A hepatitis B virus causes chronic infections in equids worldwide

Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 109 mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na+/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/ HCV interplay upon coinfection

Autotrophic and heterotrophic acquisition of carbon and nitrogen by a mixotrophic chrysophyte established through stable isotope analysis

Collectively, phagotrophic algae (mixotrophs) form a functional continuum of nutritional modes between autotrophy and heterotrophy, but the specific physiological benefits of mixotrophic nutrition differ among taxa. Ochromonas spp. are ubiquitous chrysophytes that exhibit high nutritional flexibility, although most species generally fall towards the heterotrophic end of the mixotrophy spectrum. We assessed the sources of carbon and nitrogen in Ochromonas sp. strain BG-1 growing mixotrophically via short-term stable isotope probing. An axenic culture was grown in the presence of either heat-killed bacteria enriched with ^(15)N and ^(13)C, or unlabeled heat-killed bacteria and labeled inorganic substrates (^(13)C-bicarbonate and ^(15)N-ammonium). The alga exhibited high growth rates (up to 2 divisions per day) only until heat-killed bacteria were depleted. NanoSIMS and bulk IRMS isotope analyses revealed that Ochromonas obtained 84–99% of its carbon and 88–95% of its nitrogen from consumed bacteria. The chrysophyte assimilated inorganic ^(13)C-carbon and ^(15)N-nitrogen when bacterial abundances were very low, but autotrophic (photosynthetic) activity was insufficient to support net population growth of the alga. Our use of nanoSIMS represents its first application towards the study of a mixotrophic alga, enabling a better understanding and quantitative assessment of carbon and nutrient acquisition by this species

Biology of moderately halophilic aerobic bacteria

The moderately halophilic heterotrophic aerobic bacteria form a diverse group of microorganisms. The property of halophilism is widespread within the bacterial domain. Bacterial halophiles are abundant in environments such as salt lakes, saline soils, and salted food products. Most species keep their intracellular ionic concentrations at low levels while synthesizing or accumulating organic solutes to provide osmotic equilibrium of the cytoplasm with the surrounding medium. Complex mechanisms of adjustment of the intracellular environments and the properties of the cytoplasmic membrane enable rapid adaptation to changes in the salt concentration of the environment. Approaches to the study of genetic processes have recently been developed for several moderate halophiles, opening the way toward an understanding of haloadaptation at the molecular level. The new information obtained is also expected to contribute to the development of novel biotechnological uses for these organisms

Interferometric optical fiber sensor for optoacoustic endomicroscopy.

Optical fiber sensors can offer robust and miniaturized detection of wideband ultrasound, yielding high sensitivity and immunity to electromagnetic interference. However, the lack of cost-effective manufacturing methods prevents the disseminated use of these sensors in biomedical applications. In this study, we developed and optimized a simple method to create optical cavities with high-quality mirrors for acoustic sensing based on micro-manipulation of UV-curable optical adhesives and electroless chemical silver deposition. This approach enables the manufacturing of ultrasound sensors based on Fabry-Pérot Interferometers (FPI) on optical fiber tips with minimal production costs. Characterization and high-resolution optoacoustic imaging experiments show that the manufacturing process yielded a fiber sensor with a small NEP (11 mPa/ Hz ) over a broad detection bandwidth (25 MHz), generally outperforming conventional piezoelectric based transducers. We discuss how the new manufacturing process leads to a high-performance acoustic detector that, due to low cost, can be used as a disposable sensor

Optoacoustic microscopy based on pi-FBG ultrasound sensors.

We present an optoacoustic (photoacoustic) microscopy (OAM) imaging system that uses a pi-shifted Fiber Bragg Grating (pi-FBG) as ultrasound (US) sensor. The sensor has an ultra-small footprint and hence allows for the detection of optoacoustic signals in close proximity to their origin. The interrogation of the pi-FBG is performed by a broadband pulsed laser, enabling a high sensitivity of the sensor as well as the elimination of ambient noise. We characterize the pi-FBG in terms of axial and lateral resolution as well as its bandwidth and find that its performance is comparable to US sensors that are based on the piezoelectric effect. We demonstrate the system’s capabilities by images taken from ex vivo zebrafish and mouse ear samples. The results presented herein highlight that pi-FBGs are a promising tool for the comprehensive label-free optoacoustic imaging of biomedical samples

All-optical optoacoustic microscope based on wideband pulse interferometry.

Optical and optoacoustic (photoacoustic) microscopy have been recently joined in hybrid implementations that resolve extended tissue contrast compared to each modality alone. Nevertheless, the application of the hybrid technique is limited by the requirement to combine an optical objective with ultrasound detection collecting signal from the same micro-volume. We present an all-optical optoacoustic microscope based on a pi-phase-shifted fiber Bragg grating (π-FBG) with coherence-restored pulsed interferometry (CRPI) used as the interrogation method. The sensor offers an ultra-small footprint and achieved higher sensitivity over piezoelectric transducers of similar size. We characterize the spectral bandwidth of the ultrasound detector and interrogate the imaging performance on phantoms and tissues. We show the first optoacoustic images of biological specimen recorded with π-FBG sensors. We discuss the potential uses of π-FBG sensors based on CRPI

A submicrometre silicon-on-insulator resonator for ultrasound detection.

The widely available silicon-on-insulator technology is used to develop a miniaturized ultrasound detector, which is 200 times smaller than the wavelengths of sound that it can detect.Ultrasound detectors use high-frequency sound waves to image objects and measure distances, but the resolution of these readings is limited by the physical dimensions of the detecting element. Point-like broadband ultrasound detection can greatly increase the resolution of ultrasonography and optoacoustic (photoacoustic) imaging(1,2), but current ultrasound detectors, such as those used for medical imaging, cannot be miniaturized sufficiently. Piezoelectric transducers lose sensitivity quadratically with size reduction(3), and optical microring resonators(4)and Fabry-Perot etalons(5)cannot adequately confine light to dimensions smaller than about 50 micrometres. Micromachining methods have been used to generate arrays of capacitive(6)and piezoelectric(7)transducers, but with bandwidths of only a few megahertz and dimensions exceeding 70 micrometres. Here we use the widely available silicon-on-insulator technology to develop a miniaturized ultrasound detector, with a sensing area of only 220 nanometres by 500 nanometres. The silicon-on-insulator-based optical resonator design provides per-area sensitivity that is 1,000 times higher than that of microring resonators and 100,000,000 times better than that of piezoelectric detectors. Our design also enables an ultrawide detection bandwidth, reaching 230 megahertz at -6 decibels. In addition to making the detectors suitable for manufacture in very dense arrays, we show that the submicrometre sensing area enables super-resolution detection and imaging performance. We demonstrate imaging of features 50 times smaller than the wavelength of ultrasound detected. Our detector enables ultra-miniaturization of ultrasound readings, enabling ultrasound imaging at a resolution comparable to that achieved with optical microscopy, and potentially enabling the development of very dense ultrasound arrays on a silicon chip

Sensitive, small, broadband and scalable optomechanical ultrasound sensor in silicon photonics.

Ultrasonography1 and photoacoustic2,3 (optoacoustic) tomography have recently seen great advances in hardware and algorithms. However, current high-end systems still use a matrix of piezoelectric sensor elements, and new applications require sensors with high sensitivity, broadband detection, small size and scalability to a fine-pitch matrix. This work demonstrates an ultrasound sensor in silicon photonic technology with extreme sensitivity owing to an innovative optomechanical waveguide. This waveguide has a tiny 15 nm air gap between two movable parts, which we fabricated using new CMOS-compatible processing. The 20 μm small sensor has a noise equivalent pressure below 1.3 mPa Hz−1/2 in the measured range of 3–30 MHz, dominated by acoustomechanical noise. This is two orders of magnitude better than for piezoelectric elements of an identical size4. The demonstrated sensor matrix with on-chip photonic multiplexing5–7 offers the prospect of miniaturized catheters that have sensor matrices interrogated using just a few optical fibres, unlike piezoelectric sensors that typically use an electrical connection for each element

Fiber interferometer for hybrid optical and optoacoustic intravital microscopy.

The addition of optoacoustic sensing to optical microscopy may supplement fluorescence contrast with label-free measurements of optical absorption, enhancing biological observation. However, the physical dimensions of many optoacoustic systems have restricted the implementation of hybrid optical and optoacoustic (O2A) microscopy to imaging thin samples in transmission mode or to ex-vivo investigations. Here we describe a miniaturized optoacoustic sensor, based on