bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking mitochondrial dysfunction to neurodegeneration in lysosomal storage diseases
Authors: Saffari Afshin , Kölker Stefan , Hoffmann Georg F. , Ebrahimi‐Fakhari Darius 
Published: May 2017

AbstractLysosomal storage diseases (LSD) are inborn errors of metabolism resulting in multisystem disease. Central nervous system involvement, often with progressive neurodegeneration, accounts for a large portion of the morbidity and mortality seen in many LSD. Available treatments fail to prevent or correct neurologic symptoms and decline. Emerging evidence points to an important role for mitochondrial dysfunction in the pathogenesis and progression of LSD‐associated neurodegeneration. Mitochondrial dysfunction in LSD is characterized by alterations in mitochondrial mass, morphology and function. Disturbed mitochondrial metabolism in the CNS may lead to excessive production of mitochondrial reactive oxygen species and dysregulated calcium homeostasis. These metabolic disturbances ultimately result in mitochondria‐induced apoptosis and neuronal degeneration. Here, we review the current evidence for mitochondrial dysfunction in neuronal models of seven LSD, including GM1‐gangliosidosis, mucopolysaccharidosis IIIC, multiple sulfatase deficiency, Krabbe disease, Gaucher disease, Niemann Pick disease type C and the neural ceroid lipofuscinoses and outline current experimental therapies aimed at restoring mitochondrial function and neuroprotection in LSD.
Occurrence and risk assessment of trace metals and metalloids in sediments and benthic invertebrates from Dianshan Lake, China
Authors: Wu Yan , Zhou Yihui , Qiu Yanling , Chen Da , Zhu Zhiliang , Zhao Jianfu , Bergman Ǻke 
Published: May 2017

Abstract
The present study measured concentrations of Cr, Ni, Cu, Zn, As, Cd, Sb, and Pb in surface sediments and two benthic invertebrate species (Anodonta woodiana and Bellamya aeruginosa) collected from Dianshan Lake, located in the Yangtze River Delta. The Dianshan Lake acts as one of the most important drinking water sources to Shanghai, the biggest city in China. Concentrations of trace metals and metalloids ranged from 0.04 mg/kg for Cd to 288.0 mg/kg for Zn. Substantial bioaccumulation in invertebrates was observed for Zn and Cu based on the biota-sediment accumulation factor (BSAF) measurements. The results revealed that concentrations of metals and metalloids in sediments from Dianshan Lake were at the lower end of the range of levels found in other regions of China. The assessment of three significantly inter-related evaluation indices, including the geo-accumulation Index (Igeo), potential ecological risk factor (Eri), and mean probable effect concentration quotients (Qm-PEC), suggested that sediment-associated trace elements exhibited no considerable ecological risks in the studied watershed. However, the target hazard quotient and hazard index analysis suggested that selected elements (particularly As) accumulation in edible tissues of benthic invertebrates could pose potential health risks to local populations, especially fishermen. Given that wild aquatic organisms (e.g., fish and bivalves) constitute the diet of local populations as popular food/protein choices, further investigations are needed to better elucidate human health risks from metal and metalloid exposure via edible freshwater organisms.
Femoral and Lumbar Fractures During Rehabilitation for a Traumatic Spinal Cord Injury in Osteogenesis Imperfecta: A Case Presentation
Authors: Ross Brendon S. , Ripley David , Ho Anna M. , Rydberg Leslie 
Published: May 2017

AbstractOsteogenesis imperfecta (OI) is one of the most common inherited bone disorders. These individuals are high‐risk for developing fractures during their lifetime secondary to bone fragility. This case presents a female with type I OI involved in a high speed motor vehicle accident resulting in a traumatic spinal cord injury (SCI) and paraplegia. Inpatient rehabilitation was complicated by fractures of the femur and lumbar spine which impacted her level of independence upon discharge to prevent additional fractures and maintain safety. OI coupled with SCI creates a difficult combination for the rehabilitation team. This case highlights the complexity of this challenge to bring awareness to the rehabilitation team in order to safely maximize independence and minimize and prevent unnecessary injury when designing an interdisciplinary treatment plan.Level of EvidenceV
Interfang Distances of Rattlesnakes: Sexual, Interspecific, and Body Size-related Variation, and Implications for Snakebite Research and Management
Authors: Hayes William K. , Corbit Aaron G. , Cardwell Michael D. , Herbert Shelton S. 
Published: May 2017

Objectives Snakebite severity corresponds to size of snake because the amount of venom a snake injects is positively associated with snake size. Because fang marks are often present on snakebite patients, we tested whether the relationship between snake length and distance between fang puncture wounds can be generalized for rattlesnakes of genus Crotalus. Methods We measured 2 interfang distances from 79 rattlesnakes of both sexes, 5 species, and varying body length: 1) distance between fang bases in anesthetized snakes, and 2) distance between fang punctures in a membrane-covered beaker bitten defensively. Results Statistical analyses supported our 2 hypotheses, that 1) body size-related fang divergence during fang protraction (ie, anterolateral movement during fang erection), and 2) the relationship between snake length and interfang distance are similar between the sexes and among different rattlesnake species. We therefore derived a general equation to estimate snake length based on distance between fang marks, and recommended 5 snake size categories: very small (<10 mm), small (10–15 mm), medium (15–20 mm), large (20–25 mm), and very large (>25 mm). Conclusions The distance between fang marks on a snakebite patient may be used to estimate the size or size category of the offending snake, which in some cases may have predictive value for overall clinical severity of a given envenomation. Assessing interfang distance from puncture wounds can improve snakebite research and anticipation of snakebite severity.
Tiltrotor CFD Part II - aerodynamic optimisation of tiltrotor blades
Authors: Jimenez-Garcia A. , Biava M. , Barakos G.N. , Baverstock K.D. , Gates S. , Mullen P. 
Published: May 2017

ABSTRACTThis paper presents aerodynamic optimisation of tiltrotor blades with high-fidelity computational fluid dynamics. The employed optimisation framework is based on a quasi-Newton method, and the required high-fidelity flow gradients were computed using a discrete adjoint solver. Single-point optimisations were first performed to highlight the contrasting requirements of the helicopter and aeroplane flight regimes. It is then shown how a trade-off blade design can be obtained using a multi-point optimisation strategy. The parametrisation of the blade shape allowed the twist and chord distributions to be modified and a swept tip to be introduced. The work shows how these main blade shape parameters influence the optimal performance of the tiltrotor in helicopter and aeroplane modes, and how an optimised blade shape can increase the overall tiltrotor performance. Moreover, in all the presented cases, the accuracy of the adjoint gradients resulted in a small number of flow evaluations for finding the optimal solution, thus indicating gradient-based optimisation as a viable tool for modern tiltrotor design.
Data Protection and the ‘Right to be Forgotten’ in Practice: A UK Perspective
Authors: Townend Judith 
Published: May 2017

AbstractWe are in an uncertain and complex period for data protection and privacy in Europe, and especially so in the UK, following the result of the ‘Brexit’ referendum on 23 June 2016. Information law, and data protection in particular, are of increasing concern for those in the business of knowledge sharing and information dissemination: media organizations, academic institutions and libraries. The notion of the ‘right to be forgotten’ is particularly troublesome, as lawyers, archivists, historians and philosophers grapple with the theoretical and practical implications. This article presents a selection of recent European and British policy and legal developments, and discusses how they are changing social practice and citizens’ engagement with information rights.
First reported actinopterygian from the Navajo Sandstone (Lower Jurassic, Glen Canyon Group) of southern Utah, USA
Authors: Frederickson Joseph A. , Davis Brian M. 
Published: May 2017

AbstractWe report the first occurrence of an actinopterygian fish from the Lower Jurassic Navajo Sandstone, discovered in the Grand Staircase-Escalante National Monument in southern Utah, U.S.A. The site contains multiple individuals, preserved within an interdune deposit, possessing the elongate modified dorsal scales usually characterizing semionotiform fishes. The presence of moderately sized fish provides further evidence that interdune oases were occasionally persistent environmental habitats within the greater Navajo dune system, and that the paleobiota is still woefully undersampled. Additionally, this site could help fill a gap in the actinopterygian fossil record between the patchy Lower Jurassic and better-known Middle Jurassic documentation of western North America.
GIVING BIRTH TO A NEW NATION: FEMALE MEDIATION AND THE SPREAD OF TEXTUAL KNOWLEDGE IN DRACULA
Authors: Straight Alyssa 
Published: May 2017

After his harrowing escape from Castle Dracula, Jonathan Harker entrusts his journal, and the secret of his traumatic experiences with the vampire Count contained therein, to his new wife, Mina Harker (née Murray). “Here is the book,” he urges; “Take it and keep it, read it if you will, but never let me know; unless, indeed, some solemn duty should come upon me to go back to the bitter hours, asleep or awake, sane or mad, recorded here” (Stoker 100; ch. 9). Mina clasps the book, sealing it with a kiss, as she replies, “it would be an outward and visible sign for us all our lives that we trusted each other.” This scene from Bram Stoker's Dracula (1897) catalyzes the novel's concern with how knowledge transfer and technology intersect with women's bodies and labor. Not only is Mina the one trusted with the diary, but she is also the only person within the novel who has the required skills to translate its shorthand into a typed and readable document. In this solemn scene, which precedes and resembles their marriage vows, Mina both gains access to private information and is charged with deciding who else should have access to that knowledge and under what circumstances. This “trust” secures Mina as the mediator of knowledge and the curator of what will become an increasingly expansive imperial archive within the novel.
Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH
Authors: Boatz Jennifer C. , Whitley Matthew J. , Li Mingyue , Gronenborn Angela M. , van der Wel Patrick C. A. 
Published: May 2017

AbstractCataracts cause vision loss through the large-scale aggregation of eye lens proteins as a result of ageing or congenital mutations. The development of new treatments is hindered by uncertainty about the nature of the aggregates and their mechanism of formation. We describe the structure and morphology of aggregates formed by the P23T human γD-crystallin mutant associated with congenital cataracts. At physiological pH, the protein forms aggregates that look amorphous and disordered by electron microscopy, reminiscent of the reported formation of amorphous deposits by other crystallin mutants. Surprisingly, solid-state NMR reveals that these amorphous deposits have a high degree of structural homogeneity at the atomic level and that the aggregated protein retains a native-like conformation, with no evidence for large-scale misfolding. Non-physiological destabilizing conditions used in many in vitro aggregation studies are shown to yield qualitatively different, highly misfolded amyloid-like fibrils.
Protein kinase C-alpha suppresses autophagy and induces neural tube defects via miR-129-2 in diabetic pregnancy
Authors: Wang Fang , Xu Cheng , Reece E. Albert , Li Xuezheng , Wu Yanqing , Harman Christopher , Yu Jingwen , Dong Daoyin , Wang Cheng , Yang Penghua , Zhong Jianxiang , Yang Peixin 
Published: May 2017

AbstractGene deletion-induced autophagy deficiency leads to neural tube defects (NTDs), similar to those in diabetic pregnancy. Here we report the key autophagy regulators modulated by diabetes in the murine developing neuroepithelium. Diabetes predominantly leads to exencephaly, induces neuroepithelial cell apoptosis and suppresses autophagy in the forebrain and midbrain of NTD embryos. Deleting thePrkcagene, which encodes PKCα, reverses diabetes-induced autophagy impairment, cellular organelle stress and apoptosis, leading to an NTD reduction. PKCα increases the expression of miR-129-2, which is a negative regulator of autophagy. miR-129-2 represses autophagy by directly targeting PGC-1α, a positive regulator for mitochondrial function, which is disturbed by maternal diabetes. PGC-1α supports neurulation by stimulating autophagy in neuroepithelial cells. These findings identify two negative autophagy regulators, PKCα and miR-129-2, which mediate the teratogenicity of hyperglycaemia leading to NTDs. We also reveal a function for PGC-1α in embryonic development through promoting autophagy and ameliorating hyperglycaemia-induced NTDs.
Menin enhances c-Myc-mediated transcription to promote cancer progression
Authors: Wu Gongwei , Yuan Mengqiu , Shen Shengqi , Ma Xiaoyu , Fang Jingwen , Zhu Lianbang , Sun Linchong , Liu Zhaoji , He Xiaoping , Huang De , Li Tingting , Li Chenchen , Wu Jun , Hu Xin , Li Zhaoyong , Song Libing , Qu Kun , Zhang Huafeng , Gao Ping 
Published: May 2017

AbstractMenin is an enigmatic protein that displays unique ability to either suppress or promote tumorigenesis in a context-dependent manner. The role for Menin to promote oncogenic functions has been largely attributed to its essential role in forming the MLL methyltransferase complex, which mediates H3K4me3. Here, we identify an unexpected role of Menin in enhancing the transactivity of oncogene MYC in a way independent of H3K4me3 activity. Intriguingly, we find that Menin interacts directly with the TAD domain of MYC and co-localizes with MYC to E-Box to enhance the transcription of MYC target genes in a P-TEFb-dependent manner. We further demonstrate that, by transcriptionally promoting the expression of MYC target genes in cancer cells, Menin stimulates cell proliferation and cellular metabolism both in vitro and in vivo. Our results uncover a previously unappreciated mechanism by which Menin functions as an oncogenic regulatory factor that is critical for MYC-mediated gene transcription.
Exploring nonlinear topological states of matter with exciton-polaritons: Edge solitons in kagome lattice
Authors: Gulevich D. R. , Yudin D. , Skryabin D. V. , Iorsh I. V. , Shelykh I. A. 
Published: May 2017

AbstractMatter in nontrivial topological phase possesses unique properties, such as support of unidirectional edge modes on its interface. It is the existence of such modes which is responsible for the wonderful properties of a topological insulator – material which is insulating in the bulk but conducting on its surface, along with many of its recently proposed photonic and polaritonic analogues. We show that exciton-polariton fluid in a nontrivial topological phase in kagome lattice, supports nonlinear excitations in the form of solitons built up from wavepackets of topological edge modes – topological edge solitons. Our theoretical and numerical results indicate the appearance of bright, dark and grey solitons dwelling in the vicinity of the boundary of a lattice strip. In a parabolic region of the dispersion the solitons can be described by envelope functions satisfying the nonlinear Schrödinger equation. Upon collision, multiple topological edge solitons emerge undistorted, which proves them to be true solitons as opposed to solitary waves for which such requirement is waived. Importantly, kagome lattice supports topological edge mode with zero group velocity unlike other types of truncated lattices. This gives a finer control over soliton velocity which can take both positive and negative values depending on the choice of forming it topological edge modes.
Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based Delivery
Authors: Thean D. , Ebo J. S. , Luxton T. , Lee Xue’Er Cheryl , Yuen T. Y. , Ferrer F. J. , Johannes C. W. , Lane D. P. , Brown C. J. 
Published: May 2017

AbstractLinear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53. A lead peptide was identified that activated intracellular p53 with negligible nonspecific cytotoxicity, however it still bound serum avidly and only showed a marginal improvement in cellular potency. These hurdles were overcome by successfully identifying a pyridinium-based cationic lipid formulation, which significantly improved the activity of the stapled peptide in a p53 reporter cell line, principally through increased vesicular escape. These studies underscore that stapled peptides, which are cell permeable and target specific, can be identified with rigorous experimental design and that these properties can be improved through use with lipid based formulations. This work should facilitate the clinical translation of stapled peptides.
Tumor suppressor menin is required for subunit-specific nAChR α5 transcription and nAChR-dependent presynaptic facilitation in cultured mouse hippocampal neurons
Authors: Getz Angela M. , Xu Fenglian , Visser Frank , Persson Roger , Syed Naweed I. 
Published: May 2017

AbstractIn the central nervous system (CNS), cholinergic transmission induces synaptic plasticity that is required for learning and memory. However, our understanding of the development and maintenance of cholinergic circuits is limited, as the factors regulating the expression and clustering of neuronal nicotinic acetylcholine receptors (nAChRs) remain poorly defined. Recent studies from our group have implicated calpain-dependent proteolytic fragments of menin, the product of the MEN1 tumor suppressor gene, in coordinating the transcription and synaptic clustering of nAChRs in invertebrate central neurons. Here, we sought to determine whether an analogous cholinergic mechanism underlies menin’s synaptogenic function in the vertebrate CNS. Our data from mouse primary hippocampal cultures demonstrate that menin and its calpain-dependent C-terminal fragment (C-menin) regulate the subunit-specific transcription and synaptic clustering of neuronal nAChRs, respectively. MEN1 knockdown decreased nAChR α5 subunit expression, the clustering of α7 subunit-containing nAChRs at glutamatergic presynaptic terminals, and nicotine-induced presynaptic facilitation. Moreover, the number and function of glutamatergic synapses was unaffected by MEN1 knockdown, indicating that the synaptogenic actions of menin are specific to cholinergic regulation. Taken together, our results suggest that the influence of menin on synapse formation and synaptic plasticity occur via modulation of nAChR channel subunit composition and functional clustering.
Leveraging multiple genomic data to prioritize disease-causing indels from exome sequencing data
Authors: Wu Mengmeng , Chen Ting , Jiang Rui 
Published: May 2017

AbstractThe emergence of exome sequencing in recent years has enabled rapid and cost-effective detection of genetic variants in coding regions and offers a great opportunity to combine sequencing experiments with subsequent computational analysis for dissecting genetic basis of human inherited diseases. However, this strategy, though successful in practice, still faces such challenges as limited sample size and substantial number or diversity of candidate variants. To overcome these obstacles, researchers have been concentrated in the development of advanced computational methods and have recently achieved great progress for analysing single nucleotide variant. Nevertheless, it still remains unclear on how to analyse indels, another type of genetic variant that accounts for substantial proportion of known disease-causing variants. In this paper, we proposed an integrative method to effectively identify disease-causing indels from exome sequencing data. Specifically, we put forward a statistical method to combine five functional prediction scores, four genic association scores and a genic intolerance score to produce an integrated p-value, which could then be used for prioritizing candidate indels. We performed extensive simulation studies and demonstrated that our method achieved high accuracy in uncovering disease-causing indels. Our software is available at http://bioinfo.au.tsinghua.edu.cn/jianglab/IndelPrioritizer/.
Indirect meta-analysis comparing clinical outcomes of total cervical disc replacements with fusions for cervical degenerative disc disease
Authors: Xu Bin , Ma Jian-xiong , Tian Jin-hui , Ge Long , Ma Xin-long 
Published: May 2017

AbstractAnterior cervical discectomy and fusion (ACDF) and total cervical disc replacement (TDR) are considered effective treatments for patients with cervical degenerative disc disease (CDDD). An indirect meta-analysis including 19 randomized controlled trials (5343 patients) was conducted to compare the clinical outcomes of ACDF with TDR. Primary outcomes including functional indicators (NDI [neck disability index] score, neurological success and patient satisfaction), secondary outcomes including surgical outcomes (operation time, blood loss and length of stay) and secondary surgical procedures (secondary surgery at an adjacent level, secondary surgery at the index level, secondary surgery at both levels, removal, reoperation, revision and supplemental fixation) were included in the study. TDR using the Bryan disc was associated with a greater improvement in NDI score than ACDF (MD = −5.574, 95% CrIs [credible intervals] −11.73–−0.219). For neurological success, the Bryan (odds ratio [OR] = 0.559, 95% CrIs 0.323–0.955) and Prestige (OR = 0.474, 95% CrIs 0.319–0.700) discs were superior to ACDF. However, no differences in the patient satisfaction rate were shown between TDR and ACDF. For patients with CDDD, ACDF using allograft and a plate is most effective for determining the surgical parameters. Moreover, TDR using the ProDisc-C, Mobi-C, Prestige and Bryan discs are good choices for improving functional outcomes and reducing secondary surgeries.