A sex-based analysis of 5-year outcomes following stenting for the treatment of aorto-iliac occlusive disease.

OBJECTIVES: The aim of this study was to evaluate the impact of sex on mid-term outcomes following stenting for aorto-iliac occlusive disease (AIOD). METHODS: The Covered versus Balloon Expandable Stent Trial (COBEST) compared the safety and efficacy of the covered stent (CS) with those of the bare metal stent (BMS) in the treatment of hemodynamically significant AIOD. It was identified that CS provided a significant benefit. The primary endpoint of our analysis was the rate of primary patency 5 years following stenting for AIOD (inclusive of both CS and BMS) in both sexes. RESULTS: Of the 168 lesions treated, 103 (61%) were present in men and 65 (39%) were present in women. Of the concomitant comorbidities, diabetes mellitus was significantly more common in women (17.5% vs 41.5%, p = .006). Although chronic limb threatening ischemia (CLTI) at the time of intervention was more common in women, the difference was not significant (16.5% vs 24.6%, p = .395). Sex was not associated with the primary patency rate (male; 0.70, 95% confidence interval [CI]: 0.23-2.19, p = .543). When considering both male sex and the utilization of BMS, no significant impact was found on the primary patency rate (hazard ratio [HR]: 3.43, 95% CI: 0.69-17.10, p = .133). All-cause mortality at 60 months was 22.6% in men compared to 19.4% in women (p = .695). CONCLUSIONS: No significant difference was identified in the primary patency rate between the sexes. Further investigation is warranted to ascertain whether sex-specific interventional guidelines are required in this regard.

A rise-to-threshold process for a relative-value decision.

Whereas progress has been made in the identification of neural signals related to rapid, cued decisions1-3, less is known about how brains guide and terminate more ethologically relevant decisions in which an animal's own behaviour governs the options experienced over minutes4-6. Drosophila search for many seconds to minutes for egg-laying sites with high relative value7,8 and have neurons, called oviDNs, whose activity fulfills necessity and sufficiency criteria for initiating the egg-deposition motor programme9. Here we show that oviDNs express a calcium signal that (1) dips when an egg is internally prepared (ovulated), (2) drifts up and down over seconds to minutes-in a manner influenced by the relative value of substrates-as a fly determines whether to lay an egg and (3) reaches a consistent peak level just before the abdomen bend for egg deposition. This signal is apparent in the cell bodies of oviDNs in the brain and it probably reflects a behaviourally relevant rise-to-threshold process in the ventral nerve cord, where the synaptic terminals of oviDNs are located and where their output can influence behaviour. We provide perturbational evidence that the egg-deposition motor programme is initiated once this process hits a threshold and that subthreshold variation in this process regulates the time spent considering options and, ultimately, the choice taken. Finally, we identify a small recurrent circuit that feeds into oviDNs and show that activity in each of its constituent cell types is required for laying an egg. These results argue that a rise-to-threshold process regulates a relative-value, self-paced decision and provide initial insight into the underlying circuit mechanism for building this process.

An internal expectation guides Drosophila egg-laying decisions.

To better understand how animals make ethologically relevant decisions, we studied egg-laying substrate choice in Drosophila. We found that flies dynamically increase or decrease their egg-laying rates while exploring substrates so as to target eggs to the best, recently visited option. Visiting the best option typically yielded inhibition of egg laying on other substrates for many minutes. Our data support a model in which flies compare the current substrate's value with an internally constructed expectation on the value of available options to regulate the likelihood of laying an egg. We show that dopamine neuron activity is critical for learning and/or expressing this expectation, similar to its role in certain tasks in vertebrates. Integrating sensory experiences over minutes to generate an estimate of the quality of available options allows flies to use a dynamic reference point for judging the current substrate and might be a general way in which decisions are made.

Multicentre Covariate Adjustment Analysis of Short-Term and 5-Year Outcomes after Endovascular Repair according to Sex.

BACKGROUND: Several studies have reported worse outcomes in women compared to men after endovascular aneurysm repair (EVAR). This study aimed to evaluate sex-specific short-term and 5-year outcomes after EVAR. METHODS: A total of 409 consecutive patients underwent elective EVAR from 2004 to 2017 at two tertiary hospitals in Western Australia. Baseline, intraoperative, and postoperative variables were examined retrospectively according to sex. The primary outcome was 30-day mortality (death within 30 days after EVAR). Secondary outcomes were 30-day composite endpoint, length of stay after EVAR, 5-year survival, freedom from reintervention, residual aneurysm size after EVAR, and major adverse event rate at 5-year follow-up. RESULTS: A cohort of 409 patients, comprising 57 women (14%) and 352 men (86%), was analysed. Female patients were older (median age, 76.8 versus 73.5 years, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%. CONCLUSION: This study found no significant differences in 30-day and 5-year outcomes between female and male patients treated with EVAR, implying that EVAR remains a safe treatment choice for female patients.

Nitinol stent-assisted maturation of the dysfunctional cannulation zone in the immature arteriovenous fistula.

INTRODUCTION: The native arteriovenous fistula may remain immature despite adequate arterial inflow after formation. This may occur when the puncturable vein segment (cannulation zone) is too small to be reliably punctured, occluded or too deep under the skin for needle access. We performed stenting (stent-assisted maturation) of arteriovenous fistulas with an immature cannulation zone, allowing for a large subcutaneous channel which could then be immediately punctured for dialysis. METHODS: We performed a retrospective review of 49 patients (mean age was 58.7 ± 16.09 (12-83) years, mean arteriovenous fistula age of 162.6 ± 27.28 days) with end-stage renal failure who underwent balloon dilatation and bare-metal stent implantation (1.6 ± 0.67 (1-3) stents, median diameter and length of 8 (5-14) mm and 80 (40-150) mm, respectively) through their cannulation zone (forced maturation). Radiocephalic (35 arteriovenous fistulas), brachiocephalic (10 arteriovenous fistulas) and autogenous loop arteriovenous fistulas (4 arteriovenous fistulas) were included with 30 patients (61.2%) having an inadequate cannulation zone venous diameter, 9 patients (18.4%) having an absent cannulation zone and 10 patients (20.4%) having a patent cannulation zone deeper than 1 cm which was not reliably puncturable. The study was conducted over 9 years (January 2008-December 2016) with implantation of the SMART® stent and Absolute Pro® stent in 61.2% and 38.8%, respectively. Long-term outcomes including primary useable segmental and access circuit patency as well as assisted primary access circuit patency, rate of re-intervention, technical success and complications were analysed. RESULTS: At 6 months, 12 months and 4 years, respectively, cannulation zone primary patency was 84.4%, 74.4% and 56.1% and access circuit primary patency was 62.2%, 45.3% and 23.2%; however, assisted primary access circuit patency was 95.6%, 91.1% and 83.8%, achieved with an endovascular re-intervention rate of 0.53 procedures/year with only four thrombosed circuits occurring. DISCUSSION: Forced maturation using nitinol stents allows for long-term haemodialysis access with a low rate of re-intervention.

A neural heading estimate is compared with an internal goal to guide oriented navigation.

Goal-directed navigation is thought to rely on the activity of head-direction cells, but how this activity guides moment-to-moment actions remains poorly understood. Here we characterize how heading neurons in the Drosophila central complex guide moment-to-moment navigational behavior. We establish an innate, heading-neuron-dependent, tethered navigational behavior where walking flies maintain a straight trajectory along a specific angular bearing for hundreds of body lengths. While flies perform this task, we use chemogenetics to transiently rotate their neural heading estimate and observe that the flies slow down and turn in a direction that aims to return the heading estimate to the angle it occupied before stimulation. These results support a working model in which the fly brain quantitatively compares an internal estimate of current heading with an internal goal heading and uses the sign and magnitude of the difference to determine which way to turn, how hard to turn and how fast to walk forward.

Durability of the balloon-expandable covered versus bare-metal stents in the Covered versus Balloon Expandable Stent Trial (COBEST) for the treatment of aortoiliac occlusive disease.

OBJECTIVE: The Covered vs Balloon Expandable Stent Trial (COBEST) is the first multicenter trial to investigate the patency of covered stents (CSs) and bare-metal stents (BMSs) in the treatment of aortoiliac arterial disease. The short-term results demonstrated that CSs were superior to BMSs in maintaining patency for TransAtlantic Inter-Society Consensus (TASC) C and D lesions at 18 months and were equivalent to BMSs for TASC B lesions. The current study was conducted to determine if the initial patency advantage of CSs over BMSs was sustained at the 5-year follow-up. METHODS: A retrospective post hoc analysis of COBEST was performed. Originally, 125 patients with 168 iliac arteries were prospectively enrolled and randomly assigned to receive a CS or BMS. In this study, 77 of the 125 patients (61.6%; 119 limbs) were assessed at 60 months for the primary and secondary end points, with particular attention paid to the outcomes stratified according to TASC lesion severity. The primary end point was the rate of binary stenosis or freedom from stent occlusion of the treated area, as determined by ultrasound imaging or quantitative visual angiography. RESULTS: The 5-year results of the COBEST showed that the CS had a significantly higher patency rate than the BMS at 18, 24, 48, and 60 months (95.1%, 82.1%, 79.9%, 74.7% for CS vs 73.9%, 70.9%, 63% and 62.5% for BMS; log-rank test, P = .01). On multivariate analysis, the type of stent used (hazard ratio [HR], 2.797; 95% confidence interval [CI], 1.471-5.318; P = .002) and the Rutherford classification (HR, 2.019; 95% CI, 1.278-3.191; P = .026) significantly affected the adjusted primary patency. On subgroup analysis, the CS showed significantly higher patency and a survival benefit compared with the BMS in TASC C and D lesions (HR, 8.639; 95% CI, 54.253-75.753; P = .003). Moreover, fewer patients received target limb revascularization in the CS group than in the BMS group (odds ratio, 2.32; 95% CI, 1.47-3.36; P = .02); however, there was no statistically significant difference in the rate of amputations between the groups. CONCLUSIONS: The 5-year results of the COBEST demonstrated that the CS has an enduring patency advantage over the BMS in both the short and long terms. Furthermore, the CS showed acceptable patency rates for the treatment of more severe TASC C and D lesions, and patients who received a CS required fewer revascularization procedures. However, the choice of stent did not affect the rate of major limb amputations.

Transradial approach for challenging vascular access interventions.

BACKGROUND: Percutaneous interventional procedures for vascular access are usually performed using the draining cephalic or basilic vein. The transradial approach, which has been extensively investigated for coronary angiography and intervention, could be an attractive new technique for peri-anastomotic arteriovenous fistula stenosis. METHOD: From June 2012 to February 2013, 30 patients with end-stage renal failure were evaluated for transradial vascular access intervention. A 4-French (Fr) micropuncture kit was used to access the radial artery and then subsequently upgraded to a 5-Fr sheath. Fourteen patients required an upgrade to a 6-Fr sheath for the final intervention. RESULTS: Primary technical success (residual stenosis <30%) was achieved in all cases where angioplasty was performed. Technical success regarding access was achieved in all patients. There were no peri-procedural complications. The post-interventional primary patency was calculated as 100%, 100%, 88.4% and 32.8% at 1, 6, 9 and 12 months, respectively. The post-interventional primary assisted patency was calculated as 100%, 100%, 100% and 63.3% at 1, 6, 9 and 12 months, respectively. Based on colour-coded Duplex scan and/or photoelectric plethysmography, all access-site arteries showed normal perfusion; however, the freedom from significant radial artery restenosis was 92.4% at 12-month follow-up. CONCLUSION: The transradial approach for vascular access endovascular interventions is technically feasible and safe. It allows simultaneous treatment of peri-anastomotic lesions in fistulas with complex venous anatomy as well as lesions in the arterial inflow and central outflow.

Trend of management of traumatic thoracic aortic injuries in a single center.

The purpose of this study was to review the shift in the trend of management and mid-term outcomes of all patients who sustain thoracic aortic injury. A Retrospective analysis was performed of all patients sustaining blunt thoracic aortic trauma admitted to our unit. Forty-seven patients were presented with injury to the thoracic aorta following blunt chest injury. Ten patients underwent open surgical repair of their thoracic aortic injury. The mean age ± SD (range) was 29.4 ± 7.9 years (18-41) with a mean Injury Severity Score (ISS) of 41 ± 14.7 (25-75). Fifteen patients underwent thoracic endovascular repair for blunt aortic transections with a mean age of 35.1 ± 14.5 years (17-65), mean ISS of 40.8 ± 13.9 (20-75) and an average length of hospital stay of 25.6 ± 14.5 days (3-77). The mean aortic diameter proximal to the aortic injury was 23.46 ± 3.02 mm (19-28) with a mean aortic angulation of 58.46° ± 17.73 (44-80°). The mean oversizing was 24.4 ± 5.4% (17-32%). At our institution, there has been a paradigm shift in the emergent repair of blunt thoracic aortic injury from open surgery to endovascular repair. Oversizing of the stent-graft did not translate to a poorer outcome.

Incidence and prognosis of vascular complications after transcatheter aortic valve implantation.

OBJECTIVE: Transcatheter aortic valve implantation (TAVI) has gained increasing global popularity as a minimally invasive option for high-risk cardiac patients. However, this operation is not without risk, particularly of significant vascular complications that increase the morbidity, mortality, and overall cost of the procedure. We aim to present our experience of TAVI-related vascular complications, including the morbidity and cost impacts of these events. METHODS: A case-series study was performed for all patients undergoing TAVI at our center. Vascular complications were defined according to the 2011 Valve Academic Research Consortium standardized end points. The data were prospectively collected from February 2009 to April 2012, and the outcomes were entered into a database and cross-checked with the hospital notes. RESULTS: TAVI was performed on 100 patients in our center during the study period, and the 30-day mortality was 6%. Access approaches included 81 transfemoral, 18 transapical, and one trans-subclavian access. The average patient age was 84.9 years, and 65% of the patients were male. Among the transfemoral procedures, there were 16 vascular access-related complications (VAC), including nine major and seven minor complications. The major complications included aortic dissection, iliac arterial rupture, femoral dissection, false aneurysms, and distal embolization, all of which required surgical or endovascular repair. An apical false aneurysm and an apical tear were major VAC of the transapical group, with the latter resulting in death. Patients with VAC had higher blood transfusion requirements (4.1 ± 4.5 units vs 0.9 ± 2.2 units; P = .004), greater length of hospital stay (16.4 ± 10.7 days vs 6.5 ± 5.1 days; P = .001), and increased cost (A$93,448 ± 21,435 vs A$69,932 ± 15,007; P = .002) compared with the non-VAC group. The predictors of vascular complications using multivariate analysis included European System for Cardiac Operative Risk Evaluation (odds ratio, 1.06; 95% confidence interval, 1.02-1.10; P = .001) and diabetes mellitus (odds ratio, 5.07; 95% confidence interval, 1.17-21.88; P = .03). Occurrence of major VAC did not affect in-hospital or 30-day mortality rates and was not associated with poorer survival. CONCLUSIONS: Vascular complications affect perioperative management and outcomes following TAVI. Our findings show that these complications often require urgent surgical or endovascular repair and result in increased blood transfusions, greater length of hospital stay, and significantly increased costs. Diabetes mellitus and logistic European System for Cardiac Operative Risk Evaluation may be predictive of VAC and should be considered during TAVI patient selection.

A difficult case of retrieval of an aortic valve and balloon during a transcatheter aortic valve implantation.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) represents an emerging therapy for valve replacement in patients not suitable for traditional open repair. As awareness of the procedure grows, case numbers are increasing worldwide. Though this procedure represents a less invasive approach to aortic valve replacement, it is not without complications. PRESENTATION OF CASE: This case presentation describes a serious, previously unreported, complication incurred in an 83-year-old male in whom TAVI was attempted. During deployment of the valve at the aortic annulus, both the valve and accompanying balloon embolised into the thoracic aorta and this was further complicated by migration of the balloon into the abdominal aorta and an aortic dissection. The false lumen of the dissection at the level of the infrarenal aorta was tacked to the aortic adventitial wall using interrupted sutures through a laparotomy. A completion angiogram demonstrated that a flow limited dissection did extend up to both common iliac arteries. This was managed with balloon-expandable covered stents deployed in both common iliac arteries with satisfactory outcome. DISCUSSION: This case occurred as a combination of multiple factors that include lack of burst pacing and poor timing of the balloon inflation. The aortic balloon and the valve had to be removed urgently to avoid ventricular embolization of these structures that can result in a fatal situation. CONCLUSION: This case presentation describes the management of these complications using a combined open and endovascular approach in a well-equipped hybrid operating theatre, resulting in the patient survival.

Endovascular repair of abdominal aortic aneurysms with reverse taper neck anatomy using the Endurant stent-graft: analysis of stent-graft oversizing.

PURPOSE: To evaluate endovascular repair of infrarenal abdominal aortic aneurysms (AAA) using the Endurant stent-graft and compare the outcomes of patients with different neck anatomies, particularly as pertains to stent-graft oversizing. METHODS: A retrospective review was conducted of 75 consecutive patients (69 men; mean age 75 years) undergoing endovascular AAA repair using the Endurant Stent Graft System from December 2008 to September 2011. The mean AAA size was 57±10 mm (range 51-92), with a mean proximal neck length of 33±10 mm (9-127) and a mean infrarenal neck angulation of 25°±15° (0°-91°). Patients were stratified according to neck anatomy [reverse taper (n=22) vs. inside (n=44) and outside (n=9) the Instructions for Use (IFU) criteria]. Standard safety and efficacy outcome measures were augmented by measurements of the percent oversizing at the proximal and distal neck and volumes of the proximal neck and stent-graft. RESULTS: Technical success was 100% in all groups, with no early or late type Ia endoleak detected in any group. Procedure time, contrast volumes, and radiation dosages were comparable in all groups. The reverse taper neck group had stent-graft diameters and volumes that were significantly larger (p=0.007) than the other groups. The proximal neck oversizing of the endograft was significantly greater (p=0.008) in the reverse taper neck group (42.9%±17.5%) compared to the within the IFU group (30.1%±11.7%). Over a mean follow-up of 20 months (range 14-46), there were no aneurysm-related deaths and 9 type II endoleaks (5 in the reverse taper neck group; overall, 3 were treated and 6 resolved spontaneously). The outside the IFU group suffered no endoleak of any type and had no secondary interventions. CONCLUSION: The Endurant stent-graft can be utilized with acceptable results in more challenging neck anatomies, such as those with a reverse taper, as long as there is adequate oversizing of the stent-graft.

Stent outcomes for infrapopliteal arterial occlusive disease.

This study aimed to determine if the different stent types used in the treatment of infrapopliteal arterial occlusive disease provide any significant advantage over one another at 6 and 12-month follow-up. Consecutive patients undergoing stenting of infrapopliteal lesions were enrolled into a non-randomised prospective registry and followed-up for 1 year. Outcome measures included binary restenosis, target lesion revascularisation, major amputation, and change in Rutherford-Becker score and ankle-brachial index (ABI).Thirty-three patients were enrolled including four patients with bilateral disease. There were 20 target vessels in the drug-eluting stent (DES) group, 13 target vessels in the balloon-expandable bare metal stent (BE-BMS) group and 14 target vessels in the self expandableb are metal stent (SE-BMS) group. Most of the patients in the study were octogenarians except in the SE-BMS group where the mean age was 73 ± 9 years. At 12 months, seven patients had died (DES = 6, BE-BMS = 1) from cardiac and cancer-related diseases. In-stent and peri-stent binary restenosis were non-statistically different between all three groups. There was a nonstatistically significant trend towards higher target vessel revascularisation in the BE-BMS group. Survival curves in all stent types demonstrated restenosis to occur within the first 6 months post-procedure. There was no significant difference in the change in Rutherford-Becker score or ABI between the groups. No major limb amputations occurred during the 12-month period. In conclusion,we did not detect a significant difference in stent performance between the different stent types used to treat infrapopliteal arterial occlusive disease. The choice of stent did not seem to affect patient survival or major amputation-free survival at 1-year follow-up.

Sequence determinants of circadian gene expression phase in cyanobacteria.

The cyanobacterium Synechococcus elongatus PCC 7942 exhibits global biphasic circadian oscillations in gene expression under constant-light conditions. Class I genes are maximally expressed in the subjective dusk, whereas class II genes are maximally expressed in the subjective dawn. Here, we identify sequence features that encode the phase of circadian gene expression. We find that, for multiple genes, an ∼70-nucleotide promoter fragment is sufficient to specify class I or II phase. We demonstrate that the gene expression phase can be changed by random mutagenesis and that a single-nucleotide substitution is sufficient to change the phase. Our study provides insight into how the gene expression phase is encoded in the cyanobacterial genome.

Spatial ordering of chromosomes enhances the fidelity of chromosome partitioning in cyanobacteria.

Many cyanobacteria have been shown to harbor multiple chromosome copies per cell, yet little is known about the organization, replication, and segregation of these chromosomes. Here, we visualize individual chromosomes in the cyanobacterium Synechococcus elongatus via time-lapse fluorescence microscopy. We find that chromosomes are equally spaced along the long axis of the cell and are interspersed with another regularly spaced subcellular compartment, the carboxysome. This remarkable organization of the cytoplasm along with accurate midcell septum placement allows for near-optimal segregation of chromosomes to daughter cells. Disruption of either chromosome ordering or midcell septum placement significantly increases the chromosome partitioning error. We find that chromosome replication is both asynchronous and independent of the position of the chromosome in the cell and that spatial organization is preserved after replication. Our findings on chromosome organization, replication, and segregation in S. elongatus provide a basis for understanding chromosome dynamics in bacteria with multiple chromosomes.

A comparison of covered vs bare expandable stents for the treatment of aortoiliac occlusive disease.

OBJECTIVE: This trial was conducted to determine if covered stents offer a patency advantage over bare-metal stents in the treatment of aortoiliac arterial occlusive disease. METHODS: The Covered Versus Balloon Expandable Stent Trial (COBEST), a prospective, multicenter, randomized controlled trial, was performed involving 168 iliac arteries in 125 patients with severe aortoiliac occlusive disease who were randomly assigned to receive a covered balloon-expandable stent or bare-metal stent. Patient demographic data, clinical signs and symptoms, TransAtlantic Inter-Society Consensus (TASC) classification, and preprocedure and postprocedure ankle-brachial index measurements were recorded. The primary end points included freedom from binary restenosis and stent occlusion of the treated area, as determined by ultrasound imaging or quantitative visual angiography, or both. Postprocedural follow-up was at 1, 6, 12, and 18 months. RESULTS: Aortoiliac lesions treated with a covered stent were significantly more likely to remain free from binary restenosis than those that were treated with a bare-metal stent (hazard ratio [HR], 0.35; 95% confidence interval (CI), 0.15-0.82; P = .02). Freedom from occlusion was also higher in lesions treated with covered stents than in those treated with a bare-metal stent (HR, 0.28; 95% CI, 0.07-1.09); however, this did not reach statistical significance (P = .07). Subgroup analyses demonstrated a significant difference in freedom from binary restenosis for covered stents in TASC C and D lesions compared with a bare stent (HR, 0.136; 95% CI, 0.042-0.442). This difference was not demonstrated for TASC B lesions (HR, 0.748; 95% CI, 0.235-2.386). CONCLUSIONS: COBEST demonstrates covered and bare-metal stents produce similar and acceptable results for TASC B lesions. However, covered stents perform better for TASC C and D lesions than bare stents in longer-term patency and clinical outcome.

A high resolution map of a cyanobacterial transcriptome.

BACKGROUND: Previous molecular and mechanistic studies have identified several principles of prokaryotic transcription, but less is known about the global transcriptional architecture of bacterial genomes. Here we perform a comprehensive study of a cyanobacterial transcriptome, that of Synechococcus elongatus PCC 7942, generated by combining three high-resolution data sets: RNA sequencing, tiling expression microarrays, and RNA polymerase chromatin immunoprecipitation sequencing. RESULTS: We report absolute transcript levels, operon identification, and high-resolution mapping of 5' and 3' ends of transcripts. We identify several interesting features at promoters, within transcripts and in terminators relating to transcription initiation, elongation, and termination. Furthermore, we identify many putative non-coding transcripts. CONCLUSIONS: We provide a global analysis of a cyanobacterial transcriptome. Our results uncover insights that reinforce and extend the current views of bacterial transcription.

RNA-mediated epigenetic regulation of DNA copy number.

Increasing evidence suggests that parentally supplied RNA plays crucial roles during eukaryotic development. This epigenetic contribution may regulate gene expression from the earliest stages. Although present in a variety of eukaryotes, maternally inherited characters are especially prominent in ciliated protozoa, in which parental noncoding RNA molecules instruct whole-genome reorganization. This includes removal of nearly all noncoding DNA and sorting the remaining fragments, producing extremely gene-rich somatic genomes. Chromosome fragmentation and extensive replication produce variable DNA copy numbers in the somatic genome. Understanding the forces that drive and regulate copy number change is fundamental. We show that RNA molecules present in parental cells during sexual reproduction can regulate chromosome copy number in the developing nucleus of the ciliate Oxytricha. Experimentally induced changes in RNA abundance can both increase and decrease the levels of corresponding DNA molecules in progeny, demonstrating epigenetic inheritance of chromosome copy number. These results suggest that maternal RNA, in addition to controlling gene expression or DNA processing, can also program DNA amplification levels.