Predicting visual function from the measurements of retinal nerve fiber layer structure

Purpose: To develop and validate a method for predicting visual function from retinal nerve fibre layer (RNFL) structure in glaucoma. Methods: RNFL thickness (RNFLT) measurements from GDxVCC scanning laser polarimetry (SLP) and visual field (VF) sensitivity from standard automated perimetry were made available from 535 eyes from three centres. In a training dataset, structure-function relationships were characterized using linear regression and a type of neural network: Radial Basis Function customised under a Bayesian framework (BRBF). These two models were used in a test dataset to 1) predict sensitivity values at individual VF locations from RNFLT measurements and 2) predict the spatial relationship between VF locations and positions at a peripapillary RNFLT measurement annulus. Predicted spatial relationships were compared with a published anatomical structure-function map. Results: Compared with linear regression, BRBF yielded a nearly two-fold improvement (P<0.001; paired t-test) in performance of predicting VF sensitivity in the test dataset (mean absolute prediction error of 2.9dB (standard deviation (SD) 3.7dB) versus 4.9dB (SD 4.0dB)). The predicted spatial structure-function relationship accorded better (P<0.001; paired t-test) with anatomical prior knowledge when the BRBF was compared with the linear regression (median absolute angular difference of 15° versus 62°). Conclusions: The BRBF generates clinically useful relationships that relate topographical maps of RNFL measurement to VF locations and allows the VF sensitivity to be predicted from structural measurements. This method may allow clinicians to evaluate structural and functional measures in the same domain. It could also be generalized to use other structural measures

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

Variation in resistance to multiple pathogen species:anther-smuts of Silene uniflora

The occurrence of multiple pathogen species on a shared host species is unexpected when they exploit the same micro-niche within the host individual. One explanation for such observations is the presence of pathogen-specific resistances segregating within the host population into sites that are differentially occupied by the competing pathogens. This study used experimental inoculations to test whether specific resistances may contribute to the maintenance of two species of anther-smut fungi, Microbotryum silenes-inflatae and Microbotryum lagerheimii, in natural populations of Silene uniflora in England and Wales. Overall, resistance to the two pathogens was strongly positively correlated among host populations and to a lesser degree among host families within populations. A few instances of specific resistance were also observed and confirmed by replicated inoculations. The results suggest that selection for resistance to one pathogen may protect the host from the emergence via host shifts of related pathogen species, and conversely that co-occurrence of two species of pathogens may be dependent on the presence of host genotypes susceptible to both

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

Inhomogeneous Metal Distribution in the Intra-Cluster Medium

The hot gas that fills the space between galaxies in clusters is rich in metals. In their large potential wells, galaxy clusters accumulate metals over the whole cluster history and hence they retain important information on cluster formation and evolution. We use a sample of 5 cool core clusters to study the distribution of metals in the ICM. We investigate whether the X-ray observations yield good estimates for the metal mass and whether the heavy elements abundances are consistent with a certain relative fraction of SN Ia to SNCC. We derive detailed metallicity maps of the clusters from XMM - Newton observations and we use them as a measure for the metal mass in the ICM. We determine radial profiles for several elements and using population synthesis and chemical enrichment models, we study the agreement between the measured abundances and the theoretical yields. We show that even in relaxed clusters the distribution of metals show a lot of inhomogeneities. Using metal maps usually gives a metal mass 10-30% higher than the metal mass computed using a single extraction region, hence it is expected that most previous metal mass determination have underestimated metal mass. The abundance ratio of {\alpha}-elements to Fe, even in the central parts of clusters, are consistent with an enrichment due to the combination of SN Ia and SNCC

Table of Contents and Prologue

Editorial board, Table of contents, and Prologue, an introduction to volume 1

The ‘Lost Caravan’ of Ma’den Ijafen revisited: Re-appraising its cargo of cowries, a medieval global commodity

The lost caravan of Ma’den Ijafen, Mauritania, with its cargo of cowries and brass, is widely discussed in African archaeology, providing significant insight into the nature of long-distance trade in the medieval period. While the brass bars recovered by Théodore Monod during his expedition to the site in 1962 have received considerable attention, the cowrie shells described in his comprehensive publication of the assemblage in 1969 have received much less coverage. This issue was addressed during a recent visit to the Institut Fondamental d’Afrique Noire (IFAN) in Dakar, Senegal in May 2017, when the authors re-examined the shells as part of a wider project which also involved archaeological and environmental surveys in the Maldives, the oft-assumed source of these shells. Examinations of natural history collections of cowries, ethnographic interviews in the Maldives, and environmental surveys in East Africa were also carried out. Drawing on insights from these surveys, we systematically compared the Ma’den Ijafen cowrie assemblage to three others from the Maldives, focussing on four criteria: species composition and diversity, shell size and evidence of modifications. This analysis enabled us to shed new light on the nature of the Ma’den Ijafen cowries and their wider significance to understanding the role of the shells in West African trade networks. La caravane perdue du Ma’den Ijafen, en Mauritanie, avec son chargement de cauris et de laiton, a fait l’objet de beaucoup de discussions en archéologie africaine, car elle offre des données importantes sur la nature du commerce médiéval à longue distance. Si les barres de laiton découvertes par Théodore Monod lors de son expédition sur le site en 1962 ont attiré beaucoup d’attention, les cauris, dont il offre une description dans sa publication de 1969, n’en ont presque pas reçu. Cette lacune a été comblée lors d’une visite en mai 2017 à l’Institut Fondamental d’Afrique Noire (IFAN) de Dakar. Lors de cette étude, les auteurs ont pu réexaminer, compter et décrire les cauris. Ceci a été fait dans le cadre d’un projet plus vaste qui a aussi permis des prospections environnementales et archéologiques aux Maldives, la source présumée de ces coquillages. L’étude de collections de cauris dans des musées d’histoire naturelle, des entretiens ethnographiques aux Maldives, et des prospections environnementales en Afrique de l’Est ont aussi été conduites. Ces éléments nous ont fourni un précieux éclairage lors de notre comparaison systématique des cauris du Ma’den Ijafen avec trois collections de cauris retrouvées aux Maldives. Nous avons pris en compte les espèces présentes et leur diversité, la taille des coquillages, et les indications de modifications. Cette analyse nous permet de jeter un nouveau regard sur la nature des cauris du Ma’den Ijafen et leur signification pour l’Afrique de l’Ouest.This article is in Englis

Hydrodynamic coupling in microbially mediated fracture mineralization : formation of self-organized groundwater flow channels

Evidence of fossilized microorganisms embedded within mineral veins and mineral-filled fractures has been observed in a wide range of geological environments. Microorganisms can act as sites for mineral nucleation and also contribute to mineral precipitation by inducing local geochemical changes. In this study, we explore fundamental controls on microbially induced mineralization in rock fractures. Specifically, we systematically investigate the influence of hydrodynamics (velocity, flow rate, aperture) on microbially mediated calcite precipitation. Our experimental results demonstrate that a feedback mechanism exists between the gradual reduction in fracture aperture due to precipitation, and its effect on the local fluid velocity. This feedback results in mineral fill distributions that focus flow into a small number of self-organizing channels that remain open, ultimately controlling the final aperture profile that governs flow within the fracture. This hydrodynamic coupling can explain field observations of discrete groundwater flow channeling within fracture-fill mineral geometries where strong evidence of microbial activity is reported

Solar Signals in CMIP-5 Simulations: The Ozone Response

A multiple linear regression statistical method is applied to model data taken from the Coupled Model Intercomparison Project, phase 5 (CMIP-5) to estimate the 11-yr solar cycle responses of stratospheric ozone, temperature, and zonal wind during the 1979-2005 period. The analysis is limited to the six CMIP-5 models that resolve the stratosphere (high-top models) and that include interactive ozone chemistry. All simulations assumed a conservative 11-yr solar spectral irradiance (SSI) variation based on the NRL model. These model responses are then compared to corresponding observational estimates derived from two independent satellite ozone profile data sets and from ERA Interim Reanalysis meteorological data. The models exhibit a range of 11-yr responses with three models (CESM1-WACCM, MIROC-ESM-CHEM, and MRI-ESM1) yielding substantial solar-induced ozone changes in the upper stratosphere that compare favorably with available observations. The remaining three models do not, apparently because of differences in the details of their radiation and photolysis rate codes. During winter in both hemispheres, the three models with stronger upper stratospheric ozone responses produce relatively strong latitudinal gradients of ozone and temperature in the upper stratosphere that are associated with accelerations of the polar night jet under solar maximum conditions. This behavior is similar to that found in the satellite ozone and ERA Interim data except that the latitudinal gradients tend to occur at somewhat higher latitudes in the models. The sharp ozone gradients are dynamical in origin and assist in radiatively enhancing the temperature gradients, leading to a stronger zonal wind response. These results suggest that simulation of a realistic solar-induced variation of upper stratospheric ozone, temperature and zonal wind in winter is possible for at least some coupled climate models even if a conservative SSI variation is adopted

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site