Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation.

Unlabelled: The fission yeast regulon genes , , and -encoding a cell surface-associated acid phosphatase (Pho1), a plasma membrane inorganic phosphate transporter (Pho84), and a plasma membrane glycerophosphocholine transporter (Tgp1)-are strongly upregulated in response to acute phosphate starvation, as are the and genes that encode putative 5'-nucleotidase paralogs of the binuclear metallophosphoesterase enzyme superfamily. Via proteomic analysis of the medium harvested from phosphate-replete and phosphate-starved fission yeast, we define a starvation secretome that includes SPBPB2B2.06c (renamed Efn1, for xtracellular ive-prime ucleotidase), SPAC1039.

Safety, pharmacokinetics, and pharmacodynamics of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in uncomplicated urinary tract infections due to Escherichia coli (ELIMINATE): the randomised, open-label, first part of a two-part phase 2 trial.

Background: The rate of antibiotic resistance continues to grow, outpacing small-molecule-drug development efforts. Novel therapies are needed to combat this growing threat, particularly for the treatment of urinary tract infections (UTIs), which are one of the largest contributors to antibiotic use and associated antibiotic resistance. LBP-EC01 is a novel, genetically enhanced, six-bacteriophage cocktail developed by Locus Biosciences (Morrisville, NC, USA) to address UTIs caused by Escherichia coli, regardless of antibiotic resistance status.

Activities and genetic interactions of fission yeast Aps1, a Nudix-type inositol pyrophosphatase and inorganic polyphosphatase.

Unlabelled: Inositol pyrophosphate 1,5-IP regulates expression of a fission yeast phosphate homeostasis regulon, comprising phosphate acquisition genes , , and , via its action as an agonist of precocious termination of transcription of the upstream lncRNAs that repress mRNA synthesis. 1,5-IP levels are dictated by a balance between the Asp1 N-terminal kinase domain that converts 5-IP to 1,5-IP and three inositol pyrophosphatases-the Asp1 C-terminal domain (a histidine acid phosphatase), Siw14 (a cysteinyl-phosphatase), and Aps1 (a Nudix enzyme). In this study, we report the biochemical and genetic characterization of Aps1 and an analysis of the effects of Asp1, Siw14, and Aps1 mutations on cellular inositol pyrophosphate levels.

Suppression of inositol pyrophosphate toxicosis and hyper-repression of the fission yeast regulon by loss-of-function mutations in chromatin remodelers Snf22 and Sol1.

Inositol pyrophosphates are signaling molecules that regulate cellular phosphate homeostasis in eukaryal taxa. In fission yeast, where the phosphate regulon (comprising phosphate acquisition genes , , and ) is repressed under phosphate-replete conditions by lncRNA-mediated transcriptional interference, mutations of inositol pyrophosphatases that increase IP levels derepress the regulon by eliciting precocious termination of lncRNA transcription. Asp1 pyrophosphatase mutations resulting in too much IP are cytotoxic in YES medium owing to overexpression of glycerophosphodiester transporter Tgp1.

Factors governing the transcriptome changes and chronological lifespan of fission yeast during phosphate starvation.

Starvation of Schizosaccharomyces pombe for inorganic phosphate elicits adaptive transcriptome changes in which mRNAs driving ribosome biogenesis, tRNA biogenesis, and translation are globally downregulated, while those for autophagy and phosphate mobilization are upregulated. Here, we interrogated three components of the starvation response: upregulated autophagy; the role of transcription factor Pho7 (an activator of the PHO regulon); and upregulated expression of ecl3, one of three paralogous genes (ecl1, ecl2, and ecl3) collectively implicated in cell survival during other nutrient stresses. Ablation of autophagy factor Atg1 resulted in early demise of phosphate-starved fission yeast, as did ablation of Pho7.

Characterization of tRNA splicing enzymes RNA ligase and tRNA 2'-phosphotransferase from the pathogenic fungi Mucorales.

Fungal Trl1 is an essential trifunctional tRNA splicing enzyme that heals and seals tRNA exons with 2',3'-cyclic-PO and 5'-OH ends. Trl1 is composed of C-terminal cyclic phosphodiesterase and central polynucleotide kinase end-healing domains that generate the 3'-OH,2'-PO and 5'-PO termini required for sealing by an N-terminal ATP-dependent ligase domain. Trl1 enzymes are present in many human fungal pathogens and are promising targets for antifungal drug discovery because their domain structures and biochemical mechanisms are unique compared to the mammalian RtcB-type tRNA splicing enzyme.

Genetic suppressor screen identifies Tgp1 (glycerophosphocholine transporter), Kcs1 (IP kinase), and Plc1 (phospholipase C) as determinants of inositol pyrophosphate toxicosis in fission yeast.

The inositol pyrophosphate signaling molecule 1,5-IP is an agonist of RNA 3-processing and transcription termination in fission yeast that regulates the expression of phosphate acquisition genes , , and . IP is synthesized from 5-IP by the Asp1 N-terminal kinase domain and catabolized by the Asp1 C-terminal pyrophosphatase domain. mutations that delete or inactivate the Asp1 pyrophosphatase domain elicit growth defects in yeast extract with supplements (YES) medium ranging from severe sickness to lethality.

Activities, substrate specificity, and genetic interactions of fission yeast Siw14, a cysteinyl-phosphatase-type inositol pyrophosphatase.

The inositol pyrophosphate signaling molecule 1,5-IP modulates fission yeast phosphate homeostasis via its action as an agonist of RNA 3'-processing and transcription termination. Cellular 1,5-IP levels are determined by a balance between the activities of the inositol polyphosphate kinase Asp1 and several inositol pyrophosphatase enzymes. Here, we characterize Siw14 (SpSiw14) as a cysteinyl-phosphatase-family pyrophosphatase enzyme capable of hydrolyzing the phosphoanhydride substrates inorganic pyrophosphate, inorganic polyphosphate, and inositol pyrophosphates 5-IP, 1-IP, and 1,5-IP.

Initialization of Nanowire or Cluster Growth Critically Controlled by the Effective V/III Ratio at the Early Nucleation Stage.

For self-catalyzed nanowires (NWs), reports on how the catalytic droplet initiates successful NW growth are still lacking, making it difficult to control the yield and often accompanying a high density of clusters. Here, we have performed a systematic study on this issue, which reveals that the effective V/III ratio at the initial growth stage is a critical factor that governs the NW growth yield. To initiate NW growth, the ratio should be high enough to allow the nucleation to extend to the entire contact area between the droplet and substrate, which can elevate the droplet off of the substrate, but it should not be too high in order to keep the droplet.

Ecological drivers of fine-scale distribution of arbuscular mycorrhizal fungi in a semiarid Mediterranean scrubland.

Background And Aims: Arbuscular mycorrhizal (AM) fungi enhance the uptake of water and minerals by the plant hosts, alleviating plant stress. Therefore, AM fungal-plant interactions are particularly important in drylands and other stressful ecosystems. We aimed to determine the combined and independent effects of above- and below-ground plant community attributes (i.

Duf89 abets lncRNA control of fission yeast phosphate homeostasis via its antagonism of precocious lncRNA transcription termination.

Fission yeast phosphate homeostasis gene is actively repressed during growth in phosphate-rich medium by transcription in of a long noncoding (lnc) RNA from the 5' flanking gene. Pho1 expression is: (i) derepressed by genetic maneuvers that favor precocious lncRNA 3'-processing and termination, in response to DSR and PAS signals in ; and (ii) hyperrepressed in genetic backgrounds that dampen 3'-processing/termination efficiency. Governors of 3'-processing/termination include the RNA polymerase CTD code, the CPF (cleavage and polyadenylation factor) complex, termination factors Seb1 and Rhn1, and the inositol pyrophosphate signaling molecule 1,5-IP Here, we present genetic and biochemical evidence that fission yeast Duf89, a metal-dependent phosphatase/pyrophosphatase, is an antagonist of precocious 3'-processing/termination.

Inorganic polyphosphate abets silencing of a sub-telomeric gene cluster in fission yeast.

Inorganic polyphosphate is a ubiquitous polymer with myriad roles in cell and organismal physiology. Whereas there is evidence for nuclear polyphosphate, its impact on transcriptional regulation in eukaryotes is unkown. Transcriptional profiling of fission yeast cells lacking polyphosphate (via deletion of the catalytic subunit Vtc4 of the Vtc4/Vtc2 polyphosphate polymerase complex) elicited de-repression of four protein-coding genes located within the right sub-telomeric arm of chromosome I that is known to be transcriptionally silenced by the TORC2 complex.

Cellular responses to long-term phosphate starvation of fission yeast: Maf1 determines fate choice between quiescence and death associated with aberrant tRNA biogenesis.

Inorganic phosphate is an essential nutrient acquired by cells from their environment. Here, we characterize the adaptative responses of fission yeast to chronic phosphate starvation, during which cells enter a state of quiescence, initially fully reversible upon replenishing phosphate after 2 days but resulting in gradual loss of viability during 4 weeks of starvation. Time-resolved analyses of changes in mRNA levels revealed a coherent transcriptional program in which phosphate dynamics and autophagy were upregulated, while the machineries for rRNA synthesis and ribosome assembly, and for tRNA synthesis and maturation, were downregulated in tandem with global repression of genes encoding ribosomal proteins and translation factors.

Recent and ancient evolutionary events shaped plant elemental composition of edaphic endemics: a phylogeny-wide analysis of Iberian gypsum plants.

The analysis of plant elemental composition and the underlying factors affecting its variation are a current hot topic in ecology. Ecological adaptation to atypical soils may shift plant elemental composition. However, no previous studies have evaluated its relevance against other factors such as phylogeny, climate or individual soil conditions.

Long-Term Stability and Optoelectronic Performance Enhancement of InAsP Nanowires with an Ultrathin InP Passivation Layer.

The influence of nanowire (NW) surface states increases rapidly with the reduction of diameter and hence severely degrades the optoelectronic performance of narrow-diameter NWs. Surface passivation is therefore critical, but it is challenging to achieve long-term effective passivation without significantly affecting other qualities. Here, we demonstrate that an ultrathin InP passivation layer of 2-3 nm can effectively solve these challenges.

Bi incorporation and segregation in the MBE-grown GaAs-(Ga,Al)As-Ga(As,Bi) core-shell nanowires.

Incorporation of Bi into GaAs-(Ga,Al)As-Ga(As,Bi) core-shell nanowires grown by molecular beam epitaxy is studied with transmission electron microscopy. Nanowires are grown on GaAs(111)B substrates with Au-droplet assisted mode. Bi-doped shells are grown at low temperature (300 °C) with a close to stoichiometric Ga/As flux ratio.

Fission yeast Duf89 and Duf8901 are cobalt/nickel-dependent phosphatase-pyrophosphatases that act via a covalent aspartyl-phosphate intermediate.

Domain of Unknown Function 89 (DUF89) proteins are metal-dependent phosphohydrolases. Exemplary DUF89 enzymes differ in their metal and phosphosubstrate preferences. Here, we interrogated the activities and structures of two DUF89 paralogs from fission yeast-Duf89 and Duf8901.

Ferroelectric incommensurate spin crystals.

Ferroics, especially ferromagnets, can form complex topological spin structures such as vortices and skyrmions when subjected to particular electrical and mechanical boundary conditions. Simple vortex-like, electric-dipole-based topological structures have been observed in dedicated ferroelectric systems, especially ferroelectric-insulator superlattices such as PbTiO/SrTiO, which was later shown to be a model system owing to its high depolarizing field. To date, the electric dipole equivalent of ordered magnetic spin lattices driven by the Dzyaloshinskii-Moriya interaction (DMi) has not been experimentally observed.

Thermally-driven formation method for growing (quantum) dots on sidewalls of self-catalysed thin nanowires.

Embedding quantum dots (QDs) on nanowire (NW) sidewalls allows the integration of multi-layers of QDs into the active region of radial p-i-n junctions to greatly enhance light emission/absorption. However, the surface curvature makes the growth much more challenging compared with growths on thin-films, particularly on NWs with small diameters (Ø < 100 nm). Moreover, the {110} sidewall facets of self-catalyzed NWs favor two-dimensional growth, with the realization of three-dimensional Stranski-Krastanow growth becoming extremely challenging.

Cleavage-Polyadenylation Factor Cft1 and SPX Domain Proteins Are Agents of Inositol Pyrophosphate Toxicosis in Fission Yeast.

Inositol pyrophosphate (IPP) dynamics govern expression of the fission yeast phosphate homeostasis regulon via their effects on lncRNA-mediated transcription interference. The growth defects (ranging from sickness to lethality) elicited by fission yeast mutations that inactivate IPP pyrophosphatase enzymes are exerted via the agonistic effects of too much 1,5-IP8 on RNA 3'-processing and transcription termination. To illuminate determinants of IPP toxicosis, we conducted a genetic screen for spontaneous mutations that suppressed the sickness of Asp1 pyrophosphatase mutants.

When the Donor Surprises You: A Case Report.

The possibility of transplanting a graft from a cadaveric donor with unknown membranous nephropathy (MN) has been described in the literature. We present the case of 2 patients who received their first kidney transplant (KT) from a 27-year-old male donor with no relevant medical history. The first recipient was a 50-year-old man with stage 5 chronic kidney disease secondary to diabetic kidney disease.

Implementation of contact isolation strategy for the containment of extended-spectrum β-lactamase carriers in a University Hospital positively affects the epidemiology of carbapenemase-producing Enterobacterales.

Introduction: The lack of consensus of control measures to prevent extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) transmission in the hospital setting is of great concern. We describe the prevalence and species distribution of ESBL-E and carbapenemase producing Enterobacterales (CPE) in patients admitted in a tertiary Hospital during an active surveillance screening program for detecting ESBL-E carriers and reducing the ESBL-E transmission (R-GNOSIS Project).

Methods: From March-2014 to March-2016, 15,556 rectal swabs were collected from 8209 patients admitted in two medical (Gastroenterology, Pneumology) and two surgical (Neurosurgery, Urology) wards.

Characterization of Solar-Aged Porous Silicon Carbide for Concentrated Solar Power Receivers.

Porous silicon carbide is a promising material for ceramic receivers in next-generation concentrated solar power receivers. To investigate its tolerance to thermal shock, accelerated ageing of large coupons (50 × 50 × 5 mm) was conducted in a solar furnace to investigate the effects of thermal cycling up to 1000 °C, with gradients of up to 22 °C/mm. Non-destructive characterization by computed X-ray tomography and ultrasonic inspection could detect cracking from thermal stresses, and this informed the preparation of valid specimens for thermophysical characterization.

Self-Catalyzed AlGaAs Nanowires and AlGaAs/GaAs Nanowire-Quantum Dots on Si Substrates.

Self-catalyzed AlGaAs nanowires (NWs) and NWs with a GaAs quantum dot (QD) were monolithically grown on Si(111) substrates via solid-source molecular beam epitaxy. This growth technique is advantageous in comparison to the previously employed Au-catalyzed approach, as it removes Au contamination issues and renders the structures compatible with complementary metal-oxide-semiconductor (CMOS) technology applications. Structural studies reveal the self-formation of an Al-rich AlGaAs shell, thicker at the NW base and thinning towards the tip, with the opposite behavior observed for the NW core.