1,418 research outputs found
The presence of GC-AG introns in Neurospora crassa and other euascomycetes determined from analyses of complete genomes: implications for automated gene prediction
AbstractA combination of experimental and computational approaches was employed to identify introns with noncanonical GC-AG splice sites (GC-AG introns) within euascomycete genomes. Evaluation of 2335 cDNA-confirmed introns from Neurospora crassa revealed 27 such introns (1.2%). A similar frequency (1.0%) of GC-AG introns was identified in Fusarium graminearum, in which 3 of 292 cDNA-confirmed introns contained GC-AG splice sites. Computational analyses of the N. crassa genome using a GC-AG intron consensus sequence identified an additional 20 probable GC-AG introns in this fungus. For 8 of the 47 GC-AG introns identified in N. crassa a GC donor site is also present in a homolog from Magnaporthe grisea, F. graminearum, or Aspergillus nidulans. In most cases, however, homologs in these fungi contain a GT-AG intron or no intron at the corresponding position. These findings have important implications for fungal genome annotation, as the automated annotations of euascomycete genomes incorrectly identified intron boundaries for all of the confirmed and probable GC-AG introns reported here
Comparative Safety Analysis of Opioid Agonist Treatment in Pregnant Women with Opioid Use Disorder: A Population-Based Study
Introduction and Objective:
Receipt of opioid agonist treatment during early and late pregnancy for opioid use disorder may relate to varying perinatal risks. We aimed to assess the effect of time-varying prenatal exposure to opioid agonist treatment using buprenorphine or methadone on adverse neonatal and pregnancy outcomes.
Methods:
We conducted a retrospective cohort study of pregnant women with opioid use disorder using Rhode Island Medicaid claims data and vital statistics during 2008–16. Time-varying exposure was evaluated in early (0–20 weeks) and late (≥ 21 weeks) pregnancy. Marginal structural models with inverse probability of treatment weighting were applied.
Results:
Of 400 eligible pregnancies, 85 and 137 individuals received buprenorphine and methadone, respectively, during early pregnancy. Compared with 152 untreated pregnancies with opioid use disorders, methadone exposure in both periods was associated with an increased risk of preterm birth (adjusted odds ratio [aOR]: 2.52; 95% confidence interval [CI] 1.07–5.95), low birth weight (aOR: 2.99; 95% CI 1.34–6.66), neonatal intensive care unit admission (aOR, 5.04; 95% CI 2.49–10.21), neonatal abstinence syndrome (aOR: 11.36; 95% CI 5.65–22.82), respiratory symptoms (aOR, 2.71; 95% CI 1.17–6.24), and maternal hospital stay \u3e 7 days (aOR, 14.51; 95% CI 7.23–29.12). Similar patterns emerged for buprenorphine regarding neonatal abstinence syndrome (aOR: 10.27; 95% CI 4.91–21.47) and extended maternal hospital stay (aOR: 3.84; 95% CI 1.83–8.07). However, differences were found favoring the use of buprenorphine for preterm birth versus untreated pregnancies (aOR: 0.17; 95% CI 0.04–0.77), and for several outcomes versus methadone.
Conclusions:
Methadone and buprenorphine prescribed for the treatment of opioid use disorder during pregnancy are associated with varying perinatal risks. However, buprenorphine may be preferred in the setting of pregnancy opioid agonist treatment. Further research is necessary to confirm our findings and minimize residual confounding
Severe muscle trauma triggers heightened and prolonged local musculoskeletal inflammation and impairs adjacent tibia fracture healing
Objectives:
Complicated fracture healing is often associated with the severity of surrounding muscle tissue trauma. Since inflammation is a primary determinant of musculoskeletal health and regeneration, it is plausible that delayed healing and non-unions are partly caused by compounding local inflammation in response to concomitant muscle trauma.
Methods and results:
To investigate this possibility, a Lewis rat open fracture model [tibia osteotomy with adjacent tibialis anterior (TA) muscle volumetric muscle loss (VML) injury] was interrogated. We observed that VML injury impaired tibia healing, as indicated by diminished mechanical strength and decreased mineralized bone within the fracture callus, as well as continued presence of cartilage instead of woven bone 28 days post-injury. The VML injured muscle presented innate and adaptive immune responses that were atypical of canonical muscle injury healing. Additionally, the VML injury resulted in a perturbation of the inflammatory phase of fracture healing, as indicated by elevations of CD3+ lymphocytes and CD68+ macrophages in the fracture callus at 3 and 14d post-injury, respectively.
Conclusions:
These data indicate that heightened and sustained innate and adaptive immune responses to traumatized muscle are associated with impaired fracture healing and may be targeted for the prevention of delayed and non-union following musculoskeletal trauma
A consideration of the challenges involved in supervising international masters students
This paper explores the challenges facing supervisors of international postgraduate students at the dissertation stage of the masters programme. The central problems of time pressure, language difficulties, a lack of critical analysis and a prevalence of personal problems among international students are discussed. This paper makes recommendations for the improvement of language and critical thinking skills, and questions the future policy of language requirements at HE for international Masters students
Characterization of a Fusarium graminearum Salicylate Hydroxylase
Salicylic acid (SA) plays an important role in regulating plant defense responses against pathogens. However, pathogens have evolved ways to manipulate plant SA-mediated defense signaling. Fusarium graminearum causes Fusarium head blight (FHB) and reduces crop yields and quality by producing various mycotoxins. In this study, we aimed to identify the salicylate hydroxylase in F. graminearum and determine its role in wheat head blight development. We initially identified a gene in F. graminearum strain NRRL 46422 that encodes a putative salicylate hydroxylase (designated FgShyC). However, the FgShyC deletion mutant showed a similar ability to degrade SA as wild-type strain 46422; nor did overexpression of FgShyC in E. coli convert SA to catechol. The results indicate that FgShyC is not involved in SA degradation. Further genome sequence analyses resulted in the identification of eight salicylate hydroxylase candidates. Upon addition of 1 mM SA, FGSG_03657 (designated FgShy1), was induced approximately 400-fold. Heterologous expression of FgShy1 in E. coli converted SA to catechol, confirming that FgShy1 is a salicylate hydroxylase. Deletion mutants of FgShy1 were greatly impaired but not completely blocked in SA degradation. Expression analyses of infected tissue showed that FgShy1 was induced during infection, but virulence assays revealed that deletion of FgShy1 alone was not sufficient to affect FHB severity. Although the Fgshy1 deletion mutant did not reduce pathogenicity, we cannot rule out that additional salicylate hydroxylases are present in F. graminearum and characterization of these enzymes will be necessary to fully understand the role of SA-degradation in FHB pathogenesis
Language and anxiety: an ethnographic study of international postgraduate students
This paper presents some findings from an ethnographic study of international postgraduate students at a university in the South of England, which involved interviews and participant observation over a twelve-month academic year. One of the major themes that emerged from this research was students’ anxiety over their level of English language. Although all students entered their course with a minimum level of IELTS 6, the majority felt disadvantaged by particularly poor spoken English, and suffered feelings of anxiety, shame and inferiority. Low self-confidence meant that they felt ill-equipped to engage in class discussion and in social interaction which used English as the medium of communication. A common reaction to stress caused by language problems was to retreat into monoethnic communication with students from the same country, further inhibiting progress in language. Whilst some linguistic progress was made by nearly all students during the academic sojourn, the anxiety suffered by students in the initial stage must not be underestimated, and appropriate support systems must be put in place to alleviate their distress
Impairment of early fracture healing by skeletal muscle trauma is restored by FK506
BACKGROUND:
Heightened local inflammation due to muscle trauma or disease is associated with impaired bone regeneration.
METHODS:
We hypothesized that FK506, an FDA approved immunomodulatory compound with neurotrophic and osteogenic effects, will rescue the early phase of fracture healing which is impaired by concomitant muscle trauma in male (~4 months old) Lewis rats. FK506 (1 mg/kg; i.p.) or saline was administered systemically for 14 days after an endogenously healing tibia osteotomy was created and fixed with an intermedullary pin, and the overlying tibialis anterior (TA) muscle was either left uninjured or incurred volumetric muscle loss injury (6 mm full thickness biopsy from middle third of the muscle).
RESULTS:
The salient observations of this study were that 1) concomitant TA muscle trauma impaired recovery of tibia mechanical properties 28 days post-injury, 2) FK506 administration rescued the recovery of tibia mechanical properties in the presence of concomitant TA muscle trauma but did not augment mechanical recovery of an isolated osteotomy (no muscle trauma), 3) T lymphocytes and macrophage presence within the traumatized musculature were heightened by trauma and attenuated by FK506 3 days post-injury, and 4) T lymphocyte but not macrophage presence within the fracture callus were attenuated by FK506 at 14 days post-injury. FK506 did not improve TA muscle isometric torque production CONCLUSION: Collectively, these findings support the administration of FK506 to ameliorate healing of fractures with severe muscle trauma comorbidity. The results suggest one potential mechanism of action is a reduction in local T lymphocytes within the injured musculoskeletal tissue, though other mechanisms to include direct osteogenic effects of FK506 require further investigation
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