Fast Proliferation Research Articles

Mobile crowd sensing of human-like intelligence using social sensors: A survey

Abstract Recently, with the fast proliferation of smart phones, mobile phone has the powerful ability of not only communication but also computation. Human beings are not only data consumers, but data producer with their objective or subjective sensing needs. Mobile crowd sensing is an emerging computing paradigm that tasks everyday mobile devices to form participatory sensor networks. It allows the increasing number of mobile phone users to share local knowledge acquired by their sensor-enhanced devices. Social sensors, social sensor receiver platform, and mobile crowd sensing paradigm compose a process by which physical sensors present in mobile devices such as GPS are used to infer social relationships and human activities. In this survey, we review the mobile crowd sensing applications on social sensors based on social sensor receiver platform (e.g., Weibo and Twitter) from three categories: public security, smart city, and location based services. Most applications adopted in current works fit in one of these categories. Existing works on applications of mobile crowd sensing on social sensors are collected and studied. Some possible future directions of potential new application category are proposed and analyzed.

Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1\u03b2

BackgroundInduced pluripotent stem cells (iPSC) provide an unlimited patient-specific cell source for regenerative medicine. Adult cells have had limited success in cartilage repair, but juvenile chondrocytes (from donors younger than 13 years of age) have been identified to generate superior cartilage. With this perspective, the aim of these studies was to compare the human iPSC-derived chondrocytes (hiChondrocytes) to adult and juvenile chondrocytes and identify common molecular factors that govern their function.MethodsPhenotypic and functional characteristics of hiChondrocytes were compared to juvenile and adult chondrocytes. Analyses of global gene expression profiling, independent gene expression, and loss-of-function studies were utilized to test molecular factors having a regulatory effect on hiChondrocytes and juvenile chondrocyte function.ResultsHere, we report that the iPSC-derived chondrocytes mimic juvenile chondrocytes in faster cell proliferation and resistance to IL-1β compared to adult chondrocytes. Whole genome transcriptome analyses revealed unique ECM factors and immune response pathways to be enriched in both juvenile and iPSC-derived chondrocytes as compared to adult chondrocytes. Loss-of-function studies demonstrated that CD24, a cell surface receptor enriched in both juvenile chondrocytes and hiChondrocytes, is a regulatory factor in both faster proliferation and resistance to proinflammatory cues in these chondrocyte populations.ConclusionsOur studies identify that hiChondrocytes mimic juvenile chondrocytes for the dual advantage of faster proliferation and a reduced response to the inflammatory cytokine IL-1β. While developmental immaturity of iPSC-derived cells can be a challenge for tissues like muscle and brain, our studies demonstrate that it is advantageous for a tissue like cartilage that has limited regenerative ability in adulthood.

Alendronate-loaded, biodegradable smart hydrogel: a promising injectable depot formulation for osteoporosis

Alendronate (ALN) is a BCS III bone resorption inhibitor, with very poor oral bioavailability. Our approach is to develop a minimally invasive thermogelling system for prolonged local delivery of ALN. For this, different chitosan-based thermogels were developed and characterised in terms of gelation time, injectability, pH, viscosity and thermoreversibility. Chitosan/β-glycerophosphate (CS/βGP) hydrogel pursued temperature-dependent, thermoreversible gelation behaviour and was thus selected for drug loading. Increasing ALN concentration resulted in hydrogels with lower porosity and higher density. FTIR and DSC proved interaction between ALN, CS with βGP. CS/βGP hydrogel ensured controlled ALN release over 45–65 days depending on initial ALN loading. Freeze drying improved the shelf-life stability with minor impact on thermogelling character. In vivo injection of plain and ALN-loaded hydrogel in rats rapidly gelled 15 min post-injection. Based on histological examination, ALN-loaded thermogel showed less inflammatory response, faster proliferation and maturation of granulation tissue relative to plain thermogel. Hydrogels excised 21-days post-injection proved the biocompatibility and biodegradability of the system. The presented chitosan-based thermogel has significant positive attributes for site-specific, time-controlled, intra-articular delivery of ALN.

Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1.

Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca2+ entry (SOCE) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca2+ oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown. The present study shows that zinc supplementation significantly inhibits proliferation of ESCC cell lines and that the effect of zinc is reversible with N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine, a specific Zn2+ chelator, whereas nontumorigenic esophageal epithelial cells are significantly less sensitive to zinc treatment. Fluorescence live cell imaging revealed that extracellular Zn2+ exerted rapid inhibitory effects on Orai1-mediated SOCE and on intracellular Ca2+ oscillations in the ESCC cells. Knockdown of Orai1 or expression of Orai1 mutants with compromised zinc binding significantly diminished sensitivity of the cancer cells to zinc treatment in both SOCE and cell proliferation analyses. These data suggest that zinc may inhibit cell proliferation of esophageal cancer cells through Orai1-mediated intracellular Ca2+ oscillations and reveal a possible molecular basis for zinc-induced cancer prevention and Orai1-SOCE signaling pathway in cancer cells.-Choi, S., Cui, C., Luo, Y., Kim, S.-H., Ko, J.-K., Huo, X., Ma, J., Fu, L.-W., Souza, R. F., Korichneva, I., Pan, Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1.

UV-C as a means to combat biofilm proliferation on prehistoric paintings: evidence from laboratory experiments.

A laboratory investigation of UV-C effects was conducted over a 62-h period: a much higher dose than in classic UV-C treatment was applied to five pigments and two painting binders used by prehistoric humans. Colorimetric parameters were compared to a control to see if UV-C can change pigment and binder color. Infrared spectroscopy, scanning electron microscopy, inductively coupled plasma and X-ray crystallography were also carried out to confirm colorimetric measurement. In order to understand how microorganism may physically deteriorate paintings, limestone blocks were painted and monitored until their complete colonization by algae, cyanobacteria, fungi and/or mosses. The results show that UV-C has no effect on mineral compounds. Conversely, it is noteworthy that binder color changed under both UV-C light conditions as well as in visible light. Concerning painted blocks, a fast proliferation has been observed with deterioration of the paintings. These results show the high importance of treating biofilm as soon as possible. Moreover, these findings may be a promising avenue inducing cave managers to use friendly UV-C light to treat contaminated cave paintings and also in the prevention of biodeterioration by lampenflora.

Abstract 5767: Ex vivo three-dimensional tumor growth assay: 3DX-TGA

Abstract With a 7% likelihood of regulatory approval, oncology drug registration failure rates lead all therapeutic areas. Further complicating the drug development process, preclinical oncology models poorly reflect tumor tissue biology and produce a high level of false positive data. Yet, monocellular two-dimensional (2D) tissue culture remains the preferred platform for most laboratory preclinical studies. The popularity of 2D tissue culture was driven predominantly by fast and dependable proliferation of human tumor cells rather than alignment to the pathophysiology of human cancer. As a consequence of this artificial selection bias, many registered oncology drugs today are highly toxic with a propensity to attack any dividing cell (i.e., non-targeted). Fortunately, recent advances in genomics, metabolomics and immunology have aided in development of new targeted agents, many of which have achieved regulatory approval. Nevertheless, rational drug combinations and identification of clinically meaningful drug targets persist as major challenges in oncology, and each can be meaningfully addressed using more diverse and biologically relevant preclinical models. Ex vivo tumor tissue transplant models, such as patient-derived xenografts (PDX) offer greater model diversity and more faithfully reflect patient tumor genetics. However, cost and scalability barriers tend to limit widespread and practical model utility. In addition, there remains a strong selection bias for autocrine human tumors that can quickly adapt to a cross-species mouse host. As a practical alternative to PDX models, we established, serially propagated and molecularly characterized 300 ex vivo 3D (3DX) models spanning 15 tumor indications. Given patient tumor seeding success rates of over 95%, the 3DX-TGA model enabled diverse pharmacologic evaluation for the vast majority of cancer patient models attempted. After achieving sufficient tumor biomass, typically within 7 to 8 weeks, thirty-one drugs were screened for proliferation and viability endpoints over a three-log dose range. Resistance and sensitivity profiles mirrored population-based response rates for indication-aligned FDA-registered drugs. Taken together, the 3DX-TGA model represents a powerful preclinical ex vivo model that: (1.) more faithfully recapitulates human tumor biology, (2.) can be scaled at a fraction of time and cost compared to PDX models, and (3.) provide a superior screening platform for novel drugs and drug-drug combinations. Citation Format: Praveen Nair, Dileep Nair, Kaede Hinata, Cyrus Mirsaidi, Junjie Wu, Yong Hu, Brett M. Hall. Ex vivo three-dimensional tumor growth assay: 3DX-TGA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5767. doi:10.1158/1538-7445.AM2017-5767

An efficient framework for real-time tweet classification

Increasing popularity of social networking sites like facebook, twitter, google+ etc. is contributing in fast proliferation of big data. Amongst social Networking sites, twitter is one of the most common source of big data where people from across the world share their views on various topics and subjects. With daily Active user count of 100-million+ users twitter is becoming a rich information source for finding trends and current happenings around the world. Twitter does provide a limited “trends” feature. To make twitter trends more interesting and informative, in this paper we propose a framework that can analyze twitter data and classify tweets on some specific subject to generate trends. We illustrate the use of framework by analyzing the tweets on “Politics” domain as a subject. In order to classify tweets we propose a tweet classification algorithm that efficiently classify the tweets.

SDN-Assisted Learning Approach for Data Offloading in 5G HetNets

With the fast proliferation of the smartphone usage, the mobile traffic has far more exceeded than the capacity of the LTE-A (Long Term Evolution-Advanced) networks. Hence, the Mobile Network Operators (MNOs) are looking for alternative opportunities to handle the network traffic instead of deploying cost-incurring classical devices. Mobile data offloading, which refers to diverting traffic from cellular networks to other complementary technologies such as WiFi access points offer to be a promising solution. APs provides better data services due to the small coverage area (100 m) and improves battery life. WiFi offloading, when implemented using Software-Defined Networking (SDN) helps in the dynamic management of a complex Heterogeneous Networks (HetNets). In this paper, we propose a novel SDN-Assisted Learning Approach (SALA) to provide better Quality of Experience (QoE) for both the cell edge users and intensive network users at the LTE-A base station using the unlicensed spectrum of the APs. We then verify our novel SALA framework against simulations based on real-world usage, and offer insight to the expected offloading gains in practice.

A simple and effective protocol for fast isolation of human Tenon\u2019s fibroblasts from a single trabeculectomy biopsy \u2013 a comparison of cell behaviour in different culture media

BackgroundHuman Tenon’s fibroblasts (HTFs) play a crucial role in wound healing. They cause postoperative scarring of the filtering bleb and are thus responsible for trabeculectomy failure. This study aimed to find an effective and fast protocol for HTF isolation from trabeculectomy biopsies. The protocol was compared with the commonly recommended HTF isolation procedure, which uses Dulbecco’s modified Eagle’s medium (DMEM). We used Eagle’s minimum essential medium (EMEM) enriched with fibroblast growth factor (FGF), which selectively promoted the proliferation of HTF cells. A secondary goal was to compare HTF morphology, metabolism and growth during parallel cultivation of the isolated cells in FGF-enriched EMEM and DMEM.ResultsStandard procedures for HTF isolation from tissue biopsies require a 20- to 30-day culture of the explants to obtain the first monolayer. Our protocol yielded the first monolayer after approx. 15 days. More importantly, the majority of the cells were fibroblasts with only individual epithelium-derived cells present. Using FGF-enriched EMEM allowed 1.3 × 106 vimentin-positive fibroblasts to be obtained from a single biopsy within approx. 25 days. Using DMEM resulted in isolation failure and required exchange to FGF-enriched medium to recover the fibroblast culture. HTFs maintained in FGF-enriched EMEM also showed faster proliferation and a different type I collagen production ability compared to HTFs cultured in DMEM. Thus, FGF-enriched EMEM is recommended for fast propagation of HTFs unless the aim of the study is to assess the effect of a tested agent on proliferation ability or type I collagen production.ConclusionsOur fast protocol for HTF isolation allows easy setup of cell banks by researchers under laboratory conditions and could be very useful during testing of novel ophthalmologic anti-fibrotic agents in vitro. Molecular analysis of HTFs isolated from patients with known treatment histories may provide valuable information on the effects of some medications taken before glaucoma surgery on the subsequent wound-healing process and potential for trabeculectomy failure.

Abstract P1-09-16: Randomized study of COX2 inhibition on systemic inflammation in obese and non-obese subjects

Abstract Introduction: Obesity is associated with poor breast cancer outcomes in postmenopausal women. Our prior retrospective studies have shown that use of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced recurrence in obese breast cancer patients and a doubling of time to recurrence. Because it was recently determined that CD163+ M2 macrophages were clinically associated with fast proliferation, poor differentiation, estrogen receptor negativity and histological duct type in human primary breast tumors, the mechanism proposed was a decrease in prostaglandin E2 (PGE2) and aromatase locally in the breast with a concomitant decrease in circulating M2-activated tumor associated macrophages (TAMs). Methods: Postmenopausal women of varying body habitus were recruited at the CTRC in San Antonio and underwent randomized assignment to 1 of 3 arms: Aspirin (ASA) at 81mg daily, 1500mg of docosahexaenoic acid (DHA) and 2500mg eicosapentaenoic acid (EPA) given daily, or combined ASA and DHA/EPA. Sera were collected prior to and following 28 days of exposure, and cytokines including prostaglandin E2 were assessed via enzyme ­linked immunosorbent assay (ELISA). 28 circulating cytokines/chemokines were assessed by Luminex array using Millipore Milliplex MAP to look for associations between cytokine array profiles, PGE2 production and macrophage activation. Circulating class M-1 activated and M-2 activated macrophages were enumerated by flow cytometry to assess how PGE2 modulation influences macrophage phenotype and function. Investigators were blinded to randomization until analysis was complete. Results: A total of 122 patients were randomized with 2 drop outs and 115 completing the 28 days of intervention as planned. The median BMI was 31.4, with 12.8% normal (BMI <25.0), 27.3% overweight (25.0-29.9), and 59.9% obese (>29.9). Patients had a median age of 63 (47-76), 91% white, and 46.0 % Hispanic. A positive correlation was observed between BMI and baseline PGE2 levels. The most consistent impact on PGE2 was observed with ASA with 81% obtaining a decrease from baseline (median change -28%); by comparison 55.1% (-1%) and 65.6% (-22%) of subjects showed decrease in the DHA/EPA and combined groups respectively. As of today, full cytokine profiling was performed on a subset of 38 patients and revealed a positive correlation with change in PGE2 and cytokines: EGF, Eotaxin, GM-CSF, IL1Ra, IL5, IL8, MIP1b, and TNFa. Conclusion: Aspirin alone most consistently impacted patient circulating PGE2 levels, and will be used in planned studies as an adjunct to adjuvant endocrine therapy in obese hormone receptor positive post-menopausal patients. Full cytokine and macrophage activation status will be reported. Citation Format: Brenner AJ, Lengfelder L, Quach DK, Cavazos DA, Ramirez RJ, Gruslova A, Kist K, Lathrup K, Kaklamani V, Beeram M, deGraffenried LA. Randomized study of COX2 inhibition on systemic inflammation in obese and non-obese subjects [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-16.

Clinical Development of Anti-mitotic Drugs in Cancer.

Mitosis is one of the most fundamental processes of life by which a mammalian cell divides into two daughter cells. Mitosis has been an attractive target for anticancer therapies since fast proliferation was identified as one of the hallmarks of cancer cells. Despite efforts into developing specific inhibitors for mitotic kinases and kinesins, very few drugs have shown the efficiency of microtubule targeting-agents in cancer cells with paclitaxel being the most successful. A deeper translational research accompanying clinical trials of anti-mitotic drugs will help in identifying potent biomarkers predictive for response. Here, we review the current knowledge of mitosis targeting agents that have been tested so far in the clinics.

Anestesthesiological approach to pediatric patient for lobectomy due to lung abscess: Lung separation and epidural analgesia (lung separation and epidural analgesia)

Introduction: Acute lymphoblastic leukemia is the most common malignancy in childhood. Main characteristics of the disease are fast proliferation of lymphoblastic cells in bone marrow, destruction of other cells, causing insufficiency in the bone marow and infiltration of the liver, spleen and the lymphatic nodes. Pulmonary abscess and necrotizing pneumonia are rarely found in pediatric population and usually represent a significant problem for treatment. These conditions often require some surgical treatment modalities. The main goal of anesthesiological approach is to provide good and safe perioperative conditions and adequate analgesia. Case report: During treatment of acute leukemia in a 15-year-old boy, complication inform absenting pneumonia left side lung was developed. After four months antibiotic and antifungal therapy wide broad,(nije jasno) decision of consilium was to perform left inferior lobectomy. Antibiotic prophylaxis with Ceftazidime 50 mg/kg BM. We performed a combination of general anesthesia and thoracic epidural anesthesia. Intubation with Robertshaw double lume tube. Ultrasound guided central venous catheter in left jugular veine and arterial line in right radial arteria. Anesthesia depth was controlled with entropy method. Epidural catheter was intoduded on level Thl0-Th 11. Conclusion: One ventilation with double lumen tube prevents spillage of infection sputum into the healthy lung. Epidural analgesia in this clinical situation held numerous benefits especially as a way to reduce postoperative respiratory complications caused by acute pain.

Achaete-Scute Homolog 1 Expression Controls Cellular Differentiation of Neuroblastoma

Neuroblastoma, the major cause of infant cancer deaths, results from fast proliferation of undifferentiated neuroblasts. Treatment of high-risk neuroblastoma includes differentiation with retinoic acid (RA); however, the resistance of many of these tumors to RA-induced differentiation poses a considerable challenge. Human achaete-scute homolog 1 (hASH1) is a proneural basic helix-loop-helix transcription factor essential for neurogenesis and is often upregulated in neuroblastoma. Here, we identified a novel function for hASH1 in regulating the differentiation phenotype of neuroblastoma cells. Global analysis of 986 human neuroblastoma datasets revealed a negative correlation between hASH1 and neuron differentiation that was independent of the N-myc (MYCN) oncogene. Using RA to induce neuron differentiation in two neuroblastoma cell lines displaying high and low levels of hASH1 expression, we confirmed the link between hASH1 expression and the differentiation defective phenotype, which was reversed by silencing hASH1 or by hypoxic preconditioning. We further show that hASH1 suppresses neuronal differentiation by inhibiting transcription at the RA receptor element. Collectively, our data indicate hASH1 to be key for understanding neuroblastoma resistance to differentiation therapy and pave the way for hASH1-targeted therapies for augmenting the response of neuroblastoma to differentiation therapy.

Stable knockdown of CREB, HIF-1 and HIF-2 by replication-competent retroviruses abrogates the responses to hypoxia in hepatocellular carcinoma

The fast proliferation of tumor cells develops faster than the vasculature, resulting, in most malignant tumors, in generation of hypoxic regions. Hypoxia renders solid tumors resistant to radiation and chemotherapeutics while providing opportunities for tumor-selective therapies targeting tumor hypoxia. Here we exploit two properties of tumors: propagation of tumor cells and ongoing generation of hypoxic regions to construct a system that preferentially leads to the death of tumor cells and thus hinders tumor growth. We constructed murine leukemia virus replication-competent (RCR) viruses that infect only propagating cells. These viruses express small hairpin RNAs (shRNAs) targeting cyclic AMP-response-element binding protein (CREB), hypoxia-inducible factors 1 (HIF)-1 or HIF-2 individually or all three together (X3). These viruses efficiently infected in vitro human hepatocellular carcinoma (HepG2 and FLC4) cells and established persistence of the virus and knocked down the expression of the regulators of the hypoxia-responding genes. Knockdown of either HIF-1 or CREB or both in hypoxia reduced the expression of hypoxia-response elements- and CRE-mediated gene expression, diminished cell proliferation and increased caspase-3 activity. We did not detect any significant effect of the efficiently knocked down HIF-2 on any of the functions tested in vitro. Moreover, severe combined immunodeficiency mice implanted subcutaneously with HepG2 stably infected with recombinant RCRs showed reduction of tumor growth and vascular endothelial growth factor expression, and no hypoxia-guided neovascularization. Combined treatment (RCRs+doxorubicin) improved efficacy in the context of in vitro hypoxia and in vivo (with either vACE-CREB or vACE-X3). This synergistic effect may lead to an improved efficacy and safety profile of the treatment that may result in fewer side effects.

Control devices development of multi‐microgrids based on hierarchical structure

With the fast proliferation of microgrids integrated into the power grid, several nearby microgrids with common benefit have been coupled to be multi-microgrids (MMGs), which is a significant stage for developing the smart grid. A suitable control structure and corresponding control device need to be proposed for the MMGs operating efficiently. However, mostly micrgrid control devices are still restricted to the single microgrid and have limited application without the common design. The authors develop control devices with a prodigious popularisation value for the MMGs based on the hierarchical control structure. According to the proposed four-layer control architecture (scheduling layer, central control layer, integrated terminal layer and bottom layer), the hardware and software design suitable for the MMGs control devices and its multi-time scale communication architecture has been presented. Furthermore, the appearance design and interface exploitation were introduced as well. Experimental results are provided to demonstrate the validity of the proposed MMGs control structure and devices, which could contribute to the large-scale application of MMGs control devices and provide a reference for other MMGs projects.

Investigating cytokinesis failure as a strategy in cancer therapy.

Effective therapeutics exploit common characteristics shared amongst cancers. As many cancers present chromosomal instability (CIN), one possible approach to treat these cancers could be to increase their CIN above a threshold that would affect their viability. Here, we investigated whether causing polyploidy by cytokinesis failure could represent a useful approach. We show that cytokinesis failure caused by depletion of Citron kinase (CIT-K) dramatically decreased cell proliferation in breast, cervical and colorectal cancer cells. CIT-K depletion activated the Hippo tumor suppressor pathway in normal, but not in cancer cells, indicating that cancer cells have evolved mechanisms to bypass this control. CIT-K depleted cancer cells died via apoptosis in a caspase 7 dependent manner and, consistent with this, p53-deficient HCT116 colon carcinoma cells failed to induce apoptosis after cytokinesis failure. However, other p53-mutated cancer cells were able to initiate apoptosis, indicating that cytokinesis failure can trigger apoptosis through a p53-independent mechanism. Finally, we found that actively dividing and, in some cases, polyploid cancer cells were more susceptible to CIT-K depletion. In sum, our findings indicate that inducing cytokinesis failure could be a promising anti-cancer therapeutic approach for a wide range of cancers, especially those characterized by fast cell proliferation and polyploidy.

Hypoxia-induced CCL28 promotes recruitment of regulatory T cells and tumor growth in liver cancer.

Tumor cells craft microenvironment to overcome growth disadvantages and adjust to escape the immunosurveillance during tumorigenesis and metastasis. The evolving adaption to the changing microenvironment is exemplified by the development of strategies to deal with hypoxia resulted from fast proliferation of the tumor cells. In this study, we found that hypoxia hepatocellular carcinoma (HCC) cells recruited Regulatory T cells (Tregs) and expressed more Chemokine (C-C motif) ligand 28 (CCL28). Deletion of CCL28 inhibited Treg recruitment. Furthermore, overexpression of CCL28 promoted tumor growth and Treg infiltration in vivo. Enhanced angiogenesis and VEGF expression was also observed. Moreover, inhibition of HIF1α reversed hypoxia-induced CCL28 upregulation. Taken together, our results demonstrate that HCC recruits Tregs to promote angiogenesis under hypoxic condition by upregulating CCL28 expression. These findings establish a link between Tregs and hypoxia in HCC growth and may provide a new potential therapeutic target for treating HCC.

A novel culture platform for fast proliferation of human annulus fibrosus cells.

Tissue engineering provides a promising approach to treat degenerative disc disease, which usually requires a large quantity of seed cells. A simple and reliable in vitro culture system to expand seed cells in a timely fashion is necessary to implement the application clinically. Here, we sought to establish a cost-effective culture system for expanding human annulus fibrosus cells using extracellular matrix (ECM) proteins as culture substrates. Cells were cultured onto a plastic surface coated with various types of ECMs, including fibronectin, vitronectin, collagen type I, gelatin and cell-free matrix deposited by human nucleus pulposus cells. AF cell morphology, growth, adhesion and phenotype (anabolic and catabolic markers) were assessed by microscopy, real-time RT-PCR, western blotting, zymography, immunofluorescence staining and biochemical assays. Fibronectin, collagen and gelatin promoted cell proliferation and adhesion in a dose-dependent manner. Fibronectin elevated mRNA expression of proteoglycan and enhanced glycosaminoglycan production. Both collagen and gelatin increased protein expression of type II collagen. Consistent with increased cell adhesion, collagen and fibronectin promoted formation of focal adhesion complexes in the cell-matrix junction, suggesting enhanced binding of the actin network with both ECM substrates. On the other hand, fibronectin, collagen and gelatin decreased expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in media. Finally, a mixture of fibronectin (1.7μg/mL) and collagen (1.3μg/mL) was identified as the most promising in vitro culture substrate system in promoting proliferation and maintaining anabolic-catabolic balance. Our method provides a simple and cost-effective platform for tissue engineering applications in intervertebral disc research.

Root architecture might account for contrasting establishment success of Pseudotsuga menziesii var. menziesii and Pinus sylvestris in Central Europe under dry conditions

Pinus sylvestris seedlings quickly expand their roots to deeper soil layers while Pseudotsuga menziesii concentrates its root system in the topsoil, thereby running the risk of desiccation during long dry spells, as indicated by lower survival after simulated summer drought. Pseudotsuga menziesii (Douglas-fir) is regarded as a promising species to maintain the productivity of Central European lowland forests given the projected increase of long dry spells. Will the species be able to regenerate from seed and spread outside plantations in a drier temperate Europe? We measured the relative growth rate, biomass allocation, root architecture, and phenotypic plasticity of Pseudotsuga menziesii seedlings sown in a common garden and grown under current precipitation and prolonged drought, respectively. The species’ competitive ability with respect to Pinus sylvestris L., the most drought-tolerant native conifer in Central Europe, was assessed during three growing seasons. Pinus sylvestris seedlings had higher relative growth rates than did Pseudotsuga menziesii seedlings, first in terms of aboveground biomass and later in terms of shoot height. This resulted in heavier and taller seedlings after three growing seasons under both moist and dry conditions. Shorter vertical roots corresponded with lower survival of Pseudotsuga menziesii seedlings under dry conditions. Fast root proliferation allows Pinus sylvestris seedlings to reach deeper water pools that are less rapidly depleted during transient drought. By contrast, the shallow root system might put Pseudotsuga menziesii seedlings at the risk of desiccation during prolonged dry spells.

Fatostatin Inhibits Cancer Cell Proliferation by Affecting Mitotic Microtubule Spindle Assembly and Cell Division

The sterol regulatory element-binding protein (SREBP) transcription factors have become attractive targets for pharmacological inhibition in the treatment of metabolic diseases and cancer. SREBPs are critical for the production and metabolism of lipids and cholesterol, which are essential for cellular homeostasis and cell proliferation. Fatostatin was recently discovered as a specific inhibitor of SREBP cleavage-activating protein (SCAP), which is required for SREBP activation. Fatostatin possesses antitumor properties including the inhibition of cancer cell proliferation, invasion, and migration, and it arrests cancer cells in G2/M phase. Although Fatostatin has been viewed as an antitumor agent due to its inhibition of SREBP and its effect on lipid metabolism, we show that Fatostatin's anticancer properties can also be attributed to its inhibition of cell division. We analyzed the effect of SREBP activity inhibitors including Fatostatin, PF-429242, and Betulin on the cell cycle and determined that only Fatostatin possessed antimitotic properties. Fatostatin inhibited tubulin polymerization, arrested cells in mitosis, activated the spindle assembly checkpoint, and triggered mitotic catastrophe and reduced cell viability. Thus Fatostatin's ability to inhibit SREBP activity and cell division could prove beneficial in treating aggressive types of cancers such as glioblastomas that have elevated lipid metabolism and fast proliferation rates and often develop resistance to current anticancer therapies.