bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Hearing 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

Murine 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

The 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

The 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

Inelastic 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

The 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

Human 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

Genome-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

The 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

When 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

In 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

Small 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

Natural 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

Orchid 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

Multiple 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

Colloidal 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.
Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1
Authors: Sankar Savita , Yellajoshyula Dhananjay , Zhang Bo , Teets Bryan , Rockweiler Nicole , Kroll Kristen L.
Published: November 2016

Neural cell fate acquisition is mediated by transcription factors expressed in nascent neuroectoderm, including Geminin and members of the Zic transcription factor family. However, regulatory networks through which this occurs are not well defined. Here, we identified Geminin-associated chromatin locations in embryonic stem cells and Geminin- and Zic1-associated locations during neural fate acquisition at a genome-wide level. We determined how Geminin deficiency affected histone acetylation at gene promoters during this process. We integrated these data to demonstrate that Geminin associates with and promotes histone acetylation at neurodevelopmental genes, while Geminin and Zic1 bind a shared gene subset. Geminin- and Zic1-associated genes exhibit embryonic nervous system-enriched expression and encode other regulators of neural development. Both Geminin and Zic1-associated peaks are enriched for Zic1 consensus binding motifs, while Zic1-bound peaks are also enriched for Sox3 motifs, suggesting co-regulatory potential. Accordingly, we found that Geminin and Zic1 could cooperatively activate the expression of several shared targets encoding transcription factors that control neurogenesis, neural plate patterning, and neuronal differentiation. We used these data to construct gene regulatory networks underlying neural fate acquisition. Establishment of this molecular program in nascent neuroectoderm directly links early neural cell fate acquisition with regulatory control of later neurodevelopment.
Exercise training attenuates renovascular hypertension partly via RAS- ROS- glutamate pathway in the hypothalamic paraventricular nucleus
Authors: Zhang Yan , Yu Xiao-Jing , Chen Wen-Sheng , Gao Hong-Li , Liu Kai-Li , Shi Xiao-Lian , Fan Xiao-Yan , Jia Lin-Lin , Cui Wei , Zhu Guo-Qing , Liu Jin-Jun , Kang Yu-Ming
Published: November 2016

Exercise training (ExT) has been reported to benefit hypertension; however, the exact mechanisms involved are unclear. We hypothesized that ExT attenuates hypertension, in part, through the renin-angiotensin system (RAS), reactive oxygen species (ROS), and glutamate in the paraventricular nucleus (PVN). Two-kidney, one-clip (2K1C) renovascular hypertensive rats were assigned to sedentary (Sed) or treadmill running groups for eight weeks. Dizocilpine (MK801), a glutamate receptor blocker, or losartan (Los), an angiotensin II type1 receptor (AT1-R) blocker, were microinjected into the PVN at the end of the experiment. We found that 2K1C rats had higher mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These rats also had excessive oxidative stress and overactivated RAS in PVN. Eight weeks of ExT significantly decreased MAP and RSNA in 2K1C hypertensive rats. ExT inhibited angiotensin-converting enzyme (ACE), AT1-R, and glutamate in the PVN, and angiotensin II (ANG II) in the plasma. Moreover, ExT attenuated ROS by augmenting copper/zinc superoxide dismutase (Cu/Zn-SOD) and decreasing p47phox and gp91phox in the PVN. MK801or Los significantly decreased blood pressure in rats. Together, these findings suggest that the beneficial effects of ExT on renovascular hypertension may be, in part, through the RAS-ROS-glutamate pathway in the PVN.
Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals Promotes HIV-Induced IFN-α Production
Authors: Lum Thomas , Green Jon A.
Published: November 2016

A majority of adults without HIV infection and with a low risk of HIV-exposure have plasma IgG antibodies that enhance the rate and magnitude of HIV-induced interferon alpha (IFN-α) production. Fc-dependent IgG-HIV complexes induce IFN-α rapidly and in high titers in response to HIV concentrations that are too low to otherwise stimulate an effective IFN-α response. IFN-α promoting antibody (IPA) counters HIV-specific inhibition of IFN-α production, and compensates for the inherent delay in IFN-α production common to HIV infection and other viruses. Naturally occurring IPA has the potential to initiate a potent IFN-α response early in the course of HIV mucosal invasion in time to terminate infection prior to the creation of a pool of persistently infected cells. The current study adds IPA as a mediator of an Fc-dependent antiviral state capable of preventing HIV infection.
In-situ restoration of one-stage partial nitritation-anammox process deteriorated by nitrate build-up via elevated substrate levels
Authors: Wang Xiaolong , Gao Dawen
Published: November 2016

The one-stage partial nitritation and anammox process (PN/A) has been a promising microbial process to remove ammonia from wastewater especially with low carbon/nitrogen ratio. The main breakdown was the deterioration caused by overgrowth of nitrite oxidizing bacteria (NOB) resulting effluent nitrate build-up in the PN/A process. This study presented an in-situ restoring strategy for suppressing NOB activity in a one-stage granular PN/A system deteriorated over 2 months, using elevated concentrations of substrates (ammonia and nitrite) under limited dissolved oxygen level. The results showed that the NOB activity was successfully suppressed after 56 days of restoration, and finally the ratio of produced nitrate/consumed ammonium was reduced from 36.8% to 7%. On day 66 the nitrogen removal rate obtained as 1.2 kg N/(m3·d). The high FA level (5–40 mg/L) and low dissolved oxygen (<0.13 mg/L) were responsible for NOB suppression. From quantitative PCR (qPCR) analysis, after this restoration, anammox bacteria had a widely growth, and AOB stay stable, but Nitrospira increase and Nitrobacter declined. High amount of NOB was still persistent in the granules, which was not easy to wash-out and threaten the deammonification performance.
Bandicoot fossils and DNA elucidate lineage antiquity amongst xeric-adapted Australasian marsupials
Authors: Kear Benjamin P. , Aplin Ken P. , Westerman Michael
Published: November 2016

Bandicoots (Peramelemorphia) are a unique order of Australasian marsupials whose sparse fossil record has been used as prima facie evidence for climate change coincident faunal turnover. In particular, the hypothesized replacement of ancient rainforest-dwelling extinct lineages by antecedents of xeric-tolerant extant taxa during the late Miocene (~10 Ma) has been advocated as a broader pattern evident amongst other marsupial clades. Problematically, however, this is in persistent conflict with DNA phylogenies. We therefore determine the pattern and timing of bandicoot evolution using the first combined morphological + DNA sequence dataset of Peramelemorphia. In addition, we document a remarkably archaic new fossil peramelemorphian taxon that inhabited a latest Quaternary mosaic savannah-riparian forest ecosystem on the Aru Islands of Eastern Indonesia. Our phylogenetic analyses reveal that unsuspected dental homoplasy and the detrimental effects of missing data collectively obscure stem bandicoot relationships. Nevertheless, recalibrated molecular clocks and multiple ancestral area optimizations unanimously infer an early diversification of modern xeric-adapted forms. These probably originated during the late Palaeogene (30–40 Ma) alongside progenitors of other desert marsupials, and thus occupied seasonally dry heterogenous habitats long before the onset of late Neogene aridity.
SCOUT: simultaneous time segmentation and community detection in dynamic networks
Authors: Hulovatyy Yuriy , Milenković Tijana
Published: November 2016

Many evolving complex real-world systems can be modeled via dynamic networks. An important problem in dynamic network research is community detection, which finds groups of topologically related nodes. Typically, this problem is approached by assuming either that each time point has a distinct community organization or that all time points share a single community organization. The reality likely lies between these two extremes. To find the compromise, we consider community detection in the context of the problem of segment detection, which identifies contiguous time periods with consistent network structure. Consequently, we formulate a combined problem of segment community detection (SCD), which simultaneously partitions the network into contiguous time segments with consistent community organization and finds this community organization for each segment. To solve SCD, we introduce SCOUT, an optimization framework that explicitly considers both segmentation quality and partition quality. SCOUT addresses limitations of existing methods that can be adapted to solve SCD, which consider only one of segmentation quality or partition quality. In a thorough evaluation, SCOUT outperforms the existing methods in terms of both accuracy and computational complexity. We apply SCOUT to biological network data to study human aging.
Helicity within the vortex filament model
Authors: Hänninen R. , Hietala N. , Salman H.
Published: November 2016

Kinetic helicity is one of the invariants of the Euler equations that is associated with the topology of vortex lines within the fluid. In superfluids, the vorticity is concentrated along vortex filaments. In this setting, helicity would be expected to acquire its simplest form. However, the lack of a core structure for vortex filaments appears to result in a helicity that does not retain its key attribute as a quadratic invariant. By defining a spanwise vector to the vortex through the use of a Seifert framing, we are able to introduce twist and henceforth recover the key properties of helicity. We present several examples for calculating internal twist to illustrate why the centreline helicity alone will lead to ambiguous results if a twist contribution is not introduced. Our choice of the spanwise vector can be expressed in terms of the tangential component of velocity along the filament. Since the tangential velocity does not alter the configuration of the vortex at later times, we are able to recover a similar equation for the internal twist angle to that of classical vortex tubes. Our results allow us to explain how a quasi-classical limit of helicity emerges from helicity considerations for individual superfluid vortex filaments.
CHFR negatively regulates SIRT1 activity upon oxidative stress
Authors: Kim Myungjin , Kwon Young Eun , Song Jae Oh , Bae Sung Jun , Seol Jae Hong
Published: November 2016

SIRT1, the NAD+-dependent protein deacetylase, controls cell-cycle progression and apoptosis by suppressing p53 tumour suppressor. Although SIRT1 is known to be phosphorylated by JNK1 upon oxidative stress and subsequently down-regulated, it still remains elusive how SIRT1 stability and activity are controlled. Here, we have unveiled that CHFR functions as an E3 Ub-ligase of SIRT1, responsible for its proteasomal degradation under oxidative stress conditions. CHFR interacts with and destabilizes SIRT1 by ubiquitylation and subsequent proteolysis. Such CHFR-mediated SIRT1 inhibition leads to the increase of p53 acetylation and its target gene transcription. Notably, CHFR facilitates SIRT1 destabilization when SIRT1 is phosphorylated by JNK1 upon oxidative stress, followed by prominent apoptotic cell death. Meanwhile, JNK inhibitor prevents SIRT1 phosphorylation, leading to elevated SIRT1 protein levels even in the presence of H2O2. Taken together, our results indicate that CHFR plays a crucial role in the cellular stress response pathway by controlling the stability and function of SIRT1.
Construction of a Miniaturized Chromatic Acclimation Sensor from Cyanobacteria with Reversed Response to a Light Signal
Authors: Nakajima Mitsuharu , Ferri Stefano , Rögner Matthias , Sode Koji
Published: November 2016

Cyanobacteria harbor unique photoreceptors, designated as cyanobacteriochromes (CBCRs). In this study, we attempted to engineer the chromatic acclimation sensor CcaS, a CBCR derived from the cyanobacterium Synechocystis sp. PCC 6803. The wild-type CcaS induces gene expression under green light illumination and represses it under red light illumination. We focused on the domain structure of CcaS, which consists of an N-terminal transmembrane helix; a GAF domain, which serves as the sensor domain; a linker region (L1); two PAS domains; a second linker region (L2); and a C-terminal histidine kinase (HK) domain. Truncated versions of the photoreceptor were constructed by removing the L1 linker region and the two PAS domains, and fusing the GAF and HK domains with a truncated linker region. Thus constructed “miniaturized CcaSs” were grouped into four distinct categories according to their responses toward green and red light illumination, with some showing improved gene regulation compared to the wild type. Remarkably, one of the miniaturized CcaSs induced gene expression under red light and repressed it under green light, a reversed response to the light signal compared to wild type CcaS. These characteristics of engineered photoreceptors were discussed by analyzing the CcaS structural model.
Ultra-wideband filtering of spoof surface plasmon polaritons using deep subwavelength planar structures
Authors: Hu Ming Zhe , Zhang Hao Chi , Yin Jia Yuan , Ding Zhao , Liu Jun Feng , Tang Wen Xuan , Cui Tie Jun
Published: November 2016

Novel ultra-wideband filtering of spoof surface plasmon polaritons (SPPs) is proposed in the microwave frequency using deep subwavelength planar structures printed on thin and flexible dielectric substrate. The proposed planar SPPs waveguide is composed of two mirror-oriented metallic corrugated strips, which are further decorated with parallel-arranged slots in the main corrugated strips. This compound structure provides deep subwavelength field confinement as well as flexible parameters when employed as a plasmonic waveguide, which is potential to construct miniaturization. Using momentum and impedance matching technology, we achieve a smooth conversion between the proposed SPPs waveguide and the conventional transmission line. To verify the validity of the design, we fabricate a spoof SPPs filter, and the measured results illustrate excellent performance, in which the reflection coefficient is less than −10 dB within the −3 dB passband from 1.21 GHz to 7.21 GHz with the smallest insertion loss of 1.23 dB at 2.21 GHz, having very good agreements with numerical simulations. The ultra-wideband filter with low insertion loss and high transmission efficiency possesses great potential in modern communication systems.
Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging
Authors: Swales John G. , Strittmatter Nicole , Tucker James W. , Clench Malcolm R. , Webborn Peter J. H. , Goodwin Richard J. A.
Published: November 2016

Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.
Immune signatures of protective spleen memory CD8 T cells
Authors: Brinza Lilia , Djebali Sophia , Tomkowiak Martine , Mafille Julien , Loiseau Céline , Jouve Pierre-Emmanuel , de Bernard Simon , Buffat Laurent , Lina Bruno , Ottmann Michèle , Rosa-Calatrava Manuel , Schicklin Stéphane , Bonnefoy Nathalie , Lauvau Grégoire , Grau Morgan , Wencker Mélanie , Arpin Christophe , Walzer Thierry , Leverrier Yann , Marvel Jacqueline
Published: November 2016

Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.
Electrical Switching in Semiconductor-Metal Self-Assembled VO2 Disordered Metamaterial Coatings
Authors: Kumar Sunil , Maury Francis , Bahlawane Naoufal
Published: November 2016

As a strongly correlated metal oxide, VO2 inspires several highly technological applications. The challenging reliable wafer-scale synthesis of high quality polycrystalline VO2 coatings is demonstrated on 4” Si taking advantage of the oxidative sintering of chemically vapor deposited VO2 films. This approach results in films with a semiconductor-metal transition (SMT) quality approaching that of the epitaxial counterpart. SMT occurs with an abrupt electrical resistivity change exceeding three orders of magnitude with a narrow hysteresis width. Spatially resolved infrared and Raman analyses evidence the self-assembly of VO2 disordered metamaterial, compresing monoclinic (M1 and M2) and rutile (R) domains, at the transition temperature region. The M2 mediation of the M1-R transition is spatially confined and related to the localized strain-stabilization of the M2 phase. The presence of the M2 phase is supposed to play a role as a minor semiconducting phase far above the SMT temperature. In terms of application, we show that the VO2 disordered self-assembly of M and R phases is highly stable and can be thermally triggered with high precision using short heating or cooling pulses with adjusted strengths. Such a control enables an accurate and tunable thermal control of the electrical switching.
Structural and functional probing of PorZ, an essential bacterial surface component of the type-IX secretion system of human oral-microbiomic Porphyromonas gingivalis.
Authors: Lasica Anna M. , Goulas Theodoros , Mizgalska Danuta , Zhou Xiaoyan , de Diego Iñaki , Ksiazek Mirosław , Madej Mariusz , Guo Yonghua , Guevara Tibisay , Nowak Magdalena , Potempa Barbara , Goel Apoorv , Sztukowska Maryta , Prabhakar Apurva T. , Bzowska Monika , Widziolek Magdalena , Thøgersen Ida B. , Enghild Jan J. , Simonian Mary , Kulczyk Arkadiusz W. , Nguyen Ky-Anh , Potempa Jan , Gomis-Rüth F. Xavier
Published: November 2016

Porphyromonas gingivalis is a member of the human oral microbiome abundant in dysbiosis and implicated in the pathogenesis of periodontal (gum) disease. It employs a newly described type-IX secretion system (T9SS) for secretion of virulence factors. Cargo proteins destined for secretion through T9SS carry a recognition signal in the conserved C-terminal domain (CTD), which is removed by sortase PorU during translocation. Here, we identified a novel component of T9SS, PorZ, which is essential for surface exposure of PorU and posttranslational modification of T9SS cargo proteins. These include maturation of enzyme precursors, CTD removal and attachment of anionic lipopolysaccharide for anchorage in the outer membrane. The crystal structure of PorZ revealed two β-propeller domains and a C-terminal β-sandwich domain, which conforms to the canonical CTD architecture. We further documented that PorZ is itself transported to the cell surface via T9SS as a full-length protein with its CTD intact, independently of the presence or activity of PorU. Taken together, our results shed light on the architecture and possible function of a novel component of the T9SS. Knowledge of how T9SS operates will contribute to our understanding of protein secretion as part of host-microbiome interactions by dysbiotic members of the human oral cavity.
Two novel viruses associated with the Apis mellifera pathogenic mite Varroa destructor
Authors: Levin Sofia , Sela Noa , Chejanovsky Nor
Published: November 2016

Varroa destructor infestation of Apis mellifera colonies carries and/or promotes replication of honey bee viruses like the Deformed wing virus, the Varroa destructor virus-1, the Acute bee paralysis virus, the Israeli acute bee paralysis virus and the Kashmir bee virus that have been well described and characterized; but viruses exclusively associated with Varroa were not found. To look for viruses that may associate with- or infect V. destructor we performed deep sequencing (RNA-seq) of RNA extracted from honey bees and mites in Varroa-infested untreated colonies. Comparative bioinformatic analysis of the two separate contig-assemblies generated from the sequences’ reads annotated using Blastx enabled identification of new viruses unique to Varroa and absent in A. mellifera: an Iflavirus and a virus with homology to Ixodes scapularis associated virus 2, that we named Varroa destructor virus 2 (VDV-2) and 3(VDV-3), respectively. We validated these findings sequencing the mite- and honey bee-viromes and in separate mites and honey bees randomly sampled. The complete genomes of VDV-2 and VDV-3 bear 9576 nucleotides and 4202 nucleotides, respectively. Phylogenetic analysis of VDV-3 suggests that it belongs to a new group of viruses. Our results open venues for investigating the pathogenicity of these V. destructor viruses.
The Warburg Effect Mediator Pyruvate Kinase M2 Expression and Regulation in the Retina
Authors: Rajala Raju V. S. , Rajala Ammaji , Kooker Christopher , Wang Yuhong , Anderson Robert E.
Published: November 2016

The tumor form of pyruvate kinase M2 (PKM2) undergoes tyrosine phosphorylation and gives rise to the Warburg effect. The Warburg effect defines a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose, even in the presence of oxygen. Retinal photoreceptors are highly metabolic and their energy consumption is equivalent to that of a multiplying tumor cell. In the present study, we found that PKM2 is the predominant isoform in both rod- and cone-dominant retina, and that it undergoes a light-dependent tyrosine phosphorylation. We also discovered that PKM2 phosphorylation is signaled through photobleaching of rhodopsin. Our findings suggest that phosphoinositide 3-kinase activation promotes PKM2 phosphorylation. Light and tyrosine phosphorylation appear to regulate PKM2 to provide a metabolic advantage to photoreceptor cells, thereby promoting cell survival.
Acceleration toward polarization singularity inspired by relativistic E×B drift
Authors: Yu Sunkyu , Piao Xianji , Park Namkyoo
Published: November 2016

The relativistic trajectory of a charged particle driven by the Lorentz force is different from the classical one, by velocity-dependent relativistic acceleration term. Here we show that the evolution of optical polarization states near the polarization singularity can be described in analogy to the relativistic dynamics of charged particles. A phase transition in parity-time symmetric potentials is then interpreted in terms of the competition between electric and magnetic ‘pseudo’-fields applied to polarization states. Based on this Lorentz pseudo-force representation, we reveal that zero Lorentz pseudo-force is the origin of recently reported strong polarization convergence to the singular state at the exceptional point. We also demonstrate the deterministic design of achiral and directional eigenstates at the exceptional point, allowing an anomalous linear polarizer which operates orthogonal to forward and backward waves. Our results linking parity-time symmetry and relativistic electrodynamics show that previous PT-symmetric potentials for the polarization singularity with a chiral eigenstate are the subset of optical potentials for the E×B “polarization” drift.
Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and macrophage cytokine production in response to the influenza virus
Authors: Uematsu Takayuki , Fujita Tomoko , Nakaoka Hiroki J. , Hara Toshiro , Kobayashi Noritada , Murakami Yoshinori , Seiki Motoharu , Sakamoto Takeharu
Published: November 2016

Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity. In macrophages, Mint3 depletion attenuated NF-κB signalling and the resultant cytokine/chemokine production in response to IFV infection by increasing IκBα and activating the cellular energy sensor AMPK, respectively. Thus, Mint3 might represent one of the likely therapeutic targets for the treatment of severe influenza pneumonia without affecting host anti-viral defence through suppressing macrophage cytokine/chemokine production.