- Alpha-Synuclein Pathology and the Role of the Microbiota in Parkinson's Disease. [Review]
- FNFront Neurosci 2019; 13:369
- There is a principle in science, known as Occam's razor, that says the correct solution is usually the one with the simplest explanation. The microbiota-gut-brain axis, an interdependent series of co…
There is a principle in science, known as Occam's razor, that says the correct solution is usually the one with the simplest explanation. The microbiota-gut-brain axis, an interdependent series of communication loops between the enteric nervous system (ENS), the microbiota, the gut, and the brain, offers important insight into how changes in our gut affect distant organs like our brains. The inherent complexity of this axis with the crosstalk between the immune system, inflammatory states, and the thousands of bacteria, viral, and fungal species that together make up the microbiota make studying the interactions that govern this axis difficult and far from parsimonious. It is becoming increasingly clear that the microbiota is integral to this axis. Disruption of the healthy flora, a phenomenon collectively referred to as dysbiosis, has been implicated as a driver for several diseases such as irritable bowel syndrome, rheumatoid arthritis, obesity, diabetes, liver disease, and neurological disorders such as depression, anxiety, and Parkinson's disease (PD). Teasing apart these complex interactions as they pertain to PD is critical for our understanding of this debilitating disease, but more importantly, for the development of future treatments. So far, treatments have been unable to stop this neurodegenerative disease, succeeding only in briefly dampening symptoms and buying patients time before the inevitable loss of function ensues. Given that the 10 years prognosis for death or life-limiting disability with someone diagnosed with PD is upwards of 80%, there is a desperate need for curative treatments that go beyond symptom management. If PD does begin in the periphery with bidirectional communication between the microbiota and the immune system, as recent literature suggests, there is an exciting possibility that progression could be stopped before it reaches the brain. This systematic review assesses the current literature surrounding the role of the microbiota in the pathogenesis of alpha-synucleinopathies and explores the hypothesis that alpha-synuclein folding is modulated by the microbiota. Furthermore, we discuss how changes in the gut environment can lead to pathology and outline the implications that advances in understanding the interactions between host and microbiota will have on future research and the development of potential biomarkers.
- Occam's Razor. [Editorial]
- GWGround Water 2019; 57(3):349
- Diffusion-weighted Imaging of Prostate Cancer: Revisiting Occam's Razor. [Comment]
- RRadiology 2019; 291(2):398-399
- A Third Strike Against Perfect Phylogeny. [Journal Article]
- SBSyst Biol 2019 Feb 14
- Perfect phylogenies are fundamental in the study of evolutionary trees because they capture the situation when each evolutionary trait emerges only once in history; if such events are believed to be …
Perfect phylogenies are fundamental in the study of evolutionary trees because they capture the situation when each evolutionary trait emerges only once in history; if such events are believed to be rare, then by Occam's Razor such parsimonious trees are preferable as a hypothesis of evolution. A classical result states that 2-state characters permit a perfect phylogeny precisely if each subset of 2 characters permits one. More recently, it was shown that for 3-state characters the same property holds but for size-3 subsets. A long-standing open problem asked whether such a constant exists for each number of states. More precisely, it has been conjectured that for any fixed number of states $r$ there exists a constant $f(r)$ such that a set of $r$-state characters $C$ has a perfect phylogeny if and only if every subset of at most $f(r)$ characters has a perfect phylogeny. Informally, the conjecture states that checking fixed-size subsets of characters is enough to correctly determine whether input data permits a perfect phylogeny, irrespective of the number of characters in the input. In this article, we show that this conjecture is false. In particular, we show that for any constant $t$, there exists a set $C$ of $8$-state characters such that $C$ has no perfect phylogeny, but there exists a perfect phylogeny for every subset of at most $t$ characters. Moreover, there already exists a perfect phylogeny when ignoring just one of the characters, independent of which character you ignore. This negative result complements the two negative results ("strikes") of Bodlaender et al. (1992,2000). We reflect on the consequences of this third strike, pointing out that while it does close off some routes for efficient algorithm development, many others remain open.
- Presentation and evaluation of the zero-dimensional biofilm model 0DBFM. [Journal Article]
- WSWater Sci Technol 2019; 79(1):35-40
- A zero-dimensional biofilm model, i.e. 0DBFM, has been developed for dynamic simulation of moving bed bioreactors (MBBRs). This mini-review aims at presenting and evaluating 0DBFM. 0DBFM is presented…
A zero-dimensional biofilm model, i.e. 0DBFM, has been developed for dynamic simulation of moving bed bioreactors (MBBRs). This mini-review aims at presenting and evaluating 0DBFM. 0DBFM is presented in Petersen matrix format and is based on the activated sludge model ASM1, which is an explicit and quite complex model (eight processes, 13 state variables, and 19 parameters) that has found wide application in engineering practice. 0DBFM is thus based on existing knowledge in biological wastewater treatment. The ASM1 approach has been confirmed by respirometry since the resulting respirograms were successfully simulated with ASM1. 0DBFM distinguishes between attached and suspended biomass and incorporates attachment of suspended matter from the bulk liquid onto the biofilm and detachment of biofilm into the bulk liquid. Still, 0DBFM respects the golden rule of modelling, which says that 'models should be as simple as possible and as complex as needed' and resists Occam's razor. The practicability of 0DBFM has been shown on a pilot-scale plant since nine days of wastewater treatment were successfully simulated and effluent quality was dynamically predicted. Finally, 0DBFM can be inspiring and the applicability of 0DBFM to other biofilm systems can be tested.
- Attempts to strengthen and simplify the tumor vascular normalization strategy using tumor vessel normalization promoting nanomedicines. [Journal Article]
- BSBiomater Sci 2019 Feb 26; 7(3):1147-1160
- Tumor vascular normalization theory opened the door for the rational use of antiangiogenic agents and chemotherapeutics. However, efforts to seize the normalization window have constrained the develo…
Tumor vascular normalization theory opened the door for the rational use of antiangiogenic agents and chemotherapeutics. However, efforts to seize the normalization window have constrained the development of vascular normalization therapy in clinical applications owing to the lack of circulating biomarkers and the tedious dosage regimes. Applying "Occam's Razor" to therapeutic design inspired us to construct an effective and simple tumor vascular normalization prompting strategy. Herein, we developed tumor vessel normalization prompting nanomedicine lipid derivative conjugates (LGCs) made of anti-angiogenic agents with low molecular weight heparin (LMWH) and gemcitabine (Gem). This treatment exploits the complementary action of anti-vascular endothelial growth factor (VEGF) therapy and metronomic chemotherapy (MET) to strengthen the tumor vascular normalization effect. Furthermore, by loading cytotoxic drugs, such as paclitaxel (PTX), into the LGCs we constructed a "nano-community" to simultaneously restore the tumor vasculature and deliver the loaded drugs. Accordingly, improved drug delivery and therapeutic outcomes were achieved with no need to identify the precise time of the normalization window. Overall, our studies suggest that tumor vessel normalization therapy and nanomedicine design could be combined in one entity, using two waves of normalization strategies to achieve optimal chemo drug delivery into solid tumors.
- If extraordinary data are not first corroborated, we risk being led astray: Occam's razor does not support the existence of plasmid-prophage chimeras. Comment on 'Effects of cryptic prophage regions in a plasmid carrying a carbapenemase gene on survival against antibiotic stress'. [Letter]
- IJInt J Antimicrob Agents 2018 Dec 27
- When occam's razor can fail- active mycobacteria infection and lung cancer: A case of neuroendocrine lung cancer diagnosed in the setting of refractory mycobacterium avium-intracellulare. [Case Reports]
- CCClin Case Rep 2018; 6(11):2156-2159
- The link between Myobacterium avium-intracellulare and lung cancer remains underemphasized in literature. Our objective is to increase awareness of Myobacterium avium-intracellulare and coexisting lu…
The link between Myobacterium avium-intracellulare and lung cancer remains underemphasized in literature. Our objective is to increase awareness of Myobacterium avium-intracellulare and coexisting lung cancer and to emphasize the need in establishing prevalence and specific testing guidelines in this patient population.
- An Occam's razor approach to chemical hardness: lex parsimoniae. [Journal Article]
- JMJ Mol Model 2018 Nov 06; 24(12):332
- The term "chemical hardness" refers to the resistance to deformation of the electronic density of a system; the greater this resistance, the "harder" the system. Polarizability, a physical property, …
The term "chemical hardness" refers to the resistance to deformation of the electronic density of a system; the greater this resistance, the "harder" the system. Polarizability, a physical property, is an inverse measure of resistance to deformation and thus should be inversely related to hardness. This is indeed generally accepted. Hardness has been postulated to be the second derivative of a system's energy with respect to its number of electrons, despite the fact that this involves the differentiation of a noncontinuous function. This second derivative is typically approximated as the difference between the ionization energy I and the electron affinity A of the ground-state system, which results in ambiguity in that many molecules do not form stable negative ions. For atoms, the quantity I - A does vary approximately inversely with polarizability, but this is only because the electron affinity is usually relatively low and ionization energy is known to be inversely related to polarizability for atoms. However, molecular polarizability depends primarily upon volume, and so does not show an acceptable inverse correlation with I - A. Since both hardness and polarizability refer to the same property of a system-its resistance to deformation of the electronic density, we propose that the reciprocal of polarizability be taken to be a measure of hardness. We show that polarizabilities that are not known can be estimated quite accurately in terms of the average local ionization energies on the atomic or molecular surfaces and, for molecules, their volumes.
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- Liver transplantation for inferior vena cava leiomyosarcoma: from a Maslow's hammer to the Occam's razor. [Case Reports]
- BCBMJ Case Rep 2018 Sep 28; 2018
- Leiomyosarcoma (LMS) of primary vascular origin is a rare entity with only potentially curative option being complete surgical resection; despite which the prognosis remains dismal. Tumour recurrence…
Leiomyosarcoma (LMS) of primary vascular origin is a rare entity with only potentially curative option being complete surgical resection; despite which the prognosis remains dismal. Tumour recurrence is very common, and the benefits of adjuvant therapy are undefined. A 39-year-old woman presented with 6 months' history of abdominal pain, abdominal distension and pedal oedema. On evaluation, she was diagnosed to have chronic Budd-Chiari syndrome (BCS) secondary to a tumour arising from the inferior vena cava (IVC) on evaluation. Her liver decompensation included jaundice, gastrointestinal bleed and ascites. Following a detailed multidisciplinary team discussion, she underwent complete excision of the tumour along with a segment of the IVC with living donor liver transplantation. She remains disease-free 24 months following surgery. This is the first reported case of liver transplantation for IVC LMS causing chronic BCS.