bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel gene encoding a unique luciferase from the fireworm Odontsyllis undecimdonta
Authors: Mitani Yasuo , Yasuno Rie , Isaka Minato , Mitsuda Nobutaka , Futahashi Ryo , Kamagata Yoichi , Ohmiya Yoshihiro 
Published: August 2018

AbstractLuciferases identified or engineered so far emit violet, blue, blue-green, green, yellow, red or near infra-red light. The unique and beautiful bluish-green bioluminescence of fireworms Odontosyllis spp. has attracted particular interest, however, their molecular basis is totally unknown partly due to the difficulty of animal collection. Here we report a novel type of luciferase gene from the Japanese fireworm O. undecimdonta. The major SDS-PAGE band of the luminous mucus showed luciferase activity. A highly sensitive mass spectrometry analysis in combination with RNA sequencing technique revealed that this band was product of a single gene with no homology to any other sequences in public databases. The recombinant protein of this putative luciferase gene expressed in mammalian cells produced the same unique bluish-green emission peak as the fireworm crude extract, indicating that this novel gene is the genuine fireworm luciferase with an evolutionary different origin from other luciferases previously described. Our findings extend the repertoire of luciferin/luciferase system to previously unavailable wavelength range.
Characterization of membrane penetration and cytotoxicity of C9orf72-encoding arginine-rich dipeptides
Authors: Kanekura Kohsuke , Harada Yuichiro , Fujimoto Mao , Yagi Takuya , Hayamizu Yuhei , Nagaoka Kentaro , Kuroda Masahiko 
Published: August 2018

AbstractCell-penetrating peptides (CPPs) including arginine-rich peptides are attracting a lot of attention due to their potential as a novel intracellular drug delivery tool without substantial toxicity. On the other hand, disease-associated arginine-rich CPPs, such as poly-PR and poly-GR translated from C9orf72 gene, also efficiently enter neuronal cells and then kill them. Although both non-harmful CPPs and harmful poly-PR/GR penetrate the plasma membrane using same arginine residues, little is known about the factors which determine the toxicity of the pathogenic CPPs. Here, we show that poly-PR and poly-GR, but not other Arg-rich CPPs, specifically distributed to nucleolus via interaction with RNA. Importantly, C9orf72-dipeptides, but not other Arg-rich CPPs, caused inhibition of protein translation and cell death. Raising extracellular pH enhanced the cell penetration of poly-PR. The repeat number of (PR) affected the secondary structure and determined the intracellular delivery rate and neurotoxicity, and enforced intracellular delivery of non-penetrating short poly-PR peptide caused cell death, suggesting that modulation of extracellular environment to inhibit the uptake of Arg-rich dipeptides might be a drug target against poly-PR/GR-mediated neurotoxicity.
Evaluating Tumor Evolution via Genomic Profiling of Individual Tumor Spheroids in a Malignant Ascites
Authors: Kim Sungsik , Kim Soochi , Kim Jinhyun , Kim Boyun , Kim Se Ik , Kim Min A. , Kwon Sunghoon , Song Yong Sang 
Published: August 2018

AbstractEpithelial ovarian cancer (EOC) is a silent but mostly lethal gynecologic malignancy. Most patients present with malignant ascites and peritoneal seeding at diagnosis. In the present study, we used a laser-aided isolation technique to investigate the clonal relationship between the primary tumor and tumor spheroids found in the malignant ascites of an EOC patient. Somatic alteration profiles of ovarian cancer-related genes were determined for eight spatially separated samples from primary ovarian tumor tissues and ten tumor spheroids from the malignant ascites using next-generation sequencing. We observed high levels of intra-tumor heterogeneity (ITH) in copy number alterations (CNAs) and single-nucleotide variants (SNVs) in the primary tumor and the tumor spheroids. As a result, we discovered that tumor cells in the primary tissues and the ascites were genetically different lineages. We categorized the CNAs and SNVs into clonal and subclonal alterations according to their distribution among the samples. Also, we identified focal amplifications and deletions in the analyzed samples. For SNVs, a total of 171 somatic mutations were observed, among which 66 were clonal mutations present in both the primary tumor and the ascites, and 61 and 44 of the SNVs were subclonal mutations present in only the primary tumor or the ascites, respectively. Based on the somatic alteration profiles, we constructed phylogenetic trees and inferred the evolutionary history of tumor cells in the patient. The phylogenetic trees constructed using the CNAs and SNVs showed that two branches of the tumor cells diverged early from an ancestral tumor clone during an early metastasis step in the peritoneal cavity. Our data support the monophyletic spread of tumor spheroids in malignant ascites.
Selection scan reveals three new loci related to high altitude adaptation in Native Andeans
Authors: Jacovas Vanessa C. , Couto-Silva Cainã M. , Nunes Kelly , Lemes Renan B. , de Oliveira Marcelo Z. , Salzano Francisco M. , Bortolini Maria Cátira , Hünemeier Tábita 
Published: August 2018

AbstractThe Andean Altiplano has been occupied continuously since the late Pleistocene, ~12,000 years ago, which places the Andean natives as one of the most ancient populations living at high altitudes. In the present study, we analyzed genomic data from Native Americans living a long-time at Andean high altitude and at Amazonia and Mesoamerica lowland areas. We have identified three new candidate genes - SP100, DUOX2 and CLC - with evidence of positive selection for altitude adaptation in Andeans. These genes are involved in the TP53 pathway and are related to physiological routes important for high-altitude hypoxia response, such as those linked to increased angiogenesis, skeletal muscle adaptations, and immune functions at the fetus-maternal interface. Our results, combined with other studies, showed that Andeans have adapted to the Altiplano in different ways and using distinct molecular strategies as compared to those of other natives living at high altitudes.
Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
Authors: Kumar Parvin , Efstathopoulos Paschalis , Millischer Vincent , Olsson Eric , Wei Ya Bin , Brüstle Oliver , Schalling Martin , Villaescusa J. Carlos , Ösby Urban , Lavebratt Catharina 
Published: August 2018

AbstractMitochondrial pathology has been implicated in the pathogenesis of psychotic disorders. A few studies have proposed reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder type I, compared to healthy controls. However, it is unknown if mtDNA copy number alteration is driven by psychosis, comorbidity or treatment. Whole blood mtDNA copy number was determined in 594 psychosis patients and corrected for platelet to leukocyte count ratio (mtDNAcnres). The dependence of mtDNAcnres on clinical profile, metabolic comorbidity and antipsychotic drug exposure was assessed. mtDNAcnres was reduced with age (β = −0.210, p < 0.001), use of clozapine (β = −0.110,p = 0.012) and risperidone (β = −0.109,p = 0.014), dependent on prescribed dosage (p = 0.006 and p = 0.026, respectively), and the proportion of life on treatment (p = 0.006). Clozapine (p = 0.0005) and risperidone (p = 0.0126) had a reducing effect on the mtDNA copy number also in stem cell-derived human neurons in vitro at therapeutic plasma levels. For patients not on these drugs, psychosis severity had an effect (β = −0.129, p = 0.017), similar to age (β = −0.159, p = 0.003) and LDL (β = −0.119, p = 0.029) on whole blood mtDNAcnres. Further research is required to determine if mtDNAcnres reflects any psychosis-intrinsic mitochondrial changes.
Assessment of the ability of open- and closed-loop cueing to improve turning and freezing in people with Parkinson’s disease
Authors: Mancini Martina , Smulders Katrijn , Harker Graham , Stuart Samuel , Nutt John G. 
Published: August 2018

AbstractTurning impairments are common in Parkinson’s disease (PD) and can elicit freezing of gait (FoG). Extensive examination of open-loop cueing interventions has demonstrated that they can ameliorate gait deficits in PD; less is known about efficacy to improve turning. Here, we investigate the immediate effectiveness of open- and closed-loop cueing in improving turning characteristics in people with PD. Twenty-five subjects with and 18 subjects without FoG participated in the study. Subjects turned in place for one minute under single- and dual-task for 3 randomized conditions: (i) Baseline; (ii) Turning to the beat of a metronome (open-loop); and (iii) Turning with phase-dependent tactile biofeedback (closed-loop). Objective measures of freezing, such as % time spent freezing and FoG-ratio, significantly improved when turning with both open-loop and closed-loop cueing compared to baseline. Dual-tasking did not worsen FoG in freezers, but significantly slowed down turns in both groups. Both cueing modalities significantly improved turning smoothness in both groups, but reduced turning velocity and number of turns compared to baseline. Both open and closed-loop cueing markedly improved turning in people with PD. These preliminary observations warrant further exploration of vibrotactile closed-loop cueing to improve mobility in everyday life.
Prevention of posterior capsule opacification through intracapsular hydrogen peroxide or distilled water treatment in human donor tissue
Authors: D’Antin Justin Christopher , Barraquer Rafael I. , Tresserra Francisco , Michael Ralph 
Published: August 2018

AbstractIn order to determine whether posterior capsule opacification after cataract surgery, could be delayed or inhibited through the application of hydrogen peroxide (H2O2) or distilled water (H2Od),we extracted lens capsules from 25 human donor eye globes. Samples were treated for 5 min with either 30 mM H2O2 or H2Od or used as controls, and cultured for one month, during which dark field and tilt illumination photos were taken. These were used to observe and quantify, time until cellular growth and confluence on the posterior capsule. After culture, histological sections were stained for H&E, α-SMA, Ki-67 and vimentin and evaluated. We prevented cellular growth in 50% of H2Od and 58% H2O2 of treated samples. The overall prevention of cell growth compared to cultured controls was significant for both treatments while there was no significant difference between them. In the cases where cellular growth was not prevented, both treatments significantly delay cellular growth. Until day 28 none of the treated samples of either type that had shown growth reached total confluence. All cultured controls reached total confluence before treated samples (median = day 11.5). Also, histologically, there was a clear morphological difference between cultured controls and treated samples.
Characterization and induction of prophages in human gut-associated Bifidobacterium hosts
Authors: Mavrich Travis N. , Casey Eoghan , Oliveira Joana , Bottacini Francesca , James Kieran , Franz Charles M. A. P. , Lugli Gabriele Andrea , Neve Horst , Ventura Marco , Hatfull Graham F. , Mahony Jennifer , van Sinderen Douwe 
Published: August 2018

AbstractIn the current report, we describe the identification of three genetically distinct groups of prophages integrated into three different chromosomal sites of human gut-associated Bifidobacterium breve and Bifidobacterium longum strains. These bifidobacterial prophages are distantly related to temperate actinobacteriophages of several hosts. Some prophages, integrated within the dnaJ2 gene, are competent for induction, excision, replication, assembly and lysis, suggesting that they are fully functional and can generate infectious particles, even though permissive hosts have not yet been identified. Interestingly, several of these phages harbor a putative phase variation shufflon (the Rin system) that generates variation of the tail-associated receptor binding protein (RBP). Unlike the analogous coliphage-associated shufflon Min, or simpler Cin and Gin inversion systems, Rin is predicted to use a tyrosine recombinase to promote inversion, the first reported phage-encoded tyrosine-family DNA invertase. The identification of bifidobacterial prophages with RBP diversification systems that are competent for assembly and lysis, yet fail to propagate lytically under laboratory conditions, suggests dynamic evolution of bifidobacteria and their phages in the human gut.
An eco-friendly synthesized mesoporous-silica particle combined with WSe2-graphene-TiO2 by self-assembled method for photocatalytic dye decomposition and hydrogen production
Authors: Zhu Lei , Nguyen Dinh Cung Tien , Woo Jung-Hun , Zhang Qinfang , Cho Kwang Youn , Oh Won-Chun 
Published: August 2018

AbstractTo address the limitations of titanium dioxide (TiO2) and expand the applicability of the photocatalytic activity of TiO2,WSe2 and silica, an eco-friendly, self-assembled method for combining a silica precursor with a WSe2-graphene-TiO2 composite with cetyltrimethylammonium bromide (CTAB) as surface active agents is proposed. Firstly, for the main target, the photocatalytic degradation of organic dye solutions with different initial pH levels and catalyst dosages under visible light irradiation was surveyed. The as-synthesized sample exhibited highly efficient photocatalytic effects for the treatment of the SO dye solution in the optimal conditions of this study, which included a solution with a pH level of 11 and 0.05-gram dosage of the catalyst. Secondly, previous photocatalytic hydrogen production studies reported markedly better outcomes with SiO2/WSe2-graphene-TiO2 than with the binary WSe2-graphene and ternary WSe2-graphene-TiO2 composites under ambient conditions with and without 20% methanol sacrificing reagents. The SiO2/WSe2-graphene-TiO2 composite is promising to become a potential candidate for photocatalytic performance that performs excellently as well as offer an efficient heterosystem for hydrogen production.
Thermodynamic and microstructural study of Ti2AlNb oxides at 800 °C
Authors: Xiang J. M. , Mi G. B. , Qu S. J. , Huang X. , Chen Z. , Feng A. H. , Shen J. , Chen D. L. 
Published: August 2018

AbstractThe high-temperature structural applications of Ti2AlNb-based alloys, such as in jet engines and gas turbines, inevitably require oxidation resistance. The objective of this study is to seek fundamental insight into the oxidation behavior of a Ti2AlNb-based alloy via detailed microstructural characterization of oxide scale and scale/substrate interface after oxidation at 800 °C using X-ray diffraction (XRD), scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and transmission electron microscopy (TEM). The oxide scale exhibits a complex multi-layered structure consisting of (Al,Nb)-rich mixed oxide layer (I)/mixed oxide layer (II)/oxygen-rich layer (III)/substrate from the outside to inside, where the substrate is mainly composed of B2 and O-Ti2AlNb phases. High-resolution TEM examinations along with high-angle annular dark-field (HAADF) imaging reveal: (1) the co-existence of two types (α and δ) of Al2O3 oxides in the outer scale, (2) the presence of metastable oxide products of TiO and Nb2O5, (3) an amorphous region near the scale/substrate interface including the formation of AlNb2, and (4) O-Ti2AlNb phase oxidized to form Nb2O5, TiO2 and Al2O3.
Simultaneous reinforcing and toughening of PTFE/glass fabric composites based on polyaniline/carbon microcapsule network
Authors: Zhang Bin , Jiang Yujie 
Published: August 2018

Through designing dispersed well and assembled orderly structures, a series of polyaniline (PANI)/carbon (CB) microcapsules were successfully synthesised. In the formation of the PANI/CB microcapsules, PANI/CB microcapsules were in good dispersion and ordered state, which resulted in exceptional mechanical properties and electrical conductivity for polytetrafluoroethylene (PTFE)/glass fabric (GF) composites. Here, the authors have developed the PTFE/GF composites that have not only tensile strength up to 21.5 MPa, but also toughness up to 17.5 MJ/m3, and surface resistivity up to 5 × 108 Ω cm, it is difficult to obtain by other methods. This was achieved by only assembled orderly and ordered arrangement for forming highly ordered network structures in an oriented direction, without introducing a third component or chemical cross‐linker as in interfacial systems. More importantly, they believe that the design principles and processing strategies, which can be applied to other material systems to develop superconducting, strong and flexible materials.
Designing metrics; the delta metric for curves
Authors: Mennucci Andrea C.G. 
Published: August 2018

In the first part, we revisit some key notions. Let M be a Riemannian manifold. Let G be a group acting on M. We discuss the relationship between the quotient M∕G, “horizontality” and “normalization”. We discuss the distinction between path-wise invariance and point-wise invariance and how the former positively impacts the design of metrics, in particular for the mathematical and numerical treatment of geodesics. We then discuss a strategy to design metrics with desired properties.
In the second part, we prepare methods to normalize some standard group actions on the curve; we design a simple differential operator, called the delta operator, and compare it to the usual differential operators used in defining Riemannian metrics for curves.
In the third part we design two examples of Riemannian metrics in the space of planar curves. These metrics are based on the “delta” operator; they are “modular”, they are composed of different terms, each associated to a group action. These are “strong” metrics, that is, smooth metrics on the space of curves, that is defined as a differentiable manifolds, modeled on the standard Sobolev space H2. These metrics enjoy many important properties, including: metric completeness, geodesic completeness, existence of minimal length geodesics. These metrics properly project on the space of curves up to parameterization; the quotient space again enjoys the above properties.
Managing Neurophobia: How Can We Meet the Current and Future Needs of Our Students?
Authors: Józefowicz Ralph , Tarolli Christopher 
Published: August 2018

AbstractNeurophobia was defined more than two decades ago as a “fear of neural sciences and clinical neurology” among medical students. Despite recognition of the ailment and research into underlying causes, medical students and neurological educators continue to struggle with neurophobia today. At our institution, we have been successful at mitigating neurophobia. Here, we define the underlying drivers of neurophobia, based on the relevant literature. We also describe our strategies for battling neurophobia in the preclinical and clinical years by (1) establishing a continuum of neurological education; (2) incorporating active and observed learning throughout neurological education; and (3) enhancing socialization into neurology. Finally, we consider the future of neurological education, describe strategies for educators to mitigate neurophobia, and propose a call to action to further understand neurophobia. Neurophobia is not inevitable; effective curricula and dedicated faculty can engage students and ensure students better understand and enjoy their neurological education.
Megalencephaly Capillary Malformation Syndrome
Authors: Polizzi Agata , Salafia Stefania , Praticò Elena , Garozzo Maria , Sullo Federica , Catanzaro Stefano , Belfiore Giuseppe , Pirrone Concetta , Zanghì Antonio , Fiumara Agata , Ruggieri Martino , Resta Nicoletta , Praticò Andrea 
Published: August 2018

AbstractMegalencephaly capillary malformation polymicrogyria (MCAP) syndrome is characterized by the sporadic occurrence of congenital and progressive megalencephaly, brain malformations including polymicrogyria, pre- and postnatal overgrowth with body asymmetry, cutaneous vascular malformations (including capillary malformation and cutis marmorata), digital anomalies connective tissue dysplasia (including skin and joint laxity), and developmental delay. In the past 10 years, the specific cause of the disease has been found in gain-of-function mutations of PIK3CA gene, mostly somatic/postzygotic but in rare cases also de novo germline. Such gene encodes for PI3K, a critical member of the PI3K-AKT-mTOR pathway: genetic changes lead to an over-activation of this signaling system, with increased vascular, limb, and brain cell development, progression, and survival. Interestingly, mutations in the same gene can cause other clinically heterogeneous syndromes, including CLOVE syndrome, macrodactyly, focal adipose overgrowth, epidermal nevi, facial infiltrating lipomatosis: all these syndromes (even if heterogeneous) are now considered a unique spectrum, known as PIK3CA-related overgrowth syndrome. On the contrary, a disease strictly similar to MCAP, characterized by megalencephaly, polymicrogyria, polydactyly, and hydrocephalus has been found to be caused by mutations in two other PI3K-AKT-mTOR-releted genes, AKT3 and PIK3R2, and for this reason is not included in the upper mentioned group of syndromes. With the exception of neurosurgery strategies for hydrocephalus and posterior fossa overcrowding, therapeutic options are nowadays limited, even if gene-targeted treatment protocols have been proposed and protocols with such agents (i.e., Arq092) are currently ongoing in small groups of patients with promising results.
Cerebellotrigeminal Dermal Dysplasia (Gómez-López-Hernández Syndrome)
Authors: Sullo Federica , Polizzi Agata , Catanzaro Stefano , Mantegna Selene , Lacarrubba Francesco , Micali Giuseppe , Fiumara Agata , Smilari Pierluigi , Greco Filippo , Schepis Carmelo , Pirrone Concetta , Zanghì Antonio , Pascual-Castroviejo Ignacio , Ruggieri Martino , Praticò Andrea 
Published: August 2018

Cerebellotrigeminal dermal (CTD) dysplasia is a rare neurocutaneous disorder characterized by a triad of symptoms: bilateral parieto-occipital alopecia, facial anesthesia in the trigeminal area, and rhombencephalosynapsis (RES), confirmed by cranial magnetic resonance imaging. CTD dysplasia is also known as Gómez-López-Hernández syndrome. So far, only 35 cases have been described with varying symptomatology. The etiology remains unknown. Either spontaneous dominant mutations or de novo chromosomal rearrangements have been proposed as possible explanations. In addition to its clinical triad of RES, parietal alopecia, and trigeminal anesthesia, CTD dysplasia is associated with a wide range of phenotypic and neurodevelopmental abnormalities.Treatment is symptomatic and includes physical rehabilitation, special education, dental care, and ocular protection against self-induced corneal trauma that causes ulcers and, later, corneal opacification. The prognosis is correlated to the mental development, motor handicap, corneal–facial anesthesia, and visual problems. Follow-up on a large number of patients with CTD dysplasia has never been reported and experience is limited to few cases to date. High degree of suspicion in a child presenting with characteristic alopecia and RES has a great importance in diagnosis of this syndrome.