CD11cHi monocyte-derived macrophages are a major cellular compartment infected by Mycobacterium tuberculosis

During tuberculosis, lung myeloid cells have two opposing roles: they are an intracellular niche occupied by Mycobacterium tuberculosis, and they restrict bacterial replication. Lung myeloid cells from mice infected with yellow-fluorescent protein expressing M. tuberculosis were analyzed by flow cytometry and transcriptional profiling to identify the cell types infected and their response to infection. CD14, CD38, and Abca1 were expressed more highly by infected alveolar macrophages and CD11cHi monocyte-derived cells compared to uninfected cells. CD14, CD38, and Abca1 triple positive (TP) cells had not only the highest infection rates and bacterial loads, but also a strong interferon-gamma signature and nitric oxide synthetase-2 production indicating recognition by T cells. Despite evidence of T cell recognition and appropriate activation, these TP macrophages are a cellular compartment occupied by M. tuberculosis long-term. Defining the niche where M. tuberculosis resists elimination promises to provide insight into why inducing sterilizing immunity is a formidable challenge

Nanocuration workflows: Establishing best practices for identifying, inputting, and sharing data to inform decisions on nanomaterials

There is a critical opportunity in the field of nanoscience to compare and integrate information across diverse fields of study through informatics (i.e., nanoinformatics). This paper is one in a series of articles on the data curation process in nanoinformatics (nanocuration). Other articles in this series discuss key aspects of nanocuration (temporal metadata, data completeness, database integration), while the focus of this article is on the nanocuration workflow, or the process of identifying, inputting, and reviewing nanomaterial data in a data repository. In particular, the article discusses: 1) the rationale and importance of a defined workflow in nanocuration, 2) the influence of organizational goals or purpose on the workflow, 3) established workflow practices in other fields, 4) current workflow practices in nanocuration, 5) key challenges for workflows in emerging fields like nanomaterials, 6) examples to make these challenges more tangible, and 7) recommendations to address the identified challenges. Throughout the article, there is an emphasis on illustrating key concepts and current practices in the field. Data on current practices in the field are from a group of stakeholders active in nanocuration. In general, the development of workflows for nanocuration is nascent, with few individuals formally trained in data curation or utilizing available nanocuration resources (e.g., ISA-TAB-Nano). Additional emphasis on the potential benefits of cultivating nanomaterial data via nanocuration processes (e.g., capability to analyze data from across research groups) and providing nanocuration resources (e.g., training) will likely prove crucial for the wider application of nanocuration workflows in the scientific community

Will seasonally dry tropical forests be sensitive or resistant to future changes in rainfall regimes?

Seasonally dry tropical forests (SDTF) are located in regions with alternating wet and dry seasons, with dry seasons that last several months or more. By the end of the 21st century, climate models predict substantial changes in rainfall regimes across these regions, but little is known about how individuals, species, and communities in SDTF will cope with the hotter, drier conditions predicted by climate models. In this review, we explore different rainfall scenarios that may result in ecological drought in SDTF through the lens of two alternative hypotheses: 1) these forests will be sensitive to drought because they are already limited by water and close to climatic thresholds, or 2) they will be resistant/resilient to intra- and inter-annual changes in rainfall because they are adapted to predictable, seasonal drought. In our review of literature that spans microbial to ecosystem processes, a majority of the available studies suggests that increasing frequency and intensity of droughts in SDTF will likely alter species distributions and ecosystem processes. Though we conclude that SDTF will be sensitive to altered rainfall regimes, many gaps in the literature remain. Future research should focus on geographically comparative studies and well-replicated drought experiments that can provide empirical evidence to improve simulation models used to forecast SDTF responses to future climate change at coarser spatial and temporal scales

Pharmacologic IRE1/XBP1s Activation Confers Targeted ER Proteostasis Reprogramming

Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) is a promising strategy to correct defects in endoplasmic reticulum (ER) proteostasis implicated in diverse diseases. However, no pharmacologic activators of this pathway identified to date are suitable for ER proteostasis remodeling through selective activation of IRE1/XBP1s signaling. Here, we use high-throughput screening to identify non-toxic compounds that induce ER proteostasis remodeling through IRE1/XBP1s activation. We employ transcriptional profiling to stringently confirm that our prioritized compounds selectively activate IRE1/XBP1s signaling without activating other cellular stress-responsive signaling pathways. Furthermore, we demonstrate that our compounds improve ER proteostasis of destabilized variants of amyloid precursor protein (APP) through an IRE1-dependent mechanism and reduce APP-associated mitochondrial toxicity in cellular models. These results establish highly selective IRE1/XBP1s activating compounds that can be widely employed to define the functional importance of IRE1/XBP1s activity for ER proteostasis regulation in the context of health and disease. [Figure not available: see fulltext.]

Ideologies of time: How elite corporate actors engage the future

Our paper deals with how elite corporate actors in a Western capitalist-democratic society conceive of and prepare for the future. Paying attention to how senior officers of ten important Danish companies make sense of the future will help us to identify how particular temporal narratives are ideologically marked. This ideological dimension offers a common sense frame that is structured around a perceived inevitability of capitalism, a market economy as the basic organizational structure of the social and economic order, and an assumption of confident access to the future. Managers envisage their organization?s future and make plans for organizational action in a space where ?business as usual? reigns, and there is little engagement with the future as fundamentally open; as a time-yet-to-come. In using a conceptual lens inspired by the work of Fredric Jameson, we first explore the details of this presentism and a particular colonization of the future, and then linger over small disruptions in the narratives of our interviewees which point to what escapes or jars their common sense frame, explore the implicit meanings they assign to their agency, and also find clues and traces of temporal actions and strategies in their narratives that point to a subtly different engagement with time

The Comparative Oncology Trials Consortium: Using Spontaneously Occurring Cancers in Dogs to Inform the Cancer Drug Development Pathway

Chand Khanna and colleagues describe the work of the Comparative Oncology Trials Consortium (COTC), which provides infrastructure and resources to integrate naturally occurring dog cancer models into the development of new human cancer drugs, devices, and imaging techniques

Which outcomes are most important to measure in patients with COVID-19 and how and when should these be measured? Development of an international standard set of outcomes measures for clinical use in patients with COVID-19: a report of the International Consortium for Health Outcomes Measurement (ICHOM) COVID-19 Working Group.

Objectives: The COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives. Design: A list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance. Results: The outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors. Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research.</p

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin