bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma
Authors: Bollard Catherine M. , Tripic Tamara , Cruz Conrad Russell , Dotti Gianpietro , Gottschalk Stephen , Torrano Vicky , Dakhova Olga , Carrum George , Ramos Carlos A. , Liu Hao , Wu Meng-Fen , Marcogliese Andrea N. , Barese Cecilia , Zu Youli , Lee Daniel Y. , O’Connor Owen , Gee Adrian P. , Brenner Malcolm K. , Heslop Helen E. , Rooney Cliona M. 
Published: January 2018

Purpose Transforming growth factor-β (TGF-β) production in the tumor microenvironment is a potent and ubiquitous tumor immune evasion mechanism that inhibits the expansion and function of tumor-directed responses; therefore, we conducted a clinical study to discover the effects of the forced expression of a dominant-negative TGF-β receptor type 2 (DNRII) on the safety, survival, and activity of infused tumor-directed T cells. Materials and Methods In a dose escalation study, eight patients with Epstein Barr virus–positive Hodgkin lymphoma received two to 12 doses of between 2 × 107 and 1.5 × 108 cells/m2 of DNRII-expressing T cells with specificity for the Epstein Barr virus–derived tumor antigens, latent membrane protein (LMP)-1 and LMP-2 (DNRII-LSTs). Lymphodepleting chemotherapy was not used before infusion. Results DNRII-LSTs were resistant to otherwise inhibitory concentrations of TGF-β in vitro and retained their tumor antigen–specific activity. After infusion, the signal from transgenic T cells in peripheral blood increased up to 100-fold as measured by quantitative polymerase chain reaction for the transgene, with a corresponding increase in the frequency of functional LMP-specific T cells. Expansion was not associated with any acute or long-term toxicity. DNRII-LSTs persisted for up to ≥ 4 years. Four of the seven evaluable patients with active disease achieved clinical responses that were complete and ongoing in two patients at > 4 years, including in one patient who achieved only a partial response to unmodified tumor-directed T cells. Conclusion TGF-β–resistant tumor-specific T cells safely expand and persist in patients with Hodgkin lymphoma without lymphodepleting chemotherapy before infusion. DNRII-LSTs can induce complete responses even in patients with resistant disease. Expression of DNRII may be useful for the many other tumors that exploit this potent immune evasion mechanism.
Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and by a double-assurance survival role for Transformer in females
Authors: Garner Sarah Rose C. , Castellanos Monica C. , Baillie Katherine E. , Lian Tianshun , Allan Douglas W. 
Published: January 2018

ABSTRACT
Female-specific Ilp7 neuropeptide-expressing motoneurons (FS-Ilp7 motoneurons) are required in Drosophila for oviduct function in egg laying. Here, we uncover cellular and genetic mechanisms underlying their female-specific generation. We demonstrate that programmed cell death (PCD) eliminates FS-Ilp7 motoneurons in males, and that this requires male-specific splicing of the sex-determination gene fruitless (fru) into the FruMC isoform. However, in females, fru alleles that only generate FruM isoforms failed to kill FS-Ilp7 motoneurons. This blockade of FruM-dependent PCD was not attributable to doublesex gene function but to a non-canonical role for transformer (tra), a gene encoding the RNA splicing activator that regulates female-specific splicing of fru and dsx transcripts. In both sexes, we show that Tra prevents PCD even when the FruM isoform is expressed. In addition, we found that FruMC eliminated FS-Ilp7 motoneurons in both sexes, but only when Tra was absent. Thus, FruMC-dependent PCD eliminates female-specific neurons in males, and Tra plays a double-assurance function in females to establish and reinforce the decision to generate female-specific neurons.
The G protein-coupled receptor Gpr161 regulates forelimb formation, limb patterning and skeletal morphogenesis in a primary cilium-dependent manner
Authors: Hwang Sun-hee , White Kevin A. , Somatilaka Bandarigoda N. , Shelton John M. , Richardson James A. , Mukhopadhyay Saikat 
Published: January 2018

ABSTRACT
The role of basal suppression of the sonic hedgehog (Shh) pathway and its interaction with Indian hedgehog (Ihh) signaling during limb/skeletal morphogenesis is not well understood. The orphan G protein-coupled receptor Gpr161 localizes to primary cilia and functions as a negative regulator of Shh signaling by promoting Gli transcriptional repressor versus activator formation. Here, we show that forelimb buds are not formed in Gpr161 knockout mouse embryos despite establishment of prospective limb fields. Limb-specific deletion of Gpr161 resulted in prematurely expanded Shh signaling and ectopic Shh-dependent patterning defects resulting in polysyndactyly. In addition, endochondral bone formation in forearms, including formation of both trabecular bone and bone collar was prevented. Endochondral bone formation defects resulted from accumulation of proliferating round/periarticular-like chondrocytes, lack of differentiation into columnar chondrocytes, and corresponding absence of Ihh signaling. Gpr161 deficiency in craniofacial mesenchyme also prevented intramembranous bone formation in calvarium. Defects in limb patterning, endochondral and intramembranous skeletal morphogenesis were suppressed in the absence of cilia. Overall, Gpr161 promotes forelimb formation, regulates limb patterning, prevents periarticular chondrocyte proliferation and drives osteoblastogenesis in intramembranous bones in a cilium-dependent manner.
Towards stem cell based therapies for Parkinson's disease
Authors: Parmar Malin 
Published: January 2018

ABSTRACT
Treating neurodegenerative diseases with cell transplantation has been within reach since the first pioneering clinical trials in which dopamine neuron progenitors from the fetal brain were transplanted to individuals with Parkinson's disease. However, the use of fetal tissue is problematic in terms of low availability and high variability, and it is also associated with ethical concerns that vary between countries. For decades, the field has therefore investigated new scalable source of therapeutic cells from stem cells or via reprogramming. Now it is possible to generate authentic midbrain dopaminergic neurons from pluripotent stem cells and clinical trials using such cells are rapidly approaching.
Multidimensional quantitative analysis of mRNA expression within intact vertebrate embryos
Authors: Trivedi Vikas , Choi Harry M. T. , Fraser Scott E. , Pierce Niles A. 
Published: January 2018

ABSTRACT
For decades, in situ hybridization methods have been essential tools for studies of vertebrate development and disease, as they enable qualitative analyses of mRNA expression in an anatomical context. Quantitative mRNA analyses typically sacrifice the anatomy, relying on embryo microdissection, dissociation, cell sorting and/or homogenization. Here, we eliminate the trade-off between quantitation and anatomical context, using quantitative in situ hybridization chain reaction (qHCR) to perform accurate and precise relative quantitation of mRNA expression with subcellular resolution within whole-mount vertebrate embryos. Gene expression can be queried in two directions: read-out from anatomical space to expression space reveals co-expression relationships in selected regions of the specimen; conversely, read-in from multidimensional expression space to anatomical space reveals those anatomical locations in which selected gene co-expression relationships occur. As we demonstrate by examining gene circuits underlying somitogenesis, quantitative read-out and read-in analyses provide the strengths of flow cytometry expression analyses, but by preserving subcellular anatomical context, they enable bi-directional queries that open a new era for in situ hybridization.
Wnt inhibition promotes vascular specification of embryonic cardiac progenitors
Authors: Reichman David E. , Park Laura , Man Limor , Redmond David , Chao Kenny , Harvey Richard P. , Taketo Makoto M. , Rosenwaks Zev , James Daylon 
Published: January 2018

ABSTRACT
Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSCs). However, few studies have investigated the role of Wnt signaling in the specification of cardiac progenitor cells (CPCs) toward downstream fates. Using transgenic mice and hPSCs, we tracked endothelial cells (ECs) that originated from CPCs expressing NKX2.5. Analysis of EC-fated CPCs at discrete phenotypic milestones during hPSC differentiation identified reduced Wnt activity as a hallmark of EC specification, and the enforced activation or inhibition of Wnt reduced or increased, respectively, the degree of vascular commitment within the CPC population during both hPSC differentiation and mouse embryogenesis. Wnt5a, which has been shown to exert an inhibitory influence on Wnt signaling during cardiac development, was dynamically expressed during vascular commitment of hPSC-derived CPCs, and ectopic Wnt5a promoted vascular specification of hPSC-derived and mouse embryonic CPCs.
RDGBα localization and function at membrane contact sites is regulated by FFAT–VAP interactions
Authors: Yadav Shweta , Thakur Rajan , Georgiev Plamen , Deivasigamani Senthilkumar , Krishnan Harini , Ratnaparkhi Girish , Raghu Padinjat 
Published: January 2018

ABSTRACT
Phosphatidylinositol transfer proteins (PITPs) are essential regulators of PLC signalling. The PI transfer domain (PITPd) of multi-domain PITPs is reported to be sufficient for in vivo function, questioning the relevance of other domains in the protein. In Drosophila photoreceptors, loss of RDGBα, a multi-domain PITP localized to membrane contact sites (MCSs), results in multiple defects during PLC signalling. Here, we report that the PITPd of RDGBα does not localize to MCSs and fails to support function during strong PLC stimulation. We show that the MCS localization of RDGBα depends on the interaction of its FFAT motif with dVAP-A. Disruption of the FFAT motif (RDGBFF/AA) or downregulation of dVAP-A, both result in mis-localization of RDGBα and are associated with loss of function. Importantly, the ability of the PITPd in full-length RDGBFF/AA to rescue mutant phenotypes was significantly worse than that of the PITPd alone, indicating that an intact FFAT motif is necessary for PITPd activity in vivo. Thus, the interaction between the FFAT motif and dVAP-A confers not only localization but also intramolecular regulation on lipid transfer by the PITPd of RDGBα.
This article has an associated First Person interview with the first author of the paper.
Theoretical study of a series of phenol derivatives: molecular properties vs. cytotoxicity
Authors: Michalík Martin , Sádecká Lívia , Lukeš Vladimír 
Published: January 2018

Abstract
The quantum chemical calculations using DFT were performed for 2-alkyl-4X and 2,6-dialkyl-4-X substituted phenols. Based on the optimal geometries the bond dissociation enthalpies (BDEs), proton enthalpies (PAs) and the lipophilicities were computed. Additionally, simple geometry parameter was found correlating well with experimental leukemia cell toxicity of substituted phenols. Next, we have found no linear dependence between PA or BDE values and log1/C values in gas phase or in water despite the radical toxicity mechanism proposed in the literature.
Aflatoxins: biosynthesis, prevention and eradication
Authors: Šimončicová Juliana , Kaliňáková Barbora , Kryštofová Svetlana 
Published: January 2018

AbstractFilamentous fungi belonging to Aspergilli genera produce many compounds through various biosynthetic pathways. These compounds include a spectrum of products with beneficial medical properties (lovastatin) as well as those that are toxic and/or carcinogenic which are called mycotoxins. Aspergillus flavus, one of the most abundant soil-borne fungi, is a saprobe that is able growing on many organic nutrient sources, such as peanuts, corn and cotton seed. In many countries, food contamination by A. flavus is a huge problem, mainly due to the production of the most toxic and carcinogenic compounds known as aflatoxins. In this paper, we briefly cover current progress in aflatoxin biosynthesis and regulation, pre- and postharvest preventive measures, and decontamination procedures.
Properties of crackers with buckwheat sourdough
Authors: Selimović Amel , Miličević Dijana , Selimović Amra , Žuljević Sanja Oručević , Jašića Amela , Vranac Amila 
Published: January 2018

Abstract
Effects of additions of buckwheat flour and sourdough on the total phenols content, antioxidant activity, and sensory properties of crackers were examined. Different mixtures of wheat flour with addition of buckwheat flour and sourdough were used for the prepartion of crackers. Two types of lactic acid bacteria (Lactobacillus plantarum and Lactobacillus brevis) were used for the preparation of buckwheat sourdough. Properties of crackers made with addition of buckwheat flour and sourdough were analysed in comparison to control crackers made only with wheat flour. Significant increase of total phenols in comparison to wheat flour dough (0.73 mg gallic acid equivalent (GA)/g of dry basis (d.b.)) was accomplished by adding buckwheat flour (1.12 mg GA/g d.b.) and sourdough (1.77 and 1.79 mg GA/g d.b.) regardless of the type of lactic acid bacteries used. All samples showed the decrease in total phenol content during baking process. Crackers with sourdough had higher antioxidant activity (16.84 and 15.84 mmol Fe3+/g d.b.) compared to crackers made with addition of buckwheat flour (10.42 mmol Fe3+/g d.b.) and control sample (7.76 mmol Fe3+/g d.b.). The result of sensory analysis showed positive influence of sourdough on taste and texture of crackers and insignificant differences in odour and appearance of tested samples. Also, the chewiness of crackers made with the addition of buckwheat flour and sourdough was improved compared to control crackers made from wheat flour.
Description of a Feline Injection-Site Fibrosarcoma with Metastasis in the Cerebellum
Authors: Cora Roxana , Gal Adrian Florin , Taulescu Marian , Tăbăran Flaviu , Vidrighinescu Raluca , Cătoi Cornel 
Published: January 2018

AbstractFeline injection-site sarcomas were initially described by Hendrick and Goldschmidt (1991). The link between vaccination site and sarcoma occurrence suggested the term of vaccine-associated sarcomas. Our paper describes an unusual feline injection-site fibrosarcoma with cerebellar metastasis. A 7-year-old female domestic short-hair cat was submitted to the Pathology Department (Faculty of Veterinary Medicine Cluj- Napoca, Romania) for necropsy. A subcutaneous tumor (relapse) in the interscapular region and multiple metastatic masses in the lungs, kidneys, subcutaneous tissue (scapular and thigh regions) and cerebellum were observed. Cytological, histological and immunohistochemical (for vimentin, desmin, multi-cytokeratin, α-smooth muscle actin, S100 and CD45) analyses from all tumors were performed. Cytological examination identifi ed highly pleomorphic spindle-shaped cells admixed with neoplastic multinucleated giant cells. Histologically, all neoplastic masses were composed of numerous spindle cells arranged into interlacing bundles. Extensive intratumoral areas of necrosis along with a neutrophilic infiltrate were also detected. A fibrillary material was present among neoplastic cells (green stained by Masson’s trichrome method), suggesting a collagenous structure. In all tumors assessed, immunohistochemistry showed an intense reaction only for vimentin in numerous neoplastic cells. Based on the history, gross, cytological, histological and immunohistochemical data, the final diagnosis was recurrent feline injection-site fibrosarcoma, with multiple metastases (including in the cerebellum). Overall, an uncommon case of feline injection-site fibrosarcoma has been reported. This is the first consistent record of an injection site sarcoma in a cat with cerebellar metastasis.
Acute Pancreatitis Associated With Peritoneal Migration of Grass Awn in Two Dogs
Authors: Citi Simonetta , Mannucci Tommaso , Pedala’ Francesca , Vannozzi Iacopo , Vignoli Massimo 
Published: January 2018

Abstract
A 12 year old male Fox Terrier (case 1) and a one year old female Poodle (case 2) were presented with a history of dysorexia and vomiting, and case 2 also with distress associated with eating. Both dogs were diagnosed with acute pancreatitis based on clinical signs, blood analysis and ultrasonography which revealed the presence of a vegetable foreign body in the proximity of the pancreatic right lobe. Laparatomy enabled the gramineae awns to be removed which led to full resolution of clinical signs. We believe that these are the first reported cases of acute pancreatitis due to grass awns.
Monthly variation in the chemical composition and biological activity of Sargassum horridum
Authors: Di Filippo-Herrera Dania Andrea , Hernández-Carmona Gustavo , Muñoz-Ochoa Mauricio , Arvizu-Higuera Dora Luz , Rodríguez-Montesinos Yoloxochitl Elizabeth 
Published: January 2018

Abstract
The proximate chemical composition of Sargassum horridum was determined monthly, including extract yields of alginate, crude fucoidan, and ethanolic extract. In addition, the biological activity (antioxidant and antibacterial) of the ethanolic extract and anticoagulant activity of the fucoidan were examined. Significant monthly variation was found in the chemical composition (moisture, protein, ash, crude lipids, crude fiber, carbohydrates, and gross energy), as well as in the alginate, fucoidan, and ethanolic extract yields. The maximum yield of crude fucoidan (13.5% dry weight) and alginate (21.4% dry weight) occurred in May. Crude fucoidan increased the clotting time at all concentrations tested during all months, based on activated partial thromboplastin and prothrombin time assays. The maximum yield of ethanolic extract occurred in April and August (6% dry weight). The ethanolic extract was evaluated for free radical scavenging activity using the 2,2-diphenyl-1-picrylhydrazyl method, with the highest reduction percentage in April (53%). Only the extracts from March, July and August showed slight antibacterial activity against Vibrio parahaemolyticus, V. alginolyticus, and Staphylococcus aureus. Sargassum horridum thus represents a potential source of carbohydrates, anticoagulant, antioxidants and antibacterial compounds. The best time of year for harvesting the alga is from May to July.
Cyclic carburization-oxidation behavior of Hastelloy-X at 1000°C
Authors: Hayashi Shigenari , Matsukawa Chihiro , Yakuwa Hiroshi , Kishikawa Tadahiko 
Published: January 2018

Abstract
Cyclic corrosion, consisting of carburization in Ar+4% CH4+3% H2 for 1 h and oxidation in air for 1 h, of Ni-base in a wrought alloy, Hastelloy-X, was investigated at 1000°C to understand the significant metal loss occurring in fuel injection nozzles of gas turbine combustor operated using natural gas. The mass gain of cyclic corrosion was relatively low up to about eight cycles of corrosion by formation of a Cr2O3 scale in each oxidation stage, but it increased rapidly due to formation of a Fe- and Ni-rich oxide scale as the number of corrosion cycles increases. The Cr content in the subsurface region rapidly decreased under the cyclic corrosion condition compared with a continuous single oxidation or carburization, which resulted in the formation of non-protective Fe- and Ni-rich oxide scale in a small number of corrosion cycles. The formation of a Cr3C2 scale from the protective Cr2O3 scale in the carburization stage was detrimental for the oxidation resistance of Hastelloy-X and was considered to have a similar effect to spallation of a Cr2O3 scale; therefore, it accelerated Cr consumption from the alloy subsurface region.
An Efficient Algorithm Based on Extrapolation for the Solution of Nonlinear Parabolic Equations
Authors: Ghasemi M. 
Published: January 2018

AbstractTwo numerical procedures are developed to approximate the solution of one-dimensional parabolic equations using extrapolated collocation method. By defining two different end conditions and forcing cubic spline to satisfy the interpolation conditions along with one of the end conditions, we obtain fourth- (CBS4) and sixth-order (CBS6) approximations to the solution in spatial direction. Also in time direction, a weighted finite-difference discretization is used to approximate the solution at each time level. The convergence analysis of the methods is discussed in detail and some error bounds are obtained theoretically. Finally, some different examples of Burgers’ equations with applications in fluid mechanics as well as convection–diffusion problems with applications in transport problems are solved to show the applicability and good performance of the procedures.
Asymmetric Trade Costs: Agricultural Trade among Developing and Developed Countries
Authors: Eum Jihyun , Sheldon Ian , Thompson Stanley 
Published: January 2018

Abstract
In this article, the reasons why developing countries trade fewer agricultural products than developed countries are analyzed. Based on earlier findings that low trade volume in the agricultural sector is due to high trade costs, the focus is on evaluating the extent to which bilateral trade costs in the agricultural sector differ among trading partners. Using a neo-Ricardian trade model, the results show that systematically, asymmetric bilateral trade costs and variation in the level of agricultural productivity across all countries in the sample, are the main barriers to developing countries’ agricultural exports. In addition, low-income countries face higher trade costs to export than do high-income countries.
Phylogenetic Taxonomy of Artemisia L. Species from Kazakhstan Based on Matk Analyses
Authors: Turuspekov Yerlan , Genievskaya Yuliya , Baibulatova Aida , Zatybekov Alibek , Kotuhov Yuri , Ishmuratova Margarita , Imanbayeva Akzhunis , Abugalieva Saule 
Published: January 2018

Abstract
The genus Artemisia is one of the largest of the Asteraceae family. It is abundant and diverse, with complex taxonomic relations. In order to expand the knowledge about the classification of Kazakhstan species and compare it with classical studies, matK genes of nine local species including endemic were sequenced. The infrageneric rank of one of them (A. kotuchovii) had remained unknown. In this study, we analysed results of sequences using two methods — NJ and MP and compared them with a median-joining haplotype network. As a result, monophyletic origin of the genus and subgenus Dracunculus was confirmed. Closeness of A. kotuchovii to other species of Dracunculus suggests its belonging to this subgenus. Generally, matK was shown as a useful barcode marker for the identification and investigation of Artemisia genus.