LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

OBJECTIVE: To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles. METHODS: The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4). CONCLUSION The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.
Female ; Fetus ; Genomics ; Humans ; Mutation ; Olivopontocerebellar Atrophies ; Pregnancy ; Whole Exome Sequencing

In order to explore the microbial communities and functions of activated sludge in an Anaerobic-anoxic-oxic (A²/O) process under the start-up of Actinic reaction enzyme system (ARES) system and to understand the impact of the ARES system in domestic sewage treatment process, the activated sludge microbial community structure in the A²/O process system before and after ARES system start-up was analyzed by Illumina-HiSeq 2000 high-throughput sequencing platform. By combining with the main parameters related to the effect of sewage treatment, we analyzed the environmental functions of the microbial communities. The microbial community structure of activated sludge was significantly different before and after the ARES system start-up. There were 9 main bacterial phyla in the system (average relative abundance ≥1%), accounting for 96%-98% of the total bacteria sequenced. After the ARES system was started, the relative abundance of Betaproteobacteria and Chlorobi increased by 3.45%-3.85% and 0.45%-2.61%, respectively. In the anaerobic unit, the relative abundance of Bacteroidetes increased by 12.97%, while the Actinobacteria and Firmicutes decreased by 9.60% and 1.45%, respectively. At the genus level of bacteria, the relative abundance of Denitratisoma increased by 0.80%-3.27%, while the Haliangium and Arcobacter decreased by 3.36%-4.52% and 1.48%-3.45%, respectively. The relative abundance of bacteria was significantly different before and after the ARES system start-up. There were 7 abundant fungi phyla (average relative abundance ≥1%) in the system. After the ARES system was started, the relative abundance of Rozellomycota decreased by 42.71%-46.77%. In the anaerobic unit, the relative abundance of Ascomycota decreased by 13.39%, while the relative abundance of Glomeromycota increased by 13.86%. At the genus level of fungi. The relative abundance of Entomophthoraceae sp. and Glomcromycota sp. increased by 31.35%-36.50% and 6.27%-13.84%, respectively, while the Rozellomycota sp. and Xylochrysis lucida decreased by 42.71%-46.77% and 3.67%-5.54%, respectively. Our results showed that the application of ARES system caused the response of the microbial community to environmental changes, especially for the fungi communities, in the meanwhile, improved the effluent quality, especially the removal rate of total nitrogen.
Anaerobiosis ; Ascomycota ; Bioreactors ; Microbiota ; Nitrogen ; Sewage ; Waste Disposal, Fluid

Objective To detect potential variant in a male fetus suspected for Ectrodactyly,Ectodermal dysplasia,Cleft lip/palate (EEC) syndrome.Methods Peripheral blood samples of the fetus and his parents were collected for the extraction of DNA.Whole-exome sequencing was carried out to detect potential variants.Suspected variants were verified by Sanger sequencing.Results The fetus was found to carry a heterozygous c.673C＞T missense variant of the Tp63 gene,which was known to underlie splithand/split-foot malformation.The same variant was not found in either parents.Conclusion The heterozygous c.673C＞ T missense variant of the Tp63 gene probably underlies the EEC syndrome in the fetus.Above finding also expanded the phenotypic spectrum for this variant.

Objective To investigate the therapeutic effect of damage control neurosurgery (DCNS) on patients with bilateral frontal contusion.Methods Thirty-three patients with bilateral frontal contusion,admitted to and accepted DCNS in our hospital from September 2017 to January 2019,were chosen in our study.According to DCNS rules,the disease condition changes of these patients were monitored,the internal environment disorders after trauma were adjusted,plasma osmotic pressure was increased,and blood oxygen saturation was maintained;once the patients grew worse,craniotomy and decompression should be undertaken immediately;the patients were followed up for 6 months after the injury and Glasgow outcome scale (GOS) was used to determine the prognoses of these patients.Results Among the 33 patients,25 (76％) received conservative treatment successfully,8 (24％) were converted to surgery during conservative treatment.Among the 8 patients,5 received unilateral craniotomy and three received bilateral craniotomy.The lower the Glasgow coma scale scores,the lower the proportion of conservative patients.GOS 6 months after injury showed good recovery in 11 patients,mild disability in 16 patients,severe disability in 4 patients,and plant survival in two patients;22 patients from the conservative treatment group and 5 from the surgery group had good recovery or mild disability.Conclusion DCNS can reduce the operation rate and its complications so as to make the patients recover earlier and better in the treatment of bilateral frontal contusion.

OBJECTIVETo explore the molecular basis for three pedigrees affected with hypophosphatemia vitamin D resistant rickets (X-linked hypophosphatemia, XLH).

METHODSPeripheral blood samples from the three pedigrees were collected. Following DNA extraction, the 11 exons and flanking regions of the PHEX gene were subjected to PCR amplification and direct sequencing. Pathogenicity of identified mutations was evaluated through genotype-phenotype correlation.

RESULTSFor pedigrees 1 and 2, pathogenic mutations were respectively identified in exon 8 (c.871C>T, p.R291X) and exon 15 (c.1601C>T, p.P534L) of the PHEX gene. For pedigree 3, a novel mutation (c.1234delA, p.S412Vfs*12) was found in exon 11 of the PHEX gene, which caused shift the reading frame and premature termination of protein translation.

CONCLUSIONThe three mutations probably account for the XLH in the affected pedigrees. The discovery of novel mutations has enriched the spectrum of PHEX gene mutations.

OBJECTIVETo detect potential mutations in two neonates suspected for Cornelia de Lange syndrome (CdLS).

METHODSPeripheral blood samples from the neonates and their parents were collected and analyzed for CdLS-related genes using targeted sequence capture and next-generation sequencing. Suspected mutations were confirmed by direct Sanger sequencing.

RESULTSThe neonates were found to respectively carry mutations c.7219C to T and p.D2339Lfs*4 of the NIPBL gene, among which the p.D2339Lfs*4 mutation has not been reported previously. No pathogenic mutation was found in other CdLS-related genes including NIPBL, SMC1A, SMC3, RAD21 and HDAC8.

CONCLUSIONThe c.7219C to T and p.D2339Lfs*4 mutations of the NIPBL gene probably account for the disease in both patients.

Goose hemorrhagic polyomavirus (GHPV) is not a naturally occurring infection in geese in China; however, GHPV infection has been identified in Pekin ducks, a domestic duck species. Herein, we investigated the prevalence of GHPV in five domestic duck species (Liancheng white ducks, Putian black ducks, Shan Sheldrake, Shaoxing duck, and Jinyun Sheldrake) in China. We determined that the Jinyun Sheldrake duck species could be infected by GHPV with no clinical signs, whereas no infection was identified in the other four duck species. We sequenced the complete genome of the Jinyun Sheldrake origin GHPV. Genomic data comparison suggested that GHPVs share a conserved genomic structure, regardless of the host (duck or geese) or region (Asia or Europe). Jinyun Sheldrake origin GHPV genomic characterization and epidemiological studies will increase our understanding of potential heterologous reservoirs of GHPV.
China ; Ducks ; Epidemiologic Studies ; Geese ; Genome ; Polyomavirus ; Prevalence

OBJECTIVETo explore the genetic cause of a female patient with severe mental retardation and a history of adverse pregnancy.

METHODSThe patient was subjected to G-banded chromosome analysis and single nucleotide polymorphism array (SNP-array) assaying. The correlation between genomic variations and the phenotype was explored.

RESULTSThe patient was found to have a complex chromosome rearrangement involving 5 chromosomes. The karyotypes of her parents were both normal. SNP-array assay has identified a 1.6 Mb microdeletion at chromosome 15q21.3 which involved 15 RefSeq genes and a 0.5 Mb microdeletion at 5q21.1 which involved one RefSeq gene.

CONCLUSIONThe microdeletions, which involved TCF12, ADMA10 and AQP9 genes, probably underlie the mental retardation shown by the patient.

Adult ; Chromosome Banding ; methods ; Chromosome Deletion ; Chromosomes ; genetics ; Female ; Genetic Testing ; methods ; Humans ; Intellectual Disability ; genetics ; Karyotype

OBJECTIVETo explore the genetic cause for a child with developmental delay.

METHODSThe karotypes of the child and her parents were analyzed with G-banding analysis. Their genome DNA was analyzed with low-coverage massively parallel copy number variation sequencing (CNV-seq) and verified by single nucleotide polymorphism array (SNP-array).

RESULTSThe karyotype of the child was ascertained as 46,XX,r(15)(p13q26.3), while both parents showed a normal karyotype. CNV-seq and SNP-array have identified a de novo 15q26.2-q26.3 deletion in the child with a size of approximately 3.60 Mb.

CONCLUSIONThe abnormal phenotype of the patient carrying the ring chromosome 15 may be attributed to the presence of the 15q26.2-q26.3 microdeletion. The deletion and haploinsufficiency of the IGF1R gene probably underlie the main clinical features of the patient.

Child, Preschool ; Chromosome Banding ; Chromosomes, Human, Pair 15 ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Karyotyping ; Mosaicism ; Ring Chromosomes ; Sequence Deletion