bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel DNA Catalysts Based on G‐Quadruplex for Organic Synthesis
Authors: Wang Li‐Xia , Xiang Jun‐Feng , Tang Ya‐Lin 
Published: December 2014

AbstractDouble‐stranded DNA (dsDNA) as a catalytic species has been applied in various key asymmetric reactions. Compared with dsDNA, G‐quadruplex DNAs (G4DNAs) have unique conformational structures and versatile complexation properties, and act expectedly as hosts to recognize planar aromatic molecules through π–π stacking. Based on the specific recognition for small molecules, G4DNA‐based catalysts have been used to assist the catalytic function, and have been applied in asymmetric organic reactions.magnified image
Familial cardiofaciocutaneous syndrome in a father and a son with a novel MEK2 mutation
Authors: Karaer Kadri , Lissewski Christina , Zenker Martin 
Published: December 2014

ABSTRACTCardiofaciocutaneous (CFC) syndrome is a rare genetic disorder belonging to the group of RASopathies. It is typically characterized by congenital heart defects, short stature, dysmorphic craniofacial features, intellectual disability, failure to thrive, and ectodermal abnormalities such as hyperkeratosis and sparse, brittle, curly hair. CFC syndrome is caused by dominant mutations in one of the four genes BRAF, MEK1, MEK2, and KRAS. Only three familial cases of CFC syndrome have been reported to date, whereas the vast majorities are sporadic cases due to de novo mutations. We report on a fourth familial case with transmission of CFC syndrome from father to son due to a novel heterozygous sequence change c.376A>G (p.N126D) in exon 3 of MEK2 gene. This observation further documents the possibility of vertical transmission of CFC syndrome, which appears to be associated with rare mutations and relatively mild intellectual disability in affected individual. The hypomorphic effect of specific mutations particularly regarding neurocognitive issues may be related to the variable fertility of affected individuals. © 2014 Wiley Periodicals, Inc.
Synthesis of Allokainic Acid: A Review
Authors: Bhat Chinmay , Kumar Amit 
Published: December 2014

AbstractThis Focus Review discusses the synthesis of an important member of the kainoid family; allokainic acid. The members of the kainoid family have attracted worldwide attention since their first isolation in 1953 due to their vast and potential medicinal applications, especially in neuroscience. The review focuses on the synthesis of allokainic acid using different synthetic methods from its first synthesis to the most recent one, covering 1953‐2014.
The safety of self‐administered allergen immunotherapy during the buildup and maintenance phases
Authors: Schaffer Frederick M. , Naples Andrew R. , Ebeling Myla , Hulsey Thomas C. , Garner Larry M. 
Published: December 2014

BackgroundSelf‐administered allergen immunotherapy is considered controversial. We believe the implementation of a self‐administration protocol characterized by patient preselection and a slow buildup phase is safe.MethodsWe analyzed 23,614 patient records and associated immunotherapy injections for systemic reactions (SR) during a 1‐year period (2011 to 2012). SRs were graded in accordance with the World Allergy Organization (WAO) criteria.ResultsThirty‐seven SRs were reported for 23,614 patients who self‐administered 2,021,600 injections yielding an annual SR rate of 0.16% (per patient) or 0.002% (per injection). Only 9 of 4643 pediatric (0.19%) and 28 of 18,971 adult patients (0.15%) experienced 1 or more SRs. No deaths (grade V SR) occurred. From 2009 through early 2014, over 90,000 patients received more than 10 million injections in accordance with the United Allergy Services (UAS) protocol without fatalities.ConclusionWe believe this safety profile is due to a preselection of patients to exclude those with a high risk for adverse reactions and a slow immunotherapy buildup phase. In contrast, previous studies documented office‐based SRs ranging from approximately 3% to greater than 14%. Thus, the UAS home‐immunotherapy SR rate is significantly lower than office‐based immunotherapy SR rates (p < 0.0001). The enhanced safety of this protocol results in a decreased frequency and severity of SRs. This safety report, derived from analyses of one of the largest patient cohorts studied, corroborates and expands the observations of previous studies of self‐administered subcutaneous immunotherapy in a low‐risk patient population by assessing self‐administered allergen immunotherapy during the buildup and maintenance phases.
No evidence for human papillomavirus infection in focal cortical dysplasiaIIb
Authors: Coras Roland , Korn Klaus , Bien Christian G. , Kalbhenn Thilo , Rössler Karl , Kobow Katja , Giedl Johannes , Fleckenstein Bernhard , Blumcke Ingmar 
Published: December 2014

ObjectiveThe etiology of focal cortical dysplasia type IIb (FCDIIb) remains enigmatic in patients suffering from drug‐resistant epilepsy, and an aberrant activation of the mammalian target of rapamycin complex 1 signaling pathway (mTORC1) was detected in this developmental brain malformation. Recently, the human papillomavirus (HPV) oncoprotein E6 has been identified as a potent activator of mTORC1, and HPV16 E6 has been described to persist in balloon cells obtained from surgical FCDIIb specimens. Although this observation was replicated by an independent second report, it contradicts current knowledge of HPV biology. HPV infects the squamous or mucocutaneous epithelium; hematogenic spread into other tissues has not been observed. In addition, brain carcinogenesis has never been reported in FCDIIb patients. Herein, we have tried to confirm 2 previous reports of HPV16 E6 infection using an independent series of 14 surgical specimens with histopathologically confirmed FCDIIb.MethodsSnap‐frozen FCDIIb specimens were tested for HPV DNA using the primer set for amplification of the complete E6 reading frame of HPV16 and 3 other sets of primers (2 consensus primer sets detecting multiple HPV genotypes, and another primer set specifically used for HPV16). Furthermore, formalin‐fixed and paraffin‐embedded histopathological preparations were immunohistochemically analyzed using previously described antibodies directed against the HPV E6 oncoprotein.ResultsAll 14 FCDIIb specimens were negative for HPV DNA with all 4 primer sets. Antibodies directed against the HPV E6 epitope showed weak labeling of cytoplasm in balloon cells, as previously described in FCDIIb, but also in other cell populations.InterpretationOur data did not confirm previously reported evidence for HPV16 detection in FCDIIb. Ann Neurol 2015;77:312–319
Marriage of Scintillator and Semiconductor for Synchronous Radiotherapy and Deep Photodynamic Therapy with Diminished Oxygen Dependence
Authors: Zhang Chen , Zhao Kuaile , Bu Wenbo , Ni Dalong , Liu Yanyan , Feng Jingwei , Shi Jianlin 
Published: December 2014

AbstractStrong oxygen dependence and limited penetration depth are the two major challenges facing the clinical application of photodynamic therapy (PDT). In contrast, ionizing radiation is too penetrative and often leads to inefficient radiotherapy (RT) in the clinic because of the lack of effective energy accumulation in the tumor region. Inspired by the complementary advantages of PDT and RT, we present herein the integration of a scintillator and a semiconductor as an ionizing‐radiation‐induced PDT agent, achieving synchronous radiotherapy and depth‐insensitive PDT with diminished oxygen dependence. In the core–shell CeIII‐doped LiYF4@SiO2@ZnO structure, the downconverted ultraviolet fluorescence from the CeIII‐doped LiYF4 nanoscintillator under ionizing irradiation enables the generation of electron–hole (e−–h+) pairs in ZnO nanoparticles, giving rise to the formation of biotoxic hydroxyl radicals. This process is analogous to a type I PDT process for enhanced antitumor therapeutic efficacy.
Beeinflussung der Aufnahme und lysosomalen Azidifizierung durch die Steifigkeit kolloidaler Partikel in vitro
Authors: Hartmann Raimo , Weidenbach Marcel , Neubauer Martin , Fery Andreas , Parak Wolfgang J. 
Published: December 2014

AbstractDas Aufnahmeverhalten von Zellen wird maßgeblich durch die physikalisch‐chemischen Eigenschaften kolloidaler Partikel bestimmt. Um die Auswirkungen mechanischer Steifigkeit auf den Endozytosevorgang zu untersuchen, wurde ausschließlich dieser Parameter variiert, während weitere Eigenschaften wie Größe, Form und Ladung konstant gehalten wurden. Durch die Analyse einzelner Partikel‐Trajektorien während des Aufnahmevorgangs ließen sich bei gleichzeitiger Aufzeichnung des lokalen pH‐Werts um jedes einzelne Partikel Rückschlüsse über den jeweiligen Endozytoseverlauf ziehen. Insgesamt ergeben sich genügend Anhaltspunkte dafür, dass weichere Partikel schneller in lysosomale Strukturen transportiert werden als steifere.
Highly Enantioselective Intermolecular Cross Rauhut–Currier Reaction Catalyzed by a Multifunctional Lewis Base Catalyst
Authors: Dong Xuelin , Liang Ling , Li Erqing , Huang You 
Published: December 2014

AbstractThe highly enantioselective intermolecular cross Rauhut–Currier reaction of different active olefins catalyzed by a multifunctional chiral Lewis base was reported. The RC products were obtained in excellent yields (up to 98 %), high chemo‐ and enantioselectivity (up to 96 % ee). The reaction could be performed on a gram scale using 1 mol % of the multifunctional phosphine catalyst.
High‐Resolution N6‐Methyladenosine (m6A) Map Using Photo‐Crosslinking‐Assisted m6A Sequencing
Authors: Chen Kai , Lu Zhike , Wang Xiao , Fu Ye , Luo Guan‐Zheng , Liu Nian , Han Dali , Dominissini Dan , Dai Qing , Pan Tao , He Chuan 
Published: December 2014

AbstractN6‐methyladenosine (m6A) is an abundant internal modification in eukaryotic mRNA and plays regulatory roles in mRNA metabolism. However, methods to precisely locate the m6A modification remain limited. We present here a photo‐crosslinking‐assisted m6A sequencing strategy (PA‐m6A‐seq) to more accurately define sites with m6A modification. Using this strategy, we obtained a high‐resolution map of m6A in a human transcriptome. The map resembles the general distribution pattern observed previously, and reveals new m6A sites at base resolution. Our results provide insight into the relationship between the methylation regions and the binding sites of RNA‐binding proteins.
Terpenoid Biosynthesis Off the Beaten Track: Unconventional Cyclases and Their Impact on Biomimetic Synthesis
Authors: Baunach Martin , Franke Jakob , Hertweck Christian 
Published: December 2014

AbstractTerpene and terpenoid cyclizations are counted among the most complex chemical reactions occurring in nature and contribute crucially to the tremendous structural diversity of this largest family of natural products. Many studies were conducted at the chemical, genetic, and biochemical levels to gain mechanistic insights into these intriguing reactions that are catalyzed by terpene and terpenoid cyclases. A myriad of these enzymes have been characterized. Classical textbook knowledge divides terpene/terpenoid cyclases into two major classes according to their structure and reaction mechanism. However, recent discoveries of novel types of terpenoid cyclases illustrate that nature’s enzymatic repertoire is far more diverse than initially thought. This Review outlines novel terpenoid cyclases that are out of the ordinary.
Stabilization of the Cysteine‐Rich Conotoxin MrIA by Using a 1,2,3‐Triazole as a Disulfide Bond Mimetic
Authors: Gori Alessandro , Wang Ching‐I A. , Harvey Peta J. , Rosengren K. Johan , Bhola Rebecca F. , Gelmi Maria L. , Longhi Renato , Christie Macdonald J. , Lewis Richard J. , Alewood Paul F. , Brust Andreas 
Published: December 2014

AbstractThe design of disulfide bond mimetics is an important strategy for optimising cysteine‐rich peptides in drug development. Mimetics of the drug lead conotoxin MrIA, in which one disulfide bond is selectively replaced of by a 1,4‐disubstituted‐1,2,3‐triazole bridge, are described. Sequential copper‐catalyzed azide–alkyne cycloaddition (CuAAC; click reaction) followed by disulfide formation resulted in the regioselective syntheses of triazole–disulfide hybrid MrIA analogues. Mimetics with a triazole replacing the Cys4–Cys13 disulfide bond retained tertiary structure and full in vitro and in vivo activity as norepinephrine reuptake inhibitors. Importantly, these mimetics are resistant to reduction in the presence of glutathione, thus resulting in improved plasma stability and increased suitability for drug development.
New polynomial strain energy function; application to rubbery circular cylinders under finite extension and torsion
Authors: Bahreman Marzieh , Darijani Hossein 
Published: December 2014

ABSTRACTIn this article, a strain energy density function is proposed in terms of the principal invariants of the left Cauchy‐Green strain tensor for Rubber‐like materials. This model due to its mathematical structure lies in the category of polynomial hyperelastic models. To compare the performance of the proposed model with the Rivlin set, some test data of rubber‐like materials with pure homogeneous deformations are used. It is shown that the proposed model has better agreement with the test data compared to the selected model. As an application of the proposed model, it is used to obtain a closed form solution for analysis of rubbery solid circular cylinders with S‐shaped and semi J‐shaped mechanical behavior under the torsion superimposed on the axial extension. Moreover, the results predicted from the proposed model are compared to classic models to investigate the results accuracy for simplification done. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41718.
Pharmacokinetic evaluation of tissue distribution of pirfenidone and its metabolites for idiopathic pulmonary fibrosis therapy
Authors: Togami Kohei , Kanehira Yukimune , Tada Hitoshi 
Published: December 2014

AbstractPirfenidone is the first and only clinically used anti‐fibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). It was reported previously that pirfenidone metabolites (5‐hydroxypirfenidone and 5‐carboxypirfenidone) also have anti‐fibrotic effects. The present study evaluated the distribution of pirfenidone and its metabolites in the lung, liver and kidney tissues in rats. The time course for the different concentrations of pirfenidone, 5‐hydroxypirfenidone and 5‐carboxypirfenidone in the lung tissue following oral administration (30 mg/kg) to rats was lower than that in plasma, and the area under the drug concentration–time curve (AUC) ratios of lung/plasma for pirfenidone, 5‐hydroxypirfenidone and 5‐carboxypirfenidone were 0.52, 0.40 and 0.61, respectively. In in vitro transport experiments, the basolateral‐to‐apical transport of pirfenidone and its metabolites through the model of lung epithelial cell (Calu‐3) monolayers was not significantly different from their apical‐to‐basolateral transport. In binding experiments, the binding rate of these drugs to the lung tissue was lower than that to the plasma protein. These findings suggest that the low distribution of pirfenidone and its metabolites in the lungs was based on their low affinities with lung tissue and not the transport characteristics of lung epithelial cells. On the other hand, the AUC ratios of liver/plasma for pirfenidone and 5‐carboxypirfenidone were 2.3 and 6.5 and the AUC ratios of kidney/plasma were 1.5 and 20, respectively. The binding rates to the liver and kidney tissues were higher than those to the plasma protein. These results suggest that high concentrations of these drugs were found in the liver and kidney tissues. Copyright © 2014 John Wiley & Sons, Ltd.
A retrospective study of venous thromboembolism in acute leukemia patients treated at the University of Texas MD Anderson Cancer Center
Authors: Vu Khanh , Luong Nhiem V. , Hubbard Julie , Zalpour Ali , Faderl Stefan , Thomas Deborah A. , Yang Daisy , Kantarjian Hagop , Kroll Michael H. 
Published: December 2014

AbstractThe purpose was to determine the incidence and prevalence of venous thromboembolism (VTE) in acute leukemia patients from our institution. We conducted a retrospective study on newly diagnosed acute leukemia patients who presented at our institution from November 1999 to May 2005. Descriptive statistics and cross‐tabulation were used to describe patient characteristics. Measures of morbidity were used to address VTE risk. Chi‐square testing, Fisher's exact testing, Mann–Whitney analyses, or median testing were used to determine between‐group differences. Data analyses were conducted using Stata version 11 (Stata Corp., College Station, TX). Two hundred and ninety‐nine patients with acute lymphoblastic leukemia (ALL) and 996 patients with acute myeloid leukemia (AML) were included. After excluding patients diagnosed with VTE prior to or at the time of leukemia diagnosis, during the mean time follow‐up period of 2.5 years (range: 0.0025–10.3 years), the overall incidence rate of VTE was 3.7 per 100 person‐years: 4.2 per 100 person‐years for ALL and 3.4 per 100 person‐years for AML. Among all patients, the majority (80.6%) developed VTE within 12 months after diagnosis and during thrombocytopenia. The most common VTE was central venous catheter (CVC)‐associated upper‐extremity deep venous thrombosis. Pulmonary embolism occurred in 15% of ALL patients and 8% of AML patients. VTE recurred in 20.7% of ALL patients and 18.6% of AML patients. VTE occurs frequently in patients with acute leukemia. Studies are needed to identify risk factors for the development and recurrence of VTE among patients with acute leukemia and to establish more effective methods for preventing and treating VTEs in leukemia patients who have thrombocytopenia and/or CVC.
Chloranthones A – D: Minor and Unprecedented Dinor‐Eudesmenes from Chloranthus elatior
Authors: Liu Shu‐Ting , Xiong Juan , Tang Yu , Wang Wen‐Xuan , Bui Van‐Binh , Ma Guang‐Lei , Huang Ya , Zhao Yun , Yang Guo‐Xun , Hu Jin‐Feng 
Published: December 2014

AbstractFour novel naturally occurring diastereoisomers of dinor‐eudesmenes, named chloranthones A–D (1–4, resp.), were isolated as minor components from the EtOH extract of the aerial parts of Chloranthus elatior. The unprecedented framework was established using extensive 2D‐NMR techniques. Their absolute configurations were deduced from the observed Cotton effects in their circular dichroism (CD) spectra. A plausible biosynthetic pathway to the dinor‐eudesmenes is proposed.
Sesquiterpenoids from Chloranthus henryi and Their Anti‐neuroinflammatory Activities
Authors: Wang Li‐Jun , Xiong Juan , Liu Shu‐Ting , Liu Xin‐Hua , Hu Jin‐Feng 
Published: December 2014

AbstractFive new and seven known mono‐sesquiterpenoids (1–5 and 6–12, resp.) together with five known lindenane‐type disesquiterpenoids, 13–17, were isolated from the whole plant of Chloranthus henryi. Based on spectroscopic methods, the new structures were established to be (5S,6R,8S,10R)‐6‐hydroxyeudesma‐4(15),7(11)‐diene‐12,8‐olide (1), 6α‐hydroxyeudesma‐4(15),7(11),8(9)‐triene‐12,8‐olide (2), 8,12‐epoxy‐1β‐hydroxyeudesma‐4(15),7,11‐trien‐6‐one (3), 12‐oxochloraniolide A (4), and (4α)‐8‐hydroxy‐12‐norcardina‐6,8,10‐trien‐11‐one (5), respectively. Among the isolates, compound 2, zederone epoxide (8), spicachlorantin G (13), chloramultilide A (14), shizukaol B (15), and spicachlorantin B (17) showed significant anti‐neuroinflammatory effects by inhibiting nitric‐oxide (NO) production in lipopolysaccharide (LPS)‐stimulated murine BV‐2 microglial cells with relatively low cytotoxicity.
Two New Butenolides Produced by an Actinomycete Streptomyces sp.
Authors: Wang Tang , Jiang Yi , Ma Kai‐Xia , Li Yi‐Qing , Huang Rong , Xie Xiao‐Song , Wu Shao‐Hua 
Published: December 2014

AbstractTwo new butenolides, (4S)‐4,10‐dihydroxydodec‐2‐en‐1,4‐olide (1) and (4S)‐4,8,10‐trihydroxy‐10‐methyldodec‐2‐en‐1,4‐olide (2), together with three known compounds, MKN‐003B (3), MKN‐003C (4), and cyclo(Ala‐Leu) (5), were isolated from the culture broth of a bacterium of the genus Streptomyces derived from soil environment. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The inhibitory activities of the butenolides against eight pathogenic fungi were evaluated. All of the butenolides showed moderate‐or‐weak antifungal activities in a broth microdilution assay.
Cytotoxic Mannopyranosides of Indole Alkaloids from Zanthoxylum nitidum
Authors: Hu Jiang , Shi Xiaodong , Mao Xia , Chen Jiangang , Li Hui 
Published: December 2014

AbstractThree new mannopyranosides of indole alkaloids, methyl 7‐(β‐D‐mannopyranosyloxy)‐1H‐indole‐2‐carboxylate (1), methyl 7‐[(3‐O‐acetyl‐β‐D‐mannopyranosyl)oxy]‐1H‐indole‐2‐carboxylate (2), and 2‐methyl‐1H‐indol‐7‐yl β‐D‐mannopyranoside (3), were isolated from an EtOH extract of the roots of Zanthoxylum nitidum. Their structures were identified as new compounds on the basis of the spectroscopic analyses. Bioactivity evaluation revealed that these alkaloids possess significant cytotoxicities against all the tested tumor cell lines with IC50 values of less than 30 μM.
Automated Identification of Depsipeptide Natural Products by an Informatic Search Algorithm
Authors: Skinnider Michael A. , Johnston Chad W. , Zvanych Rostyslav , Magarvey Nathan A. 
Published: December 2014

AbstractNonribosomal depsipeptides are a class of potent microbial natural products, which include several clinically approved pharmaceutical agents. Genome sequencing has revealed a large number of uninvestigated natural‐product biosynthetic gene clusters. However, while novel informatic search methods to access these gene clusters have been developed to identify peptide natural products, depsipeptide detection has proven challenging. Herein, we present an improved version of our informatic search algorithm for natural products (iSNAP), which facilitates the detection of known and genetically predicted depsipeptides in complex microbial culture extracts. We validated this technology by identifying several depsipeptides from novel producers, and located a large number of novel depsipeptide gene clusters for future study. This approach highlights the value of chemoinformatic search methods for the discovery of genetically encoded metabolites by targeting specific areas of chemical space.
Base Modification Strategies to Modulate Immune Stimulation by an siRNA
Authors: Valenzuela Rachel Anne P. , Suter Scott R. , Ball‐Jones Alexi A. , Ibarra‐Soza José M. , Zheng Yuxuan , Beal Peter A. 
Published: December 2014

AbstractImmune stimulation triggered by siRNAs is one of the major challenges in the development of safe RNAi‐based therapeutics. Within an immunostimulatory siRNA sequence, this hurdle is commonly addressed by using ribose modifications (e.g., 2′‐OMe or 2′‐F), which results in decreased cytokine production. However, as immune stimulation by siRNAs is a sequence‐dependent phenomenon, recognition of the nucleobases by the trigger receptor(s) is also likely. Here, we use the recently published crystal structures of Toll‐like receptor 8 (TLR8) bound to small‐molecule agonists to generate computational models for ribonucleotide binding by this immune receptor. Our modeling suggested that modification of either the Watson–Crick or Hoogsteen face of adenosine would disrupt nucleotide/TLR8 interactions. We employed chemical synthesis to alter either the Watson–Crick or Hoogsteen face of adenosine and evaluated the effect of these modifications in an siRNA guide strand by measuring the immunostimulatory and RNA interference properties. For the siRNA guide strand tested, we found that modifying the Watson–Crick face is generally more effective at blocking TNFα production in human peripheral blood mononuclear cells (PBMCs) than modification at the Hoogsteen edge. We also observed that modifications near the 5′‐end were more effective at blocking cytokine production than those placed at the 3′‐end. This work advances our understanding of how chemical modifications can be used to optimize siRNA performance.