Altered White Matter Architecture in BDNF Met Carriers

Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin''s activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects'' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture.     

Assessment of Hepatic Detoxification Activity: Proposal of an Improved Variant of the 13C-Methacetin Breath Test

Breath tests based on the administration of a ¹³C-labeled drug and subsequent monitoring of ¹³CO₂ in the breath (quantified as DOB – delta over baseline) liberated from the drug during hepatic CPY-dependent detoxification are important tools in liver function diagnostics. The capability of such breath tests to reliably indicate hepatic CYP performance is limited by the fact that ¹³CO₂ is not exclusively exhaled but also exchanged with other compartments of the body. In order to assess this bias caused by variations of individual systemic CO₂ kinetics we administered intravenously the test drug ¹³C-methacetin to 25 clinically liver-healthy individuals and monitored progress curves of DOB and the plasma concentration of ¹³C-methacetin. Applying compartment modelling we estimated for each individual a set of kinetic parameters characterizing the time-dependent exchange of the drug and of CO₂ with the liver and non-hepatic body compartments. This analysis revealed that individual variations in the kinetics of CO₂ may account for up to 30% deviation of DOB curve parameters from their mean at otherwise identical ¹³C-methacetin metabolization rates. In order to correct for this bias we introduced a novel detoxification score which ideally should be assessed from the DOB curve of a 2-step test (“2DOB”) which is initialized with the injection of a standard dose of ¹³C-labeled bicarbonate (in order to provide information on the actual CO₂ status of the individual) followed by injection of the ¹³C-labeled test drug (the common procedure). Computer simulations suggest that the predictive power of the proposed 2DOB breath test to reliably quantity the CYP-specific hepatic detoxification activity should be significantly higher compared to the conventional breath test.     

Assessing “Dangerous Climate Change”: Required Reduction of Carbon Emissions to Protect Young People,Future Generations and Nature

We assess climate impacts of global warming using ongoing observations and paleoclimate data. We use Earth’s measured energy imbalance, paleoclimate data, and simple representations of the global carbon cycle and temperature to define emission reductions needed to stabilize climate and avoid potentially disastrous impacts on today’s young people, future generations, and nature. A cumulative industrial-era limit of ∼500 GtC fossil fuel emissions and 100 GtC storage in the biosphere and soil would keep climate close to the Holocene range to which humanity and other species are adapted. Cumulative emissions of ∼1000 GtC, sometimes associated with 2°C global warming, would spur “slow” feedbacks and eventual warming of 3–4°C with disastrous consequences. Rapid emissions reduction is required to restore Earth’s energy balance and avoid ocean heat uptake that would practically guarantee irreversible effects. Continuation of high fossil fuel emissions, given current knowledge of the consequences, would be an act of extraordinary witting intergenerational injustice. Responsible policymaking requires a rising price on carbon emissions that would preclude emissions from most remaining coal and unconventional fossil fuels and phase down emissions from conventional fossil fuels.     

Phenotypic Variants of Staphylococci and Their Underlying Population Distributions Following Exposure to Stress

This study investigated whether alterations in environmental conditions would induce the formation of small colony variant phenotypes (SCV) with associated changes in cell morphology and ultra-structure in S. aureus, s. epidermidis, and S. lugdunensis. Wild-type clinical isolates were exposed to low temperature (4°C), antibiotic stress (penicillin G and vancomycin; 0-10,000 µg mL^-1), pH stress (pH 3-9) and osmotic challenge (NaCl concentrations of 0-20%). Changes in cell diameter, cell-wall thickness, and population distribution changes (n ≥ 300) were assessed via scanning and transmission electron microscopy (SEM and TEM), and compared to control populations. Our analyses found that prolonged exposure to all treatments resulted in the subsequent formation of SCV phenotypes. Observed SCVs manifested as minute colonies with reduced haemolysis and pigmentation (NaCl, pH and 4°C treatments), or complete lack thereof (antibiotic treatments). SEM comparison analyses revealed significantly smaller cell sizes for SCV populations except in S. aureus and S. epidermidis 10% NaCl, and S. epidermidis 4°C (p<0.05). Shifts in population distribution patterns were also observed with distinct sub-populations of smaller cells appearing for S. epidermidis, and S. lugdunensis. TEM analyses revealed significantly thicker cell-walls in all treatments and species except S. lugdunensis exposed to 4°C. These findings suggest that staphylococci adapted to environmental stresses by altering their cell size and wall thickness which could represent the formation of altered phenotypes which facilitate survival under harsh conditions. The phenotypic response was governed by the type of prevailing environmental stress regime leading to appropriate alterations in ultra-structure and size, suggesting downstream changes in gene expression, the proteome, and metabolome.     

Chemical preservation of tail feathers from Anchiornis huxleyi,a theropod dinosaur from the Tiaojishan Formation (Upper Jurassic,China)

A panel of geochemical techniques is used here to investigate the taphonomy of fossil feathers preserved in association with the skeleton of the Jurassic theropod Anchiornis huxleyi. Extant feathers were analysed in parallel to test whether the soft tissues morphologically preserved in the fossil also exhibit a high degree of chemical preservation. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) indicate that clays and iron oxide pseudomorphs occur in the surrounding sediment and also reveal the preservation of melanosome-like microbodies in the fossil. Carbon gradient along a depth profile and co-occurrence of carbon and sulphur are shown in the fossil by elastic backscattering (EBS) and particle-induced x-ray emission (PIXE), which are promising techniques for the elemental analysis of fossil soft tissues. The molecular composition of modern and fossil soft tissues was assessed from micro-attenuated total reflectance fourier transform infrared spectroscopy (micro-ATR FTIR), solid-state ¹³C nuclear magnetic resonance (CP-MAS ¹³C NMR) and pyrolysis gas chromatography mass spectrometry in the presence of TMAH (TMAH-Py-GC-MS). Results indicate that the proteinaceous material that comprises the modern feathers is not present in the fossil feathers. The fossil feathers and the embedding sediment exhibit a highly aliphatic character. However, substantial differences exist between these samples, revealing that the organic matter of the fossil feathers is, at least partially, derived from original constituents of the feathers. Our results suggest that, despite the morphological preservation of Anchiornis feathers, original proteins, that is keratin, were probably not preserved in the 160-myr-old feathers.     

Resting Stages of Skeletonema marinoi Assimilate Nitrogen From the Ambient Environment Under Dark,Anoxic Conditions

The planktonic marine diatom Skeletonema marinoi forms resting stages, which can survive for decades buried in aphotic, anoxic sediments and resume growth when re-exposed to light, oxygen, and nutrients. The mechanisms by which they maintain cell viability during dormancy are poorly known. Here, we investigated cell-specific nitrogen (N) and carbon (C) assimilation and survival rate in resting stages of three S. marinoi strains. Resting stages were incubated with stable isotopes of dissolved inorganic N (DIN), in the form of ¹⁵N-ammonium (NH₄⁺) or -nitrate (NO₃⁻) and dissolved inorganic C (DIC) as ¹³C-bicarbonate (HCO₃⁻) under dark and anoxic conditions for 2 months. Particulate C and N concentration remained close to the Redfield ratio (6.6) during the experiment, indicating viable diatoms. However, survival varied between <0.1% and 47.6% among the three different S. marinoi strains, and overall survival was higher when NO₃⁻ was available. One strain did not survive in the NH₄⁺ treatment. Using secondary ion mass spectrometry (SIMS), we quantified assimilation of labeled DIC and DIN from the ambient environment within the resting stages. Dark fixation of DIC was insignificant across all strains. Significant assimilation of ¹⁵N-NO₃⁻ and ¹⁵N-NH₄⁺ occurred in all S. marinoi strains at rates that would double the nitrogenous biomass over 77–380 years depending on strain and treatment. Hence, resting stages of S. marinoi assimilate N from the ambient environment at slow rates during darkness and anoxia. This activity may explain their well-documented long survival and swift resumption of vegetative growth after dormancy in dark and anoxic sediments.     

Lotka–Volterra approximations for evolutionary trait-substitution processes

Journal of Mathematical Biology - A set of axioms is formulated characterizing ecologically plausible community dynamics. Using these axioms, it is proved that the transients following an invasion...     

A synthetic biology approach for the fabrication of functional (fluorescent magnetic) bioorganic–inorganic hybrid materials in sponge primmorphs

During evolution, sponges (Porifera) have honed the genetic toolbox and biosynthetic mechanisms for the fabrication of siliceous skeletal components (spicules). Spicules carry a protein scaffold embedded within biogenic silica (biosilica) and feature an amazing range of optical, structural, and mechanical properties. Thus, it is tempting to explore the low-energy synthetic pathways of spiculogenesis for the fabrication of innovative hybrid materials. In this synthetic biology approach, the uptake of multifunctional nonbiogenic nanoparticles (fluorescent, superparamagnetic) by spicule-forming cells of bioreactor-cultivated sponge primmorphs provides access to spiculogenesis. The ingested nanoparticles were detected within intracellular vesicles resembling silicasomes (silica-rich cellular compartments) and as cytosolic clusters where they lent primmorphs fluorescent/magnetic properties. During spiculogenesis, the nanoparticles initially formed an incomplete layer around juvenile, intracellular spicules. In the mature, extracellular spicules the nanoparticles were densely arranged as a surface layer that rendered the resulting composite fluorescent and magnetic. By branching off the conventional route of solid-state materials synthesis under harsh conditions, a new pathway has been opened to a versatile platform that allows adding functionalities to growing spicules as templates in living cells, using nonbiogenic nanoscale building blocks with multiple functionalities. The magnet-assisted alignment renders this composite with its fluorescent/magnetic properties potentially suitable for application in biooptoelectronics and microelectronics (e.g., microscale on-chip waveguides for applications of optical detection and sensing).