Heterozygosity for the IVS-I-5(G→C) mutation with a G→A change at codon 18 (Val→Met; Hb Baden) in cis and a T→G mutation at codon 126 (Val→Gly; Hb Djonburi) in trans resulting in a thalassemia intermedia

We have analyzed the hemoglobins of a young German patient with β-thalassemia intermedia and of his immediate family and included in these studies an evaluation of possible nucleotide changes in the β-globin through sequencing of amplified DNA. One chromosome of the propositus and one of his father's carried the $\text{G}\text{T}\text{G}\text{→}\text{G}\text{G}\text{G}$ mutation at codon 126 leading to the synthesis of Hb Dhoburi or α₂β₂126(H₄)Val→Gly; this variant is slightly unstable and is associated with mild thalassemic features. His second chromosome and one of his mother's had the common IVS-I-5 (G→C) mutation that leads to a rather severe β⁺-thalassemia and the $\text{G}\text{TG}\text{→}\text{A}\text{TG}$ mutation at codon 18, resulting in the replacement of a valine residue by a methionine residue. This newly discovered β-chain variant, named Hb Baden, was present for only 2–3% in both the patient and his mother. This low amount results from a decreased splicing of RNA at the donor splice-site of the first intron that is nearly completely deactivated by the IVS-I-5 (G→C) thalassemic mutation. The chromosome with the codon 18 ($\text{G}\text{TG}\text{→}\text{A}\text{TG}$) and the IVS-I-5 (G→C) mutations has thus far been found only in this German family; analysis of 51 chromosomes from patients with the IVS-I-5 (G→C) mutation living in different countries failed to detect the codon 18 ($\text{G}\text{TG}\text{→}\text{A}\text{TG}$) change.     

A novel missense mutation in the antithrombin III gene (Ala387→Val) causing recurrent venous thrombosis

A novel GCTGTT transition in the antithrombin III (ATIII) gene, resulting in an Ala387Val substitution near the reactive site, was detected in a patient with recurrent venous thrombosis and ATIII activity/antigen levels consistent with type I ATIII deficiency.     

Hb Mobile [α2β2 73(E17)Asp → Val]: A new variant

A new hemoglobin variant found in a mother and her child was characterized by column chromatography of the tryptic hydrolysate of the aminoethylated, glycinamidated -chain, followed by chymotryptic digestion of the abnormal T-9 peptide and amino acid analyses. It was shown to be _{2 2} 73(E17) Asp Val and named Hb Mobile.This work was supported in part by Research Grants AM0780 and AM13173 from the National Institute for Arthritis and Metabolic Disease.     

Polymerization of deoxyhemoglobin CHarlem (β6 Glu → Val, β73 Asp → Asn): The effect of β73 asparagine on the gelation and crystallization of hemoglobin

The kinetics of aggregation and the solubility of deoxy Hb2 C_Harlem (α₂β₂ 6 Val, 73 Asn) in concentrated phosphate buffers were studied in comparison with those of deoxy Hb S and deoxy Hb A. Deoxy Hb C_Harlem aggregated with a clear exhibition of a delay time. The length of the delay and aggregation times and the degree of the aggregation depended upon the initial hemoglobin concentration.The initial hemoglobin concentration required for the aggregation of deoxy Hb C_Harlem was approximately 200% of its solubility, a value much higher than that required for the aggregation of deoxy Hb S (120%). With the same hemoglobin concentration, the delay time for the aggregation of deoxy Hb C_Harlem was approximately 100 times longer than that of deoxy Hb S. The logarithmic plotting of the delay time versus hemoglobin concentration in 1.8 m-phosphate buffer (pH 7.4) showed linear lines with a slope (n) of 4.0 for deoxy Hb C_Harlem. In contrast to the results for the aggregation of deoxy Hb S, n values for deoxy Hb C_Harlem were unchanged with phosphate concentrations varying from 1.2 m to 2.0 m. The solubilities of deoxy Hb S and deoxy Hb C_Harlem were increased exponentially by lowering the pH of the medium, with the increase being more conspicuous for Hb C_Harlem. The gels (or aggregates) of Hb C_Harlem were converted to crystals at a rate much faster than were those of Hb A and Hb S. The kinetics for gelation and crystallization of deoxy Hb C_Harlem can be explained by the following scheme, where nuclei G and nuclei C are formed before gelation and crystallization, respectively. Monomenc deoxy Hb

The hemoglobin concentration required for the crystallization of deoxy Hb C_Harlem was about ten times lower than that required for deoxy Hb A. The solubility of deoxy Hb C_Harlem after aggregation was about twice that of deoxy Hb S, suggesting that the substitution of Asn for Asp at the β73 residue inhibits the formation of nuclei G and accelerates the formation of nuclei C.     

TheX → Y → Z scheme after 23 years

Mathematical modelling of the course of the immune response is undoubtedly one of the most progressive and most promising areas of modern immunology. Mathematical models (along with computer programs) can be taken as "the only means of thoroughly testing and examining a large and intricate theory" (Partridge et al. 1984). The first phase of construction of mathematical models is the formulation of assumptions based on the knowledge of the facts to be modelled (manifested usually in a scheme of the presumed course of the modelled process). The first mathematical models of immune response were based on the hypothesis of a two-stage differentiation of cells participating in the humoral response, published in Prague 23 years ago (Sercarz and Coons 1962; Sterzl 1962) and illustrated by the X----Y----Z scheme. Many contemporary mathematical models still stem from this scheme which undoubtedly fits the fundamental data concerning the immune system.     

PAH 399 GTA(Val)→GTT(Val), a new silent mutation found in the Chinese

Summary A silent mutation or sequence polymorphism, an A to T substitution at codon 399 in exon 11 of the phenylalanine hydroxylase (PAH) gene has been identified by DNA sequence analysis in the Chinese. The frequencies of this new mutation in normal and abnormal (phenylketonuria; PKU) genes are 0.005 and 0.09, respectively, based on the analyses of 100 apparently normal individuals and 39 PKU patients, as demonstrated by DNA amplification with polymerase chain reaction (PCR) and oligonucleotide hybridization methods. The results suggest that there is linkage disequilibrium between this polymorphism and PKU mutations in the PAH gene; approximately 10% of defect PAH alleles in the Chinese population may be identified with this sequence polymorphic marker.     

“脊髓→皮层→脊髓”环路易化触觉信息传递

正在躯体感觉研究领域,人们长期关注从外周到脊髓再到大脑,这样一条由下至上(bottom up)的传递通路,而对于来自大脑尤其是皮层发出的由上至下(top down)的感觉调控通路研究还比较少。2018年9月哈佛医学院何志刚和Clifford J.Woolf教授以及美国国立卫生研究院Wang Hongkuan教授团队共同在Nature杂志发表论文,指出躯体感觉皮层可通过皮质脊髓束     

在教学过程中贯穿激发→实现→强化学习动机的探索

学生动机是指推动学生学习的内在力量,是学生学习的推动者。课堂教学中学习动机分为激发、实现、强化3个阶段。因此,在教学过程中应贯穿激发学习动机一实现学习动机一强化学习动机,从而提高教学效果。l动机的激发阶段1．l有趣的导言或提出令人迷惑不解的矛盾问题激发学生的学习动机。例如：教师说："鸟为什么能飞？也许你会回答,因为鸟有翅膀,那么在人的双臂上缚上人工的翅膀人能不能像鸟一样S翔呢？"学生产生需要知道的心理,而要彻底明白这个道理,他们必须认真去听课。又例如在讲无机盐对植物的作用一节,教师可先讲一个小故事："…     

Association of GSTP1 p.Ile105Val (rs1695, c.313A > G) Variant with the Risk of Breast Carcinoma among Egyptian Women

Biochemical Genetics - Several reports examined the association of the GSTP1 p.Ile105Val (rs1695, c.313A?>?G) variant with the elevated risk of multiple cancerous diseases...     

Über Zahnbeinkugeln bei einem Lippfisch (Semicossyphus reticulatus Val.)

Zusammenfassung Bei dem Lippfisch Semicossyphus reticulatus Val. wurden in einem Unterkieferzahn 10 Dentinkugeln beobachtet — die erste Feststellung derartiger Gebilde bei recenten Fischen. Die Kügelchen sind außen deutlich geschichtet, während im Centrum ihre Struktur gestört erscheint; hier vor allem lassen sich Zahnbeinkanälchen von unregelmäßigem Verlauf beobachten. Polarisationsoptische Prüfung ergab, daß in jeder Schicht der Kügelchen die Kollagenfibrillen wechselnden Verlauf auf der betreffenden Kugelschale aufweisen und oft auch unterschiedlichen in benachbarten Schichten. Dies äußert sich am Polarisationsbilde im Erscheinen eines dunklen Kreuzes mit ausgezackten Balken, und in Unterschieden der Helligkeit benachbarter Schichten. An tangentialen Kugelabschnitten (Kalotten) tritt das Kreuz bis zum Verschwinden zurück und es zeigt sich ein dunkler Ring, der sich beim Drehen des Objekttisches erweitert oder verengt. Auch in einem zweiten Zahn fanden sich zwei kleine Zahnbeinkügelchen ähnlicher Art.     

Induction of T → G and T → A transversions by 5-formyluracil in mammalian cells

Oxidatively damaged thymine, 5-formyluracil (5-fU), was incorporated into a predetermined site of double-stranded shuttle vectors. The nucleotide sequences in which the modified base was incorporated were 5′-CFTAAG-3′ and 5′-CTFAAG-3′ (F represents 5-fU), the recognition site for the restriction enzyme AflII (5′-CTTAAG-3′). The 5-fU was incorporated into a template strand of either the leading or lagging strand of DNA replication. The modified DNAs were transfected into simian COS-7 cells, and the DNAs replicated in the cells were recovered and were analyzed after the second transfection into Escherichia coli. The 5-fU did not block DNA replication in mammalian cells. The 5-fU residues were weakly mutagenic, and their mutation frequencies in double-stranded vectors were 0.01–0.04%. The T → G and T → A transversions were the mutations found most frequently, suggesting the formation of 5-fU·C and 5-fU·T base pairs, respectively. This is the first report that clearly shows the induction of transversion mutations by an oxidized pyrimidine base in DNA in mammalian cells.     

上消化道大出血105例临床分析

上消化道大出血是病变复杂又需要紧急救治的常见病。尽管诊疗技术在为断进步,其病死率仍在９％～２９％之间。误诊率可高达２０％。我院１９８３年６月至１９９８年６月共收治上消化道大出血１０５例,现分析如下。１临床资料１．１一般资料１０５例中,男７９例,女２６...     

B → A → B Transitions in a Molecular Dynamics Trajectory of Low Salt DNA Solution

A molecular dynamics simulation of the DNA dodecamer d(CGCATATATGCG) has been performed with AMBER 5.0 under low salt conditions. Both B A and A B transitions are observed. This may have biological significance for the formation of complexes between DNA and TATA-box binding proteins.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1007/s0089400060654     

"应用→原理→应用创新"教学模式在高中生物学复习教学中的尝试

“应用→原理→应用创新”教学模式,强调在培养广大普通劳动者的基础上继续培养创新型人才,这不但有利于提高学生的学业成绩,同时也有利于提高学生的学习兴趣、培养动手和实践能力等。以高中生物学复习教学为例,简单介绍了本教学模式的具体应用及其效果。     

Association between M467T and 114 C→A variants within the SLC3A1 gene and some phenotypical traits in cystinuria patients from Spain

Cystinuria is an inherited metabolic disease characterized by an abnormal urinary excretion of cystine and dibasic amino acids. Formation of renal calculi, recurrent infections and renal failure are the main complications of this disease. The SLC3A1 gene, which codes for a dibasic amino acid transporter protein, is involved in the pathogenesis of cystinuria. We investigated the possible association between molecular variants (M467T, E483X, T216 M and 114 C-->A) within the SLC3A1 gene and some phenotypical traits in a Spanish area. The study population consisted of 45 cystinuria patients, 42 cystinuria relatives and 81 healthy control subjects. Only the M467T mutation was found in chromosomes of cystinuria patients and relatives. However, the 114 C-->A polymorphism was detected in cystinuria patients, in relatives and in control subjects but with different prevalences. Moreover, a statistically significant association between this polymorphism and urinary amino acid levels was found in cystinuria patients (P<0.05). Subjects with the C/C genotype showed significantly higher urinary levels of cystine, arginine and their sum as compared with carriers of the A allele (P<0.05). When multiple linear regression analysis was performed in cystinuria patients, the 114 C-->A polymorphism remained significantly associated (P=0.047) with cystine levels even after controlling for age, gender and the M467T mutation. Furthermore, we also found a statistically significant interaction term (P=0.028) between M467T and 114 C-->A in determining urinary cystine levels. According to our results, the 114 C-->A polymorphism might be a marker of a functional variant in the SLC3A1 gene or in other genes related to urinary amino acid excretion in cystinuria patients.