The Influence of Developmental Dyslexia-associated Gene KIAA0319 on Brain Development——From Animals to Humans / 生物化学与生物物理进展

Developmental dyslexia (DD) is a prevalent learning disorder, and the KIAA0319 gene is a DD-associated gene, potentially affecting reading ability by influencing brain development. This review provides an overview of the impact of KIAA0319 gene on brain development in fish, non-primate mammals, primate mammals, and humans. In studies involving fish, the kiaa0319 gene was found to be expressed in the brain, eyes and ears of zebrafish. In mammalian studies, abnormal Kiaa0319 gene expression affected neuronal migration direction and final position, as well as dendritic morphology during embryonic development in rats, leading to abnormal white and gray matter development. Knocking down the Kiaa0319 gene impaired the primary auditory cortex in rats, resulting in phoneme processing impairment similar to DD. In mice, Kiaa0319 overexpression affected the neuronal migration process, causing delayed radial migration of neurons to the cortical plate. Knockout of the Kiaa0319 gene led to abnormal development of the gray matter in mice, resulting in reduced volume of the medial geniculate nucleus and then impacting auditory processing. In primate studies, research on marmosets found that KIAA0319 gene is expressed in the visual, auditory, and motor pathways, while studies on chimpanzees revealed that KIAA0319 gene abnormalities primarily affected the gray matter volume and microstructure of the posterior superior temporal gyrus, morphology of the superior temporal sulcus and gray matter volume of the inferior frontal gyrus. The impact of KIAA0319 gene on human brain development is mainly concentrated in the left temporal lobe, where abnormal KIAA0319 gene expression caused reduced gray matter in the left inferior temporal gyrus, middle temporal gyrus and fusiform gyrus, as well as reduced white matter volume in the left temporoparietal cortex. Abnormalities in KIAA0319 gene also led to decreased hemispheric asymmetry in the superior temporal sulcus. The above-mentioned brain regions are crucial for language and reading processing. It is analyzed that the abnormalities in the DD-associated KIAA0319 gene affect neuronal migration and morphology during brain development, resulting in abnormal development of subcortical structures (such as the medial geniculate nucleus and lateral geniculate nucleus) and cortical structures (including the left temporal cortex, temporoparietal cortex and fusiform gyrus) which are involved in human visual and auditory processing as well as language processing. Impairment of the medial geniculate nucleus affects the information transmission to the auditory cortex, leading to impaired phoneme processing. Abnormalities in the magnocellular layers within the lateral geniculate nucleus hinder the normal transmission of visual information to the visual cortex, affecting the dorsal visual pathway. The left temporal lobe is closely related to language and reading, and abnormalities in its gray matter and connections with other brain areas can affect the language and word processing. In summary, abnormalities in the KIAA0319 gene can partly explain current research findings on the cognitive and neural mechanisms of DD, providing a genetic basis for theoretical models related to DD (such as general sensorimotor theory and the magnocellular theory). However, the mechanism of developmental dyslexia is complex, and there are mutual influences between different DD-associated genes and between genes and the environment, which require further exploration.

Physical interactions and mutational analysis of MoYpt7 in Magnaporthe oryzae / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

In this study, we analyzed the physical interactions of the dominant negative isoform of MoYpt7. Our results show that MoYpt7 interacts with MoGdi1. The dominant negative isoform of MoYpt7 (dominant negative isoform, N125I) is essential for colony morphology, conidiation, and pathogenicity in the rice blast fungus. These results further demonstrate the biological functions of MoYpt7 in Magnaporthe oryzae.

Effect of glutathione and sodium selenite on the metabolism of arsenic in mice exposed to arsenic through drinking water / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the effect of glutathione (GSH) and sodium selenite on the metabolism of arsenic in the liver, kidney and blood of mice exposed to iAsIII through drinking water.</p><p><b>METHODS</b>The mice were randomly divided into control, arsenic, GSH and sodium selenite group, respectively. And each group had eight mice and the mice were exposed to 50 mg/L arsenite by drinking water for 4 weeks. Mice were intraperitoneally injected with GSH (600 mg/kg) and sodium selenite (1 mg/kg) for seven days from the beginning of the fourth week. At the end of the fourth week, liver, kidney and blood were sampled to assess the concentrations of inorganic arsenic (iAs), monomethylarsenic acid (MMA), dimethylarsenic acid (DMA) by hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry.</p><p><b>RESULTS</b>The liver DMA (233.76 +/- 60.63 ng/g) concentration in GSH group was significantly higher than the arsenic group (218.36 +/- 42.71 ng/g). The concentration of DMA (88.52 +/- 30.86 ng/g) and total arsenic (TAs) (162.32 +/- 49.45 ng/g) in blood of GSH group was significantly higher than those [(45.32 +/- 12.19 ng/g), (108.51 +/- 18.00 ng/g), respectively] of arsenic groups(q values were 3.06, 6.40, 10.72 respectively, P < 0.05). The primary methylated index (PMI) (0.65 +/- 0.050) and secondary methylated index (SMI) (0.55 +/- 0.050) in liver sample of GSH group were significantly higher than those (0.58 +/- 0.056, 0.44 +/- 0. 093) in arsenic group. In blood samples, the PMI (0.85 +/- 0.066) in GSH group was significantly higher than that (0.54 +/- 0.113) in arsenic group (q values were 3.75, 5.26, 4.21 respectively, P < 0.05). However, no significant difference was identified between sodium selenite and arsenic groups in liver, kidney or blood samples. And no significant difference was detected in kidney samples among all arsenic exposing groups.</p><p><b>CONCLUSION</b>Exogenous GSH could promote the methylated metabolism of iAsIII, but sodium selenite showed no significant effects.</p>

Determination and evaluation of arsenic speciation and glutathione level in lever and blood of mice subchronically exposed to inorganic arsenic / 中国地方病学杂志

Objective To explore the distribution of arsenic speciafion and to estimate the effect of arsenic on glutathione(GSH)levels in the blood and liver of mice exposed to different concentrations of inorganic AsⅢ through drinking water.Methods Mice drank water containing arsenite at concentrations of iAsⅢ of 0(contr01),25,50,100 ms/L for 6 weeks.Blood and liver were sampled to asses$the levels of inorganic arsenic(iAs),monomethylarsenic acid(MMA),dimethylarsenic acid(DMA)by the method of hydride generation trapping and ultra-hypothermia coupled with atomic absorption spectrometry,and the level of GSH by the method of 5,5'-Dithio-bis (2-Nitrobenzoic acid).Results Leveh of iAs.MMA and DMA in blood and in liver increased along with the increase of iAs concentrations in drinking water.Primary methylated index(PMI)and secondary methylation index (SMI)of liver and blood were significantly higher in exposed groups than those in control group(P＜0.05).SMI of liver in 50 mg/L exposed group[(50.45±2.94)%]was significantly higher than those in 25 mg/L and 100 mg/Lgroups[(41.68±7.09)%and(41.19±8.87)%,respectively],the difference being statistically significant(P＜0.05).The ratio of iAs.MMA and DMA in blood and liver in exposed group were 2:3:5 and 4:3:3,the percentage of level of organic arsenic(MMA+DMA)were 80%and 60%.GSH in blood and liver in exposed group decreased along with iAs concentrations in drinking water and had significant differences compared with those in control group (P＜0.05).However,levels of GSH in liver and blood did not differ significantly between exposed groups and control group(P＞0.05).Conclusions Membolism of iAs in liver is maximized when the iAs concentrations in drinking water increases to a certain level.However,the percentage of arsenic speciation in blood is different from that in liver,suggesting that other organs and tissues may be capable of methylation of inorganic arsenic.The level of GSH in liver and blood in mice is a good mark tO reflect the toxicity of arsenic.

Investigation of ulinastatin on protection of organ functions in patients with severe disease / 中国中西医结合急救杂志

Objective To study the mechanism and protection of ulinastatin on organ functions in patients with severe disease.Methods Sixty patients in the intensive care unit(ICU)from October 2005 to July 2007 were randomly divided into a control group and an ulinastatin treatment group(each 30 cases).The patients in the control group received the conventional therapy,and the cases in the other treatment group accepted ulinastatin and conventional therapy.According to the disease situations,ulinastatin was administered 200-400 kU once,2-4 times a day,sequentially for 5-7 days.On the day of admission and 3, 5,and 7 days after admission in ICU respectively,blood samples were obtained for measuring alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(Cr),blood urea nitrogen(BUN), activated partial thromboplastin time(APTT),fibrinogen(FIB)and oxygenation index(PaO_2/FiO_2); whether breathing machine or hematodialysis was used and the end results were recorded.Results The rate of usage of breathing machine(23.3%),the incidences of hepatosis(3.3%)and renal dysfunction(10.0%) and fatality(3.3%)in ulinastatin treatment group were obviously lower than those of the control group (63.3%,23.3%,46.7%,10.0%,P0.05).Only one patient received bematodialysis in control group.Conclusion Ulinastatin can protect liver,renal and lung functions markedly and lower the incidence of multiple organ dysfunction syndrome and mortality in patients with severe disease.

Structural changes of oviduct of freshwater shrimp, Macrobrachium nipponense (Decapoda, Palaemonidae), during spawning / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The structural change of the oviduct of freshwater shrimp (Macrobrachium nipponense) during spawning was examined by electron microscopy. The oviduct wall structural characteristics seem to be influenced significantly by the spawning process. Before the parturition and ovulation, two types of epithelial cells (types I and II) are found in the epithelium. The free surfaces of type I and type II cells have very dense long microvilli. Under the type I and type II cells, are a relatively thick layer of secreting material and a layer of mostly dead cells. After ovulation, two other types of epithelial cells (types III and IV) are found in the oviduct wall epithelium. The free surface of type III cells only has short microvilli scattered on the surface. The thick layer with secreting material and the dead cell layer disappeared at this stage. In some type III cells, the leaking out of cytoplasm from broken cell membrane led to the death of these type III cells. The transformation of all four types of epithelial cells was in the order: IV-->I-->II-->III.

Representative appressorium stage cDNA library of Magnaporthe grisea / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

A mature appressorium cDNA library of rice blast fungus, Magnaporthe grisea, was constructed in a lambdaTriplEx2 vector by SMART cDNA library containing 2.37x10(6) independent clones about 100% of which harbor foreign cDNA inserts with average size of 660 bp. Of 9 randomly selected clones, 2 expressed sequence tags (ESTs) sequences did not have homologous EST sequences of M. grisea in GenBank. The appressorium cDNA library is suitable for gene expression analysis and function analysis of the late stages of appressorium formation and the early stages of penetration of M. grisea.