Ibsenbeck2437

Inorganic pyrophosphatases (PPases) catalyze the hydrolysis of pyrophosphate to phosphates. PPases play essential roles in growth and development, and are found in all kingdoms of life. Human possess two PPases, PPA1 and PPA2. PPA1 is present in all tissues, acting largely as a housekeeping enzyme. Besides pyrophosphate hydrolysis, PPA1 can also directly dephosphorylate phosphorylated c-Jun N-terminal kinases 1 (JNK1). Upregulated expression of PPA1 has been linked to many human malignant tumors. PPA1 knockdown induces apoptosis and decreases proliferation. PPA1 is emerging as a potential prognostic biomarker and target for anti-cancer drug development. In spite of the biological and physiopathological importance of PPA1, there is no detailed study on the structure and catalytic mechanisms of mammalian origin PPases. Here we report the crystal structure of human PPA1 at a resolution of 2.4 Å. We also carried out modeling studies of PPA1 in complex with JNK1 derived phosphor-peptides. The monomeric protein fold of PPA1 is similar to those found in other family I PPases. PPA1 forms a dimeric structure that should be conserved in animal and fungal PPases. Analysis of the PPA1 structure and comparison with available structures of PPases from lower organisms suggest that PPA1 has a largely pre-organized and relatively rigid active site for pyrophosphate hydrolysis. Results from the modeling study indicate the active site of PPA1 has the potential to accommodate double-phosphorylated peptides from JNK1. In short, results from the study provides new insights into the mechanisms of human PPA1 and basis for structure-based anti-cancer drug developments using PPA1 as the target.Cellular sugar status is essentially maintained during normal growth conditions but is impacted negatively during various environmental perturbations. Drought presents one such unfavorable environmental cue that hampers the photosynthetic fixation of carbon into sugars and affects their transport by lowering the cellular osmotic potential. The transport of cellular sugar is facilitated by a specific set of proteins known as sugar transporters. These transporter proteins are the key determinant of influx/ efflux of various sugars and their metabolite intermediates that support the plant growth and developmental process. Abiotic stress and especially drought stress-mediated injury results in reprogramming of sugar distribution across the cellular and subcellular compartments. Here, we have reviewed the imperative role of sugar accumulation, signaling, and transport under typical and atypical stressful environments. We have discussed the physiological effects of drought on sugar accumulation and transport through different transporter proteins involved in monosaccharide and disaccharide sugar transport. Further, we have illustrated sugar-mediated signaling and regulation of sugar transporter proteins along with the overall crosstalk of this signaling with the phytohormone module of abiotic stress response under osmotic stress. Overall, the present review highlights the critical role of sugar transport, distribution and signaling in plants under drought stress conditions.

Tear fluid N-Glycome from patients affected with vernal (VKC) and atopic keratoconjunctivitis (AKC) was investigated to identify specific changes in tears and to recognize possible glyco-biomarkers.

The analysis of the N-glycans was performed using matrix-assisted laser desorption ionization mass spectrometry on single tear samples. Tears from control normal subjects (CTRL), VKC and AKC patients were processed and treated with peptide N-glycosidase F (PNGase F) to deglycosylate N-glycoproteins. Released N-glycans were purified, permethylated, and analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and tandem mass spectrometry (MALDI-TOF MS and MALDI-TOF MS/MS).

More than 150 complex N-glycans, including highly fucosylated biantennary, triantennary, tetra-antennary, and bisecting species, were observed in our spectra. Three distinct patterns for CTRL, VKC, and AKC patients were identified in terms of relative intensities for some N-glycans structures. Major variations better comprehension of VKC and AKC alterations at the molecular level.Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT and consequently, a lack of information on how AIT effectively works in real life. To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will usethe RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic "real-world" database using systematic data collection.Based on the current RWE base,and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. There is a need to establish more AIT registries that collect data in a cohesive way, using standardised protocols. This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.

Dermatology is under-represented in UK undergraduate curricula, and with a diagnostic and educational toolkit that is heavily centred on face-to-face (F2F) clinical examination, dermatology education has been disproportionately affected by the COVID-19 pandemic. Online channel-based messaging apps such as Slack offer an opportunity to engage students in remote, multimodal collaborative learning by reproducing a classroom environment in the virtual space.

To determine the feasibility, acceptability and proof of concept for an online Slack community in undergraduate dermatology education.

Undergraduate medical students participated in an online classroom for a 6-week programme encompassing case-based discussions, seminars and journal clubs. The platform was facilitated by junior doctors (n=10) and patient educators (n=6). Students and faculty completed a post-course evaluation. UNC6852 Students additionally completed a pre- and post-intervention dermatology quiz. Mixed methods analyses included quantitative analyatology education to undergraduate medical students. Its ease of use and supportive nature may also facilitate patient involvement. Such advances may provide vital safeguards against the reduction in F2F learning that has accompanied the COVID-19 pandemic.

The aim of this retrospective population-based cohort study was to determine whether the mode of delivery and maternal and neonatal outcomes differ between planned home VBAC (HBAC) and planned hospital VBAC.

All midwifery clients with at least one prior cesarean birth delivered between April 2000 and March 2017 (N=4741; n=4180 planned hospital VBAC, n=561 planned HBAC) were included. Multivariate binomial logistic regression analyses were conducted to calculate the odds ratios adjusted for the potential covariates. The primary outcome was the mode of delivery, and the secondary outcomes were uterine rupture/dehiscence, postpartum hemorrhage, nonintact perineum, episiotomy, obstetric trauma, Apgar score<7 at 5minutes, neonatal resuscitation requiring positivepressure ventilation, neonatal intensive care unit admission, and a composite outcome of severe neonatal mortality and morbidity and maternal mortality and morbidity.

Planned HBAC was associated with a significant 39% decrease in the odds of having a cesarean birth (aOR 0.61, 95% CI 0.47-0.79) adjusting for the prepregnancy and pregnancy characteristics. Severe adverse outcomes were relatively rare in both settings; thus, our study did not have sufficient power to detect the true differences associated with the place of birth.

Home births for those eligible for VBACs and attended by registered midwives within an integrated health system were associated with higher vaginal birth rates compared with planned hospital VBACs. Severe adverse outcomes were relatively rare in both settings.

Home births for those eligible for VBACs and attended by registered midwives within an integrated health system were associated with higher vaginal birth rates compared with planned hospital VBACs. Severe adverse outcomes were relatively rare in both settings.This study established an oligoasthenospermic rat model using tripterygium glycosides (TGs) and investigated the mechanism by which Qilin pills (QLPs) ameliorate reproductive hypofunction. Thirty-two male Sprague Dawley rats were allocated to four equal-sized groups (1) the control group received continuous physiological levels of saline; (2) the oligoasthenospermia model group was induced with TGs by daily intragastric administration for 28 days; (3 and 4) oligoasthenospermic rats were treated intragastrically with low dose (1.62 g kg-1 d-1 ) and high dose (3.24 g kg-1 d-1 ) of QLPs once daily for 60 days. The QLP-treated rats showed a marked increase (p less then .05) in testicular mass, testicular index and semen parameters compared with the untreated rats. Histopathologically, the QLP-treated groups exhibited restored seminiferous tubules in contrast to the model group. Reactive oxygen species and malondialdehyde levels were dramatically decreased (p less then .05) in the testes of the QLP-treated rats. QLP treatment partly reverted (p less then .05) the circulatory levels of reproductive hormones (FSH, LH, testosterone, prolactin and SHBG) and hepatic and renal function (AST, Cr and urea). Our results showed that oral QLP treatment had a curative effect on the testicular mass, sperm quality, testicular pathomorphology, antioxidants, plasmatic hormones, and liver and renal function of rats.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients present with fever in the early phase, with some progressing to a hyperinflammatory phase. Ethanol (EtOH) exposure may lead to systemic inflammation. Network meta-analysis was conducted to examine possible relationships between EtOH consumption and COVID-19 pathologies.

Molecules affected by EtOH exposure were identified by analysis with QIAGEN Knowledge Base. Molecules affected by COVID-19 were identified from studies in MEDLINE, bioRxiv, and medRxiv reporting gene expression profiles in COVID-19 patients, QIAGEN Coronavirus Network Explorer, and analysis of the RNA-sequencing data of autopsied lungs of COVID-19 patients retrieved from the GEO database. Network meta-analysis was then conducted on these molecules using QIAGEN Ingenuity Pathway Analysis (IPA).

Twenty-eight studies reporting significant gene expression changes in COVID-19 patas increased during the COVID-19 pandemic. The findings also call for further investigation into how alcohol exposure affects viral infections.

Our meta-analyses demonstrate that EtOH exposure may augment SARS-CoV-2-induced inflammation by altering the activity of key inflammatory mediators. Our findings suggest that it is important for clinicians to caution patients about the risk of alcohol consumption, which has increased during the COVID-19 pandemic. The findings also call for further investigation into how alcohol exposure affects viral infections.