bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatic mutations in leukocytes infiltrating primary breast cancers
Authors: Kleppe Maria , Comen Elizabeth , Wen Hannah Y , Bastian Lennart , Blum Brian , Rapaport Franck T , Keller Matthew , Granot Zvika , Socci Nicolas , Viale Agnès , You Daoqi , Benezra Robert , Weigelt Britta , Brogi Edi , Berger Michael F , Reis-Filho Jorge S , Levine Ross L , Norton Larry 
Published: June 2015

Abstract
Background:
Malignant transformation requires the interaction of cancer cells with their microenvironment, including infiltrating leukocytes. However, somatic mutational studies have focused on alterations in cancer cells, assuming that the microenvironment is genetically normal. Because we hypothesized that this might not be a valid assumption, we performed exome sequencing and targeted sequencing to investigate for the presence of pathogenic mutations in tumor-associated leukocytes in breast cancers.

Methods:
We used targeted sequencing and exome sequencing to evaluate the presence of mutations in sorted tumor-infiltrating CD45-positive cells from primary untreated breast cancers. We used high-depth sequencing to determine the presence/absence of the mutations we identified in breast cancer-infiltrating leukocytes in purified tumor cells and in circulating blood cells.

Results:
Capture-based sequencing of 15 paired tumor-infiltrating leukocytes and matched germline DNA identified variants in known cancer genes in all 15 primary breast cancer patients in our cohort. We validated the presence of mutations identified by targeted sequencing in infiltrating leukocytes through orthogonal exome sequencing. Ten patients harbored alterations previously reported as somatically acquired variants, including in known leukemia genes (DNTM3A, TET2, and BCOR). One of the mutations observed in the tumor-infiltrating leukocytes was also detected in the circulating leukocytes of the same patients at a lower allele frequency than observed in the tumor-infiltrating cells.

Conclusions:
Here we show that somatic mutations, including mutations in known cancer genes, are present in the leukocytes infiltrating a subset of primary breast cancers. This observation allows for the possibility that the cancer cells interact with mutant infiltrating leukocytes, which has many potential clinical implications.
Why do patients with Parkinson’s disease fall? A cross-sectional analysis of possible causes of falls
Authors: Schrag Anette , Choudhury Mahbuba , Kaski Diego , Gallagher David A 
Published: June 2015

Abstract
Background:
Falls in Parkinson’s disease (PD) are associated with significant injury, disability, hospitalization, and reduced quality of life.

Aims:
To identify modifiable medical causes of falls in a cohort of PD patients.

Methods:
Eighty seven PD patients were interviewed and examined using validated scales assessing motor and nonmotor aspects of PD, comorbidities and medication use. The frequency of falls in the last month was the primary outcome measure. Falls were hypothesized to be associated with increasing age, advanced motor severity, particularly axial features (e.g., freezing and postural instability), and dyskinesia. Nonmotor features hypothesized to be associated with falls included; cognitive impairment, psychosis, sleep disorders, cardiovascular dysfunction, and ophthalmological and medical comorbidities.

Results:
Fallers had longer disease duration, higher Levodopa-equivalent doses, greater ‘On’ time with dyskinesia (all P<0.005), and higher scores on some Movement Disorder Society-Unified Parkinson’s Disease Rating Scale items, particularly axial scores. However, patients with falls did not differ from non-fallers in age or overall motor UPDRS scores. Severity of psychosis, executive cognitive impairment, autonomic (particularly cardiovascular) dysfunction and sleep disturbances (particularly REM sleep behavioral disorder) were significantly associated with falls (all P<0.005). Fallers more frequently reported use of antidepressants (both tricyclics and SSRIs) and neuroleptics (P<0.001), but not hypnotics. There was no difference in medical comorbidities, ophthalmological assessments, fatigue, and apathy scores between the groups. In logistic regression analysis, cardiovascular dysfunction, antidepressant use, and REM sleep behavioral disorder were significantly associated with falls.

Conclusions:
The causes of falls in PD are multifactorial and extend beyond motor impairment and dyskinesia; addressing these in patients already treated with dopaminergic medications has the potential to improve this important complication of PD.
Modelling the Transport of Nanoparticles under Blood Flow using an Agent-based Approach
Authors: Fullstone Gavin , Wood Jonathan , Holcombe Mike , Battaglia Giuseppe 
Published: June 2015

AbstractBlood-mediated nanoparticle delivery is a new and growing field in the development of therapeutics and diagnostics. Nanoparticle properties such as size, shape and surface chemistry can be controlled to improve their performance in biological systems. This enables modulation of immune system interactions, blood clearance profile and interaction with target cells, thereby aiding effective delivery of cargo within cells or tissues. Their ability to target and enter tissues from the blood is highly dependent on their behaviour under blood flow. Here we have produced an agent-based model of nanoparticle behaviour under blood flow in capillaries. We demonstrate that red blood cells are highly important for effective nanoparticle distribution within capillaries. Furthermore, we use this model to demonstrate how nanoparticle size can selectively target tumour tissue over normal tissue. We demonstrate that the polydispersity of nanoparticle populations is an important consideration in achieving optimal specificity and to avoid off-target effects. In future this model could be used for informing new nanoparticle design and to predict general and specific uptake properties under blood flow.
Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library
Authors: Litovchick Alexander , Dumelin Christoph E. , Habeshian Sevan , Gikunju Diana , Guié Marie-Aude , Centrella Paolo , Zhang Ying , Sigel Eric A. , Cuozzo John W. , Keefe Anthony D. , Clark Matthew A. 
Published: June 2015

AbstractA chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library and successfully identified inhibitors of the enzyme soluble epoxide hydrolase.
TonEBP suppresses adipogenesis and insulin sensitivity by blocking epigenetic transition of PPARγ2
Authors: Lee Jun Ho , Lee Hwan Hee , Ye Byeong Jin , Lee-Kwon Whaseon , Choi Soo Youn , Kwon Hyug Moo 
Published: June 2015

AbstractTonEBP is a key transcription factor in cellular adaptation to hypertonic stress and also in macrophage activation. Since TonEBP is involved in inflammatory diseases such as rheumatoid arthritis and atherosclerosis, we asked whether TonEBP played a role in adipogenesis and insulin resistance. Here we report that TonEBP suppresses adipogenesis and insulin signaling by inhibiting expression of the key transcription factor PPARγ2. TonEBP binds to the PPARγ2 promoter and blocks the epigenetic transition of the locus which is required for the activation of the promoter. When TonEBP expression is reduced, the epigenetic transition and PPARγ2 expression are markedly increased leading to enhanced adipogenesis and insulin response while inflammation is reduced. Thus, TonEBP is an independent determinant of adipose insulin sensitivity and inflammation. TonEBP is an attractive therapeutic target for insulin resistance in lieu of PPARγ agonists.
Waveguide integrated superconducting single-photon detectors with high internal quantum efficiency at telecom wavelengths
Authors: Kahl Oliver , Ferrari Simone , Kovalyuk Vadim , Goltsman Gregory N. , Korneev Alexander , Pernice Wolfram H. P. 
Published: June 2015

AbstractSuperconducting nanowire single-photon detectors (SNSPDs) provide high efficiency for detecting individual photons while keeping dark counts and timing jitter minimal. Besides superior detection performance over a broad optical bandwidth, compatibility with an integrated optical platform is a crucial requirement for applications in emerging quantum photonic technologies. Here we present SNSPDs embedded in nanophotonic integrated circuits which achieve internal quantum efficiencies close to unity at 1550 nm wavelength. This allows for the SNSPDs to be operated at bias currents far below the critical current where unwanted dark count events reach milli-Hz levels while on-chip detection efficiencies above 70% are maintained. The measured dark count rates correspond to noise-equivalent powers in the 10−19 W/Hz−1/2 range and the timing jitter is as low as 35 ps. Our detectors are fully scalable and interface directly with waveguide-based optical platforms.
Understanding the association of Escherichia coli with diverse macroalgae in the lagoon of Venice
Authors: Quero Grazia M. , Fasolato Luca , Vignaroli Carla , Luna Gian Marco 
Published: June 2015

AbstractRecent studies provided evidence that the macroalga Cladopohora in lakes hosts associated Escherichia coli, with consequences on the environmental and human health. We expanded these investigations to other macroalgae (Ulva spp., Sargassum muticum and Undaria pinnatifida) widespread in the lagoon of Venice (Italy). Attached E. coli were abundant, accounting up to 3,250 CFU gram−1 of alga. Macroalgal-associated isolates belonged to all E. coli phylogroups, including pathogenic ones and to Escherichia cryptic clades. Attached E. coli showed potential to grow even at in situ temperature on macroalgal extracts as only source of carbon and nutrients and ability to produce biofilm in vitro. The genotypic diversity of the attached isolates was high, with significant differences between algae and the overlying water. Our evidences suggest that attached populations consist of both resident and transient strains, likely resulting from the heterogeneous input of fecal bacteria from the city. We report that cosmopolitan and invasive macroalgae may serve as source of E. coli, including pathogenic genotypes and that this habitat can potentially support their growth. Considering the global diffusion of the macroalgae here studied, this phenomenon is likely occurring in other coastal cities worldwide and deserves further investigations from either the sanitary and ecological perspectives.
Ubiquitin-specific protease 14 modulates degradation of cellular prion protein
Authors: Homma Takujiro , Ishibashi Daisuke , Nakagaki Takehiro , Fuse Takayuki , Mori Tsuyoshi , Satoh Katsuya , Atarashi Ryuichiro , Nishida Noriyuki 
Published: June 2015

AbstractPrion diseases are fatal neurodegenerative disorders characterized by the accumulation of prion protein (PrPC). To date, there is no effective treatment for the disease. The accumulated PrP, termed PrPSc, forms amyloid fibrils and could be infectious. It has been suggested that PrPSc is abnormally folded and resistant to proteolytic degradation and also inhibits proteasomal functions in infected cells, thereby inducing neuronal death. Recent work indicates that the ubiquitin-proteasome system is involved in quality control of PrPC. To reveal the significance of prion protein ubiqitination, we focused on ubiquitin-specific protease 14 (USP14), a deubiqutinating enzyme that catalyzes trimming of polyubiquitin chains and plays a role in regulation of proteasomal processes. Results from the present study showed that treatment with a selective inhibitor of USP14 reduced PrPC, as well as PrPSc, levels in prion-infected neuronal cells. Overexpression of the dominant negative mutant form of USP14 reduced PrPSc, whereas wildtype USP14 increased PrPSc in prion-infected cells. These results suggest that USP14 prevents degradation of both normal and abnormal PrP. Collectively, a better understanding about the regulation of PrPSc clearance caused by USP14 might contribute greatly to the development of therapeutic strategies for prion diseases.
Pentamethylquercetin (PMQ) reduces thrombus formation by inhibiting platelet function
Authors: Liang Ming-Lu , Da Xing-Wen , He Ao-Di , Yao Guang-Qiang , Xie Wen , Liu Gang , Xiang Ji-Zhou , Ming Zhang-Yin 
Published: June 2015

AbstractFlavonoids exert both anti-oxidant and anti-platelet activitiesin vitroandin vivo. Pentamethylquercetin (PMQ), a polymethoxylated flavone derivative, has been screened for anti-carcinogenic and cardioprotective effects. However, it is unclear whether PMQ has anti-thrombotic effects. In the present study, PMQ (20 mg/kg) significantly inhibited thrombus formation in the collagen- epinephrine- induced acute pulmonary thrombosis mouse model and the ferric chloride-induced carotid injury model. To explore the mechanism, we evaluated the effects of PMQ on platelet function. We found that PMQ inhibited platelet aggregation and granule secretion induced by low dose agonists, including ADP, collagen, thrombin and U46619. Biochemical analysis revealed that PMQ inhibited collagen-, thrombin- and U46619-induced activation of Syk, PLCγ2, Akt, GSK3β and Erk1/2. Therefore, we provide the first report to show that PMQ possesses anti-thrombotic activityin vivoand inhibited platelet functionin vitro, suggesting that PMQ may represent a potential therapeutic candidate for the prevention or treatment of thrombotic disorders.
Ectopic clustering of Cajal–Retzius and subplate cells is an initial pathological feature in Pomgnt2-knockout mice, a model of dystroglycanopathy
Authors: Nakagawa Naoki , Yagi Hirokazu , Kato Koichi , Takematsu Hiromu , Oka Shogo 
Published: June 2015

AbstractAberrant glycosylation of dystroglycan causes congenital muscular dystrophies associated with cobblestone lissencephaly, classified as dystroglycanopathy. However, pathological features in the onset of brain malformations, including the precise timing and primary cause of the pial basement membrane disruption and abnormalities in the migration of pyramidal neurons, remain unexplored. Using the Pomgnt2-knockout (KO) mouse as a dystroglycanopathy model, we show that breaches of the pial basement membrane appeared at embryonic day 11.5, coinciding with the ectopic clustering of Cajal–Retzius cells and subplate neurons and prior to the migration onset of pyramidal neurons. Furthermore, in the Pomgnt2-KO cerebral cortex, preplate splitting failure likely occurred due to the aggregation of Cajal–Retzius and subplate cells and migrating pyramidal neurons lost polarity and radial orientation. Our findings demonstrate the initial pathological events in dystroglycanopathy mice and contribute to our understanding of how dystroglycan dysfunction affects brain development and progresses to cobblestone lissencephaly.
Extracting entangled qubits from Majorana fermions in quantum dot chains through the measurement of parity
Authors: Dai Li , Kuo Watson , Chung Ming-Chiang 
Published: June 2015

AbstractWe propose a scheme for extracting entangled charge qubits from quantum-dot chains that support zero-energy edge modes. The edge mode is composed of Majorana fermions localized at the ends of each chain. The qubit, logically encoded in double quantum dots, can be manipulated through tunneling and pairing interactions between them. The detailed form of the entangled state depends on both the parity measurement (an even or odd number) of the boundary-site electrons in each chain and the teleportation between the chains. The parity measurement is realized through the dispersive coupling of coherent-state microwave photons to the boundary sites, while the teleportation is performed via Bell measurements. Our scheme illustrates localizable entanglement in a fermionic system, which serves feasibly as a quantum repeater under realistic experimental conditions, as it allows for finite temperature effect and is robust against disorders, decoherence and quasi-particle poisoning.
Metabolite-enabled mutualistic interaction between Shewanella oneidensis and Escherichia coli in a co-culture using an electrode as electron acceptor
Authors: Wang Victor Bochuan , Sivakumar Krishnakumar , Yang Liang , Zhang Qichun , Kjelleberg Staffan , Loo Say Chye Joachim , Cao Bin 
Published: June 2015

AbstractMutualistic interactions in planktonic microbial communities have been extensively studied. However, our understanding on mutualistic communities consisting of co-existing planktonic cells and biofilms is limited. Here, we report a planktonic cells-biofilm mutualistic system established by the fermentative bacteriumEscherichia coliand the dissimilatory metal-reducing bacteriumShewanella oneidensisin a bioelectrochemical device, where planktonic cells in the anode media interact with the biofilms on the electrode. Our results show that the transfer of formate is the key mechanism in this mutualistic system. More importantly, we demonstrate that the relative distribution ofE. coliandS. oneidensisin the liquid media and biofilm is likely driven by their metabolic functions towards an optimum communal metabolism in the bioelectrochemical device. RNA sequencing-based transcriptomic analyses of the interacting organisms in the mutualistic system potentially reveal differential expression of genes involved in extracellular electron transfer pathways in both species in the planktonic cultures and biofilms.
Tin-Doped Inorganic Amorphous Films for Use as Transparent Monolithic Phosphors
Authors: Masai Hirokazu , Miyata Hiroki , Yamada Yasuhiro , Okumura Shun , Yanagida Takayuki , Kanemitsu Yoshihiko 
Published: June 2015

AbstractAlthough inorganic crystalline phosphors can exhibit high quantum efficiency, their use in phosphor films has been limited by a reliance on organic binders that have poor durability when exposed to high-power and/or high excitation energy light sources. To address this problem, Sn2+ -doped transparent phosphate films measuring several micrometers in thickness have been successfully prepared through heat treatment and a subsequent single dip-coating process. The resulting monolithic inorganic amorphous film exhibited an internal quantum efficiency of over 60% and can potentially utilize transmitted light. Analysis of the film’s emissivity revealed that its color can be tuned by changing the amount of Mn and Sn added to influence the energy transfer from Sn2+ to Mn2+. It is therefore concluded that amorphous films containing such emission centers can provide a novel and viable alternative to conventional amorphous films containing crystalline phosphors in light-emitting devices.
A live attenuated vaccine prevents replication and transmission of H7N9 virus in mammals
Authors: Kong Huihui , Zhang Qianyi , Gu Chunyang , Shi Jianzhong , Deng Guohua , Ma Shujie , Liu Jinxiong , Chen Pucheng , Guan Yuntao , Jiang Yongping , Chen Hualan 
Published: June 2015

AbstractThe continued spread of the newly emerged H7N9 viruses among poultry in China, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. An MF59-adjuvant H7N9 inactivated vaccine is reported to be well-tolerated and immunogenic in humans; however a study in ferrets indicated that while a single dose of the inactivated H7N9 vaccine reduced disease severity, it did not prevent virus replication and transmission. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H7N9 vaccine (H7N9/AAca) that contains wild-type HA and NA genes from AH/1 and the backbone of the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AAca). H7N9/AAca was attenuated in mice and ferrets and induced robust neutralizing antibody responses in rhesus mice, ferrets and guinea pigs immunized once or twice intranasally. The animals immunized twice were completely protected from H7N9 virus challenge. Importantly, the animals vaccinated once were fully protected from transmission when exposed to or in contact with the H7N9 virus-inoculated animals. These results demonstrate that a cold-adapted H7N9 vaccine can prevent H7N9 virus transmission; they provide a compelling argument for further testing of this vaccine in human trials.
The role of calcineurin signaling in microcystin-LR triggered neuronal toxicity
Authors: Li Guangyu , Yan Wei , Dang Yao , Li Jing , Liu Chunsheng , Wang Jianghua 
Published: June 2015

AbstractMicrocystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing neurotoxicity, but the exact mechanisms of action still remain unclear. Using proteomic analysis, forty-five proteins were identified to be significantly altered in hippocampal neurons of rats treated with MCLR. Among them, Ca2+-activated phosphatase calcineurin (CaN) and the nuclear factor of activated T-cells isoform c3 (NFATc3) were up-regulated remarkably. Validation of the changes in CaN and NFATc3 expression by Western blotting demonstrated CaN cleavage and subsequent NFATc3 nuclear translocation were generated, suggesting that exposure to MCLR leads to activation of CaN, which in turn activates NFATc3. Activation of CaN signaling has been reported to result in apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member Bad. In agreement with this, our results revealed that treatment of neurons with the CaN inhibitor FK506 blocked the reduction in Bad dephosphorylation and cytochrome c (cyt c) release triggered by MCLR. Consistent with these biochemical results, we observed a marked decrease in apoptotic and necrotic cell death after MCLR exposure in the presence of FK506, supporting the hypothesis that MCLR appeared to cause neuronal toxicity by activation of CaN and the CaN-mediated mitochondrial apoptotic pathway.
Versatile control of metal-assisted chemical etching for vertical silicon microwire arrays and their photovoltaic applications
Authors: Um Han-Don , Kim Namwoo , Lee Kangmin , Hwang Inchan , Hoon Seo Ji , Yu Young J. , Duane Peter , Wober Munib , Seo Kwanyong 
Published: June 2015

AbstractA systematic study was conducted into the use of metal-assisted chemical etching (MacEtch) to fabricate vertical Si microwire arrays, with several models being studied for the efficient redox reaction of reactants with silicon through a metal catalyst by varying such parameters as the thickness and morphology of the metal film. By optimizing the MacEtch conditions, high-quality vertical Si microwires were successfully fabricated with lengths of up to 23.2 μm, which, when applied in a solar cell, achieved a conversion efficiency of up to 13.0%. These solar cells also exhibited an open-circuit voltage of 547.7 mV, a short-circuit current density of 33.2 mA/cm2 and a fill factor of 71.3% by virtue of the enhanced light absorption and effective carrier collection provided by the Si microwires. The use of MacEtch to fabricate high-quality Si microwires therefore presents a unique opportunity to develop cost-effective and highly efficient solar cells.