1. Exploring synthetic lethality of mitochondrial pyruvate carrier knockout cells. 2. MPC1-like: a novel mitochondrial pyruvate carrier subunit

First, we studied the synthetic lethality of mitochondrial pyruvate carrier (MPC) knockout cells. Selective transport of pyruvate across the inner mitochondrial membrane (IMM) by the MPC is a fundamental step that couples cytosolic and mitochondrial metabolism. MPC is unfunctional in many tumors, participating in the metabolic shift that sustains tumorigenesis, and thus represents a potential target for synthetic lethal interventions specific to cancer cells. Here we report the development of cellular models for systematic investigation of both genetic and chemical synthetic lethal partners of MPC. Second, we report for the first time a highly specific expression pattern of a novel placental mammal-specific MPC subunit termed MPC1-like (MPC1L). We show that MPC1L is localized almost exclusively in testis and more specifically in post-meiotic spermatids and sperm cells. This is in marked contrast to MPC1/MPC2 which are ubiquitously expressed throughout the organism

Unmodified foraminiferal raw eDNA data in form of 'reads' with ASV, OTU and taxonomic assignations from sediment surface samples at stations REF, IF20-12, IF20-10, IF20-18, IF20-01 and IF20-04

The eDNA analysis was done using a DNeasy® PowerLyzer PowerSoil Kit (QIAGEN), processed using the DADA2 pipeline and the taxonomic assignations were estimated using a sequence bank at ID-Gene ecodiagnostics lab in Geneva Switzerland

MPC1-like Is a Placental Mammal-specific Mitochondrial Pyruvate Carrier Subunit Expressed in Postmeiotic Male Germ Cells

Selective transport of pyruvate across the inner mitochondrial membrane by the mitochondrial pyruvate carrier (MPC) is a fundamental step that couples cytosolic and mitochondrial metabolism. The recent molecular identification of the MPC complex has revealed two interacting subunits, MPC1 and MPC2. Although in yeast, an additional subunit, MPC3, can functionally replace MPC2, no alternative MPC subunits have been described in higher eukaryotes. Here, we report for the first time the existence of a novel MPC subunit termed MPC1-like (MPC1L), which is present uniquely in placental mammals. MPC1L shares high sequence, structural, and topological homology with MPC1. In addition, we provide several lines of evidence to show that MPC1L is functionally equivalent to MPC1: 1) when co-expressed with MPC2, it rescues pyruvate import in a MPC-deleted yeast strain; 2) in mammalian cells, it can associate with MPC2 to form a functional carrier as assessed by bioluminescence resonance energy transfer; 3) in MPC1 depleted mouse embryonic fibroblasts, MPC1L rescues the loss of pyruvate-driven respiration and stabilizes MPC2 expression; and 4) MPC1- and MPC1L-mediated pyruvate imports show similar efficiency. However, we show that MPC1L has a highly specific expression pattern and is localized almost exclusively in testis and more specifically in postmeiotic spermatids and sperm cells. This is in marked contrast to MPC1/MPC2, which are ubiquitously expressed throughout the organism. To date, the biological importance of this alternative MPC complex during spermatogenesis in placental mammals remains unknown. Nevertheless, these findings open up new avenues for investigating the structure-function relationship within the MPC complex

Multi-marker eDNA metabarcoding survey to assess the environmental impact of three offshore gas platforms in the North Adriatic Sea (Italy)

The environmental DNA (eDNA) metabarcoding represents a new promising tool for biomonitoring and environmental impact assessment. One of the main advantages of eDNA metabarcoding, compared to the traditional morphotaxonomy-based methods, is to provide a more holistic biodiversity information that includes inconspicuous morphologically non-identifiable taxa. Here, we use eDNA metabarcoding to survey marine biodiversity in the vicinity of the three offshore gas platforms in North Adriatic Sea (Italy). We isolated eDNA from 576 water and sediment samples collected at 32 sampling sites situated along four axes at increasing distances from the gas platforms. We obtained about 46 million eDNA sequences for 5 markers from nuclear 18S V1V2, 18S V4, 18S 37F and mitochondrial 16S and COI genes that cover a wide diversity of benthic and planktonic eukaryotes. Our results showed some impact of platform activities on benthic and pelagic communities at very close distance (<50 m), while communities for intermediate (125 m, 250 m, 500 m) and reference (1000 m, 2000 m) sites did not show any particular biodiversity changes that could be related to platforms activities. The most significant community change along the distance gradient was obtained with the 18S V1V2 marker targeting benthic eukaryotes, even though other markers showed similar trends, but to a lesser extent. These results were congruent with the AMBI index inferred from the eDNA sequences assigned to benthic macrofauna. We finally explored the relation between various physicochemical parameters, including hydrocarbons, on benthic community in the case of one of the platforms. Our results showed that these communities were not significantly impacted by most of hydrocarbons, but rather by macro-elements and sediment texture

Environmental genomics for benthic monitoring of North Sea oil and gas offshore platforms

During the last decade, considerable efforts have been undertaken to achieve a “good ecological status” of European coastal waters and ensuring the development of methodological standards for the evaluation of this status. However, the current routine biomonitoring implicates time-consuming and costly manual sorting and morphological identification of benthic macrofauna. In our study, we tested the performance of environmental DNA metabarcoding targeting microbial communities and meiofauna as an alternative to traditional macrofauna-based monitoring. We focused on environmental impact assessment of offshore oil and gas industry. We used three genetic markers (18S V1V2, 18S V9 and COI) to assess the environmental pressures induced by the platforms. All markers showed patterns of alpha and beta diversity consistent with morphology-based macrofauna analyses, significantly changing along distance gradients from the platforms. The impact of the operational discharges was also detected by the variation of biotic indices values, AMBI index showing the best correlation between morphological and eDNA datasets. Finally, the sediment physicochemical parameters were used to build a local de novo pressure index that served as benchmark to test the potential of a taxonomy-free approach. Our study demonstrates that metabarcoding approach outperforms morphology-based approach and can be used as a cost and time-saving alternative solution to the traditional morphology-based monitoring in order to monitor more efficiently the impact of industrial activities on marine biodiversity

Video processing acceleration using reconfigurable logic and graphics processors

A vexing question is `which architecture will prevail as the core feature of the next state of the art video processing system?' This thesis examines the substitutive and collaborative use of the two alternatives of the reconfigurable logic and graphics processor architectures. A structured approach to executing architecture comparison is presented - this includes a proposed `Three Axes of Algorithm Characterisation' scheme and a formulation of perfor- mance drivers. The approach is an appealing platform for clearly defining the problem, assumptions and results of a comparison. In this work it is used to resolve the advanta- geous factors of the graphics processor and reconfigurable logic for video processing, and the conditions determining which one is superior. The comparison results prompt the exploration of the customisable options for the graphics processor architecture. To clearly define the architectural design space, the graphics processor is first identifed as part of a wider scope of homogeneous multi-processing element (HoMPE) architectures. A novel exploration tool is described which is suited to the investigation of the customisable op- tions of HoMPE architectures. The tool adopts a systematic exploration approach and a high-level parameterisable system model, and is used to explore pre- and post-fabrication customisable options for the graphics processor. A positive result of the exploration is the proposal of a reconfigurable engine for data access (REDA) to optimise graphics processor performance for video processing-specific memory access patterns. REDA demonstrates the viability of the use of reconfigurable logic as collaborative `glue logic' in the graphics processor architecture.EThOS - Electronic Theses Online ServiceDonal Morphy and Engineering and Physical Sciences Research CouncilGBUnited Kingdo

Assessment of the ecological quality status of the Sepetiba Bay (SE Brazil): When metabarcoding meets morphology on foraminifera

In recent years, the region surrounding Sepetiba Bay (SB; SE Brazil) has become a hub of intense urban expansion and economic exploitation in response to ore transport and industrial and port activities. As a result, contaminants have been introduced into the bay, leading to an overall worsening of the environmental quality. The present work applies for the first time a foraminiferal morphology-based approach (M) and eDNA-based metabarcoding sequencing (G), along with geochemical data to assess the ecological quality status (EcoQS) in the SB. Principal component analysis shows that the eDNA and morphospecies diversity as well as most of the taxa relative abundance decline in response to the environmental stress (ES) gradient related to total organic carbon (TOC) and metal pollution. Based on ecological indices, Exp(H'bc) (G), Exp(H'bc) (M), foraminifera ATZI marine biotic index (Foram-AMBI), Foram Stress Index (FSI), and geochemical indices (TOC and Potential Ecological Risk Index), the lowest values of EcoQS (i.e., bad to moderate) are inferred in the innermost part of the SB. Despite minor discrepancies among the six EcoQS indices, an agreement has been found for 63% of the stations. To improve the agreement between the ecological indices, it is necessary to fill the gap in species ecology; information on the ecology of many species is still unknown. This work reinforces the importance of molecular analysis and morphological methods in environmental impact studies and confirms the reliability of foraminiferal metabarcoding in EcoQS assessment. This is the first study evaluating the EcoQS in the South Atlantic by using combined foraminiferal eDNA metabarcoding with morphological data

Treatment of Atrial Fibrillation in Patients with Dementia : A Cohort Study from the Swedish Dementia Registry

BACKGROUND: Patients with dementia might have higher risk for hemorrhagic complications with anticoagulant therapy prescribed for atrial fibrillation (AF). OBJECTIVE: This study assesses the risks and benefits of warfarin, antiplatelets, and no treatment in patients with dementia and AF. METHODS: Of 49,792 patients registered in the Swedish Dementia Registry 2007-2014, 8,096 (16%) had a previous diagnosis of AF. Cox proportional hazards models were used to calculate the risk for ischemic stroke (IS), nontraumatic intracranial hemorrhage, any-cause hemorrhage, and death. RESULTS: Out of the 8,096 dementia patients with AF, 2,143 (26%) received warfarin treatment, 2,975 (37%) antiplatelet treatment, and 2,978 (37%) had no antithrombotic treatment at the time of dementia diagnosis. Patients on warfarin had fewer IS than those without treatment (5.2% versus 8.7%; p &lt; 0.001) with no differences compared to antiplatelets. In adjusted analyses, warfarin was associated with a lower risk for IS (HR 0.76, CI 0.59-0.98), while antiplatelets were associated with increased risk (HR 1.25, CI 1.01-1.54) compared to no treatment. For any-cause hemorrhage, there was a higher risk with warfarin (HR 1.28, CI 1.03-1.59) compared to antiplatelets. Warfarin and antiplatelets were associated with a lower risk for death compared to no treatment. CONCLUSIONS: Warfarin treatment in Swedish patients with dementia is associated with lower risk of IS and mortality, and a small increase in any-cause hemorrhage. This study supports the use of warfarin in appropriate cases in patients with dementia. The low percentage of patients on warfarin treatment indicates that further gains in stroke prevention are possible

Benthic foraminiferal metabarcoding and morphology-based assessment around three offshore gas platforms: Congruence and complementarity

Since the 1960 s, there has been a rapid expansion of drilling activities in the central and northern Adriatic Sea to meet the increasing global energy demand. The discharges of organic and inorganic pollutants, as well as the alteration of the sediment substrate, are among the main impacts associated with these activities. In the present study, we evaluate the response of benthic foraminifera to the activities of three gas platforms in the northwestern Adriatic Sea, with a special focus on the Armida A platform for which extensive geochemical data (organic matter, trace elements, polycyclic aromatic hydrocarbons, other hydrocarbons, and volatile organic compounds) are available. The response to disturbance is assessed by analyzing the foraminiferal diversity using the traditional morphology-based approach and by 18S rDNA-based metabarcoding. The two methods give congruent results, showing relatively lower foraminiferal diversity and higher dominance values at stations closer to the platforms (<50 m). The taxonomic compositions of the morphological and metabarcoding datasets are very different, the latter being dominated by monothalamous, mainly soft-walled species. However, compositional changes consistently occur at 50 m from the platform and can be related to variations in sediment grain-size variation and higher concentrations of Ni, Zn, Ba, hydrocarbons and total organic carbon. Additionally, several morphospecies and Molecular Operational Taxonomic Units (MOTUs) show strong correlations with distance from the platform and with environmental parameters extracted from BIOENV analysis. Some of these MOTUs have the potential to become new bioindicators, complementing the assemblage of hard-shelled foraminiferal species detected through microscopic analyses. The congruence and complementarity between metabarcoding and morphological approaches support the application of foraminiferal metabarcoding in routine biomonitoring surveys as a reliable, time- and cost-effective methodology to assess the environmental impacts of marine industries

Expanding ecological assessment by integrating microorganisms into routine freshwater biomonitoring

Bioindication has become an indispensable part of water quality monitoring in most countries of the world, with the presence and abundance of bioindicator taxa, mostly multicellular eukaryotes, used for biotic indices. In contrast, microbes (bacteria, archaea and protists) are seldom used as bioindicators in routine assessments, although they have been recognized for their importance in environmental processes. Recently, the use of molecular methods has revealed unexpected diversity within known functional groups and novel metabolic pathways that are particularly important in energy and nutrient cycling. In various habitats, microbial communities respond to eutrophication, metals, and natural or anthropogenic organic pollutants through changes in diversity and function. In this review, we evaluated the common trends in these changes, documenting that they have value as bioindicators and can be used not only for monitoring but also for improving our understanding of the major processes in lotic and lentic environments. Current knowledge provides a solid foundation for exploiting microbial taxa, community structures and diversity, as well as functional genes, in novel monitoring programs. These microbial community measures can also be combined into biotic indices, improving the resolution of individual bioindicators. Here, we assess particular molecular approaches complemented by advanced bioinformatic analysis, as these are the most promising with respect to detailed bioindication value. We conclude that microbial community dynamics are a missing link important for our understanding of rapid changes in the structure and function of aquatic ecosystems, and should be addressed in the future environmental monitoring of freshwater ecosystems