Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species.
, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin ...concentration in Tibetans. We provide evidence for an association between an adaptive
variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at
contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.
Improving the ability to predict livestock performance using biomarkers will provide a benefit for livestock genetic evaluation and improvement. The most practical biological sample to screen for ...development of biomarkers is serum due to the ease of collection. However, protein profiles in serum are complex and dynamic. Strategies are needed to manage variation in serum proteins used for biomarker identification. Albumin is the most abundant protein in serum, comprising over 50% of the overall protein content, and has historically been depleted from serum before biomarker identification. The objective of this study was to investigate the use of gel-based proteomic techniques to evaluate the need for porcine albumin depletion in biomarker identification. Albumin is known to bind many proteins in the blood, thus potential biomarkers could be removed during albumin depletion. Using two-dimensional difference in gel electrophoresis (2D-DIGE), we show whole serum can be used for biomarker discovery. The data obtained show that albumin removal methods are effective for porcine sera. Over 85% of the protein spots resolved on at least half of the gels were changed in abundance between whole and albumin depleted sera. Of the 204 protein spots significantly altered in abundance, 59 were changed over 400%. However, albumin removal also altered the serum proteome in an unpredictable manner; in the depleted sera, 86 protein spots were increased in abundance and 118 were decreased. Furthermore, the abundance of 59.4% of the protein spots in the albumin depleted samples had a larger standard error than whole sera. However, the resolution of albumin in 2D-DIGE analysis of whole sera permitted the detection and quantification of substantial numbers of proteins. Thus, it is proposed that whole serum can be used in a gel-based proteomics system for the identification of porcine biomarkers.
Measurement-Device-Independent Quantum Key Distribution (MDI-QKD) is a two-photon protocol devised to eliminate eavesdropping attacks that interrogate or control the detector in realized quantum key ...distribution systems. In MDI-QKD, the measurements are carried out by an untrusted third party, and the measurement results are announced openly. Knowledge or control of the measurement results gives the third party no information about the secret key. Error-free implementation of the MDI-QKD protocol requires the crypto-communicating parties, Alice and Bob, to independently prepare and transmit single photons that are physically indistinguishable, with the possible exception of their polarization states. In this paper, we apply the formalism of quantum optics and Monte Carlo simulations to quantify the impact of small errors in wavelength, bandwidth, polarization and timing between Alice’s photons and Bob’s photons on the MDI-QKD quantum bit error rate (QBER). Using published single-photon source characteristics from two-photon interference experiments as a test case, our simulations predict that the finite tolerances of these sources contribute ( 4.04 ± 20 / N sifted ) % to the QBER in an MDI-QKD implementation generating an N sifted -bit sifted key.
Abstract
Sericea lespedeza (SL; Lespedeza cuneata) is a legume rich in condensed tannins that can be grazed or fed to small ruminants for parasite control. Condensed tannins, a secondary plant ...compound in SL, may lead to unintended consequences such as changes in production. In our preliminary research, there was consistently a reduction in serum and liver concentrations of Mo. The objective of this study was to determine the effect of SL with or without Mo supplementation on changes in BW, hematology, and serum biochemistry in lambs. Thirty ram lambs weaned in May (84 ± 1.5 d of age; 27 ± 1.1 kg) were blocked by BW, breed type (full or three-fourths Katahdin), and EBV of parasite resistance and randomly assigned to be fed 900 g of alfalfa-based supplement (CON; n = 10) or SL-based supplement (n = 20) for 103 d. Supplements were formulated to be isonitrogenous and isocaloric and to meet trace mineral requirements. Within the SL diet, half of the lambs received 490 mg sodium molybdate weekly (SLMO). Body condition scores and BW were determined every 14 d and blood and feces collected to determine hematological and serum biochemical profiles and fecal egg counts (FEC). Data were analyzed using a mixed model with repeated measures and orthogonal contrasts. The white blood cell counts tended to be reduced in SL- and SLMO-fed lambs compared with CON-fed lambs (P < 0.06), which was associated with a reduction in neutrophils (P < 0.001). Red blood cell counts were also reduced in SL but not SLMO lambs compared with CON lambs (P < 0.04). There was a reduction in blood packed cell volume (P < 0.04) and serum concentrations of albumin (P < 0.001) and creatinine (P < 0.02) in both SL and SLMO lambs compared with CON lambs. Similarly, concentrations of blood urea nitrogen were reduced in both SL and SLMO lambs, but differences among dietary treatments disappeared after 42 d of feeding (treatment × day, P < 0.004). Serum concentrations of total proteins were reduced only in SLMO lambs compared with other lambs (P < 0.001). Body weight and FEC were similar among dietary treatments. Means of all measurements were within a normal range, even though there were subtle but significant differences between dietary groups. Feeding a diet high in condensed tannin–rich SL did not lead to serious effects on hematology or serum biochemistry in lambs.
The use of microarrays for parallel screening of nucleic acid profiles has become an industry standard. Similar efforts for screening protein‐protein interactions are gaining momentum, however, they ...remain limited by the requirement for relatively large sample volumes. One strategy for overcoming this problem is to significantly decrease the size and consequently the sample volume of the protein interaction assay. We report here on our progress over the last two years in the construction of ultraminiaturized, functional protein capture assays. Each one micron spot in these array‐based assays covers less than 1/1000th of the surface area of a conventional microarray spot while still maintaining enough antibodies to provide a useful dynamic range. These nanoarray assays can be read by conventional optical fluorescence microscopy as well as by novel label‐free methods such as atomic force microscopy. The size reduction realized by functional protein nanoarrays also creates opportunities for novel applications including highly multiplexed single cell analysis and integration with microfluidics and other “lab‐on‐a‐chip” technologies.
PDF
