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BACKGROUND: Epidemiological and experimental studies suggest that preeclampsia has a negative impact on maternity and offspring health. Previous studies report that dysregulation in utero-environment increases risk for elderly disease such as cardiovascular disease. However, the underlying mechanisms remain elusive. Specific microRNAs (miRNAs) are packaged in exosomes may regulate microvascular dysfunction in offspring of mothers with preeclampsia. The present study aimed to identify the differential expression profiles of microRNAs in the serum exosomes between patients with preeclampsia and normal pregnancies. METHODS: A comprehensive miRNA sequence-based approach was performed to compare exosomes carry miRNAs (Exo-miRNAs) expression levels in umbilical serum between normal and preeclampsia patients. Exosomes were isolated using the ExoQuick precipitation kit. Serum exosomes were then viewed under electron microscopy, and their characteristics determined by western blotting and nanoparticle-tracking analysis. Illumina platform was used to perform sequencing. Bioinformatics analysis was used to explore differentially expressed Exo-miRNAs in umbilical serum. RESULTS: Based on sequence similarity, 1733 known miRNAs were retrieved. Furthermore, 157 mature miRNAs in serum exosomes were significantly differential expressed between PE and those control groups (P<0.05, log2|FC| > 1). Out, of the 157 miRNAs, 96 were upregulated miRNAs whereas 61 miRNAs were downregulated. The 157 differentially expressed miRNAs targeted 51,424 differentially expressed genes. Functional analysis through KEGG pathway and Gene Ontology results uncovered that target genes of miRNAs with differential expression were significantly linked to several pathways and biological processes. CONCLUSION: The findings of this study showed differential expression of umbilical serum Exo-miRNAs in normal compared with PE patients, implying that these Exo-miRNAs may associate with microvascular dysfunction in offspring of mothers with preeclampsia.
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Exossomos/metabolismo , Sangue Fetal/metabolismo , MicroRNAs/metabolismo , Pré-Eclâmpsia/sangue , Regulação para Baixo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Gravidez , Análise de Sequência de RNA , Transdução de Sinais , Regulação para CimaRESUMO
BACKGROUND: There is a lack of data regarding the prevalence of invasive group B streptococcus (GBS) infection among neonates in China. This study aimed to investigate the incidence and mortality of invasive GBS infection and to identify the risk factors in our hospital. METHODS: Seventy-four cases admitted between January 2011 and December 2016 was included in this study. A retrospective matched case-control study was conducted in a tertiary maternity and paediatric hospital. Risk factors for the acquisition of invasive GBS infection and mortality were analysed by univariable and multivariable analysis. RESULTS: We collected and analysed data from 74 infants aged < 3 months with invasive GBS infection. Among 67,985 live births, we calculated an incidence of 1.09 per 1000 live births (95%CI:0.81-1.37%); the incidence of Early-onset GBS disease (EOD, n = 65) and Late-onset GBS disease (LOD, n = 9) were 0.96(95%CI:0.73-1.19%) and 0.13(95%CI:0.04-0.22%), respectively. Overall, pneumonia accounted 63.1% (41/65) of EOD, and sepsis accounted 88.9% (8/9) cases of LOD, respectively. The overall case fatality rate was 8.11% (6/74), including 7.69% (5/65) among cases of EOD and 11.1% (1/9) among cases of LOD. No predictor of mortality was found. Membrane stripping (P = 0.005, aOR: 3.68, 95% CI: 1.48-9.13) and non-resident mother (P < 0.001, aOR: 5.88, 95% CI: 2.36-14.61) were independent risk factors for EOD; no increased risk was found for LOD. CONCLUSIONS: This study demonstrates remarkable country-specific variation in comparison with other countries. Our findings can improve awareness of neonatal GBS infection and lay a cornerstone to ensure accurate representation of the burden.
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Pneumonia Bacteriana/epidemiologia , Infecções Estreptocócicas/epidemiologia , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Maternidades/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Mortalidade , Mães/estatística & dados numéricos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Infecções Estreptocócicas/mortalidade , Streptococcus agalactiae/isolamento & purificaçãoRESUMO
Using DIVA-GIS software to study the spatial accumulation of Citrus species, an important economic crop in China. Draw the distribution maps of Citrus to concerning altitude and vegetation, and use DIVA-GIS' Bioclim ecological model and maximum information entropy model Maxent software to estimate the potential distribution areas of various Citrus species. The results show that the Citrus genus is located in the south of Qinling Mountains, mainly in the southwest of China and the coast of southeastern China. Sichuan and Chongqing are the most densely distributed regions of Citrus. The distribution of Citrus is closely related to the vegetation type and altitude. The vegetation types in the distribution area is evergreen broad-leaved forest, evergreen shrub, deciduous broad-leaved forest, mixed-leaf forest coverage area, deciduous coniferous forest, farmland, trees, other vegetation coverage, and evergreen coniferous forest. The current potential distribution area of Citrus is mainly in Guizhou, Hubei, Hunan, Guangdong, Guangxi, Yunnan, Sichuan, Chongqing, and other provinces and municipalities and their borders, while the potential distribution area in the future moves northward and enter Henan and southern Gansu. At the same time, climate warming changes the distribution of suitable areas of Citrus, which makes the suitable areas of C. sinensis Osbeck, C. reticulata Blanco, and other crops greatly increased. Planning the planting area will effectively improve the yield and quality in the future. Planning presents new challenges.
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Clima , Árvores , China , Florestas , AltitudeRESUMO
Background: Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function, characterized by an inability to reach cognitive, emotional, and motor developmental milestones. The pathology of NDDs is complex. A recent study found that variants in the SRRM2 gene cause NDDs. However, genetic conditions play the most important role in the etiology of NDD. The genetic causes of NDD are extremely heterogeneous, leading to certain challenges in clinical diagnosis. Methods: A pregnant woman with congenital intelligence disorder came to our hospital for genetic diagnosis to predict the status of her fetus. Her mother and a brother also suffer from congenital intelligence disorder. She has a daughter with speech delay. Whole exome sequencing was used to identify a mutation (c.1415C>G) in the SRRM2 gene of this family that resulted in a change in the 472nd amino acid residue of the SRRM2 protein from serine to terminated. Conclusion: We report a family with an autosomal dominant genetic disorder caused by variants in the SRRM2 gene causing NDDs. Prenatal diagnosis can help patients with this genetic disorder to have healthy offspring.
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Aminoácidos , Transtornos do Neurodesenvolvimento , Humanos , Masculino , Feminino , Gravidez , Emoções , Feto , Heterozigoto , Transtornos do Neurodesenvolvimento/genética , Proteínas de Ligação a RNARESUMO
Background: Glycogen storage diseases (GSDs) are a group of heterogeneous inherited metabolic disorders with an incidence of 4%-5%. There are 19 types of GSDs, making diagnosis one of the greatest challenges. Methods: The proband and his parents were referred to our hospital for genetic diagnosis. Ultrasound screening suggested hepatomegaly. A novel insertion variant NM_000292 c.1155_1156insT (p. 386N>*) in PHKA2 gene was identified using trio whole exome sequencing (Trio-WES), which resulted in the codon of amino acid 386 from asparagine to termination (p. 386N>*). The 3D mutant protein structure was predicted using AlphaFold, and the results showed that the truncated PHKA2 protein contained 385 of the 1,235 amino acids of the mature protein. Conclusion: We describe a previously unreported case of a GSDs IXa type Chinese boy caused by a novel PHKA2 variant. This clinical case contributes to the understanding of the characteristics of GSDs type IXa and expands the variants spectrum of genes related to GSDs type IXa. Our findings demonstrated the significance of genetic testing in the diagnosis of GSDs.
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Aminoácidos , Doença de Depósito de Glicogênio , Fosforilase Quinase , Humanos , Masculino , Doença de Depósito de Glicogênio/diagnóstico , Doença de Depósito de Glicogênio/genética , Fosforilase Quinase/genética , População do Leste Asiático , CriançaRESUMO
Abdominal fat deposition (AFD) in chickens is closely related to the gut microecological balance. In this study, the gut microbiota from high-AFD chickens was transplanted into the same strain of 0-day-old chicks via fecal microbiota transplantation (FMT). The FTM from chickens with high AFD had no obvious effects on growth traits, adult body weight, carcass weight, abdominal fat weight, and abdominal fat percentage, but did reduce the coefficient of variation of AFD traits. FMT significantly decreased cecal microbiome richness, changed the microbiota structure, and regulated the biological functions associated with energy metabolism and fat synthesis. Additionally, the cecal metabolite composition and metabolic function of FMT recipient chickens were also significantly altered from those of the controls. Transplantation of high-AFD chicken gut microbiota promoted fatty acid elongation and biosynthesis and reduced the metabolism of vitamins, steroids, and carbohydrates in the cecum. These findings provide insights into the mechanisms by which chicken gut microbiota affect host metabolic profiles and fat deposition.
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Neonatal leukemia, a congenital form of leukemia, is a rare and fatal disease occurring in the neonatal period. Its etiology and pathogenesis have remained to be fully elucidated and the clinical manifestations differ due to age variability. Acute myeloid leukemia (AML) occurring after birth indicates genetic abnormalities and possibly intrauterine exposure to radiation, drugs or other toxins. The present report described the case of a premature neonate without phenotypic signs of Down syndrome, but with an elevated white blood cell count, mainly pertaining to the monocytes of peripheral blood. At 31 weeks of gestation, delivery by Caesarean section was performed due to fetal distress; however, the infant died three days after birth. Further laboratory examination indicated pediatric myeloid leukemia. The present case report described a case of fetal AML. According to the results of peripheral blood smear and targeted-panel sequencing, 5 missense mutations with clinical significance and a novel AFF1-KMT2A fusion gene were detected, which may be the main causes of AML and death.
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INTRODUCTION: The progression of placental diseases such as preeclampsia is closely related to trophoblast dysfunction. Recent studies indicated the dysregulation of N6-methyladenosine (m6A) RNA modification in trophoblast disorders, while the function of METTL3, a methyltransferase of m6A, in trophoblasts remains to be studied. METHODS: The expression of METTL3 was determined by real-time PCR and immunoblotting. METTL3 expression in trophoblast cell lines HTR-8/SVneo and JEG-3 was knocked down using shRNA. The invasion of trophoblast cells in Matrigel was determined using xCELLigence. The m6A-containing transcripts was determined by m6A-sequencing in HTR-8/SVneo cells. The myosin light chain kinase (MYLK) gene was transfected into HTR-8/SVneo cells. RESULTS: The expression of METTL3 was downregulated in preeclamptic placentae compared to normal placentae. Knockdown of METTL3 repressed the invasion of extravillous trophoblast cells. Mechanistically, METTL3 promoted the stability of MYLK mRNA through m6A modification. Overexpression of MYLK rescued retarded cell invasion by METTL3 depletion. DISCUSSION: Collectively, our results highlight an essential role of METTL3-MYLK axis in trophoblast invasion.
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Pré-Eclâmpsia , Trofoblastos , Feminino , Gravidez , Humanos , Trofoblastos/metabolismo , Placenta/metabolismo , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/metabolismo , Linhagem Celular Tumoral , Metiltransferases/genética , Metiltransferases/metabolismo , Movimento Celular , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Proteínas de Ligação ao Cálcio/metabolismoRESUMO
Introduction: Previous studies have demonstrated that exposed to the initial suboptimal intrauterine environment of gestational diabetes mellitus (GDM) may increase risk of cardiovascular disease in adulthood. Methods: In order to investigate the underlying mechanisms involved in the increased risk of cardiovascular diseases (CVDs) in the offspring of GDM, we applied a high-throughput proteomics approach to compare the proteomic expression profile of human umbilical vessels of normal and GDM offspring. Results: A total of significantly different 100 proteins were identified in umbilical vessels from GDM group compared with normal controls, among which 31 proteins were up-regulated, while 69 proteins were down-regulated. Differentially expressed proteins (DEPs) are validated using Western blotting analysis. The analysis of these differently expressed proteins (DEPs) related diseases and functions results, performed by Ingenuity Pathway Analysis (IPA) software. Based on "Diseases and Disorders" analysis, 17 proteins (ACTA2, ADAR, CBFB, DDAH1, FBN1, FGA, FGB, FGG, GLS, GSTM1, HBB, PGM3, PPP1R13L, S100A8, SLC12A4, TPP2, VCAN) were described to be associated with CVD, especially in Anemia, Thrombus and Myocardial infarction. Functional analysis indicated that DEPs involved in many cardiovascular functions, especially in "vasoconstriction of blood vessel" (related DEPs: ACTA2, DDAH1, FBN1, FGA, FGB, and FGG). Upstream regulator analyses of DEPs identifies STAT3 as inhibitor of ACTA2, FGA, FGB, and FGG. Conclusion: The results of this study indicate that intrauterine hyperglycemia is associated with an elevated risk of cardiovascular risk in the offspring.
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Background: Fetal congenital heart disease (CHD) is the most common congenital defect, with an incidence of 0.6-0.8%, accounting for 30-50% of infant congenital disease deaths. The pathogenesis of CHD is still unclear, so an active and effective prenatal diagnosis is very important for the prevention and control of CHD. Herein, a Chinese CHD patient with rare compound heterozygous mutations in the DNAH9 gene was reported, and the 3D structure and functional changes of DNAH9 protein were predicted. Case presentation: A 23-year-old pregnant woman came to our hospital for prenatal diagnosis at 27 weeks of gestation. Both she and her partner were unaffected. Fetal CHD was detected by ultrasound screening. Copy number variation sequencing (CNV-seq) revealed an 81 kb deletion at chr17p12 (11,486,795-11,568,385), including exons 1-15 of DNAH9 gene, which plays a key role in cardiac development. Then, whole exome sequencing (WES) was used and identified a nonsense mutation (c.10975C>T) in DNAH9, which resulted in the mutation of amino acid 3,659 from glutamine to termination. The 3D mutant protein structures were predicted using SWISS-MODEL and showed structural changes from functional ß-sheet and α-helix to termination, respectively. Conclusion: We describe a case of fetal CHD caused by DNAH9 mutations and provide an effective diagnostic technique for identifying intragenic deletions. This diagnostic process can be implicated in prenatal diagnosis of CHD.
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The blue egg is both of biological interest and economic importance for consumers, egg retailers, and scientists. To date, the genetic mechanisms underlying pigment have mainly focused on protein-coding genes. However, the underpinning mechanism of non-coding RNAs on the pigment deposition among different eggshell colors remains unknown. In this study, RNA sequencing was employed to profile the uterine gland transcriptome (lncRNA and mRNA) of 15 Changshun blue eggshell layers, to better understand the genetic mechanisms of deposition of blue eggshell color. Results showed that differentially expressed mRNAs, GO terms, and KEGG pathways among pink-eggshell and blue-eggshell chickens were mainly targeting immune- and transporter-related terms with the SLC family, IgJ, CD family, and MTMR genes. Furthermore, the progesterone-mediated oocyte maturation and cortisol synthesis and secretion pathway with targeted gene PGR and Pbx1 were significantly enriched between blue- and pink-eggshell chickens. Integrating analysis of lncRNA and mRNA profiles predicted 4 and 25 lncRNA-gene pairs by antisense and cis analysis. They were relative to immune, nerve, and lipids and amino acid metabolisms, porphyrin, and chlorophyll metabolism with targeted gene FECH and oxidative phosphorylation and cardiac muscle contraction pathways with targeted gene COX6A1. Within blue-eggshell chickens, the GO terms hindbrain tangential cell migration and phosphatidylinositol monophosphate phosphatase activity with targeted gene Plxna2 and MTRM1 were identified. Integrating analysis of lncRNA and mRNA profiles predicted 8 and 22 lncRNA-gene pairs. Most pathways were mainly enriched on lipid-related metabolisms as found in mRNA sequencing. The lncRNAs did exert similar functions in color formation by modulating pigment disposition and immune- and lipid-related metabolisms. Our results provide a catalog of chicken uterine lncRNAs and genes worthy of further studies to understand their roles in the selection for blue eggshell color layers.
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Progesterone (P4) belongs to a factor that affects stress response and is a potential carcinogen, and saliva levels are expected to be a standard measurement for clinical diagnosis. In this study, a new type of nanoflower with both recognition functionality and catalytic substrate ability was prepared by copper phosphate, Pt/IrO2 nanocomposites (Pt/IrO2 NPs), streptavidin (SA) and horseradish peroxidase (HRP) via a one-pot co-precipitation strategy. Due to the enhanced catalytic activity and stability of Pt/IrO2@SA@HRP nanoflowers, we developed a powerful and sensitive multiple-catalysis ELISA to monitor progesterone in saliva. Multiple-catalysis ELISA based on a specific antibody and Pt/IrO2@SA@HRP nanoflowers exhibited a linear interval range from 0.217 ng mL-1 to 7.934 ng mL-1. The median inhibitory concentration (IC50) for progesterone is 1.311 ng mL-1 and the limit of detection (LOD = IC10) is 0.076 ng mL-1 in the proposed method. Satisfactory recoveries were in a range of 79.6-107% with an acceptable coefficient of variation (below 10.6%). Results of the multiple-catalysis ELISA and LC-MS/MS had a good coincidence. Our result unraveled that multiple-catalysis ELISA is a potentially serviceable tool for the detection of progesterone in saliva.
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Colorimetria , Progesterona , Cromatografia Líquida , Peroxidase do Rábano Silvestre , Irídio , Nanoestruturas , Platina , Saliva , Estreptavidina , Espectrometria de Massas em TandemRESUMO
Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC or ACCPN) is an autosomal recessive disease caused by the disruption of the SLC12A6 gene, which encodes the K-Cl cotransporter-3 (KCC3). A ubiquitous deletion of KCC3 in mice leads to severe locomotor deficits similar to ACCPN patients. However, the underlying pathological mechanism leading to the disease remains unclear. Even though a recent study suggests that the neuropathic features of ACCPN are mostly due to neuronal loss of KCC3, the specific cell type responsible for the disease is still unknown. Here we established four tissue specific KCC3 knockout mouse lines to explore the cell population origin of ACCPN. Our results showed that the loss of KCC3 in parvalbumin-positive neurons led to significant locomotor deficit, suggesting a crucial role of these neurons in the development of the locomotor deficit. Interestingly, mice in which KCC3 deletion was driven by the neuron-specific enolase (NSE) did not develop any phenotype. Furthermore, we demonstrated that nociceptive neurons targeted with Nav1.8-driven CRE and Schwann cells targeted with a desert hedgehog-driven CRE were not involved in the development of ACCPN. Together, these results establish that the parvalbumin-positive neuronal population is an important player in the pathogenic development of ACCPN.
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Agenesia do Corpo Caloso , Gânglios Espinais/metabolismo , Transtornos dos Movimentos/etiologia , Neurônios/metabolismo , Parvalbuminas/metabolismo , Doenças do Sistema Nervoso Periférico , Simportadores/deficiência , Agenesia do Corpo Caloso/complicações , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/patologia , Análise de Variância , Animais , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Gânglios Espinais/patologia , Camundongos , Camundongos Transgênicos , Atividade Motora/genética , Transtornos dos Movimentos/genética , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/patologia , Fosfopiruvato Hidratase/metabolismo , Desempenho Psicomotor/fisiologia , Tempo de Reação/genética , Medula Espinal/patologia , Simportadores/genéticaRESUMO
Pollen and phytolith analyses were undertaken at the Jiangli site in Suzhou, Jiangsu Province, combined with studies on macrofossils by flotation. The concentration of pollen decreased while the percentage of Poaceae pollen in the profile increased from the late phase of the Majiabang Culture to the Songze Culture suggesting that human impact on the local environment intensified gradually. The discovery of rice paddy implies a relatively advanced rice cultivation in this area during the middle-late Holocene. Other than phytoliths, the high percentage of Oryza-type Poaceae pollen (larger than 40 µm) supplied robust evidence for the existence of rice paddy. Moreover, the fact that the farther from the rice paddy, the lower the concentration and percentage of Poaceae pollen also proves that the dispersal and deposition of pollen is inversely proportional to the distance.
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Mudança Climática , Produtos Agrícolas , Fósseis , Oryza/crescimento & desenvolvimento , Poaceae/crescimento & desenvolvimento , Pólen , China , Meio Ambiente , HumanosRESUMO
Pollen and phytolith analyses were undertaken at the Jiangli site in Suzhou, Jiangsu Province, combined with studies on macrofossils by flotation. The concentration of pollen decreased while the percentage of Poaceae pollen in the profile increased from the late phase of the Majiabang Culture to the Songze Culture suggesting that human impact on the local environment intensified gradually. The discovery of rice paddy implies a relatively advanced rice cultivation in this area during the middle-late Holocene. Other than phytoliths, the high percentage of Oryza-type Poaceae pollen (larger than 40 µm) supplied robust evidence for the existence of rice paddy. Moreover, the fact that the farther from the rice paddy, the lower the concentration and percentage of Poaceae pollen also proves that the dispersal and deposition of pollen is inversely proportional to the distance.
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Mudança Climática , Produtos Agrícolas , Fósseis , Oryza/crescimento & desenvolvimento , Poaceae/crescimento & desenvolvimento , Pólen , China , Meio Ambiente , HumanosRESUMO
The K-Cl cotransporter (KCC) functions in maintaining chloride and volume homeostasis in a variety of cells. In the process of cloning the mouse KCC3 cDNA, we came across a cloning mutation (E289G) that rendered the cotransporter inactive in functional assays in Xenopus laevis oocytes. Through biochemical studies, we demonstrate that the mutant E289G cotransporter is glycosylation-deficient, does not move beyond the endoplasmic reticulum or the early Golgi, and thus fails to reach the plasma membrane. We establish through co-immunoprecipitation experiments that both wild-type and mutant KCC3 with KCC2 results in the formation of hetero-dimers. We further demonstrate that formation of these hetero-dimers prevents the proper trafficking of the cotransporter to the plasma membrane, resulting in a significant decrease in cotransporter function. This effect is due to interaction between the K-Cl cotransporter isoforms, as this was not observed when KCC3-E289G was co-expressed with NKCC1. Our studies also reveal that the glutamic acid residue is essential to K-Cl cotransporter function, as the corresponding mutation in KCC2 also leads to an absence of function. Interestingly, mutation of this conserved glutamic acid residue in the Na(+)-dependent cation-chloride cotransporters had no effect on NKCC1 function in isosmotic conditions, but diminished cotransporter activity under hypertonicity. Together, our data show that the glutamic acid residue (E289) is essential for proper trafficking and function of KCCs and that expression of a non-functional but full-length K-Cl cotransporter might results in dominant-negative effects on other K-Cl cotransporters.