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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

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

Changes in the colon microbiota and intestinal cytokine gene expression following minimal intestinal surgery

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World Journal of Gastroenterology 2015年第14期21卷 4150-4158页

作者： Susan Lapthorne Julie E Bines Fiona Fouhy Nicole L dellios Guineva Wilson Sarah L Thomas Michelle Scurr Catherine Stanton paul d.cotter Prue M Pereira-Fantini Intestinal Failure and Clinical Nutrition group Murdoch Childrens Research InstituteRoyal Children’s Hospital Intestinal Failure and Clinical Nutrition group Murdoch Childrens Research Institute department of Paediatrics the University of Melbourne department of Gastroenterology and Clinical Nutrition Royal Children’s Hospital Teagasc Food Research Centre MooreparkFermoyCorkIreland department of Microbiology University College Cork department of Surgery Monash Medical Centre Alimentary Pharmabiotic Centre University College Cork

AIM: To investigate the impact of minor abdominal surgery on the caecal microbial population and on markers of gut ***: Four week old piglets were randomly allocated to a no-surgery "control" group(n = 6) or a "transection surgery" group(n = 5).during the transection surgery procedure, a conventional midline incision of the lower abdominal wall was made and the small intestine was transected at a site 225 cm proximal to the ileocaecal valve, a 2 cm segment was removed and the intestine was *** received a polymeric infant formula diet throughout the study period and were sacrificed at two weeks *** outcomes including weight, stool consistency and presence of stool fat globules were *** throughput dNA sequencing of colonic content was used to detect surgery-relateddisturbances in microbial composition at phylum, family and genus *** and richness estimates were calculated for the control and minor surgery *** disturbances in the gut microbial community are linked to inflammation we compared the gene expression of key inflammatory cytokines(TNF, IL1 B, IL18, IL12, IL8, IL6 and IL10) in ileum, terminal ileum and colon mucosal extracts obtained from control and abdominal surgery groups at two weeks ***: Changes in the relative abundance of bacterial species at family and genus level were confined to bacterial members of the Proteobacteria and Bacteroidetes *** level compositional shifts included a reduction in the relative abundance of Enterobacteriaceae(22.95 ± 5.27 vs 2.07 ± 0.72, P daceae(2.54 ± 0.56 vs 0.86 ± 0.43, P d Rhodospirillaceae(0.40 ± 0.14 vs 0.00 ± 0.00, P d with transection surgery were restricted to members of the Proteobacteria and Bacteroidetes phyla and included decreased relative abundance of Enterobacteriaceae(29.20 ± 6.74 vs 2.88 ±

关键词： Surgery Intestinal Microbiota dysbiosis Inflammati

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

Enhanced Trust Based Access Control for Multi-Cloud Environment

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Computers, Materials & Continua 2021年第12期69卷 3079-3093页

作者： N.R.Rejin paul d.paul Raj Technology PuduvoyalGummidipoondi601206India R M d Engineering College KavaraipettaiGummidipoondi601206India

Security is an essential part of the cloud *** ensuring the security of the data being communicated to and from the cloud server,a significant parameter called trust was ***-based security played a vital role in ensuring that the communication between cloud users and service providers remained unadulterated and *** most cloud-based data distribution environments,emphasis is placed on accepting trusted client users’requests,but the cloud servers’integrity is seldom *** paper designs a trust-based access control model based on user and server characteristics in a multi-cloud environment to address this *** proposed methodology consists of data encryption using Cyclic Shift Transposition Algorithm and trust-based access control *** this trust-based access control mechanism framework,trust values are assigned to cloud users using direct trust *** direct trust degree is estimated based on the following metrics:success and failure rate of interactions,service satisfaction index,and dishonesty *** addition to this,trust values are assigned to cloud servers based on the metrics:server load,service rejection rate,and service access *** role-Based Access control policy of each user is modified based on his trust *** the server fails to meet the minimum trust level,then another suitable server will be *** proposed system is found to outperform other existing systems in a multi-cloud environment.

关键词： Cloud computing trust access control cloud service provider cloud data user CSTA

Testosterone and cardiovascular disease in men

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Asian Journal of Andrology 2012年第3期14卷 428-435,I0007页

作者： paul d Morris Kevin S Channer Sheffield Teaching Hospital NHS Trust Sheffield S10 2JF UK

despite regional variations in the prevalence of coronary artery disease （CAd）, men are consistently more at risk of developing and dying from CAd than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ＇Perspectives＇ article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ＇cause＇ versus ＇effect＇ controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease.

关键词： atherosclerosis chronic heart failure ischaemic heart disease replacement therapy testosterone

Assessing mixing characteristics of particle-mixing and granulation devices

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Particuology 2008年第6期6卷 419-444页

作者： paul W. Cleary Matthew d. Sinnott CSIRO Mathematical and Information Sciences

The mixing of particulates such as powders is an important process in many industries including pharmaceuticals, plastics, household products （such as detergents） and food processing. The quality of products depends on the degree of mixing of their constituent materials which in turn depends on both geometric design and operating conditions. Unfortunately, due to lack of understanding of the interaction between mixer geometry and the granular material, limited progress has been made in optimizing mixer design. The discrete element method （dEM） is a computational technique that allows particle systems to be simulated and mixing to be predicted. Simulation is an effective way of acquiring information on the performance of different mixers that is difficult and/or expensive to obtain using traditional experimental approaches. Here we demonstrate how dEM can be used to unravel flow dynamics and assess mixing in several different types of devices. These devices used for mixing and/or granulation of particulates, are classified broadly as gravity controlled, bladed and high shear. We also explore the role of particle shape in mixing performance and use dEM to test whether Froude number scaling is suitable for predicting scale performance of rotating mixers.

关键词： discrete element modelling Mixing Mixers Blenders Granulation Scale up Particle shape