Eubacterium album sp. nov., a butyrate-producing bacterium isolated from faeces of a healthy human.

An oval to rod-shaped, Gram-stain-positive, strictly anaerobic bacterium, designated LFL-14T, was isolated from the faeces of a healthy Chinese woman. Cells of the strain were non-spore-forming, grew optimally at 37 °C (growth range 30-45 °C) and pH 7.0 (growth range 6.0-9.0) under anaerobic conditions in the liquid modified Gifu anaerobic medium (mGAM). The result of 16S rRNA gene-based analysis indicated that LFL-14T shared an identity of 94.7 0% with Eubacterium ventriosum ATCC 27560T, indicating LFL-14T represented a novel taxon. The results of genome-based analysis revealed that the average nucleotide identity (ANI), the digital DNA-DNA hybridisation (dDDH) and average amino acid identity (AAI) between LFL-14T and its phylogenetically closest neighbour, Eubacterium ventriosum ATCC 27560T, were 77.0 %, 24.6 and 70.9 %, respectively, indicating that LFL-14T represents a novel species of the genus Eubacterium. The genome size of LFL-14T was 2.92 Mbp and the DNA G+C content was 33.14 mol%. We analysed the distribution of the genome of LFL-14T in cohorts of healthy individuals, type 2 diabetes patients (T2D) and patients with non-alcoholic fatty liver disease (NAFLD). We found that its abundance was higher in the T2D cohort, but it had a low average abundance of less than 0.2 % in all three cohorts. The percentages of frequency of occurrence in the T2D, healthy and NAFLD cohorts were 48.87 %, 16.72 % and 13.10 % respectively. The major cellular fatty acids of LFL-14T were C16 : 0 (34.4 %), C17 : 0 2-OH (21.4 %) and C14 : 0 (11.7 %). Additionally, the strain contained diphosphatidylglycerol (DPG) and phosphatidylethanolamine (PE), as well as unidentified phospholipids and unidentified glycolipids. The glucose fermentation products of LFL-14T were acetate and butyrate. In summary, On the basis of its chemotaxonomic, phenotypic, phylogenetic and phylogenomic properties, strain LFL-14T (= CGMCC 1.18005T = KCTC 25580T) is identified as representing a novel species of the genus Eubacterium, for which the name Eubacterium album sp. nov. is proposed.

Laparoscopic surgery for oncologic extended resection of T1b and T2 incidental gallbladder carcinoma at a high-volume center: a single-center experience in China.

BACKGROUND: Surgical treatment is still the most effective treatment for gallbladder cancer. For the patients with stage T1b and above, the current guidelines recommend the extended radical operation, and oncologic extended resection can benefit the survival of the patients. The laparoscopic approach is still in the early phase, and its safety and oncological outcomes are not well known. OBJECTIVE: To evaluate the technical feasibility and oncological outcomes of laparoscopic surgery for oncologic extended resection of early-stage incidental gallbladder carcinoma. RESULTS: This study included 18 male and 32 female patients. Twenty patients underwent laparoscopic oncologic extended resection and 30 patients underwent open oncologic extended resection. All of the patients had R0 resection. A laparoscopic approach was associated with less intraoperative blood loss (242 ± 108.5 vs 401 ± 130.3; p < 0.01) and shorter duration of postoperative hospital stay (6.2 ± 2.4 vs 8.6 ± 2.3; p < 0.01). There was no statistically significant difference between two groups for lymph nodes yield (5.4 ± 3.5 vs 5.8 ± 2.1; p > 0.05), incidence of lymphatic metastasis (15% vs 16.67%; p > 0.05), residual disease (20% vs 23.3%; p > 0.05), and postoperative morbidity (15% vs 20%; p > 0.05). During follow-up time of median 20.95 (12-29.5) months, no significant difference was found between the two groups for early tumor recurrence (10% vs 13.33%; p > 0.05) and disease-free survival (p > 0.05). CONCLUSION: Laparoscopic surgery may offer similar intraoperative, perioperative, and short-term oncological outcomes as an open oncologic extended resection for incidental gallbladder carcinoma.

Schwannoma in the hepatoduodenal ligament with portal vein invasion: A case report.

RATIONALE: Schwannomas are mesenchymal tumors with low malignant potential that originate from Schwann cells. They can occur in most parts of the body, such as the head, neck, and extremities. Schwannoma in the hepatoduodenal ligament is extremely rare, and only four cases have been reported in the literature. PATIENT CONCERNS: Herein, we describe a 58-year-old female who presented with right epigastric pain for 10 days. Preoperative computed tomographic (CT) revealed a 4.5 cm × 3.8 cm tumor in the hepatic hilar area. DIAGNOSES: Schwannoma in the hepatoduodenal ligament with portal vein invasion. INTERVENTIONS: Intraoperative findings revealed that the tumor was identified in the hepatoduodenal ligament, and the left branch of the portal vein was compressed. Complete tumor resection with reparation of the portal vein was performed for the patient. Postoperative pathological examination confirmed the final diagnosis of benign schwannoma, characterized by abundant spindle-shaped cells and positive reactivity for S-100 protein. OUTCOMES: The patient had a good prognosis and had no recurrence after 37 months of follow-up. LESSONS: Our case of schwannoma in the hepatoduodenal ligament is unique owing to the portal vein invasion, aimed at helping recognize the difficulty of preoperative diagnosis.

Is radical resection of hilar cholangiocarcinoma plus partial resection of pancreatic head justified for advanced hilar cholangiocarcinoma?

BACKGROUND: To outline our experience with the radical resection of hilar cholangiocarcinoma (HCCA) combined with the partial resection of the pancreatic head (RRHCCAPRPH) as a treatment for HCCA with distal bile duct involvement and to appraise the feasibility of this challenging procedure. METHODS: Between 2007 and 2017, 205 patients with HCCA who underwent curative surgery at our hospital were included. Among the patients, extrahepatic bile duct resection combined with hepatectomy (EBDRH), RRHCCAPRPH and hepatopancreaticoduodenectomy (HPD) was performed in 168, 21 and 16 patients, respectively. Clinical pathological factors, post-operative complications and survival were compared between the three groups. RESULTS: There was a significant difference in operative blood loss, operative time, post-operative hospital stay and tumour size between EBDRH group, RRHCCAPRPH group and HPD group (P < 0.05). In terms of post-operative complications, there was no statistical difference between the three groups (P = 0.177). Further analysis showed that the incidence of pancreatic fistula (43.8%) and delayed gastric emptying (25%) after HPD were significantly higher than the other two groups. The median survival time and overall survival rate for 172 patients with R0 resection were 33 months and 85.5% at 1 year, 47.7% at 3 years, 28.4% at 5 years. Furthermore, the 1-, 3- and 5-year survival rates of patients with EBDRH, RRHCCAPRPH and HPD after R0 resection were 86.2%, 48.7%, 29.2%; 85.0%, 44.0%, 24.7% and 78.6%, 42.9%, 22.9%, respectively (P = 0.948). CONCLUSION: The RRHCCAPRPH in some selected patients can actually replace HPD as a surgical treatment for HCCA with distal bile duct involvement.

Overall Postoperative Morbidity and Pancreatic Fistula Are Relatively Higher after Central Pancreatectomy than Distal Pancreatic Resection: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the intraoperative and postoperative outcomes of central pancreatectomy (CP) with distal pancreatectomy (DP). METHODS: A systematic literature search was performed on electronic databases from MEDLINE, Embase, and PubMed from 1998 to 2018. Statistical analysis and meta-analysis were performed using statistics/data analysis (Stata®) software, version 12.0 (StataCorp LP, College Station, Texas 77845, USA). Dichotomous variables were analyzed by estimation of relative risk (RR) with a 95 percent (%) confidence interval (CI) and continuous variables were analyzed by standardized mean differences (SMD) with 95% CI. RESULTS: Twenty-four studies with 593 CP and 1226 DP were included in the meta-analysis. CP had significantly longer operation time (SMD: 1.03; 95% CI 0.62 to 1.44; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.001) and lengthier postoperative hospital stay (SMD: 0.63; 95% CI 0.20 to 1.05; P < 0.01). Estimated blood loss was significantly lower in CP (SMD: -0.34; 95% CI -0.58 to -0.09; P = 0.007). Overall postoperative morbidity (RR: 1.30; 95% CI: 1.13 to 1.50; P < 0.001), overall pancreatic fistula (RR: 1.41; 95% CI: 1.20 to 1.66; P < 0.001), clinically relevant fistula (RR: 1.64; 95% CI: 1.25 to 2.16; P < 0.001), and postoperative hemorrhage (RR: 1.90; 95% CI: 1.18 to 3.06; P < 0.05) were all significantly higher after CP. On long-term follow-up, DP patients were more likely to have postoperative exocrine (RR: 0.56; 95% CI: 0.37 to 0.84; P < 0.05) and endocrine (RR: 0.27; 95% CI: 0.18 to 0.40; P < 0.001) insufficiency. There was no statistically significant difference in transfusion requirement, postoperative mortality, reoperation, and tumor recurrence. CONCLUSION: CP is associated with significantly higher morbidity and clinically relevant pancreatic fistula. CP should only be reserved for selected patients who require postoperative pancreatic function preservation.

Characterizing the heterogeneity in 5-aminolevulinic acid-induced fluorescence in glioblastoma.

OBJECTIVE: 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is an effective surgical adjunct for the intraoperative identification of tumor tissue during resection of high-grade gliomas. The use of 5-ALA-induced PpIX fluorescence in glioblastoma (GBM) has been shown to double the extent of gross-total resection and 6-month progression-free survival. The heterogeneity of 5-ALA-induced PpIX fluorescence observed during surgery presents a technical and diagnostic challenge when utilizing this tool intraoperatively. While some regions show bright fluorescence after 5-ALA administration, other regions do not, despite that both regions of the tumor may be histopathologically indistinguishable. The authors examined the biological basis of this heterogeneity using computational methods. METHODS: The authors collected both fluorescent and nonfluorescent GBM specimens from a total of 14 patients undergoing surgery and examined their gene expression profiles. RESULTS: In this study, the authors found that the gene expression patterns characterizing fluorescent and nonfluorescent GBM surgical specimens were profoundly different and were associated with distinct cellular functions and different biological pathways. Nonfluorescent tumor tissue tended to resemble the neural subtype of GBM; meanwhile, fluorescent tumor tissue did not exhibit a prominent pattern corresponding to known subtypes of GBM. Consistent with this observation, neural GBM samples from The Cancer Genome Atlas database exhibited a significantly lower fluorescence score than nonneural GBM samples as determined by a fluorescence gene signature developed by the authors. CONCLUSIONS: These results provide a greater understanding regarding the biological basis of differential fluorescence observed intraoperatively and can provide a basis to identify novel strategies to maximize the effectiveness of fluorescence agents.

Cervicofacial necrotising fasciitis by clindamycin-resistant and methicillin-resistant Staphylococcus aureus (MRSA) in a young healthy man.

An otherwise healthy 24-year-old man presented with 1 week of fever, facial pain and swelling. He initially sought care at an outside hospital, where he was diagnosed with folliculitis and sent home with oral antibiotics. On arrival at our institution, CT neck was ordered, which demonstrated diffuse submental phlegmon, prompting incision and drainage. After initial improvement, the patient experienced high fevers and increased swelling just 12 hours later. The decision was made to take the patient for operative exploration, and wide debridement was performed due to suspicion for necrotising fasciitis intraoperatively that was ultimately confirmed on final pathology. Final speciation of intraoperative culture demonstrated a clindamycin-resistant and methicillin-resistant strain of Staphylococcus aureus The patient was managed with intravenous antibiotics, additional debridement and careful wound care. Delayed partial closure of wound was eventually performed once patient showed marked and persistent clinical improvement. The patient was discharged on hospital day 12 with close follow-up.

Developmental profiling of microRNAs in the human embryonic inner ear.

Due to the extreme inaccessibility of fetal human inner ear tissue, defining of the microRNAs (miRNAs) that regulate development of the inner ear has relied on animal tissue. In the present study, we performed the first miRNA sequencing of otic precursors in human specimens. Using HTG miRNA Whole Transcriptome assays, we examined miRNA expression in the cochleovestibular ganglion (CVG), neural crest (NC), and otic vesicle (OV) from paraffin embedded (FFPE) human specimens in the Carnegie developmental stages 13-15. We found that in human embryonic tissues, there are different patterns of miRNA expression in the CVG, NC and OV. In particular, members of the miR-183 family (miR-96, miR-182, and miR-183) are differentially expressed in the CVG compared to NC and OV at Carnegie developmental stage 13. We further identified transcription factors that are differentially targeted in the CVG compared to the other tissues from stages 13-15, and we performed gene set enrichment analyses to determine differentially regulated pathways that are relevant to CVG development in humans. These findings not only provide insight into the mechanisms governing the development of the human inner ear, but also identify potential signaling pathways for promoting regeneration of the spiral ganglion and other components of the inner ear.

Insulin-Mediated Signaling Facilitates Resistance to PDGFR Inhibition in Proneural hPDGFB-Driven Gliomas.

Despite abundant evidence implicating receptor tyrosine kinases (RTK), including the platelet-derived growth factor receptor (PDGFR), in the pathogenesis of glioblastoma (GBM), the clinical use of RTK inhibitors in this disease has been greatly compromised by the rapid emergence of therapeutic resistance. To study the resistance of proneural gliomas that are driven by a PDGFR-regulated pathway to targeted tyrosine kinase inhibitors, we utilized a mouse model of proneural glioma in which mice develop tumors that become resistant to PDGFR inhibition. We found that tumors resistant to PDGFR inhibition required the expression and activation of the insulin receptor (IR)/insulin growth-like factor receptor (IGF1R) for tumor cell proliferation and survival. Cotargeting IR/IGF1R and PDGFR decreased the emergence of resistant clones in vitro Our findings characterize a novel model of glioma recurrence that implicates the IR/IGF1R signaling axis in mediating the development of resistance to PDGFR inhibition and provide evidence that IR/IGF1R signaling is important in the recurrence of the proneural subtype of glioma in which PDGF/PDGFR is most commonly expressed at a high level. Mol Cancer Ther; 16(4); 705-16. ©2017 AACR.

Lymphoepithelioma-like hepatocellular carcinoma: A case report and brief review of literature.

RATIONAL: Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare variant of hepatocellular carcinoma (HCC). To date, few cases have been reported in the literature, and almost no report in analyzing the different features of LEL-HCC. PATIENT CONCERNS: We describe a 37-year-old female patient with a 32 × 30 mm mass in the right liver. INTERVENTIONS: Complete surgical resection of the lesion was performed. DIAGNOSES: Histopathological examination of the resected tumor revealed undifferentiated HCC cells with significant lymphocytes infiltration. Immunohistochemically, the tumor cells were positive for AFP (alpha fetoprotein), hepatocyte, CK8, and glypican-3. The patient was diagnosed with LEL-HCC. OUTCOMES: The patient had a favorable clinical outcome, and was free from tumor recurrence after a 52-months follow-up. LESSONS: Our case was the youngest patient of all the reported cases, and the third case who was infected with both hepatitis B virus (HBV) and hepatitis C virus (HCV). LEL-HCC is a rare variant of HCC, with a relatively favorable prognosis. Further research recruiting more patients is required to determine the accurate causes and mechanism of LEL-HCC.

[Determination of residual aluminium Ion in Huoxiang Zhengqi pellets by GFAAS with EDTA complexation extraction].

To establish an EDTA complexation extraction pretreatment combining with GFAAS method for the determination of residual aluminium ion in Huoxiang zhengqi pellets without digestive treatment, systematical investigation was made on sample preparation, and EDTA was used for the complexation extraction of residual aluminium ion in samples. The pH, concentration and volume of extraction solution, the temperature and time of microwave extraction, and graphite furnace temperature program were investigated. The results were compared with the microwave digestion. It was showed that, 0.1 g of sample weight was added in 20 mL 0.05 mol x L(-1) EDTA solution (pH 3.5), followed by heating at 150 degrees C for 10 min in the microwave extraction device. The determination of GFAAS was performed at optimized detection wavelength (257.4 nm) as well as graphite furnace temperature program, the detection limits and quantification limits were 2.37 µg x L(-1) and 7.89 µg x L(-1), respectively. The precision (RSD) was less than 2.3%. The average recovery was 96.9% -101%. The present method is easy, rapid and accurate for the determination of residual aluminium ion in Huoxiang zhengqi pellets.

Study of enrichment factors for six ß-blockers in aliphatic alcohols by hollow-fiber liquid-phase microextraction.

The selectivity of a suitable organic solvent is key for extraction in liquid-phase microextraction experiments. Nevertheless, the screening process remains a daunting task. Our research aimed to study the relationship between extraction efficiency and extraction solvents, analytes, and finally select the appropriate extraction solvent. In the present article, ß-blockers and six extraction solvents were chosen as the models and hollow-fiber liquid-phase microextraction was conducted. The relationship was built by statistical analysis on the data. Factors affecting extraction efficiency including the logarithms of the octanol/water partition coefficient (logPo/w ) of analytes, acid dissociation constants, the logarithms of the octanol/water partition coefficient of solvents and pH of the sample solution were investigated. The results showed that a low water solubility of extraction solvent is the foundation to ensure higher extraction efficiency. Moreover, when ΔlogPo/w > 0, a higher extraction efficiency is observed at lower ΔlogPo/w , on the contrary, when ΔlogPo/w < 0, extraction efficiency is higher as the absolute value of ΔlogPo/w becomes greater. Finally, the relationship between enrichment factor and extraction solvents, analytes was established and a helpful guidance was provided for the selection of an optimal solvent to obtain the best extraction efficiency by liquid-phase microextraction.

[Determination of aflatoxin B1, B2, G1, G2 in Ben Lamge granules by HPLC-FLD after multi-pretreatment clean-up].

To establish a multi-pretreatment method for the determination of aflatoxin B1, B2, G1, G2 in Chinese patent medicines, aflatoxins were analyzed by high performance liquid chromatography-fluorescence detector with post-column derivatization, after the multi-pretreatment of samples. The results showed that after the samples extracted with MeOH-H2O, dehydrated by anhydrous magnesium sulphate and sodium chloride, and finally purified by neutral alumina, the impurity interference of different sources in Chinese patent medicines matrix can be effectively removed, and the main peak can be nicely separated from the impurity peak. The detection limits were 0.25, 0.25, 0.50, 0.25 µg x L(-1) for AFB1, AFB2, AFG1, AFG2, respectively. The quantification limits were 1.00, 0.50, 1.00, 0.50 µg x L(-1), respectively. Aflatoxin B1, G1 showed a good linear relationship at a range of 1.0-50 µg x L(-1), aflatoxin B2, G2 at a range of 0.5-12.5 µg x L(-1) (R2 > 0.99). The average recovery was 80.40% - 108.6%. The present method is simple, reproducible with the reasonable recoveries and can be applied for the determination of aflatoxins in Chinese patent medicines.

Id2 mediates oligodendrocyte precursor cell maturation arrest and is tumorigenic in a PDGF-rich microenvironment.

Maturation defects occurring in adult tissue progenitor cells have the potential to contribute to tumor development; however, there is little experimental evidence implicating this cellular mechanism in the pathogenesis of solid tumors. Inhibitor of DNA-binding 2 (Id2) is a transcription factor known to regulate the proliferation and differentiation of primitive stem and progenitor cells. Id2 is derepressed in adult tissue neural stem cells (NSC) lacking the tumor suppressor Tp53 and modulates their proliferation. Constitutive expression of Id2 in differentiating NSCs resulted in maturation-resistant oligodendroglial precursor cells (OPC), a cell population implicated in the initiation of glioma. Mechanistically, Id2 overexpression was associated with inhibition of the Notch effector Hey1, a bHLH transcription factor that we here characterize as a direct transcriptional repressor of the oligodendroglial lineage determinant Olig2. Orthotopic inoculation of NSCs with enhanced Id2 expression into brains of mice engineered to express platelet-derived growth factor in the central nervous system resulted in glioma. These data implicate a mechanism of altered NSC differentiation in glioma development and characterize a novel mouse model that reflects key characteristics of the recently described proneural subtype of glioblastoma multiforme. Such findings support the emerging concept that the cellular and molecular characteristics of tumor cells are linked to the transformation of distinct subsets of adult tissue progenitors.

Proliferation-independent control of tumor glycolysis by PDGFR-mediated AKT activation.

The differences in glucose metabolism that distinguish most malignant and normal tissues have called attention to the importance of understanding the molecular mechanisms by which tumor energy metabolism is regulated. Receptor tyrosine kinase (RTK) pathways that are implicated in proliferation and transformation have been linked to several aspects of tumor glucose metabolism. However, the regulation of glycolysis has invariably been examined under conditions in which proliferation is concomitantly altered. To determine whether RTKs directly regulate glycolysis without prerequisite growth modulation, we first identified a specific RTK signaling pathway, platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) that regulates glycolysis in glioma-derived tumor stem-like cells from a novel mouse model. We determined that PDGF-regulated glycolysis occurs independent of PDGF-regulated proliferation but requires the activation of AKT, a known metabolic regulator in tumor. Our findings identifying a key characteristic of brain tumors, aerobic glycolysis, mediated by a pathway with multiple therapeutic targets suggests the possibility of inhibiting tumor energy metabolism while also treating with agents that target other pathways of pathologic significance.

Genetics of glioblastoma: a window into its imaging and histopathologic variability.

Glioblastoma is a highly malignant brain tumor that relentlessly defies therapy. Efforts over the past decade have begun to tease out the biochemical details that lead to its aggressive behavior and poor prognosis. There is hope that this new understanding will lead to improved treatment strategies for patients with glioblastoma, in the form of targeted, molecularly based therapies that are individualized to specific changes in individual tumors. However, these new therapies have the potential to fundamentally alter the biologic behavior of glioblastoma and, as a result, its imaging appearance. Knowledge about common genetic alterations and the resultant cellular and tissue changes (ie, induced angiogenesis and abnormal cell survival, proliferation, and invasion) in glioblastomas is important as a basis for understanding imaging findings before treatment. It is equally critical that radiologists understand which genetic pathway is targeted by each specific therapeutic agent or class of agents in order to accurately interpret changes in the imaging appearances of treated tumors.

Inhibitor of DNA binding 4 (ID4) regulation of adipocyte differentiation and adipose tissue formation in mice.

Inhibitor of DNA binding 4 (ID4) is a helix-loop-helix protein that heterodimerizes with basic helix-loop-helix transcription factors inhibiting their function. ID4 expression is important for adipogenic differentiation of the 3T3-L1 cell line, and inhibition of ID4 is associated with a concomitant decrease in CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma mRNA and protein expression. Mice with a homozygous deletion of Id4 (Id4(-/-)) have reduced body fat and gain much less weight compared with wild-type littermates when placed on diets with high fat content. Mouse embryonic fibroblasts (MEFs) isolated from Id4(-/-) mice have reduced adipogenic potential when compared with wild-type MEFs. In agreement with changes in morphological differentiation, the levels of CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma were also reduced in MEFs from Id4(-/-) mice. Our results demonstrate the importance of ID4 in adipocyte differentiation and the implications of this regulation for adipose tissue formation.

Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development.

The E2f7 and E2f8 family members are thought to function as transcriptional repressors important for the control of cell proliferation. Here, we have analyzed the consequences of inactivating E2f7 and E2f8 in mice and show that their individual loss had no significant effect on development. Their combined ablation, however, resulted in massive apoptosis and dilation of blood vessels, culminating in lethality by embryonic day E11.5. A deficiency in E2f7 and E2f8 led to an increase in E2f1 and p53, as well as in many stress-related genes. Homo- and heterodimers of E2F7 and E2F8 were found on target promoters, including E2f1. Importantly, loss of either E2f1 or p53 suppressed the massive apoptosis in double-mutant embryos. These results identify E2F7 and E2F8 as a unique repressive arm of the E2F transcriptional network that is critical for embryonic development and control of the E2F1-p53 apoptotic axis.