Unraveling the Predictors for Delirium and ICU Stay Duration in Patients with Heart Failure and Reduced Ejection Fraction (HFrEF) Undergoing Coronary Artery Bypass Grafting-A Multicentric Analysis.

Objective: This study assesses predictors for postoperative delirium (POD) and ICU stay durations in HFrEF patients undergoing CABG, focusing on ONCAB versus OPCAB surgical methods. Summary Background Data: In cardiac surgery, especially CABG, POD significantly impacts patient recovery and healthcare resource utilization. With varying incidences based on surgical techniques, this study provides an in-depth analysis of POD in the context of HFrEF patients, a group particularly susceptible to this complication. Methods: A retrospective analysis of 572 patients who underwent isolated CABG surgery with a preoperative ejection fraction under 40% was conducted at four German university hospitals. Patients were categorized into ONCAB and OPCAB groups for comparative analysis. Results: Age and Euro Score II were significant predictors of POD. The ONCAB group showed higher incidences of re-sternotomy (OR: 3.37), ECLS requirement (OR: 2.29), and AKI (OR: 1.49), whereas OPCAB was associated with a lower incidence of delirium. Statistical analysis indicated a significant difference in ICU stay durations between the two groups, influenced by surgical complexity and postoperative complications. Conclusions: This study underscores the importance of surgical technique in determining postoperative outcomes in HFrEF patients undergoing CABG. OPCAB may offer advantages in reducing POD incidence. These findings suggest the need for tailored surgical decisions and comprehensive care strategies to enhance patient recovery and optimize healthcare resources.

DistSNE: Distributed computing and online visualization of DNA methylation-based central nervous system tumor classification.

The current state-of-the-art analysis of central nervous system (CNS) tumors through DNA methylation profiling relies on the tumor classifier developed by Capper and colleagues, which centrally harnesses DNA methylation data provided by users. Here, we present a distributed-computing-based approach for CNS tumor classification that achieves a comparable performance to centralized systems while safeguarding privacy. We utilize the t-distributed neighborhood embedding (t-SNE) model for dimensionality reduction and visualization of tumor classification results in two-dimensional graphs in a distributed approach across multiple sites (DistSNE). DistSNE provides an intuitive web interface (https://gin-tsne.med.uni-giessen.de) for user-friendly local data management and federated methylome-based tumor classification calculations for multiple collaborators in a DataSHIELD environment. The freely accessible web interface supports convenient data upload, result review, and summary report generation. Importantly, increasing sample size as achieved through distributed access to additional datasets allows DistSNE to improve cluster analysis and enhance predictive power. Collectively, DistSNE enables a simple and fast classification of CNS tumors using large-scale methylation data from distributed sources, while maintaining the privacy and allowing easy and flexible network expansion to other institutes. This approach holds great potential for advancing human brain tumor classification and fostering collaborative precision medicine in neuro-oncology.

Leveraging Attention-Based Convolutional Neural Networks for Meningioma Classification in Computational Histopathology.

Convolutional neural networks (CNNs) are becoming increasingly valuable tools for advanced computational histopathology, promoting precision medicine through exceptional visual decoding abilities. Meningiomas, the most prevalent primary intracranial tumors, necessitate accurate grading and classification for informed clinical decision-making. Recently, DNA methylation-based molecular classification of meningiomas has proven to be more effective in predicting tumor recurrence than traditional histopathological methods. However, DNA methylation profiling is expensive, labor-intensive, and not widely accessible. Consequently, a digital histology-based prediction of DNA methylation classes would be advantageous, complementing molecular classification. In this study, we developed and rigorously assessed an attention-based multiple-instance deep neural network for predicting meningioma methylation classes using tumor methylome data from 142 (+51) patients and corresponding hematoxylin-eosin-stained histological sections. Pairwise analysis of sample cohorts from three meningioma methylation classes demonstrated high accuracy in two combinations. The performance of our approach was validated using an independent set of 51 meningioma patient samples. Importantly, attention map visualization revealed that the algorithm primarily focuses on tumor regions deemed significant by neuropathologists, offering insights into the decision-making process of the CNN. Our findings highlight the capacity of CNNs to effectively harness phenotypic information from histological sections through computerized images for precision medicine. Notably, this study is the first demonstration of predicting clinically relevant DNA methylome information using computer vision applied to standard histopathology. The introduced AI framework holds great potential in supporting, augmenting, and expediting meningioma classification in the future.

On- vs. Off-Pump CABG in Heart Failure Patients with Reduced Ejection Fraction (HFrEF): A Multicenter Analysis.

OBJECTIVE: This study aimed to compare postoperative outcomes and 30-day mortality in patients with reduced ejection fraction (<40%) who underwent isolated coronary artery bypass grafting (CABG) with (ONCAB) and without (OPCAB) the use of cardiopulmonary bypass. METHODS: data from four university hospitals in Germany, spanning from January 2017 to December 2021, were retrospectively analyzed. A total of 551 patients were included in the study, and various demographic, intraoperative, and postoperative data were compared. RESULTS: demographic parameters did not exhibit any differences. However, the OPCAB group displayed notably higher rates of preoperative renal insufficiency, urgent surgeries, and elevated EuroScore II and STS score. During surgery, the ONCAB group showed a significantly higher rate of complete revascularization, whereas the OPCAB group required fewer intraoperative transfusions. No disparities were observed in 30-day/in-hospital mortality for the entire cohort and the matched population between the two groups. Subsequent to surgery, the OPCAB group demonstrated significantly shorter mechanical ventilation times, reduced stays in the intensive care unit, and lower occurrences of ECLS therapy, acute kidney injury, delirium, and sepsis. CONCLUSIONS: the study's findings indicate that OPCAB surgery presents a safe and viable alternative, yielding improved postoperative outcomes in this specific patient population compared to ONCAB surgery. Despite comparable 30-day/in-hospital mortality rates, OPCAB patients enjoyed advantages such as decreased mechanical ventilation durations, shorter ICU stays, and reduced incidences of ECLS therapy, acute kidney injury, delirium, and sepsis. These results underscore the potential benefits of employing OPCAB as a treatment approach for patients with coronary heart disease and reduced ejection fraction.

Beyond ribosome biogenesis: noncoding nucleolar RNAs in physiology and tumor biology.

The nucleolus, the largest subcompartment of the nucleus, stands out from the nucleoplasm due to its exceptionally high local RNA and low DNA concentrations. Within this central hub of nuclear RNA metabolism, ribosome biogenesis is the most prominent ribonucleoprotein (RNP) biogenesis process, critically determining the structure and function of the nucleolus. However, recent studies have shed light on other roles of the nucleolus, exploring the interplay with various noncoding RNAs that are not directly involved in ribosome synthesis. This review focuses on this intriguing topic and summarizes the techniques to study and the latest findings on nucleolar long noncoding RNAs (lncRNAs) as well as microRNAs (miRNAs) in the context of nucleolus biology beyond ribosome biogenesis. We particularly focus on the multifaceted roles of the nucleolus and noncoding RNAs in physiology and tumor biology.

Association Between Metastatic Pattern and Prognosis in Stage IV Gastric Cancer: Potential for Stage Classification Reform.

PURPOSE: This study aims to clarify the association between metastatic pattern and prognosis in stage IV gastric cancer, with a focus on patients presenting with metastases limited to nonregional lymph nodes. METHODS: In this retrospective cohort study, the National Cancer Database was used to identify patients ≥ 18 years of age diagnosed with stage IV gastric cancer between 2016 and 2019. Patients were stratified according to pattern of metastatic disease at diagnosis: nonregional lymph nodes only ("stage IV-nodal"), single systemic organ ("stage IV-single organ"), or multiple organs ("stage IV-multi-organ"). Survival was assessed by Kaplan-Meier curves and multivariable Cox models in unadjusted and propensity score-matched samples. RESULTS: Overall, 15,050 patients were identified, including 1,349 (8.7%) stage IV-nodal patients. Most patients in each group received chemotherapy [68.6% of stage IV-nodal patients, 65.2% of stage IV-single organ patients, and 63.5% of stage IV-multi-organ patients (p = 0.003)]. Stage IV-nodal patients exhibited better median survival (10.5 months, 95% CI 9.7-11.9, p < 0.001) than single organ (8.0, 95% CI 7.6-8.2) and multi-organ (5.7, 95% CI 5.4-6.0) patients. In the multivariable Cox model, stage IV-nodal patients also exhibited better survival (HR 0.79, 95% CI 0.73-0.85, p < 0.001) than single organ (reference) and multi-organ (HR 1.27, 95% CI 1.22-1.33, p < 0.001) patients. CONCLUSIONS: Nearly 9% of clinical stage IV gastric cancer patients have their distant disease confined to nonregional lymph nodes. These patients were managed similarly to other stage IV patients but experienced a better prognosis, suggesting opportunities to introduce M1 staging subclassifications.

Treatment of Complex Two-Vessel Coronary Heart Disease with Single Left Internal Mammary Artery as T-Graft with Itself-A Retrospective Double Center Analysis of Short-Term Outcomes.

Background and Objectives: The strategy of revascularization may be constrained in patients with insufficient bypass grafts and with increased risk of wound healing disorders. Among those with complex left-sided double-vessel disease in whom a percutaneous coronary intervention (PCI), as well as the surgical procedure of minimally invasive coronary artery bypass grafting via left minithoracotomy (MICS CABG), is not a treatment option, CABG using the left internal mammary artery as a T-graft with itself may be an effective treatment strategy. Materials and Methods: We reviewed the data from patients treated in Cologne and Tuebingen from 2019 to 2022. We included 40 patients who received left internal mammary artery (LIMA) grafting, and additional T-graft with the LIMA itself. The objective was focused on intraoperative and short-term outcomes. Results: A total of 40 patients were treated with the LIMA-LIMA T-graft procedure with a Fowler score calculated at 20.1 ± 3.0. A total of 37.5% of all patients had lacking venous graft material due to prior vein stripping, and 21 patients presented severe vein varicosis. An overall of 2.6 ± 0.5 distal anastomoses (target vessels were left anterior descending, diagonal, intermediate branch, and/or left marginal ramus) were performed, partly sequentially. Mean flow of LIMA-Left anterior descending (LAD) anastomosis was 59.31 ± 11.04 mL/min with a mean PI of 1.21 ± 0.18. Mean flow of subsequent T-Graft accounted for 51.31 ± 3.81 mL/min with a mean PI of 1.39 ± 0.47. Median hospital stay was 6.2 (5.0; 7.5) days. No incidence of postoperative wound healing disorders was observed, and all patients were discharged. There was one 30-day readmission with a diagnosis of pericardial effusion (2.5%). There was no 30-day mortality within the cohort. Conclusions: Patients requiring surgical myocardial revascularization due to complex two-vessel coronary artery disease (CAD) can be easily managed with LIMA alone, despite an elevated Fowler score and a promising outcome. A prospective study needs to be conducted, as well as longer term surveillance, to substantiate and benchmark the long-term results, as well as the patency rates.

Thoracoscopic mesh implantation as a definitive treatment approach for peritoneal dialysis-associated hydrothorax.

Pleuroperitoneal leakage with the formation of hydrothorax is a rare complication of peritoneal dialysis, usually necessitating termination of peritoneal dialysis. We hypothesized that implantation of a polypropylene mesh on the diaphragm using video-assisted thoracoscopic surgery might induce permanent closure of pleuroperitoneal leakage. We report a case series of n = 12 peritoneal dialysis patients with pleuroperitoneal leakage and right-sided hydrothorax who underwent video-assisted thoracoscopy with mesh implantation from 2011 to 2020. Pleuroperitoneal leakage had been confirmed before surgery by intraperitoneal administration of toluidine blue, contrast-enhanced computer tomography or glucose determination from the pleural effusion. Median time from the start of peritoneal dialysis to manifestation of pleuroperitoneal leakage was 52 days. Video-assisted thoracoscopic surgery revealed multiple penetration points in the tendinous part of the diaphragm in all patients, which appeared as blebs. These were closed by covering the whole diaphragm with a polypropylene mesh. In all patients, peritoneal dialysis was paused for three months and bridged by hemodialysis. After restarting peritoneal dialysis and a median follow-up time of 1.9 years, none of the patients experienced a recurrence of pleuroperitoneal leakage. This case series demonstrates that pleuroperitoneal leakage in peritoneal dialysis patients can be permanently closed using thoracoscopic mesh implantation and allows peritoneal dialysis to be continued as renal replacement therapy.

Comparison of the investigation and treatment of acute appendicitis in our surgical department during the pre-pandemic period of COVID-19 and in the III. pandemic wave / Akut appendicitis kivizsgálásának és kezelésének összehasonlítása sebészeti osztályunkon a COVID-19-pandémia elotti idoszak és a pandémia III. hulláma alatt

Introduction. Appendicitis is one of the most common causes of acute abdominal surgical indications. WHO declared the SARS-CoV-2 (COVID-19) virus infection a pandemic on the 11.03.2020., affecting all segments of healthcare. Management of the acute cases also faced new challenges as a result of the restrictive measures taken during the pandemic, affecting the population and healthcare providers. In our surgical department, during the medical care of those diagnosed with acute appendicitis, in the absence of uniform professional protocols, we often required individual considerations. In the absence of universal professional guidelines, during the medical care of those who had been diagnosed with acute appendicitis we often required individual considerations in our surgical department. Aim. the comparison of the time elapsed between the onset of the symptoms and the time the patients arrived to our surgical department, the frequency of hospitalisation and the frequency and difference between postoperative complications in patients diagnosed with acute appendicitis during the pre-pandemic period of SARS-CoV-2 and the III. wave of COVID-19. Methods. in our retrospective analysis we included those more than 18-years old patients who were diagnosed with the clinic-radiological picture of acute appendicitis during the pre-pandemic 6 months (16. 09. 2019. ­ 16. 03. 2020.) and the III. wave of COVID-19 (01. 11. 2020. ­ 01. 04. 2021.). We compared the length of time between the onset of symptoms and the beginning of hospitalisation, the complexity of appendicitis, the method of surgery used, the duration of hospitalisation and the development of postoperative complications. Statistical significance was examined by t-test and Fischer-test. Results. 64 patients were included, 47 in the pre-pandemic period and 17 in the III. wave of COVID-19. During the pandemic, the number of people diagnosed with acute appendicitis showed a declining trend, however the incidence of complicated appendicitis increased (26% « 35%). In the III. wave of COVID-19, the time between the onset of symptoms and the examination was 27,3 h longer on average (P = 0.275), the hospitalisation was 17.3 h longer (P = 0.412) and the postoperative complications (2.12% « 23.5%) and surgical conversions (0% « 21%) were also significantly different (P = 0.264), but there was no significant correlation in either case. Conclusion. although there was no significant correlation in our analysis, it appears that during the pandemic, patients sought medical attention later and with more severe symptoms, resulting in progression of acute appendicitis.

Long-Term Follow-Up of Survivors of Extracorporeal Life Support Therapy for Cardiogenic Shock: Are They Really Survivors?

Background and Objectives: Cardiogenic shock (CS) is a medical emergency associated with a high mortality rate. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for CS. Despite widely available data for short-term survival rates, there are only limited data available regarding long-term outcomes following successful VA-ECMO therapy. Materials and Methods: We analyzed the demographics, past medical history, adverse events, and outcomes of survivors who received VA-ECMO support for CS at our center from January 2012 to December 2019. Post-cardiotomy cases were excluded. Results: A total of 578 VA-ECMO implantations on 564 consecutive patients due to CS were identified during the study period. Successful weaning was achieved in 207 (36.7%) patients. Among the survivors, 126 (63%) patients received VA-ECMO therapy without preceding cardiac surgery during their current admission. A follow-up exceeding 12 (mean: 36 ± 20.9) months was available in a total of 55 (43.7%) survivors. The mean VA-ECMO perfusion time was 10.9 (±7.7) days with a mean intensive care unit (ICU) stay of 38.2 (±29.9) days and a mean hospital stay of 49.9 (±30.5) days. A total of 3 deaths were recorded during long-term follow-up (mean survival of 26 ± 5.3 months). Conclusions: Despite the high mortality associated with VA-ECMO therapy, a long-term follow-up with an acceptably low rate of negative cardiac events can be achieved in many survivors. We observed an acceptable low rate of new cardiac events. Further evaluation, including a quality-of-life assessment and a close follow-up for rarer complications in these patients, is needed to elucidate the longer-term outcomes for survivors of invasive VA-ECMO therapy.

The impact of 3D printed models on spatial orientation in echocardiography teaching.

PURPOSE: During our transthoracic echocardiography (TTE) courses, medical students showed difficulty in spatial orientation. We implemented the use of 3D printed cardiac models of standard TTE views PLAX, PSAX, and A4C and assessed their efficacy in TTE-teaching. METHODS: One hundred fifty-three participants were split into two groups. A pre-test-retest of anatomy, 2D -, and 3D orientation was conducted. The intervention group (n = 77) was taught using 3D models; the control group (n = 76) without. Both were comparable with respect to baseline parameters. Besides test-scores, a Likert scale recorded experiences, difficulties, and evaluation of teaching instruments. RESULTS: From the 153 students evaluated, 123 improved, 20 did worse, and ten achieved the same result after the course. The median overall pre-test score was 29 of 41 points, and the retest score was 35 (p < 0.001). However, the intervention group taught with the 3D models, scored significantly better overall (p = 0.016), and in 2D-thinking (p = 0.002) and visual thinking (p = 0.006) subtests. A backward multivariate linear regression model revealed that the 3D models are a strong individual predictor of an excellent visual thinking score. In addition, our study showed that students with difficulty in visual thinking benefited considerably from the 3D models. CONCLUSION: Students taught using the 3D models significantly improved when compared with conventional teaching. Students regarded the provided models as most helpful in their learning process. We advocate the implementation of 3D-printed heart models featuring the standard views for teaching echocardiography. These findings may be transferable to other evidence based medical and surgical teaching interventions.

An Interesting Case of a Cold Left Arm.

Inter-arm variability in blood pressure readings typically signifies arterial disease between the aortic arch and the subclavian artery. The differential diagnosis includes thoracic aortic dissection, atherosclerosis, thoracic outlet syndrome, and subclavian artery stenosis and thrombosis. In patients with prior coronary artery bypass grafting, including the internal mammary artery, several of those conditions can compromise coronary blood flow and lead to myocardial ischemia. Here we discuss a case of left subclavian artery thrombosis, which compromised left internal mammary artery blood flow and led to ischemic ventricular tachycardia.

Is it Safe for Patients with Left Ventricular Assist Devices to Undergo Non-Cardiac Surgery?

Background and Objectives: Since the first use of ventricular assist devices (VADs) as bridge to recovery and bridge to cardiac transplantation in the early 1990s, significant technological advances have transformed VAD implantation into a routine destination therapy. With improved survival, many patients present for cardiac surgery for conditions not directly related to their permanent mechanical circulatory support. The aim of this study was to analyze the indications and outcomes of non-cardiac surgeries (NCSs) of left ventricular assist device (LVAD) patients in tertiary center. Material and Methods: We present a single-center experience after 151 LVAD implantations in 138 consecutive patients between 2012-2019 who had to undergo NCS during a follow-up period of 37 +/- 23.4 months on left ventricular assist device (LVAD). Results: A total of 105 procedures was performed in 63 LVAD recipients, resulting in peri-operative mortality of 3.8%. Twenty-five (39.7%) of patients underwent multiple surgeries. We found no significant difference in cumulative survival associated with the performed surgical interventions (p = 0.469). Conclusion: We demonstrated good overall clinical outcomes in LVAD patients undergoing NCS. With acceptable peri-operative mortality, NCS can be safely performed in LVAD patients on long-term support.

Video assisted thoracoscopic sympathectomy for intractable recurrent VT after minimal-invasive LVAD implantation.

BACKGROUND: Recurrent ventricular tachycardia (VT) can occur after left ventricular assist device (LVAD) implantation. In this case, medical treatment might be insufficient. We report a case of a left-sided thoracoscopic sympathectomy as a feasible treatment escalation in intractable VT. CASE REPORT: A 72-year-old patient underwent an internal cardioverter defibrillator (ICD) implantation as primary prophylaxis for VTs in the setting of staged heart failure therapy. Afterwards, due to a progressive dilative cardiomyopathy he underwent a minimal-invasive LVAD implantation (HeartWare, Medtronic). After an uneventful minimal-invasive LVAD-implantation the patient was discharged to a rehabilitation program. However, after 7 weeks he developed recurrent VTs which were successfully terminated by ICD shocks deliveries leading to severe discomfort and frequent hospitalizations. Eventually, the patient was admitted with an electrical VT storm. Successful endocardial catheter ablation of all inducible VTs were performed combined with multiple rearrangements of his oral antiarrhythmic medication. However, all these treatments could not suppress further occurrence of VTs. After an interdisciplinary discussion the patient agreed to a left-sided video-assisted thoracoscopic sympathectomy. After a follow up of 150 days the patient was free from VTs apart from one short event. CONCLUSION: We believe video-assisted thoracoscopic sympathectomy might be a surgical treatment option in patients with intractable recurrent VTs after catheter ablation of VT reentrant substrate even after minimal-invasive LVAD implantation.

KLF4K409Q-mutated meningiomas show enhanced hypoxia signaling and respond to mTORC1 inhibitor treatment.

Meningioma represents the most common primary brain tumor in adults. Recently several non-NF2 mutations in meningioma have been identified and correlated with certain pathological subtypes, locations and clinical observations. Alterations of cellular pathways due to these mutations, however, have largely remained elusive. Here we report that the Krueppel like factor 4 (KLF4)-K409Q mutation in skull base meningiomas triggers a distinct tumor phenotype. Transcriptomic analysis of 17 meningioma samples revealed that KLF4K409Q mutated tumors harbor an upregulation of hypoxia dependent pathways. Detailed in vitro investigation further showed that the KLF4K409Q mutation induces HIF-1α through the reduction of prolyl hydroxylase activity and causes an upregulation of downstream HIF-1α targets. Finally, we demonstrate that KLF4K409Q mutated tumors are susceptible to mTOR inhibition by Temsirolimus. Taken together, our data link the KLF4K409Q mediated upregulation of HIF pathways to the clinical and biological characteristics of these skull base meningiomas possibly opening new therapeutic avenues for this distinct meningioma subtype.

Extended resection of a cardiac paraganglioma-A rare neuroendocrine manifestation of the heart.

BACKGROUND: Cardiac paragangliomas are rare tumors that develop from neural crest cells. They account for about 2% of all paragangliomas and there is only limited evidence of malignant transformation. CASE PRESENTATION: We present a young woman with atypical symptoms, which are related to the mass effect of the 40 × 49mm cardiac tumor on top of the left atrium. The patient underwent an extensive resection of the tumor including the root of the pulmonary trunk, the ascending aorta, and the left main artery. CONCLUSIONS: The present case is of great importance showing the need for multidisciplinary approach in the management of cardiac tumors that infiltrate multiple anatomic structures.

Cardiac surgery residents training in Germany-Status quo and future prospects.

Residency training for specialization in cardiac surgery in Germany recently underwent a series of changes. A new 6-year integrated curriculum has been created that is based on acquisition of specific expertise rather than a rigid time frame. In effect, the training paradigm is one that is competency-based. After compliance with the curricular requirements and successfully completion of an examination, the Federal Medical Chamber grants the status of a licensed specialized physician ("Facharzt") and issues a certificate, which allows for independent clinical practice. There is no recertification during the course of the physicians' professional career. The educational curricula for specialized training are issued by the National Medical Chamber in cooperation with the respective surgical societies and passed by the German Medical Assembly.

Disruption of the UBF gene induces aberrant somatic nucleolar bodies and disrupts embryo nucleolar precursor bodies.

The nucleolus is the site of ribosome biogenesis and forms around the actively transcribed ribosomal RNA (rRNA) genes. However, the nucleolus is also implicated in cell cycle regulation, tumour suppression and chromosome segregation and nucleolar disfunction is linked to a wide range of human diseases. Interestingly, the nucleolus is also required for genome reprogramming and the establishment of heterochromatin in the mammalian embryo. Mammalian oocytes contain a subnuclear structure that is believed to be the precursor of the functional nucleolus, the Nucleolar Precursor Body (NPB). But the NPB is also required for the organisation of the zygotic heterochromatin and the establishment of pluripotency. We found that disruption of the mouse Upstream Binding Factor (UBF (UBTF)) gene caused disassembly of somatic nucleoli and the accumulation of the key rRNA gene transcription factors into dense subnuclear foci resembling NPBs. Here we show that UBF deletion causes the rRNA genes to collapse onto their centromere-proximal chromosomal sites spatially distinct from NPB-like structures, and that these structures contain rRNA gene transcription factors but not all nucleolar proteins. We further find that embryonic NPBs and their surrounding heterochromatin are both disrupted in UBF-null mouse embryos. These embryos also display subnuclear foci containing the rRNA gene transcription factors and arrest development before completing the forth cleavage division. The data suggest that the rRNA gene transcription factors have an intrinsic ability to interact and form a discrete nuclear compartment even in the absence of any rRNA gene activity and that the formation or maintenance of the zygotic NPB and surrounding heterochromatin requires UBF.

The extended AT-hook is a novel RNA binding motif.

The AT-hook has been defined as a DNA binding peptide motif that contains a glycine-arginine-proline (G-R-P) tripeptide core flanked by basic amino acids. Recent reports documented variations in the sequence of AT-hooks and revealed RNA binding activity of some canonical AT-hooks, suggesting a higher structural and functional variability of this protein domain than previously anticipated. Here we describe the discovery and characterization of the extended AT-hook peptide motif (eAT-hook), in which basic amino acids appear symmetrical mainly at a distance of 12-15 amino acids from the G-R-P core. We identified 80 human and 60 mouse eAT-hook proteins and biochemically characterized the eAT-hooks of Tip5/BAZ2A, PTOV1 and GPBP1. Microscale thermophoresis and electrophoretic mobility shift assays reveal the nucleic acid binding features of this peptide motif, and show that eAT-hooks bind RNA with one order of magnitude higher affinity than DNA. In addition, cellular localization studies suggest a role for the N-terminal eAT-hook of PTOV1 in nucleocytoplasmic shuttling. In summary, our findings classify the eAT-hook as a novel nucleic acid binding motif, which potentially mediates various RNA-dependent cellular processes.