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1.
J Virol ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376620

RESUMO

Virus entry into host cells is a complex process that is largely regulated by the access to specific cellular receptors. Human adenoviruses (HAdVs) and many other viruses use cell adhesion molecules such as the Coxsackievirus and adenovirus receptor (CAR) for attachment to and entry into target cells. These molecules are rarely expressed on the apical side of polarized epithelial cells, which raise the question how adenovirus - and other viruses that engage cell adhesion molecules - enter polarized cells from the apical side to initiate infection. We have previously shown that species C HAdVs utilize lactoferrin - a common innate immune component secreted to respiratory mucosa for infection via unknown mechanisms. Using a series of biochemical, cellular, and molecular biology approaches, we map this effect to the proteolytically cleavable, positively charged, N-terminal 49 residues of human lactoferrin (hLF) known as lactoferricin (hLfcin). Lfcin binds to the hexon protein on the viral capsid, and anchors the virus to an unknown receptor of target cells, resulting in infection. These findings suggests that HAdVs use distinct cell entry mechanisms at different stages of infection. To initiate infection, entry is likely to occur at the apical side of polarized epithelial cells largely by means of hLF and hLfcin bridging HAdV capsids via hexons to as yet unknown receptors, and when infection is established, progeny virions released from the basolateral side enter neighbouring cells by means of hLF/hLfcin and CAR in parallel.IMPORTANCE Many viruses enter target cells using cell adhesion molecules as receptors. Paradoxically, these molecules are abundant on the lateral and basolateral side of intact, polarized, epithelial target cells, but absent on the apical side that must be penetrated by incoming viruses to initiate infection. Our study provides a model whereby viruses use different mechanisms to infect polarized epithelial cells depending on which side of the cell - apical or lateral/basolateral - is attacked. This study may also be useful to understand the biology of other viruses that use cell adhesion molecules as receptors.

2.
EMBO Rep ; 21(5): e50521, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32337821

RESUMO

Synthetic biology needs to adopt sound scientific and industry-like standards in order to achieve its ambitious goals of efficient and accurate engineering of biological systems.

3.
Chembiochem ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323410

RESUMO

Xenobiology is the science of estranged life forms. More specifically, this is an emergent technoscience that combines advances in genetic engineering with the design of biological systems based on unusual biochemistries delivered by chemical compounds of mostly anthropogenic origin. Xenobiology enables us to create and study strange new life forms, "aliens", not in the way science fiction books do it, but in terms of enlightened science, design, and engineering.

4.
ACS Sens ; 5(3): 879-886, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32103665

RESUMO

Tracking and analyzing the individual diffusion of nanoscale objects such as proteins and viruses is an important methodology in life science. Here, we show a sensor that combines the efficiency of light line illumination with the advantages of fluidic confinement. Tracking of freely diffusing nano-objects inside water-filled hollow core fibers with core diameters of tens of micrometers using elastically scattered light from the core mode allows retrieving information about the Brownian motion and the size of each particle of the investigated ensemble individually using standard tracking algorithms and the mean squared displacement analysis. Specifically, we successfully measure the diameter of every gold nanosphere in an ensemble that consists of several hundreds of 40 nm particles, with an individual precision below 17% (±8 nm). In addition, we confirm the relevance of our approach with respect to bioanalytics by analyzing 70 nm λ-phages. Overall these features, together with the strongly reduced demand for memory space, principally allows us to record thousands of frames and to achieve high frame rates for high precision tracking of nanoscale objects.

5.
Nanoscale ; 12(5): 3146-3156, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31967162

RESUMO

Understanding the dynamics of single nano-scale species at high spatiotemporal resolution is of utmost importance within fields such as bioanalytics or microrheology. Here we introduce the concept of axial position retrieval via scattered light at evanescent fields inside a corralled geometry using optofluidic microstructured optical fibers allowing to unlock information about diffusing nano-scale objects in all three spatial dimensions at kHz acquisition rate for several seconds. Our method yields the lateral positions by localizing the particle in a wide-field microscopy image. In addition, the axial position is retrieved via the scattered light intensity of the particle, as a result of the homogenized evanescent fields inside a microchannel running parallel to an optical core. This method yields spatial localization accuracies <3 nm along the transverse and <21 nm along the retrieved directions. Due to its unique properties such as three dimensional tracking, straightforward operation, mechanical flexibility, strong confinement, fast and efficient data recording, long observation times, low background scattering, and compatibility with microscopy and fiber circuitry, our concept represents a new paradigm in light-based nanoscale detection techniques, extending the capabilities of the field of nanoparticle tracking analysis and potentially allowing for the observation of so far inaccessible processes at the nanoscale level.

6.
Curr Biol ; 30(1): R38-R49, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31910377

RESUMO

For many decades, sleep researchers have sought to determine which species 'have' rapid eye movement (REM) sleep. In doing so, they relied predominantly on a template derived from the expression of REM sleep in the adults of a small number of mammalian species. Here, we argue for a different approach that focuses less on a binary decision about haves and have nots, and more on the diverse expression of REM sleep components over development and across species. By focusing on the components of REM sleep and discouraging continued reliance on a restricted template, we aim to promote a richer and more biologically grounded developmental-comparative approach that spans behavioral, physiological, neural, and ecological domains.

7.
Mol Inform ; 39(5): e1900135, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31943843

RESUMO

Carbon (C), hydrogen (H), nitrogen (N), oxygen (O), and sulfur (S) atoms intrigue as they are the foundation for amino acid (AA) composition and the folding and functions of proteins and thus define and control the survival of a cell, the smallest unit of life. Here, we calculated the proteomic atom distribution in >1500 randomly selected species across the entire current phylogenetic tree and identified uracil-5-methyltransferase (U5MTase) of the protozoan parasite Plasmodium falciparum (Pf, strain Pf3D7), with a distinct atom and AA distribution pattern. We determined its apicoplast location and in silico 3D protein structure to refocus attention exclusively on U5MTase with tremendous potential for therapeutic intervention in malaria. Around 300 million clinical cases of malaria occur each year in tropical and subtropical regions of the world, resulting in over one million deaths annually, placing malaria among the most serious infectious diseases. Genomic and proteomic research of the clades of parasites containing Pf is progressing slowly and the functions of most of the ∼5300 genes are still unknown. We applied a 'bottom-up' comparative proteomic atomics analysis across the phylogenetic tree to visualize a protein molecule on its actual basis - i. e., its atomic level. We identified a protruding Pf3D7-specific U5MTase, determined its 3D protein structure, and identified potential inhibitory drug molecules through in silico drug screening that might serve as possible remedies for the treatment of malaria. Besides, this atomic-based proteome map provides a unique approach for the identification of parasite-specific proteins that could be considered as novel therapeutic targets.

8.
Phys Rev Lett ; 123(21): 213903, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31809183

RESUMO

We experimentally observe an effective PT-phase transition through the exceptional point in a hybrid plasmonic-dielectric waveguide system. Transmission experiments reveal fundamental changes in the underlying eigenmode interactions as the environmental refractive index is tuned, which can be unambiguously attributed to a crossing through the plasmonic exceptional point. These results extend the design opportunities for tunable non-Hermitian physics to plasmonic systems.

9.
Spinal Cord ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811245

RESUMO

The German Association of the Scientific Medical Societies guideline for pregnancy, childbirth, and puerperium in women with a spinal cord injury (SCI) addresses a range of topics from the desire to have a child to different stages of pregnancy and birth. Given that a generally accessible and evidence-based presentation of this complex issue does not yet exist, this new guideline contributes to the standardization of gynecological, obstetric, and maternal care of women with SCI. This guideline aims to provide practice-oriented support for the care and counseling of women in the pre-, intra-, and postpartum periods; to close identified gaps in medical care; foster collaboration among clinicians of relevant disciplines; and inspire research.

10.
Opt Express ; 27(25): 36221-36230, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31873405

RESUMO

Confinement in fiber traps with two optical fibers facing one another relies on balancing the optical forces originating from the interaction of a scattering micro-object with the light beams delivered through the fibers. Here we demonstrate a novel type of dual fiber trap that involves the use of nanobore fibers, having a nano-channel located in the center of their fiber cores. This nano-element leads to a profound redistribution of the optical intensity and to considerably higher field gradients, yielding a trapping potential with greatly improved tuning properties compared to standard step-index fiber types. We evaluate the trap performance as a function of the fiber separation and find substantially higher stiffness for the nanobore fiber trap, especially in the range of short inter-fiber separations, while intermediate distances exhibit axial stiffness below that of the standard fiber. The results are in agreement with theoretical predictions and reveal that the exploitation of nanobore fibers allows for combinations of transverse and axial stiffness that cannot be accessed with common step-index fibers.

11.
Opt Lett ; 44(21): 5169-5172, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674958

RESUMO

Understanding the impact of geometric changes on the properties of otherwise symmetric nanostructures is of essential importance for nanophotonics. In this Letter, we show that intra- and inter-unit cell symmetry breaking can substantially modify the optical properties of nanotrimers from both the experimental and simulation aspect. Specifically, shifting the location of one nano-dot within the trimer unit cell leads to the formation of magnetic Fano resonances with loop-like polarization patterns that are not present in the symmetric configuration. We further unlock the impact of lattice modification on the optical response of square arrays of trimers with broken three-fold rotation symmetry and with intra-trimer distances as small as 25 nm, showing distinctively different spectral evolutions of the electric and magnetic Fano resonances. The results achieved highlight the symmetry breaking as an essential tool to unlock and strengthen predefined resonances, which can have important applications, particularly in the field of sensing.

12.
Opt Express ; 27(21): 29491-29500, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684209

RESUMO

Nonlinear pulse propagation inside highly nonlinear media requires accurate knowledge on the temporal response function of the materials used particular in the case of liquids. Here we study the impact of deuteration on the ultrafast dynamics of toluene and nitrobenzene via all optical Kerr gating, showing substantially different electronic and molecular contributions, which was quantified by fitting a multichannel decay model to the data points. Specifically we found that deuteration imposes the time-integrated nonlinearities to reduce particular for toluene which could be caused by both reduced electronic hyperpolarizabilities as well as weaker intermolecular interactions. The results achieved reveal that deuterated organic solvents represent promising materials for infrared photonics since they offer extended infrared transmission compared to their non-deuterated counterparts while maintained strong nonlinear responses.

13.
Opt Lett ; 44(16): 4016-4019, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415538

RESUMO

Efficient waveguiding inside low refractive index media is of key importance for a great variety of applications that demand strong light-matter interaction on small geometric footprints. Here, we demonstrate efficient light guidance in single-defect dual-ring light cages over millimeter distances that are integrated on silicon chips via direct laser writing. The cages consist of two rings of high aspect-ratio polymer strands (length 5 mm, aspect ratio >1000) hexagonally arranged around a hollow core. Clear-core mode formation via the photonic band gap effect is observed, with the experiments showing pronounced transmission bands with fringe and polarization contrasts of >20 dB and >15 dB, respectively. Numerical simulations confirm our experiments and reveal the dual-ring arrangement to be the optimal geometry within the light cage concept. Particularly, the side-wise access to the core regions and the chip integration makes the light cage concept attractive for a great number of fields such as bioanalytics or quantum technology.

14.
Biosystems ; 185: 104015, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31408698

RESUMO

Analysing or engineering the genetic code has mainly been considered as an approach to reduce or increase the mutational robustness of the genetic code, i.e. the error tolerance in DNA mutations, or to enable the incorporation of non-canonical amino acids. The approach of "semantic containment", however, is less interested in altering the mutational tolerance of the standard code, but to create synthetic alternative genetic codes that limit or all together impede horizontal gene transfer between a natural and genomically recoded organisms (GRO). A major claim or conjecture of semantic containment is: "the farther, the safer", meaning, the less similarity there is between two codes, the less chance of a horizontal gene transfer, and the stronger the genetic firewall. So far, no metrics were available to measure and quantify the "genetic distance" between different genetic codes. Such a metric, however, is iis paramount to allow the experimental testing and evaluation of the validity of semantic biocontainment for the first time. Here, we introduce a metric space to measure exactly the distance (dissimilarity) between different genetic codes, in order to provide a framework to evaluate the relation between distance and strength of a genetic firewall. Results are presented that incorporate bespoken metrics when producing alternative genetic codes according to predefined goals, specifications and limitations. Finally, as an outlook, implications and challenges for genetic firewall(s) are discussed for dual- and multi-code systems.

15.
Sci Rep ; 9(1): 9600, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270355

RESUMO

Photoautotrophic microbes present vast opportunities for sustainable lipid production, CO2 storage and green chemistry, for example, using microalgae beds to generate biofuels. A major challenge of microalgae cultivation and other photochemical reactors is the efficiency of light delivery. In order to break even on large scale, dedicated photon management will be required across all levels of reactor hierarchy - from the harvesting of light and its efficient injection and distribution inside of the reactor to the design of optical antenna and pathways of energy transfer on molecular scale. Here, we discuss a biomimetic approach for light dilution which enables homogeneous illumination of large reactor volumes with high optical density. We show that the immersion of side-emitting optical fiber within the reactor can enhance the fraction of illuminated volume by more than two orders of magnitude already at cell densities as low as ~5 104 ml-1. Using the green algae Haematococcus pluvialis as a model system, we demonstrate an increase in the rate of reproduction by up to 93%. Beyond micoralgae, the versatile properties of side-emitting fiber enable the injection and dilution of light with tailored spectral and temporal characteristics into virtually any reactor containment.

16.
Curr Biol ; 29(12): 1976-1987.e4, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31155350

RESUMO

Ambient temperature (Ta) warming toward the high end of the thermoneutral zone (TNZ) preferentially increases rapid eye movement (REM) sleep over non-REM (NREM) sleep across species. The control and function of this temperature-induced REM sleep expression have remained unknown. Melanin-concentrating hormone (MCH) neurons play an important role in REM sleep control. We hypothesize that the MCH system may modulate REM sleep as a function of Ta. Here, we show that wild-type (WT) mice dynamically increased REM sleep durations specifically during warm Ta pulsing within the TNZ, compared to both the TNZ cool and baseline constant Ta conditions, without significantly affecting either wake or NREM sleep durations. However, genetically engineered MCH receptor-1 knockout (MCHR1-KO) mice showed no significant changes in REM sleep as a function of Ta, even with increased sleep pressure following a 4-h sleep deprivation. Using MCH-cre mice transduced with channelrhodopsin, we then optogenetically activated MCH neurons time locked with Ta warming, showing an increase in REM sleep expression beyond what Ta warming in yellow fluorescent protein (YFP) control mice achieved. Finally, in mice transduced with archaerhodopsin-T, semi-chronic optogenetic MCH neuronal silencing during Ta warming completely blocked the increase in REM sleep seen in YFP controls. These data demonstrate a previously unknown role for the MCH system in the dynamic output expression of REM sleep during Ta manipulation. These findings are consistent with the energy allocation hypothesis of sleep function, suggesting that endotherms have evolved neural circuits to opportunistically express REM sleep when the need for thermoregulatory defense is minimized.

17.
Opt Lett ; 44(9): 2236-2239, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042192

RESUMO

Due to their unique properties such as transparency, tunability, nonlinearity, and dispersion flexibility, liquid-core fibers represent an important approach for future coherent mid-infrared light sources. However, the damage thresholds of these fibers are largely unexplored. Here we report on the generation of soliton-based supercontinua in carbon disulfide (CS2) liquid-core fibers at average power levels as high as 0.5 W operating stably for a long term (>70 h) without any kind of degradation or damage. Additionally, we also show stable high-power pulse transmission through liquid-core fibers exceeding 1 W of output average power for both CS2 and tetrachloroethylene as core materials.

18.
J Neurol ; 266(9): 2137-2143, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31127382

RESUMO

Previous studies reported high sensitivity and specificity of the Swiss Narcolepsy Scale (SNS) for the diagnosis of narcolepsy type 1. We used data from the Bern Sleep-Wake Database to investigate the discriminating capacity of both the SNS and the Epworth Sleepiness Scale (ESS) to identify narcolepsy type 1 and type 2 in patients with central disorders of hypersomnolence (CDH) or sleepy patients with obstructive sleep apnea (OSA). In addition, we aimed to develop a simplified version of the SNS. We created the two-item short-form SNS (sSNS), based on the discriminative capability of the models including all possible combinations of the five questions of the SNS. Using the previously published co-efficiencies, we confirmed the high capacity of the SNS in identifying narcolepsy type 1. The updated SNS (based on new co-efficiencies and cutoff) and the sSNS showed high capacity and were both superior to ESS in identifying narcolepsy type 1. The sSNS correlated significantly with the SNS (r = - 0.897, p < 0.001). No scale showed sufficient discrimination for narcolepsy type 2. This is the largest cohort study that confirms the discriminating power of SNS for narcolepsy type 1 in patients with hypersomnolence and the first study to assess its discriminative power for narcolepsy type 2. The easy-to-use and easy-to-calculate short-form scale has a high discriminating power for narcolepsy type 1 and may be used as screening tool, especially among general practitioners, to identify patients and accelerate their referral to a center of expertise.


Assuntos
Bases de Dados Factuais/normas , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Narcolepsia/diagnóstico , Sono/fisiologia , Inquéritos e Questionários/normas , Vigília/fisiologia , Adulto , Estudos de Coortes , Diagnóstico Diferencial , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/epidemiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Suíça , Adulto Jovem
19.
Opt Express ; 27(7): 10009-10021, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045148

RESUMO

Precise knowledge of modal behavior is of essential importance for understanding light guidance, particularly in hollow-core fibers. Here we present a semi-analytical model that allows determination of bands formed in revolver-type anti-resonant hollow-core fibers. The approach is independent of the actual arrangement of the anti-resonant elements, does not enforce artificial lattice arrangements and allows determination of the effective indices of modes of preselected order. The simulations show two classes of modes: (i) low-order modes exhibiting effective indices with moderate slopes and (ii) a high number of high-order modes with very strong effective index dispersion, forming a quasi-continuum of modes. It is shown that the mode density scales with the square of the normalized frequency, being to some extent similar to the behavior of multimode fibers.

20.
Nat Commun ; 10(1): 1939, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31028275

RESUMO

Accurate and fast aligners are required to handle the steadily increasing volume of sequencing data. Here we present an approach allowing performant alignments of short reads (Illumina) as well as long reads (Pacific Bioscience, Ultralong Oxford Nanopore), while achieving high accuracy, based on a universal three-stage scheme. It is also suitable for the discovery of insertions and deletions that originate from structural variants. We comprehensively compare our approach to other state-of-the-art aligners in order to confirm its performance with respect to accuracy and runtime. As part of our algorithmic scheme, we introduce two line sweep-based techniques called "strip of consideration" and "seed harmonization". These techniques represent a replacement for chaining and do not rely on any specially tailored data structures. Additionally, we propose a refined form of seeding on the foundation of the FMD-index.


Assuntos
Algoritmos , DNA/química , Análise de Sequência de DNA/estatística & dados numéricos , Software , Sequência de Bases , DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutagênese Insercional , Alinhamento de Sequência , Análise de Sequência de DNA/métodos , Deleção de Sequência , Homologia de Sequência do Ácido Nucleico
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