Strictly Toral Dynamics

This article deals with nonwandering (e.g. area-preserving) homeomorphisms of the torus $\mathbb{T}^2$ which are homotopic to the identity and strictly toral, in the sense that they exhibit dynamical properties that are not present in homeomorphisms of the annulus or the plane. This includes all homeomorphisms which have a rotation set with nonempty interior. We define two types of points: inessential and essential. The set of inessential points $ine(f)$ is shown to be a disjoint union of periodic topological disks ("elliptic islands"), while the set of essential points $ess(f)$ is an essential continuum, with typically rich dynamics (the "chaotic region"). This generalizes and improves a similar description by J\"ager. The key result is boundedness of these "elliptic islands", which allows, among other things, to obtain sharp (uniform) bounds of the diffusion rates. We also show that the dynamics in $ess(f)$ is as rich as in $\mathbb{T}^2$ from the rotational viewpoint, and we obtain results relating the existence of large invariant topological disks to the abundance of fixed points.Comment: Incorporates suggestions and corrections by the referees. To appear in Inv. Mat

Surface water monitoring in small water bodies: potential and limits of multi-sensor Landsat time series

Hydrometric monitoring of small water bodies (1–10&thinsp;ha) remains rare, due to their limited size and large numbers, preventing accurate assessments of their agricultural potential or their cumulative influence in watershed hydrology. Landsat imagery has shown its potential to support mapping of small water bodies, but the influence of their limited surface areas, vegetation growth, and rapid flood dynamics on long-term surface water monitoring remains unquantified. A semi-automated method is developed here to assess and optimize the potential of multi-sensor Landsat time series to monitor surface water extent and mean water availability in these small water bodies. Extensive hydrometric field data (1999–2014) for seven small reservoirs within the Merguellil catchment in central Tunisia and SPOT imagery are used to calibrate the method and explore its limits. The Modified Normalised Difference Water Index (MNDWI) is shown out of six commonly used water detection indices to provide high overall accuracy and threshold stability during high and low floods, leading to a mean surface area error below 15&thinsp;%. Applied to 546 Landsat 5, 7, and 8 images over 1999–2014, the method reproduces surface water extent variations across small lakes with high skill (R2 = 0.9) and a mean root mean square error (RMSE) of 9300&thinsp;m2. Comparison with published global water datasets reveals a mean RMSE of 21&thinsp;800&thinsp;m2 (+134&thinsp;%) on the same lakes and highlights the value of a tailored MNDWI approach to improve hydrological monitoring in small lakes and reduce omission errors of flooded vegetation. The rise in relative errors due to the larger proportion and influence of mixed pixels restricts surface water monitoring below 3&thinsp;ha with Landsat (Normalised RMSE&thinsp; = &thinsp;27&thinsp;%). Interferences from clouds and scan line corrector failure on ETM+ after 2003 also decrease the number of operational images by 51&thinsp;%, reducing performance on lakes with rapid flood declines. Combining Landsat observations with 10&thinsp;m pansharpened Sentinel-2 imagery further reduces RMSE to 5200&thinsp;m2, displaying the increased opportunities for surface water monitoring in small water bodies after 2015.</p

PHYMYCO-DB: A curated database for analyses of fungal diversity and evolution.

International audienceBackground: In environmental sequencing studies, fungi can be identified based on nucleic acid sequences, using either highly variable sequences as species barcodes or conserved sequences containing a high-quality phylogenetic signal. For the latter, identification relies on phylogenetic analyses and the adoption of the phylogenetic species concept. Such analysis requires that the reference sequences are well identified and deposited in public-access databases. However, many entries in the public sequence databases are problematic in terms of quality and reliability and these data require screening to ensure correct phylogenetic interpretation. Methods and Principal Findings: To facilitate phylogenetic inferences and phylogenetic assignment, we introduce a fungal sequence database. The database PHYMYCO-DB comprises fungal sequences from GenBank that have been filtered to satisfy stringent sequence quality criteria. For the first release, two widely used molecular taxonomic markers were chosen: the nuclear SSU rRNA and EF1-a gene sequences. Following the automatic extraction and filtration, a manual curation is performed to remove problematic sequences while preserving relevant sequences useful for phylogenetic studies. As a result of curation, ,20% of the automatically filtered sequences have been removed from the database. To demonstrate how PHYMYCO-DB can be employed, we test a set of environmental Chytridiomycota sequences obtained from deep sea samples. Conclusion: PHYMYCO-DB offers the tools necessary to: (i) extract high quality fungal sequences for each of the 5 fungal phyla, at all taxonomic levels, (ii) extract already performed alignments, to act as 'reference alignments', (iii) launch alignments of personal sequences along with stored data. A total of 9120 SSU rRNA and 672 EF1-a high-quality fungal sequences are now available. The PHYMYCO-DB is accessible through the URL http://phymycodb.genouest.org/

Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients

OBJECTIVES: The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir). PATIENTS AND METHODS: Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23). RESULTS: Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P &lt; 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P &lt; 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004). CONCLUSIONS: This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen

PGL-III, a rare intermediate of Mycobacterium leprae phenolic glycolipid biosynthesis, is a potent Mincle ligand

Although leprosy(Hansen's disease) is one ofthe oldestknown diseases, the pathogenicity of Mycobacterium leprae (M. leprae) remains enigmatic. Indeed, the cellwall components responsible for the immune response against M. leprae are as yet largely unidentified. We reveal herephenolic glycolipid-III (PGL-III) as an M. leprae-specific ligand for the immune receptor Mincle. PGL-III is a scarcelypresent trisaccharide intermediate in the biosynthetic pathway toPGL-I, an abundant and characteristic M. leprae glycolipid.Using activity-based purification, we identified PGL-III as a Mincleligand that is more potent than the well-known M. tuberculosis trehalose dimycolate. The cocrystal structure of Mincle and a syntheticPGL-III analogue revealed a unique recognition mode, implying thatit can engage multiple Mincle molecules. In Mincle-deficient miceinfected with M. leprae, increased bacterial burdenwith gross pathologies were observed. These results show that PGL-IIIis a noncanonical ligand recognized by Mincle, triggering protectiveimmunity.PGL-III, a potent immunostimulatory glycolipid,is limitedin M. leprae by the quick addition of a single methylgroup to convert it into immunosuppressive PGL-I, which confers immuneescape.Bio-organic Synthesi

TP53 mutation p.R337H in gastric cancer tissues of a 12-year-old male child - evidence for chimerism involving a common mutant founder haplotype: case report

<p>Abstract</p> <p>Background</p> <p>Gastric adenocarcinoma is rare in children and adolescents, with about 17 cases under age 21 in the world's literature. We report a case of invasive well-differentiated metastatic gastric cancer in a Brazilian 12-year-old boy without documented familial history of cancer.</p> <p>Case presentation</p> <p>The patient, diagnosed with metastatic disease, died seven months after surgery. DNA from intra-surgical specimens revealed a <it>TP53 </it>mutation at codon 337 (p.R337H) in samples with neoplastic cells (dysplasia, tumor and metastasis) but not in non-transformed cells (incomplete intestinal metaplasia and non-involved celiac lymph node). In all mutation-positive tissues, p.R337H occurred on the same background, a founder allele identified by a specific haplotype previously described in Brazilian Li-Fraumeni syndrome patients. The same mutant haplotype, corresponding to a founder mutation present in 0.3% of the general population in Southern Brazil, was found in the genome of the father. Presence of this inherited haplotype in the tumor as well as in the father's germline, suggests a rare case of microchimerism in this patient, who may have harbored a small number of mutant cells originating in another individual, perhaps a dizygotic twin that died early in gestation.</p> <p>Conclusion</p> <p>This case represents one of the earliest ages at diagnosis of gastric cancer ever reported. It shows that cancer inheritance can occur in the absence of an obvious germline mutation, calling for caution in assessing early cancers in populations with common founder mutations such as p.R337H in Southern Brazil.</p

DNA methylome analysis identifies accelerated epigenetic aging associated with postmenopausal breast cancer susceptibility

Aim of the study A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as ‘epigenetic clock’, has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Methods Here, we profiled DNA methylation changes in a nested case–control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. Results We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007–1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007–1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020–1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03–1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Conclusion Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility

Co-Housing Rodents with Different Coat Colours as a Simple, Non-Invasive Means of Individual Identification:Validating Mixed-Strain Housing for C57BL/6 and DBA/2 Mice

Standard practice typically requires the marking of laboratory mice so that they can be individually identified. However, many of the common methods compromise the welfare of the individuals being marked (as well as requiring time, effort, and/or resources on the part of researchers and technicians). Mixing strains of different colour within a cage would allow them to be readily visually identifiable, negating the need for more invasive marking techniques. Here we assess the impact that mixed strain housing has on the phenotypes of female C57BL/6 (black) and DBA/2 (brown) mice, and on the variability in the data obtained from them. Mice were housed in either mixed strain or single strain pairs for 19 weeks, and their phenotypes then assessed using 23 different behavioural, morphological, haematological and physiological measures widely used in research and/or important for assessing mouse welfare. No negative effects of mixed strain housing could be found on the phenotypes of either strain, including variables relevant to welfare. Differences and similarities between the two strains were almost all as expected from previously published studies, and none were affected by whether mice were housed in mixed- or single-strain pairs. Only one significant main effect of housing type was detected: mixed strain pairs had smaller red blood cell distribution widths, a measure suggesting better health (findings that now need replicating in case they were Type 1 errors resulting from our multiplicity of tests). Furthermore, mixed strain housing did not increase the variation in data obtained from the mice: the standard errors for all variables were essentially identical between the two housing conditions. Mixed strain housing also made animals very easy to distinguish while in the home cage. Female DBA/2 and C57BL/6 mice can thus be housed in mixed strain pairs for identification purposes, with no apparent negative effects on their welfare or the data they generate. This suggests that there is much value in exploring other combinations of strains

Inhibition of Dengue Virus Entry and Multiplication into Monocytes Using RNA Interference

Prevention and treatment of dengue infection remain a serious global public health priority. Extensive efforts are required toward the development of vaccines and discovery of potential therapeutic compounds against the dengue viruses. Dengue virus entry is a critical step for virus reproduction and establishes the infection. Hence, the blockade of dengue virus entry into the host cell is an interesting antiviral strategy as it represents a barrier to suppress the onset of infection. This study was achieved by using RNA interference to silence the cellular receptor, and the clathrin mediated endocytosis that enhances the entry of dengue virus in monocytes. Results showed a marked reduction of infected monocytes by flow cytometry. In addition, both intracellular and extracellular viral RNA load was shown to be reduced in treated monocytes when compared to untreated monocytes. Based on these findings, this study concludes that this therapeutic strategy of blocking the virus replication at the first stage of multiplication might serve as a hopeful drug to mitigate the dengue symptoms, and reduction the disease severity