Safety of an ethanolic extract of the dried biomass of the microalga Phaeodactylum tricornutum as a novel food pursuant to Regulation (EU) 2015/2283

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an ethanolic extract of the dried biomass of the microalga Phaeodactylum tricornutum as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an ethanolic extract of the dried biomass of the microalga P. tricornutum diluted in a medium-chain triglyceride oil carrier, with standardised fucoxanthin and tocopherol content. The main component of the NF is fat (78% on average), followed by crude protein (10% on average). The Panel is of the view that a consistent and safe production process has not been demonstrated. Additionally, the Panel considers that the information provided on the composition of the NF is not complete and may raise safety concerns. The applicant proposed to use the NF as a food supplement at the use level of 437 mg/day, with the target population being adults, excluding pregnant and breastfeeding women. There is no history of use of the NF or of its source, i.e. P. tricornutum. The Panel notes that the source of the NF, P. tricornutum, was not granted the qualified presumption of safety (QPS) status by the EFSA Panel on Biological Hazards (BIOHAZ), due to the lack of a safe history of use in the food chain and on its potential for production of bioactive compounds with toxic effects. There were no concerns regarding genotoxicity of the NF. In the 90-day study provided, a number of adverse effects were observed, some of them seen already at the lowest dose tested (750 mg/kg body weight (bw) day), which was identified by the Panel as the lowest-observed-adverse-effect-level (LOAEL). The potential phototoxicity of pheophorbide A and pyropheophorbide A in the NF was not addressed in this study. Although noting the uncertainties identified by the Panel regarding the analytical determination of these substances in the NF and the limitations in the publicly available toxicity data, a low margin of exposure (MoE) was calculated for these substances at the proposed use levels. The Panel concludes that the safety of the NF under the proposed uses and use levels has not been established

DHX9 Helicase promotes R-loop formation in cells with impaired RNA splicing

Unresolved R-loops can represent a threat to genome stability. Here the authors reveal that DHX9 helicase can promote R-loop formation in the absence of splicing factors SFPQ and SF3B3

An Anaerobic-Type α-Ketoglutarate Ferredoxin Oxidoreductase Completes the Oxidative Tricarboxylic Acid Cycle of Mycobacterium tuberculosis

Aerobic organisms have a tricarboxylic acid (TCA) cycle that is functionally distinct from those found in anaerobic organisms. Previous reports indicate that the aerobic pathogen Mycobacterium tuberculosis lacks detectable α-ketoglutarate (KG) dehydrogenase activity and drives a variant TCA cycle in which succinyl-CoA is replaced by succinic semialdehyde. Here, we show that M. tuberculosis expresses a CoA-dependent KG dehydrogenase activity, albeit one that is typically found in anaerobic bacteria. Unlike most enzymes of this family, the M. tuberculosis KG: ferredoxin oxidoreductase (KOR) is extremely stable under aerobic conditions. This activity is absent in a mutant strain deleted for genes encoding a previously uncharacterized oxidoreductase, and this strain is impaired for aerobic growth in the absence of sufficient amounts of CO2. Interestingly, inhibition of the glyoxylate shunt or exclusion of exogenous fatty acids alleviates this growth defect, indicating the presence of an alternate pathway that operates in the absence of β-oxidation. Simultaneous disruption of KOR and the first enzyme of the succinic semialdehyde pathway (KG decarboxylase; KGD) results in strict dependence upon the glyoxylate shunt for growth, demonstrating that KG decarboxylase is also functional in M. tuberculosis intermediary metabolism. These observations demonstrate that unlike most organisms M. tuberculosis utilizes two distinct TCA pathways from KG, one that functions concurrently with β-oxidation (KOR-dependent), and one that functions in the absence of β-oxidation (KGD-dependent). As these pathways are regulated by metabolic cues, we predict that their differential utilization provides an advantage for growth in different environments within the host

A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection

There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease- prepared siRNA) library, we isolate genes that control the recombination/endjoining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP

Rad3ATR Decorates Critical Chromosomal Domains with γH2A to Protect Genome Integrity during S-Phase in Fission Yeast

Schizosaccharomyces pombe Rad3 checkpoint kinase and its human ortholog ATR are essential for maintaining genome integrity in cells treated with genotoxins that damage DNA or arrest replication forks. Rad3 and ATR also function during unperturbed growth, although the events triggering their activation and their critical functions are largely unknown. Here, we use ChIP-on-chip analysis to map genomic loci decorated by phosphorylated histone H2A (γH2A), a Rad3 substrate that establishes a chromatin-based recruitment platform for Crb2 and Brc1 DNA repair/checkpoint proteins. Unexpectedly, γH2A marks a diverse array of genomic features during S-phase, including natural replication fork barriers and a fork breakage site, retrotransposons, heterochromatin in the centromeres and telomeres, and ribosomal RNA (rDNA) repeats. γH2A formation at the centromeres and telomeres is associated with heterochromatin establishment by Clr4 histone methyltransferase. We show that γH2A domains recruit Brc1, a factor involved in repair of damaged replication forks. Brc1 C-terminal BRCT domain binding to γH2A is crucial in the absence of Rqh1Sgs1, a RecQ DNA helicase required for rDNA maintenance whose human homologs are mutated in patients with Werner, Bloom, and Rothmund–Thomson syndromes that are characterized by cancer-predisposition or accelerated aging. We conclude that Rad3 phosphorylates histone H2A to mobilize Brc1 to critical genomic domains during S-phase, and this pathway functions in parallel with Rqh1 DNA helicase in maintaining genome integrity

Search for three-nucleon short-range correlations in light nuclei

We present new data probing short-range correlations (SRCs) in nuclei through the measurement of electron scattering off high-momentum nucleons in nuclei. The inclusive ^{4}He/^{3}He cross section ratio is observed to be both x and Q^{2} independent for 1.52, our data support the hypothesis that a previous claim of three-nucleon correlation dominance was an artifact caused by the limited resolution of the measurement. While 3N-SRCs appear to have an important contribution, our data show that isolating 3N-SRCs is significantly more complicated than for 2N-SRCs.United States. Department of Energy (Contract DE-AC05-06OR23177)United States. Department of Energy (Contract DE-AC02-06CH11357)United States. Department of Energy (Contract DE-FG02-96ER40950

Probing the Repulsive Core of the Nucleon-Nucleon Interaction via the 4He(e,e'pN) Triple-Coincidence Reaction

We studied simultaneously the 4He(e,e'p), 4He(e,e'pp), and 4He(e,e'pn) reactions at Q^2=2 [GeV/c]2 and x_B>1, for a (e,e'p) missing-momentum range of 400 to 830 MeV/c. The knocked-out proton was detected in coincidence with a proton or neutron recoiling almost back to back to the missing momentum, leaving the residual A=2 system at low excitation energy. These data were used to identify two-nucleon short-range correlated pairs and to deduce their isospin structure as a function of missing momentum in a region where the nucleon-nucleon force is expected to change from predominantly tensor to repulsive. Neutron-proton pairs dominate the high-momentum tail of the nucleon momentum distributions, but their abundance is reduced as the nucleon momentum increases beyond ~500 MeV/c. The extracted fraction of proton-proton pairs is small and almost independent of the missing momentum in the range we studied. Our data are compared with ab-initio calculations of two-nucleon momentum distributions in 4He.Comment: 6 pages, 2 figure

Völkisch und sozial? : Neonazistische Agitation gegen die neue EU-Freizügigkeit für Arbeitnehmerinnen

Wnt/β-catenin signalling pathway is crucial for the formation of many tissues and organs during development. In recent years, this pathway has also been found to regulate the biology of stem cells in the intestine and probably in other organs in adult life. Abnormal activation of Wnt/β-catenin signalling, which controls the expression of a high number of genes, is critical for the initiation and progression of most colorectal cancers. In line with this, the gene expression signature induced by activation of the Wnt/β-catenin pathway defines the intestinal stem cells present at the bottom of the crypts and also colon cancer stem cells. This supports the importance of inhibitors of the Wnt/β-catenin pathway as potential agents in colorectal cancer therapy. However, the complexity, wide activity in the organism modulating the biology of several cell types, and characteristics of this pathway have delayed the identification of suitable targets and so, the development of such inhibitors that are only now reaching the clinic.Peer reviewe