This research illuminates a key paradox progressive policy is implemented, yet the overdose crisis escalates in communities where various forms of racialized exclusions are firmly entrenched. (Am J Public Health. 2022;112(S2)S173-S181. https//doi.org/10.2105/AJPH.2022.306767).Objectives. To examine how operational rules are established and enforced at an unsanctioned safe consumption site (SCS) operating in the United States. Methods. We conducted 44 qualitative interviews with people who use drugs, staff members, and volunteers at an unsanctioned SCS and analyzed them using an inductive thematic approach. Results. Rule-making processes were largely driven by concerns raised by service users rather than driven by external pressures, and iterated rapidly in response to changing needs. The unsanctioned nature of the site produced an environment where bottom-up rule-making was critical to generating a shared sense of ownership of the site and where enforcement was necessarily fluid. Conclusions. Removing external restrictions on operational rules for SCSs results in a flexible set of rules that are highly responsive to the social and public health needs of people who use drugs. Legislation and regulations of SCSs should aim to place as few hard limits on operating conditions as possible to maximize involvement of and responsiveness to people who use drugs. (Am J Public Health. 2022;112(S2)S166-S172. https//doi.org/10.2105/AJPH.2022.306714).Plant-microbe interactions in the rhizosphere play a vital role in plant health and productivity. The composition and function of root-associated microbiomes is strongly influenced by their surrounding environment, which is often customized by their host. How microbiomes change with respect to space and time across plant roots remains poorly understood, and methodologies that facilitate spatiotemporal metaproteomic studies of root-associated microbiomes are yet to be realized. Here, we developed a method that provides spatially resolved metaproteome measurements along plant roots embedded in agar-plate culture systems, which have long been used to study plants. Spatially defined agar „plugs” of interest were excised and subsequently processed using a novel peptide extraction method prior to metaproteomics, which was used to infer both microbial community composition and function. As a proof-of-principle, a previously studied 10-member community constructed from a Populus root system was grown in an agar plate with a 3-week-old Populus trichocarpa plant. Metaproteomics was performed across two time points (24 and 48 h) for three distinct locations (root base, root tip, and a region distant from the root). The spatial resolution of these measurements provides evidence that microbiome composition and expression changes across the plant root interface. Interrogation of the individual microbial proteomes revealed functional profiles related to their behavioral associations with the plant root, in which chemotaxis and augmented metabolism likely supported predominance of the most abundant member. This study demonstrated a novel peptide extraction method for studying plant agar-plate culture systems, which was previously unsuitable for (meta)proteomic measurements.Dual leucine-zipper kinase (DLK; a MAP3K) mediates neuronal responses to diverse injuries and insults through the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein kinases (MAPKs). Here, we identified two ways through which DLK is coupled to the neural-specific isoform JNK3 to control prodegenerative signaling. JNK3 catalyzed positive feedback phosphorylation of DLK that further activated DLK and locked the DLK-JNK3 module in a highly active state. Neither homologous MAP3Ks nor a homologous MAPK could support this positive feedback loop. Unlike the related JNK1 isoform JNK2 and JNK3 promote prodegenerative axon-to-soma signaling and were endogenously palmitoylated. Moreover, palmitoylation targeted both DLK and JNK3 to the same axonal vesicles, and JNK3 palmitoylation was essential for axonal retrograde signaling in response to optic nerve crush injury in vivo. These findings provide previously unappreciated insights into DLK-JNK signaling relevant to neuropathological conditions and answer long-standing questions regarding the selective prodegenerative roles of JNK2 and JNK3.Preventing the metalloprotease MT1-MMP from cleaving an anorexigenic receptor may be an anti-obesity strategy.Cerebral blood flow must be exquisitely regulated to match the metabolic demands of neurons. In this issue of Science Signaling, Sancho et al. characterize functional ATP-sensitive K+ (KATP) channels in cerebral capillary endothelial cells and pericytes that can be activated by adenosine signaling, thereby leading to increases in capillary blood flow.The dense network of capillaries composed of capillary endothelial cells (cECs) and pericytes lies in close proximity to all neurons, ideally positioning it to sense neuron- and glial-derived compounds that enhance regional and global cerebral perfusion. The membrane potential (VM) of vascular cells serves as the physiological bridge that translates brain activity into vascular function. In other beds, the ATP-sensitive K+ (KATP) channel regulates VM in vascular smooth muscle, which is absent in the capillary network. Here, with transgenic mice that expressed a dominant-negative mutant of the pore-forming Kir6.1 subunit specifically in brain cECs or pericytes, we demonstrated that KATP channels were present in both cell types and robustly controlled VM. We further showed that the signaling nucleotide adenosine acted through A2A receptors and the Gαs/cAMP/PKA pathway to activate capillary KATP channels. Moreover, KATP channel stimulation in vivo increased cerebral blood flow (CBF), an effect that was blunted by expression of the dominant-negative Kir6.1 mutant in either capillary cell type. These findings establish an important role for KATP channels in cECs and pericytes in the regulation of CBF.Bubble evolution plays a fundamental role in boiling and gas-evolving electrochemical systems. One key stage is bubble departure, which is traditionally considered to be buoyancy-driven. However, conventional understanding cannot provide the full physical picture, especially for departure events with small bubble sizes commonly observed in water splitting and high heat flux boiling experiments. Here, we report a new regime of bubble departure owing to the coalescence of two bubbles, where the departure diameter can be much smaller than the conventional buoyancy limit. We show the significant reduction of the bubble base area due to the dynamics of the three-phase contact line during coalescence, which promotes bubble departure. More importantly, combining buoyancy-driven and coalescence-induced bubble departure modes, we demonstrate a unified relationship between the departure diameter and nucleation site density. By elucidating how coalescing bubbles depart from a wall, our work provides design guidelines for energy systems which can largely benefit from efficient bubble departure.We used atomistic simulations and compared the prediction of three different implementations of force fields, namely, the original full partial charge system, the scaled partial charge system, and the Drude oscillator polarizable force field and its effect on the structural and dynamic properties of a polymeric ionic liquid, poly(1-butyl-3-methyl-imidazolium hexafluorophosphate). We found that both the scaled and the polarizable force field models yield comparable predictions of structural and dynamic properties, although the scaled charge model artificially lowers the first-neighbor peak of the radial distribution function and therefore leads to a slight reduction in density. The full charge model was not accurate in its prediction of the dynamic properties but could reproduce the structural properties. With a refined analysis method for the ion-hopping mechanisms, we found that all three methods produce very similar conclusions, namely, that the mobile anion is associated with three cations from two distinct polymer chains and that the fractions of inter- and intramolecular hopping events are comparable. Our results demonstrate that the scaled charge force fields provide a computationally efficient means to capture polarizability effects on both the structural and dynamic properties of polymeric ionic liquid systems.A Landau theory is constructed for the gel/fluid transition of a lipid bilayer wrapped around a spherical nanoparticle (lipid-wrapped nanoparticle, LNP). The bilayer is regarded as a regular solution of gel and fluid lipids with distinct inter- and intralayer interactions plus the interaction of the core with the inner layer. It is required that both the inner and the outer surfaces of the bilayer are perfectly covered with lipids, with the gel and fluid lipids having different areas/lipid. The equilibrium state is found by minimizing the free energy as a function of the fractions of fluid lipids in the inner and outer layers. The transition has been studied extensively for lamellar membranes in the thermodynamic limit. LNP have significant curvature and are not in the thermodynamic limit. The increase of the gel energy with curvature, identified in our previous work as its most important effect, is included. The focus of the paper is the dependence of the transition on the core radius, R, controlling curvature, and the core-lipid interaction. With decreasing R, trends found in experiment are reproduced in a model calculation (1) decrease of the transition temperature, Tm, (2) decoupling of the transitions in the inner and outer layers, and (3) possibility of lower Tm in the inner layer. The disruption of gel packing by curvature and the interaction of the core with the inner layer are highlighted as the most important determinants of deviation from bulk behavior.An N-heterocyclic carbene organocatalytic 1,4-difunctionalization of 1,3-enynes was developed. This organocatalytic strategy was suitable for a broad spectrum of substrates to efficiently synthesize allenic ketones bearing diverse substituents. Preliminary mechanistic studies suggest a radical reaction pathway for this organocatalytic acylalkylation process.Gaucher disease (GD) is a lysosomal storage disorder resulting from a biallelic mutation in the gene GBA1, leading to deficiencies in the enzyme β-glucocerebrosidase (Gcase). Inabilities of the Gcase to catabolize its substrate result in the accumulation of sphingolipids in macrophages, which impairs the cell functions and ultimately leads to multisystemic clinical manifestations. Important variability in symptoms and manifestations may lead to challenging diagnosis and patient care. Plasma glucosylsphingosine (lyso-Gb1) is a biomarker frequently used for prognosis, monitoring, and patient follow-up. While lyso-Gb1 appears to be a valid biomarker, few studies have investigated other matrices for potential GD biomarkers. The main objective of this study was to investigate the urine matrix as a potential source of new GD biomarkers by performing a metabolomic study using time-of-flight mass spectrometry. Our study highlighted a significant increase of eight urinary lyso-Gb1 analogues. Moreover, a novel class of biomarkers, named polycyclic lyso-Gb1 analogues, was identified.