bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double deficiency of toll-like receptors 2 and 4 alters long-term neurological sequelae in mice cured of pneumococcal meningitis
Authors: Too Lay Khoon , Yau Belinda , Baxter Alan G. , McGregor Iain S. , Hunt Nicholas H. 
Published: November 2019

AbstractToll-like receptor (TLR) 2 and 4 signalling pathways are central to the body’s defence against invading pathogens during pneumococcal meningitis. Whereas several studies support their importance in innate immunity, thereby preventing host mortality, any role in protecting neurological function during meningeal infection is ill-understood. Here we investigated both the acute immunological reaction and the long-term neurobehavioural consequences of experimental pneumococcal meningitis in mice lacking both TLR2 and TLR4. The absence of these TLRs significantly impaired survival in mice inoculated intracerebroventricularly withStreptococcus pneumoniae. During the acute phase of infection, TLR2/4-deficient mice had lower cerebrospinal fluid concentrations of interleukin-1β, and higher interferon-γ, than their wild-type counterparts. After antibiotic cure, TLR2/4 double deficiency was associated with aggravation of behavioural impairment in mice, as shown by diurnal hypolocomotion throughout the adaptation phases in the Intellicage of TLR-deficient mice compared to their wild-type counterparts. While TLR2/4 double deficiency did not affect the cognitive ability of mice in a patrolling task, it aggravated the impairment of cognitive flexibility. We conclude that TLR2 and TLR4 are central to regulating the host inflammatory response in pneumococcal meningitis, which may mediate diverse compensatory mechanisms that protect the host not only against mortality but also long-term neurological complications.
Neural correlates of theory of mind in typically-developing youth: Influence of sex, age and callous-unemotional traits
Authors: Gao Yidian , Rogers Jack C. , Pauli Ruth , Clanton Roberta , Baker Rosalind , Birch Philippa , Ferreira Lisandra , Brown Abigail , Freitag Christine M. , Fairchild Graeme , Rotshtein Pia , De Brito Stephane A. 
Published: November 2019

AbstractTheory of mind (ToM), or the ability to infer and predict the intentions, thoughts and beliefs of others, involves cognitive perspective taking (cognitive ToM/cToM) and understanding emotions (affective ToM/aToM). While behavioral evidence indicates that ToM is influenced by sex and age, no study has examined the influence of these variables on the neural correlates of cToM and aToM in late childhood/adolescence. Using fMRI with 35 typically-developing youths (aged 9–18 years, 12 males), we investigated the influence of sex and age on the neural correlates of cToM and aToM. We also examined how callous-unemotional traits, indexing a lack of empathy, were related to brain responses during aToM. Across both conditions, we found convergent activity in ToM network regions, such as superior temporal sulcus/temporoparietal junction (TPJ) and precuneus across males and females, but males recruited the left TPJ significantly more than females during cToM. During aToM, age was negatively correlated with brain responses in frontal, temporal and posterior midline regions, while callous-unemotional traits were positively correlated with right anterior insula responses. These results provide the first evidence in youth that sex influences the neural correlates of cToM, while age and callous-unemotional traits are specifically related to brain responses during aToM.
Discovery of Novel Multi-target Inhibitor of angiotensin type 1 receptor and neprilysin inhibitors from Traditional Chinese Medicine
Authors: Huo Xiaoqian , Qiao Liansheng , Chen Yankun , Chen Xi , He Yusu , Zhang Yanling 
Published: November 2019

AbstractAngiotensin II type-1 receptor–neprilysin inhibitor (ARNi) is consisted of Angiotensin II type-1 receptor (AT1) antagonist and neprilysin (NEP) inhibitor, which could simultaneously increase the vasodilators of the natriuretic peptides and antagonize vasoconstrictors of Ang II. ARNi has been proved a superior effect and lower risks of death on chronic heart failure (CHF) and hypertension. In this paper, ARNi from Traditional Chinese Medicines (TCM) was discovered based on target combination of AT1 and NEP by virtual screening, biological assay and molecular dynamics (MD) simulations. Two customized strategies of combinatorial virtual screening were implemented to discover AT1 antagonist and NEP inhibitor based on pharmacophore modeling and docking computation respectively. Gyrophoric acid (PubChem CID: 135728) from Parmelia saxatilis was selected as AT1 antagonist and assayed with IC50 of 29.76 μM by calcium influx assay. And 3,5,3′-triiodothyronine (PubChem CID: 861) from Bos taurus domesticus was screened as NEP inhibitor and has a dose dependent inhibitory activity by biochemistry fluorescence assay. Combined with MD simulations, these compounds can generate interaction with the target, key interactive residues of ARG167, TRP84, and VAL108 in AT1, and HIS711 in NEP were also identified respectively. This study designs the combinatorial strategy to discover novel frames of ARNi from TCM, and gyrophoric acid and 3,5,3′-triiodothyronine could provide the clues and revelations of drug design and therapeutic method of CHF and hypertension for TCM clinical applications.
Docosahexaenoyl ethanolamide mitigates IgE-mediated allergic reactions by inhibiting mast cell degranulation and regulating allergy-related immune cells
Authors: Nishi Kosuke , Kanayama Yoshiki , Kim In-Hae , Nakata Akihiro , Nishiwaki Hisashi , Sugahara Takuya 
Published: November 2019

AbstractDocosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid mainly found in fish oil. Although several studies have suggested that it can alleviate allergy symptoms, its mechanism of action remains to be elucidated. In the present study, we found that docosahexaenoyl ethanolamide (DHEA), a metabolite of DHA produced in the human body, exerts the anti-allergic activityin vitroandin vivo. DHEA suppressed degranulation of rat basophilic leukemia RBL-2H3 cells and bone marrow-derived mast cells in a dose-dependent manner without cytotoxicity. This occurred due to a decrease in Ca2+influx, which is critical for mast cell degranulation. DHEA also suppressed IgE-mediated passive cutaneous anaphylaxis reaction in mice. In addition, DHEA was demonstrated to lessen an allergic symptom in a mouse model of pollinosis and to alter the production of IgE and cytokines secreted by splenocytes collected from the pollinosis mice. Taken together, this study indicates that DHEA is a promising anti-allergic agent as it inhibits mast cell degranulation and modulates other immune cells.
Recent Lake Area Changes in Central Asia
Authors: Liu Haijun , Chen Yaning , Ye Zhaoxia , Li Yupeng , Zhang Qifei 
Published: November 2019

AbstractUsing Moderate Resolution Imaging Spectroradiometer (MODIS) 500 m spatial resolution global water product data, Least Squares Method (LSM) was applied to analyze changes in the area of 14 lakes in Central Asia from 2001 to 2016. Interannual changes in lake area, along with seasonal change trends and influencing factors, were studied for the months of April, July and September. The results showed that the total lakes area differed according to interannual variations and was largest in April and smallest in September, measuring −684.9 km2/a, −870.6 km2/a and −827.5 km2/a for April, July and September, respectively. The change rates for the total area of alpine lakes during the same three months were 31.1 km2/a, 29.8 km2/a and 30.6 km2/a, respectively, while for lakes situated on plains, the change rates were −716.1 km2/a, −900.5 km2/a, and −858 km2/a, respectively. Overall, plains lakes showed a declining trend and alpine lakes showed an expanding trend, the latter likely due to the warmer and wetter climate. Furthermore, there was a high correlation (r = 0.92) between area changes rate of all alpine lakes and the lakes basin supply coefficient, although there was low correlation (r = 0.43) between area changes rate of all alpine lakes area and glacier area/lake area. This indicates that lakes recharge via precipitation may be greater than lakes recharge via glacier meltwater. The shrinking of area changes for all plains lakes in the study region was attributable to climate change and human activities.
Spleen Stiffness as Predictor of Esophageal Varices in Cirrhosis of Different Etiologies
Authors: Fierbinteanu-Braticevici Carmen , Tribus Laura , Peagu Razvan , Petrisor Ana , Baicus Cristian , Cretoiu Dragos , Pasternak Artur , Oprea Gabriela , Purcareanu Adina , Moldoveanu Alexandru C. 
Published: November 2019

AbstractThe purpose of this study is to determine whether esophageal varices (EV) can be identified through the evaluation of spleen stiffness (SSM) via acoustic radiation force impulse (ARFI). A total of 135 patients suffering from cirrhosis underwent a clinical exam, laboratory tests, abdominal ultrasound, liver stiffness (LSM) measurement, SSM evaluation and upper gastrointestinal endoscopy. Based on the endoscopy results, the patients were classified into three groups: those with no evident EV, those with small EV and those with varices needing treatment (VNT). Patients with EV of any grade had significantly higher average SSM values over those with no EV (3.37 m/s versus 2.79 m/s, p-value < 0.001), while patients with VNT showed an even greater difference (3.96 m/s versus 2.93 m/s, p-value < 0.001). SSM proved to be an excellent method of predicting patients with VNT.
Quantitative Gait Analysis and Cerebrospinal Fluid Tap Test for Idiopathic Normal-pressure Hydrocephalus
Authors: Lim Yong-Hyun , Ko Pan-Woo , Park Ki-Su , Hwang Sung Kyoo , Kim Sung-Hee , Han Jaehwan , Yoon Uicheul , Lee Ho-Won , Kang Kyunghun 
Published: November 2019

AbstractWe investigated gait performance utilizing a quantitative gait analysis for 2 groups: (1) idiopathic normal-pressure hydrocephalus (INPH) patients who had a positive response to the cerebrospinal fluid tap test (CSFTT) and (2) healthy controls. The aims of the study were (1) to analyze the characteristics of gait features, (2) to characterize changes in gait parameters before and after the CSFTT, and (3) to determine whether there was any relationship between stride time and stride length variability and Frontal Assessment Battery (FAB) scores in INPH patients. Twenty-three INPH patients and 17 healthy controls were included in this study. Compared with healthy controls, the gait of INPH patients was characterized by lower velocity, shorter stride length, and more broad-based gait. Patients with INPH had a longer stance phase with increased double-limb support. Variability in stride time and stride length was increased in INPH patients. Stride time and stride length variability were correlated with FAB score. After the CSFTT, gait velocity, stride length, and step width significantly improved. There were significant decreases in stride time and stride length variability. These results suggest that the CSFTT for INPH patients might improve the so-called balance-related gait parameter (ie, step width) as well. Stride time and stride length variability also responded to the CSFTT. Association between FAB scores and both stride time and stride length variability suggests involvement of similar circuits producing gait variability and frontal lobe functions in INPH patients.
Defining the impact of exoribonucleases in the shift between exponential and stationary phases
Authors: Pobre Vânia , Barahona Susana , Dobrzanski Tatiane , Steffens Maria Berenice Reynaud , Arraiano Cecília M. 
Published: November 2019

AbstractThe transition between exponential and stationary phase is a natural phenomenon for all bacteria and requires a massive readjustment of the bacterial transcriptome. Exoribonucleases are key enzymes in the transition between the two growth phases. PNPase, RNase R and RNase II are the major degradative exoribonucleases in Escherichia coli. We analysed the whole transcriptome of exponential and stationary phases from the WT and mutants lacking these exoribonucleases (Δpnp, Δrnr, Δrnb, and ΔrnbΔrnr). When comparing the cells from exponential phase with the cells from stationary phase more than 1000 transcripts were differentially expressed, but only 491 core transcripts were common to all strains. There were some differences in the number and transcripts affected depending on the strain, suggesting that exoribonucleases influence the transition between these two growth phases differently. Interestingly, we found that the double mutant RNase II/RNase R is similar to the RNase R single mutant in exponential phase while in stationary phase it seems to be closer to the RNase II single mutant. This is the first global transcriptomic work comparing the roles of exoribonucleases in the transition between exponential and stationary phase.
Nutritional status of honey bee (Apis mellifera L.) workers across an agricultural land-use gradient
Authors: Smart Matthew D. , Otto Clint R. V. , Lundgren Jonathan G. 
Published: November 2019

AbstractLand use, habitat, and forage quality have emerged as critical factors influencing the health, productivity, and survival of honey bee colonies. However, characterization of the mechanistic relationship between differential land-use conditions and ultimate outcomes for honey bee colonies has been elusive. We assessed the physiological health of individual worker honey bees in colonies stationed across a gradient of agricultural land use to ask whether indicators of nutritional physiology including glycogen, total sugar, lipids, and protein were associated with land-use conditions over the growing season and colony population size the subsequent spring during almond pollination. Across the observed land-use gradient, we found that September lipid levels related to growing-season land use, with honey bees from apiaries surrounded by more favorable land covers such as grassland, pasture, conservation land, and fallow fields having greater lipid reserves. Further, we observed a significant relationship between total protein during September and population size of colonies during almond pollination the following February. We demonstrate and discuss the utility of quantifying nutritional biomarkers to infer land-use quality and predict colony population size.
The biological activity of bispecific trastuzumab/pertuzumab plant biosimilars may be drastically boosted by disulfiram increasing formaldehyde accumulation in cancer cells
Authors: Komarova Tatiana V. , Sheshukova Ekaterina V. , Kosobokova Ekaterina N. , Kosorukov Vyacheslav S. , Shindyapina Anastasia V. , Lipskerov Fedor A. , Shpudeiko Polina S. , Byalik Tatiana E. , Dorokhov Yuri L. 
Published: November 2019

AbstractStudies of breast cancer therapy have examined the improvement of bispecific trastuzumab/pertuzumab antibodies interacting simultaneously with two different epitopes of the human epidermal growth factor receptor 2 (HER2). Here, we describe the creation and production of plant-made bispecific antibodies based on trastuzumab and pertuzumab plant biosimilars (bi-TPB-PPB). Using surface plasmon resonance analysis of bi-TPB-PPB antibodies binding with the HER2 extracellular domain, we showed that the obtained Kd values were within the limits accepted for modified trastuzumab and pertuzumab. Despite the ability of bi-TPB-PPB antibodies to bind to Fcγ receptor IIIa and HER2 oncoprotein on the cell surface, a proliferation inhibition assay did not reveal any effect until α1,3-fucose and β1,2-xylose in the Asn297-linked glycan were removed. Another approach to activating bi-TPB-PPB may be associated with the use of disulfiram (DSF) a known aldehyde dehydrogenase 2 (ALDH2) inhibitor. We found that disulfiram is capable of killing breast cancer cells with simultaneous formaldehyde accumulation. Furthermore, we investigated the capacity of DSF to act as an adjuvant for bi-TPB-PPB antibodies. Although the content of ALDH2 mRNA was decreased after BT-474 cell treatment with antibodies, we only observed cell proliferation inhibiting activity of bi-TPB-PPB in the presence of disulfiram. We concluded that disulfiram can serve as a booster and adjuvant for anticancer immunotherapy.
Association of anthropometric parameters with amplitude and crosstalk of mechanomyographic signals during forearm flexion, pronation and supination torque tasks
Authors: Talib Irsa , Sundaraj Kenneth , Lam Chee Kiang 
Published: November 2019

AbstractThis study aimed to quantify the association of four anthropometric parameters of the human arm, namely, the arm circumference (CA), arm length (LA), skinfold thickness (ST) and inter-sensor distance (ISD), with amplitude (RMS) and crosstalk (CT) of mechanomyography (MMG) signals. Twenty-five young, healthy, male participants were recruited to perform forearm flexion, pronation and supination torque tasks. Three accelerometers were employed to record the MMG signals from the biceps brachii (BB), brachialis (BRA) and brachioradialis (BRD) at 80% maximal voluntary contraction (MVC). Signal RMS was used to quantify the amplitude of the MMG signals from a muscle, and cross-correlation coefficients were used to quantify the magnitude of the CT among muscle pairs (BB & BRA, BRA & BRD, and BB & BRD). For all investigated muscles and pairs, RMS and CT showed negligible to low negative correlations with CA, LA and ISD (r = −0.0001–−0.4611), and negligible to moderate positive correlations with ST (r = 0.004–0.511). However, almost all of these correlations were statistically insignificant (p > 0.05). These findings suggest that RMS and CT values for the elbow flexor muscles recorded and quantified using accelerometers appear invariant to anthropometric parameters.
Speeding up maximum population transfer in periodically driven multi-level quantum systems
Authors: Carrasco Sebastián , Rogan José , Valdivia Juan Alejandro 
Published: November 2019

AbstractA fast and robust approach to controlling the quantum state of a multi-level quantum system is investigated using a twofrequency time-varying potential. A comparison with other related approaches in the context of a two-level system is also presented, showing similar times and fidelities. As a concrete example, we study the problem of a particle in a box with a periodically oscillating infinite square-well potential, from which we obtain results that can be applied to systems with periodically oscillating boundary conditions. We show that the transition between the ground and first excited state is about 20 times faster than the one performed using a single frequency, both with fidelity of 99.97%. The transition time is about 3.5 times the minimum allowed by quantum mechanics. A test of the robustness of the approach is presented, concluding that, counter-intuitively, it is not only faster but also easier to tune up two frequencies than one. This robustness makes the approach suitable for real applications.
Differential Inhibition of Human and Trypanosome Ubiquitin E1S by TAK-243 Offers Possibilities for Parasite Selective Inhibitors
Authors: Boer D. Roeland , Bijlmakers Marie-José 
Published: November 2019

AbstractNovel strategies to target Trypanosoma brucei, Trypanosoma cruzi and Leishmania are urgently needed to generate better and safer drugs against Human African Trypanosomiasis, Chagas disease and Leishmaniasis, respectively. Here, we investigated the feasibility of selectively targeting in trypanosomatids the ubiquitin E1 activating enzyme (UBA1), an essential eukaryotic protein required for protein ubiquitination. Trypanosomatids contain two UBA1 genes in contrast to mammals and yeast that only have one, and using T. brucei as a model system, we show that both are active in vitro. Surprisingly, neither protein is inhibited by TAK-243, a potent inhibitor of human UBA1. This resistance stems from differences with the human protein at key amino acids, which includes a residue termed the gatekeeper because its mutation in E1s leads to resistance to TAK-243 and related compounds. Importantly, our results predict that trypanosomatid selective UBA1 inhibition is feasible and suggest ways to design novel compounds to achieve this.
Computational and NMR studies of RNA duplexes with an internal pseudouridine-adenosine base pair
Authors: Deb Indrajit , Popenda Łukasz , Sarzyńska Joanna , Małgowska Magdalena , Lahiri Ansuman , Gdaniec Zofia , Kierzek Ryszard 
Published: November 2019

AbstractPseudouridine (Ψ) is the most common chemical modification present in RNA. In general, Ψ increases the thermodynamic stability of RNA. However, the degree of stabilization depends on the sequence and structural context. To explain experimentally observed sequence dependence of the effect of Ψ on the thermodynamic stability of RNA duplexes, we investigated the structure, dynamics and hydration of RNA duplexes with an internal Ψ-A base pair in different nearest-neighbor sequence contexts. The structures of two RNA duplexes containing 5′-GΨC/3′-CAG and 5′-CΨG/3′-GAC motifs were determined using NMR spectroscopy. To gain insight into the effect of Ψ on duplex dynamics and hydration, we performed molecular dynamics (MD) simulations of RNA duplexes with 5′-GΨC/3′-CAG, 5′-CΨG/3′-GAC, 5′-AΨU/3′-UAA and 5′-UΨA/3′-AAU motifs and their unmodified counterparts. Our results showed a subtle impact from Ψ modification on the structure and dynamics of the RNA duplexes studied. The MD simulations confirmed the change in hydration pattern when U is replaced with Ψ. Quantum chemical calculations showed that the replacement of U with Ψ affected the intrinsic stacking energies at the base pair steps depending on the sequence context. The calculated intrinsic stacking energies help to explain the experimentally observed sequence dependent changes in the duplex stability from Ψ modification.
Roots compact the surrounding soil depending on the structures they encounter
Authors: Lucas Maik , Schlüter Steffen , Vogel Hans-Jörg , Vetterlein Doris 
Published: November 2019

AbstractContradictory evidence exists regarding whether and to which extend roots change soil structure in their vicinity. Here we attempt to reconcile disparate views allowing for the two-way interaction between soil structure and root traits, i.e. changes in soil structure due to plants and changes in root growth due to soil structure. Porosity gradients extending from the root/biopore surface into the bulk soil were investigated with X-ray µCT for undisturbed soil samples from a field chronosequence as well as for a laboratory experiment with Zea mays growing into three different bulk densities. An image analysis protocol was developed, which enabled a fast analysis of the large sample pool (n > 300) at a resolution of 19 µm. Lab experiment showed that growing roots only compact the surrounding soil if macroporosity is low and dominated by isolated pores. When roots can grow into a highly connected macropore system showing high connectivity the rhizosphere is more porous compared to the bulk soil. A compaction around roots/biopores in the field chronosequence was only observed in combination with high root/biopore length densities. We conclude that roots compact the rhizosphere only if the initial soil structure does not offer a sufficient volume of well-connected macropores.