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Evidence supporting the relationship between maternal asthma and risk for autism spectrum disorders

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Neural Regeneration Research 2025年第4期20卷 1101-1102页

作者： Hadley Osman paul Ashwood department of Medical Microbiology and Immunology and the M.I.N.D.InstituteUniversity of California at DavisSacramentoCAUSA

during pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing *** has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASd)in the *** is characterized by increased repetitive and stereotyped behaviors and decreased *** of 2020,1 in 36 children are diagnosed with ASd by the age of 8 years,with ASd rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ***,the etiology of ASd is largely unknown,however,genetic components and environmental factors can contribute to increased *** allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.

关键词： disorders epidemiology fetus

Emerging insights into the function of very long chain fatty acids at cerebellar synapses

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Neural Regeneration Research 2025年第6期20卷 1709-1710页

作者： Martin-paul Agbaga Mohiuddin Ahmad department of Cell Biology and Ophthalmology University of Oklahoma Health Sciences Centerand Dean McGee Eye InstituteOklahoma CityOKUSA

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

关键词： functions function insight

Plant-available water capacity of soils at a regional scale:Analysis of fixed and dynamic field capacities

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Pedosphere 2024年第3期34卷 590-605页

作者： Vinod PHOGAT paul RPETRIE Casandra collins Marcos BONAdA South Australian Research and development Institute GPO Box 397Adelaide SA 5001(Australia) School of Agriculture Food and WineWaite Research InstituteUniversity of AdelaideWaite CampusPMB1Glen Osmond SA 5064(Australia) College of Science and Engineering Flinders UniversityBedford Park SA 5042(Australia) The University of New South Wales Sydney NSW 2052(Australia) ARC Training Centre for Innovative Wine Production University of AdelaidePMB1Glen Osmond SA 5064(Australia)

Estimation of the plant-available water capacity(PAWC)of soils at a regional scale helps in adopting better land use planning,developing suitable irrigation schedules for crops,and optimizing the use of scarce water *** the current study,72 soil profiles were sampled from the Barossa region of South Australia to estimate pedo-transfer functions deduced from easily estimated soil *** functions were then used to estimate the fixed(10 and 33 kPa)and dynamic pressure head(h_(fc))water contents at field capacity(FC)for minimum drainage flux(0.01 and 0.001 cm d^(-1)),which serves as the upper boundary for plant-available water in *** estimated residual water content was corrected for subsoil constraints,especially the exchangeable sodium percentage(ESP).The results showed that the mean values of h_(fc)in sand-dominated light and medium textured soils(i.e.,sand,loamy sand,sandy loam,and loam)varied in a narrow range(15.8-18.2 kPa),whereas those in the clay-dominated heavy textured soils(i.e.,clay loam)showed a wide range(11.3-49.3 kPa).There were large differences in PAWC for dynamic FC(PAWC_(fc))and fixed FC at 10 kPa(PAWC10),33 kPa(PAWC33),and a mix of 10and 33 kPa(PAWC_(10,33))pressure heads depending on soil ***,the difference between PAWC at 10 kPa and h_(fc)(ΔPAWC_(10))was positive,whereas that between 33 kPa and h_(fc)(ΔPAWC_(33))was negative across all ***,the estimation of PAWC assuming a fixed FC at 10 and 33 kPa pressures(i.e.,PAWC_(10,33))for sandy,clay,and silty soils reduced the difference between fixed and dynamic pressure PAWCs tod by incorporating the impact of subsoil constraints,such as high ESP,which was more pronounced for clay and silty *** findings demonstrate the inherent inconsistencies between static pressure and flux-based dynamic FC estimations in *** heterogeneity,intra-texture variability,subsoil constraints,and swell

关键词： crop lower limit drained upper limit pedo-transfer function soil hydraulic parameter soil texture

The gut microbiome: an orchestrator of xenobiotic metabolism

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Acta Pharmaceutica Sinica B 2020年第1期10卷 19-32页

作者： Stephanie L.collins Andrew d.Patterson department of Biochemistry Microbiologyand Molecular Biologythe Pennsylvania State UniversityUniversity ParkPA 16802USA department of Veterinary and Biomedical Science the Pennsylvania State UniversityUniversity ParkPA 16802USA

Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic *** gut microbiome,the collection of microorganisms in the gastrointestinal tract,can alter the metabolic outcome of pharmaceuticals,environmental toxicants,and heavy metals,thereby changing their *** chemical modification of xenobiotics by the gut microbiome,either through the intestinal tract or re-entering the gut via enterohepatic circulation,can lead to increased metabolism or bioactivation,depending on the enzymatic activity within the microbial *** enzymes encoded within the microbiome include those that reverse the modifications imparted by host detoxification ***,the microbiome can limit xenobiotic absorption in the small intestine by increasing the expression of cell-cell adhesion proteins,supporting the protective mucosal layer,and/or directly sequestering ***,host gene expression is regulated by the microbiome,including CYP450s,multi-drug resistance proteins,and the transcription factors that regulate *** the microbiome affects the host and pharmacokinetics of the xenobiotic,xenobiotics can also influence the viability and metabolism of the *** understanding of the complex interconnectedness between host,microbiome,and metabolism will advance with new modeling systems,technology development and refinement,and mechanistic studies focused on the contribution of human and microbial metabolism.

关键词： Gut microbiome Xenobiotic metabolism Absorption Gastrointestinal tract Pharmacokinetics Enterohepatic circulation Bioactivation

Immune dysfunction in acute alcoholic hepatitis

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World Journal of Gastroenterology 2015年第42期21卷 11904-11913页

作者： Ashwin d dhanda Peter L collins School of Clinical Sciences University of Bristol NIHR Academic Clinical Lecturer in Hepatology Institute of Translational and Stratified Medicine Plymouth University Peninsula Schools of Medicine and Dentistry South West Liver Unit Plymouth Hospitals NHS Trust department of Liver Medicine University Hospitals Bristol NHS Foundation Trust

Acute alcoholic hepatitis(AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogenassociated molecular particles(PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors(mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this.

关键词： Alcoholic hepatitis Alcoholic liver disease Toll-l

distinct expression profiles of transcriptional coactivators for thyroid hormone receptors during Xenopus laevis metamorphosis

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Cell Research 2003年第6期13卷 459-464页

作者： BINdU d paul National Institutes of Health Laboratory of Gene Regulation and development National Institute of Child Health and Human development Bldg. USA.

The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orchestrated developmental changes, which ultimately result in the conversion of an aquatic herbivorous tadpole to a terrestrial carnivorous frog. T3 is presumed to bind to TRs, which in turn recruit coactivators, leading to gene activation. The best-studied coactivators belong to the p160 or SRC family. Members of this family include SRC1/ NCoA-1, SRC2/TIF2/GRIP1, and SRC3/pCIP/ACTR/AIB-l/RAC-3/TRAM-1. These SRCs interact directly with liganded TR and function as adapter molecules to recruit other coactivators such as p300/CBP. Here, we studied the expression patterns of these coactivators during various stages of development. Amongst the coactivators cloned in Xenopus laevis, SRC3 was found to be dramatically upregulated during natural and T3-induced metamorphosis, and SRC2 and p300 are express

关键词： transcription coactivators thyroid hormone receptor Xenopus laevis metamorphosis histone acetylation.

Increased Light, Moderate, and Severe Clear-Air Turbulence in Response to Climate Change

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Advances in Atmospheric Sciences 2017年第5期34卷 576-586页

作者： paul d. WILLIAMS department of Meteorology University of Reading Reading RG6 6BB United Kingdom

Anthropogenic climate change is expected to strengthen the vertical wind shears at aircraft cruising altitudes within the atmospheric jet streams. Such a strengthening would increase the prevalence of the shear instabilities that generate clear-air turbulence. Climate modelling studies have indicated that the amount of moderate-or-greater clear-air turbulence on transatlantic flight routes in winter will increase significantly in future as the climate changes. However,the individual responses of light,moderate,and severe clear-air turbulence have not previously been studied,despite their importance for aircraft operations. Here,we use climate model simulations to analyse the transatlantic wintertime clear-air turbulence response to climate change in five aviation-relevant turbulence strength categories. We find that the probability distributions for an ensemble of 21 clear-air turbulence diagnostics generally gain probability in their right-hand tails when the atmospheric carbon dioxide concentration is doubled. By converting the diagnostics into eddy dissipation rates,we find that the ensembleaverage airspace volume containing light clear-air turbulence increases by 59%(with an intra-ensemble range of 43%–68%),light-to-moderate by 75%(39%–96%),moderate by 94%(37%–118%),moderate-to-severe by 127%(30%–170%),and severe by 149%(36%–188%). These results suggest that the prevalence of transatlantic wintertime clear-air turbulence will increase significantly in all aviation-relevant strength categories as the climate changes.

关键词： turbulence climate change aviation jet stream

High-resolution geological maps of central London, UK： Comparisons with the London Underground

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Geoscience Frontiers 2016年第2期7卷 273-286页

作者： Jonathan d. paul department of Earth Sciences Bullard Laboratories University of Cambridge Madingley Rise Cambridge CB3 0EZ UK

This study presents new thickness maps of post-Cretaceous sedimentary strata beneath central London. 〉1100 borehole records were analysed. London Clay is thickest in the west; thicker deposits extend as a narrow finger along the axis of the London Basin. More minor variations are probably governed by periglacial erosion and faulting. A shallow anticline in the Chalk in north-central London has resulted in a pronounced thinning of succeeding strata. These results are compared to the position of London Underground railway tunnels. Although tunnels have been bored through the upper levels of London Clay where thick, some tunnels and stations are positioned within the underlying, more lithologically variable, Lower London Tertiary deposits. Although less complex than other geological models of the London Basin, this technique is more objective and uses a higher density of borehole data. The high resolution of the resulting maps emphasises the power of modelling an expansive dataset in a rigorous but simnle fashion.

关键词： London London Underground London Clay Lambeth Group Chalk Tunnelling Boreholes

Chronic kidney disease and the skeleton

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Bone Research 2014年第4期2卷 205-217页

作者： paul d Miller Colorado Center for Bone Research LakewoodCO.USA

Fractures across the stages of chronic kidney disease （CKd） could be due to osteoporosis, some form of renal osteodystrophy defined by specific quantitative histomorphometry or chronic kidney disease-mineral and bone disorder （CKd-MBd）. CKd-MBd is a systemic disease that links disorders of mineral and bone metabolism due to CKd to either one or all of the following： abnormalities of calcium, phosphorus, parathyroid hormone or vitamin d metabolism; abnormalities in bone turnover, mineralization, volume, linear growth or strength; or vascular or other soft-tissue calcification. Osteoporosis, as defined by the National Institutes of Health, may coexist with renal osteodystrophy or CKd-MBd. differentiation among these disorders is required to manage correctly the correct disorder to reduce the risk of fractures. While the World Health Organization （WHO） bone mineral density （BMd） criteria for osteoporosis can be used in patients with stages 1-3 CKd, the disorders of bone turnover become so aberrant by stages 4 and 5 CKd that neither the WHO criteria nor the occurrence of a fragility fracture can be used for the diagnosis of osteoporosis. The diagnosis of osteoporosis in stages 4 and 5 CKd is one of the exclusion--excluding either renal osteodystrophy or CKd- MBd as the cause of low BMd or fragility fractures. differentiations among the disorders of renal osteodystrophy, CKd-MBd or osteoporosis are dependent on the measurement of specific biochemical markers, including serum parathyroid hormone （PTH） and/or quantitative bone histomorphometry. Management of fractures in stages 1-3 CKd does not differ in persons with or without CKd with osteoporosis assuming that there is no evidence for CKd-MBd, clinically suspected by elevated PTH, hyperphosphatemia or fibroblast growth factor 23 due to CKd. Treatment of fractures in persons with osteoporosis and stages 4 and 5 CKd is not evidence-based, with the exception of post-hoc analysis suggesting efficacy and safety of specific o

关键词： CKd GFR PTH MBd