Autophagy is an evolutionarily conserved catabolic process that plays an essential role in maintaining cellular homeostasis by degrading unneeded cell components. When exposed to hostile ...environments, such as hypoxia or nutrient starvation, cells hyperactivate autophagy in an effort to maintain their longevity. In densely packed solid tumors, such as glioblastoma, autophagy has been found to run rampant due to a lack of oxygen and nutrients. In recent years, targeting autophagy as a way to strengthen current glioblastoma treatment has shown promising results. However, that protective autophagy inhibition or autophagy overactivation is more beneficial, is still being debated. Protective autophagy inhibition would lower a cell’s previously activated defense mechanism, thereby increasing its sensitivity to treatment. Autophagy overactivation would cause cell death through lysosomal overactivation, thus introducing another cell death pathway in addition to apoptosis. Both methods have been proven effective in the treatment of solid tumors. This systematic review article highlights scenarios where both autophagy inhibition and activation have proven effective in combating chemoresistance and radioresistance in glioblastoma, and how autophagy may be best utilized for glioblastoma therapy in clinical settings.
Pedestrians regularly engage with their mobile phone whilst walking. The current study investigated how mobile phone use affects where people look (visual search behaviour) and how they negotiate a ...floor based hazard placed along the walking path. Whilst wearing a mobile eye tracker and motion analysis sensors, participants walked up to and negotiated a surface height change whilst writing a text, reading a text, talking on the phone, or without a phone. Differences in gait and visual search behaviour were found when using a mobile phone compared to when not using a phone. Using a phone resulted in looking less frequently and for less time at the surface height change, which led to adaptations in gait by negotiating it in a manner consistent with adopting an increasingly cautious stepping strategy. When using a mobile phone, writing a text whilst walking resulted in the greatest adaptions in gait and visual search behaviour compared to reading a text and talking on a mobile phone. Findings indicate that mobile phone users were able to adapt their visual search behaviour and gait to incorporate mobile phone use in a safe manner when negotiating floor based obstacles.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a photometric study of the dwarf galaxy population in the core region ( rvir/4) of the Fornax galaxy cluster based on deep u′g′i′ photometry from the Next Generation Fornax Cluster Survey. ...All imaging data were obtained with the Dark Energy Camera mounted on the 4 m Blanco telescope at the Cerro Tololo Interamerican Observatory. We identify 258 dwarf galaxy candidates with luminosities −17 Mg′ −8 mag, corresponding to typical stellar masses of , reaching ∼3 mag deeper in point-source luminosity and ∼4 mag deeper in surface brightness sensitivity compared to the classic Fornax Cluster Catalog. Morphological analysis shows that the dwarf galaxy surface-brightness profiles are well represented by single-component Sérsic models with average Sérsic indices of and average effective radii of . Color-magnitude relations indicate a flattening of the galaxy red sequence at faint galaxy luminosities, similar to the one recently discovered in the Virgo cluster. A comparison with population synthesis models and the galaxy mass-metallicity relation reveals that the average faint dwarf galaxy is likely older than ∼5 Gyr. We study galaxy scaling relations between stellar mass, effective radius, and stellar mass surface density over a stellar mass range covering six orders of magnitude. We find that over the sampled stellar mass range several distinct mechanisms of galaxy mass assembly can be identified: (1) dwarf galaxies assemble mass inside the half-mass radius up to , (2) isometric mass assembly occurs in the range , and (3) massive galaxies assemble stellar mass predominantly in their halos at and above.
Precise genome editing using CRISPR-Cas9 is a promising therapeutic avenue for genetic diseases, although off-target editing remains a significant safety concern. Guide RNAs shorter than 16 ...nucleotides in length effectively recruit Cas9 to complementary sites in the genome but do not permit Cas9 nuclease activity. Here we describe CRISPR Guide RNA Assisted Reduction of Damage (CRISPR GUARD) as a method for protecting off-targets sites by co-delivery of short guide RNAs directed against off-target loci by competition with the on-target guide RNA. CRISPR GUARD reduces off-target mutagenesis while retaining on-target editing efficiencies with Cas9 and base editor. However, we discover that short guide RNAs can also support base editing if they contain cytosines within the deaminase activity window. We explore design rules and the universality of this method through in vitro studies and high-throughput screening, revealing CRISPR GUARD as a rapidly implementable strategy to improve the specificity of genome editing for most genomic loci. Finally, we create an online tool for CRISPR GUARD design.
Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, ...the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile drug-delivery microparticles, pH sensors, and 3D microfluidic devices that we could not produce using traditional 3D printing. SEAL allows us to generate microstructures with complex geometry at high resolution, produce fully enclosed internal cavities containing a solid or liquid, and use potentially any thermoplastic material without processing additives.
Voice and face processing occur through convergent neural systems that facilitate speaker recognition. Neuroimaging studies suggest that familiar voice processing engages early visual cortex, ...including the bilateral fusiform gyrus (FG) on the basal temporal lobe. However, what role the FG plays in voice processing and whether it is driven by bottom-up or top-down mechanisms is unresolved. In this study we directly examined neural responses to famous voices and faces in human FG with direct cortical surface recordings (electrocorticography) in epilepsy surgery patients. We tested the hypothesis that neural populations in human FG respond to famous voices and investigated the temporal properties of voice responses in FG. Recordings were acquired from five adult participants during a person identification task using visual and auditory stimuli from famous speakers (U.S. Presidents Barack Obama, George W. Bush, and Bill Clinton). Patients were presented with images of presidents or clips of their voices and asked to identify the portrait/speaker. Our results demonstrate that a subset of face-responsive sites in and near FG also exhibit voice responses that are both lower in magnitude and delayed (300-600 ms) compared with visual responses. The dynamics of voice processing revealed by direct cortical recordings suggests a top-down feedback-mediated response to famous voices in FG that may facilitate speaker identification.
Interactions between auditory and visual cortices play an important role in person identification, but the dynamics of these interactions remain poorly understood. We performed direct brain recordings of fusiform face cortex in human epilepsy patients performing a famous voice naming task, revealing the dynamics of famous voice processing in human fusiform face cortex. The findings support a model of top-down interactions from auditory to visual cortex to facilitate famous voice recognition.
Economic development, population growth and poor resource management have combined to alter the planet's natural environment in dramatic and alarming ways. For over twenty years, considerable ...research and debate have focused on clarifying or disputing linkages between various forms of environmental change and various understandings of security. At one extreme lie sceptics who contend that the linkages are weak or even non-existent; they are simply attempts to harness the resources of the security arena to an environmental agenda. At the other extreme lie those who believe that these linkages may be the most important drivers of security in the 21st century; indeed, the very future of humankind may be at stake.
This book brings together contributions from a range of disciplines to present a critical and comprehensive overview of the research and debate linking environmental factors to security. It provides a framework for representing and understanding key areas of intellectual convergence and disagreement, clarifying achievements of the research as well as identifying its weaknesses and gaps. Part I explores the various ways environmental change and security have been linked, and provides principal critiques of this linkage. Part II explores the linkage through analysis of key issue areas such as climate change, energy, water, food, population, and development. Finally, the book concludes with a discussion of the value of this subfield of security studies, and with some ideas about the questions it might profitably address in the future.
This volume is the first to provide a comprehensive overview of the field. With contributions from around the world, it combines established and emerging scholars to offer a platform for the next wave of research and policy activity. It is invaluable for both students and practitioners interested in international relations, environment studies and human geography.
This study investigated the efficacy of quercetin (QCT) in combination with sodium butyrate (NaB) in enhancing apoptosis in rat C6 and human T98G glioblastoma cells though blockage of autophagy under ...nutrient-starvation. The most synergistic doses of the drugs were determined to be 25 µM QCT and 1 mM NaB in both cell lines. After QCT and QCT + NaB treatments, autophagy quantification with acridine orange staining showed a drastic decrease in protective autophagy in the cells under nutrient-starvation. Decrease in autophagy was correlated with decreases in expression of Beclin-1 and LC3B II. Combination treatment increased the morphological signs of apoptosis including membrane blebbing, nuclear fragmentation, and chromatin condensation. Annexin V staining was also performed for detection and quantification of increases in apoptosis. Western blotting results showed that combination of QCT and NaB increased apoptosis by decreasing anti-apoptotic Bcl-2 and increasing pro-apoptotic Bax, decreasing survivin, activating caspase-3, and degrading poly (ADP-ribose) polymerase (PARP). This study demonstrated the therapeutic potentials of a novel combination therapy in inhibiting protective autophagy to enhance apoptosis in rat C6 and human T98G glioblastoma cells.
A contemporary examination of what information is represented, how that information is presented, and who gets to participate (and serve as gatekeeper) in the world's largest online repository for ...information, Wikipedia. Bridging contemporary education research that addresses the 'experiential epistemology' of learning to use Wikipedia with an understanding of how the inception and design of the platform assists this, the book explores the complex disconnect between the encyclopedia's formalized policy and the often unspoken norms that govern its knowledge-making processes. At times both laudatory and critical, this book illustrates Wikipedia's struggle to combat systemic biases and lack of representation of marginalized topics as it becomes the standard bearer for equitable and accessible representation of reality in an age of digital disinformation and fake news. Being an important and timely contribution to the field of media and communication studies, this book will appeal to academics and researchers interested in digital disinformation, information literacy, and representation on the Internet, as well as students studying these topics.
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