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Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

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Neural Regeneration Research 2024年第2期19卷 355-359页

作者： Courtney j.Rouse Victoria N.jensen coy d.Heldermon Lacerta Therapeutics AlachuaFLUSA University of Florida College of Medicine GainesvilleFLUSA

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for *** results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological *** treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢ***-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential *** group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy ***,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.

关键词： adeno-associated virus central nervous system gene therapy heparan sulfate immune response mucopolysaccharidoses type IIIB N-acetyl-alpha-glucosaminidase newborn screening

Photoionisation detection of a single Er3+ ion with sub-100-ns time resolution

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National Science Review 2024年第4期11卷 38-45页

作者： Yangbo Zhang Wenda Fan jiliang Yang Hao Guan Qi Zhang Xi Qin Changkui duan Gabriele G.de Boo Brett C.johnson jeffrey C.mc Callum Matthew j.Sellars Sven Rogge Chunming Yin jiangfeng du CAS Key Laboratory of Microscale Magnetic Resonance and School of Physical Sciences University of Science and Technology of China CAS Center for Excellence in Quantum Information and Quantum Physics University of Science and Technology of China Hefei National Laboratory University of Science and Technology of China Centre of Excellence for Quantum Computation and Communication Technology School of Physics University of New South Wales Centre of Excellence for Quantum Computation and Communication Technology School of Engineering RMIT University Centre of Excellence for Quantum Computation and Communication Technology School of Physics University of Melbourne Centre of Excellence for Quantum Computation and Communication Technology Research School of Physics and Engineering Australian National University

Efficient detection of single optical centres in solids is essential for quantum information processing, sensing and single-photon generation *** this work,we use radio-frequency（RF） reflectometry to electrically detect the photoionisation induced by a single Er3+ion in *** high bandwidth and sensitivity of the RF reflectometry provide sub-100-ns time resolution for the photoionisation *** this technique,the optically excited state lifetime of a single Er3+ion in a Si nano-transistor is measured for the first time to be 0.49±0.04μ*** results demonstrate an efficient approach for detecting a charge state change induced by Er excitation and *** approach could be used for fast readout of other single optical centres in solids and is attractive for large-scale integrated optical quantum systems thanks to the multi-channel RF reflectometry demonstrated with frequency multiplexing techniques.

关键词： single optical centres erbium ions RF reflectometry photoionisation detection

Mineral concentrations of chickpea and lentil cultivars and breeding lines grown in the *** Northwest

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The Crop journal 2018年第3期6卷 253-262页

作者： George j.VANdemark Michael A.Grusak Rebecca j.mc Gee USdA-ARS Grain Legume Genetics and Physiology Research Unit USdA-ARS Red River Valley Agricultural Research Center

diseases and health complications caused by mineral deficiencies afflict billions of people globally. developing pulse crops with elevated seed mineral concentrations can contribute to reducing the incidence of these deficiencies. The objectives of this study were to estimate variance components conditioning seed mineral concentrations of chickpea and lentil grown in Washington and Idaho, determine correlations between different mineral concentrations and between mineral concentrations and yield, 100-seed weight, and days to flowering, and compare seed mineral concentrations between chickpeas and lentils grown in adjacent plots. Genotype effects, although significant in chickpea and lentil for all minerals except selenium, tended to be minimal compared to location, year, and their interaction effects. In both chickpeas and lentils high positive correlations were observed between seed concentrations of phosphorus and potassium, phosphorus and zinc, and potassium and zinc. Correlations between mineral concentration and yield, and mineral concentration and days to 50% flowering were similar for chickpeas and lentils across the majority of minerals. These results may reflect similarities between the two crops in physiological processes for mineral uptake and partitioning. Lentils had higher concentrations of iron and zinc than chickpea when the two crops were grown in adjacent plots,whereas chickpeas had higher concentrations of calcium and manganese. Plant genotypes that are more efficient at obtaining minerals from growing environments will be useful as parental materials to develop improved chickpea and lentil cultivars that have good yield potential coupled with high seed mineral concentrations.

关键词： Chickpea Lentil Mineral Nutrition Pulse

Factors associated with increased incidence of severe toxicities following yttrium-90 resin microspheres in the treatment of hepatic malignancies

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World journal of Gastroenterology 2016年第10期22卷 3006-3014页

作者： john d Roberson II Andrew M mc donald Craig j Baden Chee Paul Lin Rojymon jacob Omer L Burnett III School of Medicine University of Alabama at Birmingham Birmingham AL 35294-3412 United States department of Radiation Oncology University of Alabama at Birmingham Birmingham AL 35233 United States Center for Clinical and Translational Science University of Alabama at Birmingham Birmingham AL 35205 United States

AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (90Y) ***: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following 90Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P ded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe ***: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELd) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELd, and colorectal histology when choosing appropriate candidates for 90Y microsphere therapy.

关键词： Yttrium-90 microspheres Liver metastases Multivariate analysis Toxicity incidence Colorectal adenocarcinoma

苜蓿属不同种NaCl耐性的组织培养评价:细胞与植株的反应

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核农学通报 1988年第1期 23-24页

作者： T.j.mc coy 郑企成

研究证明,筛选耐 NaCl 细胞系是一种简易而有效的方法。几乎所有耐 NaCl 细胞系的培养筛选都依靠自然变异。当利用突变体时,如在柑桔耐 NaCl 细胞系的选择中,发现其回复率并未增加。尽管耐 NaCl 细胞系是容易选择的,但只有少数离体筛选... 详细信息

研究证明,筛选耐 NaCl 细胞系是一种简易而有效的方法。几乎所有耐 NaCl 细胞系的培养筛选都依靠自然变异。当利用突变体时,如在柑桔耐 NaCl 细胞系的选择中,发现其回复率并未增加。尽管耐 NaCl 细胞系是容易选择的,但只有少数离体筛选能够获得可遗传的耐性植株。Nabors 等获得了可耐3.3%NaCl 的烟草可遗传株。不过在多数情况下,选出的耐 NaCl 细胞系不能再生植株或未能

关键词：耐性细胞水平 NaCl 愈伤组织创伤组织植株细胞反应

Effects of live yeast on differential genetic and functional attributes of rumen microbiota in beef cattle

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journal of Animal Science and Biotechnology 2019年第4期10卷 1101-1107页

作者： Ibukun M.Ogunade jerusha Lay Kenneth Andries Christina j.mc Manus Frederick Bebe College of Agriculture Communities and the Environment Kentucky State University

Several studies have evaluated the effects of live yeast supplementation on rumen microbial population;however,its effect on differential microbial genes and their functional potential has not been described. Thus, this study applied shotgun metagenomic sequencing to evaluate the effects of live yeast supplementation on genetic and functional potential of the rumen microbiota in beef cattle. Eight rumen-cannulated Holstein steers were randomly assigned to two treatments in a cross-over design with two 25-day experimental periods and a 10-day wash-out between the two periods. The steers were housed in individual pens and fed 50% concentrate-mix and 50% red clover/orchard hay ad libitum. Treatments were(1) control(CON;basal diet without additive) and(2) yeast(YEA;basal diet plus 15 g/d of live yeast product). Rumen fluid samples were collected at 3, 6, and 9 h after feeding on the last d of each period. Sequencing was done on an Illumina Hi Seq 2500 platform. dietary yeast supplementation increased the relative abundance of carbohydrate-fermenting bacteria(such as Ruminococcus albus, ***, R. bromii, and R. obeum) and lactate-utilizing bacteria(such as Megasphaera elsdenii, desulfovibrio desulfuricans, and d. vulgaris). A total of 154 differentially abundant genes(dEGs) were obtained(false discovery rate dia of Genes and Genomes(KEGG) annotation analysis of the dEGs revealed that 10 pathways, including amino sugar and nucleotide sugar metabolism, oxidative phosphorylation, lipopolysaccharide biosynthesis, pantothenate and coenzyme A biosynthesis, glutathione metabolism, beta-alanine metabolism,polyketide sugar unit biosynthesis, protein export, ribosome, and bacterial secretory system, were enriched in steers fed YEA. Annotation analysis of the dEGs in the carbohydrate-active enzymes(CAZy) database revealed that the abundance of genes coding for enzymes belonging to glycoside hydrolases, glycosyltransferases, and carbohydrate bindi

关键词： Functional potential Live yeast Rumen

delayed gastric emptying following pancreaticoduodenectomy:Incidence,risk factors,and healthcare utilization

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World journal of Gastrointestinal Surgery 2017年第3期9卷 73-81页

作者： Somala Mohammed George Van Buren II Amy mc Elhany Eric j Silberfein William E Fisher Elkins Pancreas Center Michael E DeBakey Department of SurgeryBaylor College of MedicineHoustonTX 77030United States

AIM To characterize incidence and risk factors for delayed gastric emptying(dGE) following pancreaticoduodenectomy and examine its implications on healthcare utilization. METHOdS A prospectively-maintained database was reviewed. dGE was classified using International Study Group of Pancreatic Surgery criteria. Patients who developed dGE and those who did not were compared. RESULTS Two hundred and seventy-six patients underwent pancreaticoduodenectomy(Pd)(> 80% pyloruspreserving, antecolic-reconstruction). dGE developed in 49 patients(17.8%): 5.1% grade B, 3.6% grade C. demographic, clinical, and operative variables were similar between patients with dGE and those without. dGE patients were more likely to present multiplecomplications(32.6% vs 4.4%, ≥ 3 complications, P ding postoperative pancreatic fistula(POPF)(42.9% vs 18.9%, P = 0.001) and intra-abdominal abscess(IAA)(16.3% vs 4.0%, P = 0.012). Patients with dGE had longer hospital stay(median, 12 d vs 7 d, P d were more likely to require transitional care upon discharge(24.5% vs 6.6%, P dictors for dGE included POPF [OR = 3.39(1.35-8.52), P = 0.009] and IAA [OR = 1.51(1.03-2.22), P = 0.035].CONCLUSION Although dGE occurred in d, it was associated with increased healthcare utilization. Patients with POPF and IAA were at risk for dGE. Anticipating dGE can help individualize care and allocate resources to high-risk patients.

关键词： delayed gastric emptying Pancreaticoduodenectomy Post-operative pancreatic fistula

Rumen-protected methionine during the peripartal period in dairy cows and its effects on abundance of major species of ruminal bacteria

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journal of Animal Science and Biotechnology 2018年第2期9卷 460-466页

作者： Mohamed K.Abdelmegeid Ahmed A.Elolimy Zheng Zhou Vincenzo Lopreiato joshua C.mc Cann juan j.Loor department of Animal Sciences Mammalian Nutri Physio GenomicsUniversity of Illinois department of Animal Medicine Faculty of Veterinary Medicine Kafrelsheikh University department of Animal and Veterinary Sciences Clemson University department of Health Science Interdepartmental Services Centre of Veterinary for Human and Animal Health Magna Gr?cia University of Catanzaro division of Nutritional Sciences Illinois Informatics Institute University of Illinois

Background: Extensive degradation of amino acids in the rumen via microbial deamination decreases the postruminal availability of dietary indispensable amino acids. Together with the normal decrease in voluntary dry matter intake(dMI) around parturition in dairy cows, microbial metabolism contributes to a markedly negative balance of indispensable amino acids, including methionine which may be the first-limiting for milk production. The main objective of the current study was to profile changes in major bacterial species with key functions in cel ulose and hemicel ulose digestion, xylan breakdown, proteolytic action, propionic acid production, lactate utilization and ruminal biohydrogenation in cows supplemented with rumen-protected Methionine(SM; Smartamine M, Adisseo NA, Alpharetta,GA, USA) from-23 through 30 d relative to parturition. Because ~90% of the methionine in SM bypasses the rumen,~10% of the methionine is released into the rumen and can be utilized by ***: As expected, there was an increase in overall dMI after parturition(day, P during which cows consumed on average 19.6 kg/d versus 13.9 kg/d in the prepartum period. The postpartum diet contained greater concentrations of lipid and highly-fermentable carbohydrate from corn grain, which likely explains the increases in the relative abundance of Anaerovibrio lipolytica, Megasphaera elsdenii, Prevotella bryantii, Selenomonas ruminantium,Streptococcus bovis, and Succinimonas amylolytica. despite similar dMI prepartum, cows fed SM had greater(Treatment × day, P dance prepartum of Fibrobacter succinogenes, Succinimonas amylolytica, and Succinivibrio dextrinosolvens. However, the greater dMI in cows fed SM after parturition(19.6 kg/d versus 13.9 kg/d) was associated with lower abundance of Fibrobacter succinogenes(2.13 × 10-3 versus 2.25 × 10-4) and Selenomonas ruminantium(2.98 × 10-1 versus 4.10 × 10-1). A lower abundance(day, P detected on d 20 compared with d-10

关键词： Microbiome Rumen microbes Transition cow

When will it end? Long-lived intracontinental reactivation in central Australia

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Geoscience Frontiers 2019年第1期10卷 149-164页

作者： Raphael Quentin de Gromard Christopher L.Kirkland Heather M.Howard Michael T.d.Wingate Fred jourdan Brent I.A.mc Innes Martin danisik Noreen j.Evans Bradley j.mcdonald R.Hugh Smithies Geological Survey of Western Australia Department of Mines Industry Regulation and Safety School of Earth and Planetary Science/john de Laeter Centre/TIGeR Curtin University

The post-Mesoproterozoic tectonometamorphic history of the Musgrave Province, central Australia, has previously been solely attributed to intracontinental compressional deformation during the 580 -520 Ma Petermann Orogeny. However, our new structurally controlled multi-mineral geochronology results,from two north-trending transects, indicate protracted reactivation of the Australian continental interior over ca. 715 million years. The earliest events are identified in the hinterland of the orogen along the western transect. The first tectonothermal event, at ca. 715 Ma, is indicated by40 Ar/39 Ar muscovite and U e Pb titanite ages. Another previously unrecognised tectonometamorphic event is dated at ca. 630 Ma by Ue Pb analyses of metamorphic zircon rims. This event was followed by continuous cooling and exhumation of the hinterland and core of the orogen along numerous faults, including the Woodroffe Thrust,from ca. 625 Ma to 565 Ma as indicated by muscovite, biotite, and hornblende40 Ar/39 Ar cooling ages. We therefore propose that the Petermann Orogeny commenced as early as ca. 630 Ma. Along the eastern transect,40 Ar/39 Ar muscovite and zircon(Ue Th)/He data indicate exhumation of the foreland fold and thrust system to shallow crustal levels between ca. 550 Ma and 520 Ma, while the core of the orogen was undergoing exhumation to mid-crustal levels and cooling below 600-660℃. Subsequent cooling to 150 -220℃ of the core of the orogen occurred between ca. 480 Ma and 400 Ma(zircon [Ue Th]/He data)during reactivation of the Woodroffe Thrust, coincident with the 450 -300 Ma Alice Springs *** of the footwall of the Woodroffe Thrust to shallow depths occurred at ca. 200 Ma. More recent tectonic activity is also evident as on the 21 May, 2016(Sydney date), a magnitude 6.1 earthquake occurred, and the resolved focal mechanism indicates that compressive stress and exhumation along the Woodroffe Thrust is continuing to the present day. Overall, these results

关键词： Intracontinental deformation Thermochronology Petermann orogen Musgrave Province Plate tectonics Cratonization