RNA viruses carry out selective packaging of their genomes in a variety of ways, many involving a genomic packaging signal. The first coronavirus packaging signal was discovered nearly thirty years ...ago, but how it functions remains incompletely understood. This review addresses the current state of knowledge of coronavirus genome packaging, which has mainly been studied in two prototype species, mouse hepatitis virus and transmissible gastroenteritis virus. Despite the progress that has been made in the mapping and characterization of some packaging signals, there is conflicting evidence as to whether the viral nucleocapsid protein or the membrane protein plays the primary role in packaging signal recognition. The different models for the mechanism of genomic RNA packaging that have been prompted by these competing views are described. Also discussed is the recent exciting discovery that selective coronavirus genome packaging is critical for in vivo evasion of the host innate immune response.
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•Selective incorporation of the coronavirus genome into virions is mediated by a cis-acting RNA packaging signal.•Packaging signals vary across different coronavirus genera and lineages.•Different lines of evidence attribute packaging signal recognition to either the nucleocapsid or the membrane protein.•Selective coronavirus genome packaging plays a role in evasion of host innate immunity.
Rock art has long been considered an archaeological artifact reflecting activities from the past, yet it is also a phenomenon with present-day meaning and relevance to both indigenous and ...non-indigenous communities.Relating to Rock Art in the Contemporary Worldchallenges traditional ways of thinking about this highly recognizable form of visual heritage and provides insight into its contemporary significance.One of the most visually striking forms of material culture embedded in landscapes, rock art is ascribed different meanings by diverse groups of people including indigenous peoples, governments, tourism offices, and the general public, all of whom relate to images and sites in unique ways. In this volume, leading scholars from around the globe shift the discourse from a primarily archaeological basis to one that examines the myriad ways that symbolism, meaning, and significance in rock art are being renegotiated in various geographical and cultural settings, from Australia to the British Isles. They also consider how people manage the complex meanings, emotions, and cultural and political practices tied to rock art sites and how these factors impact processes relating to identity construction and reaffirmation today.Richly illustrated and geographically diverse,Relating to Rock Art in the Contemporary Worldconnects archaeology, anthropology, and heritage studies. The book will appeal to students and scholars of archaeology, anthropology, heritage, heritage management, identity studies, art history, indigenous studies, and visual theory, as well as professionals and amateurs who have vested or avocational interests in rock art.Contributors: Agustín Acevedo, Manuel Bea, Jutinach Bowonsachoti, Gemma Boyle, John J. Bradley, Noelene Cole, Inés Domingo, Kurt E. Dongoske, Davida Eisenberg-Degen, Dánae Fiore, Ursula K. Frederick, Kelley Hays-Gilpin, Catherine Namono, George H. Nash, John Norder, Marianna Ocampo, Joshua Schmidt, Duangpond Singhaseni, Benjamin W. Smith, Atthasit Sukkham, Noel Hidalgo Tan, Watinee Tanompolkrang, Luke Taylor, Dagmara Zawadzka
The haematopoietic stem cell (HSC) microenvironment in the bone marrow, termed the niche, ensures haematopoietic homeostasis by controlling the proliferation, self-renewal, differentiation and ...migration of HSCs and progenitor cells at steady state and in response to emergencies and injury. Improved methods for HSC isolation, driven by advances in single-cell and molecular technologies, have led to a better understanding of their behaviour, heterogeneity and lineage fate and of the niche cells and signals that regulate their function. Niche regulatory signals can be in the form of cell-bound or secreted factors and other local physical cues. A combination of technological advances in bone marrow imaging and genetic manipulation of crucial regulatory factors has enabled the identification of several candidate cell types regulating the niche, including both non-haematopoietic (for example, perivascular mesenchymal stem and endothelial cells) and HSC-derived (for example, megakaryocytes, macrophages and regulatory T cells), with better topographical understanding of HSC localization in the bone marrow. Here, we review advances in our understanding of HSC regulation by niches during homeostasis, ageing and cancer, and we discuss their implications for the development of therapies to rejuvenate aged HSCs or niches or to disrupt self-reinforcing malignant niches.
The bone marrow niche has mystified scientists for many years, leading to widespread investigation to shed light into its molecular and cellular composition. Considerable efforts have been devoted ...toward uncovering the regulatory mechanisms of hematopoietic stem cell (HSC) niche maintenance. Recent advances in imaging and genetic manipulation of mouse models have allowed the identification of distinct vascular niches that have been shown to orchestrate the balance between quiescence, proliferation and regeneration of the bone marrow after injury. Here we highlight the recently discovered intrinsic mechanisms, microenvironmental interactions and communication with surrounding cells involved in HSC regulation, during homeostasis and in regeneration after injury and discuss their implications for regenerative therapy.
Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate ...quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2
cells, but not from sinusoidal LepR
cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR
cells, but not NG2
cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.
Steady-state hematopoietic stem cells’ (HSCs) self-renewal and differentiation toward their mature progeny in the adult bone marrow is tightly regulated by cues from the microenvironment. Recent ...insights into the cellular and molecular constituents have uncovered a high level of complexity. Here, we review emerging evidence showing how HSCs and their progeny are regulated by an interdependent network of mesenchymal stromal cells, nerve fibers, the vasculature, and also other hematopoietic cells. Understanding the interaction mechanisms in these intricate niches will provide great opportunities for HSC-related therapies and immune modulation.
The adult bone marrow provides essential niches for hematopoietic stem cell (HSC) maintenance and differentiation, which are not fully understood. Here we review the currently known cellular and molecular components of the niche for hematopoietic stem cells and their progeny, highlight their heterogeneity and interdependency, and discuss some open questions in the field.
•Biomolecular force fields (FFs) have progressed rapidly in the past five years.•Fixed-charge FF accuracy has improved, but challenges remain for complex systems.•Early studies using polarizable FFs ...for complex systems show their promise.•New FF paradigms and parameterization methods are emerging.
Biomolecular force field development has been instrumental in improving the predictive power of molecular simulations over the past four decades. More recently, the era of large quantitative experimental datasets and ubiquitous high performance computing power has enabled rapid progress in the field. In this review we summarize recent developments in all-atom protein, nucleic acid, and small molecule force fields, paying specific attention to developments in parameterization methods and improvements in the representations of nonbonded interactions that are critical for solving the challenging biophysical problems of the present. We also sketch out new avenues for force field development and grand challenge applications for the near future.
Although the function of the autonomic nervous system (ANS) in mediating the flight-or-fight response was recognized decades ago, the crucial role of peripheral innervation in regulating cell ...behavior and response to the microenvironment has only recently emerged. In the hematopoietic system, the ANS regulates stem cell niche homeostasis and regeneration and fine-tunes the inflammatory response. Additionally, emerging data suggest that cancer cells take advantage of innervating neural circuitry to promote their progression. These new discoveries outline the need to redesign therapeutic strategies to target this underappreciated stromal constituent. Here, we review the importance of neural signaling in hematopoietic homeostasis, inflammation, and cancer.
Hanoun et al. review how neural signals regulate hematopoietic homeostasis and the inflammatory response and discuss the impact of the autonomous nervous system in cancer progression.
Western Arnhem Land, in the Top End of Australia’s Northern Territory, has a rich archaeological landscape, ethnographic record and body of rock art that displays an astonishing array of imagery on ...shelter walls and ceilings. While the archaeology goes back to the earliest period of Aboriginal occupation of the continent, the rock art represents some of the richest, most diverse and visually most impressive regional assemblages anywhere in the world. To better understand this multi-dimensional cultural record, The Archaeology of Rock Art in Western Arnhem Land, Australia focuses on the nature and antiquity of the region’s rock art as revealed by archaeological surveys and excavations, and the application of novel analytical methods. This volume also presents new findings by which to rethink how Aboriginal peoples have socially engaged in and with places across western Arnhem Land, from the north to the south, from the plains to the spectacular rocky landscapes of the plateau. The dynamic nature of Arnhem Land rock art is explored and articulated in innovative ways that shed new light on the region’s deep time Aboriginal history.
This paper describes the association between workplace violence and job satisfaction among physicians and nurses in Macau. Convenience sampling was sourced from six health centers under the Macau ...Health Bureau.
This study uses a cross-sectional self-administrative survey. The study used case studies research instruments for workplace violence in the health sector by country (from the ILO, ICN, WHO, PSI), the Minnesota Satisfaction Questionnaire and Perceived Stress Scale. The data collection period spanned from August to December, 2014.
Multiple logistic regression examines levels of intrinsic and extrinsic satisfaction in physicians and nurses and significant correlates affecting their job satisfaction.
A total of 720 (14.9% physicians) participants were recruited. 57.2% of participants reported physical and psychological workplace violence in the preceding year. The most common forms of workplace violence were verbal abuse (53.4%), physical assault (16.1%), bullying / harassment (14.2%), sexual harassment (4.6%) and racial harassment (2.6%). Nurses were at a significantly higher risk of physical assault and verbal abuse compared to physicians. Patients, patients' relatives, and colleagues were the main perpetrators. Worry about WPV, on-call duty and shift work, experience of bullying and verbal abuse and employment sector emerged as significant correlates affecting the intrinsic and extrinsic job satisfaction of physicians and nurses. Frontline staff, aged 30 and 39, coming from an ethnic minority, and perceived stress were significant correlates affecting nurses' job satisfaction.
WPV remains a significant concern in healthcare settings in Macau. Stakeholders should legally enforce a zero-tolerance policy towards WPV within healthcare workplaces. WPV is detrimental to healthcare professionals' mental wellbeing, risking irreversible physical and psychological harm for its victims.
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