Phylogeography and Demographic History of Chinese Black-Spotted Frog Populations (Pelophylax nigromaculata): Evidence for Independent Refugia Expansion and Secondary Contact

<p>Abstract</p> <p>Background</p> <p>Pleistocene glaciations had considerable impact on phylogeographic patterns within and among closely related species of many vertebrates. Compared to Europe and North America, research on the phylogeography of vertebrates in East Asia, particularly in China, remains limited. The black-spotted frog (<it>Pelophylax nigromaculata</it>) is a widespread species in East Asia. The wide distribution of this species in China makes it an ideal model for the study of palaeoclimatic effects on vertebrates in East Asia. Our previous studies of <it>P. nigromaculata </it>revealed significant subdivisions between the northeast China populations and populations in other regions of the mainland. In the present study, we aim to see whether the deepest splits among lineages and perhaps subsequent genealogical divisions are temporally consistent with a Pleistocene origin and whether clade geographic distributions, with insight into expansion patterns, are similarly spatially consistent with this model.</p> <p>Results</p> <p>Using 1143 nucleotides of the mitochondrial cytochrome <it>b </it>gene from 262 individuals sampled from 28 localities, two main clades (clade A and clade B) differing by <it>c</it>. 7.72% sequence divergence were defined from parsimony analyses. The corresponding timing of lineage divergence, 0.92 Mya, indicates a most likely Pleistocene split. The A clade is further subdivided into two sub-clades, A1 and A2 with 1.22% sequence divergence. Nested clade phylogeographical and population demographic analyses suggested that the current distribution of this frog species was the result of range expansion from two independent refugia during the last interglacial period. We discovered a population within which haplotype lineages A and B of <it>P. nigromaculata </it>coexist in the Dongliao area of China by nucleotide sequences, PCR-RFLP and ISSR (inter simple sequence repeat) patterns. The ISSR result in particular supported divergence between the mitochondrial clades A and B and implied introgressive gene flow between the two divergent lineages.</p> <p>Conclusion</p> <p>Nested clade phylogeographical and population demographic analyses indicate that the current distribution of <it>P. nigromaculata </it>is the result of range expansion from two independent refugia during the last interglacial period in late Pleistocene. One refugium was in east China and the lower elevations of south-western plateau. The distribution of the other mitochondrial clade is consistent with the presence of a refugium in the Korean Peninsula. The gene flow as detected by ISSR markers suggests a range expansion of the two refugia and a secondary contact between the two highly divergent lineages in the Dongliao (DL) area of northeast China.</p

Elliptical ring distribution probability-based damage imaging method for complex aircraft structures

In engineering applications, the robustness and effectiveness of damage diagnostic imaging for guided wave-based structural health monitoring could be affected by the complexity of structures. In this study, an elliptical ring distribution probability-based diagnostic imaging algorithm is proposed to mitigate this effect using the estimated wave velocity and damage index. This algorithm improves the ability of damage localization by modifying the defect distribution probability of probability-based diagnostic imaging. The elliptical ring distribution probability of the presence of defect is used for each sensing path in the algorithm. The width of the elliptical ring distribution probability is determined by the range of estimated wave velocity. The amplitude of the elliptical ring distribution probability is determined by the damage index. The damage location is determined by the cross region of different elliptical rings for different sensing paths. The capability of the algorithm is validated by identifying damages at different locations on a complex composite fuselage panel. The results show that the proposed algorithm can identify a single damage accurately and it can identify multiple damages effectively as well

Patient-derived organoids as a platform for drug screening in metastatic colorectal cancer

Introduction: Most advanced colorectal cancers are aggressive, and there is a lack of effective methods for selecting appropriate anticancer regimens. Patient-derived organoids (PDOs) have emerged as preclinical platforms for modeling clinical responses to cancer therapy.Methods: In this study, we successfully constructed a living biobank with 42 organoids derived from primary and metastatic lesions of metastatic colorectal cancer patients. Tumor tissue was obtained from patients undergoing surgical resection of the primary or metastatic lesion and then used to establish PDOs. Immunohistochemistry (IHC) and drug sensitivity assays were performed to analyze the properties of these organoids.Results: The mCRC organoids were successfully established with an 80% success rate. The PDOs maintained the genetic and phenotypic heterogeneity of their parental tumors. The IC50 values of5-fluorouracil (5-FU), oxaliplatin, and irinotecan (CPT11) were determined for mCRC organoids using drug sensitivity assays. The in vitro chemosensitivity data revealed the potential value of PDOs for clinical applications in predicting chemotherapy response and clinical outcomes in mCRC patients.Discussion: In summary, the PDO model is an effective platform for in vitro assessment of patient-specific drug sensitivity, which can guide personalized treatment decisions for patients with end-stage CRC

Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease

SummaryLittle is known about the maintenance of intestinal stem cells (ISCs) and progenitors during immune-mediated tissue damage or about the susceptibility of transplant recipients to tissue damage mediated by the donor immune system during graft versus host disease (GVHD). We demonstrate here that deficiency of recipient-derived IL-22 increased acute GVHD tissue damage and mortality, that ISCs were eliminated during GVHD, and that ISCs as well as their downstream progenitors expressed the IL-22 receptor. Intestinal IL-22 was produced after bone marrow transplant by IL-23-responsive innate lymphoid cells (ILCs) from the transplant recipients, and intestinal IL-22 increased in response to pretransplant conditioning. However, ILC frequency and IL-22 amounts were decreased by GVHD. Recipient IL-22 deficiency led to increased crypt apoptosis, depletion of ISCs, and loss of epithelial integrity. Our findings reveal IL-22 as a critical regulator of tissue sensitivity to GVHD and a protective factor for ISCs during inflammatory intestinal damage

Demonstration of laser-produced neutron diagnostic by radiative capture gamma-rays

We report a new scenario of time-of-flight (TOF) technique in which fast neutrons and delayed gamma-ray signals were both recorded in a millisecond time window in harsh environments induced by high-intensity lasers. The delayed gamma signals, arriving far later than the original fast neutron and often being ignored previously, were identified to be the results of radiative captures of thermalized neutrons. The linear correlation between gamma photon number and the fast neutron yield shows that these delayed gamma events can be employed for neutron diagnosis. This method can reduce the detecting efficiency dropping problem caused by prompt high-flux gamma radiation, and provides a new way for neutron diagnosing in high-intensity laser-target interaction experiments

Coseismic displacements and inospheric changes of the 2013 Ms7. 0 Lushan earthquake from GPS measurements

By inverting GPS data recorded at stations of the Crustal Movement Observation Network of China (CMONOC) near the 2013 Lushan Ms7. 0 earthquake, we found a horizontal displacement of 22 mm at a site about 32 km SW of the epicenter and vertical displacements of as much as 12. 4 mm at several sites. The vertical displacements were generally uplift on the west side of the nearby Longmenshan fault zone and subsidence on the east side. We also found coseismic ionospheric disturbances about 0. 5 to 0. 9 TECU in amplitude that lasted for about one hour

Transcriptional regulation of ERBB2 gene in breast cancer

Le gène ERBB2 code un récepteur tyrosine kinase, dont l amplification et la surexpression est un mauvais pronostic observé dans 20-30% de cancer du sein et est directement associé avec la résistance de la chimiothérapie. Deux anticorps monoclonaux humain dirigés contre ERBB2 trastuzumab (Herceptin®) et pertuzumab (Omnitarg®) sont actuellement utilisés dans les traitements cliniques pour les ERBB2+ patients. Ils bloquent les activités du récepteur, cependant, la résistance et certains problèmes secondaires sont fréquents. Le facteur de transcription GATA4 a été identifié dans une liste de 29 gènes co-exprimés avec ERBB2 dans des lignées tumorales et des cellules de cancer du sein. Nous avons mis en évidence dans cette thèse une boucle d'autorégulation négative entre le gène ERBB2 et GATA4 dans des lignées cellulaires épithéliales de cancer du sein. La translocation nucléaire d ERBB2 a été décrite comme une conséquence de l'endocytose de ce récepteur. Notre étude a montré que l isoforme ERBB2b dépourvu d un peptide signal est une forme nucléaire du récepteur ERBB2. L inactivation par siRNA des deux isoformes a mise en évidence un rôle activateur de la transcription d ERBB2 pour l'isoforme a, qui correspond à la forme membranaire du récepteur, et un rôle répresseur pour l'isoforme ERBB2b. Des essais luciférase avec le promoteur d'ERBB2 ont confirma le rôle activateur de l'isoforma a. De plus, la fixation d'ERBB2 nucléaire in vivo dans la région promotrice d ERBB2 contenant un site potentiel pour le recrutement d'ERBB2 a été démontrée par Immunoprécipitation de la chromatine (ChIP). L'ensemble de ces observations ouvre de nouvelles perspectives pour notre compréhension de l'amplification préférentielle d'ERBB2 et la quasi absence de mutation dans les cancers du sein ainsi que du rôle respectifs des deux isoformes majeures du gène ERBB2 et des résistances au traitement par anticorps monoclonaux spécifiques d'ERBB2 des cancers du seinThe ERBB2 gene encodes a tyrosine kinase receptor. Amplification and overexpression of ERBB2 is a poor prognosis indicator observed in 20-30% of breast cancers and is directly associated with resistance to chemotherapy. Two humanized monoclonal antibodies trastuzumab (Herceptin®) and pertuzumab (Omnitarg®) directed against ERBB2 are currently used in clinical treatment for ERBB2+ patients by blocking the activity of the receptor; however resistance and some secondary problems are frequent. Transcription factor GATA4 was originally identified as one of the 29 genes co-expressing with ERBB2 in breast cancer cells and tumors. We reported in this thesis a negative feedback regulatory loop associating both ERBB2 and GATA4 in breast cancer cells. ERBB2 nuclear translocation was reported as a consequence of endocytosis. Our studies showed that the ERBB2b isoform which lacks the peptide signal is a nuclear form of ERBB2 receptor. siRNA assays targeted either ERBB2 isoform a or b have evidenced that isoform, corresponding to the membrane receptor, plays an activator role whereas isoform b acted as a repressor on ERBB2 transcription. Luciferase assays under the control of ERBB2 promoter have confirmed the activator role of ERBB2a. In addition, in vivo binding of nuclear ERBB2 to the promoter region of ERBB2 was determined by chromatin immunoprecipitation (ChIP) via a putative ERBB2 DNA binding motif. Further experiments are required to determine whether the recruitment of ERBB2 at its own promoter is direct or requires interaction with an unkown sequence-specific transcription factors. Altogether these original observations open new perspectives for our understanding why the ERBB2 gene is amplified and not mutated in breast cancers as well as for the respective role of the two major ERBB2 isoforms and for the resistance to ERBB2-specific monoclonal antibodies treatment of breast cancer.AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF