bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutral sphingomyelinase (SMPD3) deficiency disrupts the Golgi secretory pathway and causes growth inhibition
Authors: Stoffel Wilhelm , Hammels Ina , Jenke Bitta , Binczek Erika , Schmidt‐Soltau Inga , Brodesser Susanne , Schauss Astrid , Etich Julia , Heilig Juliane , Zaucke Frank 
Published: November 2016

AbstractSystemic loss of neutral sphingomyelinase (SMPD3) in mice leads to a novel form of systemic, juvenile hypoplasia (dwarfism). SMPD3 deficiency in mainly two growth regulating cell types contributes to the phenotype, in chondrocytes of skeletal growth zones to skeletal malformation and chondrodysplasia, and in hypothalamic neurosecretory neurons to systemic hypothalamus–pituitary–somatotropic hypoplasia. The unbiased smpd3−/− mouse mutant and derived smpd3−/− primary chondrocytes were instrumental in defining the enigmatic role underlying the systemic and cell autonomous role of SMPD3 in the Golgi compartment. Here we describe the unprecedented role of SMPD3. SMPD3 deficiency disrupts homeostasis of sphingomyelin (SM), ceramide (Cer) and diacylglycerol (DAG) in the Golgi SMPD3-SMS1 (SM-synthase1) cycle. Cer and DAG, two fusogenic intermediates, modify the membrane lipid bilayer for the initiation of vesicle formation and transport. Dysproteostasis, unfolded protein response, endoplasmic reticulum stress and apoptosis perturb the Golgi secretory pathway in the smpd3−/− mouse. Secretion of extracellular matrix proteins is arrested in chondrocytes and causes skeletal malformation and chondrodysplasia. Similarly, retarded secretion of proteo-hormones in hypothalamic neurosecretory neurons leads to hypothalamus induced combined pituitary hormone deficiency. SMPD3 in the regulation of the protein vesicular secretory pathway may become a diagnostic target in the etiology of unknown forms of juvenile growth and developmental inhibition.
ER stress inhibitor attenuates hearing loss and hair cell death in Cdh23erl/erl mutant mice
Authors: Hu Juan , Li Bo , Apisa Luke , Yu Heping , Entenman Shami , Xu Min , Stepanyan Ruben , Guan Bo-Jhih , Müller Ulrich , Hatzoglou Maria , Zheng Qing Yin 
Published: November 2016

AbstractHearing loss is one of the most common sensory impairments in humans. Mouse mutant models helped us to better understand the mechanisms of hearing loss. Recently, we have discovered that the erlong (erl) mutation of the cadherin23 (Cdh23) gene leads to hearing loss due to hair cell apoptosis. In this study, we aimed to reveal the molecular pathways upstream to apoptosis in hair cells to exploit more effective therapeutics than an anti-apoptosis strategy. Our results suggest that endoplasmic reticulum (ER) stress is the earliest molecular event leading to the apoptosis of hair cells and hearing loss in erl mice. We also report that the ER stress inhibitor, Salubrinal (Sal), could delay the progression of hearing loss and preserve hair cells. Our results provide evidence that therapies targeting signaling pathways in ER stress development prevent hair cell apoptosis at an early stage and lead to better outcomes than those targeting downstream factors, such as tip-link degeneration and apoptosis.
MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury
Authors: Thomasova Dana , Ebrahim Martrez , Fleckinger Kristina , Li Moying , Molnar Jakob , Popper Bastian , Liapis Helen , Kotb Ahmed M , Siegerist Florian , Endlich Nicole , Anders Hans-Joachim 
Published: November 2016

AbstractMurine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency. In vivo experiments in the zebrafish model demonstrated that the tubulus cells of the larvae undergo cell death after the knockdown of mdm2. Doxycycline-induced deletion of MDM2 in tubular cell-specific MDM2-knockout mice Pax8rtTa-cre; MDM2f/f caused acute kidney injury with increased plasma creatinine and blood urea nitrogen and sharp decline of glomerular filtration rate. Histological analysis showed massive swelling of renal tubular cells and later their loss and extensive tubular dilation, markedly in proximal tubules. Ultrastructural changes of tubular epithelial cells included swelling of the cytoplasm and mitochondria with the loss of cristae and their transformation in the vacuoles. The pathological phenotype of the tubular cell-specific MDM2-knockout mouse model was completely rescued by co-deletion of p53. Tubular epithelium compensates only partially for the cell loss caused by MDM2 depletion by proliferation of surviving tubular cells, with incomplete MDM2 deletion, but rather mesenchymal healing occurs. We conclude that MDM2 is a non-redundant survival factor for proximal tubular cells by protecting them from spontaneous p53 overexpression-related cell death.
Optically switched magnetism in photovoltaic perovskite CH3NH3(Mn:Pb)I3
Authors: Náfrádi B. , Szirmai P. , Spina M. , Lee H. , Yazyev O. V. , Arakcheeva A. , Chernyshov D. , Gibert M. , Forró L. , Horváth E. 
Published: November 2016

AbstractThe demand for ever-increasing density of information storage and speed of manipulation boosts an intense search for new magnetic materials and novel ways of controlling the magnetic bit. Here, we report the synthesis of a ferromagnetic photovoltaic CH3NH3(Mn:Pb)I3 material in which the photo-excited electrons rapidly melt the local magnetic order through the Ruderman–Kittel–Kasuya–Yosida interactions without heating up the spin system. Our finding offers an alternative, very simple and efficient way of optical spin control, and opens an avenue for applications in low-power, light controlling magnetic devices.
Tunable inertia of chiral magnetic domain walls
Authors: Torrejon Jacob , Martinez Eduardo , Hayashi Masamitsu 
Published: November 2016

AbstractThe time it takes to accelerate an object from zero to a given velocity depends on the applied force and the environment. If the force ceases, it takes exactly the same time to completely decelerate. A magnetic domain wall is a topological object that has been observed to follow this behaviour. Here we show that acceleration and deceleration times of chiral Neel walls driven by current are different in a system with low damping and moderate Dzyaloshinskii–Moriya exchange constant. The time needed to accelerate a domain wall with current via the spin Hall torque is much faster than the time it needs to decelerate once the current is turned off. The deceleration time is defined by the Dzyaloshinskii–Moriya exchange constant whereas the acceleration time depends on the spin Hall torque, enabling tunable inertia of chiral domain walls. Such unique feature of chiral domain walls can be utilized to move and position domain walls with lower current, key to the development of storage class memory devices.
Electromagnon dispersion probed by inelastic X-ray scattering in LiCrO2
Authors: Tóth Sándor , Wehinger Björn , Rolfs Katharina , Birol Turan , Stuhr Uwe , Takatsu Hiroshi , Kimura Kenta , Kimura Tsuyoshi , Rønnow Henrik M. , Rüegg Christian 
Published: November 2016

AbstractInelastic X-ray scattering with meV energy resolution (IXS) is an ideal tool to measure collective excitations in solids and liquids. In non-resonant scattering condition, the cross-section is strongly dominated by lattice vibrations (phonons). However, it is possible to probe additional degrees of freedom such as magnetic fluctuations that are strongly coupled to the phonons. The IXS spectrum of the coupled system contains not only the phonon dispersion but also the so far undetected magnetic correlation function. Here we report the observation of strong magnon–phonon coupling in LiCrO2 that enables the measurement of magnetic correlations throughout the Brillouin zone via IXS. We find electromagnon excitations and electric dipole active two-magnon excitations in the magnetically ordered phase and heavily damped electromagnons in the paramagnetic phase of LiCrO2. We predict that several (frustrated) magnets with dominant direct exchange and non-collinear magnetism show surprisingly large IXS cross-section for magnons and multi-magnon processes.
A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery
Authors: Ren Kewei , Liu Ying , Wu Jie , Zhang Yue , Zhu Jing , Yang Min , Ju Huangxian 
Published: November 2016

AbstractThe efficient and precise delivery of siRNA to target cells is critical to successful gene therapy. While novel nanomaterials enhance delivery efficiency, it still remains challenging for precise gene delivery to overcome nonspecific adsorption and off-target effect. Here we design a dual lock-and-key system to perform cell-subtype-specific recognition and siRNA delivery. The siRNA is self-assembled in an oligonucleotide nano vehicle that is modified with a hairpin structure to act as both the ‘smart key’ and the delivery carrier. The auto-cleavable hairpin structure can be activated on site at target cell membrane by reacting with two aptamers as ‘dual locks’ sequentially, which leads to cell-subtype discrimination and precise siRNA delivery for high efficient gene silencing. The success of this strategy demonstrates the precise delivery of siRNA to specific target cells by controlling multiple parameters, thus paving the way for application of RNAi in accurate diagnosis and intervention.
An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes
Authors: Cho Yun Sung , Kim Hyunho , Kim Hak-Min , Jho Sungwoong , Jun JeHoon , Lee Yong Joo , Chae Kyun Shik , Kim Chang Geun , Kim Sangsoo , Eriksson Anders , Edwards Jeremy S. , Lee Semin , Kim Byung Chul , Manica Andrea , Oh Tae-Kwang , Church George M. , Bhak Jong 
Published: November 2016

AbstractHuman genomes are routinely compared against a universal reference. However, this strategy could miss population-specific and personal genomic variations, which may be detected more efficiently using an ethnically relevant or personal reference. Here we report a hybrid assembly of a Korean reference genome (KOREF) for constructing personal and ethnic references by combining sequencing and mapping methods. We also build its consensus variome reference, providing information on millions of variants from 40 additional ethnically homogeneous genomes from the Korean Personal Genome Project. We find that the ethnically relevant consensus reference can be beneficial for efficient variant detection. Systematic comparison of human assemblies shows the importance of assembly quality, suggesting the necessity of new technologies to comprehensively map ethnic and personal genomic structure variations. In the era of large-scale population genome projects, the leveraging of ethnicity-specific genome assemblies as well as the human reference genome will accelerate mapping all human genome diversity.
Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression
Authors: Li Ni , Johnson David C. , Weinhold Niels , Studd James B. , Orlando Giulia , Mirabella Fabio , Mitchell Jonathan S. , Meissner Tobias , Kaiser Martin , Goldschmidt Hartmut , Hemminki Kari , Morgan Gareth J. , Houlston Richard S. 
Published: November 2016

AbstractGenome-wide association studies have identified several risk loci for multiple myeloma (MM); however, the mechanisms by which they influence MM are unknown. Here by using genetic association data and functional characterization, we demonstrate that rs4487645 G>T, the most highly associated variant (P = 5.30 × 10−25), resides in an enhancer element 47 kb upstream of the transcription start site of c-Myc-interacting CDCA7L. The G-risk allele, associated with increased CDCA7L expression (P=1.95 × 10−36), increases IRF4 binding and the enhancer interacts with the CDCA7L promoter. We show that suppression of CDCA7L limits MM proliferation through apoptosis, and increased CDCA7L expression is associated with adverse patient survival. These findings implicate IRF4-mediated CDCA7L expression in MM biology and indicate how germline variation might confer susceptibility to MM.
Sexual display complexity varies non-linearly with age and predicts breeding status in greater flamingos
Authors: Perrot Charlotte , Béchet Arnaud , Hanzen Céline , Arnaud Antoine , Pradel Roger , Cézilly Frank 
Published: November 2016

AbstractThe long-lived greater flamingo (Phoenicopterus roseus) is famous for performing conspicuous group displays during which adults try to acquire a new mate each year with varying success. We examined variation in the sexual display complexity (SDC) of wild flamingos aged between 4 and 37 yrs. SDC was defined as the product of richness (the number of different display movements) and versatility (the number of transitions between movements) within a 5 min behavioral sequence. In both sexes, date in the pairing season had a linear and positive effect on SDC, whereas age had a quadratic effect, with SDC increasing until about age 20yrs, and declining afterwards. SDC better explained pairing patterns than age, and positively influenced the probability of becoming a breeder. Our results thus support the idea that SDC is an honest signal of individual quality and further suggest that senescence in display could be an overlooked aspect of reproductive decline in species with no or weak pair bonding.
Glass-Forming Tendency of Molecular Liquids and the Strength of the Intermolecular Attractions
Authors: Koperwas Kajetan , Adrjanowicz Karolina , Wojnarowska Zaneta , Jedrzejowska Agnieszka , Knapik Justyna , Paluch Marian 
Published: November 2016

AbstractWhen we cool down a liquid below the melting temperature, it can either crystallize or become supercooled, and then form a disordered solid called glass. Understanding what makes a liquid to crystallize readily in one case and form a stable glass in another is a fundamental problem in science and technology. Here we show that the crystallization/glass-forming tendencies of the molecular liquids might be correlated with the strength of the intermolecular attractions, as determined from the combined experimental and computer simulation studies. We use van der Waals bonded propylene carbonate and its less polar structural analog 3-methyl-cyclopentanone to show that the enhancement of the dipole-dipole forces brings about the better glass-forming ability of the sample when cooling from the melt. Our finding was rationalized by the mismatch between the optimal temperature range for the nucleation and crystal growth, as obtained for a modeled Lennard-Jones system with explicitly enhanced or weakened attractive part of the intermolecular 6–12 potential.
MR Vascular Fingerprinting in Stroke and Brain Tumors Models
Authors: Lemasson B. , Pannetier N. , Coquery N. , Boisserand Ligia S. B. , Collomb Nora , Schuff N. , Moseley M. , Zaharchuk G. , Barbier E. L. , Christen T. 
Published: November 2016

AbstractIn this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.
Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma
Authors: Nientiedt Malin , Deng Mario , Schmidt Doris , Perner Sven , Müller Stefan C. , Ellinger Jörg 
Published: November 2016

AbstractSmall non-coding RNAs (sncRNA; <200 nt) regulate various cellular processes and modify gene expression. Under nutritional, biological or physiochemical stress some mature sncRNAs (e.g. tRNAs) are cleaved into halves (30–50 nt) and smaller fragments (18–22 nt); the significance and functional role of these tRNA fragments is unknown, but their existence has been linked to carcinogenesis. We used small RNA sequencing to determine the expression of sncRNAs. Subsequently the findings were validated for miR-122-5p, miR-142-3p and 5'tRNA4-Val-AAC using qPCR. We identified differential expression of 132 miRNAs (upregulated: 61, downregulated: 71) and 32 tRNAs (upregulated: 13, downregulated: 19). Read length analysis showed that miRNAs mapped in the 20–24 nt fraction, whereas tRNA reads mapped in the 30–36 nt fraction instead the expected size of 73–95 nt thereby indicating cleavage of tRNAs. Overexpression of miR-122-5p and miR-142-3p as well as downregulation of 5'tRNA4-Val-AAC was validated in an independent cohort of 118 ccRCC and 74 normal renal tissues. Furthermore, staging and grading was inversely correlated with the 5'tRNA4-Val-AAC expression. Serum levels of miR-122-5p, miR-142-3p and 5'tRNA4-Val-AAC did not differ in ccRCC and control subjects. In conclusion, 5′ cleavage of tRNAs occurs in ccRCC, but the exact functional implication of tRNA-halve deregulation remains to be clarified.
Measles virus induces persistent infection by autoregulation of viral replication
Authors: Doi Tomomitsu , Kwon Hyun-Jeong , Honda Tomoyuki , Sato Hiroki , Yoneda Misako , Kai Chieko 
Published: November 2016

AbstractNatural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity.
Habitat-driven variation in mycorrhizal communities in the terrestrial orchid genus Dactylorhiza
Authors: Jacquemyn Hans , Waud Michael , Merckx Vincent S. F. T. , Brys Rein , Tyteca Daniel , Hedrén Mikael , Lievens Bart 
Published: November 2016

AbstractOrchid species are critically dependent on mycorrhizal fungi for completion of their life cycle, particularly during the early stages of their development when nutritional resources are scarce. As such, orchid mycorrhizal fungi play an important role in the population dynamics, abundance, and spatial distribution of orchid species. However, less is known about the ecology and distribution of orchid mycorrhizal fungi. In this study, we used 454 amplicon pyrosequencing to investigate ecological and geographic variation in mycorrhizal associations in fourteen species of the orchid genusDactylorhiza. More specifically, we tested the hypothesis that variation in orchid mycorrhizal communities resulted primarily from differences in habitat conditions where the species were growing. The results showed that all investigatedDactylorhizaspecies associated with a large number of fungal OTUs, the majority belonging to the Tulasnellaceae, Ceratobasidiaceae and Sebacinales. Mycorrhizal specificity was low, but significant variation in mycorrhizal community composition was observed between species inhabiting different ecological habitats. Although several fungi had a broad geographic distribution, Species Indicator Analysis revealed some fungi that were characteristic for specific habitats. Overall, these results indicate that orchid mycorrhizal fungi may have a broad geographic distribution, but that their occurrence is bounded by specific habitat conditions.
MathIOmica: An Integrative Platform for Dynamic Omics
Authors: Mias George I. , Yusufaly Tahir , Roushangar Raeuf , Brooks Lavida R. K. , Singh Vikas V. , Christou Christina 
Published: November 2016

AbstractMultiple omics data are rapidly becoming available, necessitating the use of new methods to integrate different technologies and interpret the results arising from multimodal assaying. The MathIOmica package forMathematicaprovides one of the first extensive introductions to the use of the Wolfram Language to tackle such problems in bioinformatics. The package particularly addresses the necessity to integrate multiple omics information arising from dynamic profiling in a personalized medicine approach. It provides multiple tools to facilitate bioinformatics analysis, including importing data, annotating datasets, tracking missing values, normalizing data, clustering and visualizing the classification of data, carrying out annotation and enumeration of ontology memberships and pathway analysis. We anticipate MathIOmica to not only help in the creation of new bioinformatics tools, but also in promoting interdisciplinary investigations, particularly from researchers in mathematical, physical science and engineering fields transitioning into genomics, bioinformatics and omics data integration.
Transition from glass- to gel-like states in clay at a liquid interface
Authors: Gholamipour-Shirazi A. , Carvalho M. S. , Huila M. F. G. , Araki K. , Dommersnes P. , Fossum J. O. 
Published: November 2016

AbstractColloidal clay in water suspensions are known to exhibit a multitude of bulk phases depending on initial colloidal concentration and ionic strength, and examples of this include repulsive Wigner colloidal glasses at low ionic strength and attractive gels at higher ionic strength due to screened electrostatic forces by the electrolyte. From confocal Raman microscopy combined with elasticity measurements, we infer that clay trapped at quasi two-dimensional interfaces between oil and water also exhibit confined glass-like or gel-like states. The results can be important for the preparation of particles stabilized colloidal emulsions or colloidal capsules, and a better understanding of this phenomenon may lead to new emulsion or encapsulation technologies.