[Influence of Fetomaternal Risk Factors on Mortality and Morbidity in Extremely Preterm Infants]. / Einfluss von fetomaternalen Risikofaktoren auf die Mortalität und Morbidität von Extremfrühgeborenen.

INTRODUCTION: The management of pregnant women at risk of preterm delivery poses a challenge to the interdisciplinary team. At the edge of viability, it is crucial to take into consideration maternal and fetal risk factors when determining individual counseling and therapeutic approaches. METHODS: At a level 4 perinatal center, all preterm infants (PI) born in the years 2017 to 2020 who had a gestational age between 230/7 and 246/7 weeks and were cared for with a curative therapeutic approach were enrolled in a retrospective observational study. Divided into two groups (230/7-236/7 and 240/7-246/7 weeks of gestation), the PI were compared in terms of mortality and morbidity based on maternal and fetal risk factors. Thirteen risk factors and their prognostic relevance for survival were analyzed. RESULTS: 41 mothers with 48 PI were included. 9 neonates received primary palliative treatment and were excluded from the analyses. The survival rates between the two groups (n=21, n=27) showed no significant difference (66.7% versus 74.1%, p=0.750). A significantly higher mortality was observed in PI with an increased number of risk factors (p=0.004), the most severe of which were hypertensive disorders of pregnancy and preterm premature rupture of membranes. Data regarding morbidity showed no significant difference. CONCLUSION: Data regarding mortality correlate with national findings. Observed morbidity in the study population was recorded. The prediction of probability of survival is more precise when risk factors are taken into consideration.

From data to knowledge - big data needs stewardship, a plant phenomics perspective.

The research data life cycle from project planning to data publishing is an integral part of current research. Until the last decade, researchers were responsible for all associated phases in addition to the actual research and were assisted only at certain points by IT or bioinformaticians. Starting with advances in sequencing, the automation of analytical methods in all life science fields, including in plant phenotyping, has led to ever-increasing amounts of ever more complex data. The tasks associated with these challenges now often exceed the expertise of and infrastructure available to scientists, leading to an increased risk of data loss over time. The IPK Gatersleben has one of the world's largest germplasm collections and two decades of experience in crop plant research data management. In this article we show how challenges in modern, data-driven research can be addressed by data stewards. Based on concrete use cases, data management processes and best practices from plant phenotyping, we describe which expertise and skills are required and how data stewards as an integral actor can enhance the quality of a necessary digital transformation in progressive research.

Implementing FAIR data management within the German Network for Bioinformatics Infrastructure (de.NBI) exemplified by selected use cases.

This article describes some use case studies and self-assessments of FAIR status of de.NBI services to illustrate the challenges and requirements for the definition of the needs of adhering to the FAIR (findable, accessible, interoperable and reusable) data principles in a large distributed bioinformatics infrastructure. We address the challenge of heterogeneity of wet lab technologies, data, metadata, software, computational workflows and the levels of implementation and monitoring of FAIR principles within the different bioinformatics sub-disciplines joint in de.NBI. On the one hand, this broad service landscape and the excellent network of experts are a strong basis for the development of useful research data management plans. On the other hand, the large number of tools and techniques maintained by distributed teams renders FAIR compliance challenging.

Antitachycardia pacing at the His bundle is safer than conventional right ventricular antitachycardia pacing in a canine myocardial ischemic injury model.

INTRODUCTION: Antitachycardia pacing (ATP) is used to terminate ventricular tachycardia (VT) by delivering rapid, low energy pacing to the right ventricle (RV). Unfortunately, ATP is not effective against all VT episodes and can result in adverse outcomes, such as VT acceleration and degeneration into ventricular fibrillation (VF). Improving ATP is therefore desirable. Our objective was to compare the efficacy and safety of ATP delivered at the His bundle to traditional ATP. METHODS: Six dogs were anesthetized and pacing leads were implanted in the RV and His bundle. The left anterior descending artery was occluded for 2 h to create an ischemic injury. In a study 4-7 days later, a 128-electrode sock was placed snugly around the ventricles and VT was induced using rapid pacing. ATP was delivered from either the His bundle or RV lead, then attempted at the other location if unsuccessful. Success rates and instances of VT acceleration and degeneration into VF were calculated. RESULTS: We induced 83 runs of VT and attempted ATP 128 times. RV ATP was successful in 36% of attempts; His ATP was successful in 38% of attempts. RV ATP resulted in significantly more adverse outcomes. RV and His ATP induced VT acceleration in 9% and 3% of trains, respectively, and induced degeneration into VF in 5% and 1% of trains, respectively. CONCLUSION: His bundle ATP is safer, but not significantly more effective, than RV ATP.

Management of Enteral Feeding and Application of Probiotics in Very Low Birth Weight Infants - A National Survey in German NICUs.

BACKGROUND: The advantage of breast milk feeding, and supplementation of probiotics is well known and proven. However, the lack of reliable amounts of colostrum and/or transient breast milk during the first few postnatal days might inhibit timely enteral nutrition. METHODS: The aim of this nationwide survey in German Level-1 neonatal intensive care units (NICUs) was to collect data regarding the management of feeding in the first days of life in very low birth weight infants (VLBWIs, birth weight<1500 g). In addition, we analyzed differences in the use of probiotics. An online survey was sent to all 163 Level-1 NICUs in Germany. RESULTS: 110/163 (67.5%) hospitals participated in our study. One-fifth of all participants used exclusively breast milk. The reported incidence of necrotizing enterocolitis (NEC) was lower in NICUs that exclusively used breast milk in VLBWIs (p=0.08). Two-thirds start enteral feeding independent of gestational age during the first 12 hours postnatally with either breast milk or formula. 80% of all participants checked gastric residuals routinely. The use of probiotics differs widely concerning duration and interruption during antibiotic therapy. CONCLUSION: The exclusive use of breast milk is associated with a lower incidence of NEC. The result of our survey emphasizes the paramount importance of nutrition with mother`s milk. In case of insufficient availability of mother`s milk, the use of human donor milk still appears to be superior to formula feeding. The implementation of human donor milk banks should therefore be promoted.

Management of prolonged meconium evacuation in preterm infants: A survey-based analysis in German Neonatal Intensive Care Units.

AIM: Due to the functional immaturity of bowel motility, a delayed passage frequently requires evacuation of meconium in preterm infants. Often rectal enemas and oral laxatives are used to manage these bowel evacuation disorders. METHODS: An online survey was sent to all 163 high-level Neonatal Intensive Care Units (NICUs) in Germany. The participants were queried on rectal enemas, laxative therapy and outcome incidences. RESULTS: A total of 110/163 (67.5%) hospitals participated in the study. 103/110 (93.6%) participating sites applied rectal enemas in cases of delayed meconium evacuation and 63/110 (57.3%) additionally used oral laxatives. In total, 15 different solutions and 7 different application systems were used for rectal instillation. Preterm infants receiving enemas within the first 48 hours after birth were found to have a significantly lower incidence of FIP (p = 0.006). Altogether 8 different oral laxatives were utilised. CONCLUSION: Therapeutic approaches to the management of prolongated meconium evacuation differ widely among German NICUs. Our survey highlights the diversity of applied substances, means of application and differences in duration and frequency of interventions. Macrogol was commonly used in neonates as an oral laxative despite the lack of approval from the manufacturer.

His bundle pacing shows similar ventricular electrical activation as sinus: selective and nonselective His pacing indistinguishable.

His bundle pacing utilizes the His-Purkinje system to produce more physiological activation compared with traditional pacing therapies, but differences in electrical activation between pacing techniques are not yet quantified in terms of activation pattern. Furthermore, clinicians distinguish between selective and nonselective His pacing, but measurable differences in electrical activation remain to be seen. Hearts isolated from seven dogs were perfused using the Langendorff method. Electrograms were recorded using two 64-electrode basket catheters in the ventricles and a 128-electrode sock situated around the ventricles during sinus rhythm (right atrial pacing), right ventricular (RV) pacing, biventricular cardiac resynchronization therapy (biV-CRT), selective His pacing (selective capture of the His bundle), and nonselective His pacing (capture of nearby myocardium and His bundle). Activation maps were generated from these electrograms. Total activation time (TAT) was measured from the activation maps, and QRS duration was measured from a one-lead pseudo-ECG. Results showed that TAT, QRS duration, and activation sequence were most similar between sinus, selective, and nonselective His pacing. Bland-Altman analyses showed highest levels of similarity between all combinations of sinus, selective, and nonselective His pacing. RV and biV-CRT activation patterns were distinct from sinus and had significantly longer TAT and QRS duration. Cumulative activation graphs were most similar between sinus, selective, and nonselective His pacing. In conclusion, selective pacing and nonselective His bundle pacing are more similar to sinus compared with RV and biV-CRT pacing. Furthermore, selective pacing and nonselective His bundle pacing are not significantly different electrically.NEW & NOTEWORTHY Our high-density epicardial and endocardial electrical mapping study demonstrated that selective pacing and nonselective His bundle pacing are more electrically similar to sinus rhythm compared with right ventricular and biventricular cardiac resynchronization therapy pacing. Furthermore, small differences between selective and nonselective His bundle pacing, specifically a wider QRS in nonselective His pacing, do not translate into significant differences in the global activation pattern.

A generally applicable lightweight method for calculating a value structure for tools and services in bioinformatics infrastructure projects.

Sustainable noncommercial bioinformatics infrastructures are a prerequisite to use and take advantage of the potential of big data analysis for research and economy. Consequently, funders, universities and institutes as well as users ask for a transparent value model for the tools and services offered. In this article, a generally applicable lightweight method is described by which bioinformatics infrastructure projects can estimate the value of tools and services offered without determining exactly the total costs of ownership. Five representative scenarios for value estimation from a rough estimation to a detailed breakdown of costs are presented. To account for the diversity in bioinformatics applications and services, the notion of service-specific 'service provision units' is introduced together with the factors influencing them and the main underlying assumptions for these 'value influencing factors'. Special attention is given on how to handle personnel costs and indirect costs such as electricity. Four examples are presented for the calculation of the value of tools and services provided by the German Network for Bioinformatics Infrastructure (de.NBI): one for tool usage, one for (Web-based) database analyses, one for consulting services and one for bioinformatics training events. Finally, from the discussed values, the costs of direct funding and the costs of payment of services by funded projects are calculated and compared.

Premature atrial stimulation accentuates conduction abnormalities in cardiac surgery patients that develop postoperative atrial fibrillation.

BACKGROUND: postoperative atrial fibrillation (POAF) is a common cardiac surgery complication that is associated with increased complications and negative outcomes, but the association between presurgical atrial conduction abnormalities and POAF has not been investigated clinically during premature atrial S1S2 stimulation. This clinical study sought to examine whether intraoperative premature atrial stimulation reveals increased areas of slowed and/or blocked conduction in patients that develop POAF. METHODS: High-density intraoperative epicardial left atrial mapping was conducted in 20 cardiac surgery patients with no prior history of atrial fibrillation (AF). In 20 patients, 6 (30%) developed POAF. A flexible-array of 240-electrodes was placed on the posterior left atrial wall in between the pulmonary veins. Activation maps were generated for sinus and premature atrial S1S2 stimulated beats. The area of conduction block (CB), conduction delay (CD) and the combination of both (CDCB) for conduction velocity < 0.1, 0.1 ≤ x < 0.2 and < 0.2 m/s, respectively were quantified. RESULTS: For a premature atrial S2 beat with shortest cycle length captured, conduction velocity maps revealed a significantly higher area for CD (13.19 ± 6.59 versus 6.06 ± 4.22 mm2, p = 0.028) and CDCB (17.36 ± 8.75 versus 7.41 ± 6.39 mm2, p = 0.034), and a trend toward a larger area for CB (4.17 ± 3.66 versus 1.34 ± 2.86 mm2, p = 0.063) in patients who developed POAF in comparison to those that remained in the sinus. Sinus and S1 paced beats did not show substantial differences in abnormal conduction areas between patients with and without POAF. CONCLUSION: In comparison to sinus and S1 beats, premature atrial S2 beats accentuate conduction abnormalities in the posterior left atrial wall of cardiac surgery patients that developed POAF.

Computational aspects underlying genome to phenome analysis in plants.

Recent advances in genomics technologies have greatly accelerated the progress in both fundamental plant science and applied breeding research. Concurrently, high-throughput plant phenotyping is becoming widely adopted in the plant community, promising to alleviate the phenotypic bottleneck. While these technological breakthroughs are significantly accelerating quantitative trait locus (QTL) and causal gene identification, challenges to enable even more sophisticated analyses remain. In particular, care needs to be taken to standardize, describe and conduct experiments robustly while relying on plant physiology expertise. In this article, we review the state of the art regarding genome assembly and the future potential of pangenomics in plant research. We also describe the necessity of standardizing and describing phenotypic studies using the Minimum Information About a Plant Phenotyping Experiment (MIAPPE) standard to enable the reuse and integration of phenotypic data. In addition, we show how deep phenotypic data might yield novel trait-trait correlations and review how to link phenotypic data to genomic data. Finally, we provide perspectives on the golden future of machine learning and their potential in linking phenotypes to genomic features.

BrAPI-an application programming interface for plant breeding applications.

MOTIVATION: Modern genomic breeding methods rely heavily on very large amounts of phenotyping and genotyping data, presenting new challenges in effective data management and integration. Recently, the size and complexity of datasets have increased significantly, with the result that data are often stored on multiple systems. As analyses of interest increasingly require aggregation of datasets from diverse sources, data exchange between disparate systems becomes a challenge. RESULTS: To facilitate interoperability among breeding applications, we present the public plant Breeding Application Programming Interface (BrAPI). BrAPI is a standardized web service API specification. The development of BrAPI is a collaborative, community-based initiative involving a growing global community of over a hundred participants representing several dozen institutions and companies. Development of such a standard is recognized as critical to a number of important large breeding system initiatives as a foundational technology. The focus of the first version of the API is on providing services for connecting systems and retrieving basic breeding data including germplasm, study, observation, and marker data. A number of BrAPI-enabled applications, termed BrAPPs, have been written, that take advantage of the emerging support of BrAPI by many databases. AVAILABILITY AND IMPLEMENTATION: More information on BrAPI, including links to the specification, test suites, BrAPPs, and sample implementations is available at https://brapi.org/. The BrAPI specification and the developer tools are provided as free and open source.

Enabling reusability of plant phenomic datasets with MIAPPE 1.1.

Enabling data reuse and knowledge discovery is increasingly critical in modern science, and requires an effort towards standardising data publication practices. This is particularly challenging in the plant phenotyping domain, due to its complexity and heterogeneity. We have produced the MIAPPE 1.1 release, which enhances the existing MIAPPE standard in coverage, to support perennial plants, in structure, through an explicit data model, and in clarity, through definitions and examples. We evaluated MIAPPE 1.1 by using it to express several heterogeneous phenotyping experiments in a range of different formats, to demonstrate its applicability and the interoperability between the various implementations. Furthermore, the extended coverage is demonstrated by the fact that one of the datasets could not have been described under MIAPPE 1.0. MIAPPE 1.1 marks a major step towards enabling plant phenotyping data reusability, thanks to its extended coverage, and especially the formalisation of its data model, which facilitates its implementation in different formats. Community feedback has been critical to this development, and will be a key part of ensuring adoption of the standard.

A real-time system for selectively sensing and pacing the His-bundle during sinus rhythm and ventricular fibrillation.

BACKGROUND: The His-Purkinje (HP) system provides a pathway for the time-synchronous contraction of the heart. His bundle (HB) of the HP system is gaining relevance as a pacing site for treating non-reversible bradyarrhythmia despite limited availability of tools to identify the HB. In this paper, we describe a real-time stimulation and recording system (rt-SRS) to investigate using multi-electrode techniques to identify and selectively pace the HB. The rt-SRS can not only be used in sinus rhythm, but also during ventricular fibrillation (VF). The rt-SRS will also help investigate the so far unknown causal effects of selectively pacing the HB during VF. METHODS: The rt-SRS consists of preamplifiers, data acquisition cards interfaced with a real-time controller, a current source, and current routing switches on a remote computer, which may be interrupted to stimulate using a host machine. The remote computer hosts a series of algorithms designed to aid in identifying electrodes directly over the HB, to accurately detect activation rates without over-picking, and to deliver stimulation pulses. The performance of the rt-SRS was demonstrated in seven isolated, perfused rabbit hearts. RESULTS: The rt-SRS can visualize up to 96 channels of raw data, and spatial derivative data at 6.25-kHz sampling rate with an input-referred noise of 100 µV. The rt-SRS can send up to ± 150 V of stimuli pulses to any of the 96 channels. In the rabbit experiments, HB activations were detected in 18 ± 6.8% of the 64 electrodes used during VF. CONCLUSIONS: The rt-SRS is capable of measuring and responding to cardiac electrophysiological phenomena in real-time with precisely timed and placed electrical stimuli. This rt-SRS was shown to be an effective research tool by successfully detecting and quantifying HB activations and delivering stimulation pulses to selected electrodes in real-time.

Occlusal dysesthesia-A clinical guideline.

BACKGROUND: The diagnosis and management of patients suffering from occlusal dysesthesia (OD) remain a major challenge for dental practitioners and affected patients. OBJECTIVES: To present the results of a literature-based expert consensus intended to promote better understanding of OD and to facilitate the identification and management of affected patients. METHODS: In 2018, electronic literature searches were carried out in PubMed, Cochrane Library and Google Scholar as well as in the archives of relevant journals not listed in these databases. This approach was complemented by a careful assessment of the reference lists of the identified relevant papers. The articles were weighted by evidence level, followed by an evaluation of their contents and a discussion. The result represents an expert consensus. RESULTS: Based on the contents of the 77 articles identified in the search, the current knowledge about clinical characteristics, epidemiology, aetiology, diagnostic process, differential diagnosis and management of OD is summarised. CONCLUSIONS: Occlusal dysesthesia exists independently of the occlusion. Instead, it is the result of maladaptive signal processing. The focus should be on patient education, counselling, defocusing, cognitive behavioural therapy, supportive drug therapy and certain non-specific measures. Irreversible, specifically an exclusively dental treatment approach must be avoided.

Cotreatment with sorafenib and oleanolic acid induces reactive oxygen species-dependent and mitochondrial-mediated apoptotic cell death in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common liver malignancy, and the lack of effective chemotherapies underlines the need for novel therapeutic approaches for this disease. Recently, we discovered a novel synergistic induction of cell death by combining sorafenib, the only routinely used palliative chemotherapeutic agent, and the triterpenoid oleanolic acid (OA). However, the underlying mechanisms of action have remained obscure. Here, we report that sorafenib and OA acted in concert to trigger mitochondria-mediated apoptotic cell death, which is dependent on reactive oxygen species (ROS). Sorafenib/OA cotreatment significantly increased ROS production, which was prevented by the ROS scavengers α-tocopherol and MnTBAP. Importantly, rescue experiments showed that ROS were required for sorafenib/OA-induced apoptosis as ROS scavengers protected HCC cells against cell death. In addition, sorafenib and OA cotreatment cooperated to decrease myeloid cell leukaemia-1 expression and to activate Bak, two events that were prevented by ROS scavengers. Bak activation was accompanied by the loss of mitochondrial membrane potential, followed by PARP cleavage, DNA fragmentation and, finally, apoptotic cell death in HCC cells. By providing new insights into the molecular regulation of sorafenib/OA-mediated and ROS-dependent cell death, our study contributes toward the development of novel treatment strategies to overcome sorafenib resistance in HCC.

LAILAPS-QSM: A RESTful API and JAVA library for semantic query suggestions.

In order to access and filter content of life-science databases, full text search is a widely applied query interface. But its high flexibility and intuitiveness is paid for with potentially imprecise and incomplete query results. To reduce this drawback, query assistance systems suggest those combinations of keywords with the highest potential to match most of the relevant data records. Widespread approaches are syntactic query corrections that avoid misspelling and support expansion of words by suffixes and prefixes. Synonym expansion approaches apply thesauri, ontologies, and query logs. All need laborious curation and maintenance. Furthermore, access to query logs is in general restricted. Approaches that infer related queries by their query profile like research field, geographic location, co-authorship, affiliation etc. require user's registration and its public accessibility that contradict privacy concerns. To overcome these drawbacks, we implemented LAILAPS-QSM, a machine learning approach that reconstruct possible linguistic contexts of a given keyword query. The context is referred from the text records that are stored in the databases that are going to be queried or extracted for a general purpose query suggestion from PubMed abstracts and UniProt data. The supplied tool suite enables the pre-processing of these text records and the further computation of customized distributed word vectors. The latter are used to suggest alternative keyword queries. An evaluated of the query suggestion quality was done for plant science use cases. Locally present experts enable a cost-efficient quality assessment in the categories trait, biological entity, taxonomy, affiliation, and metabolic function which has been performed using ontology term similarities. LAILAPS-QSM mean information content similarity for 15 representative queries is 0.70, whereas 34% have a score above 0.80. In comparison, the information content similarity for human expert made query suggestions is 0.90. The software is either available as tool set to build and train dedicated query suggestion services or as already trained general purpose RESTful web service. The service uses open interfaces to be seamless embeddable into database frontends. The JAVA implementation uses highly optimized data structures and streamlined code to provide fast and scalable response for web service calls. The source code of LAILAPS-QSM is available under GNU General Public License version 2 in Bitbucket GIT repository: https://bitbucket.org/ipk_bit_team/bioescorte-suggestion.

Ultrasound assessment of gastric emptying time in preterm infants: A prospective observational study.

BACKGROUND: In paediatric anaesthesia, pre-operative fasting should be short to prevent discomfort, hunger, thirst and metabolic disorders. Current European guidelines recommend pre-operative fasting times of 4 h for breast milk and 6 h for formula milk in infants, whereas some national guidelines allow both until 4 h before anaesthesia. OBJECTIVE: We evaluated the gastric emptying times of preterm infants after breast milk and formula milk, hypothesising that the mean gastric emptying time would be less than 4 h. DESIGN: A prospective, observational, noninterventional cohort study. SETTING: Neonatal ICU of a university hospital from August to September 2017. PATIENTS: Twenty-two infants with a postmenstrual mean ±â€ŠSD (range) age of 35 ±â€Š2 (32 to 40) weeks were included. Based on their prescription plan, 10 infants received breast milk and 12 received formula milk with a total volume of 50 ±â€Š16 (24 to 70) ml. INTERVENTIONS: Gastric emptying was examined by sonographic measurements of the gastric antral area (GAA) before (FT0) and hourly after breast milk or formula milk feeding (FT1 to FT3). MAIN OUTCOME MEASURES: Estimated gastric emptying time after enteral feeding with breast milk and formula milk in preterm infants. RESULTS: The GAA of the preterm infants initially increased and subsequently decreased after feeding. GAA correlated significantly with fasting time (r = -0.53, P < 0.0001). At FT3 [199 ±â€Š16 (175 to 225) min], GAA was 0.57 (0.42 to 0.91) cm and showed no difference compared with FT0. Using a linear regression model, the calculated mean gastric emptying time was 218 min. CONCLUSION: The study shows that the mean gastric emptying time after enteral feeding with breast milk and formula milk is less than 4 h in preterm infants. These results support our current national fasting regimen of 4 h for any milk composition in infants before anaesthesia. TRIAL REGISTRATION: German registry of clinical studies (DRKS-ID: DRKS 00013893).

Seed Plant-Specific Gene Lineages Involved in Carpel Development.

Evolutionary innovations are important drivers of speciation and some are the defining characters of entire phyla. One such major innovation is the carpel, the unifying character and most complex plant organ, composed of many clearly distinct tissue types to ensure reproductive success. The origin of the carpel is unknown, but many components of the gene regulatory network (GRN) governing carpel development and their genetic interactions are known from the core eudicot Arabidopsis thaliana. To unravel the evolution of the carpel GRN and to discriminate between "early" and "late" steps in carpel evolution, we calculated thorough phylogeny reconstructions based on sequenced genomes. The A. thaliana carpel GRN members ALCATRAZ (ALC), CRABS CLAW (CRC), HALF FILLED (HAF), HECATE (HEC), INDEHISCENT (IND), NGATHA (NGA), and SPATULA (SPT) were analyzed in their phylogenetic context. We find that the carpel GRN components are of various ages, but interestingly, we identify especially high retention rates for carpel development genes in Brassicaceae. Our data suggest that genes whose A. thaliana homologs are involved in processes already present in the most recent common ancestor of seed plants, such as reproductive meristem termination or adaxial/abaxial polarity specification, are not retained in duplicates after whole genome duplications (WGD). In contrast, genes involved in processes associated with derived carpel characters in Arabidopsis, such as the transmitting tract or style development show a higher gene retention rate after WGD. This work provides a starting point for analyses of carpel genes in early diverging angiosperms which would be very informative for evolutionary studies.

An Evolutionary Framework for Carpel Developmental Control Genes.

Carpels are the female reproductive organs of flowering plants (angiosperms), enclose the ovules, and develop into fruits. The presence of carpels unites angiosperms, and they are suggested to be the most important autapomorphy of the angiosperms, e.g., they prevent inbreeding and allow efficient seed dispersal. Many transcriptional regulators and coregulators essential for carpel development are encoded by diverse gene families and well characterized in Arabidopsis thaliana. Among these regulators are AGAMOUS (AG), ETTIN (ETT), LEUNIG (LUG), SEUSS (SEU), SHORT INTERNODE/STYLISH (SHI/STY), and SEPALLATA1, 2, 3, 4 (SEP1, 2, 3, 4). However, the timing of the origin and their subsequent molecular evolution of these carpel developmental regulators are largely unknown. Here, we have sampled homologs of these carpel developmental regulators from the sequenced genomes of a wide taxonomic sampling of the land plants, such as Physcomitrella patens, Selaginella moellendorfii, Picea abies, and several angiosperms. Careful phylogenetic analyses were carried out that provide a phylogenetic background for the different gene families and provide minimal estimates for the ages of these developmental regulators. Our analyses and published work show that LUG-, SEU-, and SHI/STY-like genes were already present in the Most Recent Common Ancestor (MRCA) of all land plants, AG- and SEP-like genes were present in the MRCA of seed plants and their origin may coincide with the ξ Whole Genome Duplication. Our work shows that the carpel development regulatory network was, in part, recruited from preexisting network components that were present in the MRCA of angiosperms and modified to regulate gynoecium development.