Kernelization for Finding Lineal Topologies (Depth-First Spanning Trees) with Many or Few Leaves

For a given graph $G$, a depth-first search (DFS) tree $T$ of $G$ is an $r$-rooted spanning tree such that every edge of $G$ is either an edge of $T$ or is between a \textit{descendant} and an \textit{ancestor} in $T$. A graph $G$ together with a DFS tree is called a \textit{lineal topology} $\mathcal{T} = (G, r, T)$. Sam et al. (2023) initiated study of the parameterized complexity of the \textsc{Min-LLT} and \textsc{Max-LLT} problems which ask, given a graph $G$ and an integer $k\geq 0$, whether $G$ has a DFS tree with at most $k$ and at least $k$ leaves, respectively. Particularly, they showed that for the dual parameterization, where the tasks are to find DFS trees with at least $n-k$ and at most $n-k$ leaves, respectively, these problems are fixed-parameter tractable when parameterized by $k$. However, the proofs were based on Courcelle's theorem, thereby making the running times a tower of exponentials. We prove that both problems admit polynomial kernels with \Oh(k^3) vertices. In particular, this implies FPT algorithms running in k^{\Oh(k)}\cdot n^{O(1)} time. We achieve these results by making use of a \Oh(k)-sized vertex cover structure associated with each problem. This also allows us to demonstrate polynomial kernels for \textsc{Min-LLT} and \textsc{Max-LLT} for the structural parameterization by the vertex cover number.Comment: 16 pages, accepted for presentation at FCT 202

Efficacy of Trastuzumab in Routine Clinical Practice and After Progression for Metastatic Breast Cancer Patients: The Observational Hermine Study

Results of the Hermine study examining the use of trastuzumab for metastatic breast cancer patients in routine practice, including patients who received trastuzumab treatment beyond progression, are reported. The cardiac safety of trastuzumab in this setting is also reported

Enhanced sedimentation of elongated plankton in simple flows

Negatively buoyant phytoplankton play an important role in the sequestration of CO_2 from the atmo-sphere and are fundamental to the health of the world’s fisheries. However, there is still much to discoveron transport mechanisms from the upper photosynthetic regions to the deep ocean. In contrast to intuitive expectations that mixing increases plankton residence time in light-rich regions, recent experimental and computational evidence suggests that turbulence can actually enhance sedimentation of negatively buoyant diatoms. Motivated by these studies we dissect the enhanced sedimentation mechanisms using the simplest possible two-dimensional flows, avoiding expensive computations and obfuscation. In particular, we find that in vertical shear, preferential flow alignment and aggregation in down-welling regions both increase sedimentation, whereas horizontal shear reduces the sedimentation due only to alignment. However the magnitude of the shear does not affect the sedimentation rate. In simple vertical Kolmogorov flow elongated particles also have an enhanced sedimentation speed as they spend more time in down-welling regions of the flow with vertically aligned orientation, an effect that increases with the magnitude of shear. An additional feature is identified in horizontal Kolomogorov flow, whereby the impact of shear-dependent sedimentation speed is to cause aggregation in regions of high-shear where the sedimentation speed is minimum. In cellular flow, there is an increase in mean sedimentation speed with aspect ratio and shear strength associated with aggregation in down-welling regions. Furthermore, spatially projected trajectories can intersect and give rise to chaotic dynamics, which is associated with a depletion of particles within so called retention zones

Bumble bee parasite strains vary in resistance to phytochemicals

Nectar and pollen contain diverse phytochemicals that can reduce disease in pollinators. However, prior studies showed variable effects of nectar chemicals on infection, which could reflect variable phytochemical resistance among parasite strains. Inter-strain variation in resistance could influence evolutionary interactions between plants, pollinators, and pollinator disease, but testing direct effects of phytochemicals on parasites requires elimination of variation between bees. Using cell cultures of the bumble bee parasite Crithidia bombi, we determined (1) growth-inhibiting effects of nine floral phytochemicals and (2) variation in phytochemical resistance among four parasite strains. C. bombi growth was unaffected by naturally occurring concentrations of the known antitrypanosomal phenolics gallic acid, caffeic acid, and chlorogenic acid. However, C. bombi growth was inhibited by anabasine, eugenol, and thymol. Strains varied >3-fold in phytochemical resistance, suggesting that selection for phytochemical resistance could drive parasite evolution. Inhibitory concentrations of thymol (4.53-22.2 ppm) were similar to concentrations in Thymus vulgaris nectar (mean 5.2 ppm). Exposure of C. bombi to naturally occurring levels of phytochemicals—either within bees or during parasite transmission via flowers—could influence infection in nature. Flowers that produce antiparasitic phytochemical, including thymol, could potentially reduce infection in Bombus populations, thereby counteracting a possible contributor to pollinator decline

CFTR gene variants, epidemiology and molecular pathology

International audiencePathogenic variants of the CFTR gene are responsible for a broad phenotypic spectrum characterized by malfunction of some exocrine tissues, with an autosomal recessive mode of inheritance. More than 2,000 variants, distributed throughout the CFTR gene, have been identified, with different effects on the gene and protein expression and function. Genotype-phenotype correlation studies have associated severe variants with a typical multi-organ form of cystic fibrosis, while mild variants are involved in monosymptomatic or adult-onset diseases, called CFTR-related disorders. However, the interpretation of rare variants remains challenging. This review presents an overview of the epidemiology of CFTR variants worldwide and in France and describes the functional classification. Finally, some frequent cystic fibrosis-causing and mild CFTR variants are used as example to depict the molecular pathology of the CFTR locus. Finally, we give the recommendations concerning nomenclature and classification that are useful for appropriate genetic counseling. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS

Effect of Blue Light on Endogenous Isopentenyladenine and Endoreduplication during Photomorphogenesis and De-Etiolation of Tomato (Solanum lycopersicum L.) Seedlings

Light is one of the most important factor influencing plant growth and development all through their life cycle. One of the well-known light-regulated processes is de-etiolation, i.e. the switch from skotomorphogenesis to photomorphogenesis. The hormones cytokinins (CKs) play an important role during the establishment of photomorphogenesis as exogenous CKs induced photomorphogenesis of dark-grown seedlings. Most of the studies are conducted on the plant model Arabidopsis, but no or few information are available for important crop species, such as tomato (Solanum lycopersicum L.). In our study, we analyzed for the first time the endogenous CKs content in tomato hypocotyls during skotomorphogenesis, photomorphogenesis and de-etiolation. For this purpose, two tomato genotypes were used: cv. Rutgers (wild-type; WT) and its corresponding mutant (7B-1) affected in its responses to blue light (BL). Using physiological and molecular approaches, we identified that the skotomorphogenesis is characterized by an endoreduplication-mediated cell expansion, which is inhibited upon BL exposure as seen by the accumulation of trancripts encoding CycD3, key regulators of the cell cycle. Our study showed for the first time that iP (isopentenyladenine) is the CK accumulated in the tomato hypocotyl upon BL exposure, suggesting its specific role in photomorphogenesis. This result was supported by physiological experiments and gene expression data. We propose a common model to explain the role and the relationship between CKs, namely iP, and endoreduplication during de-etiolation and photomorphogenesis

Hedgehog pathway and its inhibitors in chronic obstructive pulmonary disease (COPD)

International audienceCOPD affects millions of people and is now ranked as the third leading cause of death worldwide. This largely untreatable chronic airway disease results in irreversible destruction of lung architecture. The small lung hypothesis is now supported by epidemiological, physiological and clinical studies. Accordingly, the early and severe COPD phenotype carries the most dreadful prognosis and finds its roots during lung growth. Pathophysiological mechanisms remain poorly understood and implicate individual susceptibility (genetics), a large part of environmental factors (viral infections, tobacco consumption, air pollution) and the combined effects of those triggers on gene expression. Genetic susceptibility is most likely involved as the disease is severe and starts early in life. The latter observation led to the identification of Mendelian inheritance via disease-causing variants of SERPINA1 - known as the basis for alpha-1 anti-trypsin deficiency, and TERT. In the last two decades multiple genome wide association studies (GWAS) identified many single nucleotide polymorphisms (SNPs) associated with COPD. High significance SNPs are located in 4q31 near HHIP which encodes an evolutionarily highly conserved physiological inhibitor of the Hedgehog signaling pathway (HH). HHIP is critical to several in utero developmental lung processes. It is also implicated in homeostasis, injury response, epithelial-mesenchymal transition and tumor resistance to apoptosis. A few studies have reported decreased HHIP RNA and protein levels in human adult COPD lungs. HHIP+/- murine models led to emphysema. HH pathway inhibitors, such as vismodegib and sonidegib, are already validated in oncology, whereas other drugs have evidenced in vitro effects. Targeting the Hedgehog pathway could lead to a new therapeutic avenue in COPD. In this review, we focused on the early and severe COPD phenotype and the small lung hypothesis by exploring genetic susceptibility traits that are potentially treatable, thus summarizing promising therapeutics for the future

Le pommier. Monographie

National audienc