Transcriptional regulation of BRD7 expression by Sp1 and c-Myc

<p>Abstract</p> <p>Background</p> <p>Bromodomain is an evolutionally conserved domain that is found in proteins strongly implicated in signal-dependent transcriptional regulation. Genetic alterations of bromodomain genes contributed to the development of many human cancers and other disorders. BRD7 is a recently identified bromodomain gene. It plays a critical role in cellular growth, cell cycle progression, and signal-dependent gene expression. Previous studies showed that BRD7 gene exhibited much higher-level of mRNA expression in normal nasopharyngeal epithelia than in nasopharyngeal carcinoma (NPC) biopsies and cell lines. However, little is known about its transcriptional regulation. In this study, we explored the transcriptional regulation of BRD7 gene.</p> <p>Method</p> <p>Potential binding sites of transcription factors within the promoter region of BRD7 gene were predicted with MatInspector Professional <url>http://genomatix.de/cgi-bin/matinspector_prof/mat_fam.pl</url>. Mutation construct methods and luciferase assays were performed to define the minimal promoter of BRD7 gene. RT-PCR and western blot assays were used to detect the endogenous expression of transcription factor Sp1, c-Myc and E2F6 in all cell lines used in this study. Electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation (ChIP) were used to detect the direct transcription factors that are responsible for the promoter activity of BRD7 gene. DNA vector-based siRNA technology and cell transfection methods were employed to establish clone pools that stably expresses SiRNA against c-Myc expression in nasopharyngeal carcinoma 5-8F cells. Real-time PCR was used to detect mRNA expression of BRD7 gene in 5-8F/Si-c-Myc cells.</p> <p>Results</p> <p>We defined the minimal promoter of BRD7 gene in a 55-bp region (from -266 to -212bp), and identified that its promoter activity is inversely related to c-Myc expression. Sp1 binds to the Sp1/Myc-Max overlapping site of BRD7 minimal promoter, and slightly positively regulate its promoter activity. c-Myc binds to this Sp1/Myc-Max overlapping site as well, and negatively regulates the promoter activity and endogenous mRNA expression of BRD7 gene. Knock-down of c-Myc increases the promoter activity and mRNA level of BRD7 gene. The luciferase activity of the mutated promoter constructs showed that Sp1/Myc-Max overlapping site is a positive regulation element of BRD7 promoter.</p> <p>Conclusion</p> <p>These studies provide for the first time the evidence that c-Myc is indeed a negative regulator of BRD7 gene. These findings will help to further understand and uncover the bio-functions of BRD7 gene involved in the pathogenesis of NPC.</p

Photocatalytic Activation of Saturated C–H Bond Over the CdS Mixed-Phase Under Visible Light Irradiation

Selective activation of saturated C–H bond in hydrocarbons to produce high-value-added chemicals is of great significance for chemical synthesis and transformation. Herein, we present a facile procedure to achieve Ni-doped CdS nanoparticles with mixed (cubic and hexagonal) phases, as well as its application to the photocatalytic activation of saturated primary C–H bond of toluene and its derivatives. The photocatalytic oxidation rate of toluene into benzaldehyde of formation reached up to 216.7 μmolh−1g−1 under visible light irradiation. The excellent photocatalytic performance of Ni(II)-doped CdS [Ni(II)/CdS] can be attributed to its unique structural assembly with cubic and hexagonal phases and also the addition of Ni ions, together taking effect in promoting the separation of photogenerated charge carriers. The possible reaction mechanism for the photocatalytic selective oxidation is illustrated in this work. The band width of the as-prepared mixed phase CdS is reduced, which can effectively expand the response range and improve photocatalytic performance

Investigation and identification of the first mushroom poisoning case caused by Amanita sychnopyramis f. subannulata in Jiangxi

Objective To investigate and identify a case caused by mushroom poisoning in May 2019 in Jiangxi Province. Methods The case was studied with the epidemiological information, clinical data, and suspicious mushroom samples were identified by morphological and molecular studies. Results The epidemiological information showed that all the patients had eaten different quantity of mushrooms which were picked and boiled by themselves, the average incubation period was 2.5 hours, and the symptoms of dizziness, gastrointestinal discomfort, vomiting, numbness of limbs and so on had existed orderly of the patients. The morphological and molecular studies identified the samples were Amanita sychnopyramis f. subannulata. Conclusion The incident was the first reported case caused by Amanita sychnopyramis f. subannulata in Jiangxi Province. The poisonous mushroom species can be identified combined with epidemiology, morphology and molecular studies. The situation of s mushroom poisoning in Jiangxi Province is still serious and the relevant departments should strengthen prevention and control

Analysis of nontyphoidal Salmonella clinical isolates antibiotic resistance based on whole genome sequencing in Jiangxi Province in 2018

Objective Understanding of bacterial antibiotic resistance is the basis for guiding clinical anti-infective therapy and monitoring antimicrobial resistance trends. The study was aimed to investigate the antibiotic resistance characteristics of nontyphoidal Salmonella isolates from foodborne disease cases in Jiangxi Province in 2018, study the correlations between resistance phenotypes and genotypes, and evaluate the application prospects of whole genome sequencing (WGS) in antimicrobial resistance surveillance. Methods In this study, 58 nontyphoidal Salmonella strains were isolated from foodborne disease patients in Jiangxi Province in 2018 and were tested for susceptibility to 14 antimicrobials using broth microdilution. The 58 isolates were subjected to WGS, and resistance genes were identified from assembled sequences that compared with ResFinder database. Results 77.59% (45/58) of isolates were resistant to tetracycline, and 72.41% (42/58) were resistant to ampicillin. 100.00% of isolates were susceptible to imipenem. 56.90% (33/58) of isolates displayed resistance to at least 3 classes of antibiotics, and 3.45% (2/58) of isolates had resistance to at least 6 of 8 classes tested. A total of 47 unique resistance genes referred to 11 classes of antibiotics, plus mutations in gyrA, gyrB and parC structural of quinolone resistance-determining region (QRDR), were identified. 100.00% (58/58) of isolates had aminoglycoside resistance genes, and 72.41% (42/58) of isolates harboured tetracycline resistance genes. Macrolide resistance genes were presented in 3.45% (2/58) of isolates. 77.59% (45/58) of isolates were contained at least 3 classes of antibiotics resistance genes, and 1.72% (1/58) of isolates harboured at least 9 classes of resistance genes. The overall resistance genotypes and phenotypes were consistent in 93.43% (611/654) of cases. Except quinolones, the correlations were above 91% for tested antibiotics. Correlations were 100% for some classes of antibiotics. Conclusion The antibiotic resistance phenomenon of these isolates was serious. The resistance phenotypes were in good accordance with genotypes, and WGS can be used as an effective tool to predict the antibiotic resistance of nontyphoidal Salmonella. As more new antibiotic resistance genes were discovered, the consistency of resistance genotypes and phenotypes will be further improved

Effects of the timing of initial feeding on growth and survival of spotted mandarin fish Siniperca scherzeri larvae

The effects of delayed first feeding on growth and survival of spotted mandarin fish Siniperca scherzeri larvae were examined under controlled conditions. Morphometric characters [yolk-sac volume, oil globule volume, head depth ( H D ), body depth ( B D ), eye diameter ( E D ), musculature height ( M H ), mouth diameter ( M D ) and total length ( L T )], body mass ( M ), specific growth rate ( S GR ) and survival were evaluated under different first-feeding time (2, 3, 4 and 5 days after hatching). Larvae began to feed exogenously at 2 days after hatching (DAH) and the point of no return ( P NR ) occurred between 5 and 6 DAH at 23° C, range ±1·0° C. The yolk volume of larvae first-fed at 2 days had a significant difference compared with that of larvae first-fed at 3, 4 and 5 days on 3 and 4 DAH. The larvae first-fed at 2 days achieved comparatively better growth performance than that of 3, 4 and 5 days. On 5 DAH, all morphometric characters had significant differences between 2 and 5 days and 2 and 4 days initial feeding, respectively. Total mortality was recorded on 9 DAH for the larvae first-fed at 5 days. On 12 DAH, significant differences were observed between 2 and 4 days and 3 and 4 days initial feeding for all morphometric characters. From 16 DAH to the end of experiment, all growth variables of the larvae first-fed at 2 days were significantly higher than those in other treatments. The S GR (2–9 DAH) first-fed at 2 and 3 days were significantly higher than 4 and 5 day treatments, and the S GR (9–16 DAH) first-fed at 2 days was significantly higher than 3 and 4 day treatments. There was no significant difference, however, of S GR (16–28 DAH) among treatments. Survival rate was significantly higher at 2 days initial feeding (27·42%) when compared with 3 (15·96%) and 4 days (7·92%) initial feeding at the end of experiment. The present study suggests that the first feeding of S. scherzeri larvae should be initiated at 2 days after hatching for achieving good growth and survival.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78713/1/j.1095-8649.2009.02328.x.pd

Structure, ontogeny and evolution of the patellar tendon in emus (Dromaius novaehollandiae) and other palaeognath birds

The patella (kneecap) exhibits multiple evolutionary origins in birds, mammals, and lizards, and is thought to increase the mechanical advantage of the knee extensor muscles. Despite appreciable interest in the specialized anatomy and locomotion of palaeognathous birds (ratites and relatives), the structure, ontogeny and evolution of the patella in these species remains poorly characterized. Within Palaeognathae, the patella has been reported to be either present, absent, or fused with other bones, but it is unclear how much of this variation is real, erroneous or ontogenetic. Clarification of the patella’s form in palaeognaths would provide insight into the early evolution of the patella in birds, in addition to the specialized locomotion of these species. Findings would also provide new character data of use in resolving the controversial evolutionary relationships of palaeognaths. In this study, we examined the gross and histological anatomy of the emu patellar tendon across several age groups from five weeks to 18 months. We combined these results with our observations and those of others regarding the patella in palaeognaths and their outgroups (both extant and extinct), to reconstruct the evolution of the patella in birds. We found no evidence of an ossified patella in emus, but noted its tendon to have a highly unusual morphology comprising large volumes of adipose tissue contained within a collagenous meshwork. The emu patellar tendon also included increasing amounts of a cartilage-like tissue throughout ontogeny. We speculate that the unusual morphology of the patellar tendon in emus results from assimilation of a peri-articular fat pad, and metaplastic formation of cartilage, both potentially as adaptations to increasing tendon load. We corroborate previous observations of a ‘double patella’ in ostriches, but in contrast to some assertions, we find independent (i.e., unfused) ossified patellae in kiwis and tinamous. Our reconstructions suggest a single evolutionary origin of the patella in birds and that the ancestral patella is likely to have been a composite structure comprising a small ossified portion, lost by some species (e.g., emus, moa) but expanded in others (e.g., ostriches)

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.

Early asymmetric cues triggering the Dorsal/Ventral Gene Regulatory Network of the sea urchin embryo

Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-containing repressor is expressed by prospective dorsal cells, spatially facing and preceding the onset of nodal transcription. We report that Hbox12 misexpression provokes DV abnormalities, attenuating nodal and nodal-dependent transcription. Reciprocally, impairing hbox12 function disrupts DV polarity by allowing ectopic expression of nodal. Clonal loss-of-function, inflicted by blastomere transplantation or gene-transfer assays, highlights that DV polarization requires Hbox12 action in dorsal cells. Remarkably, the localized knock-down of nodal restores DV polarity of embryos lacking hbox12 function. Finally, we show that hbox12 is a dorsal-specific negative modulator of the p38-MAPK activity, which is required for nodal expression. Altogether, our results suggest that Hbox12 function is essential for proper positioning of the DV organizer.

Alga-made anti-Hepatitis B antibody binds to human Fcγ receptors.

Microalgae are unicellular eukaryotic organisms which represent an emerging alternative to other cell biofactories commonly used to produce monoclonal antibodies. Microalgae display several biotechnological advantages such as their rapid growth rate and their phototrophic lifestyle allowing low production costs as protein expression is solar-fueled. Recently, a fully assembled recombinant IgG antibody directed against Hepatitis B surface antigen is produced and secreted in the culture medium of the diatom Phaeodactylum tricornutum. A biochemical characterization of this recombinant antibody demonstrated that the Asn-297 is N-glycosylated by oligomannosides. In the immune system, antibodies interact with effector molecules and cells through their Fc part and the recognition of Fcγ receptors (FcγR) which are important for inducing phagocytosis of opsonized microbes. Interactions between IgG and FcγR are influenced by the N-glycan structures present on the Asn-297. In this study, the authors characterized the binding capacity of the anti-hepatitis B recombinant IgG produced in P. tricornutum to two human Fcγ receptors (FcγRI and IIIa) using a cellular binding assay and surface plasmon resonance (SPR). This allowed us to demonstrate that the alga-made antibody is able to bind FcγRI with a reduced affinity and engages FcyRIIIa with 3-times higher affinity compared to a control human IgG1