A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19

Performance and microbial shift during acidification of a real pharmaceutical wastewater by using an anaerobic sequencing batch reactor (AnSBR)

In this study, a lab-scale anaerobic sequencing batch reactor (AnSBR) was used for the acidification of a pharmaceutical wastewater sourced from etodolac chemical synthesis tanks. The effects of the organic loading rate (OLR), and etodolac and sulfate concentrations on the acidification rate and microbial community in AnSBR were investigated at 35 degrees C with a hydraulic retention time (HRT) of 37 h, a pH of 5, and OLRs up to 5.2 kgCOD/m(3). day. The AnSBR accomplished a 60% acidification ratio and 50-60% etodolac removal at OLRs up to 2.6 kgCOD/m(3).day. However, at OLR = 3.9 kgCOD/m(3).clay, acidification was not achieved due to sulfite inhibition; pre-ozonation was applied to overcome this sulfite inhibition. Although etodolac and COD removals were improved, the wastewater was not successfully acidified. Real-time polymerase chain reaction (Q-PCR) and fluorescent in situ hybridization (FISH) analyses revealed that acidification was inhibited by the dominance of sulfate reducing bacteria (SRB) over acidification bacteria in the AnSBR. However, increasing the OLR to 5.2 kgCOD/m(3).day led to toxicity stress in the SRB due to increased sulfite concentrations. Sulfate load fundamentally affected acidification process and microbial community composition. The presence of etodolac with concentration up to 56 mg/L did not have a significant effect on VFA production and the microbial community. (C) 2018 Elsevier Ltd. All rights reserved

Improving the performance of an aerobic membrane bioreactor (MBR) treating pharmaceutical wastewater with powdered activated carbon (PAC) addition

In this study, the effects of organic loading rate (OLR) and the addition of powdered activated carbon (PAC) on the performance and membrane fouling of MBR were conducted to treat real pharmaceutical process wastewater. Over 145 days of operation, the MBR system was operated at OLRs ranging from 1 to 2 kg COD m(-3) day(-1) without sludge wasting. The addition of PAC provided an improvement in the flux, despite an increase in the OLR:PAC ratio. The results demonstrated that the hybrid PAC-MBR system maintained a reduced amount of membrane fouling and steadily increased the removal performance of etodolac. PAC addition reduced the deposition of extracellular polymeric substance and organic matter on the membrane surface and resulted an increase in COD removal even at higher OLRs with low PAC addition. Membrane fouling mechanisms were investigated using combined adsorption fouling models. Modified fouling index values and normalized mass transfer coefficient values indicated that predominant fouling mechanism was cake adsorption

Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey

Congenital myopathies (CMs) are a heterogeneous group of inherited muscle disorders characterized by muscle weakness at birth, while limb-girdle muscular dystrophies (LGMD) have a later onset and slower disease progression. Thus, detailed clinical phenotyping of genetically defined disease entities are required for the full understanding of genotype-phenotype correlations. A recently defined myopathic genetic disease entity is caused by bi-allelic variants in a gene coding for pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1) with unknown substrates. Here, we present three patients from two consanguineous Turkish families with mild LGMD, facial weakness, normal CK levels, and slow progress. Genomic analyses revealed a homozygous known pathogenic missense variant (c.464A>G, p.Asn155Ser) in family 1 with two affected females. In the affected male of family 2, we found this variant in a compound heterozygous state together with a novel frameshift variant (c.329_332delTCTG, p.Leu112Valfs*8), which is the second frameshift variant known so far in PYROXD1. We have been able to define a large homozygous region in family 1 sharing a common haplotype with family 2 in the critical region. Our data suggest that c.464A>G is a Turkish founder mutation. To gain deeper insights, we performed a systematic review of all published PYROXD1-related myopathy cases. Our analysis showed that the c.464A > G variant was found in 87% (20/23) of the patients and that it may cause either a childhood- or adult-onset phenotype, irrespective of its presence in a homozygous or compound heterozygous state. Interestingly, only four patients had elevated CK levels (up to 1000 U/L), and cardiac involvement was found in few compound heterozygous cases

An 80x80 Microbolometer Type Thermal Imaging Sensor using the LWIR-Band CMOS Infrared (CIR) Technology

This paper introduces an 80x80 microbolometer array with a 35 mu m pixel pitch operating in the 8-12 aem wavelength range, where the detector is fabricated with the LWIR-band CMOS infrared technology, shortly named as CIR, which is a novel microbolometer implementation technique developed to reduce the detector cost in order to enable the use of microbolometer type sensors in high volume markets, such as the consumer market and IoT. Unlike the widely used conventional surface micromachined microbolometer approaches, MikroSens' CIR detector technology does not require the use of special high TCR materials like VOx or a-Si, instead, it allows to implement microbolometers with standard CMOS layers, where the suspended bulk micromachined structure is obtained by only few consecutive selective MEMS etching steps while protecting the wirebond pads with a simple lithograpy step. This approach not only reduces the fabrication cost but also increases the production yield. In addition, needing simple subtractive post-CMOS fabrication steps allows the CIR technology to be carried out in any CMOS and MEMS foundry in a truly fabless fashion, where industrially mature and Au-free wafer level vacuum packaging technologies can also be carried out, leading to cost advantage, simplicity, scalability, and flexibility. The CIR approach is used to implement an 80x80 FPA with 35 mu m pixel pitch, namely MS0835A, using a 0.18 mu m CMOS process. The fabricated sensor is measured to provide NETD (Noise Equivalent Temperature Difference) value of 163 mK at 17 fps (frames per second) and 71 mK at 4 fps with F/1.0 optics in a dewar environment. The measurement results of the wafer level vacuum packaged sensors with one side AR coating shows an NETD values of 112 mK at 4 fps with F/1.1 optics, i.e., demonstrates a good performance for high volume low-cost applications like advanced presence detection and human counting applications. The CIR approach of MikroSens is scalable and can be used to reduce the pixel pitch even further while increasing the array size if necessary for various other low-cost, high volume applications

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19

The prevalence of childhood psychopathology in Turkey: a cross-sectional multicenter nationwide study (EPICPAT-T)

Conclusion: This is the largest and most comprehensive epidemiological study to determine the prevalence of psychopathologies in children and adolescents in Turkey. Our results partly higher than, and partly comparable to previous national and international studies. It also contributes to the literature by determining the independent predictors of psychopathologies in this age group

The prevalence of childhood psychopathology in Turkey: a cross-sectional multicenter nationwide study (EPICPAT-T).

Aim: The aim of this study was to determine the prevalence of childhood psychopathologies in Turkey

Prevalence of Childhood Affective disorders in Turkey: An epidemiological study

Aim: To determine the prevalence of affective disorders in Turkey among a representative sample of Turkish population. Methods: This study was conducted as a part of the "The Epidemiology of Childhood Psychopathology in Turkey" (EPICPAT-T) Study, which was designed by the Turkish Association of Child and Adolescent Mental Health. The inclusion criterion was being a student between the second and fourth grades in the schools assigned as study centers. The assessment tools used were the K-SADS-PL, and a sociodemographic form that was designed by the authors. Impairment was assessed via a 3 point-Likert type scale independently rated by a parent and a teacher. Results: A total of 5842 participants were included in the analyses. The prevalence of affective disorders was 2.5 % without considering impairment and 1.6 % when impairment was taken into account. In our sample, the diagnosis of bipolar disorder was lacking, thus depressive disorders constituted all the cases. Among depressive disorders with impairment, major depressive disorder (MDD) (prevalence of 1.06%) was the most common, followed by dysthymia (prevalence of 0.2%), adjustment disorder with depressive features (prevalence of 0.17%), and depressive disorder-NOS (prevalence of 0.14%). There were no statistically significant gender differences for depression. Maternal psychopathology and paternal physical illness were predictors of affective disorders with pervasive impairment. Conclusion: MDD was the most common depressive disorder among Turkish children in this nationwide epidemiological study. This highlights the severe nature of depression and the importance of early interventions. Populations with maternal psychopathology and paternal physical illness may be the most appropriate targets for interventions to prevent and treat depression in children and adolescents