Trophic signature of coral reef fish assemblages : towards a potential indicator of ecosystem disturbance

Face to the increasing anthropogenic disturbances that affect coral reef ecosystems, it becomes urgent to define appropriate ecological indicators for monitoring purposes. One useful approach is to search for a simplified description of the structure of biological communities that are highly diverse and complex on coral reefs. To this end, we propose to represent the trophic structure of coral reef fish assemblages by using fractional trophic levels assigned to each fish species. Fish abundance trophic spectra (i.e., the distributions of fish abundance per trophic level) were established for the fringing reefs of two bays located in the city of Noumea (New Caledonia). The comparison of these trophic spectra revealed a similar trophic structure in the two bays, in spite of contrasted levels of fish abundance due to habitat damages. The embayment degree was characterized by changes in the fish trophic structure, reflecting a decreasing influence of urban and industrial wastes discharged in the bottom of the bays. This case of study shows the interest of using fractional trophic levels for the description of highly diverse biological communities. The trophic level-based approach offers new prospects in the search for ecological indicators, by characterizing the structure of biological communities by trophic signatures which testify to the disturbance level affecting their environment

A Multi-scale Biophysical Approach to Develop Structure-Property Relationships in Oral Biofilms

Over the last 5-10 years, optical coherence tomography (OCT) and atomic force microscopy (AFM) have been individually applied to monitor the morphological and mechanical properties of various single-species biofilms respectively. This investigation looked to combine OCT and AFM as a multi-scale approach to understand the role sucrose concentration and age play in the morphological and mechanical properties of oral, microcosm biofilms, in-vitro. Biofilms with low (0.1% w/v) and high (5% w/v) sucrose concentrations were grown on hydroxyapatite (HAP) discs from pooled human saliva and incubated for 3 and 5 days. Distinct mesoscale features of biofilms such as regions of low and high extracellular polymeric substances (EPS) were identified through observations made by OCT. Mechanical analysis revealed increasing sucrose concentration decreased Young's modulus and increased cantilever adhesion (p < 0.0001), relative to the biofilm. Increasing age was found to decrease adhesion only (p < 0.0001). This was due to mechanical interactions between the indenter and the biofilm increasing as a function of increased EPS content, due to increasing sucrose. An expected decrease in EPS cantilever contact decreased adhesion due to bacteria proliferation with biofilm age. The application OCT and AFM revealed new structure-property relationships in oral biofilms, unattainable if the techniques were used independently

Deuterium-Stabilized (R)-Pioglitazone, PXL065, for Treatment of X-Linked Adrenoleukodystrophy (ALD)

Background and aims: X-linked Adrenoleukodystrophy (ALD) is a rare neurometabolic disorder caused by ABCD1- gene mutations, leading to Very-Long-Chain Fatty Acids (VLCFA; in particular C26:0) accumulation, inflammation, mitochondrial impairment and demyelination. PXL065, a clinical-stage deuterium-stabilized(R)-stereoisomer of pioglitazone, retains pioglitazone non-genomic actions but lacks PPARγ activity. As pioglitazone exhibits beneficial effects in ALD models and PXL065 may avoid PPARγ- related side effects, we investigated PXL065 effects of in preclinical models. Methods: Patient-derived fibroblasts and lymphocytes and Abcd1-KO mouse glial cells were exposed to PXL065 (5-10μM) and pioglitazone (10μM) for 7 days. VLCFA content was measured by mass spectrometry, selected gene expression by RT-qPCR, and mitochondrial function using a Seahorse Analyzer (after 72hr). PXL065 or pioglitazone (15mg/kg QD) were administered to 6-8-week or 13-month old Abcd1-KO mice for 8 and 12 weeks, respectively. VLCFA content (mass spectrometry), sciatic nerve axonal morphology (electronic microscopy), and locomotor function (open field test) were measured. Results: In patient and mouse glial cells, PXL065 and pioglitazone corrected C26:0, improved mitochondrial function, increased compensatory Abcd2-3 transporter gene expression, and decreased inflammatory gene expression. In Abcd1-KO mice, C26:0 levels were normalized in plasma and decreased in spinal cord (-55%, p\u3c0.01) and brain (-49%, p\u3c0.0001). Pioglitazone had no effect in spinal cord. Following PXL065 and pioglitazone treatment, abnormal axonal morphology (stellate-shaped cells) was improved but only PXL065 showed significantly improved locomotor test results. Conclusion: Despite reduced PPARγ activity, PXL065 showed substantial signs of efficacy and superior therapeutic potential vs. pioglitazone (in vivo) supporting clinical development for ALD. A Phase 2a study is planned in 2022

Topographic patterning of 3D collagen scaffolds: From surface to interface engineering

Topographic patterning provides a useful tool for regulating cell function, such as adhesion, proliferation, differentiation and contact-guidance. While current (e.g.lithographic) techniques allow precise control of topographic pattern (anisotropic vs isotropic) and scale (nano- vs micro-topography) 1, they are only applicable to 2D surface patterning, which compromises their relevance to 3D tissue engineering. In this study we developed a novel method for rapid fabrication of micro-textured 3D collagen scaffolds

An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer

KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. Furthermore, FOSL1 genetic inhibition is detrimental to both KRAS-driven tumour types. Mechanistically, FOSL1 links the KRAS oncogene to components of the mitotic machinery, a pathway previously postulated to function orthogonally to oncogenic KRAS. FOSL1 targets include AURKA, whose inhibition impairs viability of mutant KRAS cells. Lastly, combination of AURKA and MEK inhibitors induces a deleterious effect on mutant KRAS cells. Our findings unveil KRAS downstream effectors that provide opportunities to treat KRAS-driven cancers

Enhanced ocean carbon storage from anaerobic alkalinity generation in coastal sediments

The coastal ocean is a crucial link between land, the open ocean and the atmosphere. The shallowness of the water column permits close interactions between the sedimentary, aquatic and atmospheric compartments, which otherwise are decoupled at long time scales (≅ 1000 yr) in the open oceans. Despite the prominent role of the coastal oceans in absorbing atmospheric CO2 and transferring it into the deep oceans via the continental shelf pump, the underlying mechanisms remain only partly understood. Evaluating observations from the North Sea, a NW European shelf sea, we provide evidence that anaerobic degradation of organic matter, fuelled from land and ocean, generates total alkalinity (AT) and increases the CO2 buffer capacity of seawater. At both the basin wide and annual scales anaerobic AT generation in the North Sea's tidal mud flat area irreversibly facilitates 7–10%, or taking into consideration benthic denitrification in the North Sea, 20–25% of the North Sea's overall CO2 uptake. At the global scale, anaerobic AT generation could be accountable for as much as 60% of the uptake of CO2 in shelf and marginal seas, making this process, the anaerobic pump, a key player in the biological carbon pump. Under future high CO2 conditions oceanic CO2 storage via the anaerobic pump may even gain further relevance because of stimulated ocean productivity

Spin-Diffusion Lengths in Metals and Alloys, and Spin-Flipping at Metal/Metal Interfaces: an Experimentalist's Critical Review

In magnetoresistive (MR) studies of magnetic multilayers composed of combinations of ferromagnetic (F) and non-magnetic (N) metals, the magnetic moment (or related 'spin') of each conduction electron plays a crucial role, supplementary to that of its charge. While initial analyses of MR in such multilayers assumed that the direction of the spin of each electron stayed fixed as the electron transited the multilayer, we now know that this is true only in a certain limit. Generally, the spins 'flip' in a distance characteristic of the metal, its purity, and the temperature. They can also flip at F/N or N1/N2 interfaces. In this review we describe how to measure the lengths over which electron moments flip in pure metals and alloys, and the probability of spin-flipping at metallic interfaces. Spin-flipping within metals is described by a spin-diffusion length,l^M(sf), where the metal M = F or N. Spin-diffusion lengths are the characteristic lengths in the current-perpendicular-to-plane (CPP) and lateral non-local (LNL) geometries that we focus upon in this review. In certain simple cases, l^N(sf) sets the distance over which the CPP-MR and LNL-MR decrease as the N-layer thickness (CPP-MR) or N-film length (LNL) increases, and l^F(sf) does the same for increase of the CPP-MR with increasing F-layer thickness. Spin-flipping at M1/M2 interfaces can be described by a parameter, delta(M1/M2), which determines the spin-flipping probability, P = 1 - exp(-delta). Increasing delta(M1/M2) usually decreases the MR. We list measured values of these parameters and discuss the limitations on their determinations.Comment: Invited Review, to appear in J. Phys. Cond. Matter. 50 pages, 18 figures. The new version contains additional material and revisions to improve clarit

Evolution of Linear Absorption and Nonlinear Optical Properties in V-Shaped Ruthenium(II)-Based Chromophores

In this article, we describe a series of complexes with electron-rich cis-{Ru^(II)(NH_3)_4}^(2+) centers coordinated to two pyridyl ligands bearing N-methyl/arylpyridinium electron-acceptor groups. These V-shaped dipolar species are new, extended members of a class of chromophores first reported by us (Coe, B. J. et al. J. Am. Chem. Soc. 2005, 127, 4845−4859). They have been isolated as their PF_6− salts and characterized by using various techniques including ^1H NMR and electronic absorption spectroscopies and cyclic voltammetry. Reversible Ru^(III/II) waves show that the new complexes are potentially redox-switchable chromophores. Single crystal X-ray structures have been obtained for four complex salts; three of these crystallize noncentrosymmetrically, but with the individual molecular dipoles aligned largely antiparallel. Very large molecular first hyperpolarizabilities β have been determined by using hyper-Rayleigh scattering (HRS) with an 800 nm laser and also via Stark (electroabsorption) spectroscopic studies on the intense, visible d → π^* metal-to-ligand charge-transfer (MLCT) and π → π^* intraligand charge-transfer (ILCT) bands. The latter measurements afford total nonresonant β_0 responses as high as ca. 600 × 10^(−30) esu. These pseudo-C_(2v) chromophores show two substantial components of the β tensor, β_(zzz) and β_(zyy), although the relative significance of these varies with the physical method applied. According to HRS, β_(zzz) dominates in all cases, whereas the Stark analyses indicate that β_(zyy) is dominant in the shorter chromophores, but β_(zzz) and β_(zyy) are similar for the extended species. In contrast, finite field calculations predict that β_(zyy) is always the major component. Time-dependent density functional theory calculations predict increasing ILCT character for the nominally MLCT transitions and accompanying blue-shifts of the visible absorptions, as the ligand π-systems are extended. Such unusual behavior has also been observed with related 1D complexes (Coe, B. J. et al. J. Am. Chem. Soc. 2004, 126, 3880−3891)