Computational Fractal-Based Neurosurgery.

Fractal geometry is a branch of mathematics used to characterize and quantify the geometrical complexity of natural objects, with many applications in different fields, including physics, astronomy, geology, meteorology, finances, social sciences, and computer graphics. In the biomedical sciences, the use of fractal parameters has allowed the introduction of novel morphometric parameters, which have been shown to be useful to characterize any biomedical images as well as any time series within different domains of applications. Specifically, in the neurosciences and neurosurgery, the use of the fractal dimension and other computationally inferred fractal parameters has offered robust morphometric quantitators to characterize the brain in its wholeness, from neurons to the cortical structure and connections, and introduced new prognostic, diagnostic, and eventually therapeutic markers of many diseases of neurosurgical interest, including brain tumors and cerebrovascular malformations, as summarized in this chapter.

The deubiquitinase function of ataxin-3 and its role in the pathogenesis of Machado-Joseph disease and other diseases.

Machado-Joseph disease (MJD) is a devastating and incurable neurodegenerative disease characterised by progressive ataxia, difficulty speaking and swallowing. Consequently, affected individuals ultimately become wheelchair dependent, require constant care, and face a shortened life expectancy. The monogenic cause of MJD is expansion of a trinucleotide (CAG) repeat region within the ATXN3 gene, which results in polyglutamine (polyQ) expansion within the resultant ataxin-3 protein.

Fractal Dimension Studies of the Brain Shape in Aging and Neurodegenerative Diseases.

The fractal dimension is a morphometric measure that has been used to investigate the changes of brain shape complexity in aging and neurodegenerative diseases. This chapter reviews fractal dimension studies in aging and neurodegenerative disorders in the literature. Research has shown that the fractal dimension of the left cerebral hemisphere increases until adolescence and then decreases with aging, while the fractal dimension of the right hemisphere continues to increase until adulthood.

Cyclin F can alter the turnover of TDP-43.

Previously, we demonstrated that the SCF complex directly mediates the poly-ubiquitylation of TDP-43, raising the question of whether cyclin F can be used to enhance the turnover of TDP-43. A hurdle to the use of cyclin F, however, is that the overexpression of cyclin F can lead to the initiation of cell death pathways. Accordingly, the aim of this study was to identify and evaluate a less toxic variant of cyclin F.

The E3 Ubiquitin Ligase SCF Cyclin F Promotes Sequestosome-1/p62 Insolubility and Foci Formation and is Dysregulated in ALS and FTD Pathogenesis.

Amyotrophic lateral sclerosis (ALS)- and frontotemporal dementia (FTD)-linked mutations in CCNF have been shown to cause dysregulation to protein homeostasis. CCNF encodes for cyclin F, which is part of the cyclin F-E3 ligase complex SCF known to ubiquitylate substrates for proteasomal degradation. In this study, we identified a function of cyclin F to regulate substrate solubility and show how cyclin F mechanistically underlies ALS and FTD disease pathogenesis.

Inter-Regional Proteomic Profiling of the Human Brain Using an Optimized Protein Extraction Method from Formalin-Fixed Tissue to Identify Signaling Pathways.

Proteomics offers vast potential for studying the molecular regulation of the human brain. Formalin fixation is a common method for preserving human tissue; however, it presents challenges for proteomic analysis. In this study, we compared the efficiency of two different protein-extraction buffers on three post-mortem, formalin-fixed human brains.

Cyclin F, Neurodegeneration, and the Pathogenesis of ALS/FTD.

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease and is characterized by the degeneration of upper and lower motor neurons of the brain and spinal cord. ALS is also linked clinically, genetically, and pathologically to a form of dementia known as frontotemporal dementia (FTD). Identifying gene mutations that cause ALS/FTD has provided valuable insight into the disease process.

TDP-43 is a ubiquitylation substrate of the SCF complex.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of upper and lower motor neurons in the brain and spinal cord. ALS and frontotemporal dementia (FTD) are overlapping diseases with shared pathological features. Affected neurons of people with ALS and FTD typically contain ubiquitin-immunoreactive inclusions, of which TDP-43 (Tar DNA-binding protein of 43 kDa) is a major component.

The converging roles of sequestosome-1/p62 in the molecular pathways of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Investigations into the pathogenetic mechanisms underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have provided significant insight into the disease. At the cellular level, ALS and FTD are classified as proteinopathies, which is motor neuron degeneration and death characterized by pathological protein aggregates or dysregulated proteostasis. At both the clinical and molecular level there are common signaling pathways dysregulated across the ALS and FTD spectrum (ALS/FTD).

Unbiased Label-Free Quantitative Proteomics of Cells Expressing Amyotrophic Lateral Sclerosis (ALS) Mutations in Reveals Activation of the Apoptosis Pathway: A Workflow to Screen Pathogenic Gene Mutations.

The past decade has seen a rapid acceleration in the discovery of new genetic causes of ALS, with more than 20 putative ALS-causing genes now cited. These genes encode proteins that cover a diverse range of molecular functions, including free radical scavenging (e.g.

ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ.

Previously, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Hallmark features of these diseases include the build-up of insoluble protein aggregates as well as the mislocalization of proteins such as transactive response DNA binding protein 43 kDa (TDP-43). In recent years, the dysregulation of SFPQ (splicing factor proline and glutamine rich) has also emerged as a pathological hallmark of ALS/FTD.

Proteomics Approaches for Biomarker and Drug Target Discovery in ALS and FTD.

Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are increasing in prevalence but lack targeted therapeutics. Although the pathological mechanisms behind these diseases remain unclear, both ALS and FTD are characterized pathologically by aberrant protein aggregation and inclusion formation within neurons, which correlates with neurodegeneration. Notably, aggregation of several key proteins, including TAR DNA binding protein of 43 kDa (TDP-43), superoxide dismutase 1 (SOD1), and tau, have been implicated in these diseases.

Maternal exposure to prostaglandin E modifies expression of Wnt genes in mouse brain - An autism connection.

Prostaglandin E (PGE) is a lipid signaling molecule important for brain development and function. Various genetic and environmental factors can influence the level of PGE and increase the risk of developing Autism Spectrum Disorder (ASD). We have previously shown that in neuronal cell lines and mouse brain, PGE can interfere with the Wnt canonical pathway, which is essential during early brain development.

Prostaglandin E2 facilitates subcellular translocation of the EP4 receptor in neuroectodermal NE-4C stem cells.

Prostaglandin E2 (PGE) is a lipid mediator released from the phospholipid membranes that mediates important physiological functions in the nervous system via activation of four EP receptors (EP1-4). There is growing evidence for the important role of the PGE/EP4 signaling in the nervous system. Previous studies in our lab show that the expression of the EP4 receptor is significantly higher during the neurogenesis period in the mouse.

Prostaglandin E2 elevates calcium in differentiated neuroectodermal stem cells.

Lipid mediator prostaglandin E2 (PGE2) is an endogenous signaling molecule that plays an important role during early development of the nervous system. Abnormalities in the PGE2 signaling pathway have been associated with neurodevelopmental disorders such as autism spectrum disorders. In this study we use ratiometric fura-2AM calcium imaging to show that higher levels of PGE2 elevate intracellular calcium levels in the cell soma and growth cones of differentiated neuroectodermal (NE-4C) stem cells.

Crooke's cell tumors of the pituitary.

Crooke's cell adenomas are a rare type of pituitary neoplasm. They produce adrenocorticotropic hormone causing Cushing's disease or may be endocrinologically silent. These tumors are usually invasive, may exhibit aggressive clinical behavior, and often recur with a low success of cure after reoperation and/or radiotherapy.

Post-Traumatic Brain Injury: Genetic Susceptibility to Outcome.

It is estimated that 2% of the population from industrialized countries live with lifelong disabilities resulting from traumatic brain injury (TBI) and roughly one in four adults are unable to return to work 1 year after injury because of physical or mental disabilities. TBI is a significant public health issue that causes substantial physical and economical repercussions for the individual and society. Electronic databases (PubMed, Web of Science, Google Scholar) were searched with the keywords traumatic brain injury, TBI, genes and TBI, TBI outcome, head injury.

Cranial sutures: a multidisciplinary review.

Introduction: Progress in cranial suture research is shaping our current understanding of the topic; however, emphasis has been placed on individual contributing components rather than the cranial sutural system as a whole. Improving our holistic view helps further guide clinicians who treat cranial sutural abnormalities as well as researchers who study them.

Materials And Methods: Information from anatomy, anthropology, surgery, and computed modeling was integrated to provide a perspective to interpret suture formation and variability within the cranial functional and structural system.