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Latrophilin (LPH) is known as an adhesion G-protein-coupled receptor which involved in multiple physiological processes in organisms. Previous studies showed that lph not only involved the susceptibility to anticholinesterase insecticides but also affected fecundity in Tribolium castaneum. However, its regulatory mechanisms in these biological processes are still not clear. Here, we identified two potential downstream carboxylesterase (cce) genes of Tclph, esterase4 and esterase6, and further characterized their interactions with Tclph. After treatment of T. castaneum larvae with carbofuran or dichlorvos insecticides, the transcript levels of Tcest4 and Tcest6 were significantly induced from 12 to 72 h. RNAi against Tcest4 or Tcest6 led to the higher mortality compared with the controls after the insecticides treatment, suggesting that these two genes play a vital role in detoxification of insecticides in T. castaneum. Furthermore, with insecticides exposure to Tclph knockdown beetles, the expression of Tcest4 was upregulated but Tcest6 was downregulated, indicating that beetles existed a compensatory response against the insecticides. Additionally, RNAi of Tcest6 resulted in 43% reductions in female egg laying and completely inhibited egg hatching, which showed the similar phenotype as that of Tclph knockdown. These results indicated that Tclph affected fecundity by positively regulating Tcest6 expression. Our findings will provide a new insight into the molecular mechanisms of Tclph involved in physiological functions in T. castaneum.
The influence of the content of trifluoroacetate (TFA), in the precursor solution, on the critical current density (Jc) of YBa2Cu3O7−x (YBCO) superconducting films was investigated. We found that a TFA/Ba ratio of 0.68 is optimal to obtain high-performance YBCO films. Using this optimal solution, we then developed an ultraviolet (UV) light soaking technique to prepare YBCO films. This resulted in the constituent elements being uniformly distributed in the films, and this then enabled enhanced Jc. The addition of water vapor during the UV soaking process decreased the content of carbon residue in the films, and further increased the Jc of the resulting YBCO films.
The present study aimed to compare the anti-biofilm activities of four commonly available antiseptic eardrops against biofilms from methicillin-resistant Staphylococcus aureus and quinolone-resistant Pseudomonas aeruginosa in vitro.
The anti-biofilm activities of 50 per cent Burow's solution, vinegar with water (1:1), 2 per cent acetic acid solution, and 4 per cent boric acid solution were evaluated using biofilm assays. Additionally, the anti-biofilm activities of the four antiseptic solutions against tympanostomy tube biofilms were compared using a scanning electron microscope.
The inhibition of biofilm formation from methicillin-resistant S aureus and quinolone-resistant P aeruginosa occurred after treatment with 4 per cent boric acid solution, 2 per cent acetic acid solution, and vinegar with water (1:1). However, 50 per cent Burow's solution did not exhibit effective anti-biofilm activity.
The results indicate that 4 per cent boric acid solution and vinegar with water (1:1) are potent inhibitors of biofilms from methicillin-resistant S aureus and quinolone-resistant P aeruginosa, and provide safe pH levels for avoiding ototoxicity.
CIC, or Capicua, encodes a transcriptional repressor that is itself repressed by RAS/MAPK signalling. CIC is a recurrent target of somatic mutation in type 1 low grade gliomas (LGG), with at least half of the alterations predicted to be deleterious. Type 1 LGGs are a cohort of tumours that are molecularly defined by the loss of heterozygosity of chromosome arms 1p and 19q and the presence of neomorphic IDH1/2 mutations. Despite the high frequency of mutations in CIC within this tumour type, CIC’s putative tumour suppressive role remains to be elucidated. It is also unclear how CIC may cooperate with neomorphic IDH1/2 to promote gliomagenesis. To comprehensively characterize the molecular consequences of CIC loss, we performed RNA-seq, Whole Genome Bisulfite Sequencing, and ChIP-seq on 6 different histone modifications on isogenic CIC-wildtype (WT) and CIC-knockout (KO) normal human astrocytes. To also investigate the collective effects of CIC deficiency and neomorphic IDH1 on the transcriptome and epigenome, we generated the same dataset in isogenic CIC-WT and CIC-KO astrocytes possessing the IDH1 R132H mutation. Analysis of differentially expressed genes illustrates the enrichment of oncogenic pathways in specifically the CIC-KO, IDH1-R132H cells, supporting a synergistic relationship between CIC loss and IDH1-R132H in driving tumour progression. Integrative analyses are ongoing to unveil the epigenetic mechanisms underpinning the regulatory changes in these isogenic cell line models.
Introduction: Diffuse intrinsic pontine glioma (DIPG) is refractory to therapy. The identification of histone H3.1/H3.3 K27M mutations in most DIPG has provided new insights. The DLX homeobox genes are expressed in the developing forebrain. The Dlx1/Dlx2 double knockout (DKO) mouse loses tangential GABAergic interneuron migration to the neocortex. We have identified genes that encode glutamic acid decarboxylase (GAD) enzymes as direct targets of DLX1/DLX2. In DIPG patients with H3.3 K27M mutations there is decreased Dlx2 and increased expression of the myelin transcription factor, Myt1. Methods and Results: We used bioinformatics approaches and chromatin immunoprecipitation (ChIP) assays to identify Olig2, Nkx2.2 and Myt1 promoter sequences as candidate DLX2 targets in vivo. DNA binding specificity was confirmed. The functional consequences of Dlx2 co-expression with reporter constructs of ChIP-isolated promoter fragments of Olig2 and Nkx2.2 demonstrated repression of gene targets in vitro. qPCR showed increased Olig2 and Nkx2.2 expression in the DKO forebrain. Stable transfection of a murine DIPG cell line with Dlx2 resulted in increased Gad1 and Gad2 and decreased Olig2 and Nkx2.2 expression. Of significance, we demonstrated decreased expression of H3.3 K27M and restoration of H3.3 K27 tri-methylation (me3). Conclusions: DLX transcription factors promote GABAergic interneuron and concomitant inhibition of oligodendroglial differentiation in neural progenitors by repression of a suite of genes including Olig2 and Nkx2.2. Restoration of H3 K27me3 expression in DIPG provides a promising lead towards exploration of differentiation as a therapeutic strategy for DIPG.
Monolithic integrated thin film tandem solar cells consisting of a high bandgap perovskite top cell and a low bandgap thin film bottom cell are expected to reach higher power conversion efficiencies (PCEs) with lower manufacturing cost and environmental impacts than the market-dominant crystalline silicon photovoltaics. There have been several demonstrations of 4-terminal and 2-terminal perovskite tandem devices with CuInGaSe2 (CIGS) or CuInSe2 (CIS) and, similar to the other tandem structures, the optimization of this device relies on optimal choice for the perovskite bandgap and thickness. Therefore, further advancement will be enabled by tuning the perovskite absorber to maximize the photocurrent limited by the current match condition. Here, we systematically study the optical absorption and transmission of perovskite thin films with varying absorber band gap. Based on these results, we model the photocurrent generations in both perovskite and CIS subcells and estimate the performances of projected tandem devices by considering the ideally functioning perovskite and CIS device. Our results show that for perovskite layers with 500 nm thickness the optimal bandgap is around 1.6 eV. With these configurations, PCEs above 20% could be achieved by monolithically integrated perovskite/CIS tandem solar cells. Also by modelling the absorption at every layer we calculate the quantum efficiency at each subcell in addition to tracking optical losses.
Methods of obtaining large grain size and high crystallinity in absorber materials play an important role in fabrication of high-performance methylammonium lead iodide (MAPbI3) perovskite solar cells. Here we study the effect of adding small concentrations of Cd2+, Zn2+, and Fe2+salts to the perovskite precursor solution used in the single-step solution fabrication process. Enhanced grain size and crystallinity in MAPbI3 films were obtained by using 0.1% of Cd2+ or Zn2+in the precursor solution. Consequently, solar cells constructed with Cd- and Zn-doped perovskite films show a significant improvement in device performance. These results suggest that the process may be an effective and facile method to fabricate high-efficiency perovskite photovoltaic devices.
Over the last 40 years, many types of population genetic markers have been used to assess the population structure of the pest moth species Helicoverpa armigera. While this species is highly vagile, there is evidence of inter-continental population structure. Here, we examine Z-chromosome molecular markers within and between Chinese and Australian populations. Using 1352 polymorphic sites from 40 Z-linked loci, we compared two Chinese populations of moths separated by 700 km and found virtually no population structure (n = 41 and n = 54, with <1% of variation discriminating between populations). The levels of nucleotide diversity within these populations were consistent with previous estimates from introns in Z-linked genes of Australian samples (π = 0.028 vs. 0.03). Furthermore, all loci surveyed in these Chinese populations showed a skew toward rare variants, with ten loci having a significant Tajima's D statistic, suggesting that this species could have undergone a population expansion. Eight of the 40 loci had been examined in a previous study of Australian moths, of which six revealed very little inter-continental population structure. However, the two markers associated with the Cyp303a1 locus that has previously been proposed to be a target of a selective sweep, exhibited allele structuring between countries. Using a separate dataset of 19 Australian and four Chinese moths, we scanned the molecular variation distributed across the entire Z-chromosome and found distinct blocks of differentiation that include the region containing Cyp303a1. We recommend some of these loci join those associated with insecticide resistance to form a set of genes best suited to analyzing population structure in this global pest.
According to social exchange theory, the motivation for organizational citizenship behavior can be understood with the help of the frameworks of obligation to reciprocate and expected reciprocity. This study predicts that the true motivation for organizational citizenship behavior could be differentiated conditional on the career plateau. These relationships predict the existence of a U-shaped nonlinear relationship between the career plateau and organizational citizenship behavior. In addition to exploring this relationship, the study attempted to discover the effect of organizational commitment and job involvement on the relationship. As a result, a U-shaped curvilinear relationship is applied between career plateau and four dimensions of organizational citizenship behavior except civic virtue. Commitment and involvement show unexpected moderating effects on those curved relationships.
Genomic selection has become increasingly important in the breeding of animals and plants. The response variable is an important factor, influencing the accuracy of genomic selection. The de-regressed proof (DRP) based on traditional estimated breeding value (EBV) is commonly used as response variable. In the current study, simulated data from 16th QTL-MAS Workshop and real data from Chinese Holstein cattle were used to compare accuracy and bias of genomic prediction with two methods of calculating DRP. Our results with simulated data showed that the correlation between genomic EBV and true breeding value achieved using the Jairath method (DRP_J) was superior to that achieved using the Garrick method (DRP_G) for simulated trait 1 but the reverse was true for simulated trait 3, and these two methods performed comparably for simulated trait 2. For all three simulated traits, DRP_J yielded larger bias of genomic prediction. However, DRP_J outperformed DRP_G in both accuracy and unbiasedness for four milk production traits in Chinese Holstein. In the estimation of genomic breeding value using genomic BLUP model, two methods for weighting diagonal elements of incidence matrix associated with residual error were also compared. With increasing the proportion of genetic variance unexplained by markers, the accuracy of genomic prediction was decreased and the bias was increased. Weighting by the reliability of DRP produced accuracy comparable to the evaluation where the proportion of genetic variance unexplained by markers was considered, but with smaller bias in general.
We have used sensitive LOw Frequency ARray (LOFAR) observations of PSR B0809+74 at 15–62 MHz to study the anomalously intensive pulses, first reported by Ulyanov et al. (2006) at 18–30 MHz. Similarly to Ulyanov et al., we found that the spectra of strong pulses consist of distinct bright patches. Moreover, these spectral patches were spotted to drift upwards in frequency over the course of several pulse sequences. We established that this drift is not pulsar-intrinsic, but is caused by the broadband ~20 second-long enhancements of recorded signal, which influenced the dispersed tracks of several pulses at once. We speculate on the cause of such enhancements (i.e. propagation or telescope-related) and the ramifications they bring to the single-pulse studies at the very low radio frequencies. Depending on the origin, the phenomenon may also affect the analysis of highly dispersed single pulses at higher radio frequencies, e.g. Fast Radio Bursts.
A 54-bed, level IV NICU in a regional academic and tertiary referral center.
PATIENTS AND PARTICIPANTS
All neonates prescribed antimicrobials from January 1, 2011, to June 30, 2016, were eligible for inclusion.
Implementation of a NICU-specific ASP beginning July 2012.
We convened a multidisciplinary team and developed guidelines for common infections, with a focus on prescriber audit and feedback. We conducted an interrupted time-series analysis to evaluate the effects of our ASP. Our primary outcome measure was days of antibiotic therapy (DOT) per 1,000 patient days for all and for select antimicrobials. Secondary outcomes included provider-specific antimicrobial prescription events for suspected late-onset sepsis (blood or cerebrospinal fluid infection at >72 hours of life) and guideline compliance.
Antibiotic utilization decreased by 14.7 DOT per 1,000 patient days during the stewardship period, although this decrease was not statistically significant (P=.669). Use of ampicillin, the most commonly antimicrobial prescribed in our NICU, decreased significantly, declining by 22.5 DOT per 1,000 patient days (P=.037). Late-onset sepsis evaluation and prescription events per 100 NICU days of clinical service decreased significantly (P<.0001), with an average reduction of 2.65 evaluations per year per provider. Clinical guidelines were adhered to 98.75% of the time.
Implementation of a NICU-specific antimicrobial stewardship program is feasible and can improve antibiotic prescribing practices.
Angiostrongylus mackerrasae is a parasitic nematode of rats found in Australia. When first reported, it was referred to as A. cantonensis. Recent molecular studies, including the mitochondrial genome, indicate that it is highly similar to A. cantonensis. These studies did not include A. malaysiensis, another member of the A. cantonensis species complex, for comparison. The present study examined the genetic distance and phylogenetic relationship between the component taxa (A. cantonensis, A. mackerrasae and A. malaysiensis) of the A. cantonensis species complex, based on the 12 protein-coding genes (PCGs) of their mitochondrial genome. Both the nucleotide and amino acid sequences were analysed. Angiostrongylus mackerrasae and A. cantonensis are members of the same genetic lineage and both are genetically distinct from A. malaysiensis. The genetic distance based on concatenated nucleotide sequences of 12 mt-PCGs between A. mackerrasae and A. cantonensis from Thailand is p = 1.73%, while that between the Thai and Chinese taxa of A. cantonensis is p = 3.52%; the genetic distance between A. mackerrasae and A. cantonensis from China is p = 3.70%. The results indicate that A. mackerrasae and A. cantonensis belong to the same genetic lineage, and that A. mackerrasae may be conspecific with A. cantonensis. It remains to be resolved whether A. mackerrasae is conspecific with A. cantonensis or undergoing incipient speciation.
Auditory verbal hallucinations (AVHs) are one of the most common and severe symptoms of schizophrenia, but the neuroanatomical abnormalities underlying AVHs are not well understood. The present study aims to investigate whether AVHs are associated with cortical thinning.
Participants were schizophrenia patients from four centers across China, 115 with AVHs and 93 without AVHs, as well as 261 healthy controls. All received 3 T T1-weighted brain scans, and whole brain vertex-wise cortical thickness was compared across groups. Correlations between AVH severity and cortical thickness were also determined.
The left middle part of the middle temporal gyrus (MTG) was significantly thinner in schizophrenia patients with AVHs than in patients without AVHs and healthy controls. Inferences were made using a false discovery rate approach with a threshold at p < 0.05. Left MTG thickness did not differ between patients without AVHs and controls. These results were replicated by a meta-analysis showing them to be consistent across the four centers. Cortical thickness of the left MTG was also found to be inversely correlated with hallucination severity across all schizophrenia patients.
The results of this multi-center study suggest that an abnormally thin left MTG could be involved in the pathogenesis of AVHs in schizophrenia.
Background: Oligodendroglioma (ODG), a molecularly defined subtype of glioma, is a treatment responsive, slow growing tumour strongly associated with IDH mutation and 1p19q co-deletion. Mutations in Capicua (CIC), located on chromosome 19q, have been found in up to 70% of IDH mutated, 1p19q co-deleted ODGs; suggesting that loss or altered function of CIC may be crucially associated with ODG’s unique biology. CIC and ATXN1L have previously been implicated in neurodegeneration, however, this interaction has not been studied in cancer. Methods: Transcriptome profiling of CIC knockout HEK293 cell lines generated using CRISPR was performed using microarray. CIC and ATXN1L interaction was confirmed using immunoprecipitation and immunofluorescence. Transcript and protein changes of CIC targets were tested using RT-qPCR and Western blot following ATXN1L siRNA knockdown. Results: Transcriptomic profiling of CIC knockout cell lines resulted in a list of candidate CIC target genes validated against clinical samples. Immunoprecipitation and immunofluorescence confirmed CIC and ATXN1L interaction. Derepression of candidate CIC targets at transcript and protein levels was seen upon siRNA knockdown of ATXN1L. Conclusions: The interaction between CIC and ATXN1L is necessary for the repression of CIC target genes, including known oncogenes. Further research into the relationship between CIC and ATXN1L may lead potentially novel avenues of therapeutic approaches for less favorable gliomas.
Radiocarbon (14C) is a radionuclide generated mainly through neutron-induced reactions in all types of nuclear reactors. Since most of the 14C released into the environment is in the form of gaseous emissions (CO2 and hydrocarbons), terrestrial plants are the primary indicators of increased 14C levels near nuclear power plants (NPPs). In 2013–2014, we collected samples of silver grasses (including common reed) and pine needles within 3 km of four South Korean NPP centers and measured 14C activities using accelerator mass spectrometry (AMS) at Seoul National University. The highest 14C activities were observed, respectively, in Wolsong>Hanul>Kori>Hanbit [220, 143, 127, and 123% modern carbon (pMC)].