Identification of KANSARL as the First Cancer Predisposition Fusion Gene Specific to the Population of European Ancestry Origin

Gene fusion is one of the hallmarks of cancer. Recent advances in RNA-seq of cancer transcriptomes have facilitated the discovery of fusion transcripts. In this study, we report identification of a surprisingly large number of fusion transcripts, including six KANSARL (KANSL1-ARL17A) transcripts that resulted from the fusion between the KANSL1 and ARL17A genes using a RNA splicingcode model. Five of these six KANSARL fusion transcripts are novel. By systematic analysis of RNA-seq data of glioblastoma, prostate cancer, lung cancer, breast cancer, and lymphoma from different regions of the World, we have found that KANSARL fusion transcripts were rarely detected in the tumors of individuals from Asia or Africa. In contrast, they exist in 30 - 52% of the tumors from North Americans cancer patients. Analysis of CEPH/Utah Pedigree 1463 has revealed that KANSARL is a familially-inherited fusion gene. Further analysis of RNA-seq datasets of the 1000 Genome Project has indicated that KANSARL fusion gene is specific to 28.9% of the population of European ancestry origin. In summary, we demonstrated that KANSARL is the first cancer predisposition fusion gene associated with genetic backgrounds of European ancestry origin

Broadband nonlinear optical response in GeSe nanoplates and its applications in all-optical diode

Germanium selenide nanoplates (GeSe NPs) are considered to have broadband nonlinear optical (NLO) properties and great potential for applications in nanophotonic devices. In this work, we systematically studied the NLO response of GeSe NPs by the open-aperture Z-scan technique. GeSe NPs exhibit strong saturable absorption at wavelengths of 400, 800, and 1064 nm with different pulse durations. Furthermore, we investigated the excited carrier dynamics of GeSe NPs by the non-degenerate pump-probe technique. The fast and slow relaxation times at different wavelengths of 800, 871, 1064, and 1100 nm were components with lifetimes of about 0.54–1.08 and 52.4–167.2 ps, respectively. The significant ultrafast NLO properties of GeSe NPs imply their potential in the development of nanophotonic devices. Here, we designed and fabricated the all-optical diode by means of the GeSe/C60 tandem structure and demonstrated that the saturable absorption behavior of GeSe NPs can be used to fabricate a photonic diode, which exhibits nonreciprocal transmission of light similar to that of an electron diode

Wavelength-tunable picosecond soliton fiber laser with topological insulator : Bi2Se3 as a mode locker

Based on the open-aperture Z-scan measurement, we firstly uncovered the saturable absorption property of the topological insulator (TI): Bi2Se3. A high absolute modulation depth up to 98% and a saturation intensity of 0.49 GWcm−2 were identified. By incorporating this novel saturable absorber material into an erbium-doped fiber laser, wavelength tunable soliton operation was experimentally demonstrated. Our result indicates that like the atomic layer graphene, the topological insulator Bi2Se3 could also operate as an effective saturable absorber for the passive mode locking of lasers at the telecommunication band.Published versio

Third order nonlinear optical property of Bi2Se3

The third order nonlinear optical property of Bi2Se3, a kind of topological insulator (TI), has been investigated under femto-second laser excitation. The open and closed aperture Z-scan measurements were used to unambiguously distinguish the real and imaginary part of the third order optical nonlinearity of the TI. When excited at 800 nm, the TI exhibits saturable absorption with a saturation intensity of 10.12 GW/cm2 and a modulation depth of 61.2%, and a giant nonlinear refractive index of 10 -14 m2/W, almost six orders of magnitude larger than that of bulk dielectrics. This finding suggests that the TI: Bi2Se 3 is indeed a promising nonlinear optical material and thus can find potential applications from passive laser mode locker to optical Kerr effect based photonic devices.Published versio

Telomere and ATM Dynamics in CD4 T-Cell Depletion in Active and Virus-Suppressed HIV Infections

CD4 T-cell depletion is a hallmark of HIV/AIDS, but the underlying mechanism is still unclear. We have recently shown that ataxia-telangiectasia-mutated (ATM) deficiency in CD4 T cells accelerates DNA damage, telomere erosion, and cell apoptosis in HIV-infected individuals on antiretroviral therapy (ART). Whether these alterations in ART-treated HIV subjects occur in vitro in HIV-infected CD4 T cells remains unknown. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the telomeric DNA damage response (DDR) and cellular apoptosis in highly permissive SupT1 cells, followed by the validation of our observations in primary CD4 T cells with active or drug-suppressed HIV infection. Specifically, we established an in vitro HIV T-cell culture system with viral replication and raltegravir (RAL; an integrase inhibitor) suppression, mimicking active and ART-controlled HIV infection in vivo. We demonstrated that HIV-induced, telomeric DDR plays a pivotal role in triggering telomere erosion, premature T-cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This in vitro model provides a new tool to investigate HIV pathogenesis, and our results shed new light on the molecular mechanisms of telomeric DDR and CD4 T-cell homeostasis during HIV infection. IMPORTANCE The hallmark of HIV infection is a gradual depletion of CD4 T cells, with a progressive decline of host immunity. How CD4 T cells are depleted in individuals with active and virus-suppressed HIV infection remains unclear. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the chromosome end (telomere) DNA damage response (DDR) and cellular apoptosis in a T-cell line (highly permissive SupT1 cells), as well as in primary CD4 T cells with active or drug-suppressed HIV infection. We demonstrated that HIV-induced telomeric DDR plays a critical role in inducing telomere loss, premature cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This study sheds new light on the molecular mechanisms of telomeric DDR and its role in CD4 T-cell homeostasis during HIV infection