Fibroblast Growth Factor Receptor 3 Is a Negative Regulator of Bone Growth

AbstractEndochondral ossification is a major mode of bone formation that occurs as chondrocytes undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. We have identified a role for fibroblast growth factor receptor 3 (FGFR-3) in this process by disrupting the murine Fgfr-3 gene to produce severe and progressive bone dysplasia with enhanced and prolonged endochondral bone growth. This growth is accompanied by expansion of proliferating and hypertrophic chondrocytes within the cartilaginous growth plate. Thus, FGFR-3 appears to regulate endochondral ossification by an essentially negative mechanism, limiting rather than promoting osteogenesis. In light of these mouse results, certain human disorders, such as achondroplasia, can be interpreted as gain-of-function mutations that activate the fundamentally negative growth control exerted by the FGFR-3 kinase

Power-Law Decay of Standing Waves on the Surface of Topological Insulators

We propose a general theory on the standing waves (quasiparticle interference pattern) caused by the scattering of surface states off step edges in topological insulators, in which the extremal points on the constant energy contour of surface band play the dominant role. Experimentally we image the interference patterns on both Bi$_2$Te$_3$ and Bi$_2$Se$_3$ films by measuring the local density of states using a scanning tunneling microscope. The observed decay indices of the standing waves agree excellently with the theoretical prediction: In Bi$_2$Se$_3$, only a single decay index of -3/2 exists; while in Bi$_2$Te$_3$ with strongly warped surface band, it varies from -3/2 to -1/2 and finally to -1 as the energy increases. The -1/2 decay indicates that the suppression of backscattering due to time-reversal symmetry does not necessarily lead to a spatial decay rate faster than that in the conventional two-dimensional electron system. Our formalism can also explain the characteristic scattering wave vectors of the standing wave caused by non-magnetic impurities on Bi$_2$Te$_3$.Comment: 4 pages, 3 figure

Millennium tree-ring reconstruction of drought variability in the eastern Qilian Mountains, northwest China

Knowledge of natural long-term drought variability is essential for water resource management and planning, especially in arid and sub-arid regions of the world. In the eastern Qilian Mountains of China, long-term drought variability based on high-resolution proxy records such as tree-ring data are still scarce to date. Here we present a new tree-ring chronology from the eastern Qilian Mountains which provides a valuable 1,002-year record (1009–2010 CE) of drought variability. The new reconstruction of June–July 5-month scale standardized precipitation and evapotranspiration index is the first millennium tree-ring estimate of past climate developed in the eastern Qilian Mountains. The record shows that this region has experienced several persistent droughts and pluvials over the past millennium, with significantly drier climate during the fifteenth century and dramatic wetting since the nineteenth century. The low frequency generally agrees with other nearby studies based on both tree-ring data and other proxy data

Research Progress on Natural Diterpenoids in Reversing Multidrug Resistance

Multidrug resistance (MDR) is one of the main impediments in successful chemotherapy in cancer treatment. Overexpression of ATP-binding cassette (ABC) transporter proteins is one of the most important mechanisms of MDR. Natural products have their unique advantages in reversing MDR, among which diterpenoids have attracted great attention of the researchers around the world. This review article summarizes and discusses the research progress on diterpenoids in reversing MDR

KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway.

Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway. Knockdown of KMT2A markedly inhibited the promoter activity and expression of hTERT, and hTERT overexpression rescued the viability inhibition caused by KMT2A knockdown. Moreover, KMT2A knockdown suppressed tumorsphere formation and the expression of cancer stem cell markers, which was also reversed by hTERT overexpression. In addition, the results from a xenograft mouse model confirmed that KMT2A promoted melanoma growth via hTERT signaling. Finally, analyses of clinical samples demonstrated that the expression of KMT2A and hTERT were positively correlated in melanoma tumor tissues, and KMT2A high expression predicted poor prognosis in melanoma patients. Collectively, our results indicate that KMT2A promotes melanoma growth by activating the hTERT signaling, suggesting that the KMT2A/hTERT signaling pathway may be a potential therapeutic target for melanoma

Pathological phenotypes and in vivo DNA cleavage by unrestrained activity of a phosphorothioate-based restriction system in Salmonella

Prokaryotes protect their genomes from foreign DNA with a diversity of defence mechanisms, including a widespread restriction–modification (R–M) system involving phosphorothioate (PT) modification of the DNA backbone. Unlike classical R–M systems, highly partial PT modification of consensus motifs in bacterial genomes suggests an unusual mechanism of PT-dependent restriction. In Salmonella enterica, PT modification is mediated by four genes dptB–E, while restriction involves additional three genes dptF–H. Here, we performed a series of studies to characterize the PT-dependent restriction, and found that it presented several features distinct with traditional R–M systems. The presence of restriction genes in a PT-deficient mutant was not lethal, but instead resulted in several pathological phenotypes. Subsequent transcriptional profiling revealed the expression of > 600 genes was affected by restriction enzymes in cells lacking PT, including induction of bacteriophage, SOS response and DNA repair-related genes. These transcriptional responses are consistent with the observation that restriction enzymes caused extensive DNA cleavage in the absence of PT modifications in vivo. However, overexpression of restriction genes was lethal to the host in spite of the presence PT modifications. These results point to an unusual mechanism of PT-dependent DNA cleavage by restriction enzymes in the face of partial PT modification.National Natural Science Foundation (China) (Grant 31170085)National Natural Science Foundation (China) (Grant 31070058)Ministry of Science and Technology of the People's Republic of China (973 and 863 Programs)China Scholarship CouncilNational Science Foundation (U.S.) (Grant CHE-1019990)Shanghai Municipal Council of Science and Technology. Shanghai Pujiang Program (Grant 12PJD021

Consistency of shared reference frames should be reexamined

In a recent Letter [G. Chiribella et al., Phys. Rev. Lett. 98, 120501 (2007)], four protocols were proposed to secretly transmit a reference frame. Here We point out that in these protocols an eavesdropper can change the transmitted reference frame without being detected, which means the consistency of the shared reference frames should be reexamined. The way to check the above consistency is discussed. It is shown that this problem is quite different from that in previous protocols of quantum cryptography.Comment: 3 pages, 1 figure, comments are welcom

KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration

Our former study demonstrated that Krüppel-like Factor 7 (KLF7) is a transcription factor that stimulates axonal regeneration after peripheral nerve injury. Currently, we used a gene therapy approach to overexpress KLF7 in Schwann cells (SCs) and assessed whether KLF7-transfected SCs graft could promote sciatic nerve regeneration. SCs were transfected by adeno-associated virus 2 (AAV2)-KLF7 in vitro. Mice were allografted by an acellular nerve (ANA) with either an injection of DMEM (ANA group), SCs (ANA + SCs group) or AAV2-KLF7-transfected SCs (ANA + KLF7-SCs group) to assess repair of a sciatic nerve gap. The results indicate that KLF7 overexpression promoted the proliferation of both transfected SCs and native SCs. The neurite length of the dorsal root ganglia (DRG) explants was enhanced. Several beneficial effects were detected in the ANA + KLF7-SCs group including an increase in the compound action potential amplitude, sciatic function index score, enhanced expression of PKH26-labeling transplant SCs, peripheral myelin protein 0, neurofilaments, S-100, and myelinated regeneration nerve. Additionally, HRP-labeled motoneurons in the spinal cord, CTB-labeled sensory neurons in the DRG, motor endplate density and the weight ratios of target muscles were increased by the treatment while thermal hyperalgesia was diminished. Finally, expression of KLF7, NGF, GAP43, TrkA and TrkB were enhanced in the grafted SCs, which may indicate that several signal pathways may be involved in conferring the beneficial effects from KLF7 overexpression. We concluded that KLF7-overexpressing SCs promoted axonal regeneration of the peripheral nerve and enhanced myelination, which collectively proved KLF-SCs as a novel therapeutic strategy for injured nerves