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Abstract Energy crops for biofuel production, especially switchgrass (Panicum virgatum), are of interest from a climate change perspective. Here, we use outputs from a crop growth model and life cycle assessment (LCA) to examine the global warming intensity (GWI; g CO2 MJ−1) and greenhouse gas (GHG) mitigation potential (Mg CO2 year−1) of biofuel systems based on a spatially explicit analysis of switchgrass grown on marginal land (abandoned former cropland) in Michigan, USA. We find that marginal lands in Michigan can annually produce over 0.57 hm3 of liquid biofuel derived from nitrogen‐fertilized switchgrass, mitigating 1.2–1.5 Tg of CO2 year−1. About 96% of these biofuels can meet the Renewable Fuel Standard (60% reduction in lifecycle GHG emissions compared with conventional gasoline; GWI ≤37.2 g CO2 MJ−1). Furthermore, 73%–75% of these biofuels are carbon‐negative (GWI less than zero) due to enhanced soil organic carbon (SOC) sequestration. However, simulations indicate that SOC levels would fail to increase and even decrease on the 11% of lands where SOC stocks >>200 Mg C ha−1, leading to carbon intensities greater than gasoline. Results highlight the strong climate mitigation potential of switchgrass grown on marginal lands as well as the needs to avoid carbon rich soils such as histosols and wetlands and to ensure that productivity will be sufficient to provide net mitigation.

Abstract Cell migration is a pivotal biological process, whose dysregulation is found in many diseases including inflammation and cancer. Advances in microscopy technologies allow now to study cell migration in vitro, within engineered microenvironments that resemble in vivo conditions. However, to capture an entire 3D migration chamber for extended periods of time and with high temporal resolution, images are generally acquired with low resolution, which poses a challenge for data analysis. Indeed, cell detection and tracking are hampered due to the large pixel size (i.e., cell diameter down to 2 pixels), the possible low signal-to-noise ratio, and distortions in the cell shape due to changes in the z-axis position. Although fluorescent staining can be used to facilitate cell detection, it may alter cell behavior and it may suffer from fluorescence loss over time (photobleaching). Here we describe a protocol that employs an established deep learning method (U-NET), to specifically convert transmitted light (TL) signal from unlabeled cells imaged with low resolution to a fluorescent-like signal (class 1 probability). We demonstrate its application to study cancer cell migration, obtaining a significant improvement in tracking accuracy, while not suffering from photobleaching. This is reflected in the possibility of tracking cells for three-fold longer periods of time. To facilitate the application of the protocol we provide WID-U, an open-source plugin for FIJI and Imaris imaging software, the training dataset used in this paper, and the code to train the network for custom experimental settings.

Atypical chemokine receptors (ACKRs) scavenge chemokines and can contribute to gradient formation by binding, internalizing, and delivering chemokines for lysosomal degradation. ACKRs do not couple to G-proteins and fail to induce typical signaling induced by chemokine receptors. ACKR3, which binds and scavenges CXCL12 and CXCL11, is known to be expressed in vascular endothelium, where it has immediate access to circulating chemokines. ACKR4, which binds and scavenges CCL19, CCL20, CCL21, CCL22, and CCL25, has also been detected in lymphatic and blood vessels of secondary lymphoid organs, where it clears chemokines to facilitate cell migration. Recently, GPR182, a novel ACKR-like scavenger receptor, has been identified and partially deorphanized. Multiple studies point towards the potential coexpression of these 3 ACKRs, which all interact with homeostatic chemokines, in defined cellular microenvironments of several organs. However, an extensive map of ACKR3, ACKR4, and GPR182 expression in mice has been missing. In order to reliably detect ACKR expression and coexpression, in the absence of specific anti-ACKR antibodies, we generated fluorescent reporter mice, ACKR3GFP/+, ACKR4GFP/+, GPR182mCherry/+, and engineered fluorescently labeled ACKR-selective chimeric chemokines for in vivo uptake. Our study on young healthy mice revealed unique and common expression patterns of ACKRs in primary and secondary lymphoid organs, small intestine, colon, liver, and kidney. Furthermore, using chimeric chemokines, we were able to detect distinct zonal expression and activity of ACKR4 and GPR182 in the liver, which suggests their cooperative relationship. This study provides a broad comparative view and a solid stepping stone for future functional explorations of ACKRs based on the microanatomical localization and distinct and cooperative roles of these powerful chemokine scavengers.

Abstract Background Identification of Anopheles gambiae s.s. and Anopheles arabiensis from field-collected Anopheles gambiae s.l. is often necessary in basic and applied research, and in operational control programmes. The currently accepted method involves use of standard polymerase chain reaction amplification of ribosomal DNA (rDNA) from the 3' 28S to 5' intergenic spacer region of the genome, and visual confirmation of amplicons of predicted size on agarose gels, after electrophoresis. This report describes development and evaluation of an automated, quantitative PCR method based upon TaqMan™ single nucleotide polymorphism (SNP) genotyping. Methods Standard PCR, and TaqMan SNP genotyping with newly designed primers and fluorophore-labeled probes hybridizing to sequences of complementary rDNA specific for either An. gambiae s.s. or An. arabiensis, were conducted in three experiments involving field-collected An. gambiae s.l. from western Kenya, and defined laboratory strains. DNA extraction was from a single leg, sonicated for five minutes in buffer in wells of 96-well PCR plates. Results TaqMan SNP genotyping showed a reaction success rate, sensitivity, and species specificity comparable to that of standard PCR. In an extensive field study, only 29 of 3,041 (0.95%) were determined to be hybrids by TaqMan (i.e., having rDNA sequences from both species), however, all but one were An. arabiensis by standard PCR, suggesting an acceptably low (ca. 1%) error rate for TaqMan genotyping in mistakenly identifying species hybrids. Conclusion TaqMan SNP genotyping proved to be a sensitive and rapid method for identification of An. gambiae s.l. and An. arabiensis, with a high success rate, specific results, and congruence with the standard PCR method.

Titan’s atmospheric composition and dynamical state have previously been studied over numerous epochs by both ground- and space-based facilities. However, stratospheric measurements remain sparse during Titan’s northern summer and fall. The lack of seasonal symmetry in observations of Titan’s temperature field and chemical abundances raises questions about the nature of the middle atmosphere’s meridional circulation and evolution over Titan’s 29 yr seasonal cycle that can only be answered through long-term monitoring campaigns. Here, we present maps of Titan’s stratospheric temperature, acetonitrile (or methyl cyanide; CH _3 CN) abundance, and monodeuterated methane (CH _3 D) abundance following Titan’s northern summer solstice obtained with Band 9 (∼0.43 mm) Atacama Large Millimeter/submillimeter Array observations. We find that increasing temperatures toward high southern latitudes, currently in winter, resemble those observed during Titan’s northern winter by the Cassini mission. Acetonitrile abundances have changed significantly since previous (sub)millimeter observations, and we find that the species is now highly concentrated at high southern latitudes. The stratospheric CH _3 D content is found to range between 4 and 8 ppm in these observations, and we infer the CH _4 abundance to vary between ∼0.9% and 1.6% through conversion with previously measured D/H values. A global value of CH _4 = 1.15% was retrieved, lending further evidence to the temporal and spatial variability of Titan’s stratospheric methane when compared with previous measurements. Additional observations are required to determine the cause and magnitude of stratospheric enhancements in methane during these poorly understood seasons on Titan.

Saturn’s moon Titan possesses stratospheric zonal winds that places it among a sparse class of planetary bodies known to have superrotation in their atmospheres. Few measurements have been made of these speeds in the upper stratosphere, leaving their seasonal variations still not well understood. We examined observations made with the extended Submillimeter Array in 2009 March ( L _s = 355°) and 2010 February ( L _s = 5°), shortly before and after Titan's northern spring equinox. Cassini observations and atmospheric models find equinoctial periods to be especially dynamic. Zonal wind calculations, derived from the Doppler frequency shift of CH _3 CN near 349.4 GHz, yielded speeds of 128 ± 27 m s ^−1 in 2009 and 209 ± 48 m s ^−1 in 2010. We estimated the measured emission to originate from vertical altitudes of ${336}_{-88}^{+112}$ km, equivalent to pressures of ${3.8}_{-3.4}^{+19.2}$ Pa, commensurate with Titan’s upper stratosphere/lower mesosphere. This suggests a possible increase in zonal speeds during this period. The results are then compared to those from previous Cassini-inferred and direct-interferometric observations of winds, as well as general circulation model simulations, to form a more complete picture of the seasonal cycle of stratospheric zonal winds.

We present best-fit values of porosity—and the corresponding effective thermal inertiae—determined from three different depths in Europa’s near-subsurface (∼1–20 cm). The porosity of the upper ∼20 cm of Europa’s subsurface varies between 75% and 50% (Γ _eff ≈ 50–140 J m ^−2 K ^−1 s ^−1/2 ) on the leading hemisphere and 50%–40% (Γ _eff ≈ 140–180 J m ^−2 K ^−1 s ^−1/2 ) on the trailing hemisphere. Residual maps produced by comparison with these models reveal thermally anomalous features that cannot be reproduced by globally homogeneous porosity models. These regions are compared to Europa’s surface terrain and known compositional variations. We find that some instances of warm thermal anomalies are co-located with known geographical or compositional features on both the leading and trailing hemisphere; cool temperature anomalies are well correlated with surfaces previously observed to contain pure, crystalline water ice and the expansive rays of Pwyll crater. Anomalous regions correspond to locations with subsurface properties different from those of our best-fit models, such as potentially elevated thermal inertia, decreased emissivity, or more porous regolith. We also find that ALMA observations at ∼3 mm sound below the thermal skin depth of Europa (∼10–15 cm) for a range of porosity values, and thus do not exhibit features indicative of diurnal variability or residuals similar to other frequency bands. Future observations of Europa at higher angular resolution may reveal additional locations of variable subsurface thermophysical properties, while those at other wavelengths will inform our understanding of the regolith compaction length and the effects of external processes on the shallow subsurface.

IntroductionPatients who suffer in-hospital cardiac arrest (IHCA) are less likely to survive if the arrest occurs during nighttime versus daytime. Diastolic blood pressure (DBP) as a measure of chest compression quality was associated with survival from pediatric IHCA. We hypothesized that DBP during CPR for IHCA is lower during nighttime versus daytime.MethodsThis is a secondary analysis of data collected from the Pediatric Intensive Care Quality of Cardiopulmonary Resuscitation Study. Pediatric or Pediatric Cardiac Intensive Care Unit patients who received chest compressions for ≥1 min and who had invasive arterial BP monitoring were enrolled. Nighttime was defined as 11:00PM to 6:59AM and daytime as 7:00AM until 10:59PM. Primary outcome was attainment of DBP ≥ 25 mmHg in infants

The tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) activating protein (GAP) activity toward the GTPase RagC. Concomitant with mTORC1 inactivation by starvation, FLCN relocalizes from the cytosol to lysosomes. To determine the lysosomal function of FLCN, we reconstituted the human lysosomal FLCN complex (LFC) containing FLCN, its partner FLCN-interacting protein 2 (FNIP2), and the RagAGDP:RagCGTP GTPases as they exist in the starved state with their lysosomal anchor Ragulator complex and determined its cryo-electron microscopy structure to 3.6 angstroms. The RagC-GAP activity of FLCN was inhibited within the LFC, owing to displacement of a catalytically required arginine in FLCN from the RagC nucleotide. Disassembly of the LFC and release of the RagC-GAP activity of FLCN enabled mTORC1-dependent regulation of the master regulator of lysosomal biogenesis, transcription factor E3, implicating the LFC as a checkpoint in mTORC1 signaling.

AimDiastolic blood pressure (DBP) during cardiopulmonary resuscitation (CPR) is associated with survival following pediatric in-hospital cardiac arrest. The relationship between intra-arrest haemodynamics and neurological status among survivors of pediatric cardiac arrest is unknown.MethodsThis study represents analysis of data from the prospective multicenter Pediatric Intensive Care Quality of cardiopulmonary resuscitation (PICqCPR) Study. Primary predictor variables were median DBP and median systolic blood pressure (SBP) over the first 10min of CPR. The primary outcome measure was "new substantive morbidity" determined by Functional Status Scale (FSS) and defined as an increase in the FSS of at least 3 points or increase of 2 in a single FSS domain. Univariable analyses were completed to investigate the relationship between new substantive morbidity and BPs during CPR.Results244 index CPR events occurred during the study period, 77 (32%) CPR events met all inclusion criteria as well as having both DBP and FSS data available. Among 77 survivors, 32 (42%) had new substantive morbidity as measured by the FSS score. No significant differences were identified in DBP (median 30.5mmHg vs. 30.9mmHg, p=0.5) or SBP (median 76.3mmHg vs. 63.0mmHg, p=0.2) between patients with and without new substantive morbidity. Children who developed new substantive morbidity were more likely to have lower pre-arrest FSS than those that did not (median [IQR]: 7.5 [6.0-9.0] versus 9.0 [7.0-13.0], p=0.01).ConclusionNew substantive morbidity determined by FSS after a pediatric IHCA was associated with baseline functional status, but not DBP during CPR.

Abstract Many countries that had early access to COVID-19 vaccines implemented vaccination strategies that prioritized health care workers and the elderly. As barriers to access eased, vaccine prioritization strategies have been relaxed. However, these strategies are still an important tool for decision makers to manage new variants, plan for future booster shots, or stage mass vaccinations. This paper explores the impact of vaccine prioritization strategies using networks that represent communities with different demographics and connectivity. The impact of vaccination is compared to non-medical intervention to reduce transmission. Several sources of uncertainty are considered, including vaccine willingness and mask effectiveness. This paper finds that while prioritization strategies can have a large impact on reducing deaths and peak hospitalization, selecting the best strategy depends on community characteristics and the desired objective. Additionally, in some cases random vaccination performs as well as more targeted prioritization strategies. Understanding these trade-offs is important when planning vaccine distribution.

Chemotaxis is an essential physiological process, often harnessed by tumors for metastasis. CXCR4, its ligand CXCL12 and the atypical receptor ACKR3 are overexpressed in many human cancers. Interfering with this axis by ACKR3 deletion impairs lymphoma cell migration towards CXCL12. Here, we propose a model of how ACKR3 controls the migration of the diffused large B-cell lymphoma VAL cells in vitro and in vivo in response to CXCL12. VAL cells expressing full-length ACKR3, but not a truncated version missing the C-terminus, can support the migration of VAL cells lacking ACKR3 (VAL-ko) when allowed to migrate together. This migration of VAL-ko cells is pertussis toxin-sensitive suggesting the involvement of a Gi-protein coupled receptor. RNAseq analysis indicate the expression of chemotaxis-mediating LTB4 receptors in VAL cells. We found that LTB4 acts synergistically with CXCL12 in stimulating the migration of VAL cells. Pharmacologic or genetic inhibition of BLT1R markedly reduces chemotaxis towards CXCL12 suggesting that LTB4 enhances in a contact-independent manner the migration of lymphoma cells. The results unveil a novel mechanism of cell-to-cell-induced migration of lymphoma.