A case study with breast cancer and brain metastasis encompassing acute onset of amnesia and altered mental status due to limbic encephalitis - biochemical and proteomic aspects

A biochemical case study is reported on a 50-year old lady known to have breast cancer. The woman was treated by mastectomy and this was followed by unraveling brain metastases three years post-diagnosis of the cancer, which was treated by radiation and chemotherapy. Two months after ending her treatment, she exhibited acute changes in her mental status manifested by severe amnesia and fever. A generalized analytical and biochemical assessment revealed the presence of paraneoplastic limbic encephalitis

Design, synthesis, antitumor activity and molecular docking study of novel 5-deazaalloxazine analogs

open access articleProtein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC50: 0.17–2.17 µM) over HeLa tumor cell lines (IC50 > 100 µM). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including −43% against (FAK), −40% against (CDKI) and −36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50

Three-dimensional digital template atlas of the Macaque brain

We present a new 3D template atlas of the anatomical subdivisions of the macaque brain, which is based on and aligned to the magnetic resonance imaging (MRI) data set and histological sections of the Saleem and Logothetis atlas. We describe the creation and validation of the atlas that, when registered with macaque structural or functional MRI scans, provides a straightforward means to estimate the boundaries between architectonic areas, either in a 3D volume with different planesof sections, or on an inflated brain surface (cortical flat map). As such, this new template atlas is intended for use as a reference standard for macaque brain research. Atlases and templates are available as both volumes and surfaces in standard NIFTI and GIFTI formats

Varying the rate of intravenous cocaine infusion influences the temporal dynamics of both drug and dopamine concentrations in the striatum

The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 vs. 90â 100 s promotes sensitization to the psychomotor and incentive motivational effects of the drug and preferentially recruits mesocorticolimbic regions. It remains unclear whether these effects are due to differences in how fast and/or how much drug reaches the brain. Here, we predicted that varying the rate of intravenous cocaine infusion between 5 and 90 s produces different rates of rise of brain drug concentrations, while producing similar peak concentrations. Freely moving male Wistar rats received acute intravenous cocaine infusions (2.0 mg/kg/infusion) over 5, 45 and 90 s. We measured cocaine concentrations in the dorsal striatum using rapidâ sampling microdialysis (1 sample/min) and highâ performance liquid chromatographyâ tandem mass spectrometry. We also measured extracellular concentrations of dopamine and other neurochemicals. Regardless of infusion rate, acute cocaine did not change concentrations of nonâ dopaminergic neurochemicals. Infusion rate did not significantly influence peak concentrations of cocaine or dopamine, but concentrations increased faster following 5â s infusions. We also assessed psychomotor activity as a function of cocaine infusion rate. Infusion rate did not significantly influence total locomotion, but locomotion increased earlier following 5â s infusions. Thus, small differences in the rate of cocaine delivery influence both the rate of rise of drug and dopamine concentrations, and psychomotor activity. A faster rate of rise of drug and dopamine concentrations might be an important issue in making rapidly delivered cocaine more addictive.Varying the rate of i.v. cocaine delivery between 5 and 90 s determines the drug’s effects on brain and behaviour. We show that injecting cocaine between 5 and 90 s in rats alters the rates of rise of cocaine and dopamine in the dorsal striatum, without significantly changing peak concentrations. Faster injections also increase locomotor behaviour earlier than slower injections. Thus, beyond achieved dose, differences in the rates of rise of cocaine and dopamine can determine outcome.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151808/1/ejn13941-sup-0002-reviewer-Comments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151808/2/ejn13941.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151808/3/ejn13941-sup-0001-FigS1-S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151808/4/ejn13941_am.pd

Regulation of Caspase-3 and Bcl-2 Expression in Dalton's Lymphoma Ascites Cells by Abrin

The role of abrin, a toxic lectin isolated from seeds of Abrus precatorius Linn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA) cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death

Ongoing neural oscillations influence behavior and sensory representations by suppressing neuronal excitability

The ability to process and respond to external input is critical for adaptive behavior. Why, then, do neural and behavioral responses vary across repeated presentations of the same sensory input? Ongoing fluctuations of neuronal excitability are currently hypothesized to underlie the trial-by-trial variability in sensory processing. To test this, we capitalized on intracranial electrophysiology in neurosurgical patients performing an auditory discrimination task with visual cues: specifically, we examined the interaction between prestimulus alpha oscillations, excitability, task performance, and decoded neural stimulus representations. We found that strong prestimulus oscillations in the alpha+ band (i.e., alpha and neighboring frequencies), rather than the aperiodic signal, correlated with a low excitability state, indexed by reduced broadband high-frequency activity. This state was related to slower reaction times and reduced neural stimulus encoding strength. We propose that the alpha+ rhythm modulates excitability, thereby resulting in variability in behavior and sensory representations despite identical input

Highly efficient adsorption of Cd(II) onto carboxylated camelthorn residues : applicability of three-parameter isotherm models, kinetics, and mechanism

A series of malonic acid treated camelthorn (MATC) sorbents were produced via the reaction of camelthorn biomass with malonic acid, and factors affecting the extent of modification were investigated, including malonic acid concentration, dehydration time and temperature. The optimum sorbent, by carboxylic acid content, was subsequently characterised for surface charge behaviour (pHPZC), surface chemical functionalities (FTIR), morphological structure (SEM), and available surface area. The sorbent was subsequently utilised for adsorption of Cd(II) ions from aqueous media, and parameters influencing adsorption at 30 °C, such as sorbent dose, initial solution pH, exposure time, metal concentration, were investigated. Isothermal analyses were performed using eight models, including two and three parameter equations, with appropriateness of fit assessed via non-linear regression analysis. The adsorption data indicated that the Langmuir model gives the most appropriate fit to experimental curves, with the models ordered as Langmuir >Hill > Toth >Sips > Jossens > Khan > Redlich-Peterson >Freundlich. The highest uptake (qmax) of 582.6 mg g-1 was determined at pH 6. The Freundlich constants, KF and n, at 30 °C were found to be 24.94 mg/g and 2.33, respectively. The value of n (2.33), being in the range 0–10, indicates that adsorption of Cd(II) ions onto malonic acid treated camelthorn biomass is favourable. Evaluation of a series of kinetic models, allowed elucidation of the adsorption mechanism, as a pseudo-second order model gave the most appropriate fit, indicating that chemisorption processes are involved. Cd(II) ions adsorption onto MATC is enhanced by a higher level of active surface sites but was show to be independent of surface area. The work presented here indicates that this sorbent offers effective adsorption potential for Cd(II) ions from water, with potential in wastewater processing

Effects of Expert Testimony and Interrogation Tactics on Perceptions of Confessions

Evidence obtained through the process of interrogation is frequently undermined by what can be perceived as overzealous interrogation tactics. Although the majority of psychologically oriented tactics are legally permissible, they nonetheless contribute to innocent suspects confessing to crimes they did not commit. The present study examined the effect of expert testimony and interrogation tactics on perceptions of a confession. 182 undergraduates read a transcript of a homicide trial that varied based on interrogation tactic: implicit threat of punishment (maximization) or leniency (minimization) and expert witness testimony (presence or absence of expert testimony). Analysis indicated that the type of interrogation tactic used in obtaining the confession affected participants\u27 perceptions of the coerciveness of the interrogation process

Attention deficit hyperactivity symptoms predict problematic mobile phone use

Attention-deficit-hyperactivity disorder (ADHD) is the most commonly diagnosed childhood disorder characterised by inattention, hyperactivity/impulsivity, or both. Some of the key traits of ADHD have previously been linked to addictive and problematic behaviours. The aim of the present study was to examine the relationship between problematic mobile phone use, smartphone addiction risk and ADHD symptoms in an adult population. A sample of 273 healthy adult volunteers completed the Adult ADHD Self-Report Scale (ASRS), the Mobile Phone Problem Usage Scale (MPPUS), and the Smartphone Addiction Scale (SAS). A significant positive correlation was found between the ASRS and both scales. More specifically, inattention symptoms and age predicted smartphone addiction risk and problematic mobile phone use. Our results suggest that there is a positive relationship between ADHD traits and problematic mobile phone use. In particular, younger adults with higher level of inattention symptoms could be at higher risk of developing smartphone addiction. The implication of our findings for theoretical frameworks of problematic mobile phone use and clinical practice are discussed