A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

High Energy Bounds on Soft N=4 SYM Amplitudes from AdS/CFT

Using the AdS/CFT correspondence, we study the high-energy behavior of colorless dipole elastic scattering amplitudes in N=4 SYM gauge theory through the Wilson loop correlator formalism and Euclidean to Minkowskian analytic continuation. The purely elastic behavior obtained at large impact-parameter L, through duality from disconnected AdS_5 minimal surfaces beyond the Gross-Ooguri transition point, is combined with unitarity and analyticity constraints in the central region. In this way we obtain an absolute bound on the high-energy behavior of the forward scattering amplitude due to the graviton interaction between minimal surfaces in the bulk. The dominant "Pomeron" intercept is bounded by alpha less than or equal to 11/7 using the AdS/CFT constraint of a weak gravitational field in the bulk. Assuming the elastic eikonal approximation in a larger impact-parameter range gives alpha between 4/3 and 11/7. The actual intercept becomes 4/3 if one assumes the elastic eikonal approximation within its maximally allowed range L larger than exp{Y/3}, where Y is the total rapidity. Subleading AdS/CFT contributions at large impact-parameter due to the other d=10 supergravity fields are obtained. A divergence in the real part of the tachyonic KK scalar is cured by analyticity but signals the need for a theoretical completion of the AdS/CFT scheme.Comment: 25 pages, 3 eps figure

New Constraints (and Motivations) for Abelian Gauge Bosons in the MeV-TeV Mass Range

We survey the phenomenological constraints on abelian gauge bosons having masses in the MeV to multi-GeV mass range (using precision electroweak measurements, neutrino-electron and neutrino-nucleon scattering, electron and muon anomalous magnetic moments, upsilon decay, beam dump experiments, atomic parity violation, low-energy neutron scattering and primordial nucleosynthesis). We compute their implications for the three parameters that in general describe the low-energy properties of such bosons: their mass and their two possible types of dimensionless couplings (direct couplings to ordinary fermions and kinetic mixing with Standard Model hypercharge). We argue that gauge bosons with very small couplings to ordinary fermions in this mass range are natural in string compactifications and are likely to be generic in theories for which the gravity scale is systematically smaller than the Planck mass - such as in extra-dimensional models - because of the necessity to suppress proton decay. Furthermore, because its couplings are weak, in the low-energy theory relevant to experiments at and below TeV scales the charge gauged by the new boson can appear to be broken, both by classical effects and by anomalies. In particular, if the new gauge charge appears to be anomalous, anomaly cancellation does not also require the introduction of new light fermions in the low-energy theory. Furthermore, the charge can appear to be conserved in the low-energy theory, despite the corresponding gauge boson having a mass. Our results reduce to those of other authors in the special cases where there is no kinetic mixing or there is no direct coupling to ordinary fermions, such as for recently proposed dark-matter scenarios.Comment: 49 pages + appendix, 21 figures. This is the final version which appears in JHE

The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression

Upon translation, the N-terminal homology box 1 (NHB1) signal anchor sequence of Nrf1 integrates it within the endoplasmic reticulum (ER) whilst its transactivation domains [TADs, including acidic domain 1 (AD1), the flanking Asn/Ser/Thr-rich (NST) domain and AD2] are transiently translocated into the ER lumen, whereupon the NST domain is glycosylated to yield an inactive 120-kDa glycoprotein. Subsequently, these TADs are retrotranslocated into extra-luminal subcellular compartments, where Nrf1 is deglycosylated to yield an active 95-kDa isoform. Herein, we report that AD1 and AD2 are required for the stability of the 120-kDa Nrf1 glycoprotein, but not that of the non-glycosylated/de-glycosylated 95-kDa isoform. Degrons within AD1 do not promote proteolytic degradation of the 120-kDa Nrf1 glycoprotein. However, repositioning of AD2-adjoining degrons (i.e. DSGLS-containing SDS1 and PEST2 sequences) into the cyto/nucleoplasm enables selective topovectorial processing of Nrf1 by the proteasome and/or calpains to generate a cleaved active 85-kDa Nrf1 or a dominant-negative 36-kDa Nrf1γ. Production of Nrf1γ is abolished by removal of SDS1 or PEST2 degrons, whereas production of the cleaved 85-kDa Nrf1 is blocked by deletion of the ER luminal-anchoring NHB2 sequence (aa 81–106). Importantly, Nrf1 activity is positively and/or negatively regulated by distinct doses of proteasome and calpain inhibitors

The arabidopsis DNA polymerase δ has a role in the deposition of transcriptionally active epigenetic marks, development and flowering

DNA replication is a key process in living organisms. DNA polymerase α (Polα) initiates strand synthesis, which is performed by Polε and Polδ in leading and lagging strands, respectively. Whereas loss of DNA polymerase activity is incompatible with life, viable mutants of Polα and Polε were isolated, allowing the identification of their functions beyond DNA replication. In contrast, no viable mutants in the Polδ polymerase-domain were reported in multicellular organisms. Here we identify such a mutant which is also thermosensitive. Mutant plants were unable to complete development at 28°C, looked normal at 18°C, but displayed increased expression of DNA replication-stress marker genes, homologous recombination and lysine 4 histone 3 trimethylation at the SEPALLATA3 (SEP3) locus at 24°C, which correlated with ectopic expression of SEP3. Surprisingly, high expression of SEP3 in vascular tissue promoted FLOWERING LOCUS T (FT) expression, forming a positive feedback loop with SEP3 and leading to early flowering and curly leaves phenotypes. These results strongly suggest that the DNA polymerase δ is required for the proper establishment of transcriptionally active epigenetic marks and that its failure might affect development by affecting the epigenetic control of master genes.Fil: Iglesias, Francisco Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Bruera, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Dergan Dylon, Leonardo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Marino, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Lorenzi, Hernán. J. Craig Venter Institute; Estados UnidosFil: Mateos, Julieta Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Turck, Franziska. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Coupland, George. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Cerdan, Pablo Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Universidad de Buenos Aires. Departamento de Ciencias Exactas; Argentin

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

High frequency of CHD7 mutations in congenital hypogonadotropic hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) is characterized by lack of normal pubertal development due to deficient gonadotropin-releasing hormone (GnRH) secretion or action, and is caused by genetic defects in several genes. Mutations in the CHD7 gene cause CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and development, Genital hypoplasia and Ear abnormalities), but have also been found in patients with isolated CHH. The aim of this study was to identify CHD7 mutations in patients with CHH. Fifty Portuguese patients with CHH were screened for mutations in the CHD7 gene by DNA sequencing. Eight (16%) patients had CHD7 rare sequence variants that consisted of six missense (p.Gly388Glu, p.His903Pro, p.Thr1082Ile, p.Val1452Leu, p.Asp1854Gly, and p.Arg2065His) and two synonymous (p.Ser559Ser, and p.Ala2785Ala) mutations. Five of these mutations have never been reported before. Three CHD7 mutations occurred in patients that had mutations in additional CHH-genes. This study uncovered novel genetic variants that expand the known spectrum of mutations associated with CHH. The frequency of CHD7 mutations in this cohort was higher than that of other major CHH-genes and confirms the importance of including CHD7 in the genetic testing of CHH, even in the absence of additional CHARGE features.info:eu-repo/semantics/publishedVersio