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

Patient-derived tumoroids and proteomic signatures: tools for early drug discovery

Onco-virotherapy is an emergent treatment for cancer based on viral vectors. The therapeutic activity is based on two different mechanisms including tumor-specific oncolysis and immunostimulatory properties. In this study, we evaluated onco-virotherapy in vitro responses on immunocompetent non-small cell lung cancer (NSCLC) patient-derived tumoroids (PDTs) and healthy organoids. PDTs are accurate tools to predict patient’s clinical responses at the in vitro stage. We showed that onco-virotherapy could exert specific antitumoral effects by producing a higher number of viral particles in PDTs than in healthy organoids. In the present work, we used multiplex protein screening, based on proximity extension assay to highlight different response profiles. Our results pointed to the increase of proteins implied in T cell activation, such as IFN-γ following onco-virotherapy treatment. Based on our observation, oncolytic viruses-based therapy responders are dependent on several factors: a high PD-L1 expression, which is a biomarker of greater immune response under immunotherapies, and the number of viral particles present in tumor tissue, which is dependent to the metabolic state of tumoral cells. Herein, we highlight the use of PDTs as an alternative in vitro model to assess patient-specific responses to onco-virotherapy at the early stage of the preclinical phases

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