International Students Sense of Belongingness and Motivation on Academic and Flight Performance

There are many factors that can affect international students’ success in flight training. Motivation, confidence, and internal achievement factors such as locus of control (LOC) and self-efficacy are important in successful learning. Moving to a new country, where language and customs may be quite different from one’s own, may adversely affect one’s confidence. A feeling of belongingness might affect students’ confidence, therefore affecting flight training performance. Belongingness can be measured by social and academic club membership, engagement in social activities, confidence in English, etc. This study explored the relationship between self-reports of social activities and confidence with academic performance and flight performance. Nineteen international students (13m, 6f) with a mean Age of 21.42 (SD = 2.29), currently enrolled in a flight training program at an aeronautical university answered an online survey. To participate students must have earned their private pilot’s license, but not obtained any higher certification. Students who participated were from North America, South America, Europe, Africa, and Asia. Significant correlations were found between LOC and confidence in the English language; self-efficacy and number of failures at the end of the Private Pilot course; confidence in the English language and social involvement; and flight training confidence and social involvement. Males reported significantly higher levels of flight training confidence than females. A regression model showed that flight training confidence can be significantly predicted by students’ self-assessed sense of belonging, academic confidence, and LOC. Knowing the characteristics that motivate international students may have positive outcomes of successful flight training performance

International Students Sense of Belongingness and Motivation on Academic and Flight Performance

There are many factors that can affect international students’ success in flight training. Motivation, confidence, and internal achievement factors such as locus of control (LOC) and self-efficacy are important in successful learning. Moving to a new country, where language and customs may be quite different from one’s own, may adversely affect one’s confidence. A feeling of belongingness might affect students’ confidence, therefore affecting flight training performance. Belongingness can be measured by social and academic club membership, engagement in social activities, confidence in English, etc. This study explored the relationship between self-reports of social activities and confidence with academic performance and flight performance. Nineteen international students (13m, 6f) with a mean Age of 21.42 (SD = 2.29), currently enrolled in a flight training program at an aeronautical university answered an online survey. To participate students must have earned their private pilot’s license, but not obtained any higher certification. Students who participated were from North America, South America, Europe, Africa, and Asia. Significant correlations were found between LOC and confidence in the English language; self-efficacy and number of failures at the end of the Private Pilot course; confidence in the English language and social involvement; and flight training confidence and social involvement. Males reported significantly higher levels of flight training confidence than females. A regression model showed that flight training confidence can be significantly predicted by students’ self-assessed sense of belonging, academic confidence, and LOC. Knowing the characteristics that motivate international students may have positive outcomes of successful flight training performance

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

Metnase promotes restart and repair of stalled and collapsed replication forks

Metnase is a human protein with methylase (SET) and nuclease domains that is widely expressed, especially in proliferating tissues. Metnase promotes non-homologous end-joining (NHEJ), and knockdown causes mild hypersensitivity to ionizing radiation. Metnase also promotes plasmid and viral DNA integration, and topoisomerase IIα (TopoIIα)-dependent chromosome decatenation. NHEJ factors have been implicated in the replication stress response, and TopoIIα has been proposed to relax positive supercoils in front of replication forks. Here we show that Metnase promotes cell proliferation, but it does not alter cell cycle distributions, or replication fork progression. However, Metnase knockdown sensitizes cells to replication stress and confers a marked defect in restart of stalled replication forks. Metnase promotes resolution of phosphorylated histone H2AX, a marker of DNA double-strand breaks at collapsed forks, and it co-immunoprecipitates with PCNA and RAD9, a member of the PCNA-like RAD9–HUS1–RAD1 intra-S checkpoint complex. Metnase also promotes TopoIIα-mediated relaxation of positively supercoiled DNA. Metnase is not required for RAD51 focus formation after replication stress, but Metnase knockdown cells show increased RAD51 foci in the presence or absence of replication stress. These results establish Metnase as a key factor that promotes restart of stalled replication forks, and implicate Metnase in the repair of collapsed forks

A dual role of BRCA1 in two distinct homologous recombination mediated repair in response to replication arrest

Homologous recombination (HR) is a major mechanism utilized to repair blockage of DNA replication forks. Here, we report that a sister chromatid exchange (SCE) generated by crossover-associated HR efficiently occurs in response to replication fork stalling before any measurable DNA double-strand breaks (DSBs). Interestingly, SCE produced by replication fork collapse following DNA DSBs creation is specifically suppressed by ATR, a central regulator of the replication checkpoint. BRCA1 depletion leads to decreased RPA2 phosphorylation (RPA2-P) following replication fork stalling but has no obvious effect on RPA2-P following replication fork collapse. Importantly, we found that BRCA1 promotes RAD51 recruitment and SCE induced by replication fork stalling independent of ATR. In contrast, BRCA1 depletion leads to a more profound defect in RAD51 recruitment and SCE induced by replication fork collapse when ATR is depleted. We concluded that BRCA1 plays a dual role in two distinct HR-mediated repair upon replication fork stalling and collapse. Our data established a molecular basis for the observation that defective BRCA1 leads to a high sensitivity to agents that cause replication blocks without being associated with DSBs, and also implicate a novel mechanism by which loss of cell cycle checkpoints promotes BRCA1-associated tumorigenesis via enhancing HR defect resulting from BRCA1 deficiency

H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues

A sequence variant of histone H2A called H2AX is one of the key components of chromatin involved in DNA damage response induced by different genotoxic stresses. Phosphorylated H2AX (γH2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress. γH2AX foci could be easily detected in cell nuclei using immunofluorescence microscopy that allows to use γH2AX as a quantitative marker of DSBs in various applications. H2AX is phosphorylated in situ by ATM, ATR, and DNA-PK kinases that have distinct roles in different pathways of DSB repair. The γH2AX serves as a docking site for the accumulation of DNA repair proteins, and after rejoining of DSBs, it is released from chromatin. The molecular mechanism of γH2AX dephosphorylation is not clear. It is complicated and requires the activity of different proteins including phosphatases and chromatin-remodeling complexes. In this review, we summarize recently published data concerning the mechanisms and kinetics of γH2AX loss in normal cells and tissues as well as in those deficient in ATM, DNA-PK, and DSB repair proteins activity. The results of the latest scientific research of the low-dose irradiation phenomenon are presented including the bystander effect and the adaptive response estimated by γH2AX detection in cells and tissues

ATR and H2AX cooperate in maintaining genome stability under replication stress

Problems during DNA replication often cause chromosomal abnormalities when replication forks become unstable and fail to progress properly. If forks stall, mechanisms become activated to maintain replication fork stability, restart progression and avoid collapse into double-strand DNA breaks (DSBs). ATR (ataxia telangiectasia and rad3-related) is thought to play an important role in maintaining replication fork stability, as evidenced by a dramatic increase in DSBs upon stalled DNA replication in ATR-deficient cells. Here we demonstrate that, upon stalled replication, ATR-deficient cells have increased H2AX phosphorylation and Rad51 foci, markers of DSB formation. The ATR-related kinases, ATM and DNA-PKcs, mediate this phosphorylation. Depletion of ATR in H2AX-deficient cells leads to increased DSBs in metaphase spreads. A significant decrease in Rad51 foci was seen in ATR knockout cells when H2AX was absent, suggesting a failure of homologous recombination-mediated repair mechanisms in the absence of H2AX. Consistent with a failure of normal repair mechanisms, sister chromatid translocation events increase in ATR/H2AX double knockout cells, suggesting that ATR and H2AX work cooperatively to suppress DSBs upon stalled DNA replication