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The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐IFTA) and its relationship to T cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials. The Banff consortium presents revisions to the diagnostic criteria for T cell– and antibody‐mediated kidney transplant rejection, including specific criteria for chronic active T cell–mediated rejection, plus prospects for integrative endpoints in clinical trials. See related articles on pages 321, 364, and 377.

What are the psychological consequences of the increasingly politicized nature of the COVID-19 pandemic in the United States relative to similar Western countries? In a two-wave study completed early (March) and later (December) in the pandemic, we found that polarization was greater in the United States ( N = 1,339) than in Canada ( N = 644) and the United Kingdom. ( N = 1,283). Political conservatism in the United States was strongly associated with engaging in weaker mitigation behaviors, lower COVID-19 risk perceptions, greater misperceptions, and stronger vaccination hesitancy. Although there was some evidence that cognitive sophistication was associated with increased polarization in the United States in December (but not March), cognitive sophistication was nonetheless consistently negatively correlated with misperceptions and vaccination hesitancy across time, countries, and party lines. Furthermore, COVID-19 skepticism in the United States was strongly correlated with distrust in liberal-leaning mainstream news outlets and trust in conservative-leaning news outlets, suggesting that polarization may be driven by differences in information environments.

Author(s): Lochmuller, Hanns; Behin, Anthony; Tournev, Ivailo; Tarnopolsky, Mark; Horvath, Rita; Pogoryelova, Oksana; Shah, Jinay; Koutsoukos, Tony; Skrinar, Alison; Kakkis, Emil; Bedrosian, Camille L; Mozaffar, Tahseen | Abstract: BackgroundGNE myopathy is a rare, autosomal recessive, muscle disease caused by mutations in GNE and is characterized by rimmed vacuoles on muscle biopsy and progressive distal to proximal muscle weakness.ObjectiveInvestigate the clinical presentation and progression of GNE myopathy.MethodsThe GNE Myopathy Disease Monitoring Program was an international, prospective, observational study in subjects with GNE myopathy. Muscle strength was assessed with hand-held dynamometry (HHD), with upper extremity (UE) and lower extremity (LE) composite scores reflecting upper and lower extremity muscle groups, respectively. The GNE myopathy-Functional Activity Scale (GNEM-FAS) was used to further assess impairment in mobility, upper extremity function, and self-care.ResultsEighty-seven of 101 enrolled subjects completed the trial until study closure by the sponsor; 60 completed 36 months. Mean (SD) HHD UE composite score decreased from 34.3 kg (32.0) at baseline to 29.4 kg (32.6) kg at month 36 (LS mean change [95%CI]: -3.8 kg [-5.9, -1.7]; P = 0.0005). Mean (SD) HHD LE composite score decreased from 32.0 kg (34.1) at baseline to 25.5 kg (31.2) at month 36 (LS mean change [95%CI]: -4.9 [-7.7, -2.2]; P = 0.0005). GNEM-FAS scores were more severe at baseline in subjects who walked l200 meters versus ≥200 meters in 6 minutes; in both groups, GNEM-FAS total, mobility, UE, and self-care scores decreased from baseline through month 36.ConclusionsThese findings demonstrate progressive decline in muscle strength in GNE myopathy and provide insight into the appropriate tools to detect clinically meaningful changes in future GNE myopathy interventional trials.

Dinoflagellates are microbial eukaryotes that have exceptionally large nuclear genomes; however, their organelle genomes are small and fragmented and contain fewer genes than those of other eukaryotes. The genus Amoebophrya (Syndiniales) comprises endoparasites with high genetic diversity that can infect other dinoflagellates, such as those forming harmful algal blooms (e.g., Alexandrium). We sequenced the genome (~100 Mb) of Amoebophrya ceratii to investigate the early evolution of genomic characters in dinoflagellates. The A. ceratii genome encodes almost all essential biosynthetic pathways for self-sustaining cellular metabolism, suggesting a limited dependency on its host. Although dinoflagellates are thought to have descended from a photosynthetic ancestor, A. ceratii appears to have completely lost its plastid and nearly all genes of plastid origin. Functional mitochondria persist in all life stages of A. ceratii, but we found no evidence for the presence of a mitochondrial genome. Instead, all mitochondrial proteins appear to be lost or encoded in the A. ceratii nucleus. The parasitic marine dinoflagellate Amoebophrya is the first known eukaryote with aerobic mitochondria without a genome.

Background: Arterial hypertension and its organ sequelae show characteristics of T cell–mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage. Methods: To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout–deficient mice received propionate (200 mmol/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg–1·d–1 subcutaneous) for 14 days. To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg·kg–1·d–1 subcutaneous) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate. Results: Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II–infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout–deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell–depleted angiotensin II–infused mice, suggesting the effect is regulatory T cell–dependent. Conclusions: Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease. Supplemental Digital Content is available in the text.

AbstractAstrocytes control synaptic activity by modulating peri-synaptic concentrations of ion and neurotransmitters including dopamine and, as such, can be critically involved in the modulation of some aspect of mammalian behavior. Here we report that genetic mouse model with a reduced medial prefrontal cortex (mPFC) dopamine levels, arising from astrocyte-specific conditional deletion of vesicular monoamine transporter 2 (VMAT2; aVMTA2cKO mice) shows excessive grooming and anxiety-like behaviour. The VMAT2cKO mice also develop a synaptic pathology, expressed through increased relative AMPA vs. NMDA receptor currents in synapses of the dorsal striatum receiving inputs from the mPFC. Importantly, behavioural and synaptic phenotypes are prevented by reexpression of mPFC VMAT2, showing that the deficits are driven by mPFC astrocytes. By analysing human tissue samples, we found that VMAT2 is expressed in human mPFC astrocytes, corroborating the potential translational relevance of our observations in mice. Our study shows that impairments of the astrocytic-control of dopamine in the mPFC has a profound impact on circuit function and behaviours, which resemble symptoms of anxiety disorders and obsessive compulsive disorder (OCD).

International audience; Phosphorus (P) is a non-renewable resource, and its recovery and recycling are necessary for meeting future P demands and environmental conservation. Ash and hydrochar from incineration and hydrothermal liquefaction (HTL) of municipal sludge, respectively, represent promising sources for efficient P recovery. The full-scale application of wet-chemical techniques has proven their technical feasibility for P recovery from sludge-derived ash. HTL for sludge treatment has received significant attention for producing biocrude with net-positive energy recovery. P recovery from the solid by-product of sludge HTL, hydrochar, is a critical step in holistic sustainable sludge management. This review aims to guide P recovery from sludge-derived ash and hydrochar by presenting recent advances in wet-chemical extraction and precipitation. By comparing their characteristics, ash and hydrochar derived from municipal sludge exhibit similar feasibilities and challenges for P recovery. Extraction is recognized as the critical step for P recovery. The advantages and disadvantages of various P extraction approaches are provided. Acidic extraction achieves high efficiency (up to 100%) but requires removal of co-extracted heavy metals. Alkaline extraction prevents metals contamination but shows low efficiency (<70%). Sequential extraction is first identified as an important advance in this review, with promising P extraction efficiencies (70–91%) and low metal interferences. Three possible fertilizers (struvite, calcium phosphates, and vivianite) are recommended through the final precipitation, given their pros and cons of recovery. Ultimately, this review highlights the need for a wastewater biorefinery integrating wastewater treatment, HTL (energy recovery), and nutrient recovery for sustainable sludge management.

Multimarginal Optimal Transport (MOT) has attracted significant interest due to applications in machine learning, statistics, and the sciences. However, in most applications, the success of MOT is severely limited by a lack of efficient algorithms. Indeed, MOT in general requires exponential time in the number of marginals k and their support sizes n. This paper develops a general theory about what "structure" makes MOT solvable in poly(n,k) time. We develop a unified algorithmic framework for solving MOT in poly(n,k) time by characterizing the "structure" that different algorithms require in terms of simple variants of the dual feasibility oracle. This framework has several benefits. First, it enables us to show that the Sinkhorn algorithm, which is currently the most popular MOT algorithm, requires strictly more structure than other algorithms do to solve MOT in poly(n,k) time. Second, our framework makes it much simpler to develop poly(n,k) time algorithms for a given MOT problem. In particular, it is necessary and sufficient to (approximately) solve the dual feasibility oracle -- which is much more amenable to standard algorithmic techniques. We illustrate this ease-of-use by developing poly(n,k) time algorithms for three general classes of MOT cost structures: (1) graphical structure; (2) set-optimization structure; and (3) low-rank plus sparse structure. For structure (1), we recover the known result that Sinkhorn has poly(n,k) runtime; moreover, we provide the first poly(n,k) time algorithms for computing solutions that are exact and sparse. For structures (2)-(3), we give the first poly(n,k) time algorithms, even for approximate computation. Together, these three structures encompass many -- if not most -- current applications of MOT. v4: to appear in Mathematical Programming, improved exposition and refs, no changes to technical results

We report spatially resolved [C ii] λ158 μm observations of HE 0433-1028, which is the first detection of a nearby luminous active galactic nucleus (AGN; redshift 0.0355) with the Field-Imaging Far-Infrared Line Spectrometer (FIFI-LS) on board the airborne Stratospheric Observatory For Infrared Astronomy (SOFIA). We compare the spatially resolved star formation tracers [C ii], as provided by our SOFIA observations, and Hα from the Multi Unit Spectroscopic Explorer (MUSE) optical integral-field spectroscopy. We find that the [C ii] emission is mainly matching the extended star formation as traced by the extinction-corrected Hα line emission but some additional flux is present. While a larger sample is needed to statistically confirm our findings and investigate possible dependencies on AGN luminosity and star formation rate, our study underlines the necessity of collecting a spatially resolved optical-far-infrared data set for nearby AGNs, and shows that it is technically feasible to collect such data sets with FIFI-LS on board SOFIA. © 2018. The American Astronomical Society. All rights reserved. Based in part on observations made with the NASA/DLR Stratospheric Observatory for Infrared Astronomy (SOFIA). SOFIA is jointly operated by the Universities Space Research Association, Inc. (USRA), under NASA contract NAS2-97001, and the Deutsches SOFIA Institut (DSI) under DLR contract 50 OK 0901 to the University of Stuttgart. We thank the anonymous referee for a constructive report that helped to clarify the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) via SFB 956, subprojects A2, and A6. The work of S.B. and C.O. was supported by NSERC (Natural Sciences and Engineering Research Council of Canada). M.G. is supported by NASA through Einstein Postdoctoral Fellowship Award No. PF5-160137 issued by the Chandra X-ray Observatory Center, which is operated by the SAO for and on behalf of NASA under contract NAS8-03060. Support for this work was also provided by Chandra grant GO7-18121X. M.K. acknowledges support by DLR 50OR1802. M.P.T. acknowledges support from the Spanish MINECO through grants AYA2012-38491-C02-02 and AYA2015-63939-C2-1-P. Peer reviewed

Atmospheric ammonia (NH3) is a precursor to fine particulate matter formation and contributes to nitrogen (N) deposition, with potential implications for the health of humans and ecosystems. Agricultural soils and animal excreta are the primary source of atmospheric NH3, but natural soils can also be an important emitter. In regions with distinct dry and wet seasons such as the Sahel, the start of the rainy season triggers a pulse of biogeochemical activity in surface soils known as the Birch effect, which is often accompanied by emissions of microbially produced gases such as carbon dioxide and nitric oxide. Field and lab studies have sometimes, but not always, observed pulses of NH3 after the wetting of dry soils; however, the potential regional importance of these emissions remains poorly constrained. Here we use satellite retrievals of atmospheric NH3 using the Infrared Atmospheric Sounding Interferometer (IASI) regridded at 0.25∘ resolution, in combination with satellite-based observations of precipitation, surface soil moisture, and nitrogen dioxide concentrations, to reveal substantial precipitation-induced pulses of NH3 across the Sahel at the onset of the rainy season in 2008. The highest concentrations of NH3 occur in pulses during March and April when NH3 biomass burning emissions estimated for the region are low. For the region of the Sahel spanning 10 to 16∘ N and 0 to 30∘ E, changes in NH3 concentrations are weakly but significantly correlated with changes in soil moisture during the period from mid-March through April when the peak NH3 concentrations occur (r=0.28, p=0.02). The correlation is also present when evaluated on an individual pixel basis during April (r=0.16, p<0.001). Average emissions for the entire Sahel from a simple box model are estimated to be between 2 and 6 mg NH3 m−2 d−1 during peaks of the observed pulses, depending on the assumed effective NH3 lifetime. These early season pulses are consistent with surface observations of monthly concentrations, which show an uptick in NH3 concentration at the start of the rainy season for sites in the Sahel. The NH3 concentrations in April are also correlated with increasing tropospheric NO2 concentrations observed by the Ozone Monitoring Instrument (r=0.78, p<0.0001), which have previously been attributed to the Birch effect. Box model results suggest that pulses occurring over a 35-day period in March and April are responsible for roughly one-fifth of annual emissions of NH3-N from the Sahel. We conclude that precipitation early in the rainy season is responsible for substantial NH3 emissions in the Sahel, likely representing the largest instantaneous fluxes of gas-phase N from the region during the year.