bluuebunny/crossref_metadata_2025 huggingface dataset:
Attachment‐Related Representations and Suicidal Ideations in Nonsuicidal Self‐Injury Adolescents with and without Suicide Attempts: A Pilot Study
Authors: Pallini Susanna , Terrinoni Arianna , Iannello Sara , Cerutti Rita , Ferrara Mauro , Fantini Fiorella , Laghi Fiorenzo
Published: March 2020

Objectives

Consistent with the debate surrounding the association between nonsuicidal self‐injury (NSSI), suicidal intent, and suicidal behavior, and between NSSI and dysregulation processes, we attempted to analyze suicide intent and emotion dysregulation in NSSI adolescents, in the framework of the attachment representations and exploring these clues of emotion dysregulation characteristics of insecure attachment. Furthermore, we intended to focus on these attachment‐related segregated systems regarding death and suicidal ideations, to explore how differently they would characterize self‐injuring adolescents with and without suicide attempts.

Methods

Thirty‐four NSSI inpatient adolescents, 17 with suicide attempts, 17 without suicide attempts, and 17 healthy controls (age 11–17) were assessed using Adult Attachment Projective, which allows for the classification of attachment status and related emotion dysregulation and segregated systems.

Results

The majority of the NSSI group with and without suicide attempts showed unresolved (disorganized) attachment‐related representations and clues of damaged reflective functions, whereas only the NSSI with suicide attempts showed clues of impaired interpersonal relationships. The two clinical groups used words expressing suicidal intent, whereas the healthy group did not.

Conclusions

Therapists are encouraged not to underestimate suicidal ideation in NSSI regardless of whether or not they have already attempted suicide.
The novel HLA‐DRB1*14:221 allele was identified during high‐resolution HLA typing
Authors: Loginova Maria , Smirnova Daria , Paramonov Igor , Kozhemyako Oxana
Published: March 2020

The new allele HLA‐DRB1*14:221 showed two nucleotide differences with HLA‐DRB1*14:33.
A multimodel regime for evaluating effectiveness of antimicrobial wound care products in microbial biofilms
Authors: Stoffel Joseph J. , Kohler Riedi Petra L. , Hadj Romdhane Brittany
Published: March 2020

Microbial biofilms have become increasingly recognized as a cause of wound chronicity. There are several topical antimicrobial wound care products available for use; however, their effectiveness has routinely been demonstrated with planktonic microorganisms. There is no target reference value for antimicrobial effectiveness of wound care products in biofilm models. In addition, data on antimicrobial activity of products in biofilm models are scattered across many test methods in a variety of studies. The aim of this work is to directly compare commercial products containing the commonly used topical antimicrobial agents iodine, silver, polyhexamethylene biguanide, octenidine, hypochlorous acid, benzalkonium chloride, and a surfactant‐based topical containing poloxamer 188. Five different in vitro biofilm models of varied complexity were used, incorporating several bacterial pathogens such as Staphylococcus, Enterococcus, Streptococcus, Pseudomonas, Acinetobacter, Klebsiella, and Enterobacter. The fungal pathogens Candida albicans and Candida auris were also evaluated. A multispecies bacterial biofilm model was also used to evaluate the products. Additionally, C. albicans was used in combination with S. aureus and P. aeruginosa in a multikingdom version of the polymicrobial biofilm model. Statistically significant differences in antimicrobial performance were observed between treatments in each model and changing microbial growth conditions or combinations of organisms resulted in significant performance differences for some treatments. The iodine and benzalkonium chloride‐containing products were overall the most effective in vitro and were then selected for in vivo evaluation in an infected immunocompromised murine model. Unexpectedly, the iodine product was statistically (P > .05) no different than the untreated control, while the benzalkonium chloride containing product significantly (P < .05) reduced the biofilm compared to untreated control. This body of work demonstrates the importance of not only evaluating antimicrobial wound care products in biofilm models but also the importance of using several different models to gain a comprehensive understanding of products' effectiveness.
Fibroblast‐specific Stat1 deletion enhances the myofibroblast phenotype during tissue repair
Authors: Medley Shayna C. , Rathnakar Bharath H. , Georgescu Constantin , Wren Jonathan D. , Olson Lorin E.
Published: March 2020

Signal transducer and activator of transcription 1 (Stat1) is a ubiquitously expressed latent transcription factor that is activated by many cytokines and growth factors. Global Stat1 knockout mice are prone to chemical‐induced lung and liver fibrosis, suggesting roles for Stat1 in tissue repair. However, the importance of Stat1 in fibroblast‐mediated and vascular smooth muscle cell (VSMC)‐mediated injury response has not been directly evaluated in vivo. Here, we focused on two models of tissue repair in conditional Stat1 knockout mice: excisional skin wounding in mice with Stat1 deletion in dermal fibroblasts, and carotid artery ligation in mice with global Stat1 deletion or deletion specific to VSMCs. In the skin model, dermal wounds closed at a similar rate in mice with fibroblast Stat1 deletion and controls, but collagen and α‐smooth muscle actin (αSMA) expression were increased in the mutant granulation tissue. Cultured Stat1
−/− and Stat1
+/− dermal fibroblasts exhibited similar αSMA+ stress fiber assembly, collagen gel contraction, proliferation, migration, and growth factor‐induced gene expression. In the artery ligation model, there was a significant increase in fibroblast‐driven perivascular fibrosis when Stat1 was deleted globally. However, VSMC‐driven remodeling and neointima formation were unchanged when Stat1 was deleted specifically in VSMCs. These results suggest an in vivo role for Stat1 as a suppressor of fibroblast mediated, but not VSMC mediated, injury responses, and a suppressor of the myofibroblast phenotype.
Antiarrhythmic drug effects on premature beats are partly determined by prior cardiac activation frequency in perfused guinea‐pig heart
Authors: Osadchii Oleg E.
Published: March 2020

New Findings

What is the central question of this study?

Can antiarrhythmic drug effects on repolarization, conduction time and excitation wavelength in premature beats be determined by prior cardiac activation frequency?

What is the main finding and its importance?

In premature beats induced after a series of cardiac activations at a slow rate, antiarrhythmics prolong repolarization but evoke little or no conduction delay, thus increasing the excitation wavelength, which indicates an antiarrhythmic effect. Fast prior activation rate attenuates prolongation of repolarization, while amplifying the conduction delay induced by drugs, which translates into the reduced excitation wavelength, indicating proarrhythmia. These findings suggest that a sudden increase in heart rate can shape adverse pharmacological profiles in patients with ventricular ectopy.

Antiarrhythmic drugs used to treat atrial fibrillation can occasionally induce ventricular tachyarrhythmia, which is typically precipitated by a premature ectopic beat through a mechanism related, in part, to the shortening of the excitation wavelength (EW). The arrhythmia is likely to occur when a drug induces a reduction, rather than an increase, in the EW of ectopic beats. In this study, I examined whether the arrhythmic drug profile is shaped by the increased cardiac activation rate before ectopic excitation. Ventricular monophasic action potential durations, conduction times and EW values were assessed during programmed stimulations applied at long (S1–S1 [basic drive cycle length] = 550 ms) and short (S1–S1 = 200 ms) cycle lengths in perfused guinea‐pig hearts. The premature activations were induced with extrastimulus application immediately upon termination of the refractory period. With dofetilide, a class III antiarrhythmic agent, a prolongation in action potential duration and the resulting increase in the EW obtained at S1–S1 = 550 ms were significantly attenuated at S1–S1 = 200 ms, in both the regular (S1) and the premature (S2) beats. With class I antiarrhythmic agents (quinidine, procainamide and flecainide), fast S1–S1 pacing was found to attenuate the drug‐induced increase in action potential duration, while amplifying drug‐induced conduction slowing, in both S1 and S2 beats. As a result, although the EW was increased (quinidine and procainamide) or not changed (flecainide) at the long S1–S1 intervals, it was invariably reduced by these agents at the short S1–S1 intervals. These findings indicate that the increased heart rate before ectopic activation shapes the arrhythmic profiles by facilitating drug‐induced EW reduction.
System Parameter Optimization for a Frequency-Up-Conversion Piezoelectric Energy Harvester With Backward Mechanical-Electric Coupling Effect
Authors: Wang Fengxia
Published: March 2020

In this work, a parametric model for a frequency-up-conversion piezoelectric energy harvester (PEH) was developed based on the Galerkin method. The PEH is composed of a piezoelectric bimorph and a stopper, which was subjected to a harmonic excitation. Although backward coupling results in a structure dynamic damping, models with neglected backward coupling were often adopted to estimate the output power of a piezoelectric energy harvester. The purpose of this work is to examine the effect of backward coupling on the dynamic response and the output power generation for a frequency-up-conversion PEH. With the same base excitations, we compared the dynamics and output energies of two cases: (1) neglecting the backward coupling effect (BCE) in the model and (2) including the BCE in the model. To obtain the optimum gap with maximum output power, we studied the relationship between the output power and the gap of the steady-state solutions. From the analytical results, it was found that the BCE can be neglected as long as there is no impact or the output power is small. However, once impacts get involved, the piezoelectric backward effect dominates the total damping due to small mechanical damping which is true for most PEH. The backward coupling will significantly diminish both the vibration and output power. Therefore, if the BCE is neglected in an impact-driven frequency-up-conversion PEH, the simplified model will exaggerate the output power.
How Chemistry Controls Engine Design
Authors: Flynn Patrick F.
Published: March 2020

A review of empirical engine data that exhibit the limits of the chemistry of fuel oxidation in engines is presented. These data have been compared to analyses using up to date fuel oxidation chemical analyses programs and shown to be in close agreement. The constraints caused by the fuel oxidation chemistry limitations are key determinants of the engine’s overall design, determining allowed intake conditions, fuel-air ratios, compression ratio requirements, and the need for such ancillary devices as those for exhaust emissions aftertreatment.
Diesel Spray Development From VCO Nozzles With Common-Rail
Authors: Bae Choongsik , Kang Jinsuk , Lee Hang-Kyung
Published: March 2020

Spray characteristics of diesel fuel injection system is one of the most important factors in diesel combustion and pollutant emissions especially in HSDI (High Speed Direct Injection) diesel engines where the interval between the onset of combustion and the evaporation of atomized fuel is relatively short.

An investigation into various spray characteristics from different holes of VCO (Valve Covered Orifice) nozzles was performed. The global characteristics of spray, including spray angle, spray tip penetration, and spray pattern were measured from the spray images, which were frozen by an instantaneous photography with a spark light source and ICCD. These spray images were acquired sequentially from the first injection to fifth injection to investigate injection-to-injection variation. For better understanding of spray development and their internal structures, a long-distance microscope was used to get magnified spray images at the vicinity of the nozzle hole with a laser sheet illumination. Also backward illuminated images with a spark light source were taken at various points of the spray field including vicinity of the nozzle hole to understand surface structures and breakup process of dense spray from VCO nozzle incorporated with common-rail injection system.

As injection pressure increases interaction between spray and ambient air becomes important to liquid penetration and spray angle. Macroscopic spray angle increases due to air entrainment as injection pressure increases though spray angle near the hole seems independent from injection pressure. Liquid penetration is initially affected by injection rate increase as needle is moving upward and liquid penetration increase rate is in accordance with injection pressure. After this stage, air entrainment and high potential of evaporation makes the increase rate slower and this tendency is more obvious for higher injection pressure. Microscopic images taken at the vicinity of the nozzle hole exit reveal that central dense region consists of thick ligaments or membranes and most of the liquid droplets are formed at the tip of ligaments from spray surface due to the waves developed on it. Some smaller liquid droplets seem to be generated from the bubble or membrane breakup process. Droplet sizing was performed from the microscopic images, which were frozen by spark light source that has light duration of 10ns and high-resolution CCD camera equipped with long distance microscope whose magnification factor is more than six. Fuel particle sizes, described as SMD (Sauter Mean Diameter) in many points, decreased during injection durations and higher injection pressure induced smaller value.
Effect of Injection Rate on the Performance and Emissions of a Direct-Injection Gasoline Engine in Comparison With the Port-Injection Operation
Authors: Shiga Seiichi , Kobayashi Kazumitsu , Hayakawa Eiji , Matsuura Takashi , Nakamura Hisao , Ishima Tsuneaki , Obokata Tomio
Published: March 2020

This paper presents a study on the effect of injection rate on the performance and emissions of a direct-injection gasoline engine operated with seven kinds of DI injection and a port-injection. The injection pressures were set at 0.3 and 7 MPa for port injection and DI operation modes respectively. The spray characteristics of DI injectors were obtained by measuring the SMD, droplet concentration and spray angle. The engine was run at a constant speed and load of 1000 rpm and 0.22 MPa of BMEP. The BSFC reduction of DI from port injection was 13% at most in which 4% was derived from the decrease in pumping loss and the remaining 9% was due to the improvement of the cycle efficiency. As for the injection rate effect in DI operation, the BSFC takes the minimum at a value of the injection rate where the maximum difference reached to 7%. It was revealed that this is due to the variation of the combustion efficiency and then corresponds to the behavior of droplet concentration. Soot emission correlated well with the SMD. Thus the performance and emissions were mostly explained by the spray characteristics.
An Experimental and Numerical Investigation of Turbulent Mixing of Subsonic Gas Jets in a Coaxial Configuration
Authors: Mahalakshmi N. V. , Ilangovan V.
Published: March 2020

Measurements of mean temperature, velocity, the normal stresses and Reynolds shear stress are reported in the mixing region of coaxial jet flows. The measurements were obtained with three different outer jet exit temperature of 15, 30 and 45°C above ambient with the constant exit Reynolds number. The satisfactory representation of the jet is dependent on adequate representation of turbulence in the jet, which determines its spread and mixing. The standard k-ε model is used to predict the mean and turbulent flow fields. The deviation of predicted results from experimental kinetic energy at high exit temperature difference can be due to the anistotropic charter of the mixing region. Measurements performed at different axial stations provide a broad database against which result of calculation procedures embodying k-ε turbulence model can be compared. The normal stress results show substantial deviations from isotropy. This clearly indicates the need to consider the normal stresses in any turbulence model of such flows.
Passenger-Car Fuel Consumption Versus Performance in Retrospect
Authors: Amann Charles A.
Published: March 2020

Over the last quarter of the 1900s, the U.S. Environmental Protection Agency (EPA) has annually tabulated the fuel economy and performance characteristics of the new passenger-car fleet. Fuel economy was measured over the EPA combined urban and highway driving schedules. The performance metric was the estimated acceleration time from a standing start to 60 miles per hour (mph). In the present study, the interplay among factors influencing these characteristics is reviewed. Then, for the average new car in a given year, the manner in which fuel consumption and acceleration time are influenced by vehicle weight and engine power are examined. The departure of individual vehicles from this average trend is considered. Finally, a few of the prominent powertrain characteristics responsible for improvements in the tradeoff between fuel consumption and performance are listed.
A Multiple-Zone Cycle Simulation for Spark-Ignition Engines: Thermodynamic Details
Authors: Caton Jerald A.
Published: March 2020

A thermodynamic cycle simulation was developed for a spark-ignition engine which included the use of multiple zones for the combustion process. This simulation was used to complete analyses for a commercial, spark-ignition V-8 engine operating at a part load condition. Specifically, the engine possessed a compression ratio of 8.1:1, and had a bore and stroke of 101.6 and 88.4 mm, respectively. A part load operating condition at 1400 rpm with an equivalence ratio of 1.0 was examined.

Results were obtained for overall engine performance, for detailed in-cylinder events, and for the thermodynamics of the individual processes. In particular, the characteristics of the engine operation with respect to the combustion process were examined. Implications of the multiple zones formulation for the combustion process are described.
Engine Variables Affecting the SI Engine Knock
Authors: Karimifar Mansoor
Published: March 2020

To program the automatic performance control loops of the modern cars at the design stage, numerical result of engine variables effecting knock intensity is the most important tool. Although general aspects of the effect of engine operating conditions on knock have been studied in previous investigations, precise numerical results of that, are not available. The procedures proposed in the past to provide the requirements of the models either predicting or measuring knock are complicated and the details are not presented.

In the current work, on the basis of the ‘sampling frequency theorem’ and in regard to the measured frequency of the knocking-pressure fluctuations, a fast on-line data acquisition system was designed and developed. The system was used on a variable compression ratio research engine using two different fuels. Large number of the engine pressure crank angle data were recorded at different operating conditions. Knock, intensity measurement was carried out using a developed criteria obtained by a careful analysis of pressure oscillations at 0.25 degree crank angle intervals. This lead to identification of cycles having specified knock intensity over a wide range of operating conditions. Effect of engine variables on knock intensity was therefore measured numerically for both fuels. Using the simple criteria to study the effect of engine operating conditions on the intensity of knock produced the results which agreed with the earlier experimental findings.
Modeling Direct-Injection Gasoline HCCI Combustion Using Detailed Chemistry and CFD
Authors: Kong Song-Charng , Reitz Rolf D.
Published: March 2020

Detailed chemical kinetics was implemented into an engine CFD code to study the combustion process in Homogeneous Charge Compression Ignition (HCCI) engines. The CHEMKIN code was implemented into KIVA-3V such that the chemistry and flow solutions were coupled. Effects of turbulent mixing on the reaction rates were also considered. The model was validated using experimental data from a direct-injection Caterpillar engine operated in the HCCI mode using gasoline. The results show that good levels of agreement were obtained using the present KIVA/CHEMKIN model for a wide range of engine conditions including various injection timings, engine speeds, and loads. It was found that the effects of turbulent mixing on the reaction rates needed to be considered to correctly simulate the combustion phasing. It was also found that the presence of residual radicals could enhance the mixture reactivity and hence shorten the ignition delay time. The NOx emissions were found to increase as the injection timing was retarded, in agreement with experimental results.
Combustion Characteristics of Spark Ignition Engine Fuelled by LPG
Authors: Shehata M. S.
Published: March 2020

Experimental studies have been carried out for investigating engine performance parameters, cylinder pressure, emissions and engine thermal balance of spark ignition engine (S.I.E.) using either gasoline or Liquefied Petroleum Gases (LPG) as a fuel at maximum brake torque (MBT) ignition timing. MBT ignition timing for LPG is found to be 2 to 10 degrees crank angle more advance than for gasoline. Maximum cylinder pressure locations for gasoline and LPG are shifted towards top dead center (TDC) with increase engine speed. At low engine speed, maximum cylinder pressure for gasoline fuel is higher than for LPG fuel. At high engine speeds maximum cylinder pressure for LPG is nearly the same as for gasoline. Maximum pressure for ignition timing 35 crank angle (CA) before top dead center (BTDC) is greater than for 45 and 25 CA respectively. Engine produces more brake power with gasoline than with LPG. Engine brake thermal efficiency (ηbth) and volumetric efficiency (ηv) with LPG is less than for gasoline. When S.I.E converted from gasoline to LPG the loss in maximum power is nearly 14% and the loss in maximum efficiency is nearly 8%. UHC and CO concentrations for LPG are nearly one-tenth of that produced by gasoline at the same ignition timing and the same engine speed. For low engine speed exhaust and oil temperatures for gasoline and LPG increase with increase engine speed but for high engine speed exhaust and oil temperature decreases with increase engine speed. For gasoline and LPG cooling water temperature decreases with increase engine speed. Lubricating oil and cooling water temperatures for gasoline and LPG increase with increase ignition timing BTDC but exhaust gas temperature decreases with increase ignition timing. LPG has higher exhausted gas temperature than gasoline but gasoline has higher oil temperature than LPG. At different ignition timing exhaust loss for LPG is greater than for gasoline but cooling water loss for gasoline is greater than for LPG.
Preliminary Investigation of Dilution Strategies to Control Engine Torque During Transient Events
Authors: Maugham R. D. , Vaughan N. D. , Brace C. J. , Murray S. W.
Published: March 2020

A continuously variable transmission (CVT) allows a powertrain controller the freedom to develop a required output power at a range of engine torque and speed conditions. This flexibility can be used to maximise fuel efficiency. Due to low frictional and pumping losses a gasoline engine’s fuel efficiency is maximised at low speed, high torque conditions. However due to the reduced torque margin available, controlling a gasoline engine in this region compromises transient vehicle response. Dilution torque control, using EGR or lean burn, has the potential to maintain the economy gains available using a CVT powertrain whilst improving a vehicle’s driveability.

This paper introduces preliminary work that has been undertaken to investigate the potential of charge dilution to control steady state engine torque. A test rig has been developed based around an engine fitted with variable cam phasing and an external EGR system. The paper contains a discussion of initial results of a lean dilution test program used to demonstrate the principle.
Optimum Design of the Continuously Variable Transmission for a Motorcycle
Authors: Huang Yuan Mao , Hu Bi Shyang
Published: March 2020

Many design parameters affect the performance of continuous variable transmissions. This paper presents the optimization of a continuous variable transmission by using the simulated annealing algorithm. The Bessel method of curve fitting and the tensor product method of surface fitting were used to facilitate the discrete fuel consumption, emissions of carbon monoxide (CO) and HC compound of experimental engine data. A compromise method was used to analyze the multi-objective functions. The values for design variables are recommended for further development.
Effect of terminal methyl group concentration on critical properties and plasma resistance of organosilicate low-k dielectrics
Authors: Rezvanov Askar A. , Miakonkikh Andrey V. , Seregin Dmitry S. , Vishnevskiy Alexey S. , Vorotilov Konstantin A. , Rudenko Konstantin V. , Baklanov Mikhail R.
Published: March 2020

Surfactant-templated porous organosilicate glass low-k films have been deposited by using a tetraethoxysilane (TEOS) and methyltriethoxysilane (MTEOS) mixture with different ratios and Brij® 30 surfactant. The deposited films contain different concentrations of terminal methyl groups that are proportional to the MTEOS concentration. Increasing the methyl group concentration by changing the TEOS/MTEOS ratio decreases the open porosity, k-value, and Young's modulus and increases the mean pore radius, although the template concentration was kept constant. The plasma etch rate well correlates with the number of fluorine atoms penetrated into pores. Plasma damage by fluorine radicals depends on the carbon concentration in the films. It can be reduced by 60% when the carbon concentration in the films exceeds 10 at. % as measured by XPS (the films deposited with the TEOS/MTEOS ratio of 40/60). Damage to the dielectrics associated with exposure to vacuum ultraviolet photons is reduced by more than 70% for the same samples.
Array directivity enhancement by leveraging angle-dependent scattering
Authors: Joffre Dagny , Niezrecki Christopher , Avitabile Peter
Published: March 2020

The quality of a sonar array's localization capabilities, often expressed as directivity, is limited by the sonar's aperture, that is, the length of the sonar array. Previous attempts to improve directivity, without increasing array size, have been moderately successful. Wave scattering within a nontraditional array, such as an array fabricated from a non-homogeneous material, could provide additional information to the localization calculations and improve array directivity without increasing the size of the array. An investigation of array directivity improvement through wave scattering is performed. This paper modifies existing localization and directivity calculations to consider the scattered waves and uses the derived equations to explain why previous proposed scattering was incapable of increasing directivity. A scattering relationship capable of enhancing array localization without increasing array size is proposed, and the directivity improvement claims are verified with beamform plot comparisons and directivity index calculations.
Effects of Drop Jumps on 1000-m Performance Time and Pacing in Elite Male and Female Endurance Runners
Authors: Boullosa Daniel , Abad César C.C. , Reis Valter P. , Fernandes Victor , Castilho Claudio , Candido Luis , Zagatto Alessandro M. , Pereira Lucas A. , Loturco Irineu
Published: March 2020

Purpose: To evaluate the effect of drop jumps (DJs) on performance time and pacing in a field test (ie, 1000 m) commonly used to evaluate endurance runners and to evaluate running and jumping performance in male and female athletes separately. Methods: Twenty elite endurance runners (male, n = 10, 27.8 [7.0] y, 62.3 [5.2] kg; female, n = 10, 25.9 [5.3] y, 51.7 [4.1] kg) competing in middle- and long-distance events participated in this study. After determination of the box height associated with the best reactive strength index, athletes randomly performed a warm-up with or without the inclusion of 5 DJs with the highest reactive strength index prior to a 1000-m track test. Performance time and pacing (250-m splits) were determined. Countermovement-jump heights at different time points and blood lactate concentration after running tests were also recorded. Results: A “possible” faster 1000-m time (162.4 vs 165.3 s) with a “very likely” faster first split (38.8 vs 40.3 s) was observed in male athletes in the DJ condition. In contrast, female athletes showed a “possible” slower running time (186.8 vs 184.8 s) and a “likely” greater blood lactate concentration after the 1000-m test in the DJ condition. Male and female athletes presented greater countermovement-jump performances after warm-up and running tests in both conditions. Conclusions: The inclusion of 5 DJs with the height associated with the best reactive strength index induced a “possible” improvement in 1000-m performance time in elite male endurance runners. The current protocol should be avoided in female athletes.
Trunk–Pelvis Kinematics Variability During Gait and Its Association With Trunk Muscle Endurance in Patients With Chronic Low Back Pain
Authors: Bagheri Rasool , Ebrahimi Takamjani Ismail , Pourahmadi Mohammad R. , Jannati Elham , Fazeli Sayyed H. , Hedayati Rozita , Akbari Mahmood
Published: March 2020

The first purpose was to investigate the trunk muscle endurance, the second aim was to evaluate the trunk–pelvis kinematics during gait, and the third was to evaluate the relationship between trunk–pelvis kinematics and the trunk muscle endurance. Thirty participants (15 nonspecific chronic low back pain [NCLBP] and 15 healthy) were included. The authors first assessed trunk muscle endurance on endurance testing protocols. The authors next measured the trunk–pelvis kinematics during gait using a 3-dimensional motion capture system. Angular displacement, waveform pattern (CVp), and offset variability (CVo) were also examined. Statistical analysis revealed a significant difference in (1) the trunk muscle endurance and (2) sagittal, frontal, and transverse planes CVp between groups (P < .05). A significant moderate correlation was found between supine double straight-leg raise and frontal CVp (r = .521, P = .03) and transverse planes CVp (r = .442, P = .05). However, a significant moderate correlation was observed between prone double straight-leg raise and sagittal plane CVp (r = .528, P = .03) and transverse plane CVp (r = .678, P = .001). The relationship between (1) lower trunk extensor endurance with transverse and sagittal planes CVp and (2) lower abdominal muscle endurance with transverse and frontal planes CVp suggests that gait variability in these planes may result because of trunk muscle deconditioning accompanying NCLBP.
Enhanced Efflux Pump Expression in
Candida
Mutants Results in Decreased Manogepix Susceptibility
Authors: Liston Sean D. , Whitesell Luke , Kapoor Mili , Shaw Karen Joy , Cowen Leah E.
Published: March 2020

Manogepix is a broad-spectrum antifungal agent that inhibits glycosylphosphatidylinositol (GPI) anchor biosynthesis. Using whole-genome sequencing, we characterized two efflux-mediated mechanisms in the fungal pathogens
Candida albicans
and
Candida parapsilosis
that resulted in decreased manogepix susceptibility. In
C. albicans
, a gain-of-function mutation in the transcription factor gene
ZCF29
activated expression of ATP-binding cassette transporter genes
CDR11
and
SNQ2
.
Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages
Authors: Volk Aaron , Hackbart Matthew , Deng Xufang , Cruz-Pulido Yazmin , O’Brien Amornrat , Baker Susan C.
Published: March 2020

Macrophages are an important cell type during coronavirus infections because they “notice” the infection and respond by inducing type I interferons, which limits virus replication. In turn, coronaviruses encode proteins that mitigate the cell’s ability to signal an interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses, one with reduced deubiquitinating activity (DUBmut) and the other containing an inactivated endoribonuclease (EndoUmut). We observed a rapid, robust, and focused response to the EndoUmut virus, which was characterized by enhanced expression of interferon and interferon-related genes. In contrast, wild-type virus and the DUBmut virus elicited a more limited interferon response and ultimately activated over 2,800 genes, including players in the unfolded protein response and proinflammatory pathways associated with progression of significant disease. This study reveals that EndoU activity substantially contributes to the ability of coronaviruses to evade the host innate response and to replicate in macrophages.
Epidermal Growth Factor Receptor and Abl2 Kinase Regulate Distinct Steps of Human Papillomavirus 16 Endocytosis
Authors: Bannach Carina , Brinkert Pia , Kühling Lena , Greune Lilo , Schmidt M. Alexander , Schelhaas Mario
Published: March 2020

Human papillomaviruses are small, nonenveloped DNA viruses that infect skin and mucosa. The so-called high-risk HPVs (e.g., HPV16, HPV18, HPV31) have transforming potential and are associated with various anogenital and oropharyngeal tumors. These viruses enter host cells by a novel endocytic pathway with unknown cellular function. To date, it is unclear how endocytic vesicle formation occurs mechanistically. Here, we addressed the role of epidermal growth factor receptor signaling, which has previously been implicated in HPV16 endocytosis and identified the kinase Abl2 as a novel regulator of virus uptake. Since other viruses, such as influenza A virus and lymphocytic choriomeningitis virus, possibly make use of related mechanisms, our findings shed light on fundamental strategies of virus entry and may in turn help to develop new host cell-targeted antiviral strategies.
Global Transcriptome Analysis Identifies a Diagnostic Signature for Early Disseminated Lyme Disease and Its Resolution
Authors: Petzke Mary M. , Volyanskyy Konstantin , Mao Yong , Arevalo Byron , Zohn Raphael , Quituisaca Johanna , Wormser Gary P. , Dimitrova Nevenka , Schwartz Ira
Published: March 2020

Lyme disease (LD), caused by
Borrelia burgdorferi
, is the most common tick-borne infectious disease in the United States. We examined gene expression patterns in the blood of individuals with early disseminated LD at the time of diagnosis (acute) and also at approximately 1 month and 6 months following antibiotic treatment. A distinct acute LD profile was observed that was sustained during early convalescence (1 month) but returned to control levels 6 months after treatment. Using a computer learning algorithm, we identified sets of 20 classifier genes that discriminate LD from other bacterial and viral infections. In addition, these novel LD biomarkers are highly accurate in distinguishing patients with acute LD from healthy subjects and in discriminating between individuals with active and resolved infection. This computational approach offers the potential for more accurate diagnosis of early disseminated Lyme disease. It may also allow improved monitoring of treatment efficacy and disease resolution.
Viral DNA Binding Protein SUMOylation Promotes PML Nuclear Body Localization Next to Viral Replication Centers
Authors: Stubbe Miona , Mai Julia , Paulus Christina , Stubbe Hans Christian , Berscheminski Julia , Karimi Maryam , Hofmann Samuel , Weber Elisabeth , Hadian Kamyar , Hay Ron , Groitl Peter , Nevels Michael , Dobner Thomas , Schreiner Sabrina
Published: March 2020

PML nuclear bodies (PML-NBs) are implicated in general antiviral defense based on recruiting host restriction factors; however, it is not understood so far why viruses would establish viral replication centers (RCs) juxtaposed to such “antiviral” compartments. To understand this enigma, we investigate the cross talk between PML-NB components and viral RCs to find the missing link connecting both compartments to promote efficient viral replication and gene expression. Taken together, the current concept is more intricate than originally believed, since viruses apparently take advantage of several specific PML-NB-associated proteins to promote productive infection. Simultaneously, they efficiently inhibit antiviral measures to maintain the viral infectious program. Our data provide evidence that SUMOylation of the viral RC marker protein E2A represents the basis of this virus-host interface and regulates various downstream events to support HAdV productive infection. These results are the basis of our current attempts to generate and screen for specific E2A SUMOylation inhibitors to constitute novel therapeutic approaches to limit and prevent HAdV-mediated diseases and mortality of immunosuppressed patients.
A Solution to Antifolate Resistance in Group B
Streptococcus
: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
Authors: Chambers Schuyler A. , Moore Rebecca E. , Craft Kelly M. , Thomas Harrison C. , Das Rishub , Manning Shannon D. , Codreanu Simona G. , Sherrod Stacy D. , Aronoff David M. , McLean John A. , Gaddy Jennifer A. , Townsend Steven D.
Published: March 2020

Group B
Streptococcus
is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.
Epstein-Barr Virus Epitope–Major Histocompatibility Complex Interaction Combined with Convergent Recombination Drives Selection of Diverse T Cell Receptor α and β Repertoires
Authors: Gil Anna , Kamga Larisa , Chirravuri-Venkata Ramakanth , Aslan Nuray , Clark Fransenio , Ghersi Dario , Luzuriaga Katherine , Selin Liisa K.
Published: March 2020

Several lines of evidence suggest that TCRα and TCRβ repertoires play a role in disease outcomes and treatment strategies during viral infections in transplant patients and in cancer and autoimmune disease therapy. Our data suggest that it is essential that we understand the basic principles of how to drive optimum repertoires for both TCR chains, α and β. We address this important issue by characterizing the CD8 TCR repertoire to a common persistent human viral infection (EBV), which is controlled by appropriate CD8 T cell responses. The ultimate goal would be to determine if the individuals who are infected asymptomatically develop a different TCR repertoire than those that develop the immunopathology of AIM. Here, we begin by doing an in-depth characterization of both CD8 T cell TCRα and TCRβ repertoires to two immunodominant EBV epitopes over the course of AIM, identifying potential factors that may be driving their selection.
Latent Toxoplasmosis Effects on Rodents and Humans: How Much is Real and How Much is Media Hype?
Authors: Johnson Hannah J. , Koshy Anita A.
Published: March 2020

Toxoplasma gondii
is a ubiquitous, intracellular protozoan parasite with a broad range of intermediate hosts, including humans and rodents. In many hosts,
T. gondii
establishes a latent long-term infection by converting from its rapidly dividing or lytic form to its slowly replicating and encysting form. In humans and rodents, the major organ for encystment is the central nervous system (CNS), which has led many to investigate how this persistent CNS infection might influence rodent and human behavior and, more recently, neurodegenerative diseases.
Cryo-electron Microscopy Structure and Transport Mechanism of a Wall Teichoic Acid ABC Transporter
Authors: Chen Li , Hou Wen-Tao , Fan Tao , Liu Banghui , Pan Ting , Li Yu-Hui , Jiang Yong-Liang , Wen Wen , Chen Zhi-Peng , Sun Linfeng , Zhou Cong-Zhao , Chen Yuxing
Published: March 2020

The wall teichoic acid (WTA) is a major component of cell wall and a pathogenic factor in methicillin-resistant
Staphylococcus aureus
(MRSA). The ABC transporter TarGH is indispensable for flipping WTA precursor from cytoplasm to the extracellular space, thus making it a promising drug target for anti-MRSA agents. The 3.9-Å cryo-EM structure of a TarGH homolog helps us to decode the binding site and inhibitory mechanism of a recently reported inhibitor, Targocil, and provides a structural platform for rational design and optimization of potential antibiotics. Moreover, we propose a “crankshaft conrod” mechanism to explain how a big substrate is translocated through subtle conformational changes of type II exporters. These findings advance our understanding of anti-MRSA drug design and ABC transporters.
Cooperation and Cheating through a Secreted Aminopeptidase in the Pseudomonas aeruginosa RpoS Response
Authors: Robinson Tanner , Smith Parker , Alberts Erin R. , Colussi-Pelaez Mariana , Schuster Martin
Published: March 2020

Bacterial stress responses are generally considered protective measures taken by individual cells. Enabled by an experimental evolution approach, we describe a contrasting property, collective nutrient acquisition, in the RpoS-dependent stress response of the opportunistic human pathogen
P. aeruginosa
. Specifically, we identify the secreted
P. aeruginosa
aminopeptidase (PaAP) as an essential RpoS-controlled function in extracellular proteolysis. As a secreted “public good,” PaAP permits cheating by
rpoS
mutants that save the metabolic costs of expressing RpoS-controlled genes dispensable under the given growth conditions. Proteolytic enzymes are important virulence factors in
P. aeruginosa
pathogenesis and constitute a potential target for antimicrobial therapy. More broadly, our work contributes to recent findings in higher organisms that stress affects not only individual fitness and competitiveness but also cooperative behavior.
Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in Escherichia coli
Authors: Hartline Christopher J. , Mannan Ahmad A. , Liu Di , Zhang Fuzhong , Oyarzún Diego A.
Published: March 2020

Rapid metabolic recovery during nutrient shift is critical to microbial survival, cell fitness, and competition among microbiota, yet little is known about the regulatory mechanisms of rapid metabolic recovery. This work demonstrates a previously unknown mechanism where rapid release of a transcriptional regulator from a metabolite-sequestered complex enables fast recovery to nutrient depletion. The work identified key regulatory architectures and parameters that control the speed of recovery, with wide-ranging implications for the understanding of metabolic adaptations as well as synthetic biology and metabolic engineering.
The Min System Disassembles FtsZ Foci and Inhibits Polar Peptidoglycan Remodeling in Bacillus subtilis
Authors: Yu Yuanchen , Zhou Jinsheng , Dempwolff Felix , Baker Joshua D. , Kearns Daniel B. , Jacobson Stephen C.
Published: March 2020

Many bacteria grow and divide by binary fission in which a mother cell divides into two identical daughter cells. To produce two equally sized daughters, the division machinery, guided by FtsZ, must dynamically localize to the midcell each cell cycle. Here, we quantitatively analyzed FtsZ dynamics during growth and found that the Min system of
Bacillus subtilis
is essential to disassemble FtsZ rings after division. Moreover, a failure to efficiently recycle FtsZ results in an increase in cell size. Finally, we show that the Min system has an additional role in inhibiting cell wall turnover and contributes to the “inert” property of cell walls at the poles.
Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance
Authors: Siao Michelle C. , Borner Janus , Perkins Susan L. , Deitsch Kirk W. , Kirkman Laura A.
Published: March 2020

Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus
Plasmodium
, and of the five species capable of infecting humans, infections with
P. falciparum
are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.
Feedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver Domain
Authors: Stein Benjamin J. , Fiebig Aretha , Crosson Sean
Published: March 2020

Two-component signal transduction systems (TCSs) are broadly conserved in the bacterial kingdom and generally contain two molecular components, a sensor histidine kinase and a receiver protein. Sensor histidine kinases alter their phosphorylation state in direct response to a physical or chemical cue, whereas receiver proteins “receive” the phosphoryl group from the kinase to regulate a change in cell physiology. We have discovered that a single-domain receiver protein, FixT, binds an Fe-S cluster and controls
Caulobacter
heme homeostasis though its function as a negative-feedback regulator of the oxygen sensor kinase FixL. We provide evidence that the Fe-S cluster protects FixT from Lon-dependent proteolysis in the cell and endows FixT with the ability to function as a second, autonomous oxygen/redox sensor in the FixL-FixJ signaling pathway. This study introduces a novel mechanism of regulated TCS feedback control by an Fe-S-binding receiver domain.
Genomic and Transcriptomic Evidence Supports Methane Metabolism in
Archaeoglobi
Authors: Liu Yi-Fan , Chen Jing , Zaramela Livia S. , Wang Li-Ying , Mbadinga Serge Maurice , Hou Zhao-Wei , Wu Xiao-Lin , Gu Ji-Dong , Zengler Karsten , Mu Bo-Zhong
Published: March 2020

Current understanding of the diversity, biology, and ecology of
Archaea
is very limited, especially considering how few of the known phyla have been cultured or genomically explored. The reconstruction of “
Ca
. Methanomixophus” MAGs not only expands the known range of metabolic versatility of the members of
Archaeoglobi
but also suggests that the phylogenetic distribution of MCR and MTR complexes is even wider than previously anticipated.