسطورية \"مايو كلينيك\" وفيه يشدد المؤلفان على القضايا التالية تبيان كيف تطورت علامة تجارية خدماتية عظيمة من القيم الرئيسية التي تغذيها وتحميها واستنباط دروس إدارية وعملية مفيدة يمكن تطبيقها خارج قطاع الرعاية الصحية وتوضيح فوائد تجميع المواهب وتشجيع العمل الجماعي ضمن فرق العمل وربط الأحداث والمفاهيم التاريخية وبين مايو كلينيك كما تعمل في يومنا هذا ومشاركة العاملين والمرضى على السواء في قصصهم وأخبارهم الملهمة.

Many lines of evidence, including epidemiologic data and extensive clinical and experimental studies, indicate that early life events play a powerful role in influencing later susceptibility to certain chronic diseases. This review synthesizes evidence from several disciplines to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation. This review synthesizes evidence from several disciplines to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation. A long latency period between an environmental trigger and the onset of subsequent disease is widely recognized in the etiology of certain cancers, yet this phenomenon is not generally considered in the etiology of other conditions such as cardiovascular disease, metabolic disease, or osteoporosis. However, many lines of evidence, including epidemiologic data and data from extensive clinical and experimental studies, indicate that early life events play a powerful role in influencing later susceptibility to certain chronic diseases. An increased understanding of developmental plasticity (defined as the ability of an organism to develop in various ways, depending on the particular environment . . .