Burkholderia cepacia: a rare cause of bacterial keratitis

We describe the first clinical case of Burkholderia cepacia keratitis registered in Southeast Asia. A man in his mid-70s with underlying poorly controlled diabetes mellitus came with complaints of painful red left eye for 4 days. This was accompanied with photophobia and blurring of vision after being injured by a wooden particle while cutting grass. Slit-lamp examination showed a paracentral anterior corneal stromal infiltrates with overlying epithelial defect. Culture of the corneal smear isolated B. cepacia that was sensitive to ceftazidime, meropenem and bactrim (trimethorprim and sulfomethoxazole). Topical ceftazidime was given intensively to the patient and the infection resolved after 6 weeks of treatment

Dacryoadenitis with multiple unilateral ocular abscesses in disseminated melioidosis

Melioidosis is caused by the gram-negative bacterium Burkholderia pseudomallei and has a wide range of manifestations in many organ systems. Ocular melioidosis is a rare manifestation of Burkholderia pseudomallei that commonly presents with orbital cellulitis rather than dacryoadenitis and multiple unilateral ocular abscesses, which are uncommon. The risk of blindness in ocular melioidosis is high because this bacterium is resistant to many antibiotics, requires a longer period of treatment with antibiotics and the diagnosis is not always straightforward. Here we describe a different presentation of ocular melioidosis manifested with left preseptal abscess, orbital cellulitis with abscess and dacryoadenitis in a 50-year-old man who was treated successfully with surgery and antibiotics, along with a brief review of the literature

Morphological and Physiological Characteristics of Ruptured Plaques in Native Arteries and Neoatherosclerotic Segments: An OCT-Based and Computational Fluid Dynamics Study.

Background Intravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure. Methods We retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress. Result Eighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 μm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model. Conclusion We reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization

Enhanced graphitic domains of unreduced graphene oxide and the interplay of hydration behaviour and catalytic activity

Previous studies indicate that the properties of graphene oxide (GO) can be significantly improved by enhancing its graphitic domain size through thermal diffusion and clustering of functional groups. Remarkably, this transition takes place below the decomposition temperature of the functional groups and thus allows fine-tuning of graphitic domains without compromising with the functionality of GO. By studying the transformation of GO under mild thermal treatment, we directly observe this size enhancement of graphitic domains from originally 40 nm2 to 200 nm2 through an extensive transmission electron microscopy (TEM) study. Additionally, we confirm the integrity of the functional groups during this process by comprehensive chemical analysis. A closer look into the process confirms the theoretically predicted relevance for the room temperature stability of GO. We further investigate the influence of enlarged graphitic domains on the hydration behaviour of GO and catalytic performance of single-atom catalysts supported by GO. Surprisingly, both, the water transport and catalytic activity are damped by the heat treatment. This allows us to reveal the critical role of water transport in laminated 2D materials as catalysts

Identification of DreI as an Antiviral Factor Regulated by RLR Signaling Pathway

BACKGROUND:Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) had been demonstrated to prime interferon (IFN) response against viral infection via the conserved RLR signaling in fish, and a novel fish-specific gene, the grass carp reovirus (GCRV)-induced gene 2 (Gig2), had been suggested to play important role in host antiviral response. METHODOLOGY/PRINCIPAL FINDINGS:In this study, we cloned and characterized zebrafish Gig2 homolog (named Danio rerio Gig2-I, DreI), and revealed its antiviral role and expressional regulation signaling pathway. RT-PCR, Western blot and promoter activity assay indicate that DreI can be induced by poly I:C, spring viremia of carp virus (SVCV) and recombinant IFN (rIFN), showing that DreI is a typical ISG. Using the pivotal signaling molecules of RLR pathway, including RIG-I, MDA5 and IRF3 from crucian carp, it is found that DreI expression is regulated by RLR cascade and IRF3 plays an important role in this regulation. Furthermore, promoter mutation assay confirms that the IFN-stimulated regulatory elements (ISRE) in the 5' flanking region of DreI is essential for its induction. Finally, overexpression of DreI leads to establish a strong antiviral state against SVCV and Rana grylio virus (RGV) infection in EPC (Epithelioma papulosum cyprinid) cells. CONCLUSIONS/SIGNIFICANCE:These data indicate that DreI is an antiviral protein, which is regulated by RLR signaling pathway

Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex

The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

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