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Identification of neuron selective androgen receptor inhibitors

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World Journal of Biological Chemistry 2017年第2期8卷 138-150页

作者： Maya otto-Duessel Ben Yi Tew Steven Vonderfecht Roger Moore jeremy o jones Department of Cancer Biology Beckman Research Institute City of Hope National Medical Center Division of Comparative Medicine Beck-man Research Institute City of Hope National Medical Center Department of Molecular Immunology Beckman Research Institute City of Hope National Medical Center

AIM To identify neuron-selective androgen receptor(AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy(SBMA), or Kennedy's disease, a neuromuscular disorder in which deterioration of motor neurons leads to progressive muscle weakness. METHoDS Cell lines representing prostate, kidney, neuron, adipose, and muscle tissue were developed that stably expressed the CFP-AR-YFP FRET reporter. We used these cells to screen a library of small molecules for cell typeselective AR inhibitors. Secondary screening in luciferase assays was used to identify the best cell-type specific AR inhibitors. The mechanism of action of a neuronselective AR inhibitor was examined in vitro using luciferase reporter assays, immunofluorescence microscopy, and immunoprecipitations. Rats were treated with the most potent compound and tissue-selective AR inhibition was examined using RT-q PCR of AR-regulated genes and *** We identified the thiazole class of antibiotics as com-pounds able to inhibit AR signaling in a neuronal cell line but not a muscle cell line. one of these antibiotics, thiostrepton is able to inhibit the activity of both wild type and polyglutamine expanded AR in neuronal GT1-7 cells with nanomolar potency. The thiazole antibiotics are known to inhibit FoXM1 activity and accordingly, a novel FoXM1 inhibitor FDI-6 also inhibited AR activity in a neuron-selective fashion. The selective inhibition of AR is likely indirect as the varied structures of these compounds would not suggest that they are competitive antagonists. Indeed, we found that FoXM1 expression correlates with cell-type selectivity, FoXM1 co-localizes with AR in the nucleus, and that sh RNA-mediated knock down of FoXM1 reduces AR activity and thiostrepton sensitivity in a neuronal cell line. Thiostrepton treatment reduces FoXM1 levels and the nuclear localization of beta-catenin, a known co-activator of both FoXM1 and AR, and reduces the associa

关键词： Androgen receptor Selective androgen receptor modulator Spinal and bulbar muscular atrophy Kennedy’s disease

An alfalfa MYB-like transcriptional factor MsMYBH positively regulates alfalfa seedling drought resistance and undergoes MsWAV3-mediated degradation

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Journal of Integrative Plant Biology 2024年第4期66卷 683-699页

作者： Kun Shi Jia Liu Huan Liang Hongbin Dong Jinli Zhang Yuanhong Wei Le Zhou Shaopeng Wang Jiahao Zhu Mingshu Cao Chris S.jones Dongmei Ma Zan Wang College of Grassland Science and Technology China Agricultural UniversityBeijing 100193China Institute of Animal Sciences Chinese Academy of Agricultural SciencesBeijing 100193China AgResearch Grasslands Research Centre Palmerston North 4442New Zealand International Livestock Research Institute Nairobi 00100Kenya School of Ecology and Environment Ningxia UniversityYinchuan 750021China

Drought is a major threat to alfalfa(Medicago sativa L.)*** discovery of important alfalfa genes regulating drought response will facilitate breeding for drought-resistant alfalfa ***,we report a genome-wide association study of drought resistance in *** identified and functionally characterized an MYB-like transcription factor gene(MsMYBH),which increases the drought resistance in *** with the wild-types,the biomass and forage quality were enhanced in MsMYBH overexpressed *** RNA-seq,proteomics and chromatin immunoprecipitation analysis showed that MsMYBH can directly bind to the promoters of MsMCP1,MsMCP2,MsPRX1A and MsCARCAB to improve their *** outcomes of such interactions include better water balance,high photosynthetic efficiency and scavenge excess H_(2)o_(2)in response to ***,an E3 ubiquitin ligase(MsWAV3)was found to induce MsMYBH degradation under long-term drought,via the 26S proteasome ***,variable-number tandem repeats in MsMYBH promoter were characterized among a collection of germplasms,and the variation is associated with promoter ***,our findings shed light on the functions of MsMYBH and provide a pivotal gene that could be leveraged for breeding drought-resistant *** discovery also offers new insights into the mechanisms of drought resistance in alfalfa.

关键词： alfalfa drought resistance E3 ubiquitin ligase MsMYBH MsWAV3 MYB-like transcriptional factor

Biodiversity responses to insular fragmentation in Amazonia: Two decades of research in the Balbina Hydroelectric Reservoir

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Zoological Research(Diversity and Conservation) 2024年第2期1卷 106-116页

作者： Ana Filipa Palmeirim Maíra Benchimol Danielle Storck-Tonon Anderson S.Bueno Isabel L.jones Gilmar Klein Carlos A.Peres CIBIo Research Centre of Biodiversity and Genetic ResourcesInBIO Associated LabVairão CampusUniversity of PortoVairão 4485-661Portugal BIoPoLIS Program in Genomics Biodiversity and Land PlanningCIBIOVairão CampusUniversity of PortoVairão 4485-661Portugal Laboratório de Ecologia AplicadaàConservação Universidade Estadual de Santa CruzIlhéusBahia 45662-900Brazil Programa de Pós-Graduação em Ambiente e Sistemas de Produção Agrícola(PPGASP) Universidade do Estado de Mato GrossoTangaráda SerraMato Grosso 78301-532Brazil Instituto Federal de Educação Ciência e Tecnologia FarroupilhaJúlio de CastilhosRio Grande do Sul 98130-000Brazil Biological and Environmental Sciences University of StirlingStirling FK94LAUK REBIo Uatumã/ICMBio Presidente FigueiredoAmazonas 69736-000Brazil Centre for Ecology Evolution and ConservationSchool of Environmental SciencesUniversity of East AngliaNorwich NR47TJUK JuruáInstitute ManausAmazonas 69057-060Brazil

As hydropower development expands across lowland tropical forests,flooding and concomitant insular fragmentation have become important threats to *** created insular landscapes serve as natural laboratories to investigate biodiversity responses to *** of these most iconic landscapes is the Balbina Hydroelectric Reservoir in Brazilian Amazonia,occupying>400000 ha and comprising>3500 forest ***,we synthesise the current knowledge on responses of a wide range of biological groups to insular fragmentation at *** has largely concentrated on a set of 22 islands and three mainland *** total,39 studies were conducted over nearly two decades,covering 17 vertebrate,invertebrate,and plant *** species responses varied according to taxonomic group,island area was consistently included and played a pivotal role in 66.7%of all studies examining patterns of species *** persistence was further affected by species traits,mostly related to species capacity to use/traverse the aquatic matrix or tolerate habitat degradation,as noted for species of vertebrates and orchid *** research is needed to improve our understanding of such effects on wider ecosystem *** Impact Assessments must account for changes in both the remaining habitat amount and configuration,and subsequent long-term species losses.

关键词： Habitat loss Hydropower dams Landbridge Local extinctions Species-area relationships Species diversity Tropical forests

Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: influence of the CpG island methylator phenotype

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World Journal of Gastrointestinal oncology 2017年第5期9卷 209-217页

作者： jeremy Stuart Williamson Huw Geraint jones Namor Williams Anthony Paul Griffiths Gareth Jenkins John Beynon Dean Anthony Harris Department of General and Colorectal Surgery Singleton Hospital Department of Pathology Singleton Hospital Department of Life Sciences Swansea University

To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer. METHoDSPatients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined upon histological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed. RESULTSThere were 160 patients analysed with a median follow-up time of 46.4 mo. Twenty-one (13%) patients demonstrated high levels of CIMP methylation (CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion (EMVI) compared with CIMP-L [8/21 (38%) vs 15/99 (15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival (P ociated with KRAS mutation (P = 0.01). There were 14 (9%) patients with a pathological complete response (pCR) compared to 116 (73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pCR had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant (P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced “T” stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurre

关键词： Rectal cancer CpG islands Methylation

Chitosan and Carboxymethylchitosan as High Turbidity Water Biocoagulants

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Journal of Renewable Materials 2020年第11期8卷 1489-1504页

作者： Raimundo N.Lima Júnior João L.I.o.Almeida jones de Andrade Flávia o.M.S.Abreu Natural Sciences Program State University of Ceará-UECEFortalezaCE 60714-903Brazil Physical-Chemistry Department Institute of ChemistryFederal University of Rio Grande do Sul-UFRGSPorto AlegreRS 91501-970Brazil

Biocoagulants emerges as a promising technology in water treatment,in order to exploit renewable and biodegradable *** present work aims to study the coagulant action of chitosan and carboxymethylchitosan on water with very high turbidity(above 300 NTU),contrasting the physicochemical results with those obtained for aluminum *** was produced by the Williamson’s ethers synthesis and characterized by potentiometric titration,FTIR and 1 *** coagulant tests were performed using synthetic water in a Jar-test equipment,through the induction of high and low velocity gradients,followed by *** results showed turbidity and color removal efficiencies above 99%for the biocoagulants,by applying dosages much lower than those used for aluminum sulphate;the volume of sedimentable solids obtained at the end of the water treatment process was much lower when chitosan and carboxymethylchitosan were used as coagulants(reduction of 25%when compared to aluminum sulphate).In summary,carboxymethylchitosan is a non-toxic,renewable,biodegradable material with high efficiency as a coagulant for waters with very high turbidity,showing promise for in natura applications.

关键词： Chitosan carboxymethylchitosan biocoagulants colloids and interfaces

Biogeography of the Shimba Hills ecosystem herpetofauna in Kenya

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Zoological Research 2018年第2期39卷 97-104页

作者： Patrick K. Malonza David M. Mulwa Joash o. Nyamache Georgina jones Section of Herpetology National Museums of Kenya Nairobi 40658-00100 Kenya Base Titanium Ltd Ukunda 1214-80400 Kenya Sino-Africa Joint Research Center Chinese Academy of Sciences Nairobi 40658-00100 Kenya

The Shimba Hills ecosystem along the south coast of Kenya is a key East African biodiversity hotspot. Historically, it is biogeographically assignable to the East African coastal biome. We examined the current Shimba Hills herpetofauna and their zoogeographical affinities to the coastal forests and nearby Eastern Arc Mountains biodiversity hotspots. The key studied sites included the Shimba Hills National Reserve, forest reserves, Kaya forests, and adjacent private land. Data on herpetofaunal richness were obtained from recent field surveys, literature, and specimens held at the National Museums of Kenya, Herpetology Section Collection, Nairobi. The Makadara, Mwele, and Longo- Mwagandi forests within the Shimba Hills National Reserve hosted the highest number of unique and rare species. Generally, the forest reserves and Kaya forests were important refuges for forest- associated species. on private land, Mukurumudzi Dam riparian areas were the best amphibian habitat and were host to three IUCN （Red List） Endangered- EN amphibian species, namely, Boulengerula changamwensis, Hyperolius rubrovermiculatus, and Afrixalus sylvaticus, as well as one snake species Elapsoidea nigra. Using herpetofauna as zoogeographic indicators, the Shimba Hills were determined to be at a crossroads between the coastal forests （13 endemic species） and the Eastern Arc Mountains （seven endemic species）. Most of the Eastern Arc Mountains endemic species were from recent records, and thus more are likely to be found in the future. This ＇hybrid＇ species richness pattern is attributable to the hilly topography of the Shimba Hills and their proximity to the Indian ocean. This has contributed to the Shimba Hills being the richest herpetofauna area in Kenya, with a total of 89 and 38 reptile and amphibian species, respectively. Because of its unique zoogeography, the Shimba Hills ecosystem is undoubtedly a key biodiversity area for conservation investment.

关键词： Amphibianscoastal forests: Easternspecies ZoogeographyReptiles Eastern AfricaArc Mountains: Indicator

Roles for the VCP co-factors Npl4 and Ufd1 in neuronal function in Drosophila melanogaster

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Journal of Genetics and Genomics 2017年第10期44卷 493-501页

作者： Dwayne J.Byrne Mark J.Harmon jeremy C.Simpson Craig Blackstone Niamh C. o'Sullivan UCD School of Biomolecular and Biomedical Science UCD Conway Institute University College Dublin Dublin 4 Ireland UCD School of Biology and Environmental Science UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin Dublin 4Ireland Cell Biology Section Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda MD 20892 USA

The VCP-Ufd1-Npl4 complex regulates proteasomal processing within cells by delivering ubiquitinated proteins to the proteasome for *** in VCP are associated with two neurodegenerative diseases,amyotrophic lateral sclerosis（ALS） and inclusion body myopathy with Paget＇s disease of the bone and frontotemporal dementia（IBMPFD）,and extensive study has revealed crucial functions of VCP within *** contrast,little is known about the functions of Npl4 or Ufd1 in *** neuronalspecific knockdown of Npl4 or Ufd1 in Drosophila melanogaster,we infer that Npl4 contributes to microtubule organization within developing motor ***,Npl4 RNAi flies present with neurodegenerative phenotypes including progressive locomotor deficits,reduced lifespan and increased accumulation of TAR DNA-binding protein-43 homolog（TBPH）.Knockdown,but not overexpression,of TBPH also exacerbates Npl4 RNAi-associated adult-onset neurodegenerative *** contrast,we find that neuronal knockdown of Ufd1 has little effect on neuromuscular junction（NMJ） organization,TBPH accumulation or adult *** findings suggest the differing neuronal functions of Npl4 and Ufd1 in vivo.

关键词： Proteasome TDP-43 accumulation Neurodegeneration Drosophila

An assessment of steady-state conditions in single slug horizontal pneumatic conveying

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Particuology 2021年第5期19卷 187-195页

作者： A.Lavrinec o.orozovic H.Rajabnia K.Williams M.G.jones G.E.Klinzing Centre for Bulk Solids and Particulate Technologies The University of NewcastleNSW 2308Australia Department of Chemical and Petroleum Engineering The University of PittsburghPA 15261USA

This study used a 3D coupled CFD–DEM model to assess how slugs tend towards steady state in single slug horizontal pneumatic *** slug length,inlet velocity and initial stationary layer fractions were systematically varied for a total of 72 *** made observation that slugs tend towards a steady state was confirmed via a theoretical *** derivation shows that slugs move towards their steady state lengths *** allowed for a calculation of a characteristic time scale which is a measure of how quickly a slug tends towards the steady *** theoretical estimate which is a function of slug porosity,steady length,velocity and stationary layer fraction has good agreement with simulated results.A link between steady slug length and solids loading ratio was also shown.

关键词： Pneumatic conveying Dense phase Slug flow Steady state

AN ANALYSIS oF THE SHEAR FAILURE oF RIGID-LINEAR HARDENING BEAMS UNDER IMPULSIVE LoADING

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Acta Mechanica Sinica 1996年第4期12卷 338-348页

作者：王礼立 Norman jones Ningbo University Ningbo 315211China and also University of Science and Technology of ChinaHefei 230026China Impact Research Centre Department of Mechanical EngineeringUniversity of Liverpool.P.O.Box 147Liverpool L69 3BXU.K.

A theoretical rigid-plastic analysis for the dynamic shear failure of beams under impulsive loading is presented when using a travelling plastic shear hinge model which tabes into account material strain hardening. The maximum dynamic shear strain and shear strain-rate can be predicted in addition to the permanent transverse deflections and other parameters. The conditions for the three modes of shear failure, i.e., excess deflection failure, excess shear strain failure and adiabatic shear failure are analyzed. The special case of an infinitesimally small plastic zone is discussed and compared with Nonaka's solution for a rigid, perfectly plastic material. The results can also be generalized to examine the dynamic response of fibre-reinforced beams.

关键词： shear failure rigid-linear hardening plastic beam dynamic response impulsive loading adiabatic shear