bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assembly and functionality of the ribosome with tethered subunits
Authors: Aleksashin Nikolay A. , Leppik Margus , Hockenberry Adam J. , Klepacki Dorota , Vázquez-Laslop Nora , Jewett Michael C. , Remme Jaanus , Mankin Alexander S. 
Published: February 2019

AbstractRibo-T is an engineered ribosome whose small and large subunits are tethered together by linking 16S rRNA and 23S rRNA in a single molecule. Although Ribo-T can support cell proliferation in the absence of wild type ribosomes, Ribo-T cells grow slower than those with wild type ribosomes. Here, we show that cell growth defect is likely explained primarily by slow Ribo-T assembly rather than its imperfect functionality. Ribo-T maturation is stalled at a late assembly stage. Several post-transcriptional rRNA modifications and some ribosomal proteins are underrepresented in the accumulated assembly intermediates and rRNA ends are incompletely trimmed. Ribosome profiling of Ribo-T cells shows no defects in translation elongation but reveals somewhat higher occupancy by Ribo-T of the start codons and to a lesser extent stop codons, suggesting that subunit tethering mildly affects the initiation and termination stages of translation. Understanding limitations of Ribo-T system offers ways for its future development.
Superstrong coupling in circuit quantum electrodynamics
Authors: Kuzmin Roman , Mehta Nitish , Grabon Nicholas , Mencia Raymond , Manucharyan Vladimir E. 
Published: February 2019

AbstractVacuum fluctuations fundamentally affect an atom by inducing a finite excited state lifetime along with a Lamb shift of its transition frequency. Here we report the reverse effect: modification of vacuum modes by a single atom in circuit quantum electrodynamics. Our one-dimensional vacuum is a long section of a high wave impedance (comparable to resistance quantum) superconducting transmission line. It is directly wired to a transmon qubit circuit. Owing to the combination of high impedance and galvanic connection, the transmon’s spontaneous emission linewidth can greatly exceed the discrete transmission line modes spacing. This condition defines a previously unexplored superstrong coupling regime of quantum electrodynamics where many frequency-resolved vacuum modes hybridize with a single atom. We establish this regime by observing the spontaneous emission line of the transmon, revealed through the mode-by-mode measurement of the vacuum’s density of states. The linewidth as well as the atom-induced dispersive photon−photon interaction are accurately described by a physically transparent Caldeira−Leggett model, with the transmon’s quartic nonlinearity treated as a perturbation. Nonperturbative modification of vacuum, including inelastic scattering of single photons, can be enabled by the superstrong coupling regime upon replacing the transmon by more anharmonic qubits, with broad implications for simulating quantum impurity models of many-body physics.
Retail liver juices enhance the survivability of Campylobacter jejuni and Campylobacter coli at low temperatures
Authors: Karki Anand B. , Wells Harrington , Fakhr Mohamed K. 
Published: February 2019

AbstractThe high prevalence of Campylobacter spp. in retail liver products was previously reported and has been linked to several outbreaks of campylobacteriosis. The main objective of this study was to investigate the influence of retail liver juices on the survivability of several strains of C. jejuni and C. coli, which were previously isolated from various retail meats at 4 °C. All tested Campylobacter strains showed higher survival in beef liver juice (BLJ) and chicken liver juice (CLJ) as compared to beef and chicken juices (BJ and CJ) or Mueller Hinton broth (MHB) at 4 °C. Overall, C. jejuni strains showed greater survival in retail liver and meat juices as compared to C. coli. CLJ enhanced biofilm formation of most C. coli strains and supported growth in favorable conditions. When diluted, retail liver and meat juices enhanced survival of Campylobacter strains at low temperatures and increased aerotolerance. In conclusion, beef and chicken liver juices enhanced the survival of C. jejuni and C. coli strains at low temperatures, which helps explain the high prevalence of Campylobacter spp. in retail liver products.
Validation of clinic-based cryptococcal antigen lateral flow assay screening in HIV-infected adults in South Africa
Authors: Drain Paul K. , Hong Ting , Krows Meighan , Govere Sabina , Thulare Hilary , Wallis Carole L. , Gosnell Bernadett I. , Moosa Mahomed-Yunus , Bassett Ingrid V. , Celum Connie 
Published: February 2019

AbstractSince rapid cryptococcal antigen lateral flow assays (CrAg LFA) may expedite treatment of HIV-associated cryptococcal infections, we sought to validate clinic-based CrAg LFA testing. Among newly-diagnosed HIV-infected adults in South Africa, a trained nurse performed clinic-based testing of urine, fingerprick capillary and venous whole blood with rapid CrAg LFA (Immy Diagnostics, Norman, USA). We performed matched laboratory-based serum cryptococcal antigen testing with an enzyme immunoassay (EIA). We assessed diagnostic accuracy using EIA as the gold-standard, and performed additional validation testing on serum and among hospitalized adults with cryptococcal meningitis. Among 5,618 participants enrolled, 1,296 were HIV-infected and screened for cryptococcal antigenemia. Overall CrAg prevalence by serum EIA was 3.6% (95% CI 2.0–6.0%) for adults with CD4 < 200 cells/mm3, and 5.7% (95% CI 2.8–10.2%) for adults with CD4 < 100 cells/mm3. Using expanded screening guidelines (CD4 < 200 cells/mm3), CrAg LFA testing of venous whole blood, fingerprick capillary blood, and urine had diagnostic sensitivities of 46% (95% CI 19–75%), 38% (95% CI 14–68%), and 54% (95% CI 25–81%), and specificities of 97%, 97%, and 86%, respectively. When tested on serum samples, CrAg LFA had sensitivity of 93% (95% CI 66–100%) and specificity of 100% (95% CI 88–100%). All venous and fingerprick whole blood CrAg LFA tests were positive among 30 hospitalized adults with cryptococcal meningitis. Two independent readers had strong agreement for all LFA results (p < 0.0001). When performed at the point-of-care by trained nurses, CrAg LFA testing was feasible, had the highest accuracy on serum specimens, and may accelerate treatment of HIV-associated cryptococcal infections.
The effect of interventions on the transmission and spread of HIV in South Africa: a phylodynamic analysis
Authors: Wilkinson Eduan , Junqueira Dennis Maletich , Lessells Richard , Engelbrecht Susan , van Zyl Gert , de Oliveira Tulio , Salemi Marco 
Published: February 2019

AbstractThe epidemic in South Africa is characterized by high genetic diversity driven by multiple independent introductions. The bulk of these introductions occurred between 1985–2000 during which time HIV prevalence increased exponentially. Epidemic growth has stabilized in recent years with the implementation of several interventions. Here we identified distinct HIV clades from a large sequence dataset of southern African HIV sequences (n = 15,332). Each clade was characterized using phylodynamic and phylogeographic methods to infer their growth through time and space. The estimated date of origin for the 18 clades that were found, fell between 1979–1992 with strong growth during the 1990’s. Phylogeographic reconstruction revealed wide dispersal of clades throughout the country with the city of Johannesburg as the focal point of viral dispersal. We found clear signs of decreasing growth rate in four of the clades since the advent of interventions, while other clades have continued to growth and expand. Our results demonstrate that interventions do not affect the HIV epidemic universally with major difference between different clades over time and space. Here we demonstrate the utility and flexibility of molecular epidemiological methods and demonstrate how they can potentially be a powerful tool in HIV epidemic monitoring in South Africa.
Downregulation of M-channels in lateral habenula mediates hyperalgesia during alcohol withdrawal in rats
Authors: Kang Seungwoo , Li Jing , Zuo Wanhong , Chen Pei , Gregor Danielle , Fu Rao , Han Xiao , Bekker Alex , Ye Jiang-Hong 
Published: February 2019

AbstractHyperalgesia often occurs in alcoholics, especially during abstinence, yet the underlying mechanisms remain elusive. The lateral habenula (LHb) has been implicated in the pathophysiology of pain and alcohol use disorders. Suppression of m-type potassium channels (M-channels) has been found to contribute to the hyperactivity of LHb neurons of rats withdrawn from chronic alcohol administration. Here, we provided evidence that LHb M-channels may contribute to hyperalgesia. Compared to alcohol naïve counterparts, in male Long-Evans rats at 24-hours withdrawal from alcohol administration under the intermittent access paradigm for eight weeks, hyperalgesia was evident (as measured by paw withdrawal latencies in the Hargreaves Test), which was accompanied with higher basal activities of LHb neurons in brain slices, and lower M-channel protein expression. Inhibition of LHb neurons by chemogenetics, or pharmacological activation of M-channels, as well as overexpression of M-channels’ subunit KCNQ3, relieved hyperalgesia and decreased relapse-like alcohol consumption. In contrast, chemogenetic activation of LHb neurons induced hyperalgesia in alcohol-naive rats. These data reveal a central role for the LHb in hyperalgesia during alcohol withdrawal, which may be due in part to the suppression of M-channels and, thus, highlights M-channels in the LHb as a potential therapeutic target for hyperalgesia in alcoholics.
A new perspective of the 2014/15 failed El Niño as seen from ocean salinity
Authors: Chi J. , Du Y. , Zhang Y. , Nie X. , Shi P. , Qu T. 
Published: February 2019

AbstractThis study investigates the 2014/15 failed El Niño using salinity from an ocean general circulation model. The results indicate that subsurface processes were especially strong in the summer of 2014 and they led to positive sea surface salinity anomalies in the central equatorial Pacific. The positive sea surface salinity anomalies induced a westward displacement of the sea surface salinity front that represents the eastern boundary of the western Pacific warm pool, preventing the warm surface water from shifting eastward as seen in a typical El Niño event. In the meantime, more salty water was transported equatorward by a strengthening subtropical cell in the South Pacific. The enhanced subsurface processes in the central equatorial Pacific conveyed the salinity anomalies of subtropical origin to the sea surface and were largely responsible for the sea surface salinity variability but had less impacts on sea surface temperature during the 2014/15 failed El Niño, suggesting some potential advantage of ocean salinity in the El Niño-Southern Oscillation prediction.
Structure of amyloid β25–35 in lipid environment and cholesterol-dependent membrane pore formation
Authors: Kandel Nabin , Matos Jason O. , Tatulian Suren A. 
Published: February 2019

AbstractThe amyloid β (Aβ) peptide and its shorter variants, including a highly cytotoxic Aβ25–35 peptide, exert their neurotoxic effect during Alzheimer’s disease by various mechanisms, including cellular membrane permeabilization. The intrinsic polymorphism of Aβ has prevented the identification of the molecular basis of Aβ pore formation by direct structural methods, and computational studies have led to highly divergent pore models. Here, we have employed a set of biophysical techniques to directly monitor Ca2+-transporting Aβ25–35 pores in lipid membranes, to quantitatively characterize pore formation, and to identify the key structural features of the pore. Moreover, the effect of membrane cholesterol on pore formation and the structure of Aβ25–35 has been elucidated. The data suggest that the membrane-embedded peptide forms 6- or 8-stranded β-barrel like structures. The 8-stranded barrels may conduct Ca2+ ions through an inner cavity, whereas the tightly packed 6-stranded barrels need to assemble into supramolecular structures to form a central pore. Cholesterol affects Aβ25–35 pore formation by a dual mechanism, i.e., by direct interaction with the peptide and by affecting membrane structure. Collectively, our data illuminate the molecular basis of Aβ membrane pore formation, which should advance both basic and clinical research on Alzheimer’s disease and membrane-associated pathologies in general.
Sex affects N-homocysteinylation at lysine residue 212 of albumin in mice
Authors: Sikora Marta , Marczak Łukasz , Perła-Kajan Joanna , Jakubowski Hieronim 
Published: February 2019

AbstractThe modification of protein lysine residues by the thioester homocysteine (Hcy)-thiolactone has been implicated in cardiovascular and neurodegenerative diseases. However, only a handful of proteins carrying Hcy on specific lysine residues have been identified and quantified in humans or animals. In the present work, we developed a liquid chromatography/mass spectrometry targeted assay, based on multiple reaction monitoring, for quantification of N-Hcy-Lys212 (K212Hcy) and N-Hcy-Lys525 (K525Hcy) sites in serum albumin in mice. Using this assay, we found that female (n = 20) and male (n = 13) Cbs−/− mice had significantly elevated levels of K212Hcy and K525Hcy modifications in serum albumin relative to their female (n = 19) and male (n = 17) Cbs+/− littermates. There was significantly more K212Hcy modification in Cbs−/− males than in Cbs−/− females (5.78 ± 4.21 vs. 3.15 ± 1.38 units, P = 0.023). Higher K212Hcy levels in males than in females were observed also in Cbs+/− mice (2.72 ± 0.81 vs. 1.89 ± 1.07 units, P = 0.008). In contrast, levels of the K525Hcy albumin modification were similar between males and females, both in Cbs−/− and Cbs+/− mice. These findings suggest that the sex-specific K212Hcy modification in albumin might have an important biological function in mice that is not affected by the Cbs genotype.
How peptide/MHC presence affects the dynamics of the LC13 T-cell receptor
Authors: Dominguez Jose Luis , Knapp Bernhard 
Published: February 2019

AbstractThe interaction between T-cell receptors (TCRs) of T-cells and potentially immunogenic peptides presented by MHCs of antigen presenting cells is one of the most important mechanisms of the adaptive human immune system. A large number of structural simulations of the TCR/peptide/MHC system have been carried out. However, to date no study has investigated the differences of the dynamics between free TCRs and pMHC bound TCRs on a large scale. Here we present a study totalling 37 100 ns investigating the LC13 TCR in its free form as well as in complex with HLA-B*08:01 and different peptides. Our results show that the dynamics of the bound and unbound LC13 TCR differ significantly. This is reflected in (a) expected results such as an increased flexibility and increased solvent accessible surface of the CDRs of unbound TCR simulations but also in (b) less expected results such as lower CDR distances and compactness as well as alteration in the hydrogen bond network around CDR3α of unbound TCR simulations. Our study further emphasises the structural flexibility of TCRs and confirms the importance of the CDR3 loops for the adoption to MHC.
Amino acid content in rice grains is affected by high temperature during the early grain-filling period
Authors: Huang Min , Zhang Hengdong , Zhao Chunrong , Chen Guanghui , Zou Yingbin 
Published: February 2019

AbstractAmino acid content in grains is an important nutritional quality trait in rice. High temperature can affect rice quality by accelerating grain filling. However, there is limited information available on the influence of high temperature on amino acid content in rice grains, especially under natural conditions. In this study, grain-filling traits and amino acid content in the grain of two rice cultivars (Luliangyou 996 and Lingliangyou 268) were compared between two years (2016 and 2017) with contrasting temperatures during the early grain-filling period under field conditions. Average daily mean temperature during the period of 0–5 days after full heading in 2016 (30.1 °C) was 5.4 °C higher than that in 2017. Initial, maximum, and mean grain-filling rates were 42–307% higher in 2016 than in 2017 for Luliangyou 996 and Lingliangyou 268. The time taken to reach the maximum grain-filling rate and active grain-filling duration were 6.3–10.7 d shorter in 2016 compared to 2017 for Luliangyou 996 and Lingliangyou 268. Grain weight was equal to or significantly higher in 2016 than in 2017 for Luliangyou 996 and Lingliangyou 268. N accumulation and N content in the grain were significantly lower in 2016 than in 2017 for both cultivars. The grain contents of all detected amino acids, except for methionine in Luliangyou 996, were significantly lower in 2016 than in 2017. Our study suggests that high temperature during the early grain-filling period can result in an accelerated grain-filling process, reduced N accumulation and content in rice grains, and consequently reduced amino acid content in the grain.
Validation of Size Estimation of Nanoparticle Tracking Analysis on Polydisperse Macromolecule Assembly
Authors: Kim Ahram , Ng Wei Beng , Bernt William , Cho Nam-Joon 
Published: February 2019

AbstractAs the physicochemical properties of drug delivery systems are governed not only by the material properties which they are compose of but by their size that they conform, it is crucial to determine the size and distribution of such systems with nanometer-scale precision. The standard technique used to measure the size distribution of nanometer-sized particles in suspension is dynamic light scattering (DLS). Recently, nanoparticle tracking analysis (NTA) has been introduced to measure the diffusion coefficient of particles in a sample to determine their size distribution in relation to DLS results. Because DLS and NTA use identical physical characteristics to determine particle size but differ in the weighting of the distribution, NTA can be a good verification tool for DLS and vice versa. In this study, we evaluated two NTA data analysis methods based on maximum-likelihood estimation, namely finite track length adjustment (FTLA) and an iterative method, on monodisperse polystyrene beads and polydisperse vesicles by comparing the results with DLS. The NTA results from both methods agreed well with the mean size and relative variance values from DLS for monodisperse polystyrene standards. However, for the lipid vesicles prepared in various polydispersity conditions, the iterative method resulted in a better match with DLS than the FTLA method. Further, it was found that it is better to compare the native number-weighted NTA distribution with DLS, rather than its converted distribution weighted by intensity, as the variance of the converted NTA distribution deviates significantly from the DLS results.
Angiotensin-converting enzyme inhibitors or angiotensin receptor blocker monotherapy retard deterioration of renal function in Taiwanese chronic kidney disease population
Authors: Zheng Cai-Mei , Wang Jia-Yi , Chen Tzu-Ting , Wu Yun-Chun , Wu Yi-Lien , Lin Hsin-Ting , Chiu Sheng-Po , Chang Tian-Jong , Zheng Jing-Quan , Chu Nain-Feng , Lin Yu-Me , Su Sui-Lung , Lu Kuo-Cheng , Chen Jin-Shuen , Sung Fung-Chang , Lee Chien-Te , Yang Yu , Hwang Shang-Jyh , Wang Ming-Cheng , Hsu Yung-Ho , Chiou Hung-Yi , Kao Senyeong , Wu Mei-Yi , Lin Yuh-Feng 
Published: February 2019

AbstractIt remains unclear how different uses of angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) influence the progression of chronic kidney disease (CKD). This study explored CKD progression in a multicentre, longitudinal cohort study that included 2639 patients with CKD stage 1–5 and hypertension. Patients treated with ACEI or ARB for ≥90 days during a 6-mo period comprised the study group, or no treatment, comprised the control group. The study group was subdivided on the basis of treatment: ACEI monotherapy or ARB monotherapy. Progression of renal deterioration was defined by an average eGFR decline of more than 5 mL/min/1.73 m2/yr or the commencement of dialysis. With at least 1-year follow up, a progression of renal deterioration was demonstrated in 29.70% of the control group and 25.09% of the study group. Patients in the study group had significantly reduced progression of CKD with adjusted odds ratio 0.79 (95% confidence interval: 0.63–0.99). However, when ACEI monotherapy and ARB monotherapy were analyzed separately, none of their associations with CKD progression was statistically significant. In conclusion, ACEI or ARB monotherapy may retard the deterioration of renal function among patients with CKD and hypertension.
Quantitative impacts of incubation phase transmission of foot-and-mouth disease virus
Authors: Arzt Jonathan , Branan Matthew A. , Delgado Amy H. , Yadav Shankar , Moreno-Torres Karla I. , Tildesley Michael J. , Stenfeldt Carolina 
Published: February 2019

AbstractThe current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs. The primary outcome was that transmission occurred approximately one day prior to development of visible signs of disease (posterior median 21 hours, 95% CI: 1.1–45.0). Updated disease state durations were incorporated into a simulation model to examine the importance of addressing preclinical transmission in the face of robust response measures. Simulation of FMD outbreaks in the US pig production sector demonstrated that including a preclinical infectious period of one day would result in a 40% increase in the median number of farms affected (166 additional farms and 664,912 pigs euthanized) compared to the scenario of no preclinical transmission, assuming suboptimal outbreak response. These findings emphasize the importance of considering transmission of FMD during the incubation phase in modeling and response planning.
Molecular mechanism of lysophosphatidic acid-induced hypertensive response
Authors: Kano Kuniyuki , Matsumoto Hirotaka , Inoue Asuka , Yukiura Hiroshi , Kanai Motomu , Chun Jerold , Ishii Satoshi , Shimizu Takao , Aoki Junken 
Published: February 2019

AbstractLysophosphatidic acid (LPA) is a blood-derived bioactive lipid with numerous biological activities exerted mainly through six defined G protein-coupled receptors (LPA1-LPA6). LPA was first identified as a vasoactive compound because it induced transient hypertension when injected intravenously in rodents. Here, we examined the molecular mechanism underlying the LPA-induced hypertensive response. The LPA-induced hypertensive response was significantly attenuated by pretreatment with a Rho kinase inhibitor, which blocks Gα12/13 signaling. Consistent with this, the response was weakened in KO mice of LPA4, a Gα12/13-coupling LPA receptor. KO mice of another Gα12/13-coupling LPA receptor, LPA6, also showed an attenuated LPA-induced hypertensive response. However, LPA6 KO mice also displayed attenuated pressor responses to an adrenergic agent and abnormal blood vessel formation. Using several LPA analogs with varied affinity for each LPA receptor, we found a good correlation between the hypertensive and LPA4 agonistic activities. Incubated mouse plasma, which contained abundant LPA, also induced a hypertensive response. Interestingly the response was completely abolished when the plasma was incubated in the presence of an ATX inhibitor. Together, these results indicate that circulating LPA produced by ATX contributes to the elevation of blood pressure through multiple LPA receptors, mainly LPA4.