The RecQ DNA helicase Rqh1 constrains Exonuclease 1-dependent recombination at stalled replication forks

Acknowledgements We thank Benoit Arcangioli, Andrei Kuzminov and Shao-Win Wang for providing strains/plasmids. This work was supported by grants 057586/Z/99/A and 090767/Z/09/Z from the Wellcome Trust.Peer reviewedPublisher PD

Clinical Comparison of the Auditory Steady-State Response with the Click Auditory Brainstem Response in Infants

ObjectivesOur goal was to determine the effectiveness of using the auditory steady state response (ASSR) as a measure of hearing thresholds in infants who are suspected of having significant hearing loss, as compared with using the click-auditory brainstem response (C-ABR).MethodsWe retrospectively analyzed the audiologic profiles of 76 infants (46 boys and 30 girls, a total of 151 ears) who ranged in age from 1 to 12 months (average age: 5.7 months). The auditory evaluations in 76 infants who were suspected of having hearing loss were done via the C-ABR and ASSR. In addition, for reference, the mean ASSR thresholds were compared to those of 39 ears of infants and 39 ears of adults with normal hearing at 0.5, 1, 2, and 4 kHz.ResultsThe highest correlation between the C-ABR and ASSR thresholds was observed at an average of 2-4 kHz (r=0.94). On comparison between the hearing of infants and adults at 0.5, 1, 2, and 4 kHz, the mean ASSR threshold in infants was 12, 7, 8, and 7 dB higher, respectively, than that in adults.ConclusionASSR testing may provide additional audiometric information for accurately predicting the hearing sensitivity, and this is essential for the management of infants with severe to profound hearing loss

PwRn1, a novel Ty3/gypsy-like retrotransposon of Paragonimus westermani: molecular characters and its differentially preserved mobile potential according to host chromosomal polyploidy

<p>Abstract</p> <p>Background</p> <p>Retrotransposons have been known to involve in the remodeling and evolution of host genome. These reverse transcribing elements, which show a complex evolutionary pathway with diverse intermediate forms, have been comprehensively analyzed from a wide range of host genomes, while the information remains limited to only a few species in the phylum Platyhelminthes.</p> <p>Results</p> <p>A LTR retrotransposon and its homologs with a strong phylogenetic affinity toward <it>CsRn1 </it>of <it>Clonorchis sinensis </it>were isolated from a trematode parasite <it>Paragonimus westermani </it>via a degenerate PCR method and from an insect species <it>Anopheles gambiae </it>by <it>in silico </it>analysis of the whole mosquito genome, respectively. These elements, designated <it>PwRn1 </it>and <it>AgCR-1 </it>– <it>AgCR-14 </it>conserved unique features including a t-RNA^Trpprimer binding site and the unusual CHCC signature of Gag proteins. Their flanking LTRs displayed >97% nucleotide identities and thus, these elements were likely to have expanded recently in the trematode and insect genomes. They evolved heterogeneous expression strategies: a single fused ORF, two separate ORFs with an identical reading frame and two ORFs overlapped by -1 frameshifting. Phylogenetic analyses suggested that the elements with the separate ORFs had evolved from an ancestral form(s) with the overlapped ORFs. The mobile potential of <it>PwRn1 </it>was likely to be maintained differentially in association with the karyotype of host genomes, as was examined by the presence/absence of intergenomic polymorphism and mRNA transcripts.</p> <p>Conclusion</p> <p>Our results on the structural diversity of <it>CsRn1</it>-like elements can provide a molecular tool to dissect a more detailed evolutionary episode of LTR retrotransposons. The <it>PwRn1</it>-associated genomic polymorphism, which is substantial in diploids, will also be informative in addressing genomic diversification following inter-/intra-specific hybridization in <it>P. westermani </it>populations.</p

PCR for Diagnosis of Male Trichomonas vaginalis Infection with Chronic Prostatitis and Urethritis

The aim of this study was to assess the usefulness of PCR for diagnosis of Trichomonas vaginalis infection among male patients with chronic recurrent prostatitis and urethritis. Between June 2001 and December 2003, a total of 33 patients visited the Department of Urology, Hanyang University Guri Hospital and were examined for T. vaginalis infection by PCR and culture in TYM medium. For the PCR, we used primers based on a repetitive sequence cloned from T. vaginalis (TV-E650). Voided bladder urine (VB1 and VB3) was sampled from 33 men with symptoms of lower urinary tract infection (urethral charge, residual urine sensation, and frequency). Culture failed to detect any T. vaginalis infection whereas PCR identified 7 cases of trichomoniasis (21.2%). Five of the 7 cases had been diagnosed with prostatitis and 2 with urethritis. PCR for the 5 prostatitis cases yielded a positive 330 bp band from bothVB1 and VB3, whereas positive results were only obtained from VB1 for the 2 urethritis patients. We showed that the PCR method could detect T. vaginalis when there was only 1 T. vaginalis cell per PCR mixture. Our results strongly support the usefulness of PCR on urine samples for detecting T. vaginalis in chronic prostatitis and urethritis patients

DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load

Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation in precision immunotherapy

Prealbumin is Not Sensitive Indicator of Nutrition and Prognosis in Critical Ill Patients

It was reported that 30-50% of inpatients are in a malnutrition status. Measuring the prealbumin level is a sensitive and cost-effective method for assessing the severity of illness in critically or chronically ill patients. However it is uncertain whether or not the prealbumin level correlates with the level of nutrition support and outcomes in critically ill patients. The aim of this study was to evaluate serum prealbumin level as an indicator of the effectiveness of nutrition support and the prognosis in critically ill patients. Forty-four patients who received total parenteral nutrition for more than 7 days at an intensive care unit (ICU) were studied. The serum prealbumin was measured at the initial time of nutrition support and at the almost seventh day since the first measurement. The patients were allocated into two groups. In Group 1 (n=31) and 2 (n=13), the prealbumin level increased and decreased, respectively. Age, APACHE II score, nutrition status, nutritional requirement and amount of supply, mortality, hospital day and ICU day in the two groups were compared. The serum prealbumin level increased in 31 out of the 44 patients. The average calorie intake was 1334 Kcal/day (83% of energy requirement) in Group 1 and 1170 kcal/day (76% of energy requirement) in Group 2 (p=0.131). The mortality was 42% in Group 1 and 54% in Group 2 (p=0.673). The average hospital day/ ICU day in Groups 1 and 2 were 80 days/38 days and 60 days/31 days respectively. In conclusion, in critically ill patients, the serum prealbumin level did not respond sensitively to nutritional support. In addition an increase in the prealbumin level dose not indicate a better prognosis for critically ill patients

Clinical Comparison of the Auditory Steady-State Response with the Click Auditory Brainstem Response in Infants

ObjectivesOur goal was to determine the effectiveness of using the auditory steady state response (ASSR) as a measure of hearing thresholds in infants who are suspected of having significant hearing loss, as compared with using the click-auditory brainstem response (C-ABR).MethodsWe retrospectively analyzed the audiologic profiles of 76 infants (46 boys and 30 girls, a total of 151 ears) who ranged in age from 1 to 12 months (average age: 5.7 months). The auditory evaluations in 76 infants who were suspected of having hearing loss were done via the C-ABR and ASSR. In addition, for reference, the mean ASSR thresholds were compared to those of 39 ears of infants and 39 ears of adults with normal hearing at 0.5, 1, 2, and 4 kHz.ResultsThe highest correlation between the C-ABR and ASSR thresholds was observed at an average of 2-4 kHz (r=0.94). On comparison between the hearing of infants and adults at 0.5, 1, 2, and 4 kHz, the mean ASSR threshold in infants was 12, 7, 8, and 7 dB higher, respectively, than that in adults.ConclusionASSR testing may provide additional audiometric information for accurately predicting the hearing sensitivity, and this is essential for the management of infants with severe to profound hearing loss