Garnet secondary ion mass spectrometry oxygen isotopes reveal crucial roles of pulsed magmatic fluid and its mixing with meteoric water in lode gold genesis.

SignificanceThere is a common consensus that lode gold deposits mostly precipitated from metamorphic fluids via fluid boiling and/or fluid-rock interaction, but whether magmatic hydrothermal fluids and the mixing of such fluids with an external component have played a vital role in the formation of lode gold deposits remains elusive. We use garnet secondary ion mass spectrometry oxygen isotope analysis to demonstrate that the world-class Dongping lode gold deposit has been formed by multiple pulses of magmatic hydrothermal fluids and their mixing with large volumes of meteoric water. This study opens an opportunity to tightly constrain the origin of lode gold deposits worldwide and other hydrothermal systems that may have generated giant ore deposits in the Earth's crust.

The draft genome of Nitzschia closterium f. minutissima and transcriptome analysis reveals novel insights into diatom biosilicification.

BACKGROUND: Nitzschia closterium f. minutissima is a commonly available diatom that plays important roles in marine aquaculture. It was originally classified as Nitzschia (Bacillariaceae, Bacillariophyta) but is currently regarded as a heterotypic synonym of Phaeodactylum tricornutum. The aim of this study was to obtain the draft genome of the marine microalga N. closterium f. minutissima to understand its phylogenetic placement and evolutionary specialization. Given that the ornate hierarchical silicified cell walls (frustules) of diatoms have immense applications in nanotechnology for biomedical fields, biosensors and optoelectric devices, transcriptomic data were generated by using reference genome-based read mapping to identify significantly differentially expressed genes and elucidate the molecular processes involved in diatom biosilicification. RESULTS: In this study, we generated 13.81 Gb of pass reads from the PromethION sequencer. The draft genome of N. closterium f. minutissima has a total length of 29.28 Mb, and contains 28 contigs with an N50 value of 1.23 Mb. The GC content was 48.55%, and approximately 18.36% of the genome assembly contained repeat sequences. Gene annotation revealed 9,132 protein-coding genes. The results of comparative genomic analysis showed that N. closterium f. minutissima was clustered as a sister lineage of Phaeodactylum tricornutum and the divergence time between them was estimated to be approximately 17.2 million years ago (Mya). CAFF analysis demonstrated that 220 gene families that significantly changed were unique to N. closterium f. minutissima and that 154 were specific to P. tricornutum, moreover, only 26 gene families overlapped between these two species. A total of 818 DEGs in response to silicon were identified in N. closterium f. minutissima through RNA sequencing, these genes are involved in various molecular processes such as transcription regulator activity. Several genes encoding proteins, including silicon transporters, heat shock factors, methyltransferases, ankyrin repeat domains, cGMP-mediated signaling pathways-related proteins, cytoskeleton-associated proteins, polyamines, glycoproteins and saturated fatty acids may contribute to the formation of frustules in N. closterium f. minutissima. CONCLUSIONS: Here, we described a draft genome of N. closterium f. minutissima and compared it with those of eight other diatoms, which provided new insight into its evolutionary features. Transcriptome analysis to identify DEGs in response to silicon will help to elucidate the underlying molecular mechanism of diatom biosilicification in N. closterium f. minutissima.

Automated bone age assessment from knee joint by integrating deep learning and MRI-based radiomics.

Bone age assessment (BAA) is a crucial task in clinical, forensic, and athletic fields. Since traditional age estimation methods are suffered from potential radiation damage, this study aimed to develop and evaluate a deep learning radiomics method based on multiparametric knee MRI for noninvasive and automatic BAA. This retrospective study enrolled 598 patients (age range,10.00-29.99 years) who underwent MR examinations of the knee joint (T1/T2*/PD-weighted imaging). Three-dimensional convolutional neural networks (3D CNNs) were trained to extract and fuse multimodal and multiscale MRI radiomic features for age estimation and compared to traditional machine learning models based on hand-crafted features. The age estimation error was greater in individuals aged 25-30 years; thus, this method may not be suitable for individuals over 25 years old. In the test set aged 10-25 years (n = 95), the 3D CNN (a fusion of T1WI, T2*WI, and PDWI) demonstrated the lowest mean absolute error of 1.32 ± 1.01 years, which is higher than that of other MRI modalities and the hand-crafted models. In the classification for 12-, 14-, 16-, and 18- year thresholds, accuracies and the areas under the ROC curves were all over 0.91 and 0.96, which is similar to the manual methods. Visualization of important features showed that 3D CNN estimated age by focusing on the epiphyseal plates. The deep learning radiomics method enables non-invasive and automated BAA from multimodal knee MR images. The use of 3D CNN and MRI-based radiomics has the potential to assist radiologists or medicolegists in age estimation.

Reducing COVID-19 diagnostic errors with dNTPαSe supplementation.

Timely and accurate diagnosis of COVID-19 is critical for controlling the pandemic. As the standard method to diagnose SARS-CoV-2, the real-time reverse transcription polymerase chain reaction (RT-qPCR) has good convenience. However, RT-qPCR still has a relatively high false-negative rate, particularly in the case of detecting low viral loads. In this study, using selenium-modified nucleoside triphosphates (dNTPαSe) in the RT-PCR reactions, we successfully increased the detection sensitivity and reduced the false-negative rate in COVID-19 diagnosis. By detecting positive controls, pseudovirus, and clinical samples with the commercial kits, we found that the dNTPαSe supplementation to these kits could generally offer smaller Ct values, permit the viral detection even in single-digit copies, and increase the detection specificity, sensitivity, and accuracy, thereby reducing the false-negative rate. Our experimental results demonstrated that dNTPαSe supplementation can make the commercial kits more specific, sensitive, and accurate, and this method is a convenient and efficient strategy for the disease detection and diagnosis.

Forensic age prediction and age classification for critical age thresholds via 3.0T magnetic resonance imaging of the knee in the Chinese Han population.

OBJECTIVES: To assess the performance of knee MRI for forensic age prediction and classification for 12-, 14-, 16-, and 18-year thresholds. METHODS: The ossification stages of distal femoral epiphyses and proximal tibial epiphyses were assessed using an integrated staging system by Schmeling et al. and Kellinghaus et al. for knee 3.0T MRI with T1-weighted turbo spin-echo (T1-TSE) in sagittal orientation among 852 Chinese Han individuals (483 males and 369 females) aged 7-30 years. Regression models for age prediction were constructed and their performances were evaluated based on mean absolute deviation (MAD) values. In addition, the performances of age classification were assessed using receiver operating characteristic (ROC) analyses. RESULTS: The intra- and inter-observer agreement levels were very good (κ > 0.80). The complete fusion of those two types of epiphyses took place before 18.0 years in our study participants. The minimum MAD values were 2.51 years (distal femur) and 2.69 years (proximal tibia) in males, and 2.75 years (distal femur) and 2.87 years (proximal tibia) in females. The specificity values of constructed prediction models were all above 90% for the 12-, 14-, and 16-year thresholds, compared to the 74.8-84.6% for the 18-year threshold. Better performances of age prediction and classification were observed in males by distal femoral epiphyses. CONCLUSIONS: Ossification stages via 3.0T MRI of the knee with T1-TSE sequence using an integrated staging system could be a reliable noninvasive method for age prediction or for age classification for 12-, 14-, and 16-year thresholds, especially in males by distal femoral epiphyses. However, assessments based on the full bony fusion of the distal femoral epiphysis and proximal tibial epiphysis seemed not reliable for age classification for the 18-year threshold in the Chinese Han population.

A study of the possible role of Fab-glycosylated IgG in tumor immunity.

Previously we reported that administration of IgG could inhibit tumor progression in mouse models. At the same time, we also found that some IgGs have glycosylation modifications on their Fab fragments, which may have different biological functions than non-glycosylated IgG. In this study, we employed mouse tumor models to explore the roles of two different forms of IgG, i.e. Fab-glycosylated and Fab-non-glycosylated IgG, in tumor progression. The two types of IgGs were separated with ConA absorption which could react with glycan on the Fab arm but could not access glycan on the Fc fragment. In addition, we performed cytokine array, ELISA, western blotting, immunocytochemistry and other techniques to investigate the possible mechanisms of the actions of Fab-glycosylated IgG in the models. We found that Fab-glycosylated IgG, unlike Fab-non-glycosylated IgG, did not inhibit tumor growth and metastasis in the model. On the contrary, Fab-glycosylated IgG may bind to antigen-bound IgG molecules and macrophages through the glycosidic chain on the Fab fragment to affect antigen-antibody binding and macrophage polarization, which are likely to help tumor cells to evade the immune surveillance. A new mechanism of immune evasion with Fab-glycosylated IgG playing a significant role was proposed.

Whole transcriptome sequencing reveals that non-coding RNAs are related to embryo morphogenesis and development in rabbits.

The roles of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in embryonic development remain unclear. We performed a comprehensive analysis of lncRNA and circRNA profiles in rabbit embryos at different stages by whole transcriptome sequencing. We identified 719 lncRNAs and 744 circRNAs that were differentially expressed between stages S1, S2 and S3. A total of 241 differentially expressed lncRNAs and 166 differentially expressed circRNAs were significantly involved in embryonic morphogenesis and development. An RNA network was established and of the embryonic development-associated RNAs, the lncRNAs TCONS_00009253 and TCONS_00010436 were persistently downregulated, while circRNA_07129, circRNA_15209, and circRNA_12526 were persistently upregulated, and their co-expressed mRNAs TBX1, WNT3 and FGFR2 were persistently downregulated during embryonic development. These candidate RNAs were mainly involved in the Wnt, PI3K-Akt, and calcium signaling pathways. This study reports candidate lncRNAs and circRNAs that may be indispensable for the morphogenesis and development of rabbit embryos.

FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence.

The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between METH-dependent patients and controls. The levels of FAAH mRNA in METH dependence were significantly lower than in controls (P < 0.001), however, its plasma protein underwent a significant ∼2-fold increase (P < 0.001). The A allele of the 385C/A polymorphism significantly increased the METH dependence risk (P < 0.001, odds ratio [OR] = 1.646, 95% confidence interval [CI] = 1.332-2.034). The carried A genotypes (AA, AC, and AA/AC) of 385C/A polymorphism also increased METH-dependence risks under a different genetic model (AA vs. CC: P = 0.017, OR = 2.454, 95%CI = 1.171-2.143; AC vs. CC: P < 0.001, OR = 1.818, 95%CI = 1.404-2.353; AC/AA vs. CC: P < 0.001, OR = 1.858, 95%CI = 1.444-2.319). The similar results were obtained after adjusting for age and sex. Unfortunately, we failed to find that any genotype of 385C/A polymorphism affected the mRNA or plasma protein levels in controls, respectively (P > 0.05). These data indicate that the FAAH may play an important role in the pathophysiological process of METH dependence, and the 385C/A polymorphism may be associated with METH dependence susceptibility in a Chinese Han population.

Enhanced ROS scavenging and sugar accumulation contribute to drought tolerance of naturally occurring autotetraploids in Poncirus trifoliata.

Tetraploids have been reported to exhibit increased stress tolerance, but the underlying molecular and physiological mechanisms remain poorly understood. In this study, autotetraploid plants were identified by screening natural seedlings of trifoliate orange (Poncirus trifoliata). The tetraploids exhibited different morphology and displayed significantly enhanced drought and dehydration tolerance in comparison with the diploid progenitor. Transcriptome analysis indicated that a number of stress-responsive genes and pathways were differentially influenced and enriched in the tetraploids, in particular those coding for enzymes related to antioxidant process and sugar metabolism. Transcript levels and activities of antioxidant enzymes (peroxidase and superoxide dismutase) and sucrose-hydrolysing enzyme (vacuolar invertase) were increased in the tetraploids upon exposure to the drought, concomitant with greater levels of glucose but lower level of reactive oxygen species (ROS). These data indicate that the tetraploids might undergo extensive transcriptome reprogramming of genes involved in ROS scavenging and sugar metabolism, which contributes, synergistically or independently, to the enhanced stress tolerance of the tetraploid. Our results reveal that the tetraploids take priority over the diploid for stress tolerance by maintaining a more robust system of ROS detoxification and osmotic adjustment via elevating antioxidant capacity and sugar accumulation in comparison with the diploid counterpart.

Low-Temperature- and Phosphate Deficiency-Responsive Elements Control DGTT3 Expression in Chlamydomonas reinhardtii.

acyl-CoA:Diacylglycerol acyltransferases (DGAT) catalyse the final step of the triacylglycerol biosynthesis. Two major gene families have been shown to encode DGATs, DGAT1, and DGAT2. Abiotic factors such as low temperatures, nitrogen, or phosphorus deficiency was reported to play important roles in the growth and development in green algae. Whether DGATs are induced by low temperatures or phosphorus deficiency, and the corresponding promoter elements are not reported yet. In this study, we found DGTT3 to have a significant response to low temperatures, phosphorus deficiency, and other stresses, such as high concentrations of NaCl, 20 µM GA, and 20 µM abscisic acid. The promoter element of DGTT3 was then studied by deletion and scanning mutagenesis method. Results revealed that the - 319/- 247 region is essential for low-temperature and phosphate-deficiency-mediated induction of DGTT3 expression. The sequence from - 312 to - 299 of the CAATAGACTGCTGCT was the core sequence of the cold responsive element, which facilitated the promoter response to cold induction. Meanwhile, the sequence from - 319 to - 275 was critical to phosphate-deficiency regulation. Furthermore, the relationship between DNA methylation and transgenic silence in -N condition was analyzed, and results showed that the DNA methylation rate of the transformed insertion region was high. This phenomenon was responsible for the decrease in ARS gene expression in the transgenic algal strain under -N conditions.

The theoretical and empirical basis of a BioPsychoSocial (BPS) risk screener for detection of older people's health related needs, planning of community programs, and targeted care interventions.

BACKGROUND: This study introduces the conceptual basis and operational measure, of BioPyschoSocial (BPS) health and related risk to better understand how well older people are managing and to screen for risk status. The BPS Risk Screener is constructed to detect vulnerability at older ages, and seeks to measure dynamic processes that place equal emphasis on Psycho-emotional and Socio-interpersonal risks, as Bio-functional ones. We validate the proposed measure and describe its application to programming. METHODS: We undertook a quantitative cross-sectional, psychometric study with n = 1325 older Singaporeans, aged 60 and over. We adapted the EASYCare 2010 and Lubben Social Network Scale questionnaires to help determine the BPS domains using factor analysis from which we derive the BPS Risk Screener items. We then confirm its structure, and test the scoring system. The score is initially validated against self-reported general health then modelled against: number of falls; cognitive impairment; longstanding diseases; and further tested against service utilization (linked administrative data). RESULTS: Three B, P and S clusters are defined and identified and a BPS managing score ('doing' well, or 'some', 'many', and 'overwhelming problems') calculated such that the risk of problematic additive BPS effects, what we term health 'loads', are accounted for. Thirty-five items (factor loadings over 0.5) clustered into three distinct B, P, S domains and were found to be independently associated with self-reported health: B: 1.99 (1.64 to 2.41), P: 1.59 (1.28 to 1.98), S: 1.33 (1.10 to 1.60). The fit improved when combined into the managing score 2.33 (1.92 to 2.83, < 0.01). The score was associated with mounting risk for all outcomes. CONCLUSIONS: BPS domain structures, and the novel scoring system capturing dynamic BPS additive effects, which can combine to engender vulnerability, are validated through this analysis. The resulting tool helps render clients' risk status and related intervention needs transparent. Given its explicit and empirically supported attention to P and S risks, which have the potential to be more malleable than B ones, especially in the older old, this tool is designed to be change sensitive.

CrMAPK3 regulates the expression of iron-deficiency-responsive genes in Chlamydomonas reinhardtii.

BACKGROUND: Under iron-deficient conditions, Chlamydomonas exhibits high affinity for iron absorption. Nevertheless, the response, transmission, and regulation of downstream gene expression in algae cells have not to be investigated. Considering that the MAPK pathway is essential for abiotic stress responses, we determined whether this pathway is involved in iron deficiency signal transduction in Chlamydomonas. RESULTS: Arabidopsis MAPK gene sequences were used as entry data to search for homologous genes in Chlamydomonas reinhardtii genome database to investigate the functions of mitogen-activated protein kinase (MAPK) gene family in C. reinhardtii under iron-free conditions. Results revealed 16 C. reinhardtii MAPK genes labeled CrMAPK2-CrMAPK17 with TXY conserved domains and low homology to MAPK in yeast, Arabidopsis, and humans. The expression levels of these genes were then analyzed through qRT-PCR and exposure to high salt (150 mM NaCl), low nitrogen, or iron-free conditions. The expression levels of these genes were also subjected to adverse stress conditions. The mRNA levels of CrMAPK2, CrMAPK3, CrMAPK4, CrMAPK5, CrMAPK6, CrMAPK8, CrMAPK9, and CrMAPK11 were remarkably upregulated under iron-deficient stress. The increase in CrMAPK3 expression was 43-fold greater than that in the control. An RNA interference vector was constructed and transformed into C. reinhardtii 2A38, an algal strain with an exogenous FOX1:ARS chimeric gene, to silence CrMAPK3. After this gene was silenced, the mRNA levels and ARS activities of FOX1:ARS chimeric gene and endogenous CrFOX1 were decreased. The mRNA levels of iron-responsive genes, such as CrNRAMP2, CrATX1, CrFTR1, and CrFEA1, were also remarkably reduced. CONCLUSION: CrMAPK3 regulates the expression of iron-deficiency-responsive genes in C. reinhardtii.

Iron deficiency response gene Femu2 plays a positive role in protecting Chlamydomonas reinhardtii against salt stress.

BACKGROUND: Iron deficiency related gene, Femu2, encodes protein homologous to a C2H2-type zinc finger protein, which participates in the regulation of FOX1 gene induced by iron (Fe) deficiency in Chlamydomonas reinhardtii. In this study, we investigate the gene function of Femu2 in response to salt stress in C. reinhardtii. METHODS: Femu2-overexpressing and Femu2-silencing transgenic cells were analyzed under salt stress. Several physiological indices were measured, and global changes in gene expression were investigated via RNA-seq. RESULTS: Compared with that of the non-treated control, the transcript levels of Femu2 were dramatically induced by iron deficiency and can also be significantly induced after algal cell exposure to Tris-acetate-phosphate (TAP) medium with 100 and 150mM NaCl. The promoter also responded to NaCl induction. Femu2-overexpressing transgenic algal cells exhibited significantly enhanced tolerance to salt stress. Conversely, Femu2-silencing cells showed higher sensitivity to salt stress than the control. Physiological analyses revealed that the overexpression of Femu2 increased the contents of proline and soluble sugars in transgenic cells under high salinity and that silencing Femu2 resulted in increased malondialdehyde level and decreased superoxide dismutase activity. RNA-seq results showed that a total of 248 genes have opposite expression profiles and that 5508 and 2120 genes were distinctly up-regulated or down-regulated in Femu2-overexpressing and Femu2-silencing transgenic cells under salt stress, respectively. CONCLUSION: Femu2 may play an important positive role in protecting C. reinhardtii against salt stress. GENERAL SIGNIFICANCE: The results of this study indicated that Femu2 may be useful in improving plant salt tolerance.

Utilizing distributional analytics and electronic records to assess timeliness of inpatient blood glucose monitoring in non-critical care wards.

BACKGROUND: Regular and timely monitoring of blood glucose (BG) levels in hospitalized patients with diabetes mellitus is crucial to optimizing inpatient glycaemic control. However, methods to quantify timeliness as a measurement of quality of care are lacking. We propose an analytical approach that utilizes BG measurements from electronic records to assess adherence to an inpatient BG monitoring protocol in hospital wards. METHODS: We applied our proposed analytical approach to electronic records obtained from 24 non-critical care wards in November and December 2013 from a tertiary care hospital in Singapore. We applied distributional analytics to evaluate daily adherence to BG monitoring timings. A one-sample Kolmogorov-Smirnov (1S-KS) test was performed to test daily BG timings against non-adherence represented by the uniform distribution. This test was performed among wards with high power, determined through simulation. The 1S-KS test was coupled with visualization via the cumulative distribution function (cdf) plot and a two-sample Kolmogorov-Smirnov (2S-KS) test, enabling comparison of the BG timing distributions between two consecutive days. We also applied mixture modelling to identify the key features in daily BG timings. RESULTS: We found that 11 out of the 24 wards had high power. Among these wards, 1S-KS test with cdf plots indicated adherence to BG monitoring protocols. Integrating both 1S-KS and 2S-KS information within a moving window consisting of two consecutive days did not suggest frequent potential change from or towards non-adherence to protocol. From mixture modelling among wards with high power, we consistently identified four components with high concentration of BG measurements taken before mealtimes and around bedtime. This agnostic analysis provided additional evidence that the wards were adherent to BG monitoring protocols. CONCLUSIONS: We demonstrated the utility of our proposed analytical approach as a monitoring tool. It provided information to healthcare providers regarding the timeliness of daily BG measurements. From the real data application, there were empirical evidences suggesting adherence of BG timings to protocol among wards with adequate power for assessing timeliness. Our approach is extendable to other areas of healthcare where timeliness of patient care processes is important.

MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma.

MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan-Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan-Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas.

Fab fragment glycosylated IgG may play a central role in placental immune evasion.

STUDY QUESTION: How does the placenta protect the fetus from immune rejection by the mother? SUMMARY ANSWER: The placenta can produce IgG that is glycosylated at one of its Fab arms (asymmetric IgG; aIgG) which can interact with other antibodies and certain leukocytes to affect local immune reactions at the junction between the two genetically distinct entities. WHAT IS KNOWN ALREADY: The placenta can protect the semi-allogenic fetus from immune rejection by the immune potent mother. aIgG in serum is increased during pregnancy and returns to the normal range after giving birth. aIgG can react to antigens to form immune complexes which do not cause a subsequent immune effector reaction, including fixing complements, inducing cytotoxicity and phagocytosis, and therefore has been called 'blocking antibody'. STUDY DESIGN, SIZE, DURATION: Eighty-eight human placentas, four trophoblast cell lines (TEV-1, JAR, JEG and BeWo), primary culture of human placental trophoblasts and a gene knock-out mouse model were investigated in this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The general approach included the techniques of cell culture, immunohistochemistry, in situ hybridization, immuno-electron microscopy, western blot, quantitative PCR, protein isolation, glycosylation analysis, enzyme digestion, gene sequencing, mass spectrophotometry, laser-guided microdissection, enzyme-linked immunosorbent assay, pulse chase assay, double and multiple staining to analyze protein and DNA and RNA analysis at the cellular and molecular levels. MAIN RESULTS AND THE ROLE OF CHANCE: Three major discoveries were made: (i) placental trophoblasts and endothelial cells are capable of producing IgG, a significant portion of which is aberrantly glycosylated at one of its Fab arms to form aIgG; (ii) the asymmetrically glycosylated IgG produced by trophoblasts and endothelial cells can react to immunoglobulin molecules of human, rat, mouse, goat and rabbit at the Fc portion; (iii) asymmetrically glycosylated IgG can react to certain leukocytes in the membrane and cytoplasm, while symmetric IgG from the placenta does not have this property. LIMITATIONS, REASONS FOR CAUTION: Most of the experiments were performed in vitro. The proposed mechanism calls for verification in normal and abnormal pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: This study identified a number of new phenomena suggesting that aIgG produced by the placenta would be able to react to detrimental antibodies and leukocytes and interfere with their immune reactions against the placenta and the fetus. This opens a new dimension for further studies on pregnancy physiology and immunology. Should the mechanism proposed here be confirmed, it will have a direct impact on our understanding of the physiology and pathology of human reproduction and offer new possibilities for the treatment of many diseases including spontaneous abortion, infertility and pre-eclampsia. It also sheds light on the mechanism of immune evasion in general including that of cancer.

Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors.

Sphingomyelin synthase (SMS) has been proved to be a potential drug target for the treatment of atherosclerosis. However, few SMS inhibitors have been reported. In this paper, structure-based virtual screening was performed on hSMS1. SAPA 1a was discovered as a novel SMS1 inhibitor with an IC50 value of 5.2 µM in enzymatic assay. A series of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) were synthesized and their biological activities toward SMS1 were evaluated. Among them, SAPA 1j was found to be the most potent SMS1 inhibitor with an IC50 value of 2.1 µM in in vitro assay. The molecular docking studies suggested the interaction modes of SMS1 inhibitors and PC with the active site of SMS1. Site-directed mutagenesis validated the involvement of residues Arg342 and Tyr338 in enzymatic sphingomyelin production. The discovery of SAPA derivatives as a novel class of SMS1 inhibitors would advance the development of more effective SMS1 inhibitors.

Expression and knockdown of the PEPC1 gene affect carbon flux in the biosynthesis of triacylglycerols by the green alga Chlamydomonas reinhardtii.

The regulation of lipid biosynthesis is important in photosynthetic eukaryotic cells. This regulation is facilitated by the direct synthesis of fatty acids and triacylglycerol (TAG), and by other controls of the main carbon metabolic pathway. In this study, knockdown of the mRNA expression of the Chlamydomonas phosphoenolpyruvate carboxylase isoform 1 (CrPEPC1) gene by RNA interference increased TAG level by 20 % but decreased PEPC activities in the corresponding transgenic algae by 39-50 %. The decrease in CrPEPC1 expression increased the expression of TAG biosynthesis-related genes, such as acyl-CoA:diacylglycerol acyltransferase and phosphatidate phosphatase. Conversely, CrPEPC1 over-expression decreased TAG level by 37 % and increased PEPC activities by 157-184 %. These observations suggest that the lipid content of algal cells can be controlled by regulating the CrPEPC1 gene.

Effect of the expression and knockdown of citrate synthase gene on carbon flux during triacylglycerol biosynthesis by green algae Chlamydomonas reinhardtii.

BACKGROUND: The regulation of lipid biosynthesis is essential in photosynthetic eukaryotic cells. This regulation occurs during the direct synthesis of fatty acids and triacylglycerols (TAGs), as well as during other controlling processes in the main carbon metabolic pathway. RESULTS: In this study, the mRNA levels of Chlamydomonas citrate synthase (CrCIS) were found to decrease under nitrogen-limited conditions, which suggests suppressed gene expression. Gene silencing by RNA interference (RNAi) was conducted to determine whether CrCIS suppression affected the carbon flux in TAG biosynthesis. Results showed that the TAG level increased by 169.5%, whereas the CrCIS activities in the corresponding transgenic algae decreased by 16.7% to 37.7%. Moreover, the decrease in CrCIS expression led to the increased expression of TAG biosynthesis-related genes, such as acyl-CoA:diacylglycerol acyltransferase and phosphatidate phosphatase. Conversely, overexpression of CrCIS gene decreased the TAG level by 45% but increased CrCIS activity by 209% to 266% in transgenic algae. CONCLUSIONS: The regulation of CrCIS gene can indirectly control the lipid content of algal cells. Our findings propose that increasing oil by suppressing CrCIS expression in microalgae is feasible.

Radon natural radioactivity measurements for evaluation of primary pollutants.

Radon is naturally released from the soil into the surface layer of the atmosphere, and by monitoring the natural radioactivity data of radon and its shot-live decay products we can get valuable information about the dilution properties of the lower boundary layer. This paper explores the dispersion characteristics of the lower layer of the atmosphere in Lanzhou, China, and the close relationship with the patterns of primary pollutants' concentrations. Measurements were conducted from July 2007 to May 2008 at one station and a fifty-day campaign was carried out at two stations in Lanzhou. The interpretation of radon radioactivity measurement showed that the measured atmospheric stability index (ASI) data at two stations in Lanzhou had statistically significant correlation, and well described the lower atmospheric layer mixing property in the area. The temporal trend of PM10 data was consistent with the temporal trend of ASI, with almost twice as high values in December than it in August. The results show that the ASI allows to highlight the dilution factor playing an important role in determining primary pollution events, and the mixing properties of the lower boundary layer is the key factor determining PM10 concentration in urban areas.