bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway
Authors: Sathyanarayanan Nitish , Cannone Giuseppe , Gakhar Lokesh , Katagihallimath Nainesh , Sowdhamini Ramanathan , Ramaswamy Subramanian , Vinothkumar Kutti R. 
Published: September 2019

AbstractSubstrate channeling is a mechanism for the internal transfer of hydrophobic, unstable or toxic intermediates from the active site of one enzyme to another. Such transfer has previously been described to be mediated by a hydrophobic tunnel, the use of electrostatic highways or pivoting and by conformational changes. The enzyme PaaZ is used by many bacteria to degrade environmental pollutants. PaaZ is a bifunctional enzyme that catalyzes the ring opening of oxepin-CoA and converts it to 3-oxo-5,6-dehydrosuberyl-CoA. Here we report the structures of PaaZ determined by electron cryomicroscopy with and without bound ligands. The structures reveal that three domain-swapped dimers of the enzyme form a trilobed structure. A combination of small-angle X-ray scattering (SAXS), computational studies, mutagenesis and microbial growth experiments suggests that the key intermediate is transferred from one active site to the other by a mechanism of electrostatic pivoting of the CoA moiety, mediated by a set of conserved positively charged residues.
Artificial colloidal liquid metacrystals by shearing microlithography
Authors: Jiang Yanqiu , Guo Fan , Xu Zhen , Gao Weiwei , Gao Chao 
Published: September 2019

AbstractMeta-periodicity beyond intrinsic atomic and molecular order, such as metacrystalline and quasicrystalline lattices, exists in solids, but is usually elusive in lyotropic liquid crystals for its energetic instability. The stable meta-periodicity in lyotropic liquid crystals in the absence of external stimuli remains unexplored, and how to achieve it keeps a great challenge. Here we create lyotropic liquid crystals with stable meta-periodicity in a free state, coined as liquid metacrystals, in colloidal systems by an invented shearing microlithography. The meta-periodicity is dynamically stabilized by the giant molecular size and strong excluded volume repulsion. Liquid metacrystals are designed to completely cover a library of symmetries, including five Bravais and six quasicrystalline lattices. Liquid metacrystal promises an extended form of liquid crystals with rich meta-periodicity and the shearing microlithography emerges as a facile technology to fabricate liquid meta-structures and metamaterials, enabling the digital design of structures and functionalities of liquid crystalline materials.
The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine
Authors: Korzelius Jerome , Azami Sina , Ronnen-Oron Tal , Koch Philipp , Baldauf Maik , Meier Elke , Rodriguez-Fernandez Imilce A. , Groth Marco , Sousa-Victor Pedro , Jasper Heinrich 
Published: September 2019

AbstractIn adult epithelial stem cell lineages, the precise differentiation of daughter cells is critical to maintain tissue homeostasis. Notch signaling controls the choice between absorptive and entero-endocrine cell differentiation in both the mammalian small intestine and the Drosophila midgut, yet how Notch promotes lineage restriction remains unclear. Here, we describe a role for the transcription factor Klumpfuss (Klu) in restricting the fate of enteroblasts (EBs) in the Drosophila intestine. Klu is induced in Notch-positive EBs and its activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) fate by repressing the action of the proneural gene Scute, which is essential for EE differentiation. Loss of Klu results in differentiation of EBs into EE cells. Our findings provide mechanistic insight into how lineage commitment in progenitor cell differentiation can be ensured downstream of initial specification cues.
In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene
Authors: Peter Cyril J. , Saito Atsushi , Hasegawa Yuto , Tanaka Yuya , Nagpal Mohika , Perez Gabriel , Alway Emily , Espeso-Gil Sergio , Fayyad Tariq , Ratner Chana , Dincer Aslihan , Gupta Achla , Devi Lakshmi , Pappas John G. , Lalonde François M. , Butman John A. , Han Joan C. , Akbarian Schahram , Kamiya Atsushi 
Published: September 2019

AbstractMany neuropsychiatric risk genes contribute to epigenetic regulation but little is known about specific chromatin-associated mechanisms governing the formation of neuronal connectivity. Here we show that transcallosal connectivity is critically dependent on C11orf46, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus. C11orf46 haploinsufficiency was associated with hypoplasia of the corpus callosum. C11orf46 knockdown disrupted transcallosal projections and was rescued by wild type C11orf46 but not the C11orf46R236H mutant associated with intellectual disability. Multiple genes encoding key regulators of axonal development, including Sema6a, were hyperexpressed in C11orf46-knockdown neurons. RNA-guided epigenetic editing of Sema6a gene promoters via a dCas9-SunTag system with C11orf46 binding normalized SEMA6A expression and rescued transcallosal dysconnectivity via repressive chromatin remodeling by the SETDB1 repressor complex. Our study demonstrates that interhemispheric communication is sensitive to locus-specific remodeling of neuronal chromatin, revealing the therapeutic potential for shaping the brain’s connectome via gene-targeted designer activators and repressor proteins.
Spontaneous whole-genome duplication restores fertility in interspecific hybrids
Authors: Charron Guillaume , Marsit Souhir , Hénault Mathieu , Martin Hélène , Landry Christian R. 
Published: September 2019

AbstractInterspecies hybrids often show some advantages over parents but also frequently suffer from reduced fertility, which can sometimes be overcome through sexual reproduction that sorts out genetic incompatibilities. Sex is however inefficient due to the low viability or fertility of hybrid offspring and thus limits their evolutionary potential. Mitotic cell division could be an alternative to fertility recovery in species such as fungi that can also propagate asexually. Here, to test this, we evolve in parallel and under relaxed selection more than 600 diploid yeast inter-specific hybrids that span from 100,000 to 15 M years of divergence. We find that hybrids can recover fertility spontaneously and rapidly through whole-genome duplication. These events occur in both hybrids between young and well-established species. Our results show that the instability of ploidy in hybrid is an accessible path to spontaneous fertility recovery.
CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain
Authors: Zhang Su-Bo , Lin Su-Yan , Liu Meng , Liu Cui-Cui , Ding Huan-Huan , Sun Yang , Ma Chao , Guo Rui-Xian , Lv You-You , Wu Shao-Ling , Xu Ting , Xin Wen-Jun 
Published: September 2019

AbstractCircular RNAs are non-coding RNAs, and are enriched in the CNS. Dorsal horn neurons of the spinal cord contribute to pain-like hypersensitivity after nerve injury in rodents. Here we show that spinal nerve ligation is associated with an increase in expression of circAnks1a in dorsal horn neurons, in both the cytoplasm and the nucleus. Downregulation of circAnks1a by siRNA attenuates pain-like behaviour induced by nerve injury. In the cytoplasm, we show that circAnks1a promotes the interaction between transcription factor YBX1 and transportin-1, thus facilitating the nucleus translocation of YBX1. In the nucleus, circAnks1a binds directly to the Vegfb promoter, increases YBX1 recruitment to the Vegfb promoter, thereby facilitating transcription. Furthermore, cytoplasmic circAnks1a acts as a miRNA sponge in miR-324-3p-mediated posttranscriptional regulation of VEGFB expression. The upregulation of VEGFB contributes to increased excitability of dorsal horn neurons and pain behaviour induced by nerve injury. We propose that circAnks1a and VEGFB are regulators of neuropathic pain.
Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions
Authors: Bornhorst Dorothee , Xia Peng , Nakajima Hiroyuki , Dingare Chaitanya , Herzog Wiebke , Lecaudey Virginie , Mochizuki Naoki , Heisenberg Carl-Philipp , Yelon Deborah , Abdelilah-Seyfried Salim 
Published: September 2019

AbstractIntra-organ communication guides morphogenetic processes that are essential for an organ to carry out complex physiological functions. In the heart, the growth of the myocardium is tightly coupled to that of the endocardium, a specialized endothelial tissue that lines its interior. Several molecular pathways have been implicated in the communication between these tissues including secreted factors, components of the extracellular matrix, or proteins involved in cell-cell communication. Yet, it is unknown how the growth of the endocardium is coordinated with that of the myocardium. Here, we show that an increased expansion of the myocardial atrial chamber volume generates higher junctional forces within endocardial cells. This leads to biomechanical signaling involving VE-cadherin, triggering nuclear localization of the Hippo pathway transcriptional regulator Yap1 and endocardial proliferation. Our work suggests that the growth of the endocardium results from myocardial chamber volume expansion and ends when the tension on the tissue is relaxed.
Conscious perception of natural images is constrained by category-related visual features
Authors: Lindh Daniel , Sligte Ilja G. , Assecondi Sara , Shapiro Kimron L. , Charest Ian 
Published: September 2019

AbstractConscious perception is crucial for adaptive behaviour yet access to consciousness varies for different types of objects. The visual system comprises regions with widely distributed category information and exemplar-level representations that cluster according to category. Does this categorical organisation in the brain provide insight into object-specific access to consciousness? We address this question using the Attentional Blink approach with visual objects as targets. We find large differences across categories in the attentional blink. We then employ activation patterns extracted from a deep convolutional neural network to reveal that these differences depend on mid- to high-level, rather than low-level, visual features. We further show that these visual features can be used to explain variance in performance across trials. Taken together, our results suggest that the specific organisation of the higher-tier visual system underlies important functions relevant for conscious perception of differing natural images.
Surface association sensitizes Pseudomonas aeruginosa to quorum sensing
Authors: Chuang Sara K. , Vrla Geoffrey D. , Fröhlich Kathrin S. , Gitai Zemer 
Published: September 2019

AbstractIn the pathogen Pseudomonas aeruginosa, LasR is a quorum sensing (QS) master regulator that senses the concentration of secreted autoinducers as a proxy for bacterial cell density. Counterintuitively, previous studies showed that saturating amounts of the LasR ligand, 3OC12-HSL, fail to induce the full LasR regulon in low-density liquid cultures. Here we demonstrate that surface association, which is necessary for many of the same group behaviors as QS, promotes stronger QS responses. We show that lasR is upregulated upon surface association, and that surface-associated bacteria induce LasR targets more strongly in response to autoinducer than planktonic cultures. This increased sensitivity may be due to surface-dependent lasR induction initiating a positive feedback loop through the small RNA, Lrs1. The increased sensitivity of surface-associated cells to QS is affected by the type IV pilus (TFP) retraction motors and the minor pilins. The coupling of physical surface responses and chemical QS responses could enable these bacteria to trigger community behaviors more robustly when they are more beneficial.
Performance analysis of 349-element adaptive optics unit for a coherent free space optical communication system
Authors: Yang Leqiang , Yao Kainan , Wang Jianli , Cao Jingtai , Lin Xudong , Liu Xinyue , Liu Wei , Gu Haijun 
Published: September 2019

AbstractAs a continuation of our previous work [Optics Express.25, 15229(2017)] in which we have verified the performance of a coherent free space optical communication (FSOC) system with a 97-element adaptive optics (AO) system, in this paper, we evaluated the performance improvement of the coherent FSOC system using a large-scale high-speed AO system with a 349-element continuous surface deformable mirror. The mixing efficiency (ME) and bit-error-rate (BER) under different Greenwood frequency (GF) were calculated as the performance metric of coherent FSOC system. The performance of FSOC system using such a large-scale AO system was quantitatively verified for the first time. The obtained results showed that the performance was obviously improved when a larger-scale high-speed AO system is employed in coherent FSOC system. This analysis result provides a performance verification for large-scale high-speed AO systems used in FSOC system which is beneficial for coherent FSOC system parameters design.
HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing
Authors: Forouzanfar F. , Ali S. , Wallet C. , De Rovere M. , Ducloy C. , El Mekdad H. , El Maassarani M. , Aït-Ammar A. , Van Assche J. , Boutant E. , Daouad F. , Margottin-Goguet F. , Moog C. , Van Lint C. , Schwartz C. , Rohr O. 
Published: September 2019

AbstractMammals have evolved many antiviral factors impacting different steps of the viral life cycle. Associated with chromatin-modifying enzymes, the cellular cofactor CTIP2 contributes to HIV-1 gene silencing in latently infected reservoirs that constitute the major block toward an HIV cure. We report, for the first time, that the virus has developed a strategy to overcome this major transcriptional block. Productive HIV-1 infection results in a Vpr-mediated depletion of CTIP2 in microglial cells and CD4+ T cells, two of the major viral reservoirs. Associated to the Cul4A-DDB1-DCAF1 ubiquitin ligase complex, Vpr promotes CTIP2 degradation via the proteasome pathway in the nuclei of target cells and notably at the latent HIV-1 promoter. Importantly, Vpr targets CTIP2 associated with heterochromatin-promoting enzymes dedicated to HIV-1 gene silencing. Thereby, Vpr reactivates HIV-1 expression in a microglial model of HIV-1 latency. Altogether our results suggest that HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing.
Epidemiology and Diversity of Rickettsiales Bacteria in Humans and Animals in Jiangsu and Jiangxi provinces, China
Authors: Lu Miao , Li Feng , Liao Yong , Shen Jin-Jin , Xu Jian-Min , Chen Yin-Zhong , Li Jian-Hua , Holmes Edward C. , Zhang Yong-Zhen 
Published: September 2019

AbstractDiseases caused by Rickettsiales bacteria are a global public health problem. To better understand the diversity and origins of Rickettsiales infection in humans and animals, we sampled 134 febrile patients, 173 rodents and 43 shrews, as well as 358 ticks, from two cities in Jiangsu and Jiangxi provinces, China. Our data revealed a relatively high prevalence of scrub typhus cases in both localities. In addition, both serological tests and genetic analysis identified three patients infected with Anaplasma bovis, Rickettsia monacensis, and Orientia tsutsugamushi bacteria. Molecular epidemiological investigation revealed the co-circulation of multiple species of Rickettsiales bacteria in small mammals and ticks in both provinces, potentially including novel bacterial species. In sum, these data demonstrate the ongoing importance of Rickettsiales infection in China and highlight the need for the regular surveillance of local arthropods, mammals and humans.
A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases
Authors: Choi Hyong Woo , Wang Lei , Powell Adrian F. , Strickler Susan R. , Wang Dekai , Dempsey D’Maris A. , Schroeder Frank C. , Klessig Daniel F. 
Published: September 2019

AbstractSalicylic acid (SA) is the major metabolite and active ingredient of aspirin; both compounds reduce pain, fever, and inflammation. Despite over a century of research, aspirin/SA’s mechanism(s) of action is still only partially understood. Here we report the results of a genome-wide, high-throughput screen to identify potential SA-binding proteins (SABPs) in human HEK293 cells. Following photo-affinity crosslinking to 4-azidoSA and immuno-selection with an anti-SA antibody, approximately 2,000 proteins were identified. Among these, 95 were enriched more than 10-fold. Pathway enrichment analysis with these 95 candidate SABPs (cSABPs) revealed possible involvement of SA in multiple biological pathways, including (i) glycolysis, (ii) cytoskeletal assembly and/or signaling, and (iii) NF-κB-mediated immune signaling. The two most enriched cSABPs, which corresponded to the glycolytic enzymes alpha-enolase (ENO1) and pyruvate kinase isozyme M2 (PKM2), were assessed for their ability to bind SA and SA’s more potent derivative amorfrutin B1 (amoB1). SA and amoB1 bound recombinant ENO1 and PKM2 at low millimolar and micromolar concentrations, respectively, and inhibited their enzymatic activities in vitro. Consistent with these results, low millimolar concentrations of SA suppressed glycolytic activity in HEK293 cells. To provide insights into how SA might affect various human diseases, a cSABP-human disorder/disease network map was also generated.
Detection of rock bridges by infrared thermal imaging and modeling
Authors: Guerin Antoine , Jaboyedoff Michel , Collins Brian D. , Derron Marc-Henri , Stock Greg M. , Matasci Battista , Boesiger Martin , Lefeuvre Caroline , Podladchikov Yury Y. 
Published: September 2019

AbstractCharacterization of rock discontinuities and rock bridges is required to define stability conditions of fractured rock masses in both natural and engineered environments. Although remote sensing methods for mapping discontinuities have improved in recent years, remote detection of intact rock bridges on cliff faces remains challenging, with their existence typically confirmed only after failure. In steep exfoliating cliffs, such as El Capitan in Yosemite Valley (California, USA), rockfalls mainly occur along cliff-parallel exfoliation joints, with rock bridges playing a key role in the stability of partially detached exfoliation sheets. We employed infrared thermal imaging (i.e., thermography) as a new means of detecting intact rock bridges prior to failure. An infrared thermal panorama of El Capitan revealed cold thermal signatures for the surfaces of two granitic exfoliation sheets, consistent with the expectation that air circulation cools the back of the partially detached sheets. However, we also noted small areas of warm thermal anomalies on these same sheets, even during periods of nocturnal rock cooling. Rock attachment via rock bridges is the likely cause for the warm anomalies in the thermal data. 2-D model simulations of the thermal behavior of one of the monitored sheets reproduce the observed anomalies and explain the temperature differences detected in the rock bridge area. Based on combined thermal and ground-based lidar imaging, and using geometric and rock fracture mechanics analysis, we are able to quantify the stability of both sheets. Our analysis demonstrates that thermography can remotely detect intact rock bridges and thereby greatly improve rockfall hazard assessment.
Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters
Authors: McLean Kyle Jarrod , Straimer Judith , Hopp Christine S. , Vega-Rodriguez Joel , Small-Saunders Jennifer L. , Kanatani Sachie , Tripathi Abhai , Mlambo Godfree , Dumoulin Peter C. , Harris Chantal T. , Tong Xinran , Shears Melanie J. , Ankarklev Johan , Kafsack Björn F. C. , Fidock David A. , Sinnis Photini 
Published: September 2019

AbstractMalaria parasites have a complex life cycle that includes specialized stages for transmission between their mosquito and human hosts. These stages are an understudied part of the lifecycle yet targeting them is an essential component of the effort to shrink the malaria map. The human parasite Plasmodium falciparum is responsible for the majority of deaths due to malaria. Our goal was to generate transgenic P. falciparum lines that could complete the lifecycle and produce fluorescent transmission stages for more in-depth and high-throughput studies. Using zinc-finger nuclease technology to engineer an integration site, we generated three transgenic P. falciparum lines in which tdtomato or gfp were stably integrated into the genome. Expression was driven by either stage-specific peg4 and csp promoters or the constitutive ef1a promoter. Phenotypic characterization of these lines demonstrates that they complete the life cycle with high infection rates and give rise to fluorescent mosquito stages. The transmission stages are sufficiently bright for intra-vital imaging, flow cytometry and scalable screening of chemical inhibitors and inhibitory antibodies.
Optimization of the energy for Breast monochromatic absorption X-ray Computed Tomography
Authors: Delogu Pasquale , Di Trapani Vittorio , Brombal Luca , Mettivier Giovanni , Taibi Angelo , Oliva Piernicola 
Published: September 2019

AbstractThe limits of mammography have led to an increasing interest on possible alternatives such as the breast Computed Tomography (bCT). The common goal of all X-ray imaging techniques is to achieve the optimal contrast resolution, measured through the Contrast to Noise Ratio (CNR), while minimizing the radiological risks, quantified by the dose. Both dose and CNR depend on the energy and the intensity of the X-rays employed for the specific imaging technique. Some attempts to determine an optimal energy for bCT have suggested the range 22 keV–34 keV, some others instead suggested the range 50 keV–60 keV depending on the parameters considered in the study. Recent experimental works, based on the use of monochromatic radiation and breast specimens, show that energies around 32 keV give better image quality respect to setups based on higher energies. In this paper we report a systematic study aiming at defining the range of energies that maximizes the CNR at fixed dose in bCT. The study evaluates several compositions and diameters of the breast and includes various reconstruction algorithms as well as different dose levels. The results show that a good compromise between CNR and dose is obtained using energies around 28 keV.
Assessment of the VDW interaction converting DMAPS from the thermal-motion form to the hydrogen-bonded form
Authors: Takahashi Masae , Matsui Hiroshi , Ikemoto Yuka , Suzuki Makoto , Morimoto Nobuyuki 
Published: September 2019

AbstractAssessment of van der Waals (VDW) interactions is fundamental to all of the central quest of structure that regulates the biological function. VDW interactions contributing to intramolecular weak hydrogen bonding are regarded as an important force to regulate the thermal stimuli-sensitive function of sulfobetaine methacrylate, DMAPS. We present here the conversion from the thermal-motion form at room temperature to the weak-hydrogen-bonded form against thermal motion as a terahertz spectral change with a definite isosbestic point from an absorption peak of one form to the other. Vibrational absorptions are used as a probe for assessing VDW interactions in conjunction with highly reliable and well-established density functional theory (DFT) calculations for analysis. Complicated spectral features and uncertain conformations of DMAPS in the amorphous state are clearly resolved under the polarizable continuum model and the dispersion correction for the pure DFT calculations.