The Conformation of the N-Terminal Tails of Deinococcus grandis Dps Is Modulated by the Ionic Strength

UIDB/04378/2020 LA/P/0140/2020 UID/Multi/04349/2019 LISBOA-01-0145-FEDER-022096 PTDC/BIA-PRO/111485/2009 PTDC/QUI/64248/2006 PD/00193/2012—UCIBIO (UIDB/04378/2020), UIDB/00068/2020 PD/BD/135476/2017 COVID/BD/152497/2022 PD/BD/135477/2017 COVID/BD/152498/2022 Grant Agreement 730872DNA-binding proteins from starved cells (Dps) are homododecameric nanocages, with N-and C-terminal tail extensions of variable length and amino acid composition. They accumulate iron in the form of a ferrihydrite mineral core and are capable of binding to and compacting DNA, forming low-and high-order condensates. This dual activity is designed to protect DNA from oxidative stress, resulting from Fenton chemistry or radiation exposure. In most Dps proteins, the DNA-binding properties stem from the N-terminal tail extensions. We explored the structural characteristics of a Dps from Deinococcus grandis that exhibits an atypically long N-terminal tail composed of 52 residues and probed the impact of the ionic strength on protein conformation using size exclusion chromatography, dynamic light scattering, synchrotron radiation circular dichroism and small-angle X-ray scattering. A novel high-spin ferrous iron-binding site was identified in the N-terminal tails, using Mössbauer spectroscopy. Our data reveals that the N-terminal tails are structurally dynamic and alter between compact and extended conformations, depending on the ionic strength of the buffer. This prompts the search for other physiologically relevant modulators of tail conformation and hints that the DNA-binding properties of Dps proteins may be affected by external factors.publishersversionpublishe

Comparison of the properties of two fossil groups of galaxies with the normal group NGC 6034 based on multiband imaging and optical spectroscopy

We collected multiband imaging and spectroscopy for two fossil groups (RX J1119.7+2126 and 1RXS J235814.4+150524) and one normal group (NGC 6034). We computed photometric redshifts in the central zones of each group, combining previous data with the SDSS five-band data. For each group we investigated the red sequence (RS) of the color-magnitude relation and computed the luminosity functions, stellar population ages and distributions of the group members. Spectroscopy allowed us to investigate the large-scale surroundings of these groups and the substructure levels in 1RXS J235814.4+150524 and NGC 6034. The large-scale environment of 1RXS J235814.4+150524 is poor, though its galaxy density map shows a clear signature of the surrounding cosmic web. RX J1119.7+2126 appears to be very isolated, while the cosmic environment of NGC 6034 is very rich. At the group scale, 1RXS J235814.4+150524 shows no substructure. Galaxies with recent stellar populations seem preferentially located in the group outskirts. A RS is discernable for all three groups in a color-magnitude diagram. The luminosity functions based on photometric redshift selection and on statistical background subtraction have comparable shapes, and agree with the few points obtained from spectroscopic redshifts. These luminosity functions show the expected dip between first and second brightest galaxies for the fossil groups only. Their shape is also regular and relatively flat at faint magnitudes down to the completeness level for RX J1119.7+2126 and NGC 6034, while there is a clear lack of faint galaxies for 1RXS J235814.4+150524. RX J1119.7+2126 is definitely classified as a fossil group; 1RXS J235814.4+150524 also has properties very close to those of a fossil group, while we confirm that NGC 6034 is a normal group.Comment: Accepted in A&A, english-improved, 5 jpeg figures, and shortened abstrac

Changing indications and socio-demographic determinants of (adeno)tonsillectomy among children in England--are they linked? A retrospective analysis of hospital data.

OBJECTIVE: To assess whether increased awareness and diagnosis of obstructive sleep apnoea syndrome (OSAS) and national guidance on tonsillectomy for recurrent tonsillitis have influenced the socio-demographic profile of children who underwent tonsillectomy over the last decade. METHOD: Retrospective time-trends study of Hospital Episodes Statistics data. We examined the age, sex and deprivation level, alongside OSAS diagnoses, among children aged <16 years who underwent (adeno)tonsillectomy in England between 2001/2 and 2011/12. RESULTS: Among children aged <16 years, there were 29,697 and 27,732 (adeno)tonsillectomies performed in 2001/2 and 2011/12, respectively. The median age at (adeno)tonsillectomy decreased from 7 (IQR: 5-11) to 5 (IQR: 4-9) years over the decade. (Adeno)tonsillectomy rates among children aged 4-15 years decreased by 14% from 350 (95%CI: 346-354) in 2001/2 to 300 (95%CI: 296-303) per 100,000 children in 2011/12. However, (adeno)tonsillectomy rates among children aged <4 years increased by 58% from 135 (95%CI: 131-140) to 213 (95%CI 208-219) per 100,000 children in 2001/2 and 2011/2, respectively. OSAS diagnoses among children aged <4 years who underwent surgery increased from 18% to 39% between these study years and the proportion of children aged <4 years with OSAS from the most deprived areas increased from 5% to 12%, respectively. CONCLUSIONS: (Adeno)tonsillectomy rates declined among children aged 4-15 years, which reflects national guidelines recommending the restriction of the operation to children with more severe recurrent throat infections. However, (adeno)tonsillectomy rates among pre-school children substantially increased over the past decade and one in five children undergoing the operation was aged <4 years in 2011/12.The increase in surgery rates in younger children is likely to have been driven by increased awareness and detection of OSAS, particularly among children from the most deprived areas

The protective effect of inflammatory monocytes during systemic C. albicans infection is dependent on collaboration between C-type lectin-like receptors

Acknowledgments The authors wish to acknowledge the NIH-sponsored Mutant Mouse Regional Resource Center (MMRRC) National System as the source of genetically-altered mice (C57BL/6-Clec4etm1.1Cfg/Mmucd 031936-UCD) for use in this study. The mice were produced and deposited to the MMRRC by the Consortium for Functional Glycomics supported by the National Institute of General Medical Sciences (GM62116). We would like to thank Catherine Neiseryan and Ann Kift-Morgan for cell sorting. We would like to thank Wales Gene Park for providing computer resources that assisted this research. Funding: SJO was funded by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 099953/Z/12/Z) and by a Wellcome Trust ISSF Cross-Disciplinary Award. LCD is supported by a Henry Wellcome Trust Postdoctoral Fellowship (103973/Z/14/Z). CL is supported by a Kidney Research UK/MedImmune Joint Fellowship Award (PDF_006_20151127). GDB is funded by a Wellcome Trust Investigator Award (102705) and the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). IRH is supported by a Wellcome Trust Senior Research Fellowship (207503/Z/17/Z). PRT is supported by a Wellcome Trust Investigator Award (107964/Z/15/Z) and the UK Dementia Research Institute. Funding URLs: https://wellcome.ac.uk/ https://royalsociety.org/ https://www.kidneyresearchuk.org/ https://mrc.ukri.org/ https://ukdri.ac.uk/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: All relevant data apart from RNAseq files are within the manuscript and its Supporting Information files. RNAseq data files are available from ArrayExpress (https://www.ebi.ac.uk/arrayexpress/), (accession number E-MTAB-8030).Peer reviewedPublisher PD

An analysis of first-time enquirers to the CancerBACUP information service: variations with cancer site, demographic status and geographical location

A retrospective comparison of cancer incidence data and, where relevant, population data with 16 955first-time users (patients, relatives and friends) of a national cancer information service (CancerBACUP) during the period April1995 to March 1996 is presented. The number of events observed was compared with the number of events expected, were the nationalrates of cancer incidence and population demographics apply. Standardized incidence ratios (SIRs) (observed – expectedratios) were used to indicate any differences. Statistically significant differences (P< 0.001) in the observed andexpected sex, age and primary site distribution of patients enquired about were found. Statistically significant differences(P< 0.001) were also identified for the age, employment status, socioeconomic class and geographical location offirst-time enquirers (patients, relatives and friends). Enquiries about brain, testis and breast cancers and non-Hodgkin'slymphoma (NHL) were substantially higher than expected; enquiries about bladder, lung, stomach and colorectal cancers were muchlower than expected. As the service is provided via a freephone number, it is available to all, and users might be expected to berandomly distributed across the variables listed. The underlying reasons for the differences identified need to be investigated,and the role of information in the care of cancer patients should be formally evaluated. © 1999 Cancer Research Campaig

Hadron Energy Reconstruction for the ATLAS Calorimetry in the Framework of the Non-parametrical Method

This paper discusses hadron energy reconstruction for the ATLAS barrel prototype combined calorimeter (consisting of a lead-liquid argon electromagnetic part and an iron-scintillator hadronic part) in the framework of the non-parametrical method. The non-parametrical method utilizes only the known $e/h$ ratios and the electron calibration constants and does not require the determination of any parameters by a minimization technique. Thus, this technique lends itself to an easy use in a first level trigger. The reconstructed mean values of the hadron energies are within $\pm 1$ of the true values and the fractional energy resolution is $[(58\pm3)/\sqrt{E}+(2.5\pm0.3)$. The value of the $e/h$ ratio obtained for the electromagnetic compartment of the combined calorimeter is $1.74\pm0.04$ and agrees with the prediction that $e/h > 1.7$ for this electromagnetic calorimeter. Results of a study of the longitudinal hadronic shower development are also presented. The data have been taken in the H8 beam line of the CERN SPS using pions of energies from 10 to 300 GeV.Comment: 33 pages, 13 figures, Will be published in NIM

Characterization of the BICEP Telescope for High-precision Cosmic Microwave Background Polarimetry

The Background Imaging of Cosmic Extragalactic Polarization (BICEP) experiment was designed specifically to search for the signature of inflationary gravitational waves in the polarization of the cosmic microwave background (CMB). Using a novel small-aperture refractor and 49 pairs of polarization-sensitive bolometers, BICEP has completed three years of successful observations at the South Pole beginning in 2006 February. To constrain the amplitude of the inflationary B-mode polarization, which is expected to be at least 7 orders of magnitude fainter than the 3 K CMB intensity, precise control of systematic effects is essential. This paper describes the characterization of potential systematic errors for the BICEP experiment, supplementing a companion paper on the initial cosmological results. Using the analysis pipelines for the experiment, we have simulated the impact of systematic errors on the B-mode polarization measurement. Guided by these simulations, we have established benchmarks for the characterization of critical instrumental properties including bolometer relative gains, beam mismatch, polarization orientation, telescope pointing, sidelobes, thermal stability, and timestream noise model. A comparison of the benchmarks with the measured values shows that we have characterized the instrument adequately to ensure that systematic errors do not limit BICEP's two-year results, and identifies which future refinements are likely necessary to probe inflationary B-mode polarization down to levels below a tensor-to-scalar ratio r = 0.1.Astronom

IL-27 Induced by Select Candida spp. via TLR7/NOD2 Signaling and IFN-β Production Inhibits Fungal Clearance

Candida spp. elicit cytokine production downstream of various pathogen recognition receptors (PRRs) including C-type lectin-like receptors (CLRs), Toll-like receptors (TLRs) and nucleotide oligomerisation domain (NOD)-like receptors (NLRs). IL-12 family members, IL-12p70 and IL-23, are important for host immunity against Candida spp. Herein we show that IL-27, another IL-12 family member, is produced by myeloid cells in response to select Candida spp. We demonstrate a novel mechanism for C. parapsilosis-mediated induction of IL-27 in a TLR7-, MyD88- and NOD2-dependent manner. Our data revealed that IFN-β is induced by C. parapsilosis, which in turn signals through the interferon-α/β receptor (IFNAR) and STAT1/2 to induce IL-27. Moreover, IL 27R (WSX-1) deficient mice systemically infected with C. parapsilosis displayed enhanced pathogen clearance compared to WT mice. This was associated with increased levels of pro-inflammatory cytokines in the serum and increased IFN-γ and IL-17 responses in the spleens of IL-27R deficient mice. Thus our data define a novel link between C. parapsilosis, TLR7, NOD2, IFN-β and IL-27 and we have identified an important role for IL-27 in the immune response against C. parapsilosis. Overall these findings demonstrate an important mechanism for the suppression of protective immune responses during infection with C. parapsilosis, which has potential relevance for infections with other fungal pathogens

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc