Similar frequency and signature of untargeted substitutions induced by abasic site analog under reduced human APE1 conditions

INTRODUCTION: We compared the physiological responses, psychomotor performances, and hypoxia symptoms between 7000 m and 7500 m (23,000 and 24,600 ft) exposure to develop a safer hypoxia training protocol.METHODS: In altitude chamber, 66 male pilots were exposed to 7000 and 7500 m. Heart rate and arterial oxygen saturation were continuously monitored. Psychomotor performance was assessed using the computational task. The hypoxic symptoms were investigated by a questionnaire.RESULTS: The mean duration time of hypoxia was 323.0 56.5 s at 7000 m and 218.2 63.3 s at 7500 m. The 6-min hypoxia training was completed by 57.6% of the pilots and 6.1% of the pilots at 7000 m and at 7500 m, respectively. There were no significant differences in pilots heart rates and psychomotor performance between the two exposures. The Spo2 response at 7500 m was slightly severer than that at 7000 m. During the 7000 m exposure, pilots experienced almost the same symptoms and similar frequency order as those during the 7500 m exposure.CONCLUSIONS: There were concordant symptoms, psychomotor performance, and very similar physiological responses between 7000 m and 7500 m during hypoxia training. The results indicated that 7000-m hypoxia awareness training might be an alternative to 7500-m hypoxia training with lower DCS risk and longer experience time.Wen D, Tu L, Wang G, Gu Z, Shi W, Liu X. Psychophysiological responses of pilots in hypoxia training at 7000 and 7500 m. Aerosp Med Hum Perform. 2020; 91(10):785789.

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Faculty Opinions recommendation of Analysis of translesion replication across an abasic site by DNA polymerase IV of Escherichia coli.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016604.201051 ◽

2003 ◽

Author(s):

Errol C Friedberg

Keyword(s):

Escherichia Coli ◽

Dna Polymerase ◽

Abasic Site ◽

Dna Polymerase Iv

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Different stress from parasites and mate choice in two female morphs of the blue-tailed damselfly

Evolutionary Ecology ◽

10.1007/s10682-021-10130-z ◽

2021 ◽

Author(s):

Erica Subrero ◽

Irene Pellegrino ◽

Marco Cucco

Keyword(s):

Mating Behaviour ◽

Adult Males ◽

Similar Frequency ◽

Male Preference ◽

Ischnura Elegans ◽

Emergence Success ◽

The Common ◽

Nw Italy ◽

Whole Life Cycle ◽

Pairing Behaviour

AbstractIn Odonates, female colour polymorphism is common and implies the presence of two or more female types with different colours and behaviours. To explain this phenomenon, several hypotheses have been proposed that consider morph frequency, population density, the presence of parasites, and mating behaviour. We studied the blue-tailed damselfly Ischnura elegans, a species with a blue androchrome morph and two gynochrome morphs (the common green infuscans, and the rare orange rufescens-obsoleta). The size of adult males and females, the presence of parasites, and pairing behaviour between males and the three female morphs was assessed in field conditions throughout the reproductive season in NW Italy. Moreover, growth and emergence success of larvae produced by the different morphs was analyzed in standardized conditions. In the field, males showed a preference for the gynochrome infuscans females, despite a similar frequency of androchrome females. In test conditions, male preference for the infuscans females was also observed. Paired males and paired androchrome females were larger than unpaired individuals, while there were no differences in size between paired and unpaired infuscans females. Males and androchrome females were more parasitized than infuscans females. The survival and emergence success of larvae produced by androchrome females was higher than those of offspring produced by the infuscans females. Our results suggest that a higher survival of progeny at the larval stage could counterbalance the higher parasitism and the lower pairing success of andromorph adult females and highlight the importance of considering the whole life-cycle in polymorphism studies.

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Exome-based investigation of the genetic basis of human pigmentary glaucoma

BMC Genomics ◽

10.1186/s12864-021-07782-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Carly van der Heide ◽

Wes Goar ◽

Kacie J. Meyer ◽

Wallace L. M. Alward ◽

Erin A. Boese ◽

...

Keyword(s):

Genetic Basis ◽

Immunohistochemical Analysis ◽

Pigment Dispersion ◽

Pigmentary Glaucoma ◽

Visual Disability ◽

Primary Analysis ◽

Human Donor ◽

Similar Frequency ◽

Pigment Dispersion Syndrome ◽

Rare Mutations

Abstract Background Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. Results Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. Conclusions We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.

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AB0423 NEUROPSYCHIATRIC OUTCOME OF CHILDREN BORN TO WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) WOMEN AND EXPOSED IN UTERO TO AZATHIOPRINE: A CASE-CONTROL STUDY.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4912 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1511.2-1511

Author(s):

M. G. Lazzaroni ◽

F. Crisafulli ◽

I. Debeni ◽

C. Nalli ◽

L. Andreoli ◽

...

Keyword(s):

Lupus Erythematosus ◽

Renal Involvement ◽

In Utero ◽

Learning Disorders ◽

Control Group ◽

In Utero Exposure ◽

Term Outcome ◽

Similar Frequency ◽

Long Term Outcome

Background:A possible increase in neurodevelopmental (ND) and learning disorders (LD) in the offspring of mothers affected by SLE have been suggested in some studies, along with the identification of different possible risk factors. Azathioprine (AZA) is commonly used during pregnancy, based on its non-teratogenicity and extended experience in women with different diseases. However, a few small studies suggested an association between in utero exposure to AZA and possible increased frequency of ND/LD in children, indirectly derived from increased request of supportive educational services.Objectives:To evaluate the medium-long term outcome in terms of ND/LD in children of school age (≥6 years) born to SLE women treated with AZA during pregnancy, as compared to that of children born to SLE mothers not treated with AZA during pregnancy.Methods:Data from our Pregnancy Clinic registry were collected for prospectively followed pregnancies of SLE women treated with AZA (cases) and compared to pregnancies of SLE women not treated with AZA (controls), that were matched for age at pregnancy, presence of renal involvement and aPL positivity. SLE patients (cases and controls) were interviewed by phone to collect data about their children, focusing on the presence of ND/LD certified by Neuropsychiatrists.Results:Data were collected for 14 SLE mothers in the AZA group and 31 in the control group, with similar age at pregnancy (30.3±5.21 vs 31.4±4.70 years, p:0.45) and frequency of renal involvement (50.0% vs 44.1%, p:0.77), aPL positivity (33.3% vs 29.4%, p:0.76) and anti-Ro/SSA positivity (27.8% vs. 26.5%, p:0.55). A SLE flare during pregnancy was more frequently recorded in the AZA group (27.8% vs. 2.94%, p:0.02). Other medications included HCQ (55.6% vs. 70.6%, p:0.36) and corticosteroids (100% vs 79.4%, p:0.08).We collected data for 18 children in the AZA group and 34 children in the control group, that had a similar mean age at the time of the interview (12.7±4.80 vs. 12.9±5.61 years, p:0.91). The two groups had also similar gestational age (37.4±2.20 weeks vs. 38.0±1.29 weeks, p:0.23), birth weight (3003±433 g vs 3011±453 g, p:0.95) and rate of male sex (61.1% vs 44.1%, p:0.38).We recorded similar frequency of ND/LD in the two groups. In particular, a ND was present in 2/18 (11.1%) of children exposed to AZA vs. 2/34 (5.88%) in the control group (p:0.60). A LD was present in 1/18 cases (5.56%) and 6/34 controls (17.6%) (p:0.40).Conclusion:The medium-long term outcome of children born to SLE mothers in the whole cohort was characterized by the presence of ND in 4/54 (7.69%) and LD in 7/52 (13.5%). ND/LD do not seem to be related to in utero exposure to AZA.Disclosure of Interests:None declared

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Myocardial infarctions, subtypes and coronary atherosclerosis in SLE: a case–control study

Lupus Science & Medicine ◽

10.1136/lupus-2021-000515 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000515

Author(s):

Isak Samuelsson ◽

Ioannis Parodis ◽

Iva Gunnarsson ◽

Agneta Zickert ◽

Claes Hofman-Bang ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Coronary Atherosclerosis ◽

Great Majority ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Medical File ◽

Similar Frequency ◽

Ventricular Ejection Fraction ◽

Increased Risk

ObjectivePatients with SLE have increased risk of myocardial infarction (MI). Few studies have investigated the characteristics of SLE-related MIs. We compared characteristics of and risk factors for MI between SLE patients with MI (MI-SLE), MI patients without SLE (MI-non-SLE) and SLE patients without MI (non-MI-SLE) to understand underlying mechanisms.MethodsWe identified patients with a first-time MI in the Karolinska SLE cohort. These patients were individually matched for age and gender with MI-non-SLE and non-MI-SLE controls in a ratio of 1:1:1. Retrospective medical file review was performed. Paired statistics were used as appropriate.ResultsThirty-four MI-SLE patients (88% females) with a median age of 61 years were included. These patients had increased number of coronary arteries involved (p=0.04), and ≥50% coronary atherosclerosis/occlusion was numerically more common compared with MI-non-SLE controls (88% vs 66%; p=0.07). The left anterior descending artery was most commonly involved (73% vs 59%; p=0.11) and decreased (<50%) left ventricular ejection fraction occurred with similar frequency in MI-SLE and MI-non-SLE patients (45% vs 36%; p=0.79). Cardiovascular disease (44%, 5.9%, 12%; p<0.001) and coronary artery disease (32%, 2.9%, 0%; p<0.001), excluding MI, preceded MI/inclusion more commonly in MI-SLE than in MI-non-SLE and non-MI-SLE patients, respectively. MI-SLE patients had lower plasma albumin levels than non-MI-SLE patients (35 (29–37) vs 40 (37–42) g/L; p=0.002).ConclusionIn the great majority of cases, MIs in SLE are associated with coronary atherosclerosis. Furthermore, MIs in SLE are commonly preceded by symptomatic vascular disease, calling for attentive surveillance of cardiovascular disease and its risk factors and early atheroprotective treatment.

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Clinical and Biological Characteristics of Medullary and Extramedullary Plasma Cell Dyscrasias

Biology ◽

10.3390/biology10070629 ◽

2021 ◽

Vol 10 (7) ◽

pp. 629

Author(s):

Snjezana Janjetovic ◽

Philipp Lohneis ◽

Axel Nogai ◽

Derya Balci ◽

Leo Rasche ◽

...

Keyword(s):

Plasma Cell ◽

Molecular Mechanisms ◽

Biological Characteristics ◽

Surface Glycoprotein ◽

Cell Surface Glycoprotein ◽

Similar Frequency ◽

Cytogenetic Aberrations ◽

A Cell ◽

Plasma Cell Dyscrasias ◽

Extramedullary Plasmocytoma

Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p < 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4;14) and t(14;16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP.

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Dynamic Stability Performance of Autonomous Microgrid Involving High Penetration Level of Constant Power Loads

Mathematics ◽

10.3390/math9090922 ◽

2021 ◽

Vol 9 (9) ◽

pp. 922

Author(s):

Mohamed Hassan ◽

Muhammed Worku ◽

Abdelfattah Eladl ◽

Mohammed Abido

Keyword(s):

Dynamic Stability ◽

Power Sharing ◽

Constant Power ◽

Similar Frequency ◽

Stability Performance ◽

High Penetration ◽

Constant Power Loads ◽

The Time Domain ◽

And Control ◽

The Impact

Nowadays, behaving as constant power loads (CPLs), rectifiers and voltage regulators are extensively used in microgrids (MGs). The MG dynamic behavior challenges both stability and control effectiveness in the presence of CPLs. CPLs characteristics such as negative incremental resistance, synchronization, and control loop dynamic with similar frequency range of the inverter disturb severely the MG stability. Additionally, the MG stability problem will be more sophisticated with a high penetration level of CPLs in MGs. The stability analysis becomes more essential especially with high-penetrated CPLs. In this paper, the dynamic stability performance of an MG involving a high penetration level of CPLs is analyzed and investigated. An autonomous MG engaging a number of CPLs and inverter distributed generations (DGs) is modeled and designed using MATLAB. Voltage, current, and power controllers are optimally designed, controlling the inverter DGs output. A power droop controller is implemented to share the output DGs powers. Meanwhile, the current and voltage controllers are employed to control the output voltage and current of all DGs. A phase-locked loop (PLL) is essentially utilized to synchronize the CPLs with the MG. The controller gains of the inverters, CPLs, power sharing control, and PLL are optimally devised using particle swarm optimization (PSO). As a weighted objective function, the error in the DC voltage of the CPL and active power of the DG is minimized in the optimal problem based on the time-domain simulation. Under the presence of high penetrated CPLs, all controllers are coordinately tuned to ensure an enhanced dynamic stability of the MG. The impact of the highly penetrated CPLs on the MG dynamic stability is investigated. To confirm the effectiveness of the proposed technique, different disturbances are applied. The analysis shows that the MG system experiences the instability challenges due to the high penetrated CPLs. The simulation results confirm the effectiveness of the proposed method to improve the MG dynamic stability performance.

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