Are eyes the windows to COVID-19? Systematic review and meta-analysis

Objective To review and critically appraise the ocular manifestation and the presence of SARS-CoV-2 through PCR positivity from ocular samples in COVID-19-related patients. Moreover, to evaluate the time and severity association of ocular manifestation to systemic disease of COVID-19. Methods and analysis A systematic literature search from PubMed, ScienceDirect and Google Scholar databases was performed using standardised Preferred Reporting Items for Systematic Reviews and MetaAnalyses guideline. Selected keywords were related to COVID-19, ocular manifestation and PCR testing of SARS-CoV-2. Studies were assessed for their validity, and the data were extracted by two independent reviewers. Observational, case series and case report studies were included if they met the selection criteria. Meta-analysis was performed to estimate the pooled prevalence of ocular manifestations and PCR positivity from tears. Results Thirty-one articles were qualitatively reviewed, and 14 studies were included in the meta-analysis. The pooled prevalence of ocular manifestation among COVID19-related patients was 0.05 (95%CI 0.02% to 0.08). The overall PCR from tears samples positivity rate from COVID19-related patients presenting with ocular manifestation was 0.38 (95% CI 0.14% to 0.65). Ocular manifestation could precede systemic manifestation in about 0.28 (95% CI 0.05% to 0.58) of COVID-19-related patients with ocular manifestations. Besides, ocular manifestation was not associated with a severe form of COVID-19. Conclusion Although the overall number of ocular manifestation and SARS-CoV-2 PCR positivity rate from ocular samples was very low, around a quarter of COVID19-related patients with ocular manifestation presented their ocular manifestation earlier than the systemic manifestation regardless of the severity. Interestingly, SARS-CoV-2 PCR was positive from one-third of ocular samples, which could potentially be the source of infection to the respiratory tract and the environment, although the infectivity is yet to be determined

An Exact Algorithm for Side-Chain Placement in Protein Design

Computational protein design aims at constructing novel or improved functions on the structure of a given protein backbone and has important applications in the pharmaceutical and biotechnical industry. The underlying combinatorial side-chain placement problem consists of choosing a side-chain placement for each residue position such that the resulting overall energy is minimum. The choice of the side-chain then also determines the amino acid for this position. Many algorithms for this NP-hard problem have been proposed in the context of homology modeling, which, however, reach their limits when faced with large protein design instances. In this paper, we propose a new exact method for the side-chain placement problem that works well even for large instance sizes as they appear in protein design. Our main contribution is a dedicated branch-and-bound algorithm that combines tight upper and lower bounds resulting from a novel Lagrangian relaxation approach for side-chain placement. Our experimental results show that our method outperforms alternative state-of-the art exact approaches and makes it possible to optimally solve large protein design instances routinely

Inverse correlation between serum complement component C1q levels and whole blood type-1 interferon signature in active tuberculosis and QuantiFERON-positive uveitis: implications for diagnosis

Objectives To examine the relation between serum C1q levels and blood type‐1 interferon signature (type‐1 IFN signature) in active pulmonary tuberculosis (APTB) and to determine whether combined measurement of serum C1q and type‐1 IFN signature may add to the diagnosis of QuantiFERON‐positive (QFT+) patients with uveitis of unknown cause. Methods C1q was determined (ELISA) in serum from two distinct Indonesian cohorts, and in total, APTB (n = 72), QFT+ uveitis of unknown aetiology (n = 58), QFT− uveitis (n = 51) patients and healthy controls (HC; n = 73) were included. The type‐1 IFN signature scores were previously determined. Results Serum C1q was higher in APTB than HC (P < 0.001). APTB patients with uveitis had higher serum C1q than APTB patients without uveitis (P = 0.0207). Serum C1q correlated inversely with type‐1 IFN signature scores in APTB (P = 0.0036, r2 = 0.3526), revealing that these biomarkers for active TB disease can be mutually exclusive. Stratification of QFT+ patients with uveitis of unknown cause, by serum C1q and type‐1 IFN signature, yielded four groups with different likelihood of suffering from active TB uveitis. Conclusion Serum C1q is elevated in APTB, e

Structure-property-function relationship in humic substances to explain the biological activity in plants

Knowledge of the structure-property-function relationship of humic substances (HSs) is key for understanding their role in soil. Despite progress, studies on this topic are still under discussion. We analyzed 37 humic fractions with respect to their isotopic composition, structural characteristics, and properties responsible for stimulating plant root parameters. We showed that regardless of the source of origin of the carbon (C3 or C4), soil-extracted HSs and humic acids (HAs) are structurally similar to each other. The more labile and functionalized HS fraction is responsible for root emission, whereas the more recalcitrant and less functionalized HA fraction is related to root growth. Labile structures promote root stimulation at lower concentrations, while recalcitrant structures require higher concentrations to promote a similar stimulus. These findings show that lability and recalcitrance, which are derived properties of humic fractions, are related to the type and intensity of their bioactivity. In summary, the comparison of humic fractions allowed a better understanding of the relationship between the source of origin of plant carbon and the structure, properties, and type and intensity of the bioactivity of HSs in plants. In this study, scientific concepts are unified and the basis for the agronomic use of HSs is established

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Detection of noncyling cows by heatmount decectors and ultrasound before treatment with progesterone

Dairy Research, 2007 is known as Dairy Day, 2007Our objective was to determine accuracy of identifying anovulatory lactating dairy cows before the application of a timed AI protocol [with or without progesterone supplementation via a controlled internal drug release (CIDR) insert and 2 different timings of AI] by using heatmount detectors and a single ovarian ultrasound examination. At 6 Midwest locations, 1,072 cows were enrolled in a Presynch protocol (2 injections of prostaglandin F2α (PGF2α) 14 days apart) with the second injection administered 14 days before initiating the Ovsynch protocol (injection of gonadotropin releasing hormone (GnRH) 7 days before and 48 hours after PGF2α injection, with timed AI at 0 or 24 hours after the second GnRH injection). Heatmount detectors were applied to cows at the time of the first Presynch injection, assessed 14 days later at the second Presynch injection and again at initiation of the Ovsynch protocol, and ovaries were examined for presence of a visible corpus luteum (CL) by ultrasound before initiation of treatment. Treatments were assigned to cows based on presence or absence of a visible CL: 1) anovulatory (no CL + CIDR insert for 7 d); 2) anovulatory (no CL + no CIDR); and 3) cycling (CL present). Further, every other cow in the 3 treatments was assigned to be inseminated concurrent with the second GnRH injection of Ovsynch (0 hour) or 24 hours later. Pregnancy was diagnosed at 33 and 61 days after the second GnRH injection. Heatmount detectors and a single ultrasound examination both underestimated proportions of cows classified as anovulatory or having no prior luteal activity compared with those classifications determined by concentrations of progesterone in blood serum. Overall accuracy of heatmount detectors and ultrasound was 71 and 84%, respectively. Application of progesterone to cows without a CL at the time of the first injection of GnRH reduced incidence of ovulation but improved pregnancy rates at day 33 or 61 compared with nontreated cows without a CL at the onset of the Ovsynch protocol. Pregnancy rates and pregnancy survival did not differ for cows having a CL before treatment compared with those not having a CL but treated with progesterone. Pregnancy rates were 1.5-fold greater for cows ovulating in response to the first GnRH injection. Timing of AI at 0 or 24 hours after the second GnRH injection did not alter pregnancy rates, but cows having prior luteal activity before treatment had improved pregnancy rates compared with anovulatory cows. We conclude that identifying anovulatory cows by ultrasound was more accurate than by heatmount detectors. Subsequent treatment of potential anovulatory cows with progesterone failed to improve fertility but had benefit for cows with prior estrous cycles at the onset of the timed AI (TAI) protocol, regardless of luteal status before the final luteolytic injection of PGF2α

Retinal Pigment Epithelial Cells Control Early Mycobacterium tuberculosis Infection via Interferon Signaling

Immunogenetics and cellular immunology of bacterial infectious disease

Structure-property-function relationship in humic substances to explain the biological activity in plants

Knowledge of the structure-property-function relationship of humic substances (HSs) is key for understanding their role in soil. Despite progress, studies on this topic are still under discussion. We analyzed 37 humic fractions with respect to their isotopic composition, structural characteristics, and properties responsible for stimulating plant root parameters. We showed that regardless of the source of origin of the carbon (C3 or C4), soil-extracted HSs and humic acids (HAs) are structurally similar to each other. The more labile and functionalized HS fraction is responsible for root emission, whereas the more recalcitrant and less functionalized HA fraction is related to root growth. Labile structures promote root stimulation at lower concentrations, while recalcitrant structures require higher concentrations to promote a similar stimulus. These findings show that lability and recalcitrance, which are derived properties of humic fractions, are related to the type and intensity of their bioactivity. In summary, the comparison of humic fractions allowed a better understanding of the relationship between the source of origin of plant carbon and the structure, properties, and type and intensity of the bioactivity of HSs in plants. In this study, scientific concepts are unified and the basis for the agronomic use of HSs is established

Progress in the shock-ignition inertial confinement fusion concept

Shock-ignition experiments with peak laser intensities of ∼8 × 1015 W/cm2 were performed. D2-filled plastic shells were compressed on a low adiabat by 40 of the 60 OMEGA beams. The remaining 20 beams were delayed and tightly focused onto the imploding shell to generate a strong shock. Up to 35% backscattering of laser energy was measured at the highest intensity. Hard x-ray measurements reveal a relatively low hot-electron temperature of ∼40 keV, independent of intensity and spike onset time