Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular analysis of glycosylphosphatidylinositol anchor deficient aerolysin resistant isolates in gulf war i veterans exposed to depleted uranium

During the First Gulf War (1991) over 100 servicemen sustained depleted uranium (DU) exposure through wound contamination, inhalation, and shrapnel. The Department of Veterans Affairs has a surveillance program for these Veterans which has included genotoxicity assays. The frequencies of glycosylphosphatidylinositol anchor (GPIa) negative (aerolysin resistant) cells determined by cloning assays for these Veterans are reported in Albertini RJ et al. (2019: Environ Mol Mutagen). Molecular analyses of the GPIa biosynthesis class A (PIGA) gene was performed on 862 aerolysin‐resistant T‐lymphocyte recovered isolates. The frequencies of different types of PIGA mutations were compared between high and low DU exposure groups. Additional molecular studies were performed on mutants that produced no PIGA mRNA or with deletions of all or part of the PIGA gene to determine deletion size and breakpoint sequence. One mutant appeared to be the result of a chromothriptic event. A significant percentage (>30%) of the aerolysin resistant isolates, which varied by sample year and Veteran, had wild‐type PIGA cDNA (no mutation). As described in Albertini RJ et al. (2019: Environ Mol Mutagen), TCR gene rearrangement analysis of these isolates indicated most arose from multiple T‐cell progenitors (hence the inability to find a mutation). It is likely that these isolates were the result of failure of complete selection against nonmutant cells in the cloning assays. Real‐time studies of GPIa resistant isolates with no PIGA mutation but with a single TCR gene rearrangement found one clone with a PIGV deletion and several others with decreased levels of GPIa pathway gene mRNAs implying mutation in other GPIa pathway genes. Environ. Mol. Mutagen. 60:470–493, 2019. © 2019 Wiley Periodicals, Inc.
Tilmicosin enteric granules and premix to pigs: Antimicrobial susceptibility testing and comparative pharmacokinetics

The purpose of this study was to compare the pharmacokinetics and relative bioavailability of tilmicosin enteric granules and premix after oral administration at a dose of 40 mg/kg in pigs. Three kinds of different respiratory pathogens were selected for determination of minimal inhibitory concentration (MIC) to tilmicosin. Eight healthy pigs were assigned to a two-period, randomized crossover design. A modified rapid, sensitive HPLC method was used for determining the concentrations of tilmicosin in plasma. Pharmacokinetic parameters were calculated by using WinNonlin 5.2 software. The MIC90 of tilmicosin against Haemophilus parasuis, Actinbacillus pleuropneumoniae, and Pasteurella multocida were all 8 μg/ml. These results indicated that these common pig respiratory bacteria are sensitive to tilmicosin. The main parameters of time to reach maximum plasma concentration (Tmax ), elimination half-life (t1/2β ), mean residence time (MRT), and apparent volume of distribution (VF ) were 2.03 ± 0.37 hr, 29.31 ± 5.56 hr, 25.22 ± 2.57 hr, 4.06 ± 1.04 L/kg, and 3.05 ± 0.08 hr, 17.06 ± 1.77 hr, 15.55 ± 1.37 hr, 2.95 ± 0.62 L/kg after the orally administrated tilmicosin enteric granules and premix. The relative bioavailability of tilmicosin enteric granules to premix was 114.97 ± 7.19%, according to the AUC0-t values. These results demonstrated that tilmicosin enteric granules produced faster tilmicosin absorption, slower elimination, larger tissue distribution, and higher bioavailability compared to the tilmicosin premix. The present study results manifest that tilmicosin enteric granules can be used as a therapeutic alternative to premix in clinical treatment.
Surface Engineered Biomimetic Inks Based on UV Cross-Linkable Wood Biopolymers for 3D Printing

Owing to their superior mechanical strength and structure similarity to the extracellular matrix, nanocelluloses as a class of emerging biomaterials have attracted great attention in three-dimensional (3D) bioprinting to fabricate various tissue mimics. Yet, when printing complex geometries, the desired ink performance in terms of shape fidelity and object resolution demands a wide catalogue of tunability on the material property. This paper describes surface engineered biomimetic inks based on cellulose nanofibrils (CNFs) and cross-linkable hemicellulose derivatives for UV-aided extrusion printing, being inspired by the biomimetic aspect of intrinsic affinity of heteropolysaccharides to cellulose in providing the ultrastrong but flexible plant cell wall structure. A facile aqueous-based approach was established for the synthesis of a series of UV cross-linkable galactoglucomannan methacrylates (GGMMAs) with tunable substitution degrees. The rapid gelation window of the formulated inks facilitates the utilization of these wood-based biopolymers as the feeding ink for extrusion-based 3D printing. Most importantly, a wide and tunable spectrum ranging from 2.5 to 22.5 kPa of different hydrogels with different mechanical properties could be achieved by varying the substitution degree in GGMMA and the compositional ratio between GGMMA and CNFs. Used as the seeding matrices in the cultures of human dermal fibroblasts and pancreatic tumor cells, the scaffolds printed with the CNF/GGMMA inks showed great cytocompatibility as well as supported the matrix adhesion and proliferative behaviors of the studied cell lines. As a new family of 3D printing feedstock materials, the CNF/GGMMA ink will broaden the map of bioinks, which potentially meets the requirements for a variety of in vitro cell–matrix and cell–cell interaction studies in the context of tissue engineering, cancer cell research, and high-throughput drug screening.
Speech perception in noise: Impact of directional microphones in users of combined electric-acoustic stimulation

Objectives Combined electric-acoustic stimulation (EAS) is a well-accepted therapeutic treatment for cochlear implant (CI) users with residual hearing in the low frequencies but severe to profound hearing loss in the high frequencies. The recently introduced SONNETeas audio processor offers different microphone directionality (MD) settings and wind noise reduction (WNR) as front-end processing. The aim of this study was to compare speech perception in quiet and noise between two EAS audio processors DUET 2 and SONNETeas, to assess the impact of MD and WNR on speech perception in EAS users in the absence of wind. Furthermore, subjective rating of hearing performance was registered. Method Speech perception and subjective rating with SONNETeas or DUET 2 audio processor were assessed in 10 experienced EAS users. Speech perception was measured in quiet and in a diffuse noise setup (MSNF). The SONNETeas processor was tested with three MD settings omnidirectional/natural/adaptive and with different intensities of WNR. Subjective rating of auditory benefit and sound quality was rated using two questionnaires. Results There was no significant difference between DUET 2 and SONNETeas processor using the omnidirectional microphone in quiet and in noise. There was a significant improvement in SRT with MD settings natural (2.2 dB) and adaptive (3.6 dB). No detrimental effect of the WNR algorithm on speech perception was found in the absence of wind. Sound quality was rated as “moderate” for both audio processors. Conclusions The different MD settings of the SONNETeas can provide EAS users with better speech perception compared to an omnidirectional microphone. Concerning speech perception in quiet and quality of life, the performance of the DUET 2 and SONNETeas audio processors was comparable.
Growth and Survival of Campylobacter fetus subsp. jejuni as a Function of Temperature and pH.

The objective of this study was to determine what effect temperature and pH have on the ability of Campylobacter fetus subsp. jejuni to grow and survive. None of three strains of C. fetus subsp. jejuni could grow at 30 C and below or at 47 C and above. The optimum temperature for growth was in the range of 42 to 45 C. Only one of three strains, FRI-CF8, could grow at pH 4.9 and none could grow at pH 4.7. The optimum pH for growth was in the range of 6.5 to 7.5; however, all strains grew well at pH 5.5 to 8.0. Rate of cell death at pH 3.0 to 4.5 was temperature-dependent. At comparable pH, cells of C. fetus subsp. jejuni died most rapidly at 42 C, less rapidly at 25 C and at the slowest rate at 4 C. For example, at pH 4.5, a 3 log10 decrease of cells occurred within 8 h when incubated at 42 C but took 4 days when incubated at 4 C. At 25 C and pH 4.5, cells were inactivated at an intermediate rate. Rates of thermal inactivation of five strains of C. fetus subsp. jejuni were determined at 48, 50, 53, and 55 C in a skim milk heating menstruum. At 48 C, D-values ranged from 7.2 to 12.8 min while at 55 C they ranged from 0.74 to 1.00 min. The times and temperatures used to pasteurize milk should be sufficient to free milk of even unusually large numbers of viable cells of C. fetus subsp. jejuni.
Reprogramming of the cambium regulators during adventitious root development upon wounding of storage tap roots in radish (Raphanus sativus L.)

ABSTRACT Cambium contains a stem cell population that produces xylem and phloem tissues in a radial direction during the secondary growth stage. The growth of many storage roots, including in the radish, Raphanus sativus L. , also depends on cambium. Interestingly, we observed numerous adventitious roots (ARs) emerging from the cambia of cut surfaces when the bases of radish storage tap roots were removed. Previous studies in Arabidopsis showed that the WOX11/12 pathway regulates AR initiation and meristem establishment in an auxin-dependent manner. Here, we provide evidence indicating the evolutionary conservation of the WOX11/12 pathway during the AR development in radishes. Additionally, we found that expression of two cambium regulators, PXY and WOX4, is induced in the cambium regions that are connected to emerging ARs via vascularization. Both AR formation and genes associated with this were induced by exogenous auxin. Our research suggests that some key cambium regulators might be reprogrammed to aid in the AR development in concert with the WOX11/12 pathway. This article has an associated First Person interview with the first author of the paper. Summary: Adventitious roots originate from cambia of cut radish taproots. This process depends on the auxin-dependent reprogramming of cambial regulators and the activation of canonical adventitious root regulators.
Adaptive evolution of butterfly wing shape: from morphology to behaviour

Butterflies display extreme variation in wing shape associated with tremendous ecological diversity. Disentangling the role of neutral versus adaptive processes in wing shape diversification remains a challenge for evolutionary biologists. Ascertaining how natural selection influences wing shape evolution requires both functional studies linking morphology to flight performance, and ecological investigations linking performance in the wild with fitness. However, direct links between morphological variation and fitness have rarely been established. The functional morphology of butterfly flight has been investigated but selective forces acting on flight behaviour and associated wing shape have received less attention. Here, we attempt to estimate the ecological relevance of morpho‐functional links established through biomechanical studies in order to understand the evolution of butterfly wing morphology. We survey the evidence for natural and sexual selection driving wing shape evolution in butterflies, and discuss how our functional knowledge may allow identification of the selective forces involved, at both the macro‐ and micro‐evolutionary scales. Our review shows that although correlations between wing shape variation and ecological factors have been established at the macro‐evolutionary level, the underlying selective pressures often remain unclear. We identify the need to investigate flight behaviour in relevant ecological contexts to detect variation in fitness‐related traits. Identifying the selective regime then should guide experimental studies towards the relevant estimates of flight performance. Habitat, predators and sex‐specific behaviours are likely to be major selective forces acting on wing shape evolution in butterflies. Some striking cases of morphological divergence driven by contrasting ecology involve both wing and body morphology, indicating that their interactions should be included in future studies investigating co‐evolution between morphology and flight behaviour.
Comorbidity of reading disabilities and ADHD: Structural and functional brain characteristics

Reading disabilities (RD) and attention‐deficit/hyperactivity disorder (ADHD) are two of the most common developmental disorders. RD and ADHD frequently co‐occur, which raises questions about how the disorders interact and to what extent they can be differentiated. To date, the underlying neural mechanisms leading to RD–ADHD comorbidity (COM) are not understood. In this study, structural and functional magnetic resonance imaging (fMRI) were combined with comprehensive behavioral testing in order to characterize the behavior, brain structure, and neural correlates of executive function, phonological processing and reading fluency in 60 children with clinical diagnoses of RD, ADHD, or COM, and controls. Whole‐brain analyses of variance were performed on cortical thickness values and on the data of the three fMRI tasks to investigate overall group differences. To validate these findings, a region of interest analysis was performed in regions that have previously been shown to exhibit group differences in children with RD or ADHD using the same paradigms. The neuroimaging results demonstrated structural and functional atypicalities for COM in regions that are frequently associated with deficits in children with isolated ADHD or RD. A combination of shared and distinctive brain alterations between the clinical groups was identified, supporting the multiple deficit model for ADHD, RD, and its comorbidity.
Identification of Anti‐Mycobacterial Biofilm Agents Based on the 2‐Aminoimidazole Scaffold

Tuberculosis (TB) remains a significant global health problem for which new therapeutic options are sorely needed. The ability of the causative agent, Mycobacterium tuberculosis, to reside within host macrophages and form biofilm‐like communities contributes to the persistent and drug‐tolerant nature of the disease. Compounds that can prevent or reverse the biofilm‐like phenotype have the potential to serve alongside TB antibiotics to overcome this tolerance, and decrease treatment duration. Using Mycobacterium smegmatis as a surrogate organism, we report the identification of two new 2‐aminoimidazole compounds that inhibit and disperse mycobacterial biofilms, work synergistically with isoniazid and rifampicin to eradicate preformed M. smegmatis biofilms in vitro, are nontoxic toward Galleria mellonella, and exhibit stability in mouse plasma.
Glycosylation of HIV Env Impacts IgG Subtype Responses to Vaccination

The envelope protein (Env) is the only surface protein of the human immunodeficiency virus (HIV) and as such the exclusive target for protective antibody responses. Experimental evidences from mouse models suggest a modulating property of Env to steer antibody class switching towards the less effective antibody subclass IgG1 accompanied with strong TH2 helper responses. By simple physical linkage we were able to imprint this bias, exemplified by a low IgG2a/IgG1 ratio of antigen-specific antibodies, onto an unrelated antigen, namely the HIV capsid protein p24. Here, our results indicate the glycan moiety of Env as the responsible immune modulating activity. Firstly, in Card9−/− mice lacking specific C-Type lectin responsiveness, DNA immunization significantly increased the IgG2a/IgG1 ratio for the Env-specific antibodies while the antibody response against the F-protein of the respiratory syncytial virus (RSV) serving as control antigen remained unchanged. Secondly, sequential shortening of the Env encoding sequence revealed the C2V3 domain as responsible for the strong IgG1 responses and TH2 cytokine production. Removing all potential N-glycosylation sites from the C2V3 domain by site-specific mutagenesis reversed the vaccine-induced immune response towards a Th1-dominated T-cell response and a balanced IgG2a/IgG1 ratio. Accordingly, the stretch of oligomannose glycans in the C2V3 domain of Env might mediate a specific uptake and/or signaling modus in antigen presenting cells by involving interaction with an as yet unknown C-type lectin receptor. Our results contribute to a deeper understanding of the impact of Env glycosylation on HIV antigen-specific immune responses, which will further support HIV vaccine development.
Microbial community composition in alpine lake sediments from the Hengduan Mountains

Microbial communities in sediments play an important role in alpine lake ecosystems. However, the microbial diversity and community composition of alpine lake sediments from the Hengduan Mountains remain largely unknown. Therefore, based on the Illumina MiSeq platform, high‐throughput sequencing analysis of the 16S rRNA gene was performed on 15 alpine lake sediments collected at different locations in the Hengduan Mountains. The abundance‐based coverage estimate (ACE), Chao1, and Shannon indices indicated that the microbial abundance and diversity of these sediments were high. There are some differences in the composition of microbial communities among sediments. However, in general, Proteobacteria accounted for the largest proportion of all sediments (22.3%–67.6%) and was the dominant phylum. Followed by Bacteroidetes, Acidobacteria, Chloroflexi, and Planctomycetes. In addition, the operational taxonomic unit (OTU) interactions network had modular structures and suggested more cooperation than competition in the microbial community. Besides, we also found that temperature has a significant contribution to the sample–environment relationship. This study revealed the diversity and composition of microbial communities in alpine lake sediments from the Hengduan Mountains, and describe the correlation between microbial community structure and different environmental variables.
Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131)

The centrosome, consisting of two centrioles surrounded by a dense network of proteins, is the microtubule-organizing center of animal cells. Polo-like kinase 4 (PLK4) is a Ser/Thr protein kinase and the master regulator of centriole duplication, but it may play additional roles in centrosome function. To identify additional proteins regulated by PLK4, we generated an RPE-1 human cell line with a genetically engineered “analog-sensitive” PLK4AS, which genetically encodes chemical sensitivity to competitive inhibition via a bulky ATP analog. We used this transgenic line in an unbiased multiplex phosphoproteomic screen. Several hits were identified and validated as direct PLK4 substrates by in vitro kinase assays. Among them, we confirmed Ser-78 in centrosomal protein 131 (CEP131, also known as AZI1) as a direct substrate of PLK4. Using immunofluorescence microscopy, we observed that although PLK4-mediated phosphorylation of Ser-78 is dispensable for CEP131 localization, ciliogenesis, and centriole duplication, it is essential for maintaining the integrity of centriolar satellites. We also found that PLK4 inhibition or use of a nonphosphorylatable CEP131 variant results in dispersed centriolar satellites. Moreover, replacement of endogenous WT CEP131 with an S78D phosphomimetic variant promoted aggregation of centriolar satellites. We conclude that PLK4 phosphorylates CEP131 at Ser-78 to maintain centriolar satellite integrity.
Structure Prior Constrained Estimation of Human Cardiac Diffusion Tensors

Objective: The purpose of this paper is to increase the accuracy of human cardiac diffusion tensor (DT) estimation in diffusion magnetic resonance imaging (dMRI) with a few diffusion gradient directions. Methods: A structure prior constrained (SPC) method is proposed. The method consists in introducing two regularizers in the conventional nonlinear least squares estimator. The two regularizers penalize the dissimilarity between neighboring DTs and the difference between estimated and prior fiber orientations, respectively. A novel numerical solution is presented to ensure the positive definite estimation. Results: Experiments on ex vivo human cardiac data show that the SPC method is able to well estimate DTs at most voxels, and is superior to state-of-the-art methods in terms of the mean errors of principal eigenvector, second eigenvector, helix angle, transverse angle, fractional anisotropy, and mean diffusivity. Conclusion: The SPC method is a practical and reliable alternative to current denoising- or regularization-based methods for the estimation of human cardiac DT. Significance: The SPC method is able to accurately estimate human cardiac DTs in dMRI with a few diffusion gradient directions.
Limits to the rate of information transmission through the MAPK pathway

Two important signaling pathways of NF-κB and ERK transmit merely one bit of information about the level of extracellular stimulation. It is thus unclear how such systems can coordinate complex cell responses to external cues. Here, we analyze information transmission in the MAPK/ERK pathway that features relaxation oscillations and responds to EGF by pulses of activated ERK. Based on an experimentally verified computational model of the MAPK/ERK pathway, we demonstrate that when input sequences of EGF pulses are transcoded to output sequences of ERK activity pulses, transmitted information increases nearly linearly with time. Moreover, the information channel capacity C (defined as the upper limit of information that can be transmitted over a sufficiently long time t, divided by t), is not limited by the bandwidth B = 1/τ, where τ ≈ 1 hour is the relaxation time. Specifically, when input is provided in the form of sequences of short binary EGF pulses separated by varying intervals that are multiples of τ/n (but are not shorter than τ), then for n = 2, C ≈ 1.39 bit/hour; and for n = 4, C ≈ 1.86 bit/hour. We hypothesize that the primary mode of operation of the MAPK pathway is to translate extracellular growth factor “bursts” into precisely timed intracellular ERK “spikes” of a predefined amplitude. Such pulse-interval transcoding allows to relay more information than the amplitude–amplitude transcoding considered previously for the ERK and NF-κB pathways. Author summary To coordinate their actions, cells communicate with each other by sending, receiving, and interpreting cytokine signals. Cells recognize chemical identity of signaling molecules and process quantitative and temporal properties of stimulation: amplitude, duration, or frequency. Previous studies indicated that the MAPK pathway transmits about one bit of information about the amplitude (concentration) of a stimulating cytokine, EGF. Sending more information may be enabled by temporal signal modulation. Here, we use the conceptual framework of information theory to support a hypothesis that the MAPK pathway, analyzed as a noisy information channel, reaches maximum information transmission rate when receiving sequences of EGF pulses that are transcoded to sequences of activity pulses of an effector kinase of the pathway, ERK. Since the pathway resetting time is about 1 hour, one could expect that—when sending EGF pulses of “0” or “1” amplitude every hour—the pathway is able transmit up to 1 bit per hour. We show, however, that when EGF pulses are separated by intervals that are not shorter than 1 hour and are multiples of 15 min (60, 75, 90 min, etc.), information rate can be nearly 2 bits per hour. We hypothesize that high information rate is necessary to control cell proliferation and motility.