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Model systems play a crucial role in biological and biomedical research, especially in the search for new treatments for challenging diseases such as glioblastoma multiforme (GBM). Organoids are 3D in vitro multicellular “middle-ground” model systems that recapitulate highly organized and heterogeneous in vivo organ-like systems, often through stem cell differentiation. Incorporating Matrigel™ or other exogenous extracellular matrices (ECMs) that do not naturally occur in the human body is common practice for organoid generation, ignoring the role of dynamic reciprocity between the cells and the ECM in tissue development. In this study, we describe a method to develop GBM organoids (GBOs) from cells without the need for exogenous ECM encapsulation and without cell culture media changes to produce stable tissue-like organoids that reach a 4 mm diameter in as little as 6 weeks. We observed a transition from homogenous cell populations to tissue-like structures when GBOs were larger than 1 mm in diameter. Transcriptomic analysis revealed that the greatest gene expression changes occurred when GBOs were 2 mm in diameter, with collagen VI as the most upregulated ECM-related gene. Quantitative and histochemical assessments further supported native ECM synthesis with significantly higher levels of glycosaminoglycans and collagen in GBOs compared with spheroids. To our knowledge, this study presents the first reproducibly large GBOs with natively produced ECMs. Organoids with natively synthesized ECMs promise to eliminate artifacts and variability from aged, homogeneic, or xenogeneic scaffolds and to provide insights for ECM-targeted drug development. 

Recent evidence has documented associations between higher levels of inflammation and social approach behaviors toward close others in laboratory-based tasks. Yet it is unknown if this translates to interactions with close others in daily life. Given that momentary experiences of social connection have both relational and health consequences, this is a critical gap in our knowledge. To address the association between inflammation and momentary social connection experiences in close relationships, 55 participants provided blood samples on two consecutive days, which were assayed for circulating levels of the inflammatory marker interleukin-6 (IL-6). After providing the first blood sample, participants received the annual influenza vaccine as a mild inflammatory challenge. Participants also reported on cognitive, affective, and behavioral indicators of social connection with a specific close other multiple times across the two study days. Results indicated that levels of IL-6 were positively associated with temporally-proximal indicators of momentary social connection with a close other. Specifically, higher levels of IL-6 were associated with greater feelings of comfort from the close other, greater desire to be near them, and higher reported relationship quality. Greater IL-6 reactivity to the vaccine was only associated with increased reported relationship quality. These data add to the existing literature suggesting that higher levels of IL-6 may motivate social approach toward a close other, extending evidence to now include momentary social connection experiences in daily life. 

Aluminum monochloride (AlCl) has been proposed as a promising candidate for laser cooling to ultracold temperatures, and recent spectroscopy results support this prediction. It is challenging to produce large numbers of AlCl molecules because it is a highly reactive open-shell molecule and must be generated in situ . Here we show that pulsed-laser ablation of stable, non-toxic mixtures of Al with alkali or alkaline earth chlorides, denoted XCl n , can provide a robust and reliable source of cold AlCl molecules. Both the chemical identity of XCl n and the Al : XCl n molar ratio are varied, and the yield of AlCl is monitored using absorption spectroscopy in a cryogenic gas. For KCl, the production of Al and K atoms was also monitored. We model the AlCl production in the limits of nonequilibrium recombination dominated by first-encounter events. The non-equilibrium model is in agreement with the data and also reproduces the observed trend with different XCl n precursors. We find that AlCl production is limited by the solid-state densities of Al and Cl atoms and the recondensation of Al atoms in the ablation plume. We suggest future directions for optimizing the production of cold AlCl molecules using laser ablation. 

Biodiversity is in crisis, and insects are no exception. To understand insect population and community trends globally, it is necessary to identify and synthesize diverse datasets representing different taxa, regions, and habitats. The relevant literature is, however, vast and challenging to aggregate. The Entomological Global Evidence Map (EntoGEM) project is a systematic effort to search for and catalogue studies with long-term data that can be used to understand changes in insect abundance and diversity. Here, we present the overall EntoGEM framework and results of the first completed subproject of the systematic map, which compiled sources of information about changes in dragonfly and damselfly (Odonata) occurrence, abundance, biomass, distribution, and diversity. We identified 45 multi-year odonate datasets, including 10 studies with data that span more than 10 years. If data from each study could be gathered or extracted, these studies could contribute to analyses of long-term population trends of this important group of indicator insects. The methods developed to support the EntoGEM project, and its framework for synthesizing a vast literature, have the potential to be applied not only to other broad topics in ecology and conservation, but also to other areas of research where data are widely distributed. 

Diabetes is one of the leading causes of death globally. Currently, the donor pancreas is the only source of human islets, placing extreme constraints on supply. Hence, it is imperative to develop renewable islets for diabetes research and treatment. To date, extensive efforts have been made to derive insulin-secreting cells from human pluripotent stem cells with substantial success. However, the in vitro generation of functional islet organoids remains a challenge due in part to our poor understanding of the signaling molecules indispensable for controlling differentiation pathways towards the self-assembly of functional islets from stem cells. Since this process relies on a variety of signaling molecules to guide the differentiation pathways, as well as the culture microenvironments that mimic in vivo physiological conditions, this review highlights extracellular matrix proteins, growth factors, signaling molecules, and microenvironments facilitating the generation of biologically functional pancreatic endocrine cells from human pluripotent stem cells. Signaling pathways involved in stepwise differentiation that guide the progression of stem cells into the endocrine lineage are also discussed. The development of protocols enabling the generation of islet organoids with hormone release capacities equivalent to native adult islets for clinical applications, disease modeling, and diabetes research are anticipated. 

Abstract The western United States (US) is a hotspot for snow drought. The Oregon Cascade Range is highly sensitive to warming and as a result has experienced the largest mountain snowpack losses in the western US since the mid‐20th century, including a record‐breaking snow drought in 2014–2015 that culminated in a state of emergency. While Oregon Cascade snowpacks serve as the state's primary water supply, short instrumental records limit water managers' ability to fully constrain long‐term natural snowpack variability prior to the influence of ongoing and projected anthropogenic climate change. Here, we use annually‐resolved tree‐ring records to develop the first multi‐century reconstruction of Oregon Cascade April 1st Snow Water Equivalent (SWE). The model explains 58% of observed snowpack variability and extends back to 1688 AD, nearly quintupling the length of the existing snowpack record. Our reconstruction suggests that only one other multiyear event in the last three centuries was as severe as the 2014–2015 snow drought. The 2015 event alone was more severe than nearly any other year in over three centuries. Extreme low‐to‐high snowpack “whiplash” transitions are a consistent feature throughout the reconstructed record. Multi‐decadal intervals of persistent below‐the‐mean peak SWE are prominent features of pre‐instrumental snowpack variability, but are generally absent from the instrumental period and likely not fully accounted for in modern water management. In the face of projected snow drought intensification and warming, our findings motivate adaptive management strategies that address declining snowpack and increasingly variable precipitation regimes.