Although much has been learned about the fibrillization kinetics, structure and toxicity of amyloid proteins, the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologi...
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Although much has been learned about the fibrillization kinetics, structure and toxicity of amyloid proteins, the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologically inert, despite evidence suggesting otherwise. To fill this knowledge gap, we examined the physical and biological characteristics of human islet amyloid polypeptide(IAPP) fibrils that were aged up to two months. Not only did aging decrease the toxicity of IAPP fibrils, but the fibrils also sequestered fresh IAPP and suppressed their toxicity in an embryonic zebrafish model. The mechanical properties of IAPP fibrils in different aging stages were probed by atomic force microscopy and sonication, which displayed comparable stiffness but age-dependent fragmentation, followed by self-assembly of such fragments into the largest lamellar amyloid structures reported to date. The dynamic structural and toxicity profiles of amyloid fibrils and plaques suggest that they play active, long-term roles in cell degeneration and may be a therapeutic target for amyloid diseases.
In this study, Gelatin/Thai silk fibroin microspheres with the size of less than 100 μm were fabricated by water in oil emulsion technique using Span80, an oil-soluble emulsifier. The G/SF microspheres were crosslink...
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ISBN:
(纸本)9781509039418
In this study, Gelatin/Thai silk fibroin microspheres with the size of less than 100 μm were fabricated by water in oil emulsion technique using Span80, an oil-soluble emulsifier. The G/SF microspheres were crosslinked by dehydrothermal treatment (DHT). The effectiveness of crosslinking on G/SF microspheres was investigated by the free amino contents of microspheres before and after crosslinking using a modified 2,4,6-trinitrobenzene sulphonic acid (TNBS) method. It was found that the DHT-crosslinked G/SF microspheres showed low crosslinking degree (36-37%) in comparison to chemical crosslinking. For the in vitro enzymatic biodegradation test, the results showed that the DHT-crosslinked G/SF microspheres were rapidly degraded in protease XIV solution (pH 7.4) at 37°C. For the entrapment efficiency of curcumin, we found that the microspheres containing high content of silk fibroin could entrap more curcumin because of the hydrophobic interaction between curcumin and silk fibroin. In addition, we found the effect of mixed solvent of ethanol and DI water on entrapment efficiency of curcumin in the microspheres. Increasing DI water content in mixed solvent result in an increased entrapment efficiency of curcumin, possibly due to water swelling ability of gelatin content leading the diffusion of curcumin into the microspheres. It was suggested that the G/SF microspheres with the size of 32-74 μm might be suitably for applied as injectable carriers for controlled release of curcumin for anti-cancer treatment.
Secondary structures of silk fibroin (SF) related directly to their gelling, degradability, mechanical properties which affects its applications. The current works investigated the changes of Thai SF's secondary s...
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ISBN:
(纸本)9781509039418
Secondary structures of silk fibroin (SF) related directly to their gelling, degradability, mechanical properties which affects its applications. The current works investigated the changes of Thai SF's secondary structure during the process of film fabrication. Thai SF from domestic silk cocoons, Bombyx mori (Nangnoi Sisaket 1) were dissolved into water soluble protein using two solvent systems, 9.3 M LiBr solution, and Ajisawa's reagent (CaCl 2 :water:EtOH at 1: 8: 2 by mole). The SF solution was subjected to liquid nitrogen followed by lyophilization to preserve the protein's structure. Films were casted from the SF solutions and were immersed in ethanol to regenerate the protein's original conformations. Attenuated totally reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was used to quantify relative contents of protein's secondary structures altered by each step of the processes. Degummed silk fibers had the highest beta sheet crystallinity of 59.1%. Random coils and beta sheet structures of the SF prepared with Ajisawa's reagent were at 41.5% and 18.2%, and those prepared with LiBr solution were at 45.8% and 14.4%, respectively. The non-treated SF films consisted of 33.8-35.0% and 23.2-25.9% of beta sheets and random coils, respectively, despite of their preparation processes. Regeneration of the SF using ethanol immersion increased the beta sheet contents by 10-12% compared to the non-treated ones. Relative contents of beta turn, alpha helix, and tyrosine side chains were unchanged. The EtOH-regenerated Thai SF films contained 11-17% lower in beta sheet structures than the native fiber, suggesting the silk II formation was partially regained.
S1 Health literacy and health education in adolescence Catarina Cardoso Tomás S2 The effect of a walking program on the quality of life and well-being of people with schizophrenia Emanuel Oliveira, D. Sousa, M. U...
S1 Health literacy and health education in adolescence Catarina Cardoso Tomás S2 The effect of a walking program on the quality of life and well-being of people with schizophrenia Emanuel Oliveira, D. Sousa, M. Uba-Chupel, G. Furtado, C. Rocha, A. Teixeira, P. Ferreira S3 Diagnosis and innovative treatments - the way to a better medical practice Celeste Alves S4 Simulation-based learning and how it is a high contribution Stefan Gisin S5 Formative research about acceptability, utilization and promotion of a home fortification programme with micronutrient powders (MNP) in the Autonomous Region of Príncipe, São Tomé and Príncipe Elisabete Catarino, Nelma Carvalho, Tiago Coucelo, Luís Bonfim, Carina Silva S6 Safety culture of the patient: a reflexion about the therapeutic approach on the patient with vocal pathology Débora Franco S7 About wine, fortune cookies and patient experience Jesús Alcoba González O1 The psychological impact on the emergency crews after the disaster event on February 20, 2010 Helena G. Jardim, Rita Silva O2 Musculoskeletal disorders in midwives Cristina L. Baixinho, Mª Helena Presado, Mª Fátima Marques, Mário E. Cardoso O3 Negative childhood experiences and fears of compassion: Implications for psychological difficulties in adolescence Marina Cunha, Joana Mendes, Ana Xavier, Ana Galhardo, Margarida Couto O4 Optimal age to give the first dose of measles vaccine in Portugal João G. Frade, Carla Nunes, João R. Mesquita, Maria S. Nascimento, Guilherme Gonçalves O5 Functional assessment of elderly in primary care Conceição Castro, Alice Mártires, Mª João Monteiro, Conceição Rainho O6 Smoking and coronary events in a population of Spanish health-care centre: An observational study Francisco P. Caballero, Fatima M. Monago, Jose T. Guerrero, Rocio M. Monago, Africa P. Trigo, Milagros L. Gutierrez, Gemma M. Milanés, Mercedes G. Reina, Ana G. Villanueva, Ana S. Piñero, Isabel R. Aliseda, Francisco B. Ramirez O7 Prevalence of musculoskeletal injuries in Por
Adoptive Cellular TherapyO1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cellsAndreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, J...
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Adoptive Cellular TherapyO1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cellsAndreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1, Rolf Kiessling1, Yumeng Mao11Karolinska Institutet, Stockholm, Stockholms Lan, Sweden; 2Weill Cornell Medical College, New York, NY, USA; 3Nova Southeastern University, Cell Therapy Institute, Fort Lauderdale, FL, USACorrespondence: Andreas Lundqvist (***@***)
Background
NK cell-based immunotherapy is a potential therapeutic modality in patients with advanced cancers as transfer of haploidentical NK cells induces beneficial responses in patients with hematological malignancies; and leukemia clearance correlates with persistence and in vivo expansion of NK cells after infusion. Thus, sustained NK cell activity in vivo likely represents a therapy performance-limiting factor.
Methods
We performed genome-wide analysis of cytosolic and polysome-associated mRNA from interleukin (IL)-2 and IL-15 activated NK cells. Furthermore, the ability of IL-2 and IL-15 to sustain human NK cell activity following cytokine withdrawal as well as their effect on NK cells to resist tumor-induced immunosuppression was compared.
Results
After cytokine withdrawal, IL-15-treated NK cells maintained a higher level of cytotoxicity (p < 0.05) and showed lower levels of apoptosis (p < 0.05) compared with cells treated with IL-2. IL-15 augmented mTOR signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15-induced cell function advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK cell function during cytokine activation but not following cytokine withdrawal. Upon co-culture with tumor cells or exposure to tumor cell supernatant, IL-15 activated NK cell
dasiaBrain on Chippsila technologies based on two-dimensional in-vitro neural cultures have attracted much interest in both basic and applied neuroscience over the past two decades. Extending this technology towards m...
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dasiaBrain on Chippsila technologies based on two-dimensional in-vitro neural cultures have attracted much interest in both basic and applied neuroscience over the past two decades. Extending this technology towards more brain-like three-dimensional geometries while maintaining the ability to record and/or control the neural activity is an important neural engineering challenge. We have developed a versatile new optical strategy for generating complex 3-D patterns having micron scale resolution that can be practically applied for guiding cellular outgrowth in semi-transparent bio-synthetic hydrogels. This method is based on multi-photon photoablation of the solid phase of a hydrogel material, which creates a highly localized imperfection in the amorphous hydrogel matrix. When applied to a highly cross-linked biocompatible matrix, the micro-ablations provide a conductive niche for preferential guidance of neurites and support cells. Moreover, the optical transparency of the materials make them ideal for experimental studies involving cellular optical imaging and/or optical control of neural activity and could potentially enable the future development of a dasiaBrain in Chippsila technology.
作者:
McCarthy, AliceMain Text
“In June 2003
the scientific and medical communities at MIT Harvard University and its affiliated hospitals and the Whitehead Institute banded together as collaborating partners to form the Eli and Edythe L. Broad Institute based in Cambridge MA. The Broad Institute established with initial funding from a $100 million philanthropic donation from the Los Angeles-based Broad family was primarily viewed as a marriage between the Whitehead Institute's Center for Genome Research (WICGR) and the Harvard Institute of Chemistry and Cell Biology (ICCB). Eli Broad founder and chairman of AIG SunAmerica Inc. explained “the purpose of the Broad Institute is to create a new type of research institute to build on the accomplishments of the human genome project and to move to clinical applications to both prevent and cure diseases.”
Every Thursday morning we meet with perhaps 20 faculty members and 100 other researchers to discuss what we're all doing and should be doing next. -David Altschuler
This paragraph was written five years ago when the Broad Institute was in its very earliest days as a life science research community (McCarthy 2005). Since that time “the Broad” as it's known has kept true to Eli Broad's vision having attracted a talented group of researchers faculty trainees and professional staff. This 1600 person research community known internally as “Broadies” includes faculty staff and students from throughout the MIT and Harvard biomedical research communities and beyond with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide.
“What is special about the Broad is that we have people from Harvard MIT and the Harvard hospitals come together and work on problems of shared interest that could not be solved in their own individuals labs” explains David Altshuler M.D. Ph.D. Deputy Director and one of the Broad's six core faculty members. “These problems require expertise beyond any one principal investigator and in
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