A chromosome 21 critical region does not cause specific Down syndrome phenotypes

The "Down syndrome critical region" (DSCR) is a chromosome 21 segment purported to contain genes responsible for many features of Down syndrome (DS), including craniofacial dysmorphology. We used chromosome engineering to create mice that were trisomic or monosomic for only the mouse chromosome segment orthologous to the DSCR and assessed dysmorphologies of the craniofacial skeleton that show direct parallels with DS in mice with a larger segmental trisomy. The DSCR genes were not sufficient and were largely not necessary to produce the facial phenotype. These results refute specific predictions of the prevailing hypothesis of gene action in DS.     

Teratogenicity of vitamin B6 deficiency: omphalocele, skeletal and neural defects, and splenic hypoplasia

Vitamin B(6) deficiency was induced in pregnant rats with a deficient diet and with 4-deoxypyridoxine, a B(6) antagonist. Treated animals developed typical skin changes of B(6) deficiency. Fetuses were small and appeared anemic. Major fetal malformations were omphalocele, exencephaly, cleft palate, micrognathia, digital defects, and splenic hypoplasia. This teratologic system was developed as a model for human syndromes that exhibit combined immunologic and neurologic or skeletal defects.     

头面部肿瘤切除后创面修复的探讨

目的：探讨头面部肿瘤切除后创面修复方法。方法：根据头面部肿瘤部位及大小不同，分别采用下列6种类型皮瓣转移修复：带蒂额部皮瓣、岛状额部皮瓣、前臂游离皮瓣、下颌颈皮瓣、口角瓣及局部头瓣。结果：所有皮瓣全部成活，术后随访，功能与形态满意。结论：头面部肿瘤切除后创面应以皮瓣转移修复为宜。若创面周围有充分修复材料，则以局部皮瓣转移；若无，应考虑远位皮瓣，包括带血管蒂岛状皮瓣及游离皮瓣。     

Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome

Cardio-facio-cutaneous (CFC) syndrome is a sporadic developmental disorder involving characteristic craniofacial features, cardiac defects, ectodermal abnormalities, and developmental delay. We demonstrate that heterogeneous de novo missense mutations in three genes within the mitogen-activated protein kinase (MAPK) pathway cause CFC syndrome. The majority of cases (18 out of 23) are caused by mutations in BRAF, a gene frequently mutated in cancer. Of the 11 mutations identified, two result in amino acid substitutions that occur in tumors, but most are unique and suggest previously unknown mechanisms of B-Raf activation. Furthermore, three of five individuals without BRAF mutations had missense mutations in either MEK1 or MEK2, downstream effectors of B-Raf. Our findings highlight the involvement of the MAPK pathway in human development and will provide a molecular diagnosis of CFC syndrome.     

A mouse model of the aniridia-Wilms tumor deletion syndrome

Deletion of chromosome 11p13 in humans produces the WAGR syndrome, consisting of aniridia (an absence or malformation of the iris), Wilms tumor (nephroblastoma), genitourinary malformations, and mental retardation. An interspecies backcross between Mus musculus/domesticus and Mus spretus was made in order to map the homologous chromosomal region in the mouse genome and to define an animal model of this syndrome. Nine evolutionarily conserved DNA clones from proximal human 11p were localized on mouse chromosome 2 near Small-eyes (Sey), a semidominant mutation that is phenotypically similar to aniridia. Analysis of Dickie's Small-eye (SeyDey), a poorly viable allele that has pleiotropic effects, revealed the deletion of three clones, f3, f8, and k13, which encompass the aniridia (AN2) and Wilms tumor susceptibility genes in man. Unlike their human counterparts, SeyDey/+ mice do not develop nephroblastomas. These findings suggest that the Small-eye defect is genetically equivalent to human aniridia, but that loss of the murine homolog of the Wilms tumor gene is not sufficient for tumor initiation. A comparison among Sey alleles suggests that the AN2 gene product is required for induction of the lens and nasal placodes.     

超声照射对人胚肾细胞凋亡的影响

目的了解诊断超声照射对体外培养的人胚肾（HEK-293）细胞凋亡的影响。方法 HEK-293细胞用腹部超声探头（3.5 MHz、MI 0.8）照射0、10、20、30 min,再作Hoechst 33258染色,观察细胞凋亡的变化。结果超声照射10 min后,细胞凋亡率与假照组比较差异无统计学意义（P〉0.05）;超声照射20 min后,细胞凋亡率明显高于假照组（P〈0.05）,其中以照射30 min较为显著（P〈0.01）。结论特定剂量的超声照射可诱导人胚肾细胞凋亡增加。     

Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA

The spliceosome, a ribonucleoprotein complex that includes proteins and small nuclear RNAs (snRNAs), catalyzes RNA splicing through intron excision and exon ligation to produce mature messenger RNAs, which, in turn serve as templates for protein translation. We identified four point mutations in the U4atac snRNA component of the minor spliceosome in patients with brain and bone malformations and unexplained postnatal death [microcephalic osteodysplastic primordial dwarfism type 1 (MOPD 1) or Taybi-Linder syndrome (TALS); Mendelian Inheritance in Man ID no. 210710]. Expression of a subgroup of genes, possibly linked to the disease phenotype, and minor intron splicing were affected in cell lines derived from TALS patients. Our findings demonstrate a crucial role of the minor spliceosome component U4atac snRNA in early human development and postnatal survival.     

蔬果中残留农药的生物可给性及其膳食暴露评估研究进展

运用体外模拟方法从生物可给性方面评估污染物的膳食暴露风险已逐渐成为研究热点。膳食摄入是蔬菜水果中的农药残留危害人体健康的最为主要的暴露途径,研究蔬果中农药残留生物可给性对其膳食暴露的作用规律是当前农药残留健康风险分析亟待解决的科学问题。重点综述了基于农药残留分析测定生物可给性及其关键影响因子,介绍了不同营养成分强化下蔬果中农药残留的生物可给性,着重总结了饮食习惯对农药残留生物可给性的影响;在此基础上运用生物可给性评估蔬果中农药残留的膳食暴露评估,并对其研究今后的发展方向进行了展望。     

Nitrite and nitrate are formed by endogenous synthesis in the human intestine

Studies of nitrate balance in humans and analyses of fecal and ileostomy samples indicate that nitrite and nitrate are formed de novo in the intestine, possibly by heterotrophic nitrification. These findings significantly alter our previous conceptions of human exposure to nitrite and suggest an even wider role for nitrite in the etiology of human cancer.     

Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle

Human circadian rhythms were once thought to be insensitive to light, with synchronization to the 24-hour day accomplished either through social contacts or the sleep-wake schedule. Yet the demonstration of an intensity-dependent neuroendocrine response to bright light has led to renewed consideration of light as a possible synchronizer of the human circadian pacemaker. In a laboratory study, the output of the circadian pacemaker of an elderly woman was monitored before and after exposure to 4 hours of bright light for seven consecutive evenings, and before and after a control study in ordinary room light while her sleep-wake schedule and social contacts remained unchanged. The exposure to bright light in the evening induced a 6-hour delay shift of her circadian pacemaker, as indicated by recordings of body temperature and cortisol secretion. The unexpected magnitude, rapidity, and stability of the shift challenge existing concepts regarding circadian phase-resetting capacity in man and suggest that exposure to bright light can indeed reset the human circadian pacemaker, which controls daily variations in physiologic, behavioral, and cognitive function.     

Isoantigenic variants: isolation from human diploid cells in culture

Variant human fibroblast substrains, resistant to a cytotoxic human isoantiserum, were isolated from sensitive strains by repeated exposure to isoantiserum and rabbit complement. The resistant phenotype was stable, apparently occurred at low frequency, and was associated with loss of surface isoantigens.     

Aflatoxin P-1: a new aflatoxin metabolite in monkeys

A new phenolic derivative of aflatoxin B(1), appearing mainly in conjugated form, was identified as the principal urinary metabolite of aflatoxin B(1) in rhesus monkeys. Its identification in human urine might facilitate estimation of aflatoxin exposure in human populations.     

Effect of prolonged illumination (phototherapy) on concentrations of luteinizing hormone in human infants

Concentrations of luteinizing hormone in the serums of human neonates were altered when the neonates were exposed to prolonged, intense illumination (phototherapy) with their eyes covered. Concentrations decreased after 48 to 72 hours of exposure, increased 6 to 9 days after phototherapy, and subsequently returned to levels similar to those of controls. These data suggest that light may affect pituitary-gonadal function in the human neonate.     

我国长三角地区淡水池塘养殖水产品中抗生素残留及对人体暴露的贡献评价

为探究我国长三角地区淡水养殖水产品中抗生素残留特征及食用风险,于2019年7—10月采集上海、浙江、江苏、安徽、福建等5个地区淡水养殖池塘3类水产品(鱼类、虾类、蟹类),使用高效液相色谱-串联质谱法(LC-MS/MS)检测水产品中的9种常见抗生素,并根据人体可接受的每日摄入量(ADI)及养殖水产品消费对抗生素暴露的贡献率(CR)分别评价食用安全性和暴露风险。结果表明:9种抗生素均有检出,检出频率范围为38.1%~90.5%,浓度范围为nd~25.25 ng·g^-1;估算的每日摄入量(EDI)远低于ADI;Σ抗生素的贡献率范围为<0.01%~29.77%。研究表明,水产品摄入不会对人体健康构成抗生素暴露风险,但食用水产品时,喹诺酮类和大环内酯类抗生素的摄入应引起关注。     

Virus of the 1918 influenza pandemic era: new evidence about its antigenic character

In serums of unusually isolated Pacific islanders whose only exposure to influenza occurred during the era of the 1918 pandemic the residual neutralizing antibody was greatest to the PR/8 and BH strains of human type A influenza virus, significantly lower to swine influenza virus, and absent to equine or later human type A virus strains. The pandemic virus was thus antigenically closer to human type A strains isolated during the middle 1930's than to other known influenza virus types.     

Leukocytes of humans exposed to lysergic acid diethylamide: lack of chromosomal damage

Leukocyte cultures from eight human subjects who had had recent exposure to large doses of lysergic acid diethylamide were examined for chromosome abnormalities. The number of abnormalities was not significantly greater than that in control cultures.     

TERATOGENIC SIGNIFICANCE OF IONIC AND FLUID IMBALANCES

Some agents teratogenic to the chick embryo cause serum electrolyte and fluid inmbalances which initiate an edema syndrome leading to malformations. Differences in ionic composition of serum and yolk of normal chicks help explain how these imbalances can be produced.     

固体燃料导致室内空气污染的研究动态及热点——基于文献计量学分析

室内燃用煤炭和生物质等固体燃料会造成严重的室内空气污染，全球每年约数百万过早死亡可归因于室内固体燃料燃烧排放的PM_2.5暴露。为分析固体燃料使用导致室内空气污染的研究进展和发展趋势，采用文献计量学软件CiteSpace对Web ofScience核心数据集（Core Collection）中的相关文献进行了知识网络结构的挖掘，讨论了发文数量、期刊、关键词等的特征及变化趋势，重点探讨了该领域研究的发展过程和热点。结果表明，领域内相关研究的发文量呈指数上升趋势，说明该问题受到越来越多的关注。很多研究发表在Indoor Air、Science of the Total Environment、Energy for Sustainable Development等专业或综合类环境期刊。来自美国和中国的研究团队发文量居前列。清洁炉灶、清洁能源、黑碳和PM_2.5是领域研究中较常涉及的关键词。污染暴露的健康危害、清洁干预、健康和气候共同效益是今后值得重点关注的方向。建议围绕“污染-暴露-健康风险”的过程链，开展系列研究以支撑相关人群健康保护。