bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time
Authors: Lee Bai-Yu , Clemens Daniel L. , Silva Aleidy , Dillon Barbara Jane , Masleša-Galić Saša , Nava Susana , Ding Xianting , Ho Chih-Ming , Horwitz Marcus A. 
Published: January 2017

AbstractThe current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis.
A swarm of autonomous miniature underwater robot drifters for exploring submesoscale ocean dynamics
Authors: Jaffe Jules S. , Franks Peter J. S. , Roberts Paul L. D. , Mirza Diba , Schurgers Curt , Kastner Ryan , Boch Adrien 
Published: January 2017

AbstractMeasuring the ever-changing 3-dimensional (3D) motions of the ocean requires simultaneous sampling at multiple locations. In particular, sampling the complex, nonlinear dynamics associated with submesoscales (<1–10 km) requires new technologies and approaches. Here we introduce the Mini-Autonomous Underwater Explorer (M-AUE), deployed as a swarm of 16 independent vehicles whose 3D trajectories are measured near-continuously, underwater. As the vehicles drift with the ambient flow or execute preprogrammed vertical behaviours, the simultaneous measurements at multiple, known locations resolve the details of the flow within the swarm. We describe the design, construction, control and underwater navigation of the M-AUE. A field programme in the coastal ocean using a swarm of these robots programmed with a depth-holding behaviour provides a unique test of a physical–biological interaction leading to plankton patch formation in internal waves. The performance of the M-AUE vehicles illustrates their novel capability for measuring submesoscale dynamics.
Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
Authors: Berghoff Stefan A. , Gerndt Nina , Winchenbach Jan , Stumpf Sina K. , Hosang Leon , Odoardi Francesca , Ruhwedel Torben , Böhler Carolin , Barrette Benoit , Stassart Ruth , Liebetanz David , Dibaj Payam , Möbius Wiebke , Edgar Julia M. , Saher Gesine 
Published: January 2017

AbstractMultiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.
Model dielectric function for 2D semiconductors including substrate screening
Authors: Trolle Mads L. , Pedersen Thomas G. , Véniard Valerie 
Published: January 2017

AbstractDielectric screening of excitons in 2D semiconductors is known to be a highly non-local effect, which in reciprocal space translates to a strong dependence on momentum transfer q. We present an analytical model dielectric function, including the full non-linear q-dependency, which may be used as an alternative to more numerically taxing ab initio screening functions. By verifying the good agreement between excitonic optical properties calculated using our model dielectric function, and those derived from ab initio methods, we demonstrate the versatility of this approach. Our test systems include: Monolayer hBN, monolayer MoS2, and the surface exciton of a 2 × 1 reconstructed Si(111) surface. Additionally, using our model, we easily take substrate screening effects into account. Hence, we include also a systematic study of the effects of substrate media on the excitonic optical properties of MoS2 and hBN.
Chemically-activatable alkyne-tagged probe for imaging microdomains in lipid bilayer membranes
Authors: Yamaguchi Satoshi , Matsushita Taku , Izuta Shin , Katada Sumika , Ura Manami , Ikeda Taro , Hayashi Gosuke , Suzuki Yuta , Kobayashi Koya , Tokunaga Kyoya , Ozeki Yasuyuki , Okamoto Akimitsu 
Published: January 2017

AbstractA chemically-activatable alkynyl steroid analogue probe has been synthesized for visualizing the lipid raft membrane domains by Raman microscopy. The Raman probe, in which ring A of its steroid backbone is replaced with an alkynyl group, was designed to enable activation of the alkyne signal through the Eschenmoser-Tanabe fragmentation reaction of the oxidized cholesterol precursor in lipid bilayer membranes. The alkynyl steroid analogue was observed to form liquid-ordered raft-like domains on a model giant-liposome system in a similar manner as cholesterol, and the large alkyne signal of the accumulated probe at 2120 cm−1 was mapped on the microdomains with a Raman microscope. The alkyne moiety of the probe was confirmed to be converted from the α,β-epoxy ketone group of its precursor by reaction with p-toluensulfonyl hydrazine under a mild condition. Through the reaction, the alkyne signal of the probe was activated on the lipid bilayer membrane of liposomes. Furthermore, the signal activation of the probe was also detected on living cells by stimulated Raman scattering microscopy. The ring-A-opened alkyne steroid analogue, thus, provides a first chemically-activatable Raman probe as a promising tool for potentially unravelling the intracellular formation and trafficking of cholesterol-rich microdomains.
Randomized controlled trial of the effect of phytosterols-enriched low-fat milk on lipid profile in Chinese
Authors: Cheung Ching-Lung , Ho Daniel Ka-Chun , Sing Chor-Wing , Tsoi Man-Fung , Cheng Vincent Ka-Fai , Lee Grace Koon-Yee , Ho Yuk-Nam , Cheung Bernard M. Y. 
Published: January 2017

AbstractPhytosterols found naturally in plants are known to reduce cholesterol absorption in the gut. The traditional southern Chinese diet typically contains many vegetables and not much meat, and there is high prevalence of lactose intolerance in Chinese; we therefore aimed to test if phytosterols-enriched milk is effective in lowering serum LDL-cholesterol in Chinese. Two hundred and twenty-one participants (41 men and 180 women; age 24–79) without cholesterol-lowering drugs or diabetes mellitus were randomized to daily intake of phytosterols-enriched low-fat milk which contained 1.5 g phytosterols per day (N = 110) or a conventional low-fat milk (N = 111) for three weeks. Fasting bloods were taken before and at the end of the study for the measurement of lipid and glucose profile. Physical examination was also performed. Comparing treatment with control, treatment group had significant decrease in serum LDL-cholesterol level (9.5 ± 2.0%; p < 0.0001). Phytosterols intake also decreased total cholesterol (P < 0.0001) and diastolic blood pressure (P = 0.01). Consumption of a phytosterols-enriched low-fat milk led to a significant fall in LDL-cholesterol, total cholesterol, and diastolic blood pressure in Chinese. This can be recommended as part of a healthy diet for people. (ClinicalTrials.gov identifier: NCT02541201; Date of registration: 26 Aug 2015).
Overlap Extension Barcoding for the Next Generation Sequencing and Genotyping of Plasmodium falciparum in Individual Patients in Western Kenya
Authors: Levitt Brandt , Obala Andrew , Langdon Scott , Corcoran David , O’Meara Wendy Prudhomme , Taylor Steve M. 
Published: January 2017

AbstractLarge-scale molecular epidemiologic studies of Plasmodium falciparum parasites have provided insights into parasite biology and transmission, can identify the spread of drug resistance, and are useful in assessing vaccine targets. The polyclonal nature infections in high transmission settings is problematic for traditional genotyping approaches. Next-generation sequencing (NGS) approaches to parasite genotyping allow sensitive detection of minority variants, disaggregation of complex parasite mixtures, and scalable processing of large samples sets. Therefore, we designed, validated, and applied to field parasites an approach that leverages sequencing of individually barcoded samples in a multiplex manner. We utilize variant barcodes, invariant linker sequences and modular template-specific primers to allow for the simultaneous generation of high-dimensional sequencing data of multiple gene targets. This modularity permits a cost-effective and reproducible way to query many genes at once. In mixtures of reference parasite genomes, we quantitatively detected unique haplotypes comprising as little as 2% of a polyclonal infection. We applied this genotyping approach to field-collected parasites collected in Western Kenya in order to simultaneously obtain parasites genotypes at three unlinked loci. In summary, we present a rapid, scalable, and flexible method for genotyping individual parasites that enables molecular epidemiologic studies of parasite evolution, population structure and transmission.
Comparative evaluation of rRNA depletion procedures for the improved analysis of bacterial biofilm and mixed pathogen culture transcriptomes
Authors: Petrova Olga E. , Garcia-Alcalde Fernando , Zampaloni Claudia , Sauer Karin 
Published: January 2017

AbstractGlobal transcriptomic analysis via RNA-seq is often hampered by the high abundance of ribosomal (r)RNA in bacterial cells. To remove rRNA and enrich coding sequences, subtractive hybridization procedures have become the approach of choice prior to RNA-seq, with their efficiency varying in a manner dependent on sample type and composition. Yet, despite an increasing number of RNA-seq studies, comparative evaluation of bacterial rRNA depletion methods has remained limited. Moreover, no such study has utilized RNA derived from bacterial biofilms, which have potentially higher rRNA:mRNA ratios and higher rRNA carryover during RNA-seq analysis. Presently, we evaluated the efficiency of three subtractive hybridization-based kits in depleting rRNA from samples derived from biofilm, as well as planktonic cells of the opportunistic human pathogen Pseudomonas aeruginosa. Our results indicated different rRNA removal efficiency for the three procedures, with the Ribo-Zero kit yielding the highest degree of rRNA depletion, which translated into enhanced enrichment of non-rRNA transcripts and increased depth of RNA-seq coverage. The results indicated that, in addition to improving RNA-seq sensitivity, efficient rRNA removal enhanced detection of low abundance transcripts via qPCR. Finally, we demonstrate that the Ribo-Zero kit also exhibited the highest efficiency when P. aeruginosa/Staphylococcus aureus co-culture RNA samples were tested.
Ependymal cell contribution to scar formation after spinal cord injury is minimal, local and dependent on direct ependymal injury
Authors: Ren Yilong , Ao Yan , O’Shea Timothy M. , Burda Joshua E. , Bernstein Alexander M. , Brumm Andrew J. , Muthusamy Nagendran , Ghashghaei H. Troy , Carmichael S. Thomas , Cheng Liming , Sofroniew Michael V. 
Published: January 2017

AbstractEpendyma have been proposed as adult neural stem cells that provide the majority of newly proliferated scar-forming astrocytes that protect tissue and function after spinal cord injury (SCI). This proposal was based on small, midline stab SCI. Here, we tested the generality of this proposal by using a genetic knock-in cell fate mapping strategy in different murine SCI models. After large crush injuries across the entire spinal cord, ependyma-derived progeny remained local, did not migrate and contributed few cells of any kind and less than 2%, if any, of the total newly proliferated and molecularly confirmed scar-forming astrocytes. Stab injuries that were near to but did not directly damage ependyma, contained no ependyma-derived cells. Our findings show that ependymal contribution of progeny after SCI is minimal, local and dependent on direct ependymal injury, indicating that ependyma are not a major source of endogenous neural stem cells or neuroprotective astrocytes after SCI.
Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells
Authors: Hocine Hocine R. , Costa Hicham El , Dam Noemie , Giustiniani Jerome , Palacios Itziar , Loiseau Pascale , Bensussan Armand , Borlado Luis R. , Charron Dominique , Suberbielle Caroline , Jabrane-Ferrat Nabila , Al-Daccak Reem 
Published: January 2017

AbstractAllogeneic human cardiac-derived stem/progenitor cells (hCPC) are currently under clinical investigation for cardiac repair. While cellular immune response against allogeneic hCPC could be part of their beneficial-paracrine effects, their humoral immune response remains largely unexplored. Donor-specific HLA antibodies (DSA-HLA-I/DSA-HLA-II), primary elements of antibody-mediated allograft injury, might present an unidentified risk to allogeneic hCPC therapy. Here we established that the binding strength of anti-HLA monoclonal antibodies delineates hCPC proneness to antibody-mediated injury. In vitro modeling of clinical setting demonstrated that specific DSA-HLA-I of high/intermediate binding strength are harmful for hCPC whereas DSA-HLA-II are benign. Furthermore, the Luminex-based solid-phase assays are suitable to predict the DSA-HLA risk to therapeutic hCPC. Our data indicate that screening patient sera for the presence of HLA antibodies is important to provide an immune-educated choice of allogeneic therapeutic cells, minimize the risk of precipitous elimination and promote the allogeneic reparative effects.
Hybrid fiber resonator employing LRSPP waveguide coupler for gyroscope
Authors: Qian Guang , Fu Xing-Chang , Zhang Li-Jiang , Tang Jie , Liu Yi-Ran , Zhang Xiao-Yang , Zhang Tong 
Published: January 2017

AbstractPolarization error and temperature noise are two main limits to the performance of resonant fiber optic gyroscope (RFOG). To overcome these limits, we demonstrated a hybrid resonator consisting of a polymer-based long-range surface plasmon polariton (LRSPP) waveguide coupler and a silica fiber. Single-polarization property of LRSPP waveguide and the offsetting of the opposite thermo-optical characteristics between the polymer-based LRSPP waveguide and the silica fiber can effectively inhibit both the polarization error and the temperature noise of RFOG. The measured resonance spectrum of the hybrid resonator shows the absence of polarization noise. The temperature dependence of wavelength shift (TDWS) of resonator dropped to about 2 pm/°C, or even to 0 pm/°C with optimal structure, which dramatically improves the temperature stability of gyroscope system. In addition, the hybrid resonator also shows tremendous application potential in rate-grade and tactical-grade gyroscopes.
Membrane Perturbation of ADP-insensitive Phosphoenzyme of Ca2+-ATPase Modifies Gathering of Transmembrane Helix M2 with Cytoplasmic Domains and Luminal Gating
Authors: Danko Stefania , Yamasaki Kazuo , Daiho Takashi , Suzuki Hiroshi 
Published: January 2017

AbstractCa2+ transport by sarcoplasmic reticulum Ca2+-ATPase involves ATP-dependent phosphorylation of a catalytic aspartic acid residue. The key process, luminal Ca2+ release occurs upon phosphoenzyme isomerization, abbreviated as E1PCa2 (reactive to ADP regenerating ATP and with two occluded Ca2+ at transport sites) → E2P (insensitive to ADP and after Ca2+ release). The isomerization involves gathering of cytoplasmic actuator and phosphorylation domains with second transmembrane helix (M2), and is epitomized by protection of a Leu119-proteinase K (prtK) cleavage site on M2. Ca2+ binding to the luminal transport sites of E2P, producing E2PCa2 before Ca2+-release exposes the prtK-site. Here we explore E2P structure to further elucidate luminal gating mechanism and effect of membrane perturbation. We find that ground state E2P becomes cleavable at Leu119 in a non-solubilizing concentration of detergent C12E8 at pH 7.4, indicating a shift towards a more E2PCa2-like state. Cleavage is accelerated by Mg2+ binding to luminal transport sites and blocked by their protonation at pH 6.0. Results indicate that possible disruption of phospholipid-protein interactions strongly favors an E2P species with looser head domain interactions at M2 and responsive to specific ligand binding at the transport sites, likely an early flexible intermediate in the development towards ground state E2P.
Insights into the Planktothrix genus: Genomic and metabolic comparison of benthic and planktic strains
Authors: Pancrace Claire , Barny Marie-Anne , Ueoka Reiko , Calteau Alexandra , Scalvenzi Thibault , Pédron Jacques , Barbe Valérie , Piel Joern , Humbert Jean-François , Gugger Muriel 
Published: January 2017

AbstractPlanktothrix is a dominant cyanobacterial genus forming toxic blooms in temperate freshwater ecosystems. We sequenced the genome of planktic and non planktic Planktothrix strains to better represent this genus diversity and life style at the genomic level. Benthic and biphasic strains are rooting the Planktothrix phylogenetic tree and widely expand the pangenome of this genus. We further investigated in silico the genetic potential dedicated to gas vesicles production, nitrogen fixation as well as natural product synthesis and conducted complementary experimental tests by cell culture, microscopy and mass spectrometry. Significant differences for the investigated features could be evidenced between strains of different life styles. The benthic Planktothrix strains showed unexpected characteristics such as buoyancy, nitrogen fixation capacity and unique natural product features. In comparison with Microcystis, another dominant toxic bloom-forming genus in freshwater ecosystem, different evolutionary strategies were highlighted notably as Planktothrix exhibits an overall greater genetic diversity but a smaller genomic plasticity than Microcystis. Our results are shedding light on Planktothrix evolution, phylogeny and physiology in the frame of their diverse life styles.
Design of Hierarchical Structures for Synchronized Deformations
Authors: Seifi Hamed , Javan Anooshe Rezaee , Ghaedizadeh Arash , Shen Jianhu , Xu Shanqing , Xie Yi Min 
Published: January 2017

AbstractIn this paper we propose a general method for creating a new type of hierarchical structures at any level in both 2D and 3D. A simple rule based on a rotate-and-mirror procedure is introduced to achieve multi-level hierarchies. These new hierarchical structures have remarkably few degrees of freedom compared to existing designs by other methods. More importantly, these structures exhibit synchronized motions during opening or closure, resulting in uniform and easily-controllable deformations. Furthermore, a simple analytical formula is found which can be used to avoid collision of units of the structure during the closing process. The novel design concept is verified by mathematical analyses, computational simulations and physical experiments.
Growth rate control of flagellar assembly in Escherichia coli strain RP437
Authors: Sim Martin , Koirala Santosh , Picton David , Strahl Henrik , Hoskisson Paul A. , Rao Christopher V. , Gillespie Colin S. , Aldridge Phillip D. 
Published: January 2017

AbstractThe flagellum is a rotary motor that enables bacteria to swim in liquids and swarm over surfaces. Numerous global regulators control flagellar assembly in response to cellular and environmental factors. Previous studies have also shown that flagellar assembly is affected by the growth-rate of the cell. However, a systematic study has not yet been described under controlled growth conditions. Here, we investigated the effect of growth rate on flagellar assembly inEscherichia coliusing steady-state chemostat cultures where we could precisely control the cell growth-rate. Our results demonstrate that flagellar abundance correlates with growth rate, where faster growing cells produce more flagella. They also demonstrate that this growth-rate dependent control occurs through the expression of the flagellar master regulator, FlhD4C2. Collectively, our results demonstrate that motility is intimately coupled to the growth-rate of the cell.
Characterization of novel Acidobacteria exopolysaccharides with potential industrial and ecological applications
Authors: Kielak Anna M. , Castellane Tereza C. L. , Campanharo Joao C. , Colnago Luiz A. , Costa Ohana Y. A. , Corradi da Silva Maria L. , van Veen Johannes A. , Lemos Eliana G. M. , Kuramae Eiko E. 
Published: January 2017

AbstractAcidobacteria have been described as one of the most abundant and ubiquitous bacterial phyla in soil. However, factors contributing to this ecological success are not well elucidated mainly due to difficulties in bacterial isolation. Acidobacteria may be able to survive for long periods in soil due to protection provided by secreted extracellular polymeric substances that include exopolysaccharides (EPSs). Here we present the first study to characterize EPSs derived from two strains of Acidobacteria from subdivision 1 belonging to Granulicella sp. EPS are unique heteropolysaccharides containing mannose, glucose, galactose and xylose as major components, and are modified with carboxyl and methoxyl functional groups that we characterized by Fourier transform infrared (FTIR) spectroscopy. Both EPS compounds we identified can efficiently emulsify various oils (sunflower seed, diesel, and liquid paraffin) and hydrocarbons (toluene and hexane). Moreover, the emulsions are more thermostable over time than those of commercialized xanthan. Acidobacterial EPS can now be explored as a source of biopolymers that may be attractive and valuable for industrial applications due to their natural origin, sustainability, biodegradability and low toxicity.