A female with X‐linked Nephrogenic diabetes insipidus in a family with inherited central diabetes Insipidus: Case report and review of the literature

There are two forms of diabetes insipidus, central (neurohypophyseal), and nephrogenic, caused by pathogenic variants in the AVP gene and the AVPR2 or AQP2 genes, respectively. We report on a four‐generation family, seven individuals had central diabetes insipidus (CDI) and the female index patient seen from age 16 to 26 years had (mild) nephrogenic diabetes insipidus. In her father with CDI, a known pathogenic heterozygous AVP variant c.232_234del p.(Glu78del) was identified, confirming the diagnosis of CDI in him and the other affected family members. In the proband, molecular analysis disclosed a novel heterozygous AVPR2 gene variant, c.962A > T p.(Asn321Ile) and an extremely skewed X‐inactivation, confirming X‐linked nephrogenic diabetes insipidus (XL‐NDI). Whole exome sequencing showed no further causative mutation. This is the first report on the co‐existence of CDI and NDI in one family. Our review of symptomatic female AVPR2 heterozygotes includes 23 families with at least one affected female (including this study). There were 21 different causative mutations. Mutation types in females did not differ from those in males. Both severe XL‐NDI and mild forms were reported in females. All six females with severe XL‐NDI had complete loss‐of‐function (null) mutations. The remaining 17 female probands had milder XL‐NDI caused by 14 missense variants and three null variants of the AVPR2 gene. X‐inactivation was studied in nine of these females; all showed extreme or slight skewing. The review underlines that XL‐NDI in female AVPR2 heterozygotes is always accompanied by skewed X‐inactivation, emphasizing a need for X‐inactivation studies in these females.     

COMT Gene Polymorphism Is Associated with Declarative Memory in Adulthood and Old Age

Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.     

A nonlinear model of the arterial vessels within a limb segment

The relationship between the arterial blood pressure and the volume of the arteries within a segment of an extremity is nonlinear. The present paper shows how the flow and volume pulsations of the arteries within a limb segment can be simulated taking this property into account. An electrical model was constructed comprising one resistor and two voltage dependent ‘capacitors’, the latter corresponding to the pressure dependent elasticity, or compliance, of the arteries. Adequate simulations were obtained over a wide pressure range, which is impossible with linear models. The nonlinear, i.e. pressure dependent, relationship between the volume and pressure of arteries, observed under static conditions, must also be taken into consideration when studying pulsatile events with models whether mathematical or physical.     

Hypergammaglobulinemia and autoantibody induction mechanisms in viral infections

Polyclonal hypergammaglobulinemia is a characteristic of chronic inflammatory conditions, including persisting viral infections and autoimmune diseases. Here we have studied hypergammaglobulinemia in mice infected with lymphocytic choriomeningitis virus (LCMV), which induces nonspecific immunoglobulins as a result of switching natural IgM specificities to IgG. The process is dependent on help from CD4+ T cells that specifically recognize LCMV peptides presented by B cells on major histocompatibility complex class II molecules. Thus, hypergammaglobulinemia may arise when specific helper T cells recognize B cells that have processed viral antigens irrespective of the B cell receptor specificity. This nonspecific B cell activation may contribute to antibody-mediated autoimmunity.     

Immunization with recombinant protein: conditions for cytotoxic T cell and/or antibody induction

Safe vaccines should optimally induce both cell-mediated and humoral immunity. Recently, it has been shown that protective cytotoxic T cells (CTLs) can be induced not only with live vaccines, but also with recombinant viral proteins. This report shows in C57BL/6 (H-2^b) mice that the recombinant nucleoprotein (N) of vesicular stomatitis virus (VSV) induced protective CTLs but no neutralizing antibodies in mice, whereas the recombinant glycoprotein (G) of VSV alone induced neutralizing antibodies but no CTLs. If the N and G of VSV were coinjected, both CTLs and a long-lasting neutralizing IgG response was measurable, demonstrating that mixed vaccines can be used to induce protective CTLs and antibodies with an efficiency comparable to live virus. In an attempt to define optimal conditions for CTL priming, the intravenous, intraperitoneal and subcutanous route of injection were compared. Intravenous injection of recombinant VSV-N induced up to 30 times higher responses than the latter two routes. Finally, we tried to define conditions inducing only CTLs and no antibodies binding to the native protein form, or vice versa, only antibodies and no CTLs. Intravenous injection of boiled VSV-N induced a CTL response but no antibodies specific for the native VSV-N, whereas VSV-N injected subcutanously in incomplete Freund's adjuvant induced high amounts of anti-VSV-N antibodies but virtually no CTLs. The conditions defined here permit vaccines to be designed which would function along selected and defined immunological effector pathways.     

材料参数与镍钛形状记忆合金的本构关系

在Ｔａｎａｋａ模型基础上，我们讨论了形状记忆合金热力学特性的本构关系。特别注意了桓温拉伸过程和强迫回复过程。本构方程的材料参数，即弹性模量Ｄ，变化张量Ω，热力弹性张量均以镍钛合金实验测试值来确定。在不同的应力－应变－温度关系试验中发现Ｄ和Ω与温度之间有很强的相关性。