Reevaluating the splice-altering variant in TECTA as a cause of nonsyndromic hearing loss DFNA8/12 by functional analysis of RNA.

PURPOSE: The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing (PGT)for them. METHODS: Clinical examination, pedigree analysis and exome sequencing were carried out on the family. Minigene-based splicing analysis, in vivo RNA analysis and protein structure prediction by molecular modeling were conducted on the candidate variant. PGT for the causative variation and chromosome aneuploidis based on SNP analysis has been used for avoidance of hearing loss in this family. RESULTS: All the affected individuals presented with moderate down-sloping hearing loss and whole-exome sequencing identified a novel splice-site variant c.5383+6T>A in the tested subjects within the TECTA locus. Genotyping of all the 32 family members confirmed segregation of this variant and the hearing loss phenotype in the extended family. Functional analysis of RNA and molecular modeling indicates that c.5383+6T>A is a pathogenic splice-site variant and should be considered as genetic cause of the hearing loss. Furthermore, a successful singleton pregnancy with no variation in TECTA c.5383+6 was established and a healthy male child was born by PGT. CONCLUSION: We have identified a novel variant c.5383+6T>A in TECTA ZA-ZP inter-domain, which could be attributable to the early-onset autosomal dominant hearing loss. The implications of our study are valuable in elucidating the disrupted RNA splicing and uncovering the genetic cause of hearing loss with TECTA pathogenic variants, as well as providing reproductive approaches to healthy offspring.

Portable Miniature Mass Spectrometry for Enhanced On-Site Detection of Analytes in Complex Samples by Integrating Solid-Phase Microextraction and Nano-Electrospray Ionization.

On-site mass spectrometry (MS) analysis plays a crucial role in timely understanding chemical compositions of field samples but presents a challenge to miniaturization, portability, and sensitivity. In this work, a portable MS approach was developed by integrating biocompatible solid-phase microextraction (SPME) and a nano-electrospray ionization (nESI) emitter into a kit to couple miniature MS (mMS). The SPME fiber was used for on-site extractive sampling of analytes from complex liquid samples and living organisms and was then inserted into an nESI emitter for on-site MS analysis via the facile kit. The limit of detection was found to be at the pg/mL level for various compounds tested. Acceptable relative standard deviation (RSD) values (5.5-7.6%, n = 6) were obtained for direct measurement of analytes in complex matrixes; acceptable linear responses (0.1-50 ng/mL) and matrix effects (76.0-82.6%) were also found. Enhanced detection of compounds of interest in various real samples, such as food samples, human fluids, environmental water, and living organisms, was unambiguously demonstrated. Our experimental data showed that SPME-nESI-mMS is a promising tool for on-site analysis of various complex samples in significant applications including but not limited to food safety, environmental monitoring, forensic investigation, and bioanalysis.

Chromosome-level genome of Schistosoma haematobium underpins genome-wide explorations of molecular variation.

Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting > 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital tissues, and can lead to increased susceptibility to HIV/AIDS and squamous cell carcinoma of the bladder. To complement available treatment programs and break the transmission of disease, sound knowledge and understanding of the biology and ecology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease and the effectiveness of control programs including mass drug administration. Here we report the first chromosome-contiguous genome for a well-defined laboratory line of this blood fluke. An exploration of this genome using transcriptomic data for all key developmental stages allowed us to refine gene models (including non-coding elements) and annotations, discover 'new' genes and transcription profiles for these stages, likely linked to development and/or pathogenesis. Molecular variation within S. haematobium among some geographical locations in Africa revealed unique genomic 'signatures' that matched species other than S. haematobium, indicating the occurrence of introgression events. The present reference genome (designated Shae.V3) and the findings from this study solidly underpin future functional genomic and molecular investigations of S. haematobium and accelerate systematic, large-scale population genomics investigations, with a focus on improved and sustained control of urogenital schistosomiasis.

Developmental Trends in Postnatal Thyroid Hormones and Thyroid Dysfunction in Preterm Infants Born at less than 34 weeks Gestation.

OBJECTIVES: To analyse the trends in thyroid function tests (TFT) in preterm infants, evaluate the frequency of thyroid dysfunction, and identify the factors that influence thyroid function. METHODS: The TFT results and risk factors for thyroid dysfunction in preterm infants with gestational ages (GA) between 25 and 34 weeks were analysed. RESULTS: In total, 535 infants were enrolled in this study. Thyroid hormone levels vary with gestational and postnatal age, and the total frequency of thyroid dysfunction is 50.3%. Thirty-one infants (5.8%) had delayed TSH elevation. Transient hypothyroxinaemia of prematurity remained significantly associated with both lower birth weight and GA. Congenital hypothyroidism was significantly associated with lower birth weight, 5 min Apgar score, and dopamine use. CONCLUSIONS: Thyroid hormone levels in preterm infants are related to gestation and postnatal age, the frequency of thyroid dysfunction in premature infants is high, and is negatively correlated with GA and birth weight.

miR-218-5p in endometrial microenvironment prevents the migration of ectopic endometrial stromal cells by inhibiting LASP1.

BACKGROUND: Our previous two-dimensional electrophoresis experiment showed that the expression of LASP1 in patients with endometriosis was significantly higher than that of control endometrium. However, the molecular mechanism by which LASP1 is regulated in endometriosis/adenomyosis is unknown. METHODS: Herein, qPCR was performed to analyze the expression levels of LASP1 and miR-218-5p between endometriosis (Ems) cells and control cells. Fluorescence in situ hybridization was carried out to measure the expression level of miR-218-5p in ectopic endometrium versus normal endometrium. After miR-218-5p mimic or inhibitor were transfected, the transwell experiment was carried out to see the effect of miR-218-5p on the migration of endometrial stromal cells (ESCs). EdU was used to measure cell proliferation rate. Dual-luciferase reporter assay was used to verify the binding of hsa-miR-218-5p to the 3'UTR of LASP1. Western blot and immunofluorescence analysis were carried out to identify the protein expression pattern of LASP1 and EMT markers in endometrial tissue. RESULTS: The miR-218-5p is mainly secreted from blood vessels and expressed in the muscle layer around the endometrium, which inhibits the expression level of LASP1 by binding the 3'UTR region of LASP1 in normal ESCs. Overexpression of miR-218-5p impedes the epithelial-to-mesenchymal transition (EMT) and prevents the migration of ESCs and the expression of Vimentin in Ems. CONCLUSIONS: Our findings revealed that miR-218-5p in endometrial microenvironment prevents the migration of ectopic endometrial stromal cells by inhibiting LASP1.

Factors associated with fetal karyotype in spontaneous abortion: a case-case study.

BACKGROUND: Most embryos that spontaneously abort during early pregnancy are found to have chromosomal abnormalities. The purpose of this study is to explore the factors involved in chromosome aberrations during embryogenesis. METHODS: A case-case study was performed to compare the risk factors for spontaneous abortion with and without embryo chromosome aberration. A total of 160 cases of spontaneous abortion were enrolled from a tertiary general hospital in Kunming. KaryoLite BACs-on-Beads (KL-BoBs) and fluorescence in situ hybridization (FISH) were employed to determine chromosomal constitution of abortion chorion villus samples. Maternal serum levels of homocysteine (Hcy) were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Information about clinical background and environmental exposure was collected through a self-designed questionnaire. To identify the inherited chromosomal abnormalities, couples with chromosomal abnormalities in abortus were recalled for karyotyping. RESULTS: The overall rate of chromosomal abnormalities was 62.5% (100/160, KL-BoBs combined with FISH) including 51.9% (83/160) aneuploidies, 6.3% (10/160) polyploidies, and 4.4% (7/160) structural abnormalities. Only one case of structural abnormality was found to be inherited from maternal balanced translocation. Compared to abortus with normal karyotype, abortus with abnormal karyotype showed a positive association with parental age and elevated maternal serum homocysteine (Hcy) level, but negative association with previous miscarriage and perceived noise. CONCLUSIONS: Embryonic chromosomal aberrations accounted for the majority of spontaneous abortion cases. A combination of internal and external factors may induce spontaneous abortion through fetal chromosomal aberrations or other pathogenic mechanisms.

In Vitro Inhibitory Effects of Maqian Essential Oil against Ectopic Endometrial Stromal Cells and LPS-Induced Endometrial Epithelial Cells.

Previous studies revealed that MQEO (Maqian fruits essential oil), which is extracted from the fruit of Maqian (Zanthoxylum myriacanthum var. Pubescens), had a good anti-inflammatory effect, but the effect on endometriosis in vitro remains unknown. In the present study, the inhibitory effects of MQEO against the EESCs (ectopic endometrial stromal cells) were investigated. Cells were treated with a concentration gradient (from 0.025 % to 0.15 %) of MQEO for 24 h and cell viability was detected by CCK-8. In addition, apoptotic rates were investigated using flow cytometry. The effect of MQEO on cell migration was determined by wound-healing and transwell assay. The expression of apoptosis-associated and cell adhesion-related proteins was assessed by western blotting. The transcriptional levels of IL-1, IL-6 and TNF-α were determined by Real-time qPCR. RNA-seq was used to identify the DEGs (differentially expressed genes) in MQEO-pretreated EESCs. We found that the MQEO condition dosage-dependently reduced the cell viability of EESCs. Based on flow cytometry results, the number of apoptotic cells increased significantly with dosage. The wound-healing and transwell results showed that MQEO group exhibited a significantly decreased cell motility and migration ability in comparison with the normal group. Western blotting results showed that MQEO down-regulated the expression of Bcl-2, ICAM-1 (intercellular adhesion molecule 1) and CD44, but up-regulated the cleaved caspase-3 expression in EESCs. What's more, MQEO also inhibited the LPS-induced inflammation in human EECs (endometrial epithelial cells). RNA-seq revealed that 221 DEGs were up-regulated genes and 284 DEGs were down-regulated in MQEO-pretreated EESCs. Our data uncovered the beneficial effects of MQEO in endometriosis and provided new insights into the mechanism of the effect of MQEO on EESCs, suggesting MQEO could be a promising new therapeutic agent for endometriosis.

Wooden-Tip Electrospray Mass Spectrometry Characterization of Human Hemoglobin in Whole Blood Sample for Thalassemia Screening: A Pilot Study.

Traditional analytical methods for thalassemia screening are needed to process complicated and time-consuming sample pretreatment. In recent decades, ambient mass spectrometry (MS) approaches have been proven to be an effective analytical strategy for direct sample analysis. In this work, we applied ambient MS with wooden-tip electrospray ionization (WT-ESI) for the direct analysis of raw human blood samples that were pre-identified by gene detection. A total of 319 whole blood samples were investigated in this work, including 100 α-thalassemia carriers, 67 ß-thalassemia carriers, and 152 control healthy samples. Only one microliter of raw blood sample was directly loaded onto the surface of the wooden tip, and then five microliters of organic solvent and a high voltage of +3.0 kV were applied onto the wooden tip to generate spray ionization. Multiply charged ions of human hemoglobin (Hb) were directly observed by WT-ESI-MS from raw blood samples. The signal ratios of Hb chains were used to characterize two main types of thalassemia (α and ß types) and healthy control blood samples. Our results suggested that the ratios of charged ions to Hb chains being at +13 would be an indicator for ß-thalassemia screening.

[Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows for premature ejaculation: A prospective single-center randomized controlled study].

OBJECTIVE: To investigate the efficacy and safety of Compound Chamomile and Lidocaine Hydrochloride Gel (CCLH) (Kamistad) applied at different time-windows on premature ejaculation (PE). METHODS: This prospective study included 72 PE patients treated by application of CCLH to the glans and penile body in our hospital from February to October 2021. According to the time of drug administration before insertion into the vagina, we randomly divided the patients into a 5-minute group (n = 39) and a 15-minute group (n = 33). Before and after 1 and 2 weeks of treatment, we compared the intravaginal ejaculation latency time (IELT), PE diagnostic tool (PEDT) score, quality of life, and adverse reactions between the two groups of patients. RESULTS: Totally 62 of the patients completed the follow-up, 35 in the 5-minute group and 27 in the 15-minute group, and all showed significant improvement in IELT (P < 0.01) and PEDT score (P < 0.05) after treatment compared with the baseline. No allergic reactions, such as redness and swelling, developed at the application site in any of the patients, and no adverse significant effect was observed on the erectile hardness in 61 of the cases. Six cases showed increased erectile hardness instead. Fifty-seven of the patients experienced no obvious penile numbness or reduced sexual satisfaction, and all could complete their sexual activities. CONCLUSION: Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows is effective on PE, with a 5-minute rapid onset of action before intercourse, and no obvious adverse effects.

Metabolomics Insights into Oleate-Induced Disorders of Phospholipid Metabolism in Macrophages.

BACKGROUND: Diet-induced disordered phospholipid metabolism and disturbed macrophage metabolism contribute to the pathogenesis of metabolic diseases. However, the effects of oleate, a main dietary fatty acid, on macrophage phospholipid metabolism are unclear. OBJECTIVES: We aimed to discover oleate-induced disorders of macrophage phospholipid metabolism and potential therapeutic targets for treating diet-related metabolic diseases. METHODS: RAW 264.7 cells were exposed to 65 µg oleate/mL, within the blood concentration range of humans and mice, to trigger disorders of phospholipid metabolism. Meanwhile, WY-14643 and pioglitazone, 2 drugs widely used for treating metabolic diseases, were employed to prevent oleate-induced disorders of macrophage phospholipid metabolism. Subsequently, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry was used to discover relevant metabolic disorders and potential therapeutic targets. RESULTS: We showed that 196 metabolites involved in phospholipid metabolism were altered upon oleate treatment and interventions of WY-14643 and pioglitazone (P < 0.05, 2-tailed Mann-Whitney U test). Notably, most lysophospholipids were decreased, whereas most phospholipids were increased in oleate-treated macrophages. Phosphatidylethanolamines accumulated most among phospholipids, and their acyl chain polyunsaturation increased in oleate-treated macrophages. Additionally, saturated fatty acids were decreased, whereas polyunsaturated fatty acids were increased in oleate-treated macrophages. Furthermore, changes in phosphatidylglycerols, phosphatidylinositols, cardiolipins, phosphatidates, lysophosphatidylglycerols, and acylcarnitines in oleate-treated macrophages could be attenuated or even abolished by WY-14643 and/or pioglitazone treatment. CONCLUSIONS: Oleate induced accumulation of various phospholipids, increased acyl chain polyunsaturation of phosphatidylethanolamines, and decreased lysophospholipids in RAW 264.7 macrophages. This study suggests macrophage phospholipid and fatty acid metabolism as potential therapeutic targets for intervening diet-related metabolic diseases.

Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome.

OBJECTIVE: Sick sinus syndrome (SSS) is associated with loss of HCN4 (hyperpolarization-activated cyclic nucleotide-gated potassium channel 4) function in the cardiac conduction system. The underlying mechanism for SSS remains elusive. This study is to investigate how mitochondrial oxidative stress induces HCN4 downregulation associated with in sick sinus syndrome. METHODS AND RESULTS: Trx2lox/lox mice were crossed with α-myosin heavy chain (α-Mhc)-Cre and Hcn4-CreERT2 deleter mice to generate Trx2 deletion mice in the whole heart (Trx2cKO) and in the conduction system (Trx2ccsKO), respectively. Echocardiography was applied to measure hemodynamics and heart rhythm. Histological analyses, gene profiling and chromatin immunoprecipitation were performed to define the mechanism by which thioredoxin-2 (Trx2) regulates HCN4 expression and cardiac function. Trx2cKO mice displayed dilated cardiomyopathy, low heart rate, and atrial ventricular block (AVB) phenotypes. Immunofluorescence revealed that HCN4 expression was specifically reduced within the sinoatrial node in Trx2cKO mice. Interestingly, Trx2ccsKO mice displayed low heart rate and AVB without dilated cardiomyopathy. Both mRNA and protein levels of HCN4 were reduced in the sinoatrial node, suggesting transcriptional HCN4 regulation upon Trx2 deletion. ChIP indicated that the binding of MEF2 to the HCN4 enhancer was not altered by Trx2 deletion; however, histone 3 acetylation at the MEF2 binding site was decreased, and expression of histone deacetylase 4 (HDAC4) was elevated following Trx2 deletion. Moreover, HDAC4 binding to the HCN4 enhancer was mediated by MEF2. Mitochondrial ROS were increased by Trx2 deletion and importantly, mitochondria-specific ROS scavenger MitoTEMPO suppressed HDAC4 elevation, HCN4 reduction, and sinus bradycardia in Trx2ccsKO mice. CONCLUSION: In the conduction system, Trx2 is critical for maintaining HCN4-mediated normal heart rate. Loss of Trx2 reduces HCN4 expression via a mitochondrial ROS-HDAC4-MEF2C pathway and subsequently induces sick sinus syndrome in mice.

Critical role of Lin28-TNFR2 signalling in cardiac stem cell activation and differentiation.

Tumour necrotic factor receptor-2 (TNFR2) has been to be cardiac-protective and is expressed in cardiac progenitor cells. Our goal is to define the mechanism for TNFR2-mediated cardiac stem cell activation and differentiation. By employing a protocol of in vitro cardiac stem cell (CSC) differentiation from human inducible pluripotent stem cell (hiPSC), we show that expression of TNFR2 precedes expression of CSC markers followed by expression of mature cardiomyocyte proteins. Activation of TNFR2 by a specific agonist promotes whereas inhibition of TNFR2 by neutralizing antibody diminishes hiPSC-based CSC differentiation. Interestingly, pluripotent cell factor RNA-binding protein Lin28 enhances TNFR2 protein expression in early CSC activation by directly binding to a conserved Lin28-motif within the 3'UTR of Tnfr2 mRNA. Furthermore, inhibition of Lin28 blunts TNFR2 expression and TNFR2-dependent CSC activation and differentiation. Our study demonstrates a critical role of Lin28-TNFR2 axis in CSC activation and survival, providing a novel strategy to enhance stem cell-based therapy for the ischaemic heart diseases.

Simple Fabrication of Solid-Phase Microextraction with Surface-Coated Aluminum Foil for Enhanced Detection of Analytes in Biological and Clinical Samples by Mass Spectrometry.

Rapid detection of analytes in biological and clinical samples is highly desirable, and significant progress has been made with direct mass spectrometric (MS) analysis. Rapid and sensitive detection, however, remains a major challenge in direct analysis of raw samples. In this study, we described a simple, rapid, and efficient method for enhanced detection of analytes in complex samples, using surface-coated aluminum (Al) foil that was simply made with conductive resin for physical adhesion of functional particles. The surface-coated Al foils were used as a solid-phase microextraction (SPME) tip for rapid sampling of target analytes from raw samples and then applied as an electrospray ionization (ESI) tip to couple MS for sensitive detection. Our results show that surface-coated Al foil is highly effective for enhanced detection of analytes in complex samples with excellent analytical performances, including sensitivity, reproducibility, and linear ranges. Overall, this development enabled an extremely simplified protocol to integrate SPME and ESI that is expected to have a significant impact on rapid screening of raw samples.

[Study of the phenylalanine hydroxylase gene variants in patients with phenylketonuria from Jiangxi province].

OBJECTIVE: To delineate the variants spectrum of phenytalanine hydroxylase (PAH) gene among 78 unrelated patients with phenylketonuria (PKU) from Jiangxi province. METHODS: The 13 exons and flanking intronic regions of the PAH gene were subjected to PCR amplification and sequencing. RESULTS: A total of 143 variants were detected among the 156 alleles, which included 54 types of variants, which yielded a detection rate of 91.7%. Common variants have included R243Q (26/143, 18.2%), R408Q (10/143, 7.0%), EX6-96A to G(8/143, 5.6%), IVS4-1G to A(7/143, 4.9%), R241C(7/143, 4.9%) and V399V(7/143, 4.9%). In addition, 6 novel variants were detected, which included IVS4-3T to G, Q172H, C284Y, V291L, V329del, and L430R. The variants consisted of missense, splicing, nonsense and deletion variants, which have mainly located in exons 7 (45, 31.5%), 12(17, 11.9%), 11(16, 11.2%) and 6(14, 9.8%). CONCLUSION: Variants of the PAH gene identified in Jiangxi province mainly involve exons 7, 12, 11 and 6, with the most common variants being R243Q and R408Q. Six novel variants were identified.

A Gene Encoding a DUF247 Domain Protein Cosegregates with the S Self-Incompatibility Locus in Perennial Ryegrass.

The grass family (Poaceae), the fourth largest family of flowering plants, encompasses the most economically important cereal, forage, and energy crops, and exhibits a unique gametophytic self-incompatibility (SI) mechanism that is controlled by at least two multiallelic and independent loci, S and Z. Despite intense research efforts over the last six decades, the genes underlying S and Z remain uncharacterized. Here, we report a fine-mapping approach to identify the male component of the S-locus in perennial ryegrass (Lolium perenne L.) and provide multiple evidence that a domain of unknown function 247 (DUF247) gene is involved in its determination. Using a total of 10,177 individuals from seven different mapping populations segregating for S, we narrowed the S-locus to a genomic region containing eight genes, the closest recombinant marker mapping at a distance of 0.016 cM. Of the eight genes cosegregating with the S-locus, a highly polymorphic gene encoding for a protein containing a DUF247 was fully predictive of known S-locus genotypes at the amino acid level in the seven mapping populations. Strikingly, this gene showed a frameshift mutation in self-compatible darnel (Lolium temulentum L.), whereas all of the self-incompatible species of the Festuca-Lolium complex were predicted to encode functional proteins. Our results represent a major step forward toward understanding the gametophytic SI system in one of the most important plant families and will enable the identification of additional components interacting with the S-locus.

Elevated plasma levels of lysophosphatidic acid and aberrant expression of lysophosphatidic acid receptors in adenomyosis.

BACKGROUND: Given the important roles of the receptor-mediated lysophosphatidic acid (LPA) signaling in both reproductive tract function and gynecological cancers, it will be informative to investigate the potential role of LPA in the development of adenomyosis. The objective of this study was to evaluate the levels of LPA in plasma and the expression of six LPA receptors in the endometrial tissue collected from women with and without adenomyosis. METHODS: Plasma and endometrial tissue samples were collected form women with and without adenomyosis. The levels of LPA in plasma were determined by using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Immunohistochemistry was performed to evaluate the expression of six LPA receptors (LPA1-6) in endometrial tissue samples. The effects of LPA on IL-8 production, VEGF production and cell proliferation in human endometrial stromal cells (ESCs) were also assessed. RESULTS: LPA1 staining was localized to the cytoplasm, membrances of the epithelial cells of the endometrial glands, and there was little staining in the stromal cells. LPA2-5 staining were localized to the nuclei of stromal and glandular cells. Plasma levels of LPA were increased in adenomyosis. LPA1, LPA4 and LPA5 immunoreactivity were significantly higher in the adenomyosis group than in the control group, while LPA2 and LPA3 immunoreactivity were significantly lower in the adenomyosis group than in the control group. LPA6 was undetectable in the endometria. LPA induced the release of IL-8 from ESCs but did not affect cell proliferation and VEGF production. CONCLUSION: These results indicate that elevated plasma levels of LPA and aberrant expression of LPA receptors in the endometria may be associated with the development of adenomyosis.

[Genetic analysis and prenatal diagnosis for a pregnant woman with an unbalanced t(1;2), t(6;7) translocation and intellectual disability].

OBJECTIVE: To provide genetic analysis for a pregnant woman with chromosomal translocations and intellectual disability, and to provide prenatal diagnosis for her fetus. METHODS: Routine G-banding was performed to analyze the karyotypes of the woman and her fetus. Copy number variants were determined with array comparative genomic hybridization (array-CGH). RESULTS: The pregnant woman has carried an apparently balanced translocation involving chromosomes 1, 2, 6 and 7, with a karyotype of 46, XX, t(1;2) (p22;p23), t(6;7) (q21;p15). The karyotype of her fetus was ascertained as 46, XY, t(6;7) (q21;p15) mat. Array-CGH has detected a 4 Mb microdeletion at 6q22.1-q22.31 (115 311 507-119 332 956) in both individuals. As the 6q22.1-q22.31 microdeletion may be associated with the main clinical manifestations of the woman, the family decided to terminate the pregnancy. The fetus was male and appeared to have no obvious abnormality. CONCLUSION: Prenatal diagnosis for pregnant women with translocations and mental retardation is a challenging task. Combined application of cytogenetic analysis and array-CGH may facilitate the diagnosis and genetic counseling.

[Application of BoBs technique for detecting common chromosome microdeletion and microduplication syndromes].

OBJECTIVE: To establish a strategy for screening and diagnosing common microdeletion and microduplication syndromes among children with idiopathic mental retardation and development abnormalities. METHODS: Potential chromosomal variations among patients with unexplained mental retardation, cardiac anomalies, particular facial features, learning disabilities and other clinical characteristics were detected with bacterial artificial chromosome BACs-on-Beads (BoBs) technique and karyotyping. Positive results were verified with array-based comparative genomic hybridization (Array-CGH). RESULTS: Fifty eight of the 60 patients had a normal chromosome karyotype. Ten patients with microdeletion and microduplication syndromes were detected by BoBs, which included two positive cases identified through chromosome karyotyping. Two patients were respectively diagnosed as Smith-Magenis syndrome and Prader-Willi/Angelman syndrome by BoBs and the results were confirmed by Array-CGH. CONCLUSION: BoBs is capable of detecting chromosome microdeletion and microduplication with high specificity and throughput, which can compensate the shortcomings of conventional cytogenetic technology and will be widely applied for clinical diagnosis.

ß-Arrestin2 Contributes to Cell Viability and Proliferation via the Down-Regulation of FOXO1 in Castration-Resistant Prostate Cancer.

ß-Arrestin2 has been identified to act as a corepressor of androgen receptor (AR) signaling by binding to AR and serving as a scaffold to affect the activity and expression of AR in androgen-dependent prostate cancer cells; however, little is known regarding its role in castration-resistant prostate cancer (CRPC) progression. Here, our data demonstrated that ß-arrestin2 contributes to the cell viability and proliferation of CRPC via the downregulation of FOXO1 activity and expression. Mechanistically, in addition to its requirement for FOXO1 phosphorylation induced by IGF-1, ß-arrestin2 could inhibit FOXO1 activity in an Akt-independent manner and delay FOXO1 dephosphorylation through the inhibition of PP2A phosphatase activity and the attenuation of the interaction between FOXO1 and PP2A. Furthermore, ß-arrestin2 could downregulate FOXO1 expression via ubiquitylation and proteasomal degradation. Together, our results identified a novel role for ß-arrestin2 in the modulation of the CRPC progress through FOXO1. Thus, the characterization of ß-arrestin2 may represent an alternative therapeutic target for CRPC treatment.

Insights into salt tolerance from the genome of Thellungiella salsuginea.

Thellungiella salsuginea, a close relative of Arabidopsis, represents an extremophile model for abiotic stress tolerance studies. We present the draft sequence of the T. salsuginea genome, assembled based on ~134-fold coverage to seven chromosomes with a coding capacity of at least 28,457 genes. This genome provides resources and evidence about the nature of defense mechanisms constituting the genetic basis underlying plant abiotic stress tolerance. Comparative genomics and experimental analyses identified genes related to cation transport, abscisic acid signaling, and wax production prominent in T. salsuginea as possible contributors to its success in stressful environments.