遗传性平衡易位t(3; 22) (p21; q13）家系

本文报道一例t(3; 22) (p21; q13）平衡 相互易位的家系。先证者，男性，一岁半，淋巴 细胞及皮肤成纤维细胞G带分析结果：核型均 为46, XY, t(3; 22)(p21；q13）或46, XY,t(3; 22)(3gter” 3p21：：22813” 22gter；2 2 pter” 22gl3::3p21” 3 pter )；先证者母亲（图1）与 外祖母核型均为46, XX, t(3; 22)(p21; q13) 或46, XX, t(3; 22)(3gter、3p21：:22813一 22gter; 22pter～ 22813：:3p21一3pter)。经银 染与G带复合显示技术，先证者及母亲的22der 可见清晰的AgNOR区。先证者的父亲与舅父 G带分析核型正常。在此情况下，有生育正常 婴儿的可能，但必须作产前诊断。     

Mapping of the Gene Encoding Human β-Defensin-2 (DEFB2) to Chromosome Region 8p22–p23.1

We recently reported the isolation of human β-defensin-2 (hBD-2), a novel epithelia-derived peptide antibiotic belonging to the β-defensin family. hBD-2 is expressed in skin and epithelia of the airway system, where it is believed to contribute to its antimicrobial defense. By fluorescencein situhybridization using a hBD-2 genomic DNA probe and subsequent fluorescence R-banding, the hBD-2 gene (HGMW-approved symbol DEFB2) was assigned to human chromosome region 8p22–p23.1. PCR with a set of CEPH YAC clones spanning this chromosomal region revealed CEPH YACs 773G4, 920D12, and 820B4 to contain the hBD-2 gene. Relying on the preexisting physical maps of 8p22–p23.1, the hBD-2 gene was mapped in close proximity to D8S1993 (WI-9956) within the interval flanked by D8S552 and D8S1130 (CHLC.GATA25C10). The fact that all currently described genes encoding defensins map to chromosome 8p21–pter suggests that a gene cluster in this chromosomal region may play a major role in antimicrobial defense.     

一个遗传了三代的染色体易位t(1;7)(lg42;7p22）家系

在遗传咨询门诊中,我们对一名智力低下 的患儿作染色体分析,发现其7号染色体短臂 异常,其父和祖母均为1号与7号染色体易位。 现报告如下。     

‘Complete’ trisomy 5p; de novo translocation t(2;5)(q36;p11) with isochromosome 5p

Summary A case of complete trisomy 5p due to a de novo translocation t(2;5)(q36;p11) with an isochromosome 5p is described. Complete trisomy 5p has been reported only once (Brimblecombe et al., 1977). The confusing literature relating to partial trisomy 5p is reviewed. Comparison of our case with the patients reported by Brimblecombe et al. (1977) and by Opitz and Patau (1975) is suggestive for a distinct clinical syndrome if (almost) the complete short arm of chromosome 5 is present in a trisomic state. Unfortunately the clinical findings in the case of Brimblecombe (1966, 1977) are poorly documented. The main features of this syndrome are: macrocephaly, psychomotor retardation, hypotonia, postnatal growth failure, tracheobronchial involvement, mongoloid slant of the eyes, epicanthus, low-set ears, depressed nasal bridge, short first toe, and seizures.     

一个遗传了三代的染色体易位t(1;7)(1q42;7p22)家系

在遗传咨询门诊中,我们对一名智力低下的患儿作染色体分析,发现其7号染色体短臂异常,其父和祖母均为1号与7号染色体易位。现报告如下。 病例介绍 患儿女性,17个月,第一胎足月顺产,出生后体重增长缓慢,11个月会抬头,1岁后才能独坐及翻身,至今不会叫人,智力发育迟缓。 体检:体重8.7公斤,头围48厘米,枕部     

A 9p13→p24 duplication coupled with a whole 22q translocation onto 9p24

We report on a 3-year-old girl with a typical 9p trisomy syndrome, whose 45-chromosome karyotype includes a 9p+. As assessed by G, C and Ag-NOR bands, the rearranged chromosome resulted from a 9p13-->p24 direct duplication coupled with a translocation of the whole 22q onto 9pter, had heterochromatin at the junction site, lacked both nucleolar organizing regions (NORs) and centromere dots at the unconstricted fusion point, and was present in all metaphases scored. FISH results: a 9p subtelomere probe gave a diminished signal on the 9p+ precisely at the duplication junction 9p24::9p13, but no labeling was observed at the 9;22 translocation site; a pancentromeric alphoid probe labeled all centromeres, and gave a distinct signal at the 9pter;22cen junction. Hence, her karyotype was 45,XX,rea(9;22)(9qter-->9p24::9p13-->9p24::22p10-->22qter).ish rea(9;22) (9psubtel+dim,pancen+). Parental chromosomes were normal. The distinctiveness of the present centromere-telomere fusion rests on the coupling of an intrachromosomal distal duplication with a whole-arm translocation including alphoid DNA onto the duplicated segment. The centromeric inertia of the residual alphoid DNA in the present case compares with the variable functional status of the chromosome 22 centromere in true heterodicentrics involving such a chromosome.     

深黄被孢霉M6-22

应用PCR技术,从含有深黄被孢霉△6-脂肪酸脱氢酶基因的重组质粒pTMICL6中,扩增出1.38kb的目的片段,亚克隆到大肠杆菌和酿酒酵母的穿梭表达载体pYES2.0,在大肠杆菌中筛选到含有目的基因的重组质粒pYMID6,用醋酸锂方法转化到酿酒酵母的缺陷型菌株INVSc1中,在SC-Ura合成培养基中,选择到酵母工程株YMID6.在合适的培养基及培养条件下,加入外源底物亚油酸,经半乳糖诱导后,收集菌体.通过GC-MS对酵母工程株所含的全部脂肪酸进行色谱分析,结果表明,γ-亚麻酸的含量占酵母总脂肪酸的8.69%.     

Activation of Protein Kinase C�� Increases OAT1 (SLC22A6)- and OAT3 (SLC22A8)-mediated Transport

Organic anion transporters (OATs) play a pivotal role in the clearance of small organic anions by the kidney, yet little is known about how their activity is regulated. A yeast two-hybrid assay was used to identify putative OAT3-associated proteins in the kidney. Atypical protein kinase Cζ (PKCζ) was shown to bind to OAT3. Binding was confirmed in immunoprecipitation assays. The OAT3/PKCζ interaction was investigated in rodent renal cortical slices from fasted animals. Insulin, an upstream activator of PKCζ, increased both OAT3-mediated uptake of estrone sulfate (ES) and PKCζ activity. Both effects were abolished by a PKCζ-specific pseudosubstrate inhibitor. Increased ES transport was not observed in renal slices from OAT3-null mice. Transport of the shared OAT1/OAT3 substrate, ρ-aminohippurate, behaved similarly, except that stimulation was reduced, not abolished, in the OAT3-null mice. This suggested that OAT1 activity was also modified by PKCζ, subsequently confirmed using an OAT1-specific substrate, adefovir. Inhibition of PKCζ also blocked the increase in ES uptake seen in response to epidermal growth factor and to activation of protein kinase A. Thus, PKCζ acted downstream of the epidermal growth factor to protein kinase A signaling pathway. Activation of transport was accompanied by an increase in V_max and was blocked by microtubule disruption, indicating that activation may result from trafficking of OAT3 into the plasma membrane. These data demonstrate that PKCζ activation up-regulates OAT1 and OAT3 function, and that protein-protein interactions play a central role controlling these two important renal drug transporters.Organic anion transporters (OATs)⁷ are members of the solute carrier 22A family and play a pivotal role in the renal clearance of small (<500 Dalton) anionic drugs, xenobiotics, and their metabolites. OAT substrates include a variety of drugs such as β-lactam antibiotics, non-steroidal anti-inflammatory drugs, diuretics, and chemotherapeutics (1). OATs are predominantly expressed in renal proximal tubule, with OATs 1–3 localized to the basolateral membrane and OAT4 and URAT1 on the apical membrane. OATs 1 and 3 are dicarboxylate exchangers, and are indirectly coupled to the sodium gradient maintained by Na,K-ATPase through sodium/dicarboxylate co-transport to drive the uphill basolateral step in renal organic anion secretion (2).Although the ionic gradients, electrophysiology, and underlying kinetics that drive transport by OATs 1 and 3 are well characterized, physiologically important interactions of these basolateral OATs with membrane or cytosolic proteins have yet to be identified (1). Nevertheless, there is clear evidence that other plasma membrane transporters do interact with protein partners, influencing a diverse array of functions including transport itself, cytoskeletal structure, vesicle formation, and trafficking, as well as signaling (3). Among the transporters with activity modulated by protein-protein interactions, particularly by the PDZ proteins, PDZK1 and NHERFs 1 and 2, are apical drug transporters of the SLC22A family, including OCTN1, OCTN2, OAT4, and URAT1 (4–6).In the present study, we have used a yeast two-hybrid assay to identify putative protein partners that interact directly with OAT3. The C-terminal 81 amino acids of OAT3 were used as bait to screen a human cDNA kidney library. Among the 23 positive clones (putative binding partners) was a clone encoding the C-terminal 141 amino acids of atypical protein kinase Cζ (PKCζ). Functional consequences of the putative OAT3/PKCζ interaction were investigated in rodent renal slices. The resulting data indicate that activation of PKCζ by insulin or epidermal growth factor (EGF) increased OAT3- and OAT1-mediated transport. Thus, PKCζ controls function of both major secretory organic anion transporters expressed at the basolateral face of the renal proximal tubule, positioning it to regulate the efficacy of renal drug elimination.     

Können Tiere zählen?

The “magical” number four We know already since more than 140 years that humans have the inborn ability to recognize only up to four objects correctly if counting is strictly inhibited. Many vertebrates and the honeybee workers can remember up to four objects albeit they are unable to count. This inborn numerical competence common to humans and animals raises interesting questions concerning the purpose and the evolution of this ability. The “magical” number four is obviously a neurological, historical and mythological enigma.     

Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter) due to maternal translocation t(9;12)(p12.1;p13.3)

We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient.     

一个22p＋家系的临床及分子细胞遗传学研究

本文对一例男性性腺发育不全伴有22p 标记染色体的患者及其家庭成员进行了分子细胞及临床细胞遗传学研究,结果表明,该家系中共有6名成员有22p 染色体,它们来源于先证者的外祖母。标记染色体的p 部分几乎与22q等大,C－带呈深染,G－,R－带在p 中间分别可见一条较窄的浅,深带型,Ag-显带在p＋末端见到较大的银染区,部分p 出现双NOR,型分析未见其它,D,G组或Y染色体重排,rRNA基因的染色体原位杂交银颗粒沿整个p 分布,其数目是正常D,G组染色体短臂上平均数的3．9倍,家系研究表明,在6例22p 携带者中,2例女性具有多次自然流产史,4例男性中除一例年龄12岁末见明显性腺异常外,其余3人均有不同程度性腺或外生殖器异常,结合文献,我们认为此家系中22p 可能与上述异常表型存在着一定的关系。     

p,p′-Dichlorodiphenyldichloroethylene Induces Colorectal Adenocarcinoma Cell Proliferation through Oxidative Stress

p, p′-Dichlorodiphenyldichloroethylene (DDE), the major metabolite of Dichlorodiphenyltrichloroethane (DDT), is an organochlorine pollutant and associated with cancer progression. The present study investigated the possible effects of p,p′-DDE on colorectal cancer and the involved molecular mechanism. The results indicated that exposure to low concentrations of p,p′-DDE from 10⁻¹⁰ to 10⁻⁷ M for 96 h markedly enhanced proliferations of human colorectal adenocarcinoma cell lines. Moreover, p,p′-DDE exposure could activate Wnt/β-catenin and Hedgehog/Gli1 signaling cascades, and the expression level of c-Myc and cyclin D1 was significantly increased. Consistently, p,p′-DDE-induced cell proliferation along with upregulated c-Myc and cyclin D1 were impeded by β-catenin siRNA or Gli1 siRNA. In addition, p,p′-DDE was able to activate NADPH oxidase, generate reactive oxygen species (ROS) and reduce GSH content, superoxide dismutase (SOD) and calatase (CAT) activities. Treatment with antioxidants prevented p,p′-DDE-induced cell proliferation and signaling pathways of Wnt/β-catenin and Hedgehog/Gli1. These results indicated that p,p′-DDE promoted colorectal cancer cell proliferation through Wnt/β-catenin and Hedgehog/Gli1 signalings mediated by oxidative stress. The finding suggests an association between p,p′-DDE exposure and the risk of colorectal cancer progression.     

Partial duplication of the short arm of chromosome 9 (p13→p22) in a child with typical 9p trisomy phenotype

Summary A 3-year-old girl with duplication 9 (p22p13) is reported. The presence of a classical 9p trisomy phenotype in this patient suggests that this region (or part of it) is responsible for the major, typical clinical stigmata of this partial autosomal trisomy syndrome.     

TRAF6 and p62 inhibit amyloid β-induced neuronal death through p75 neurotrophin receptor

Amyloid β (Aβ) aggregates are the primary component of senile plaques in Alzheimer disease (AD) patient’s brain. Aβ is known to bind p75 neurotrophin receptor (p75^NTR) and mediates Aβ-induced neuronal death. Recently, we showed that NGF leads to p75^NTR polyubiquitination, which promotes neuronal cell survival. Here, we demonstrate that Aβ stimulation impaired the p75^NTR polyubiquitination. TRAF6 and p62 are required for polyubiquitination of p75^NTR on NGF stimulation. Interestingly, we found that overexpression of TRAF6/p62 restored p75^NTR polyubiquitination upon Aβ/NGF treatment. Aβ significantly reduced NF-κB activity by attenuating the interaction of p75^NTR with IKKβ. p75^NTR increased NF-κB activity by recruiting TRAF6/p62, which thereby mediated cell survival. These findings indicate that TRAF6/p62 abrogated the Aβ-mediated inhibition of p75^NTR polyubiquitination and restored neuronal cell survival.     

TRAF6 and p62 inhibit amyloid β-induced neuronal death through p75 neurotrophin receptor

Amyloid β (Aβ) aggregates are the primary component of senile plaques in Alzheimer disease (AD) patient’s brain. Aβ is known to bind p75 neurotrophin receptor (p75^NTR) and mediates Aβ-induced neuronal death. Recently, we showed that NGF leads to p75^NTR polyubiquitination, which promotes neuronal cell survival. Here, we demonstrate that Aβ stimulation impaired the p75^NTR polyubiquitination. TRAF6 and p62 are required for polyubiquitination of p75^NTR on NGF stimulation. Interestingly, we found that overexpression of TRAF6/p62 restored p75^NTR polyubiquitination upon Aβ/NGF treatment. Aβ significantly reduced NF-κB activity by attenuating the interaction of p75^NTR with IKKβ. p75^NTR increased NF-κB activity by recruiting TRAF6/p62, which thereby mediated cell survival. These findings indicate that TRAF6/p62 abrogated the Aβ-mediated inhibition of p75^NTR polyubiquitination and restored neuronal cell survival.