Planning and managing Africa’s cities: what place for technology innovations?

Introduction The speed of urbanization in Africa is clear to see – all Africa’s cities will have doubled or tripled in population within a generation. Twenty or so megacities are emerging on the continent, three of them absolute giants: Cairo, Lagos and Kinshasa. The spectacular spread of these capitals should not, however, mask the equally fast growth of Africa’s secondary cities. Small and medium-size towns and cities across the continent are seeing the same rate of expansion, so the entire..

Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers

Impact of the Maturation of Human Primary Bone-Forming Cells on Their Behavior in Acute or Persistent Staphylococcus aureus Infection Models

International audienc

A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells

Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon β (IFN-β) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the transcription factor YY1 that regulates IFN-β gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated factors are recruited on the IFN-β promoter through YY1, inhibiting CBP recruitment, histone acetylation, and transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-β promoter chromatin structure

Spin crossover molecular ceramics by Cool-SPS: consequences on switching features beyond the sole microstructural effect

The sintering of spin crossover material using Spark Plasma Sintering at low temperature (Cool-SPS) lead to a new way of shaping such compounds into functional molecular ceramics. These ceramics reach a high relative density of 95%, what may address several issues for using spin crossover materials into barocaloric devices. Starting from the reference complex [Fe(Htrz)2(trz)]BF4, we first investigated the magnetic, structural, microstructural properties as well as the fatigability behavior of the starting powder using multiple magnetic measurements, X-ray diffraction and calorimetry to compare them to the elaborated ceramics. The best conditions of pressure and temperature during the SPS process to obtain reproductible molecular ceramics with high relative density where found to be between 250 and 300 °C, and 300 and 400 MPa. The same complete set of characterizations made on a molecular ceramic of 95% of relative density reveal that crystal structure as well as the abrupt hysteretic SCO of [Fe(Htrz)2(trz)]BF4 are perfectly conserved after sintering. However, ceramic presents a faster stabilization of their microstructural and magnetic properties upon cycling and a higher cooperativity at the macroscopic level was observed compared to the starting powder

Novel Loss of Function Variant in BCKDK Causes a Treatable Developmental and Epileptic Encephalopathy.

peer reviewedBranched-chain amino acids (BCAA) are essential amino acids playing crucial roles in protein synthesis and brain neurotransmission. Branched-chain ketoacid dehydrogenase (BCKDH), the flux-generating step of BCAA catabolism, is tightly regulated by reversible phosphorylation of its E1α-subunit. BCKDK is the kinase responsible for the phosphorylation-mediated inactivation of BCKDH. In three siblings with severe developmental delays, microcephaly, autism spectrum disorder and epileptic encephalopathy, we identified a new homozygous in-frame deletion (c.999_1001delCAC; p.Thr334del) of BCKDK. Plasma and cerebrospinal fluid concentrations of BCAA were markedly reduced. Hyperactivity of BCKDH and over-consumption of BCAA were demonstrated by functional tests in cells transfected with the mutant BCKDK. Treatment with pharmacological doses of BCAA allowed the restoring of BCAA concentrations and greatly improved seizure control. Behavioral and developmental skills of the patients improved to a lesser extent. Importantly, a retrospective review of the newborn screening results allowed the identification of a strong decrease in BCAA concentrations on dried blood spots, suggesting that BCKDK is a new treatable metabolic disorder probably amenable to newborn screening programs

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Urbanisation autonome : pour une autre action urbaine sur les quartiers précaires

International audienceNeighborhoods that are built autonomously and do not conform to public standards represent the largest form of urbanization in the world. With this in mind, Valérie Clerc, Laure Criqui and Guillaume Josse propose new ways to intervene on these spaces at the heart of the making of the urban.Les quartiers construits de façon autonome et non conforme aux normes publiques représentent la forme d'urbanisation majoritaire dans le monde. Forts de ce rappel, Valérie Clerc, Laure Criqui et Guillaume Josse proposent de nouvelles pistes pour intervenir sur ces espaces au coeur de la fabrique urbaine