Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness

Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein 6, also known as neuropathy target esterase (NTE), which is the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also cause human spastic paraplegia characterized by motor neuron degeneration. Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in photo-receptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness.Foundation Fighting Blindness CanadaCanadian Institutes of Health ResearchNIHCharles University institutional programmesBIOCEV-Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University, from the European Regional Development FundMinistry of Health of the Czech RepublicGraduate School of Life Sciences (University of Wuerzburg)Government of Canada through Genome CanadaOntario Genomics InstituteGenome QuebecGenome British ColumbiaMcLaughlin CentreCharles Univ Prague, Inst Inherited Metab Disorders, Fac Med 1, Prague 12000 2, Czech RepublicMcGill Univ, Dept Human Genet, Fac Med, Montreal, PQ H3A 0G1, CanadaGenome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, CanadaClin Res Inst Montreal, Cellular Neurobiol Res Unit, Montreal, PQ H2W 1R7, CanadaMcGill Univ, Montreal, PQ H3A 0G4, CanadaMcGill Univ, Ctr Hlth, Montreal Childrens Hosp, McGill Ocular Genet Lab, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Ctr Hlth, Montreal Childrens Hosp, Dept Paediat Surg, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Ctr Hlth, Montreal Childrens Hosp, Dept Human Genet, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Ctr Hlth, Montreal Childrens Hosp, Dept Ophthalmol, Montreal, PQ H3H 1P3, CanadaUniv Alberta, Royal Alexandra Hosp, Dept Ophthalmol & Visual Sci, Edmonton, AB T5H 3V9, CanadaCharles Univ Prague, Inst Biol & Med Genet, Fac Med 1, Prague 12000 2, Czech RepublicBaylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USAUniversidade Federal de São Paulo, Dept Neurol, Div Gen Neurol, BR-04021001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, Ataxia Unit, BR-04021001 São Paulo, BrazilNewcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, EnglandUniversidade Federal de São Paulo, Dept Ophthalmol, BR-04021001 São Paulo, BrazilSo Gen Hosp, Dept Clin Genet, Glasgow G51 4TF, Lanark, ScotlandCardiff Univ, Sch Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, WalesHadassah Hebrew Univ Med Ctr, Dept Ophthalmol, IL-91120 Jerusalem, IsraelOregon Hlth & Sci Univ, Oregon Inst Occupat Hlth Sci, Portland, OR 97239 USAUniv Wurzburg, Lehrstuhl Neurobiol & Genet, D-97074 Wurzburg, GermanyUniv Montreal, Dept Med, Montreal, PQ H3T 1P1, CanadaMcGill Univ, Dept Anat & Cell Biol, Div Expt Med, Montreal, PQ H3A 2B2, CanadaUniversidade Federal de São Paulo, Dept Neurol, Div Gen Neurol, BR-04021001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, Ataxia Unit, BR-04021001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, BR-04021001 São Paulo, BrazilNIH: EY022356-01NIH: EY018571-05NIH: NS047663-09Charles University institutional programmes: PRVOUK-P24/LF1/3Charles University institutional programmes: UNCE 204011Charles University institutional programmes: SVV2013/266504BIOCEV-Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University, from the European Regional Development Fund: CZ.1.05/1.1.00/02.0109Ministry of Health of the Czech Republic: NT13116-4/2012Ministry of Health of the Czech Republic: NT14015-3/2013Ontario Genomics Institute: OGI-049Web of Scienc

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Spectral and spatial decomposition of lithospheric magnetic field models using spherical Slepian functions

Global magnetic field models are typically expressed as spherical-harmonic expansion coefficients. Slepian functions are linear combinations of spherical harmonics that produce new basis functions, which vanish approximately outside chosen geographical boundaries but also remain orthogonal within the spatial region of interest. Hence, they are suitable for decomposing spherical-harmonic models into portions that have significant magnetic field strength only in selected areas. Slepian functions are spatio-spectrally concentrated, balancing spatial bias and spectral leakage. Here, we employ them as a basis to decompose the global lithospheric magnetic field model MF7 up to degree and order 72, into two distinct regions. One of the resultant fields is concentrated within the ensemble of continental domains, and the other is localized over its complement, the oceans. Our procedure neatly divides the spectral power at each harmonic degree into two parts. The field over the continents dominates the overall crustal magnetic field, and each region has a distinct power-spectral signature. The oceanic power spectrum is approximately flat, while that of the continental region shows increasing power as the spherical-harmonic degree increases.We provide a further breakdown of the field into smaller, non-overlapping continental and oceanic regions, and speculate on the source of the variability in their spectral signatures

PI3Kδ and primary immunodeficiencies.

Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110δ) and PIK3R1 (which encodes p85α) that cause a combined immunodeficiency syndrome, referred to as activated PI3Kδ syndrome (APDS; also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3Kδ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3Kδ gleaned from these patients, as well as implications of these findings for clinical therapy

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis

Influence of gel bentonite on physiological indicators of the white laboratory mice.

The evaluation of the effect of lifelong usage of sodium form of gel bentonite on some physiological parameters of mice (body weight, feed and water intake, general condition, change in coordination of movements, state of wool, fertility and mortality) was performed on 110 white laboratory mice (BALB / c line). This experimental study was carried out in two replicates. To accomplish this task, the mice were divided into two groups: control – the animals were on a standard diet, and experimental – they used water with the addition of sodium form of bentonite gel (0.5-1%). It was found that prolonged intake of bentonite gel by laboratory animals neither led to an excessive increase in their weight (the weight gain of the experimental group did not differ statistically significantly from the control group, p≤0.05), nor did it cause acute or chronic intoxication. It is also shown that the constant use of bentonite has a positive effect on the organism of experimental mice, which is expressed in the decrease of animal mortality, increase of life expectancy and pronounced positive effect on fertility functions (increase in the number of offspring). Based on the obtained data it can be assumed that the continuous intake of bentonite by the animal organism is one of the factors of their microbiome improvement, which affects on a plenty of physiological functions, including animals reproduction. It is possible that smectite sorbents also enrich the body of mice by certain essential mineral elements (silicon, etc.) and has cytomucoprotective properties concerning the mucous membranes of the macroorganism

Influence of gel bentonite on physiological indicators of the white laboratory mice.

The evaluation of the effect of lifelong usage of sodium form of gel bentonite on some physiological parameters of mice (body weight, feed and water intake, general condition, change in coordination of movements, state of wool, fertility and mortality) was performed on 110 white laboratory mice (BALB / c line). This experimental study was carried out in two replicates. To accomplish this task, the mice were divided into two groups: control – the animals were on a standard diet, and experimental – they used water with the addition of sodium form of bentonite gel (0.5-1%). It was found that prolonged intake of bentonite gel by laboratory animals neither led to an excessive increase in their weight (the weight gain of the experimental group did not differ statistically significantly from the control group, p≤0.05), nor did it cause acute or chronic intoxication. It is also shown that the constant use of bentonite has a positive effect on the organism of experimental mice, which is expressed in the decrease of animal mortality, increase of life expectancy and pronounced positive effect on fertility functions (increase in the number of offspring). Based on the obtained data it can be assumed that the continuous intake of bentonite by the animal organism is one of the factors of their microbiome improvement, which affects on a plenty of physiological functions, including animals reproduction. It is possible that smectite sorbents also enrich the body of mice by certain essential mineral elements (silicon, etc.) and has cytomucoprotective properties concerning the mucous membranes of the macroorganism