Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention

Relative exposure to microplastics and prey for a pelagic forage fish

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Chavarry, J. M., Law, K. L., Barton, A. D., Bowlin, N. M., Ohman, M. D., & Choy, C. A. Relative exposure to microplastics and prey for a pelagic forage fish. Environmental Research Letters, 17(6), (2022): 064038, https://doi.org/10.1088/1748-9326/ac7060.In the global ocean, more than 380 species are known to ingest microplastics (plastic particles less than 5 mm in size), including mid-trophic forage fishes central to pelagic food webs. Trophic pathways that bioaccumulate microplastics in marine food webs remain unclear. We assess the potential for the trophic transfer of microplastics through forage fishes, which are prey for diverse predators including commercial and protected species. Here, we quantify Northern Anchovy (Engraulis mordax) exposure to microplastics relative to their natural zooplankton prey, across their vertical habitat. Microplastic and zooplankton samples were collected from the California Current Ecosystem in 2006 and 2007. We estimated the abundance of microplastics beyond the sampled size range but within anchovy feeding size ranges using global microplastic size distributions. Depth-integrated microplastics (0–30 m depth) were estimated using a depth decay model, accounting for the effects of wind-driven vertical mixing on buoyant microplastics. In this coastal upwelling biome, the median relative exposure for an anchovy that consumed prey 0.287–5 mm in size was 1 microplastic particle for every 3399 zooplankton individuals. Microplastic exposure varied, peaking within offshore habitats, during the winter, and during the day. Maximum exposure to microplastic particles relative to zooplankton prey was higher for juvenile (1:23) than adult (1:33) anchovy due to growth-associated differences in anchovy feeding. Overall, microplastic particles constituted fewer than 5% of prey-sized items available to anchovy. Microplastic exposure is likely to increase for forage fishes in the global ocean alongside declines in primary productivity, and with increased water column stratification and microplastic pollution.This work originated from the Plastic Awareness Global Initiative (PAGI) international workshop, hosted by the Center for Marine Biodiversity and Conservation (CMBC) at Scripps Institution of Oceanography at the University of California San Diego in 2018, with support from Igor Korneitchouk and the Wilsdorf Mettler Future Foundation. We thank the workshop participants for early discussions and a collaborative meeting space. We thank Kelly Lance for her illustration contributions, and the SIO Communications Office for their support. We thank Miriam Doyle and Ryan Rykaczewski for their assistance in data acquisition, and we thank Penny Dockry and Stuart Sandin of CMBC for administrative and logistical support. Julia Chavarry was supported by the San Diego Fellowship. This paper is a contribution from the California Current Ecosystem Long Term Ecological Research site, supported by the National Science Foundation

Pimavanserin and Lorcaserin Attenuate Measures of Binge Eating in Male Sprague-Dawley Rats

Binge eating disorder (BED) is characterized by dysregulated feeding and reward-related processes, and treatment is often challenged by limited therapeutic options. The serotonin (5-HT) 5-HT2A receptor (5-HT2AR) and 5-HT2CR are implicated in both feeding-related and reward-related behaviors and are thus poised to regulate BED-related behaviors. The purpose of this study was to assess the efficacy of the FDA-approved medications pimavanserin, a 5-HT2AR antagonist/inverse agonist, and lorcaserin, a 5-HT2CR agonist, in a rodent model of binge eating. The effects of pimavanserin (0.3–3.0 mg/kg), lorcaserin (0.25–1.0 mg/kg), and the lowest effective dose of pimavanserin (0.3 mg/kg) plus lorcaserin (1.0 mg/kg) were tested in a high-fat food (HFF) intermittent access binge eating model in adult male Sprague-Dawley rats (n = 64). We assessed three measures related to binge eating – binge episode occurrence, binge intake, and weight gain associated with HFF access. Pimavanserin decreased binge intake and weight gain associated with HFF access, but did not prevent binge episode occurrence. Lorcaserin decreased binge intake, but did not prevent binge episode occurrence or weight gain associated with HFF access. Combined pimavanserin plus lorcaserin prevented binge episode occurrence in addition to decreasing binge intake and weight gain associated with HFF access. These preclinical findings in male rats suggest that pimavanserin and lorcaserin may be effective in treating patients with BED. Our studies further indicate that administration of one or both drugs may be more effective in certain sub-populations of patients with BED because of the unique profile each treatment elicits. These data support future assessment in clinical populations with BED

Numerical simulation of strongly nonlinear and dispersive waves using a Green-Naghdi model

We investigate here the ability of a Green-Naghdi model to reproduce strongly nonlinear and dispersive wave propagation. We test in particular the behavior of the new hybrid finite-volume and finite-difference splitting approach recently developed by the authors and collaborators on the challenging benchmark of waves propagating over a submerged bar. Such a configuration requires a model with very good dispersive properties, because of the high-order harmonics generated by topography-induced nonlinear interactions. We thus depart from the aforementioned work and choose to use a new Green-Naghdi system with improved frequency dispersion characteristics. The absence of dry areas also allows us to improve the treatment of the hyperbolic part of the equations. This leads to very satisfying results for the demanding benchmarks under consideration

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n = 20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon

Dark Energy or Apparent Acceleration Due to a Relativistic Cosmological Model More Complex than FLRW?

We use the Szekeres inhomogeneous relativistic models in order to fit supernova combined data sets. We show that with a choice of the spatial curvature function that is guided by current observations, the models fit the supernova data almost as well as the LCDM model without requiring a dark energy component. The Szekeres models were originally derived as an exact solution to Einstein's equations with a general metric that has no symmetries and are regarded as good candidates to model the true lumpy universe that we observe. The null geodesics in these models are not radial. The best fit model found is also consistent with the requirement of spatial flatness at CMB scales. The first results presented here seem to encourage further investigations of apparent acceleration using various inhomogeneous models and other constraints from CMB and large structure need to be explored next.Comment: 6 pages, 1 figure, matches version published in PR

Machine-Learning Approach Identifies a Pattern of Gene Expression in Peripheral Blood that can Accurately Detect Ischaemic Stroke

Early and accurate diagnosis of stroke improves the probability of positive outcome. The objective of this study was to identify a pattern of gene expression in peripheral blood that could potentially be optimised to expedite the diagnosis of acute ischaemic stroke (AIS). A discovery cohort was recruited consisting of 39 AIS patients and 24 neurologically asymptomatic controls. Peripheral blood was sampled at emergency department admission, and genome-wide expression profiling was performed via microarray. A machine-learning technique known as genetic algorithm k-nearest neighbours (GA/kNN) was then used to identify a pattern of gene expression that could optimally discriminate between groups. This pattern of expression was then assessed via qRT-PCR in an independent validation cohort, where it was evaluated for its ability to discriminate between an additional 39 AIS patients and 30 neurologically asymptomatic controls, as well as 20 acute stroke mimics. GA/kNN identified 10 genes (ANTXR2, STK3, PDK4, CD163, MAL, GRAP, ID3, CTSZ, KIF1B and PLXDC2) whose coordinate pattern of expression was able to identify 98.4% of discovery cohort subjects correctly (97.4% sensitive, 100% specific). In the validation cohort, the expression levels of the same 10 genes were able to identify 95.6% of subjects correctly when comparing AIS patients to asymptomatic controls (92.3% sensitive, 100% specific), and 94.9% of subjects correctly when comparing AIS patients with stroke mimics (97.4% sensitive, 90.0% specific). The transcriptional pattern identified in this study shows strong diagnostic potential, and warrants further evaluation to determine its true clinical efficacy

An improved ovine reference genome assembly to facilitate in depth functional annotation of the sheep genome

BACKGROUND: The domestic sheep (Ovis aries) is an important agricultural species raised for meat, wool, and milk across the world. A high-quality reference genome for this species enhances the ability to discover genetic mechanisms influencing biological traits. Furthermore, a high-quality reference genome allows for precise functional annotation of gene regulatory elements. The rapid advances in genome assembly algorithms and emergence of sequencing technologies with increasingly long reads provide the opportunity for an improved de novo assembly of the sheep reference genome. FINDINGS: Short-read Illumina (55× coverage), long-read Pacific Biosciences (75× coverage), and Hi-C data from this ewe retrieved from public databases were combined with an additional 50× coverage of Oxford Nanopore data and assembled with canu v1.9. The assembled contigs were scaffolded using Hi-C data with Salsa v2.2, gaps filled with PBsuitev15.8.24, and polished with Nanopolish v0.12.5. After duplicate contig removal with PurgeDups v1.0.1, chromosomes were oriented and polished with 2 rounds of a pipeline that consisted of freebayes v1.3.1 to call variants, Merfin to validate them, and BCFtools to generate the consensus fasta. The ARS-UI_Ramb_v2.0 assembly is 2.63 Gb in length and has improved continuity (contig NG50 of 43.18 Mb), with a 19- and 38-fold decrease in the number of scaffolds compared with Oar_rambouillet_v1.0 and Oar_v4.0. ARS-UI_Ramb_v2.0 has greater per-base accuracy and fewer insertions and deletions identified from mapped RNA sequence than previous assemblies. CONCLUSIONS: The ARS-UI_Ramb_v2.0 assembly is a substantial improvement in contiguity that will optimize the functional annotation of the sheep genome and facilitate improved mapping accuracy of genetic variant and expression data for traits in sheep

On the extraction of electromagnetic properties of the Delta(1232) excitation from pion photoproduction

Several methods for the treatment of pion photoproduction in the region of the Delta(1232) resonance are discussed, in particular the effective Lagrangian approach and the speed plot analysis are compared to a dynamical treatment. As a main topic, we discuss the extraction of the genuine resonance parts of the magnetic dipole and electric quadrupole multipoles of the electromagnetic excitation of the resonance. To this end, we try to relate the various values for the ratio R_{EM} of the E2 to M1 multipole excitation strengths for the Delta(1232) resonance as extracted by the different methods to corresponding ratios of a dynamical model. Moreover, it is confirmed that all methods for extracting resonance properties suffer from an unitary ambiguity which is due to some phenomenological contributions entering the models.Comment: 22 pages revtex including 7 postscript figure