The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation

Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.Comment: To appear in Molecular Systems Biolog

Speech Features for Discriminating Stress Using Branch and Bound Wrapper Search

Stress detection from speech is a less explored field than Automatic Emotion Recognition and it is still not clear which features are better stress discriminants. VOCE aims at doing speech classification as stressed or not-stressed in real-time, using acoustic-prosodic features only. We therefore look for the best discriminating feature subsets from a set of 6285 features – 6125 features extracted with openSMILE toolkit and 160 Teager Energy Operator (TEO) features. We use a mutual information filter and a branch and bound wrapper heuristic with an SVM classifier to perform feature selection. Since many feature sets are selected, we analyse them in terms of chosen features and classifier performance concerning also true positive and false positive rates. The results show that the best feature types for our application case are Audio Spectral, MFCC, PCM and TEO. We reached results as high as 70.36% for generalisation accuracyinfo:eu-repo/semantics/publishedVersio

Ecology: a prerequisite for malaria elimination and eradication

* Existing front-line vector control measures, such as insecticide-treated nets and residual sprays, cannot break the transmission cycle of Plasmodium falciparum in the most intensely endemic parts of Africa and the Pacific * The goal of malaria eradication will require urgent strategic investment into understanding the ecology and evolution of the mosquito vectors that transmit malaria * Priority areas will include understanding aspects of the mosquito life cycle beyond the blood feeding processes which directly mediate malaria transmission * Global commitment to malaria eradication necessitates a corresponding long-term commitment to vector ecolog

Novel scheelite‐type [Ca0.55(Nd1‐xBix)0.3]MoO4 (0.2 ≤ x ≤ 0.95) microwave dielectric ceramics with low sintering temperature

Novel scheelite‐type [Ca0.55(Nd1‐xBix)0.3]MoO4 (0.2 ≤ x ≤ 0.95) ceramics were prepared using the solid‐state reaction method. According to the X‐ray diffraction data, a solid solution was formed in 0.2 ≤ x ≤ 0.95 and all the samples belong to pure scheelite phase with the tetragonal structure. As revealed by Raman spectroscopy, the number of vibrational modes decreased with the increase in x value, which further indicated that Bi3+ ions occupied A‐site of scheelite structure. As the x value increased, the sintering temperature decreased from 740°C to 660°C; the permittivity increased from 12.6 to 20.3; the Qf value first decreased slightly and gradually remained stable. Based on the infrared reflectivity spectrum analysis, the calculated permittivity derived from the fitted data shared the same trend with the measured value. The [Ca0.55(Nd0.05Bi0.95)0.3]MoO4 ceramic sintered at 660 °C attained a near‐zero value temperature coefficient ~τf (−7.1 ppm/°C) and showed excellent microwave dielectric properties with a ɛr ~ 20.3 and a Qf ~ 33 860 GHz, making this system a promising candidate in the ultralow temperature cofired ceramic (ULTCC) technology

Geographic Coincidence of Increased Malaria Transmission Hazard and Vulnerability Occurring at the Periphery of two Tanzanian Villages.

The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection

Shifting rice cropping systems mitigates ecological footprints and enhances grain yield in central China

Intensive cereal production has brought about increasingly serious environmental threats, including global warming, environmental acidification, and water shortage. As an important grain producer in the world, the rice cultivation system in central China has undergone excessive changes in the past few decades. However, few articles focused on the environmental impacts of these shifts from the perspective of ecological footprints. In this study, a 2-year field trial was carried out in Hubei province, China, to gain insight into carbon footprint (CF), nitrogen footprint (NF), and water footprint (WF) performance. The three treatments were, namely, double-rice system (DR), ratoon rice system (RR), and rice-wheat system (RW). Results demonstrated that RR significantly increased the grain yield by 10.22–15.09% compared with DR, while there was no significant difference in the grain yield between RW and DR in 2018–2019. All of the calculation results by three footprint approaches followed the order: RR 3 field emissions were the hotspots of CF and NF, respectively. Blue WF accounts for 40.90–42.71% of DR, which was significantly higher than that of RR and RW, primarily because DR needs a lot of irrigation water in both seasons. The gray WF of RW was higher than those of DR and RR, mainly due to the higher application rate of N fertilizer. In conclusion, RR possesses the characteristics of low agricultural inputs and high grain yield and can reduce CF, NF, and WF, considering the future conditions of rural societal developments and rapid demographic changes; we highlighted that the RR could be a cleaner and sustainable approach to grain production

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)

Fully gapped topological surface states in Bi2_2Se3_3 films induced by a d-wave high-temperature superconductor

Topological insulators are a new class of materials, that exhibit robust gapless surface states protected by time-reversal symmetry. The interplay between such symmetry-protected topological surface states and symmetry-broken states (e.g. superconductivity) provides a platform for exploring novel quantum phenomena and new functionalities, such as 1D chiral or helical gapless Majorana fermions, and Majorana zero modes which may find application in fault-tolerant quantum computation. Inducing superconductivity on topological surface states is a prerequisite for their experimental realization. Here by growing high quality topological insulator Bi$_2$Se$_3$ films on a d-wave superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ using molecular beam epitaxy, we are able to induce high temperature superconductivity on the surface states of Bi$_2$Se$_3$ films with a large pairing gap up to 15 meV. Interestingly, distinct from the d-wave pairing of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$, the proximity-induced gap on the surface states is nearly isotropic and consistent with predominant s-wave pairing as revealed by angle-resolved photoemission spectroscopy. Our work could provide a critical step toward the realization of the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274