Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these "functional" pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit.

Background

End-stage renal disease (ESRD) is a disease with an aging population and a high prevalence of cognitive impairment affecting quality of life, health care costs and mortality. Structural changes in the brain with decreased white matter integrity have been observed in ESRD. Understanding the changes in cognition and associated changes in brain structure after renal transplantation can help define the mechanisms underlying cognitive impairment in ESRD.

Methods

We conducted a prospective, observational cohort study in ESRD patients listed for renal transplantation and followed them post-transplantation. We assessed their cognitive function with a battery of neuropsychological tests and brain white matter integrity with diffusion tensor imaging (DTI) both before transplant and 3 months after transplant.

Results

Eleven patients, aged 56.5 ± 10.7 years, completed the study. Cognitive measures of memory and executive function improved after the transplant, specifically on tests of logical memory I (p = 0.004), logical memory II (p = 0.003) and digit symbol (p < 0.0001). DTI metrics also improved post the transplant with an increase in fractional anisotropy (p = 0.01) and decrease in mean diffusivity (p = 0.004). These changes were more prominent in tracts associated with memory and executive function.

Conclusions

Cognitive function, particularly memory and executive function, improve post the transplant with concurrent improvements in white matter integrity in tracts associated with memory and executive function. These data suggest that abnormalities in cognition and brain structure seen in the ESRD population are at least partially reversible.

Background

Cognitive impairment is common in kidney transplant (KT) recipients and affects quality of life, graft survival, morbidity, and mortality. Failure to identify patients with cognitive impairment can withhold appropriate and timely intervention. This study determines whether measured cognition with standard screening tools offers any advantage over perceived cognition in screening transplant patients for cognitive impairment.

Methods

Cognition was assessed in 157 KT recipients using the Montreal Cognitive Assessment (MoCA; measured cognition). In addition, transplant physicians and nurse coordinators were asked to rate transplant recipients' level of cognition after routine clinical interactions (perceived cognition). Physicians and nurses were blind to MoCA scores. Perceived cognition scores were compared to MoCA scores.

Results

Perceived cognition scores fairly correlated with MOCA scores (γ = 0.24, p = 0.001 for physicians and γ = 0.33, p < 0.0001 for nurses). Physician scores moderately correlated with nurses scores (κ = 0.44, p < 0.0001). Clinical perception had a low accuracy for identifying patients with cognitive impairment (sensitivity 66% for physicians, 65% for nurses), and those without cognitive impairment (specificity 67% for physicians, 76% for nurses).

Conclusion

Clinical perception is inaccurate at detecting cognitive impairment in KT recipients. Objective tests should be considered to screen KT recipients for cognitive impairment.

Background

There is a high prevalence of cognitive impairment in dialysis patients. The prevalence of cognitive impairment after kidney transplantation is unknown.

Methods

Study Design: Cross-sectional study.

Setting and participants

Single center study of prevalent kidney transplant recipients from a transplant clinic in a large academic center.

Intervention

Assessment of cognition using the Montreal Cognitive Assessment (MoCA). Demographic and clinical variables associated with cognitive impairment were also examined. Outcomes and Measurements: a) Prevalence of cognitive impairment defined by a MoCA score of <26. b) Multivariable linear and logistic regression to examine the association of demographic and clinical factors with cognitive impairment.

Results

Data from 226 patients were analyzed. Mean (SD) age was 54 (13.4) years, 73% were white, 60% were male, 37% had diabetes, 58% had an education level of college or above, and the mean (SD) time since kidney transplant was 3.4 (4.1) years. The prevalence of cognitive impairment was 58.0%. Multivariable linear regression demonstrated that older age, male gender and absence of diabetes were associated with lower MoCA scores (p < 0.01 for all). Estimated glomerular filtration rate (eGFR) was not associated with level of cognition. The logistic regression analysis confirmed the association of older age with cognitive impairment.

Conclusion

Cognitive impairment is common in prevalent kidney transplant recipients, at a younger age compared to general population, and is associated with certain demographic variables, but not level of eGFR.

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/.