Structure of FcRY, an avian immunoglobulin receptor related to mammalian mannose receptors, and its complex with IgY

Fc receptors transport maternal antibodies across epithelial cell barriers to passively immunize newborns. FcRY, the functional counterpart of mammalian FcRn (a major histocompatibility complex homolog), transfers IgY across the avian yolk sac, and represents a new class of Fc receptor related to the mammalian mannose receptor family. FcRY and FcRn bind immunoglobulins at pH ≤6.5, but not pH ≥7, allowing receptor–ligand association inside intracellular vesicles and release at the pH of blood. We obtained structures of monomeric and dimeric FcRY and an FcRY–IgY complex and explored FcRY's pH-dependent binding mechanism using electron cryomicroscopy (cryoEM) and small-angle X-ray scattering. The cryoEM structure of FcRY at pH 6 revealed a compact double-ring “head,” in which the N-terminal cysteine-rich and fibronectin II domains were folded back to contact C-type lectin-like domains 1–6, and a “tail” comprising C-type lectin-like domains 7–8. Conformational changes at pH 8 created a more elongated structure that cannot bind IgY. CryoEM reconstruction of FcRY dimers at pH 6 and small-angle X-ray scattering analysis at both pH values confirmed both structures. The cryoEM structure of the FcRY–IgY revealed symmetric binding of two FcRY heads to the dimeric FcY, each head contacting the CH4 domain of one FcY chain. FcRY shares structural properties with mannose receptor family members, including a head and tail domain organization, multimerization that may regulate ligand binding, and pH-dependent conformational changes. Our results facilitate understanding of immune recognition by the structurally related mannose receptor family and comparison of diverse methods of Ig transport across evolution

Non-Markoffian effects of a simple nonlinear bath

We analyze a model of a nonlinear bath consisting of a single two-level system coupled to a linear bath (a classical noise force in the limit considered here). This allows us to study the effects of a nonlinear, non-Markoffian bath in a particularly simple situation. We analyze the effects of this bath onto the dynamics of a spin by calculating the decay of the equilibrium correlator of the spin's z-component. The exact results are compared with those obtained using three commonly used approximations: a Markoffian master equation for the spin dynamics, a weak-coupling approximation, and the substitution of a linear bath for the original nonlinear bath.Comment: 7 pages, 6 figure

Pan-GWAS of Streptococcus agalactiae highlights lineage-specific genes associated with virulence and niche adaptation

Streptococcus agalactiae (Group B streptococcus, GBS) is a coloniser of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterised by Clonal Complexes (CCs) with different invasive potentials. CC17 for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with co-morbidities. The genetic basis of GBS virulence and to what extent different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome wide association study approach to 1988 GBS strains isolated from different hosts and countries. Our analysis identified 279 CC-specific genes associated with virulence, disease, metabolism and regulation of cellular mechanisms that may explain the differential virulence potential of particular CCs. In CC17 and CC23 for example, we have identified genes encoding for pilus, quorum sensing proteins, and proteins for the uptake of ions and micronutrients which are absent in less invasive lineages. Moreover, in CC17, carriage and disease strains were distinguished by the allelic variants of 21 of these CC-specific genes. Together our data highlight the lineage-specific basis of GBS niche adaptation and virulence, and suggest that human-associated GBS CCs have largely evolved in animal hosts before crossing to the humans and then spreading clonally

Pan-GWAS of Streptococcus agalactiae Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation

Streptococcus agalactiae (group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with comorbidities. The genetic basis of GBS virulence and the extent to which different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome-wide association study (GWAS) approach to 1,988 GBS strains isolated from different hosts and countries. Our analysis identified 279 CC-specific genes associated with virulence, disease, metabolism, and regulation of cellular mechanisms that may explain the differential virulence potential of particular CCs. In CC17 and CC23, for example, we have identified genes encoding pilus, quorum-sensing proteins, and proteins for the uptake of ions and micronutrients which are absent in less invasive lineages. Moreover, in CC17, carriage and disease strains were distinguished by the allelic variants of 21 of these CC-specific genes. Together our data highlight the lineage-specific basis of GBS niche adaptation and virulence.IMPORTANCE GBS is a leading cause of mortality in newborn babies in high- and low-income countries worldwide. Different strains of GBS are characterized by different degrees of virulence, where some are harmlessly carried by humans or animals and others are much more likely to cause disease.The genome sequences of almost 2,000 GBS samples isolated from both animals and humans in high- and low- income countries were analyzed using a pan-genome-wide association study approach. This allowed us to identify 279 genes which are associated with different lineages of GBS, characterized by a different virulence and preferred host. Additionally, we propose that the GBS now carried in humans may have first evolved in animals before expanding clonally once adapted to the human host.These findings are essential to help understand what is causing GBS disease and how the bacteria have evolved and are transmitted

Oxidation resistance of graphene-coated Cu and Cu/Ni alloy

The ability to protect refined metals from reactive environments is vital to many industrial and academic applications. Current solutions, however, typically introduce several negative effects, including increased thickness and changes in the metal physical properties. In this paper, we demonstrate for the first time the ability of graphene films grown by chemical vapor deposition to protect the surface of the metallic growth substrates of Cu and Cu/Ni alloy from air oxidation. SEM, Raman spectroscopy, and XPS studies show that the metal surface is well protected from oxidation even after heating at 200 \degree C in air for up to 4 hours. Our work further shows that graphene provides effective resistance against hydrogen peroxide. This protection method offers significant advantages and can be used on any metal that catalyzes graphene growth

Hai Di Lao Hot Pot: From Employee Stimulation to Service Innovation

The management of Chinese restaurant chains has for some time followed the western model while accommodating Chinese customers. The new Hai Di Lao Hot Pot Restaurant chain has established its own management style, pioneering chain catering management to help the Chinese restaurant industry establish a professional image, explore a local management model, and maintain high standards of food safety. The objectives of this case study are to introduce the Hai Di Lao managerial strategy, investigate the secrets of its success from a human resources management perspective, to explore its innovative service, and to assess why it has inspired both marketers and the catering industry. The results show that human resources management can change employees’ behavior and emotional states by addressing a wide variety of needs. In addition, attention to service quality can improve customer satisfaction and retention

Laser locking to the 199Hg clock transition with 5.4x10^(-15)/sqrt(tau) fractional frequency instability

With Hg atoms confined in an optical lattice trap in the Lamb-Dicke regime, we obtain a spectral line at 265.6 nm in which the full-width at half-maximum is <15Hz. Here we lock an ultrastable laser to this ultranarrow clock transition and achieve a fractional frequency stability of 5.4x10^(-15)/sqrt(tau) for tau<=400s. The highly stable laser light used for the atom probing is derived from a 1062.6 nm fiber laser locked to an ultrastable optical cavity that exhibits a mean drift rate of -6.0x10^(-17) s^(-1) (or -16.9 mHz.s^(-1) at 282 THz) over a five month period. A comparison between two such lasers locked to independent optical cavities shows a flicker noise limited fractional frequency instability of 4x10^(-16) per cavity

Structure of the hDmc1-ssDNA filament reveals the principles of its architecture

In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination

Financial crises and the attainment of the SDGs: an adjusted multidimensional poverty approach

This paper analyses the impact of financial crises on the Sustainable Development Goal of eradicating poverty. To do so, we develop an adjusted Multidimensional Poverty Framework (MPF) that includes 15 indicators that span across key poverty aspects related to income, basic needs, health, education and the environment. We then use an econometric model that allows us to examine the impact of financial crises on these indicators in 150 countries over the period 1980–2015. Our analysis produces new estimates on the impact of financial crises on poverty’s multiple social, economic and environmental aspects and equally important captures dynamic linkages between these aspects. Thus, we offer a better understanding of the potential impact of current debt dynamics on Multidimensional Poverty and demonstrate the need to move beyond the boundaries of SDG1, if we are to meet the target of eradicating poverty. Our results indicate that the current financial distress experienced by many low-income countries may reverse the progress that has been made hitherto in reducing poverty. We find that financial crises are associated with an approximately 10% increase of extreme poor in low-income countries. The impact is even stronger in some other poverty aspects. For instance, crises are associated with an average decrease of government spending in education by 17.72% in low-income countries. The dynamic linkages between most of the Multidimensional Poverty indicators, warn of a negative domino effect on a number of SDGs related to poverty, if there is a financial crisis shock. To pre-empt such a domino effect, the specific SDG target 17.4 on attaining long-term debt sustainability through coordinated policies plays a key role and requires urgent attention by the international community