Biological Sciences

Search by keywords:
Total Articles 28 - 36 of 13510 | |

easibility of Applying Helper-Dependent Adenoviral Vectors for Cancer Immunotherapy

Author(s): Lisa M. Farzad -- Masataka Suzuki
Journal: Biomedicines
Publisher:
Abstract
| Pages: 110-131
Adenoviruses (Ads) infect a broad range of tissue types, and derived vectors have been extensively used for gene therapy. Helper-dependent Ad vectors (HDAds), devoid of viral coding sequences, allow for insertion of large or multiple transgenes in a single vector and have been preclinically used for the study of genetic disorders. However, the clinical application of Ad vectors including HDAds for genetic disorders has been hampered by an acute toxic response. This characteristic, while disadvantageous for gene replacement therapy, could be strategically advantageous for the activation of an immune response if HDAds were used as an adjunct treatment in cancer. Cancer treatments including immunotherapy are frequently limited by the inhibitory environment produced by both tumors and their stroma, each of which express numerous inhibitory molecules. Hence, multiple inhibitory mechanisms must be overcome for development of anti-tumor immunity. The large coding capacity of HDAds can accommodate multiple immune modulating transgenes that could produce a combined effect to overcome tumor-derived inhibition and ensure intratumoral effector T-cell proliferation and function. In this review, we discuss the potential advantages of HDAds to cancer immunotherapy based on potent host immune responses to Ads.

Towards Effective Non-Invasive Brain-Computer Interfaces Dedicated to Gait Rehabilitation Systems

Author(s):Thierry Castermans -- Matthieu Duvinage -- Guy Cheron -- Thierry Dutoit
Journal: Brain Sciences
Publisher:
Abstract
| Pages: 1-48
In the last few years, significant progress has been made in the field of walk rehabilitation. Motor cortex signals in bipedal monkeys have been interpreted to predict walk kinematics. Epidural electrical stimulation in rats and in one young paraplegic has been realized to partially restore motor control after spinal cord injury. However, these experimental trials are far from being applicable to all patients suffering from motor impairments. Therefore, it is thought that more simple rehabilitation systems are desirable in the meanwhile. The goal of this review is to describe and summarize the progress made in the development of non-invasive brain-computer interfaces dedicated to motor rehabilitation systems. In the first part, the main principles of human locomotion control are presented. The paper then focuses on the mechanisms of supra-spinal centers active during gait, including results from electroencephalography, functional brain imaging technologies [near-infrared spectroscopy (NIRS), functional magnetic resonance imaging (fMRI), positron-emission tomography (PET), single-photon emission-computed tomography (SPECT)] and invasive studies. The first brain-computer interface (BCI) applications to gait rehabilitation are then presented, with a discussion about the different strategies developed in the field. The challenges to raise for future systems are identified and discussed. Finally, we present some proposals to address these challenges, in order to contribute to the improvement of BCI for gait rehabilitation.

Toward a New Application of Real-Time Electrophysiology: Online Optimization of Cognitive Neurosciences Hypothesis Testing

Author(s):Gaëtan Sanchez -- Jean Daunizeau -- Emmanuel Maby -- Olivier Bertrand -- Aline Bompas -- Jérémie Mattout
Journal: Brain Sciences
Publisher:
Abstract
| Pages: 49-72
Brain-computer interfaces (BCIs) mostly rely on electrophysiological brain signals. Methodological and technical progress has largely solved the challenge of processing these signals online. The main issue that remains, however, is the identification of a reliable mapping between electrophysiological measures and relevant states of mind. This is why BCIs are highly dependent upon advances in cognitive neuroscience and neuroimaging research. Recently, psychological theories became more biologically plausible, leading to more realistic generative models of psychophysiological observations. Such complex interpretations of empirical data call for efficient and robust computational approaches that can deal with statistical model comparison, such as approximate Bayesian inference schemes. Importantly, the latter enable the optimization of a model selection error rate with respect to experimental control variables, yielding maximally powerful designs. In this paper, we use a Bayesian decision theoretic approach to cast model comparison in an online adaptive design optimization procedure. We show how to maximize design efficiency for individual healthy subjects or patients. Using simulated data, we demonstrate the face- and construct-validity of this approach and illustrate its extension to electrophysiology and multiple hypothesis testing based on recent psychophysiological models of perception. Finally, we discuss its implications for basic neuroscience and BCI itself.

The Neurotoxicity of Nitrous Oxide: The Facts and “Putative” Mechanisms

Author(s):Sinead Savage -- Daqing Ma
Journal: Brain Sciences
Publisher:
Abstract
| Pages: 73-90
Nitrous oxide is a widely used analgesic agent, used also in combination with anaesthetics during surgery. Recent research has raised concerns about possible neurotoxicity of nitrous oxide, particularly in the developing brain. Nitrous oxide is an N-methyl-d-aspartate (NMDA)-antagonist drug, similar in nature to ketamine, another anaesthetic agent. It has been linked to post-operative cardiovascular problems in clinical studies. It is also widely known that exposure to nitrous oxide during surgery results in elevated homocysteine levels in many patients, but very little work has investigated the long term effect of these increased homocysteine levels. Now research in rodent models has found that homocysteine can be linked to neuronal death and possibly even cognitive deficits. This review aims to examine the current knowledge of mechanisms of action of nitrous oxide, and to describe some pathways by which it may have neurotoxic effects.

Monomeric, Oligomeric and Polymeric Proteins in Huntington Disease and Other Diseases of Polyglutamine Expansion

Author(s):Guylaine Hoffner -- Philippe Djian
Journal: Brain Sciences
Publisher:
Abstract
| Pages: 91-122
Huntington disease and other diseases of polyglutamine expansion are each caused by a different protein bearing an excessively long polyglutamine sequence and are associated with neuronal death. Although these diseases affect largely different brain regions, they all share a number of characteristics, and, therefore, are likely to possess a common mechanism. In all of the diseases, the causative protein is proteolyzed, becomes abnormally folded and accumulates in oligomers and larger aggregates. The aggregated and possibly the monomeric expanded polyglutamine are likely to play a critical role in the pathogenesis and there is increasing evidence that the secondary structure of the protein influences its toxicity. We describe here, with special attention to huntingtin, the mechanisms of polyglutamine aggregation and the modulation of aggregation by the sequences flanking the polyglutamine. We give a comprehensive picture of the characteristics of monomeric and aggregated polyglutamine, including morphology, composition, seeding ability, secondary structure, and toxicity. The structural heterogeneity of aggregated polyglutamine may explain why polyglutamine-containing aggregates could paradoxically be either toxic or neuroprotective.

Acknowledgement to Reviewers of Brain Sciences in 2013

Author(s):Brain Sciences Editorial Office
Journal: Brain Sciences
Publisher:
Abstract
| Pages: 123-124
The editors of Brain Sciences would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2013. [...]

Gene Expression Profiling during Pregnancy in Rat Brain Tissue

Author(s): Phyllis E. Mann
Journal: Brain Sciences
Publisher:
Abstract
| Pages: 125-135
The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array) was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1) whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, andNpy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

Anaesthetics-Induced Neurotoxicity in Developing Brain: An Update on Preclinical Evidence

Author(s):Zhaowei Zhou -- Daqing Ma
Journal: Brain Sciences
Publisher:
Abstract
| Pages: 136-149
Every year millions of young people are treated with anaesthetic agents for surgery and sedation in a seemingly safe manner. However, growing and convincing preclinical evidence in rodents and nonhuman primates, together with recent epidemiological observations, suggest that exposure to anaesthetics in common clinical use can be neurotoxic to the developing brain and lead to long-term neurological sequelae. These findings have seriously questioned the safe use of general anaesthetics in obstetric and paediatric patients. The mechanisms and human applicability of anaesthetic neurotoxicity and neuroprotection have remained under intense investigation over the past decade. Ongoing pre-clinical investigation may have significant impact on clinical practice in the near future. This review represents recent developments in this rapidly emerging field. The aim is to summarise recently available laboratory data, especially those being published after 2010, in the field of anaesthetics-induced neurotoxicity and its impact on cognitive function. In addition, we will discuss recent findings in mechanisms of early-life anaesthetics-induced neurotoxicity, the role of human stem cell-derived models in detecting such toxicity, and new potential alleviating strategies.

Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes

Author(s):Dante Picchioni -- R. Michelle Reith -- Jeffrey L. Nadel -- Carolyn B. Smith
Journal: Brain Sciences
Publisher:
Abstract
| Pages: 150-201
Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders.
Page:12345678910Next