Emergence d’une spécialité scientifique dans l’espace - La réparation de l’ADN

International audienceIn the study of science, the specialty is seen as the ideal level of analysis to understand the genesis and development of scientific communities. This article uses bibliometric data to analyze the emergence of DNA repair by testing a hybrid method to identify the specialty’s appearance in geographical space by focusing on the geographical trajectories of the pioneers in this field. We try to identify the professional mobility of researchers using these bibliometric data, and if possible to highlight the structural networks of places during the emergence stage of the specialty. These networks determine places as much as they are built by individual trajectories. In this way, we try to make a place for the geography of science in the field of social studies of science.Dans l’étude des sciences, la spécialité est perçue comme le niveau d’analyse idéal pour comprendre la genèse et le développement des collectifs scientifiques. Cet article utilise des données bibliométriques pour analyser l’émergence de la Réparation de l’ADN en expérimentant une méthode mixte pour repérer son apparition dans l’espace géographique. En nous concentrant sur les trajectoires géographiques de pionniers dans cedomaine, nous tâchons de repérer leur mobilité professionnelle à l’aide de données bibliométriques dans la perspective de mettre en évidence les réseaux de lieux structurants dans la phase d’émergence de la spécialité. Ces réseaux de lieux déterminent autant qu’ils sont construits par les trajectoires individuelles. Nous essayons ainsi de faire une place à la géographie des sciences dans le domaine des études sociales des sciences

Structural variants shape the genomic landscape and clinical outcome of multiple myeloma

Deciphering genomic architecture is key to identifying novel disease drivers and understanding the mechanisms underlying myeloma initiation and progression. In this work, using the CoMMpass dataset, we show that structural variants (SV) occur in a nonrandom fashion throughout the genome with an increased frequency in the t(4;14), RB1, or TP53 mutated cases and reduced frequency in t(11;14) cases. By mapping sites of chromosomal rearrangements to topologically associated domains and identifying significantly upregulated genes by RNAseq we identify both predicted and novel putative driver genes. These data highlight the heterogeneity of transcriptional dysregulation occurring as a consequence of both the canonical and novel structural variants. Further, it shows that the complex rearrangements chromoplexy, chromothripsis and templated insertions are common in MM with each variant having its own distinct frequency and impact on clinical outcome. Chromothripsis is associated with a significant independent negative impact on clinical outcome in newly diagnosed cases consistent with its use alongside other clinical and genetic risk factors to identify prognosis

Spin-Nematic Squeezed Vacuum in a Quantum Gas

Using squeezed states it is possible to surpass the standard quantum limit of measurement uncertainty by reducing the measurement uncertainty of one property at the expense of another complementary property. Squeezed states were first demonstrated in optical fields and later with ensembles of pseudo spin-1/2 atoms using non-linear atom-light interactions. Recently, collisional interactions in ultracold atomic gases have been used to generate a large degree of quadrature spin squeezing in two-component Bose condensates. For pseudo spin-1/2 systems, the complementary properties are the different components of the total spin vector , which fully characterize the state on an SU(2) Bloch sphere. Here, we measure squeezing in a spin-1 Bose condensate, an SU(3) system, which requires measurement of the rank-2 nematic or quadrupole tensor as well to fully characterize the state. Following a quench through a nematic to ferromagnetic quantum phase transition, squeezing is observed in the variance of the quadratures up to -8.3(-0.7 +0.6) dB (-10.3(-0.9 +0.7) dB corrected for detection noise) below the standard quantum limit. This spin-nematic squeezing is observed for negligible occupation of the squeezed modes and is analogous to optical two-mode vacuum squeezing. This work has potential applications to continuous variable quantum information and quantum-enhanced magnetometry

Loss of apical monocilia on collecting duct principal cells impairs ATP secretion across the apical cell surface and ATP-dependent and flow-induced calcium signals

Renal epithelial cells release ATP constitutively under basal conditions and release higher quantities of purine nucleotide in response to stimuli. ATP filtered at the glomerulus, secreted by epithelial cells along the nephron, and released serosally by macula densa cells for feedback signaling to afferent arterioles within the glomerulus has important physiological signaling roles within kidneys. In autosomal recessive polycystic kidney disease (ARPKD) mice and humans, collecting duct epithelial cells lack an apical central cilium or express dysfunctional proteins within that monocilium. Collecting duct principal cells derived from an Oak Ridge polycystic kidney (orpkTg737) mouse model of ARPKD lack a well-formed apical central cilium, thought to be a sensory organelle. We compared these cells grown as polarized cell monolayers on permeable supports to the same cells where the apical monocilium was genetically rescued with the wild-type Tg737 gene that encodes Polaris, a protein essential to cilia formation. Constitutive ATP release under basal conditions was low and not different in mutant versus rescued monolayers. However, genetically rescued principal cell monolayers released ATP three- to fivefold more robustly in response to ionomycin. Principal cell monolayers with fully formed apical monocilia responded three- to fivefold greater to hypotonicity than mutant monolayers lacking monocilia. In support of the idea that monocilia are sensory organelles, intentionally harsh pipetting of medium directly onto the center of the monolayer induced ATP release in genetically rescued monolayers that possessed apical monocilia. Mechanical stimulation was much less effective, however, on mutant orpk collecting duct principal cell monolayers that lacked apical central monocilia. Our data also show that an increase in cytosolic free Ca2+ primes the ATP pool that is released in response to mechanical stimuli. It also appears that hypotonic cell swelling and mechanical pipetting stimuli trigger release of a common ATP pool. Cilium-competent monolayers responded to flow with an increase in cell Ca2+ derived from both extracellular and intracellular stores. This flow-induced Ca2+ signal was less robust in cilium-deficient monolayers. Flow-induced Ca2+ signals in both preparations were attenuated by extracellular gadolinium and by extracellular apyrase, an ATPase/ADPase. Taken together, these data suggest that apical monocilia are sensory organelles and that their presence in the apical membrane facilitates the formation of a mature ATP secretion apparatus responsive to chemical, osmotic, and mechanical stimuli. The cilium and autocrine ATP signaling appear to work in concert to control cell Ca2+. Loss of a cilium-dedicated autocrine purinergic signaling system may be a critical underlying etiology for ARPKD and may lead to disinhibition and/or upregulation of multiple sodium (Na+) absorptive mechanisms and a resultant severe hypertensive phenotype in ARPKD and, possibly, other diseases

Painful swollen leg – think beyond deep vein thrombosis or Baker's cyst

<p>Abstract</p> <p>Background</p> <p>The diagnosis of deep vein thrombosis of leg is very common in clinical practice. Not infrequently a range of pathologies are diagnosed after excluding a thrombosis, often after a period of anticoagulation.</p> <p>Case presentation</p> <p>This is a report of three patients who presented with a painful swollen leg and were initially treated as a deep vein thrombosis or a baker's cyst, but later diagnosed as a pleomorphic sarcoma, a malignant giant cell tumor of the muscle and a myxoid liposarcoma. A brief review of such similar reports and the relevant literature is presented.</p> <p>Conclusion</p> <p>A painful swollen leg is a common clinical scenario and though rare, tumors must be thought of without any delay, in a duplex negative, low risk deep vein thrombosis situation.</p

Theories for influencer identification in complex networks

In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks and socioeconomic systems.Comment: 24 pages, 6 figure

Compensatory Interactions between Sir3p and the Nucleosomal LRS Surface Imply Their Direct Interaction

The previously identified LRS (Loss of rDNA Silencing) domain of the nucleosome is critically important for silencing at both ribosomal DNA and telomeres. To understand the function of the LRS surface in silencing, we performed an EMS mutagenesis screen to identify suppressors of the H3 A75V LRS allele. We identified dominant and recessive mutations in histones H3, H4, and dominant mutations in the BAH (Bromo Adjacent Homology) domain of SIR3. We further characterized a surface of Sir3p critical for silencing via the LRS surface. We found that all alleles of the SIR3 BAH domain were able to 1) generally suppress the loss of telomeric silencing of LRS alleles, but 2) could not suppress SIN (Swi/Snf Independent) alleles or 3) could not suppress the telomeric silencing defect of H4 tail alleles. Moreover, we noticed a complementary trend in the electrostatic changes resulting from most of the histone mutations that gain or lose silencing and the suppressor alleles isolated in SIR3, and the genes for histones H3 and H4. Mutations in H3 and H4 genes that lose silencing tend to make the LRS surface more electronegative, whereas mutations that increase silencing make it less electronegative. Conversely, suppressors of LRS alleles in either SIR3, histone H3, or H4 also tend to make their respective surfaces less electronegative. Our results provide genetic evidence for recent data suggesting that the Sir3p BAH domain directly binds the LRS domain. Based on these findings, we propose an electrostatic model for how an extensive surface on the Sir3p BAH domain may regulate docking onto the LRS surface

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

A case of serendipity*

An account is given of how a sensitive bioassay system for measurement of the neurotransmitter acetylcholine serendipitously led to the identification of adenosine triphosphate (ATP) released in vitro from active skeletal muscle. Subsequent application of the identification procedures to exercising human muscle in vivo, cardiac muscle cells in vitro, and human erythrocytes exposed to hypoxia gave rise to the general concept of ATP as a molecule that could influence cell function from the extracellular direction. Mechanisms of ATP release from cells in terms of “trigger” events such as mechanical distortion of the membrane, depolarization of the membrane, and exposure to hypoxia are discussed. Potential therapeutic uses of extracellular ATP in cancer therapy, radiation therapy, and a possible influence upon aging are discussed. Possible roles (distant and local) of extracellular ATP released from muscle during whole body exercise are discussed