bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of dietary emulsifier and lipid source on broiler meat quality, lipids, and serum antioxidant status
Authors: Tenório Karine Isabela , Eyng Cinthia , Nunes Ricardo Vianna , Broch Jomara , Rohloff Nilton , de Souza Cleison , Savaris Vaneila Daniele Lenhardt , Polese Clauber 
Published: May 2022

This study aimed to evaluate the effects of diets containing acid soybean oil (ASO) as a substitute for degummed soybean oil (DSO), with or without an emulsifier, on the serum lipid composition, antioxidant protection, carcass yield, and meat quality of broilers. Seven hundred and four 1-day-old male chicks were distributed in a 2 × 2 factorial arrangement (with or without emulsifier × two lipid sources—ASO and DSO), with eight replicates. The dietary inclusion of ASO increased by 65.87% the serum activity of the superoxide dismutase at 21 days of age. The inclusion of the emulsifier reduced the tenderloin yield of the birds by 5.22% and the abdominal fat percentage by 10.20% at 49 days of age, interfering with serum low-density lipoprotein and triglyceride. There was an increase in the water-holding capacity, greater yellow intensity ( b*) 15 min post mortem, and lower pH 24 h post mortem for meat from broilers fed diets containing DSO. Meat from broilers fed diets containing ASO with an emulsifier showed lower shear force. The emulsifier did not provide additional metabolizable energy, as reflected by the reduced chicken tenderloin yield. The use of ASO provided better serum antioxidant status, with no deleterious effects on the carcass and meat quality of broilers.
Building the “Arctic Silk Road”: China’s New Project
Authors: Dang Thuy T. , Diem Tran Ngoc , Vu Ngo Van 
Published: May 2022

The Arctic is being seen as a hotbed of strategic competition between major powers. In recent years, not only the United States, but also Russia and China have increased their engagement within the Arctic region by the implementation of research surveys, exploration activities, and gradually increased their military presence in order to consolidate influence in the resource-wealthy region (Hân, 2021) [[Formula: see text], May 31, https://www.qdnd.vn/thoi-su-quoc-te/doi-song-quoc-te/suc-nong-cua-bac-cuc-661233 ]. Up to now, China has launched many strategies and related policies for the Arctic region. In the recently announced 14th Five-Year Plan (2021–2025), China emphasizes the importance of the “Polar Silk Road across the Arctic”, seeing it as a component of the “Belt and Road Initiative” (BRI). The Government of China also calls for enterprises to invest in the Arctic Ocean and Antarctica. The paper provides an objective and a multidimensional assessment on the formation and construction of a project known as China’s Polar Silk Road across the Arctic or Arctic Silk Road so that we can better understand this new Chinese ambition.
Construction and Evaluation of Prognosis Prediction Model for Patients with Brain Contusion and Laceration Based on Machine Learning
Authors: Li Shaoquan , Bai Limei , Zheng Zhixia 
Published: May 2022

Objective. Finding valuable risk factors for the prognosis of brain contusion and laceration can help patients understand the condition and improve the prognosis. This study is aimed at analyzing the risk factors of poor prognosis in patients with brain contusion after the operation. Methods. A total of 136 patients with cerebral contusion and laceration combined with cerebral hernia treated by neurosurgical craniotomy in our hospital were retrospectively selected and divided into a training set (

n
=
95

) and a test set (

n
=
41

) by the 10-fold crossover method. Logistic regression and back-propagation neural network prediction models were established to predict poor prognosis factors. The receiver operating characteristic curve (ROC) and the calibration curve were used to verify the differentiation and consistency of the prediction model. Results. Based on logistic regression and back-propagation neural network prediction models,

GCS

score
≤
8

on admission,

blood

loss
≥
30

ml,

mannitol
≥
2

weeks, anticoagulants before admission, and surgical treatment are the risk factors that affect the poor prognosis of patients with a cerebral contusion after the operation. The area under the ROC was 0.816 (95% CI 0.705~0.926) and 0.819 (95% CI 0.708~0.931), respectively. Conclusion. The prediction model based on the risk factors that affect the poor prognosis of patients with brain contusion and laceration has good discrimination and accuracy.
Nucleotide Sequence Variation Is Frequent in the Mitochondrial DNA Displacement Loop Region of Individual Human Tumor Cells
Authors: Yoneyama Haruko , Hara Toshiko , Kato Yo , Yamori Takao , Matsuura Etsuko T. , Koike Katsuro 
Published: May 2022

Abstract
The mitochondrial DNA (mtDNA) displacement loop (D-loop) regions of 76 various tumor cell lines were examined to investigate the existence of a specific relationship between a somatic mtDNA sequence and initiation and/or progression of a tumor. Based on molecular cloning-sequencing analysis, a nucleotide sequence in the D-loop region in each cell line was found to be homoplasmic. Several site-specific nucleotide variations were found in stomach and liver tumor cell lines more frequently than those in other tumor cell lines. Subsequently, 20 pairs of noncancerous and cancerous parts from stomach and liver tumor tissues were examined. In the liver tumor tissue, 80% of the noncancerous parts exhibited slightly higher heterogeneity than the corresponding cancerous parts. Several site-specific nucleotide variations found in 76 tumor cell lines were also detected in noncancerous or cancerous parts of stomach and liver tumor tissues. However, it remains unclear why the mtDNA D-loop sequence is homoplasmic in each tumor cell line. The data indicate that mtDNA exhibits heterogeneity even in the noncancerous part and a slight decrease in heterogeneity during tumorigenesis and/or tumor progression. Homoplasmy of the mtDNA population in the tumor cell line would be acquired in the cloning process of establishing a cell line. Site-specific nucleotide substitutions might not be directly involved in the tumorigenesis process.
E2F1 Uses the ATM Signaling Pathway to Induce p53 and Chk2 Phosphorylation and Apoptosis
Authors: Powers John T. , Hong SungKi , Mayhew Christopher N. , Rogers Pamela M. , Knudsen Erik S. , Johnson David G. 
Published: May 2022

Abstract
The p53 tumor suppressor protein is phosphorylated and activated by several DNA damage-inducible kinases, such as ATM, and is a key effector of the DNA damage response by promoting cell cycle arrest or apoptosis. Deregulation of the Rb-E2F1 pathway also results in the activation of p53 and the promotion of apoptosis, and this contributes to the suppression of tumor development. Here, we describe a novel connection between E2F1 and the ATM DNA damage response pathway. In primary human fibroblasts lacking functional ATM, the ability of E2F1 to induce the phosphorylation of p53 and apoptosis is impaired. In contrast, ATM status has no effect on transcriptional activation of target genes or the stimulation of DNA synthesis by E2F1. Cells containing mutant Nijmegen breakage syndrome protein (NBS1), a component of the Mre11-Rad50 DNA repair complex, also have attenuated p53 phosphorylation and apoptosis in response to E2F1 expression. Moreover, E2F1 induces ATM- and NBS1-dependent phosphorylation of the checkpoint kinase Chk2 at Thr68, a phosphorylation site that stimulates Chk2 activity. Delayed γH2AX phosphorylation and absence of ATM autophosphorylation at Ser1981 suggest that E2F1 stimulates ATM through a unique mechanism that is distinct from agents that cause DNA double-strand breaks. These findings identify new roles for several DNA damage response factors by demonstrating that they also participate in the oncogenic stress signaling pathway between E2F1 and p53.
Enhanced Growth of Pancreatic Tumors in SPARC-Null Mice Is Associated With Decreased Deposition of Extracellular Matrix and Reduced Tumor Cell Apoptosis
Authors: Puolakkainen Pauli A. , Brekken Rolf A. , Muneer Sabeeha , Sage E. Helene 
Published: May 2022

Abstract
SPARC, a matricellular glycoprotein, modulates cellular interaction with the extracellular matrix (ECM). Tumor growth and metastasis occur in the context of the ECM, the levels and deposition of which are controlled in part by SPARC. Tumor-derived SPARC is reported to stimulate or retard tumor progression depending on the tumor type, whereas the function of host-derived SPARC in tumorigenesis has not been explored fully. To evaluate the function of endogenous SPARC, we have examined the growth of pancreatic tumors in SPARC-null (SP−/−) mice and their wild-type (SP+/+) counterparts. Mouse pancreatic adenocarcinoma cells injected s.c. grew significantly faster in SP−/− mice than cells injected into SP+/+ animals, with mean tumor weights at sacrifice of 0.415 ± 0.08 and 0.086 ± 0.03 g (P &lt; 0.01), respectively. Lack of endogenous SPARC resulted in decreased collagen deposition and fiber formation, alterations in the distribution of tumor-infiltrating macrophages, and decreased tumor cell apoptosis. There was no difference in microvessel density of tumors from SP−/− or SP+/+ mice. However, tumors grown in SP−/− had a lower percentage of blood vessels that expressed smooth muscle α-actin, a marker of pericytes. These data reflect the importance of ECM deposition in regulating tumor growth and demonstrate that host-derived SPARC is a critical factor in the response of host tissue to tumorigenesis.
HMG-I/Y Is a c-Jun/Activator Protein-1 Target Gene and Is Necessary for c-Jun–Induced Anchorage-Independent Growth in Rat1a Cells
Authors: Hommura Fumihiro , Katabami Motoo , Leaner Virna D. , Donninger Howard , Sumter Takita F. , Resar Linda M.S. , Birrer Michael J. 
Published: May 2022

Abstract
The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible c-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by c-Jun. Following induction of c-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of c-Jun expression, and gel mobility shift assays demonstrate that induced c-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of c-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing c-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of c-Jun necessary for c-Jun–induced anchorage-independent growth in Rat1a cells.
Chromatin Association of Rad17 Is Required for an Ataxia Telangiectasia and Rad-Related Kinase-Mediated S-Phase Checkpoint in Response to Low-Dose Ultraviolet Radiation
Authors: Garg Renu , Callens Shannon , Lim Dae-Sik , Canman Christine E. , Kastan Michael B. , Xu Bo 
Published: May 2022

Abstract
Activation of the S-phase checkpoint results in an inhibition of DNA synthesis in response to DNA damage. This is an active cellular response that may enhance cell survival and limit heritable genetic abnormalities. While much attention has been paid to elucidating signal transduction pathways regulating the ionizing radiation–induced S-phase checkpoint, less is known about whether UV radiation initiates the process and the mechanism controlling it. Here, we demonstrate that low-dose UV radiation activates an S-phase checkpoint that requires the ataxia telangiectasia and Rad-related kinase (ATR). ATR regulates the S-phase checkpoint through phosphorylation of the downstream target structural maintenance of chromosomal protein 1. Furthermore, the ATPase activity of Rad17 is crucial for its chromatin association and for the functional effects of ATR activation in response to low-dose UV radiation. These results suggest that low-dose UV radiation activates an S-phase checkpoint requiring ATR-mediated signal transduction pathway.
Mice Expressing SV40 T Antigen Directed by the Intestinal Trefoil Factor Promoter Develop Tumors Resembling Human Small Cell Carcinoma of the Colon
Authors: Gum James R. , Hicks James W. , Crawley Suzanne C. , Yang Stacey C. , Borowsky Alexander D. , Dahl Christine M. , Kakar Sanjay , Kim Dong Hoon , Cardiff Robert D. , Kim Young S. 
Published: May 2022

Abstract
The colonic epithelium contains three major types of mature cells, namely, absorptive, goblet, and enteroendocrine cells. These cells are maintained by a complex process of cell renewal involving progenitor and stem cells, and colon cancers develop when this process goes awry. Much is known about the genetic and epigenetic changes that occur in cancer; however, little is known as to the specific cell types involved in carcinogenesis. In this study, we expressed the SV40 Tag oncogene in the intestinal epithelium under the control of an intestinal trefoil factor (ITF) promoter. This caused tumor formation in the proximal colon with remarkable efficiency. ITFTag tumors were rapidly growing, multifocal, and invasive. ITFTag tumor cells express synaptophysin and contain dense core secretory granules, markers of neuroendocrine differentiation. The cell type involved in the early steps of ITFTag tumorigenesis was studied by examining partially transformed crypts that contained populations of both normal and dysplastic cells. The dysplastic cell population always expressed both Tag and synaptophysin. Cells expressing Tag alone were never observed; however, normal enteroendocrine cells expressing synaptophysin but not Tag were readily visualized. This suggests that ITFTag tumor cells originate from the enteroendocrine cell lineage following a transforming event that results in Tag expression. ITFTag tumors closely resemble human small cell carcinomas of the colon, suggesting the possibility that these tumors might be derived from the enteroendocrine cell lineage as well.
Peroxisome Proliferator-Activated Receptor γ Ligands Improve the Antitumor Efficacy of Thrombospondin Peptide ABT510
Authors: Huang Hanhua , Campbell Steven C. , Bedford Dhugal F. , Nelius Thomas , Veliceasa Dorina , Shroff Emelyn H. , Henkin Jack , Schneider Andrew , Bouck Noel , Volpert Olga V. 
Published: May 2022

AbstractAn expanding capillary network is critical for several pathologic conditions. In cancer, the decrease of antiangiogenic thrombospondin-1 (TSP1) often enables an angiogenic switch, which can be reversed with exogenous TSP1 or its peptide derivative ABT510. TSP1 acts by inducing endothelial cell apoptosis via signaling cascade initiated at CD36, a TSP1 antiangiogenic receptor. Here, we show that the ligands of nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), 15-deoxy-Δ12,14-prostaglandin J2, troglitazone, and rosiglitazone increased PPARγ and CD36 expression in endothelial cells and improved the efficacy of TSP1 and ABT510 in a CD36-dependent manner. The ABT510 and PPARγ ligands cooperatively blocked angiogenic endothelial functions in vitro and neovascularization in vivo. In tumor xenografts, 15-deoxy-Δ12,14-prostaglandin J2 and troglitazone synergistically improved antiangiogenic and antitumor effects of ABT510. Our data provide one mechanism for the in vivo angioinhibitory effect of PPARγ ligands and show fine-tuning of the antiangiogenic efficacy via targeted up-regulation of the endothelial receptor.
Bcl-2-Mediated Cell Survival Promotes Metastasis of EpH4 βMEKDD Mammary Epithelial Cells
Authors: Pinkas Jan , Martin Stuart S. , Leder Philip 
Published: May 2022

Abstract
The majority of patients who succumb to cancer die from metastatic disease progression rather than from the primary tumor. Elucidation of the mechanisms underlying tissue-specific metastasis is essential to the development of effective therapies. The mitogen-activated protein kinase kinase (MEK) pathway is frequently activated in human tumors and has been shown to regulate genes involved in proliferation, migration, and invasion. Studies with MEK-transformed EpH4 mouse mammary epithelial cells showed that these cells are highly tumorigenic but have a limited metastatic ability. Detachment of epithelial cells from the extracellular matrix causes disruption of the actin cytoskeleton and induces apoptosis. Several metastatic breast carcinoma cell lines have been shown to be resistant to cell death following actin disruption. This death-resistant phenotype can be modeled by overexpressing the antiapoptotic Bcl-2 protein in cells. This suggests that mechanisms that regulate survival of extravasated tumor cells may enhance metastatic efficiency. Therefore, we examined whether expression of Bcl-2 in MEK-transformed EpH4 mammary epithelial cells could provide a survival advantage and promote metastasis. Expression of Bcl-2 in parental EpH4 mammary epithelial cells or MEK-transformed cells was insufficient to induce increased migration, invasion, or tumor development. However, Bcl-2 expression markedly enhanced spontaneous lung metastasis from orthotopically implanted primary tumors. These results clearly show that mechanisms that regulate primary tumor development are distinct from those that promote metastasis and that assays designed to isolate genes involved in transformation may fail to identify genes that are critical regulators of metastasis.
Low-Dose Radiation Hypersensitivity Is Associated With p53-Dependent Apoptosis
Authors: Enns Louise , Bogen Kenneth T. , Wizniak Juanita , Murtha Albert D. , Weinfeld Michael 
Published: May 2022

Abstract
Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses &lt;50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times postirradiation, we examined the response of human A549 lung carcinoma, T98G glioma, and MCF7 breast carcinoma cell lines exposed to γ radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses &lt;50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (Annexin V binding). We observed that caspase-3 activation and Annexin V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and Annexin V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no hyperradiosensitivity and apoptosis was not detectable by Annexin V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.
Src Regulates Actin Dynamics and Invasion of Malignant Glial Cells in Three Dimensions
Authors: Angers-Loustau Alexandre , Hering Ramm , Werbowetski Tamra E. , Kaplan David R. , Del Maestro Rolando F. 
Published: May 2022

Abstract
Malignant glioma is the major brain tumor in adults and has a poor prognosis. The failure to control invasive cell subpopulations may be the key reason for local glioma recurrence after radical tumor resection and may contribute substantially to the failure of the other treatment modalities such as radiation therapy and chemotherapy. As a model for this invasion, we have implanted spheroids from a human glioma cell line (U251) in three-dimensional collagen type I matrices, which these cells readily invade. We first observed that the Src family kinase-specific pharmacologic inhibitors PP2 and SU6656 significantly inhibited the invasion of the cells in this assay. We confirmed this result by showing that expression of two inhibitors of Src family function, dominant-negative-Src and CSK, also suppressed glioma cell invasion. To characterize this effect at the level of the cytoskeleton, we used fluorescent time-lapse microscopy on U251 cells stably expressing a YFP-actin construct and observed a rapid change in actin dynamics following addition of PP2 in both two-dimensional and three-dimensional cultures. In monolayer cultures, PP2 caused the disappearance of peripheral membrane ruffles within minutes. In three-dimensional cultures, PP2 induced the loss of actin bursting at the leading tip of the invadopodium. The inhibition of Src family activity is thus a potential therapeutic approach to treat highly invasive malignant glioma.
Enhancement of the Antiangiogenic Activity of Interleukin-12 by Peptide Targeted Delivery of the Cytokine to αvβ3 Integrin
Authors: Dickerson Erin B. , Akhtar Nasim , Steinberg Howard , Wang Zun-Yi , Lindstrom Mary J. , Padilla Marcia L. , Auerbach Robert , Helfand Stuart C. 
Published: May 2022

AbstractWe engineered a fusion protein, mrIL-12vp [mouse recombinant interleukin (IL)-12 linked to vascular peptide], linking the vascular homing peptide CDCRGDCFC (RGD-4C), a ligand for αvβ3 integrin, to mrIL-12 to target IL-12 directly to tumor neovasculature. The fusion protein stimulated IFN-γ production in vitro and in vivo, indicating its biological activity was consistent with mrIL-12. Immunofluorescence techniques showed mrIL-12vp specifically bound to αvβ3 integrin-positive cells but not to αvβ3 integrin-negative cells. In corneal angiogenesis assays using BALB/c mice treated with either 0.5 μg/mouse/d of mrIL-12vp or mrIL-12 delivered by subcutaneous continuous infusion, mrIL-12vp inhibited corneal neovascularization by 67% compared with only a slight reduction (13%) in angiogenesis in the mrIL-12-treated animals (P = 0.008). IL-12 receptor knockout mice given mrIL-12vp showed a marked decrease in the area of corneal neovascularization compared with mice treated with mrIL-12. These results indicate that mrIL-12vp inhibits angiogenesis through IL-12-dependent and IL-12-independent mechanisms, and its augmented antiangiogenic activity may be due to suppression of endothelial cell signaling pathways by the RGD-4C portion of the fusion protein. Mice injected with NXS2 neuroblastoma cells and treated with mrIL-12vp showed significant suppression of tumor growth compared with mice treated with mrIL-12 (P = 0.03). Mice did not show signs of IL-12 toxicity when treated with mrIL-12vp, although hepatic necrosis was present in mrIL-12-treated mice. Localization of IL-12 to neovasculature significantly enhances the antiangiogenic effect, augments antitumor activity, and decreases toxicity of IL-12, offering a promising strategy for expanding development of IL-12 for treatment of cancer patients.