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Understanding how phenotypes emerge from genotypes is a foundational goal in biology. As challenging as this task is when considering cellular life, it is further complicated in the case of viruses. During replication, a virus as a discrete entity (the virion) disappears and manifests itself as a metabolic amalgam between the virus and the host (the virocell). Identifying traits that unambiguously constitute a virus’s phenotype is straightforward for the virion, less so for the virocell. Here, we present a framework for categorizing virus phenotypes that encompasses both virion and virocell stages and considers functional and performance traits of viruses in the context of fitness. Such an integrated view of virus phenotype is necessary for comprehensive interpretation of viral genome sequences and will advance our understanding of viral evolution and ecology. Linking genotype to phenotype is particularly challenging for viruses because of their small size, sparse phenotypic data and interlinked viral, host and environmental factors. In this Review, DeLong and colleagues discuss traits of virions and virocells and phenotypic plasticity.

We outline a simple, low-cost design—both scalable and adaptable worldwide—to decontaminate filtering facepiece respirators (FFRs) using ultraviolet bulbs and supplies found in most hardware stores. The setup will help health care workers safely reuse FFRs in light of the shortages during the COVID-19 pandemic., Key Messages Ultraviolet germicidal irradiation (UVGI) systems can be used to decontaminate filtering facepiece respirators that are in short supply during the current COVID-19 pandemic, but are costly and scarce.Custom-built UVGI systems can be easily and affordably created using common items found in hardware stores and within research institutions.Health care workers and administrators should consider this setup as a cost-effective option to combat personal protective equipment (PPE) shortages during the current pandemic.Academic institutions should consider fostering collaborations with local health care institutions to provide idle resources to front line health care workers facing PPE shortages., As the current COVID-19 pandemic illustrates, not all hospitals and other patient care facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Health care workers around the world use filtering facepiece respirators to protect themselves and their patients, yet during this global pandemic they are forced to reuse what are intended to be single-use masks. This poses a significant risk to these health care workers along with the people they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a method to effectively decontaminate these masks between use. However, not all facilities have access to the expensive commercial ultraviolet type C (UV-C) lamp decontamination equipment required for UVGI. UV-C bulbs are sitting idle in biosafety cabinets at universities and research facilities around the world that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. We developed a method to modify existing light fixtures or create custom light fixtures that are compatible with new or existing UV-C bulbs. This system is scalable; can be created for less than US$50, on site and at the point of need; and leverages resources that are currently untapped and sitting unused in public and private research facilities during the pandemic. The freely accessible design can be easily modified for use around the world. Health care facilities can obtain this potentially lifesaving UVGI resource with minimal funds by collaborating with research facilities to obtain the UV-C meters and UV-C bulbs if they are unavailable from other sources. Although mask reuse is not ideal, we must do what we can in emergency situations to protect our health care workers responding to the pandemic and the communities they serve.

COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects.

Understanding how phenotypes emerge from genotypes is a foundational goal in biology. As challenging as this task is when considering cellular life, it is further complicated in the case of viruses. During replication, a virus as a discrete entity (the virion) disappears and manifests itself as a metabolic amalgam between the virus and the host (the virocell). Identifying traits that unambiguously constitute a virus's phenotype is straightforward for the virion, less so for the virocell. Here, we present a framework for categorizing virus phenotypes that encompasses both virion and virocell stages and considers functional and performance traits of viruses in the context of fitness. Such an integrated view of virus phenotype is necessary for comprehensive interpretation of viral genome sequences and will advance our understanding of viral evolution and ecology.

One of the largest challenges facing the field of tissue engineering is the incorporation of a functional vasculature, allowing effective nourishment of graft tissue beyond diffusion length scales. Here, we demonstrate a methodology for inducing the robust self-assembly of endothelial cells into stable three-dimensional perfusable networks on millimeter and centimeter length scales. Utilizing broadly accessible cell strains and reagents, we have rigorously tested a state space of cell densities (0.5–2.0 × 106 cell/mL) and collagen gel densities (2–6 mg/mL) that result in robust vascular network formation. Further, over the range of culture conditions with which we observed robust network formation, we advanced image processing algorithms and quantitative metrics to assess network connectivity, coverage, tortuosity, lumenization, and vessel diameter. These data demonstrate that decreasing collagen density produced more connected networks with higher coverage. Finally, we demonstrated that this methodology results in the formation of perfusable networks, is extensible to arbitrary geometries and centimeter scales, and results in networks that remain stable for 21 days without the need for the co-culture of supporting cells. Given the robustness and accessibility, this system is ideal for studies of tissue-scale biology, as well as future studies on the formation and remodeling of larger engineered graft tissues.

As the current COVID-19 pandemic illustrates, not all hospitals and other facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Healthcare workers around the world utilize N95 masks to protect themselves and their patients, yet during this global pandemic they are forced to re-wear what is intended to be single-use masks. This poses significant risk to these healthcare workers along with the populations they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a way to effectively sterilize these masks between use, however, not all facilities have access to the high cost commercial UV-C lamp sterilization equipment. However, UV-C bulbs are sitting idle in biosafety cabinets (BSCs) at universities and research facilities around the globe that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. Therefore, we have developed a method to modify existing light fixtures, or create custom light fixtures compatible with new or existing common UV-C bulbs. This system is scalable and can be created for less than 50 US dollars, on site, at the point of need, and leverages resources that are currently untapped and sitting unused in public and private research facilities. The freely-accessible design can be easily modified for use around the world. Hospitals can obtain this potentially life-saving UVGI resource with minimal funds, via collaboration between research facilities to obtain the UV-C meters and limited availability UVGI bulbs. While mask reuse is not ideal, we must do what we can in emergency situations to protect our frontline healthcare workers and the communities they serve.

Drug abuse alone has been shown to cause epigenetic changes in brain tissue that have been shown to play roles in addictive behaviors. In conjunction with HIV-1 infection, it can cause epigenetic changes at the viral promoter that can result in altered gene expression, and exacerbate disease progression overall. This review entails an in-depth look at research conducted on the epigenetic effects of three of the most widely abused drugs (cannabinoids, opioids, and cocaine), with a particular focus on the mechanisms through which these drugs interact with HIV-1 infection at the viral promoter. Here we discuss the impact of this interplay on disease progression from the point of view of the nature of gene regulation at the level of chromatin accessibility, chromatin remodeling, and nucleosome repositioning. Given the importance of chromatin remodeling and DNA methylation in controlling the retroviral promoter, and the high susceptibility of the drug abusing population of individuals to HIV infection, it would be beneficial to understand the way in which the host genome is modified and regulated by drugs of abuse.

Recruitment of immune cells such as monocytes/macrophages and dendritic cells (DCs) across the blood-brain barrier (BBB) has been documented in diseases involving neuroinflammation. Neuroinvasion by HIV leads to neurocognitive diseases and alters the permeability of the BBB. Likewise, many HIV patients use drugs of abuse such as morphine, which can further compromise the BBB. While the role of monocytes and macrophages in neuroAIDS is well established, research demonstrating the presence and role of DCs in the CNS during HIV infection has not been developed yet. In this respect, this study explored the presence of DCs in the brain parenchyma of rhesus macaques infected with a neurovirulent form of SIV (SIV mac239 R71/17E) and administered with morphine. Cells positive for DC markers including CD11c (integrin), macDC-SIGN (dendritic cell-specific ICAM-3 grabbing nonintegrin), CD83 (a maturation factor), and HLA-DR (MHC class II) were consistently found in the brain parenchyma of SIV-infected macaques as well as infected macaques on morphine. Control animals did not exhibit any DC presence in their brains. These results provide first evidence of DCs' relevance in NeuroAIDS vis-à-vis drugs of abuse and open new avenues of understanding and investigative HIV-CNS inflictions.

Economics is a key factor for application of organic light emitting diodes (OLED) in general lighting relative to OLED flat panel displays that can handle high cost materials such as indium tin oxide (ITO) or Indium zinc oxide (IZO) as the transparent conducting oxide (TCO) on display glass. However, for OLED lighting to penetrate into general illumination, economics and sustainable materials are critical. The issues with ITO have been documented at the DOE SSL R&D and Manufacturing workshops for the last 5 years and the issue is being exacerbated by export controls from China (one of the major sources of elemental indium). Therefore, ITO is not sustainable because of the fluctuating costs and the United States (US) dependency on other nations such as China. Numerous alternatives to ITO/IZO are being evaluated such as Ag nanoparticles/nanowires, carbon nanotubes, graphene, and other metal oxides. Of these other metal oxides, doped zinc oxide has attracted a lot of attention over the last 10 years. The volume of zinc mined is a factor of 80,000 greater than indium and the US has significant volumes of zinc mined domestically, resulting in the ability for the US to be self-sufficient for this element that can be used in optoelectronic applications. The costs of elemental zinc is over 2 orders of magnitude less than indium, reflecting the relative abundance and availability of the elements. Arkema Inc. and an international primary glass manufacturing company, which is located in the United States, have developed doped zinc oxide technology for solar control windows. The genesis of this DOE SSL project was to determine if doped zinc oxide technology can be taken from the commodity based window market and translate the technology to OLED lighting. Thus, Arkema Inc. sought out experts, Philips Lighting, Pacific Northwest National Laboratories (PNNL) and National Renewable Research Laboratories (NREL), in OLED devices and brought them into the project. This project had a clear focus on economics and the work plan focused both on doped ZnO process and OLED device structure that would be consistent with the new TCO. The team successfully made 6 inch OLEDs with a serial construction. More process development is required to optimize commercial OLED structures. Feasibility was demonstrated on two different light extraction technologies: 1/4 lambda refractive index matching and high-low-high band pass filter. Process development was also completed on the key precursors for the TCO, which are ready for pilot-plant scale-up. Subsequently, Arkema has developed a cost of ownership model that is consistent with DOE SSL R&D Manufacturing targets as outlined in the DOE SSL R&D Manufacturing 2010 report. The overall outcome of this project was the demonstration that doped zinc oxide can be used for OLED devices without a drop-off in performance while gaining the economic and sustainable benefits of a more readily available TCO. The broad impact of this project, is the facilitation of OLED lighting market penetration into general illumination, resulting in significant energy savings, decreased greenhouse emissions, with no environmental impact issues such as mercury found in Fluorescent technology. The primary objective of this project was to develop a commercially viable process for 'Substrates' (Substrate/ undercoat/ TCO topcoat) to be used in production of OLED devices (lamps/luminaries/modules). This project focused on using Arkema's recently developed doped ZnO technology for the Fenestration industry and applying the technology to the OLED lighting industry. The secondary objective was the use of undercoat technology to improve light extraction from the OLED device. In optical fields and window applications, technology has been developed to mitigate reflection losses by selecting appropriate thicknesses and refractive indices of coatings applied either below or above the functional layer of interest. This technology has been proven and implemented in the fenestration industry for more than 15 years. Successful completion of this project would provide doped ZnO coated on inexpensive soda lime glass resulting in a significantly lower cost relative to the current ITO coated Flat Panel Display Glass substrates. Additional benefits will be a more consistent TCO that does not need an activation step with better optical performance. Clearly, this will serve to enhance penetration of OLED technologies into the lighting market.