Stability study of a model for the Klein-Gordon equation in Kerr spacetime

The current early stage in the investigation of the stability of the Kerr metric is characterized by the study of appropriate model problems. Particularly interesting is the problem of the stability of the solutions of the Klein-Gordon equation, describing the propagation of a scalar field of mass $\mu$ in the background of a rotating black hole. Rigorous results proof the stability of the reduced, by separation in the azimuth angle in Boyer-Lindquist coordinates, field for sufficiently large masses. Some, but not all, numerical investigations find instability of the reduced field for rotational parameters $a$ extremely close to 1. Among others, the paper derives a model problem for the equation which supports the instability of the field down to $a/M \approx 0.97$.Comment: Updated version, after minor change

Pilot randomized trial demonstrating reversal of obesity-related abnormalities in reward system responsivity to food cues with a behavioral intervention

Objectives: Obesity is associated with hyperactivation of the reward system for high-calorie (HC) versus low-calorie (LC) food cues, which encourages unhealthy food selection and overeating. However, the extent to which this hyperactivation can be reversed is uncertain, and to date there has been no demonstration of changes by behavioral intervention. Subjects and methods: We used functional magnetic resonance imaging to measure changes in activation of the striatum for food images at baseline and 6 months in a pilot study of 13 overweight or obese adults randomized to a control group or a novel weight-loss intervention. Results: Compared to controls, intervention participants achieved significant weight loss (−6.3±1.0 kg versus +2.1±1.1 kg, P<0.001) and had increased activation for LC food images with a composition consistent with that recommended in the behavioral intervention at 6 months versus baseline in the right ventral putamen (P=0.04), decreased activation for HC images of typically consumed foods in the left dorsal putamen (P=0.01). There was also a large significant shift in relative activation favoring LC versus HC foods in both regions (P<0.04). Conclusions: This study provides the first demonstration of a positive shift in activation of the reward system toward healthy versus unhealthy food cues in a behavioral intervention, suggesting new avenues to enhance behavioral treatments of obesity

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Heat flow from the Southeast Indian Ridge flanks between 80°E and 140°E: Data review and analysis

International audienceWe analyze available heat flow data from the flanks of the Southeast Indian Ridge adjacent to or within the Australian-Antarctic Discordance (AAD), an area with patchy sediment cover and highly fractured seafloor as dissected by ridge- and fracture-parallel faults. The data set includes 23 new data points collected along a 14-Ma old isochron and 19 existing measurements from the 20- to 24-Ma old crust. Most sites of measurements exhibit low heat flux (from 2 to 50 mW m−2) with near-linear temperature-depth profiles except at a few sites, where recent bottom water temperature change may have caused nonlinearity toward the sediment surface. Because the igneous basement is expected to outcrop a short distance away from any measurement site, we hypothesize that horizontally channelized water circulation within the uppermost crust is the primary process for the widespread low heat flow values. The process may be further influenced by vertical fluid flow along numerous fault zones that crisscross the AAD seafloor. Systematic measurements along and across the fault zones of interest as well as seismic profiling for sediment distribution are required to confirm this possible, suspected effect

wildfire activity and land use drove 20th century changes in forest cover in the colorado front range

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Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels

Induction of the antioxidant enzyme heme oxygenase-1 (HO-1) affords cellular protection and suppresses proliferation of vascular smooth muscle cells (VSMCs) associated with a variety of pathological cardiovascular conditions including myocardial infarction and vascular injury. However, the underlying mechanisms are not fully understood. Over-expression of Cav3.2 T-type Ca2+ channels in HEK293 cells raised basal [Ca2+]i and increased proliferation as compared with non-transfected cells. Proliferation and [Ca2+]i levels were reduced to levels seen in non-transfected cells either by induction of HO-1 or exposure of cells to the HO-1 product, carbon monoxide (CO) (applied as the CO releasing molecule, CORM-3). In the aortic VSMC line A7r5, proliferation was also inhibited by induction of HO-1 or by exposure of cells to CO, and patch-clamp recordings indicated that CO inhibited T-type (as well as L-type) Ca2+ currents in these cells. Finally, in human saphenous vein smooth muscle cells, proliferation was reduced by T-type channel inhibition or by HO-1 induction or CO exposure. The effects of T-type channel blockade and HO-1 induction were non-additive. Collectively, these data indicate that HO-1 regulates proliferation via CO-mediated inhibition of T-type Ca2+ channels. This signalling pathway provides a novel means by which proliferation of VSMCs (and other cells) may be regulated therapeutically

Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management

The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation

Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes. The neuropeptide receptor Nmur1 was preferentially expressed by ILC2s at steady state and after IL-25 stimulation. Neuromedin U (NMU), the ligand of NMUR1, activated ILC2s in vitro, and in vivo co-administration of NMU with IL-25 strongly amplified allergic inflammation. Loss of NMU-NMUR1 signalling reduced ILC2 frequency and effector function, and altered transcriptional programs following allergen challenge in vivo. Thus, NMUR1 signalling promotes inflammatory ILC2 responses, highlighting the importance of neuro-immune crosstalk in allergic inflammation at mucosal surfaces