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Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

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Signal Transduction and Targeted Therapy 2021年第2期6卷 409-424页

作者： Zi Wang Pan Wang Yanan Li Hongling Peng Yu Zhu narla Mohandas Jing Liu Department of Hematology Istitute of Molecular HematologyThe Second Xiangya HospitalCentral South University41001 ChangShaHunanChina Molecular Biology Research Center and Hunan Province Key Laboratory of Basic and Applied Hematology School of Life SciencesCentral South University410078 ChangshaHunanChina Red Cell Physiology Laboratory New York Blood CenterNew YorkNYUSA

Hematopoiesis requires finely tuned regulation of gene expression at each stage of *** regulation of gene transcription involves not only individual transcription factors(TFs)but also transcription complexes(TCs)composed of transcription factor(s)and multisubunit *** their normal compositions,TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during *** integration of posttranslational and conformational modifcations in the chromatin landscape,nucleosomes,histones and interacting components via the cofactor-TF interplay is critical to optimal TF *** or translocations of cofactor genes are expected to alter cofactor-TF interactions,which may be causative for the pathogenesis of various hematologic *** TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic *** this review,we summarize the current knowledge regarding the models and functions of cofactor-TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological *** review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

关键词： hematopoiesis cofactor landscape

Heat-resistant Al_(2)O_(3) nanowire-polyetherimide separator for safer and faster lithium-ion batteries

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Journal of Materials Science & Technology 2023年第11期142卷 112-120页

作者： Wenqiang Hu Wenbin Fu Samik Jhulki Liang Chen Aashray narla Zhijian Sun Fujia Wang Alexandre Magasinski Gleb Yushin School of Materials Science and Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Institute of Materials Science and Engineering School of Mechanical and Electronic Control EngineeringBeijing Jiaotong UniversityBeijing 100044China Sila Nanotechnologies Inc AlamedaCA 94501USA School of Chemistry and Chemical Engineering Hunan Institute of Science and TechnologyYueyangHunan 414006China

Poor heat/flame-resistance of polyolefin(e.g.,polyethylene and polypropylene)separators and high flammability of organic electrolytes used in today’s lithium-ion batteries(LIBs)may trigger rare yet potentially catastrophic safety ***,we mitigate this challenge by developing a heat-resistant and flame-retardant porous composite membrane composed of polyetherimide(PEI)and Al_(2)O_(3) nanowires(NWs).The membranes are fabricated based on an industrially scalable non-solvent-induced phase separation process,which results in an intimately interconnected porous network of Al_(2)O_(3) NWs and *** produced composite membranes exhibit excellent flexibility,thermal stability,and ***,the composite membranes exhibit minimal thermal shrinkage and superior tensile strength(16 MPa)at temperatures as high as 200℃,significantly exceeding the performance of conventional polyolefin *** with commercial separators,their superior wettability and higher ionic conductivity(by up to 2.4 times)when filled with the same electrolyte,larger electrolyte uptake(-190 wt.%),as well as improved cycle and rate performance demonstrated in LiNiMnCoO_(2)(NCM)-based LIBs make them attractive choices for a variety of electrochemical energy storage devices.

关键词： Lithium-ion batteries Separators Al_(2)O_(3)NWs Polyetherimide Thermal resistance

Is the erythropoietin receptor the key to the identification of the central macrophage in erythroblastic islands?

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Blood Science 2020年第1期2卷 38-39页

作者： Lionel Blanc narla Mohandas Laboratory of Developmental Erythropoiesis Department of Molecular Medicine and PediatricsThe Feinstein Institute for Medical ResearchZucker School of Medicine at Hofstra/NorthwellManhassetNY 11030USA Red Cell Physiology Laboratory New York Blood CenterNew YorkNY 10065USA

Erythroblastic islands(EBI)are niches for mammalian erythropoiesis.1 They were first identified in 1958 by Marcel Bessis and consist of a group of differentiating erythroblasts surrounding a central macrophage.2 Over the years,a lot of attention has been paid to understand the role of the central macrophage in regulating the differentiation of the maturing erythroblasts within these islands and in defining the surface proteins thatmediate the interaction between the erythroblasts and the centralmacrophage.3–14While some progress has beenmade in these areas of investigation,the definitive identity of this central macrophage and its function is yet to be fully characterized.

关键词： macrophage. blastic interaction

CT与功能性鼻内镜手术对副鼻窦内病变诊断对比研究

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CT与功能性鼻内镜手术对副鼻窦内病变诊断对比研究

作者： narla VIVEK CHOWDARY 吉林大学

学位级别：硕士

背景:平片在诊断鼻窦赘生物性及非赘生物性病变缺乏准确性。鼻窦的成像技术已经发展到计算机断层成像(CT)和磁共振成像(MRI)。随着CT和MRI成像技术的发展,可以对鼻窦病变的范围提供更准确的定位和更详细的鉴别诊断,这为诊断和手术治疗... 详细信息

背景:平片在诊断鼻窦赘生物性及非赘生物性病变缺乏准确性。鼻窦的成像技术已经发展到计算机断层成像(CT)和磁共振成像(MRI)。随着CT和MRI成像技术的发展,可以对鼻窦病变的范围提供更准确的定位和更详细的鉴别诊断,这为诊断和手术治疗鼻窦疾病带来了充足的信息。在评估鼻窦疾病变中,CT已经取代了传统的平片成像模式成为诊断鼻窦疾病的一个重要方法,并且为临床制定治疗方案提供依据。CT可以确定疾病的范围和程度,同时还可以检查出一些解剖变异(如鼻子中隔偏移、骨刺形成及中鼻甲变异等),这些变异会增加患者在功能性鼻内窥镜下术中及术后并发症的风险,进而降低患者的发病率及死亡率。同时CT可以评估鼻窦与周围毗邻的重要的解剖结构。目前,在评估慢性鼻窦炎和明确鼻窦解剖变异中CT扫描是应用最为广泛的成像技术。在手术治疗鼻窦炎性疾病中,功能性鼻内窥镜术在很大的程度上取代了传统鼻窦手术技术,而CT的术前评估对其有着重要的作用。我们将功能性鼻内窥镜术前进行的CT评估称为鼻窦CT筛查(SSCT)。CT可为耳鼻喉科医师手术时提供手术的“路径图”同时直接决定手术方法。但是,CT在鼻窦炎的使用中是存在争议的,因此,本研究着手于CT与功能内窥镜在诊断上的关系,同时通过案例对病人的解剖变异、黏膜变化进行研究。鼻窦计算机断层成像扫描提高了对鼻窦解剖结构的可视化,并且可以更大程度上更准确的评估鼻窦疾病。通过CT检查准确的诊断疾病、病变的范围、引发的并发症、解剖变异和副鼻窦毗邻的解剖关系,可以在术前提供更可信的手术路径图。多排CT(MDCT)使我们可以获得薄层图像以及随后高质量的多层面重组图像。目的:运用功能性内窥镜鼻窦手术(FESS)为耳鼻喉医生诊断副鼻窦疾病及并发症、以及PNS的病理及解剖学变异的研究提供帮助,从而降低并发症的风险。对比研究CT与FESS在发现和诊断疾病上的准确性,有助于临床对PNS病变的具体位置及病变范围的定位及判断,从而对制定治疗方案提供帮助。方法:这是一个回顾性研究,本研究一共收集了40名患者。患者年龄在13-65岁之间,他们在功能性鼻窦内窥镜手术(FESS)前接受CT副鼻窦检查。选取中鼻甲变异、中鼻甲气化,窦口鼻道复合体病、息肉样改变、粘膜增厚,额筛窦等相关疾病作为研究对象。使用的设备是GE Bright Speed Elite 16 slice、配备高分辨率摄像头的STORZ内窥镜。患者取仰卧位,扫描区域自额窦上壁至上颌窦下壁。扫描模式是螺旋扫描。切片厚度为2.5mm,螺距1-1.5mm。本研究进行了描述性和推论性统计分析,对诊断相关的统计指标如灵敏度、特异性、阳性预测值(positive predictive value PPV)和阴性预测值(negative predictive value NPV)进行了计算。结果:本实验选取40名患者,年龄13岁至65岁,平均年龄31.9岁。大多数患者在21至30岁年龄组(约占40%),其次是31至40岁年龄组(约20%),男性患者居多(约占57.5%左右)。患者中57.5%的主要症状是头痛,47.5%在日常活动中自觉鼻部不适、鼻塞。发热较少见,约占患者的27.5%比例,少数患者同时具备多个症状。上颌窦是最常出现鼻窦炎的鼻窦,蝶窦不常被累及。鼻窦炎的病理改变大致分为息肉样粘膜增厚和粘膜聚集。息肉样粘膜增厚在所有的鼻窦炎中都是最常见的病变,其中以上颌窦(右,62.5%,左,70%)最多见。CT检查对额窦性疾病的敏感度为96.4%,特异性96.5%;在前组筛窦疾病中为86%的敏感性和97.3%的特异性;CT检出蝶窦病变的敏感性为80.9%,特异性86.4%。漏斗管是最易阻塞的窦口鼻道(右55%,左47.5%)。钩突上端的着位点最多见于中鼻甲,少数患者钩突位于筛骨纸样板,上鼻甲、筛顶和筛泡。中鼻甲的变种包括层状鼻甲和中鼻甲气化和筛窦Fovea只能在CT中进行评价。受试者中82.5%的fovea为对称存在,其中II型最常见(52.5%)。还有约17.5%患者是不对称的。鼻息肉是CT中最常见的类型,约占研究人群的17.5%,其次是口鼻型及漏斗型,它们的发病率均为10%。结论:CT检查在中鼻甲变异与鼻中隔偏曲的诊断中优于内窥镜。在缺乏经验的内镜医师操作中,中鼻甲变异容易被误认为是鼻甲泡。内镜检查中,中鼻甲气化是最常见的解剖变异,具有较高的检测率。本研究还发现息肉,中鼻道粘膜和粘液性脓肿在冠状位CT和内镜检查的准确性上并无明显差异。对疾病的过程及其相关鼻内镜下表现的理解有助于放射科医生对CT表现的解读。功能性内窥镜医师与放射科医师的合作会对疾病的诊断产生积极的结果,符合医生和患者双方利益。

关键词：计算机断层成像(CT) 功能性鼻内窥镜手术(FESS) 鼻旁窦(PNS)

Efficacy of Biological Control and Cultivar Resistance on <i>Fusarium</i>Head Blight and T-2 Toxin Contamination in Wheat

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American Journal of Plant Sciences 2012年第5期3卷 599-607页

作者： Scholastica Leah Musyimi James Wanjohi Muthomi Rama Devi narla John Maina Wagacha Department of Plant Science and Crop Protection University of Nairobi Nairobi Kenya Ministry of Agriculture Nairobi Kenya School of Biological Sciences University of Nairobi Nairobi Kenya

Laboratory and green house experiments were carried out to evaluate the efficacy of fungicides, biological agents and host resistance in managing FHB and the associated T-2 toxin. In vitro activity of fungicides and antagonists was determined by paired culture method. Effect of microbial agents on FHB severity and mycotoxin content was determined by co-inoculating F. graminearum and F. poae with Alternaria spp., Epicoccum spp. and Trichoderma spp. Fungicides Pearl? (500 g/L carbendazim), Cotaf? (50 g/L hexaconacole), Thiovit? (micronised sulphur 80% w/w) and Folicur? (430 g/L tebuconazole) were the standard checks. Host resistance was determined by inoculating F. poae and F. graminearum to four wheat cultivars and fifteen lines in pot ex-periments. Fungicides resulted in 100% inhibition of pathogen radial growth in in vitro while microbial agents suppressed pathogen growth by up to 53%. Thiovit? and Trichoderma were the most effective in reducing FHB severity in green house pot experiments. The wheat cultivars and lines varied in susceptibility with cultivar Njoro BW II showing least susceptibility while line R1104, cv. Mbuni and cv. KIBIS were most susceptible. All the wheat cultivars and lines accumulated T-2 toxin by up to 5 to 28 μg/kg. The results indicated that neither fungicides nor antagonists can solely be relied on in managing FHB and toxin accumulation. Therefore, integration of biocontrol agents, fungicides and further breeding efforts to improve lines and cultivars with promising resistance to FHB and T2-toxin contamina-tion is recommended.

关键词： Antagonists Fungicides Fusarium Head Blight T-2 Toxin Wheat

Occurrence of <i>Fusarium</i>species and associated T2-toxin in Kenyan wheat

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Agricultural Sciences 2012年第1期3卷 24-34页

作者： James W. Muthomi Scholastica L. Musyimi John M. Wagacha Rama D. narla Department of Biological Sciences University of Nairobi Nairobi Kenya Department of Plant Science and Crop Protection University of Nairobi Nairobi Kenya Ministry of Agriculture Nairobi Kenya

Survey covering 120 wheat fields was conducted in three wheat-growing districts of Kenya during the 2008 cropping season to determine the incidence of Fusarium head blight (FHB) and T2-toxin contamination in grain. FHB incidence was determined as the number of blighted ears per 10m2. Information gathered included wheat production practices, rainfall and temperature data. Fungal pathogens were isolated from wheat stems, heads, straw, grains and soil and identified based on cultural and morphological characteristics. Wheat grain samples were analyzed for T2-toxin by competitive Enzyme Linked Immunosorbent Assay (ELISA). High FHB incidences of up to 88% were recorded. Fungal genera isolated included Fusarium, Epicoccum, Trichoderma, Alternaria and Penicilium. Wheat plant parts with high infection with Alternaria and Epicoccum had corresponding low levels of Fusarium spp. Whereas Fusarium spp. were the most common fungal pathogens in stems, heads and soil, Epicoccum was frequently isolated from straw and grains. Fusarium speciesisolated included F. poae, F. graminearum, F. stilboides, F. verticilloides, F. fusarioides, F. tricinctum and F. heterosporum with F. poae and F. graminearum accounting for approximately 40% of all Fusarium infections. T-2 toxin was detected in all the grain samples and varied from 3 to 22 ppb. The study showed that FHB and T2-toxin are prevalent in the study districts and the high diversity of Fusarium species implies a challenge in FHB management as well as a risk of chronic T2-toxin exposure to humans and livestock.

关键词： Fusarium Head Blight Mycotoxins T-2 Toxin Trichothecenes Wheat

Multiple STEAP3 loss-of-function heterozygous mutations identified in the Chinese population with no phenotypic red cell alterations

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Multiple STEAP3 loss-of-function heterozygous mutations iden...

Occurrence of Fusarium species and associated T2-toxin in Kenyan wheat

第十四次全国医学遗传学学术会议

作者： Dun Liu Sheng Yi Xinhua Zhang Ping Fang Chenguang Zheng Li Lin Ren Cai Yuhua Ye Yuqiu Zhou Yunhao Liang Feng Cheng Xuelian Zhang Wanjun Zhou narla Mohandas Xiuli An Xiangmin Xu Department of Medical Genetics School of Basic Medical SciencesSouthern Medical University Department of Hematology 303rd Hospital of the People's Liberation Army Prenatal Diagnostic Center Guangxi Zhuang Autonomous Region Women and Children Care Hospital Department of Birth Health and Heredity Liuzhou Women and Children Care Hospital Department of Birth Health and Heredity Zhuhai Women and Children Care Hospital Red Cell Physiology Laboratory New York Blood Center

A ferrireductase encoded by six-transmembrane epithelial antigen of the prostate3(STEAP3)has been implicated in the regulation of iron ***3 null mice exhibit congenital hypochromic anemia and in a rare case of human anemia has been recently reported due to STEAP3 ***,there is little information on the prevelance of STEAP3 mutations in humans and their physiological *** analysis in a total of 2338 Chinese random individuals showed mutations in STEAP3,for a prevalence of 5.3%.We characterized the spectrum of these STEAP3mutations and identified sixteen functional *** three most common mutations,***261Ter,***290His and ***51Asp,accounted for 72.6%of the *** the heterozygous STEAP3 mutations resulted in either moderate or severe reductions in enzyme activities in vitro,they had little or no effects on red cell ***,when we scanned for STEAP3 mutations in 867 subjects with-thalassemia,we were unable to document the adverse effects of STEAP3 mutations on the-thalassemia *** findings imply that heterozygous STEAP3 mutations are not deleterious in humans and suggest that lack of phenotypic changes is due to the presence of sufficient residual STEAP3 activity or the presence of other ferrireductases in erythroid cells.

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肝细胞性肝癌中肿瘤抑制因子Kruppel样因子6(KLF6)的普遍失活

Agricultural Sciences（农业科学） 2012年第1期

作者： James W. Muthomi Scholastica L. Musyimi John M. Wagacha Rama D. narla

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世界核心医学期刊文摘（胃肠病学分册） 2005年第3期1卷 41-41页

作者： Kremer-Tal S. Reeves H.L. narla G. S.L. Friedman 翟惠虹 Division of Liver Diseases Box 1123 Mount Sinai School of Medicine 1425 Madison Avenue New York NY 10029 United States Dr.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, reflecting incomplete characterization of underlying mechanisms and lack of early detection. Kruppel like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcription factor that is deregulated in multiple cancers through loss of heterozygosity (LOH) and/or inactivating somatic mutation. We analyzed the potential role of the KLF6 tumor suppressor gene in 41 patients who had HCC associated with hepatitis C virus (16 patients), hepatitis B virus (12 patients, one of whom was coinfected with hepatitis C virus), and other etiologies (14 patients) by determining the presence of LOH and mutations. Overall, LOH and/or mutations were present in 20 (49%) of 41 tumors. LOH of the KLF6 gene locus was present in 39%of primary HCCs, and the mutational frequency was 15%. LOH and/or mutations were distributed across all etiologies of HCC evaluated, including patients who did not have cirrhosis. Functionally, wild type KLF6 decreased cellular proliferation of HepG2 cells, while patient derived mutants did not. In conclusion, we propose that KLF6 is deregulated by loss and/or mutation in HCC, and its inactivation may contribute to pathogenesis in a significant number of these tumors.

关键词：肝细胞性肝癌 KLF6 Kruppel 肿瘤抑制因子肿瘤抑制基因体细胞突变潜在作用基因位点杂合子野生型