Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast.

Gene expression involving RNA polymerase II is regulated by the concerted interplay between mRNA synthesis and degradation, crosstalk in which mRNA decay machinery and transcription machinery respectively impact transcription and mRNA stability. Rpb4, and likely dimer Rpb4/7, seem the central components of the RNA pol II governing these processes. In this work we unravel the molecular mechanisms participated by Rpb4 that mediate the posttranscriptional events regulating mRNA imprinting and stability. By RIP-Seq, we analysed genome-wide the association of Rpb4 with mRNAs and demonstrated that it targeted a large population of more than 1400 transcripts. A group of these mRNAs was also the target of the RNA binding protein, Puf3. We demonstrated that Rpb4 and Puf3 physically, genetically, and functionally interact and also affect mRNA stability, and likely the imprinting, of a common group of mRNAs. Furthermore, the Rpb4 and Puf3 association with mRNAs depends on one another. We also demonstrated, for the first time, that Puf3 associates with chromatin in an Rpb4-dependent manner. Our data also suggest that Rpb4 could be a key element of the RNA pol II that coordinates mRNA synthesis, imprinting and stability in cooperation with RBPs.

Inducing signal-verified lucid dreams in 40% of untrained novice lucid dreamers within two nights in a sleep laboratory setting.

Dreams in which the dreamer is aware of the dream state (lucid dreams, LD) are difficult to induce in naïve subjects in-laboratory. Recently, Stumbrys and Erlacher (2014) used a combination of existing induction techniques together with a self-developed experiment protocol and achieved comparatively high LD induction rates. In this study, we simplified their methodology slightly and repeated their experiment with twenty naïve subjects who spent one or two nights in our sleep laboratory. After about six hours of sleep, they were woken up during REM sleep and engaged in a series of cognitive tasks before going back to bed. Ten subjects reported a LD during the following period of sleep in one of the nights. Eight of these subjects gave a predefined eye signal, which was clearly visible in the electrooculogram during REM sleep. In summary, we replicated Stumbrys and Erlacher's results using a simplified version of their induction protocol.

Investigating non-inferiority of internet-delivered versus face-to-face cognitive behavioural therapy for insomnia (CBT-I): a randomised controlled trial (iSleep well).

BACKGROUND: Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment. As there is insufficient evidence regarding non-inferiority, this study directly aims to compare therapist-guided internet-delivered versus face-to-face CBT-I in terms of insomnia severity post-treatment. Furthermore, a health-economic evaluation will be conducted, and potential benefits and disadvantages of therapist-guided iCBT-I will be examined. METHODS: This study protocol describes a randomised controlled two-arm parallel-group non-inferiority trial comparing therapist-guided iCBT-I with face-to-face CBT-I in routine clinical care. A total of 422 patients with insomnia disorder will be randomised and treated at 16 study centres throughout Germany. Outcomes will be assessed at baseline, 10 weeks after randomisation (post), and 6 months after randomisation (follow-up). The primary outcome is insomnia severity measured using the Insomnia Severity Index. Secondary outcomes include depression-related symptoms, quality of life, fatigue, physical activity, daylight exposure, adverse events related to treatment, and a health-economic evaluation. Finally, potential moderator variables and several descriptive and exploratory outcomes will be assessed (e.g. benefits and disadvantages of internet-delivered treatment). DISCUSSION: The widespread implementation of CBT-I is a significant healthcare challenge. The non-inferiority of therapist-guided iCBT-I versus face-to-face CBT-I will be investigated in an adequately powered sample in routine clinical care, with the same therapeutic content and same level of therapist qualifications provided with both interventions. If this trial demonstrates the non-inferiority of therapist-guided iCBT-I, healthcare providers may be more confident recommending this treatment to their patients, contributing to the wider dissemination of CBT-I. TRIAL REGISTRATION: Trial registration number in the German Clinical Trials Register: DRKS00028153 ( https://drks.de/search/de/trial/DRKS00028153 ). Registered on 16th May 2023.

Transcriptional regulation and function during the human cell cycle.

We report here the transcriptional profiling of the cell cycle on a genome-wide scale in human fibroblasts. We identified approximately 700 genes that display transcriptional fluctuation with a periodicity consistent with that of the cell cycle. Systematic analysis of these genes revealed functional organization within groups of coregulated transcripts. A diverse set of cytoskeletal reorganization genes exhibit cell-cycle-dependent regulation, indicating that biological pathways are redirected for the execution of cell division. Many genes involved in cell motility and remodeling of the extracellular matrix are expressed predominantly in M phase, indicating a mechanism for balancing proliferative and invasive cellular behavior. Transcripts upregulated during S phase displayed extensive overlap with genes induced by DNA damage; cell-cycle-regulated transcripts may therefore constitute coherent programs used in response to external stimuli. Our data also provide clues to biological function for hundreds of previously uncharacterized human genes.

Inhibin A production after gonadotropin stimulus: a new method to detect ovarian tissue in ovotesticular disorder of sex development.

BACKGROUND/AIMS: While laboratory methods for the detection of testicular tissue are well standardized, currently there is no available test to demonstrate the presence of ovarian tissue. We evaluated the effectiveness of gonadal stimulation with luteinizing hormone (LH)/follicle-stimulating hormone (FSH) for the detection of ovarian tissue in patients with disorders of sex development (DSD). METHODS: Ten patients with congenital adrenal hyperplasia (CAH) as ovarian-positive controls, 10 with cryptorchidism (ovarian-negative controls), 13 patients with DSD of no defined etiology and 7 patients with ovotesticular DSD (true hermaphroditism, TH) were included in the study. They underwent a daily injection of both LH and FSH on 3 consecutive days. LH, FSH, estradiol, testosterone and inhibin A were measured before treatment, 24 h after the 1st dose and 24 h after the 3rd dose. RESULTS: Estradiol increased in all CAH and TH patients, with a median value of 155.1 and 92.6 pg/ml, respectively, after the 3rd injection. Inhibin A also increased in all CAH and TH patients, with a median value of 70.4 and 32.2 pg/ml, respectively, after the 3rd injection. There was no change in these hormones in the other groups. CONCLUSION: The LH/FSH stimulation test might be a useful method to detect the presence of ovarian tissue.

Picosecond photodetector for 257 nm to 1 mum laser pulses.

Picasecond temporal response and broad spectral response photodetectors have been fabricated using commercially available diode chips. Improved photoresponse sensitivity is achieved by removing the anode gold contact which obscures the active region. Junction geometry is such that the depletion region is approximately normal to the surface being illuminated, making the device especially useful for fast UV photodetection.

Ileoanal anastomosis for ulcerative colitis: results of an evolutionary surgical procedure.

BACKGROUND/AIMS: Proctocolectomy with ileoanal anastomosis (IAA) has proved to be the most suitable surgical treatment for ulcerative colitis. The aim of this study was to compare the results of IAA according to the evolution of surgical procedures and particularly to compare the results of stapled versus hand-sewn anastomosis. METHODOLOGY: From 1984 to 1996, 37 men and 31 women were operated on in our centre for ulcerative colitis. The anastomosis between the J pouch and the dentate line was handsewn in 35 patients (group 1) and stapled in 33 patients (group 2). RESULTS: The mean operative time was significantly shorter in group 2 as compared with group 1 (265+/-59 vs. 323+/-53, p<0.01, respectively), whereas morbidity and functional results were comparable in both groups. In 10 patients with stapled IAA, a diverting ileostomy was not performed and the morbidity in this group did not increase. CONCLUSIONS: These results suggest that stapled IAA anastomosis is a safe procedure. The stapling technique of IAA simplifies total excision of the rectum and could mean that a diverting ileostomy is not necessary.

[Lumbar sympathectomy by retroperitoneal endoscopy: feasibility study]. / Sympathectomie lombaire par rétropéritoneoscopie: étude de faisabilité.

Endoscopic surgery has been used as a new procedure to simplify different surgical processes. The goal of this study was to evaluate the benefits of endoscopic retroperitoneal surgery for lumbar sympathectomies. Between February 93 and November 95 we performed 35 lumbar sympathectomies using this technique. All patients were arteritic. The results were as follows: for 25% of the patients, conversion classical open technique was required; 6% complications (septic); 3% of the patients died. In comparing the various techniques of sympathectomy and sympatholysis, it would appear that the endoscopic technique produces fewer complications. However we believe that a learning period is necessary before this technique can be fully mastered.