Evolutionary Analysis of TCGA Data Using Over- and Under- Mutated Genes Identify Key Molecular Pathways and Cellular Functions in Lung Cancer Subtypes.

We identify critical conserved and mutated genes through a theoretical model linking a gene’s fitness contribution to its observed mutational frequency in a clinical cohort. “Passenger” gene mutations do not alter fitness and have mutational frequencies determined by gene size and the mutation rate. Driver mutations, which increase fitness (and proliferation), are observed more frequently than expected.

Proton export upregulates aerobic glycolysis.

Introduction: Aggressive cancers commonly ferment glucose to lactic acid at high rates, even in the presence of oxygen. This is known as aerobic glycolysis, or the "Warburg Effect." It is widely assumed that this is a consequence of the upregulation of glycolytic enzymes.

Slow update of internal representations impedes synchronization in autism.

Autism is a neurodevelopmental disorder characterized by impaired social skills, motor and perceptual atypicalities. These difficulties were explained within the Bayesian framework as either reflecting oversensitivity to prediction errors or - just the opposite - slow updating of such errors. To test these opposing theories, we administer paced finger-tapping, a synchronization task that requires use of recent sensory information for fast error-correction.

Eradicating Metastatic Cancer and the Eco-Evolutionary Dynamics of Anthropocene Extinctions.

Curative therapy for metastatic cancers is equivalent to causing extinction of a large, heterogeneous, and geographically dispersed population. Although eradication of dinosaurs is a dramatic example of extinction dynamics, similar application of massive eco-evolutionary force in cancer treatment is typically limited by host toxicity. Here, we investigate the evolutionary dynamics of Anthropocene species extinctions as an alternative model for curative cancer therapy.

The Warburg effect as an adaptation of cancer cells to rapid fluctuations in energy demand.

To maintain optimal fitness, a cell must balance the risk of inadequate energy reserve for response to a potentially fatal perturbation against the long-term cost of maintaining high concentrations of ATP to meet occasional spikes in demand. Here we apply a game theoretic approach to address the dynamics of energy production and expenditure in eukaryotic cells. Conventionally, glucose metabolism is viewed as a function of oxygen concentrations in which the more efficient oxidation of glucose to CO2 and H2O produces all or nearly all ATP except under hypoxic conditions when less efficient (2 ATP/ glucose vs.

1,3-Dinitrobenzene neurotoxicity - Passage effect in immortalized astrocytes.

Age-related disturbances in astrocytic mitochondrial function are linked to loss of neuroprotection and decrements in neurological function. The immortalized rat neocortical astrocyte-derived cell line, DI-TNC1, provides a convenient model for the examination of cellular aging processes that are difficult to study in primary cell isolates from aged brain. Successive passages in culture may serve as a surrogate of aging in which time-dependent adaptation to culture conditions may result in altered responses to xenobiotic challenge.

Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells.

The ability of a cancer cell to detach from the primary tumor and move to distant sites is fundamental to a lethal cancer phenotype. Metabolic transformations are associated with highly motile aggressive cellular phenotypes in tumor progression. Here, we report that cancer cell motility requires increased utilization of the glycolytic pathway.

Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.

Background: Symptoms of attention deficit hyperactivity disorder (ADHD), diagnosed mainly in children, often persist into adulthood. Adults in this group have a high rate of other psychiatric problems and functional difficulties in a number of key areas such as academic achievement, interpersonal relationships, and employment. Although the usefulness of immediate-release methylphenidate in children has been extensively studied, studies in adults, which are few, demonstrate varying results.

Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane.

Background: Cancer cells, and a variety of normal cells, exhibit aerobic glycolysis, high rates of glucose fermentation in the presence of normal oxygen concentrations, also known as the Warburg effect. This metabolism is considered abnormal because it violates the standard model of cellular energy production that assumes glucose metabolism is predominantly governed by oxygen concentrations and, therefore, fermentative glycolysis is an emergency back-up for periods of hypoxia. Though several hypotheses have been proposed for the origin of aerobic glycolysis, its biological basis in cancer and normal cells is still not well understood.

ADHD subjects fail to suppress eye blinks and microsaccades while anticipating visual stimuli but recover with medication.

Oculomotor behavior and parameters are known to be affected by the allocation of attention and could potentially be used to investigate attention disorders. We explored the oculomotor markers of Attention-deficit/hyperactivity disorder (ADHD) that are involuntary and quantitative and that could be used to reveal the core-affected mechanisms, as well as be used for differential diagnosis. We recorded eye movements in a group of 22 ADHD-diagnosed patients with and without medication (methylphenidate) and in 22 control observers while performing the test of variables of attention (t.

Photothermal therapy of cancer cells mediated by blue hydrogel nanoparticles.

Aim: The aim of this study was to investigate in vitro the utility of biologically compatible, nontoxic and cell-specific targetable hydrogel nanoparticles (NPs), which have Coomassie® Brilliant Blue G dye (Sigma-Aldrich, MO, USA) covalently linked into their polyacrylamide matrix, as candidates for photothermal therapy (PTT) of cancer cells.

Materials & Methods: Hydrogel NPs with Coomassie Brilliant Blue G dye covalently linked into their polyacrylamide matrix were fabricated using a reverse micelle microemulsion polymerization method and were found to be 80-95 nm in diameter, with an absorbance value of 0.52.

Cell volume changes during apoptosis monitored in real time using digital holographic microscopy.

Cellular volume changes play important roles in many processes associated with the normal cell activity, as well as various diseases. Consequently, there is a considerable need to accurately measure volumes of both individual cells and cell populations as a function of time. In this study, we have monitored cell volume changes in real time during apoptosis using digital holographic microscopy.

Nanoparticle PEBBLE sensors for quantitative nanomolar imaging of intracellular free calcium ions.

Ca(2+) is a universal second messenger and plays a major role in intracellular signaling, metabolism, and a wide range of cellular processes. To date, one of the most successful approaches for intracellular Ca(2+) measurement involves the introduction of optically sensitive Ca(2+) indicators into living cells, combined with digital imaging microscopy. However, the use of free Ca(2+) indicators for intracellular sensing and imaging has several limitations, such as nonratiometric measurement for the most-sensitive indicators, cytotoxicity of the indicators, interference from nonspecific binding caused by cellular biomacromolecules, challenging calibration, and unwanted sequestration of the indicator molecules.

Two-photon nano-PEBBLE sensors: subcellular pH measurements.

Intracellular pH mapping is of great importance as it plays a critical role in many cellular events. Also, in tissue, pH mapping can be an indicator for the onset of cancer. Here we describe a biocompatible, targeted, ratiometric, fluorescent, pH sensing nano-PEBBLE (Photonic Explorer for Biomedical use with Biologically Localized Embedding) that is based on two-photon excitation.