bluuebunny/crossref_metadata_2025 huggingface dataset:
The suppression task and first‐order predicate calculus
Authors: López‐Astorga Miguel
Published: October 2023

The suppression task challenges classical logic. Classical logic is monotonic. However, in the suppression task, an inference with the form of modus ponendo ponens is inhibited by adding a new premise. Several explanations have been given to account for this fact. The present paper indicates three of them as examples: that of the theory of mental models, that based on logic programming and closed world assumption, and that referring to Carnap's concept of state‐descriptions. Besides, the paper offers one more explanation linked to Carnap's idea of reduction. It proposes sentences akin to a reduction sentence, a pair reduction, and a bilateral reduction sentence. Those sentences are related to the initial conditional in the suppression task. This proposal tries to stay within first‐order predicate logic.
Sexual exclusion and the right to sex
Authors: Halwani Raja
Published: October 2023

Philosophers have recently expressed interest in the question as to whether there is a right to sex, a right whose justification is motivated by the existence of sexually excluded people – people who suffer from involuntary long‐term sexual deprivation (owing, say, to a chronic medical condition). This paper, after offering preliminary remarks about what a right to sex and its objects might be and who might have this right, surveys seven justifications for the right: linkage arguments, need, well‐being, a minimally decent life, being a basic good, justice, and relationships. The paper argues that a right to sex does not likely exist because none of the justifications are convincing. The paper then argues that despite the lack of justification, and because sexual exclusion is a problem worthy of attention, people's sexual needs can be addressed through the lens of goals instead of rights. This not only takes sexual exclusion seriously enough but also avoids the crucial problems associated with rights‐talk, especially that of sexual coercion.
Breakthrough invasive fungal infections on isavuconazole prophylaxis in hematologic malignancy & hematopoietic stem cell transplant patients
Authors: Khatri Akshay M. , Natori Yoichiro , Anderson Anthony , Jabr Ra'ed , Shah Shreya A. , Natori Akina , Chandhok Namrata S. , Komanduri Krishna , Morris Michele I. , Camargo Jose F. , Raja Mohammed
Published: October 2023

Background

Isavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side‐effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported.

Methods

In this single‐center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs.

Results

We evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21–91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%).

Nineteen patients (17.9%) developed bIFIs–nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8–253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 μg/mL) were comparable to industry‐sponsored clinical trials.

All‐cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co‐infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups.

Conclusion

ISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side‐effect and drug‐interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs.

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Evaluation of the addition of adrenaline in a bilateral maxillary nerve block to reduce hemorrhage in dogs undergoing sharp staphylectomy for brachycephalic obstructive airway syndrome. A prospective, randomized study
Authors: Williams Phillipa J. , De Gennaro Chiara , Demetriou Jackie L.
Published: October 2023

Objective

To assess the use of adrenaline (0.00198%) in a bilateral maxillary nerve block to reduce intraoperative hemorrhage in dogs undergoing staphylectomy for the treatment of brachycephalic obstructive airway syndrome (BOAS).

Study design

Prospective, randomized, double‐blinded controlled study.

Sample population

A total of 32 client owned, clinically affected dogs undergoing a cut and sew sharp staphylectomy for treatment of BOAS. A total of 16 dogs randomly assigned to adrenaline (A) group and 16 to no‐adrenaline (NA) group.

Methods

A bilateral maxillary nerve block was performed in all dogs prior to staphylectomy using lidocaine alone (group NA) or a combination of lidocaine and adrenaline (group A). Total hemorrhage was measured by weighing cotton‐tipped applicators and swabs used on precision scales. In addition, a semi‐quantitative hemorrhage score (1–5) was determined. Dogs were monitored for intraoperative hemodynamic stability during the procedure.

Results

Total hemorrhage was significantly (p = .013) lower in group A compared with group NA. The median semi‐quantitative hemorrhage score was significantly lower for group A (p = .029) compared with group NA. No significant adverse effects were noted due to adrenaline usage.

Conclusion

This study demonstrated that the use of adrenaline in a bilateral maxillary nerve block results in significantly lower intraoperative hemorrhage during cut and sew sharp staphylectomy and appeared safe to use.

Clinical significance

Potential clinical advantages include improved visualization, prevention of unnecessary blood loss and reduction in risk of blood aspiration.
Learning Foreign Language Towards Its Media and Identity To Motivate Student’s Personal Growth
Authors: Rahmat Wahyudi , Fitriyah Rifkah , Zulfa Z , Riza Armilia , Afrinda Putri Dian , Fitri Rahayu , Pebriani Yulia , Endila Wahyuni
Published: October 2023

Over the past few years, motivational research on language learning has focused on how learners see language knowledge as a medium and part of their inherent identity. This article presents a study that explores the significance of personal growth as a motivator for Indonesian university students learning Arabic and English. The research employs qualitative interviews to collect data and thoroughly examines the role of personal growth in student motivation. In analysis methods, the study emphasizes its comprehensive approach to investigating personal growth's role in student motivation while thoroughly examining the collected information.  Next, this article will present the main findings and argue that personal growth and the desire of Indonesian students to broaden their horizons strongly motivate them to further their education in Saudi Arabia. Finally, the article ends by finding that language and culture courses should be designed around relevant topics related to students' experiences and memories, thus allowing reflection and course content to present new ideas to students who sometimes might challenge their views.
Spiking-Free Disturbance Observer-Based Sliding-Mode Control for Mismatched Uncertain System
Authors: Wang Yang , Guan Yan , Li Huanyun
Published: October 2023

For the mismatched uncertain system, a novel spiking-free disturbance observer (DO)-based sliding-mode control (SMC) scheme is developed. First, a DO is proposed to estimate the mismatched uncertainty. A new sliding-mode surface is developed by using the system states, the estimation of mismatched uncertainty, and a spike suppression term. Then, an SMC method is proposed by using the developed sliding-mode surface. Compared with existing SMC schemes, the proposed spiking-free DO-based SMC has two advantages: (1) the mismatched uncertainty can be effectively suppressed; (2) the harmful spike problem of extended disturbance observer (EDO)-based and extended state observer (ESO)-based SMC schemes when the observer gain is high can be avoided. Finally, the simulation is presented to show the effectiveness of the proposed scheme by comparing the proposed and existing SMC schemes.
Fragility of Delay Margin Against Platoon Size in a Connected Vehicle System; Network Design and Multiple Trials
Authors: Wang Duo , Sipahi Rifat
Published: October 2023

Linear stability of a car following model is investigated considering time delays due to human reaction times and communication delays. In multiple trials, we generate networks of randomly arranged legacy and autonomous vehicles, each vehicle type respecting some connectivity rules. Next, the largest amount of delay the vehicle network can tolerate without becoming unstable is computed. This delay, also known as the delay margin (DM), can become sensitive with respect to platoon size under certain connectivity rules. We demonstrate this “fragility” property, and next propose a new network-design policy with which DM can be made robust against platoon size.
Closed-Form Dynamic Modeling and Performance Evaluation of a 4-Degrees-of-Freedom Parallel Driving Mechanism
Authors: Huang Yangyang , Zhang Jinzhu , Xiong Xiaoyan
Published: October 2023

Kinematic estimations and dynamic performance assessments are fundamental theoretical issues to realize the mechanism from conceptual design to engineering application. In this article, the closed-form dynamic formulations of a 4-degrees-of-freedom (DoFs) parallel driving mechanism are derived by combining the Lagrange method and the virtual work principle. The selection principle of generalized coordinates and the steps for inverse dynamics modeling of the manipulator are proposed. Simulation results verify the correctness of the dynamic model, and a physical prototype has been built. Based on the dynamic modeling, the concise algebraic expression of the operational space inertia matrix of the parallel driving mechanism is deduced. Because the translation and rotation degrees-of-freedom are inconsistent in the operational space, the Jacobian matrix is adopted to map the inertia matrix from the operational space to the joint space. Based on the inertia matrix in joint space, the average energy transfer efficiency (AETE) index is proposed. Finally, two control techniques for the manipulator implementable in joint space are compared. The AETE index and dynamic modeling method suggested in this article can be further used in other manipulators for dynamic analysis and motion system design.
Active Fluidic Control of a Nozzle Guide Vane Throat
Authors: Spens Alexander , Bons Jeffrey P.
Published: October 2023

Experiments were conducted to validate the building blocks of a fluidically controlled variable area turbine concept that uses injected high-pressure air to effectively reduce the choke area of the turbine inlet. Preliminary results from a simple quasi-1D converging-diverging nozzle, with an injection flow slot upstream of the throat, showed a 2.2:1 ratio between throttled mass flowrate and injected mass flowrate at a constant nozzle pressure ratio. The penetration of the injection flow and corresponding reduction in the primary flow streamtube were successfully visualized using a shadowgraph technique. Building on this success, a representative single passage nozzle guide vane transonic flowpath was constructed to demonstrate feasibility beyond the quasi-1D converging-diverging nozzle. Both secondary slot blowing from the vane pressure surface and vane suction surface just upstream of the passage throat again successfully reduced primary flow. In addition, fluidic vortex generators were used on the adjacent suction surface to reduce total pressure loss and further throttle the primary flow. Implications for the application of this active flow control technology to a variable area turbine are considered.
Enhancing Gas Turbine Power Plant Performance in Tropical Climates by Using Inlet Air Cooling With Desiccant Dehumidification and Evaporative Cooling
Authors: Sánchez Cabarcas Mateo E. , Bedoya Villegas Jose A. , Sierra Aragón Álvaro D. , Rodríguez Roldán Imanol , Álvarez Silva Daniel A. , Mesa Jaime , Bula Antonio , Gonzalez-Quiroga Arturo
Published: October 2023

Gas turbine power plants play a critical role in meeting the increasing demand for electricity. However, their performance can be affected by high ambient temperatures and humidity levels in tropical climates, which can lead to a decrease in power output. This study explores the potential benefits of using inlet air cooling with desiccant dehumidification and evaporative cooling to improve the performance of gas turbine power plants in tropical regions. The findings indicate that this method of inlet air cooling, which integrates evaporative cooling, desiccant wheel, and Maisotsenko cooler, is a viable option for mitigating the performance drop of gas turbines in hot tropical conditions. Moreover, by utilizing turbine exhaust gases to heat the regeneration air utilized in the desiccant wheel for dehumidification, the compressor inlet temperature can be reduced by an average of 11.5 °C. Additionally, the power requirement of the inlet air cooling system is about 0.9 MW, while there is an improvement of more than 2 MW in power output at peak ambient temperature. Further research is needed to understand and quantify other benefits related to inlet air cooling, such as reducing emissions of harmful pollutants and operating at higher turbine inlet temperatures.
Experimental Investigation of the Water Droplet Evaporation on Inclined Surfaces by Taguchi and ANOVA Optimization Analysis
Authors: Yildirim Atalay , Ağra Özden , Sevindir Mustafa Kemal
Published: October 2023

We experimentally investigated the evaporation characteristics of a sessile water droplet on a glass substrate with different surface roughness levels. The influence of five parameters is evaluated for the evaporation process: substrate temperature (30 °C, 45 °C, and 60 °C), surface roughness (P0, P600, and P60), droplet volume (3, 5, and 8 µL), water droplets initial temperature (30 °C, 40 °C, and 60 °C), and inclination angle (0 deg, 45 deg, and 75 deg) of the glass substrate. The Taguchi orthogonal array design of L27 is utilized to establish minimal candidate trial points for experimental works, and more trials have been conducted to quantify the effects accurately. Then, analysis of variance (ANOVA) has been used to evaluate the evaporation times for the sessile droplets. The results indicate that evaporation times decrease with rising substrate temperatures, increasing substrate inclination angle, and increasing initial water droplet temperatures. In contrast, evaporation times rise with increasing surface roughness and droplet volumes. After evaluation of the ANOVA analysis, surface roughness levels and droplet volumes are considered the most influential parameters after substrate temperatures, which is the most effective parameter on the evaporation times. On the other hand, initial water droplet temperatures and substrate inclination angle are less effective considering droplet evaporation times. A linear regression fit was derived via ANOVA analysis for the evaporation time, and the best mean deviation was found to be 10% from the experiments. The experimental outcomes were compared to previous research, and correlations were derived. The proposed correlation has given good results considering experimental and literature data.
Mixed Convective Heat Transfer Characteristics of Graphene Nanofluid Strengthened by Periodically Direction-Switching Electric Field
Authors: Chen Yanjun , Du Chenhao , Wang Zhoumiao , He Deqiang
Published: October 2023

Transformer-oil with low thermal conductivity and large viscosity has poor heat dissipation capability, which leads to the thermal drive failure caused by transient overload. To improve its cooling capability, this paper has proposed first the method which combined the periodically direction-switching electric field and graphene nanofluid to enhance the mixed convective heat transfer properties of transformer-oil, and analyzed the effects of switching periods, nanofluid concentration, electric field strength, heat flux, and Reynolds number on mixed convection heat transfer experimentally. The results show that the heat transfer characteristic of transformer-oil is improved up to 52% by the periodically direction-switching electric field and graphene nanofluid. As the switching period decreases, the thermal performance of the suspension is enhanced more significantly. Moreover, by analyzing the heat transfer mechanism, the periodically direction-switching electric field causes the nanoparticles to move reciprocally, repeatedly impacting and breaking the boundary layer of the heat exchange surface to enhance the perturbation, thus enhancing the heat transfer effect. Meanwhile, the predicted correlation has been proposed on the basis of influence factors, which are in good agreement with the experimental data.
Higher-order mode filtering by a resistive layer
Authors: Kuznetsova Svetlana , Aurégan Yves , Pagneux Vincent
Published: October 2023

A method for filtering higher-order acoustic modes using a resistive layer is proposed and applied to a two-dimensional rectangular waveguide with a quiescent fluid. An analogue of Cremer's criterion is discussed and used to obtain the optimal modal attenuation of the non-planar waves while the plane wave is preserved. Numerical validation of the concept is performed for a straight waveguide and an abrupt expansion in a waveguide.
Deletion of the gene for the African swine fever virus BCL-2 family member A179L increases virus uptake and apoptosis but decreases virus spread in macrophages and reduces virulence in pigs
Authors: Reis Ana Luisa , Rathakrishnan Anusyah , Goulding Leah V. , Barber Claire , Goatley Lynnette C. , Dixon Linda K.
Published: October 2023

The African swine fever virus (ASFV) encodes inhibitors of innate immune responses, including type I interferon and apoptosis. The BCL-2 family A179L gene was deleted from the virulent genotype I isolate Benin 97/1. In infected macrophages, this resulted in increased caspase 3 and 7 activities, Annexin V binding to surface phosphatidylserine, and DNA fragmentation, measured by terminal deoxynucleotidyl transferase nick-end labeling, compared to Benin 97/1 expressing A179L or mock-infected macrophages. These results confirmed that apoptosis was induced earlier in macrophages infected with viruses from which A179L was deleted. Increased cell entry of the A179L gene-deleted virus was indicated since the number of infected cells at early times, as measured by fluorescent protein expression, was much higher than infection with the wild-type virus. This increase in entry was reduced following blocking of the virus by binding to Annexin V, suggesting that entry was mediated by phosphatidylserine receptors. Yields of infectious viruses were similar over a single cycle but significantly lower for the A179L gene-deleted virus over a multistep growth cycle. Pigs immunized with the BeninΔA179L virus showed no clinical signs and a weak cellular response to ASFV. The immunized pigs were not protected against challenge with the virulent parental virus Benin 97/1 although viremia was lower at 3 d post-challenge than the control nonimmune pigs. Thus, reduced levels of virus replication in pigs limited the induction of a protective immune response. The results show an important role for the A179L protein in virus replication in macrophages and virulence in pigs.

IMPORTANCE

African swine fever virus (ASFV) causes a lethal disease of pigs with high economic impact in affected countries in Africa, Europe, and Asia. The virus encodes proteins that inhibit host antiviral defenses, including the type I interferon response. Host cells also activate cell death through a process called apoptosis to limit virus replication. We showed that the ASFV A179L protein, a BCL-2 family apoptosis inhibitor, is important in reducing apoptosis in infected cells since deletion of this gene increased cell death and reduced virus replication in cells infected with the A179L gene-deleted virus. Pigs immunized with the BeninΔA179L virus showed no clinical signs and a weak immune response but were not protected from infection with the deadly parental virus. The results show an important role for the A179L protein in virus replication in macrophages and virulence in pigs and suggest manipulation of apoptosis as a possible route to control infection.
The Cajal body protein p80-coilin forms a complex with the adenovirus L4-22K protein and facilitates the nuclear export of adenovirus mRNA
Authors: White Laura , Erbay Bilgi , Blair G. Eric
Published: October 2023

Cajal bodies (CBs) are major sub-nuclear structures in most eucaryotic cells. In human adenovirus 5 (Ad5) infection, CBs are reorganized into microfoci in the late phase of infection. Here we show that many CB protein components (p80-coilin, SMN-1, and WRAP53) remained stable throughout most of the infectious cycle of Ad type 5 (Ad5) in human A549 epithelial cells, even when CBs were reorganized into microfoci. Reduction of p80-coilin expression by RNA interference resulted in significant reductions in the levels of early (E1A, E2A-DBP), intermediate (pIX and IVa2), and late (L1-IIIa, L2-penton base, L3-hexon, L4-100K, and L5-fiber) proteins in Ad5-infected A549 cells. Depletion of p80-coilin did not significantly alter the total cellular levels of the corresponding Ad cytoplasmic mRNAs (with the exception of E1A 12S and 13S and pIX mRNA) or the production of the Ad5 pre-mRNAs tested (E1A, E2A-DBP, IVa2, or late pre-mRNAs containing the tripartite leader). However, the ratio of viral cytoplasmic to nuclear-spliced Ad RNAs was reduced in p80-coilin-depleted, Ad5-infected cells compared to control-infected cells. Immunofluorescent staining of Ad5-infected cells revealed co-localization of p80-coilin with areas of immunoreactivity defined by a polyclonal antibody that recognized the L4-22K and L4-33K proteins in a fraction of microfoci. Immunoprecipitation analysis showed that only the L4-22K protein formed a stable complex with p80-coilin in Ad5-infected cells and in cells co-transfected with plasmids encoding p80-coilin and either the L4-22K or L4-33K protein. p80-coilin therefore plays an important role in Ad replication by complex formation with L4-22K and facilitating nuclear export of Ad mRNAs.

IMPORTANCE

The architecture of sub-nuclear structures of eucaryotic cells is often changed during the infectious cycle of many animal and plant viruses. Cajal bodies (CBs) form a major sub-nuclear structure whose functions may include the regulation of cellular RNA metabolism. During the lifecycle of human adenovirus 5 (Ad5), CBs are reorganized from their spherical-like structure into smaller clusters termed microfoci. The mechanism of this reorganization and its significance for virus replication has yet to be established. Here we show that the major CB protein, p80-coilin, facilitates the nuclear export of Ad5 transcripts. Depletion of p80-coilin by RNA interference led to lowered levels of viral proteins and infectious virus. p80-coilin was found to form a complex with the viral L4-22K protein in Ad5-infected cells and in some reorganized microfoci. These findings assign a new role for p80-coilin as a potential regulator of infection by a human DNA virus.
ATP synthase-associated coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing proteins are critical for mitochondrial function in
Toxoplasma gondii
Authors: Usey Madelaine M. , Huet Diego
Published: October 2023

Coiled-coil-helix-coiled-coil-helix (CHCH) domains consist of two pairs of cysteine residues that are oxidized to form disulfide bonds upon mitochondrial import. Proteins containing these domains play important roles in mitochondrial ultrastructure and in the biogenesis, function, and stability of electron transport chain complexes. Interestingly, recent investigations of the
Toxoplasma gondii
ATP synthase identified subunits containing CHCH domains. As CHCH domain proteins have never been found in any other ATP synthase, their role in
T. gondii
was unclear. Using conditional gene knockdown systems, we investigated two
T. gondii
ATP synthase subunits containing CHCH domains: ATPTG8 and ATPTG9. We show that these two subunits are essential for the lytic cycle as well as stability and function of the ATP synthase. Further, we illustrated that their knockdown disrupts multiple aspects of mitochondrial morphology, including ultrastructure and cristae density. Mutation of key cysteine residues in the CHCH domains also caused mis-localization of the proteins. Our work suggests that these proteins likely provide structural support to the exceptionally large
T. gondii
ATP synthase complex and that perturbations to the structural integrity of this complex result in deleterious downstream effects on the parasite mitochondrion. These investigations add to a growing body of work focused on the divergent aspects of the apicomplexan ATP synthase, which could ultimately uncover novel drug targets.

IMPORTANCE

Members of the coiled-coil-helix-coiled-coil-helix (CHCH) domain protein family are transported into the mitochondrial intermembrane space, where they play important roles in the biogenesis and function of the organelle. Unexpectedly, the ATP synthase of the apicomplexan
Toxoplasma gondii
harbors CHCH domain-containing subunits of unknown function. As no other ATP synthase studied to date contains this class of proteins, characterizing their function will be of broad interest to the fields of molecular parasitology and mitochondrial evolution. Here, we demonstrate that that two
T. gondii
ATP synthase subunits containing CHCH domains are required for parasite survival and for stability and function of the ATP synthase. We also show that knockdown disrupts multiple aspects of the mitochondrial morphology of
T. gondii
and that mutation of key residues in the CHCH domains caused mis-localization of the proteins. This work provides insight into the unique features of the apicomplexan ATP synthase, which could help to develop therapeutic interventions against this parasite and other apicomplexans, such as the malaria-causing parasite
Plasmodium falciparum
.
Developmental dynamics of mitochondrial mRNA abundance and editing reveal roles for temperature and the differentiation-repressive kinase RDK1 in cytochrome oxidase subunit II mRNA editing
Authors: Smith Joseph T. , Tylec Brianna , Naguleswaran Arunasalam , Roditi Isabel , Read Laurie K.
Published: October 2023

Developmental regulation of mitochondrial uridine insertion/deletion editing in
Trypanosoma brucei
is necessary to modulate parasite metabolism as it shifts from dependence on glycolysis for ATP production in the mammalian bloodstream form (BSF) to oxidative phosphorylation in the insect procyclic form (PCF). However, the timing and stimuli that regulate mRNA editing have been poorly characterized. Here, we utilized a pleomorphic
T. brucei
strain and quantitative RT-PCR and droplet digital PCR analyses to evaluate the changes in total mRNA abundance and editing as parasites progressively differentiate from slender BSF to PCF and investigate the effect of individual stimuli on mitochondrial gene expression. We observed little change during the slender-to-stumpy BSF transition. Rather, we found that mainly the mitochondrial cytochrome (COI, COII, COIII, and CYb) mRNAs are upregulated within 24 h after stumpy BSF is stimulated to differentiate to PCF
in vitro
and during
in vivo
tsetse fly infections. Temperature reduction from 37°C to 27°C is a critical factor for increasing the editing of COII and COIII mRNAs and COIV protein expression but not the editing of CYb mRNA or RISP protein expression. We further demonstrate that the depletion of the differentiation-repressive kinase RDK1 couples with temperature reduction to stimulate COII mRNA editing, and the accessory factor p22 is required for the cold-responsive upregulation of COII mRNA editing. Overall, we show that cytochrome mRNAs are regulated during development by distinct stimuli through a variety of methods to increase their abundance and/or editing.

IMPORTANCE

Trypanosoma brucei
is the unicellular parasite that causes African sleeping sickness and nagana disease in livestock. The parasite has a complex life cycle consisting of several developmental forms in the human and tsetse fly insect vector. Both the mammalian and insect hosts provide different nutritional environments, so
T. brucei
must adapt its metabolism to promote its survival and to complete its life cycle. As
T. brucei
is transmitted from the human host to the fly, the parasite must regulate its mitochondrial gene expression through a process called uridine insertion/deletion editing to achieve mRNAs capable of being translated into functional respiratory chain proteins required for energy production in the insect host. Therefore, it is essential to understand the mechanisms by which
T. brucei
regulates mitochondrial gene expression during transmission from the mammalian host to the insect vector.
Respiratory syncytial virus co-opts hypoxia-inducible factor-1α-mediated glycolysis to favor the production of infectious virus
Authors: Chen Li-Feng , Cai Jun-Xing , Zhang Jing-Jing , Tang Yu-Jun , Chen Jia-Yi , Xiong Si , Li Yao-Lan , Zhang Hong , Liu Zhong , Li Man-Mei
Published: October 2023

Glycolysis, a series of oxidative reactions used to metabolize glucose and provide energy to host cells, is also required for respiratory syncytial virus (RSV) infection. However, the role of glycolysis during RSV infection and its underlying molecular mechanisms remain to be further explored. In this study, we investigated the function of hypoxia-inducible factor (HIF)-1α-mediated glycolysis in HEp-2 cells and mouse models during RSV infection. The results showed that RSV infection activated the insulin receptor (IR)-PI3K-Akt axis, upregulated the translation and activity of HIF-1α, increased the expression of glucose transporters (Glut1, Glut3, and Glut4), hexokinase (HK) 1 and 2, and platelet-type phosphofructokinase (PFKP), and promoted glucose uptake and glycolysis. In addition, mitochondrial damage induced by RSV resulted in the generation of large amounts of reactive oxygen species (ROS) in infected cells, which contributed to the stabilization and activation of HIF-1α. An energy map of the glycolytic ATP production rate (Glyco-ATP) versus the mitochondrial ATP production rate (mito-ATP) confirmed a switch from oxidative phosphorylation (OXPHOS) to glycolysis. Inhibition of IR-PI3K-Akt signaling, ROS, or HIF-1α effectively reversed the RSV-induced increase in glycolysis by blocking HIF-1α activation. Importantly, HIF-1α-mediated glycolysis provided energy for the production of progeny RSV virions. The production of infectious virions was nearly abolished after knocking down HIF-1α. PX-478, an orally active HIF-1α inhibitor, effectively inhibited RSV infection
in vivo
. Collectively, these results indicate the role of HIF-1α-mediated glycolysis in RSV infection and highlight HIF-1α as a potential target for anti-RSV drug development.

IMPORTANCE

Respiratory syncytial virus (RSV) is the leading etiological agent of lower respiratory tract illness. However, efficacious vaccines or antiviral drugs for treating RSV infections are currently not available. Indeed, RSV depends on host cells to provide energy needed to produce progeny virions. Glycolysis is a series of oxidative reactions used to metabolize glucose and provide energy to host cells. Therefore, glycolysis may be helpful for RSV infection. In this study, we show that RSV increases glycolysis by inducing the stabilization, transcription, translation, and activation of hypoxia-inducible factor (HIF)-1α in infected cells, which is important for the production of progeny RSV virions. This study contributes to understanding the molecular mechanism by which HIF-1α-mediated glycolysis controls RSV infection and reveals an effective target for the development of highly efficient anti-RSV drugs.
Construction and characterization of a saturated Tn-seq library of
Salmonella
Typhimurium ATCC 14028
Authors: Trotereau Jérôme , Jouan Romain , Naquin Delphine , Branger Maxime , Schouler Catherine , Velge Philippe , Mergaert Peter , Virlogeux-Payant Isabelle
Published: October 2023

Salmonella enterica
is an important foodborne pathogen. Here, we present the construction and characterization of a high-density transposon sequencing library of the
Salmonella
Typhimurium ATCC 14028 strain. Essential, advantageous, and disadvantageous genes for growth in rich culture medium were identified on the chromosome and the pSLT plasmid.
NDM-1- and OXA-23-producing
Acinetobacter baumannii
in wastewater of a Nigerian hospital
Authors: Odih Erkison Ewomazino , Sunmonu Gabriel Temitope , Okeke Iruka N. , Dalsgaard Anders
Published: October 2023

Carbapenem-resistant
Acinetobacter baumannii
spp. are increasingly important pathogens with limited treatment options, and there is limited knowledge on the environmental factors contributing to their spread. We determined the occurrence of carbapenem-resistant
A. baumannii
in hospital wastewater and their phylogenetic relationships with clinical
A. baumannii
isolates. Grab samples of raw and treated hospital wastewater were collected monthly at the University College Hospital, Ibadan, Nigeria, between March 2021 and February 2022.
Acinetobacter baumannii
strains were selectively isolated and identified using VITEK2, and their whole genomes were sequenced on an Illumina platform. We performed antimicrobial susceptibility testing and
in silico
genomic characterization of the strains and determined their phylogenetic relationships to previously characterized clinical
A. baumannii
strains from Nigeria.
A. baumannii
complex isolates were recovered from wastewater throughout the study. Of the 82 isolates identified based on whole-genome sequences, 77 were
A. baumannii. A. baumannii
isolates had high resistance rates (≥48.1%) to 10 of 12 antimicrobials tested, and majority (42/77, 54.5%) were resistant to carbapenems, with
bla
NDM-1
being the most common (24/77, 31.2%) carbapenem resistance gene detected, followed by
bla
OXA-23
(
n
= 22, 28.6%). There was no statistically significant difference in carbapenem resistance rates or carbapenem gene carriage between the raw and treated wastewater isolates. Most of the isolates belonged to novel or sparsely described lineages, some of which were closely related to clinical isolates. The release of inadequately treated hospital wastewater into the environment may contribute to the increased spread of carbapenem-resistant and clinically important
A. baumannii
lineages in Ibadan, Nigeria.

IMPORTANCE

Acinetobacter baumannii
is a leading cause of hospital-associated infections globally.
A. baumannii
reservoirs outside hospital settings are still unknown, and their occurrence in the environment is linked to clinical and anthropogenic activities. Although the risk of transmission of
A. baumannii
from environmental sources to humans is not fully understood, these sources pose significant risks for the continued dissemination of
A. baumannii
and their resistance traits. This study provides evidence that diverse and clinically relevant
A. baumannii
strains, many of which are resistant to carbapenems, are constantly being discharged into the environment through inadequately treated hospital wastewater. We further elucidate potential transmission routes between the environment and clinical infections and demonstrate the high prevalence of carbapenem resistance genes on highly mobile transposons among these strains. Our findings highlight the pressing need to address hospital wastewater as a crucial factor in curtailing the spread of carbapenem-resistant
A. baumannii
.
Edwardsiella ictaluri
T3SS effector EseN is a phosphothreonine lyase that inactivates ERK1/2, p38, JNK, and PDK1 and modulates cell death in infected macrophages
Authors: Koirala Ranjan , Fongsaran Chanida , Poston Tanisha , Rogge Matthew , Rogers Bryan , Thune Ronald , Dubytska Lidiya
Published: October 2023

EseN is an
Edwardsiella ictaluri
type III secretion system effector with phosphothreonine lyase activity. In this work, we demonstrate that EseN inactivates p38 and c-Jun-N-terminal kinase (JNK) in infected head-kidney-derived macrophages (HKDMs). We have previously reported inactivation of extracellular-regulated kinase 1/2 (ERK1/2). Also, for the first time, we demonstrated that EseN is involved in the inactivation of 3-phosphoinositide-dependent kinase 1 (PDK1), which has not been previously demonstrated for any of the EseN homologs in other species. We also found that EseN significantly affected mRNA expression of
IL-10
, pro-apoptotic
baxa
, and
p53
, but had no significant effect on anti-apoptotic
bcl2
or pro-apoptotic apoptotic peptidase activating factor 1. EseN is also involved in the inhibition of caspase-8 and caspase-3/7 but does not affect caspase-9 activity. Repression of apoptosis was further confirmed with flow cytometry using Alexa Fluor 647-labeled annexin V and propidium iodide. In addition, we found that the
E. ictaluri
T3SS is essential for the inhibition of IL-1β maturation, but EseN is not involved in this process. EseN did not affect cell pyroptosis, as indicated by the lack of EseN impact on the release of lactate dehydrogenase from infected HKDM. The transmission electron microscopy data also indicate that HKDM infected with WT or an
eseN
mutant died by apoptosis, while HKDM infected with the T3SS mutant more likely died by pyroptosis. Collectively, our results indicate that
E. ictaluri
EseN is involved in inactivation of ERK1/2, p38, JNK, and PDK1 signaling pathways that lead to modulation of cell death among infected HKDMs.

IMPORTANCE

This work has global significance in the catfish industry, which provides food for increasing global populations.
E. ictaluri
is a leading cause of disease loss, and EseN is an important player in
E. ictaluri
virulence. The
E. ictaluri
T3SS effector EseN plays an essential role in establishing infection, but the specific role EseN plays is not well characterized. EseN belongs to a family of phosphothreonine lyase effectors that specifically target host mitogen activated protein kinase (MAPK) pathways important in regulating host responses to infection. No phosphothreonine lyase equivalents are known in eukaryotes, making this family of effectors an attractive target for indirect narrow-spectrum antibiotics. Targeting of major vault protein and PDK1 kinase by EseN has not been reported in EseN homologs in other pathogens and may indicate unique functions of
E. ictaluri
EseN. EseN targeting of PDK1 is particularly interesting in that it is linked to an extraordinarily diverse group of cellular functions.
The Activity of a Solar-Type Star TOI-1422 and Mass Loss of the Atmosphere of the Planet TOI-1422b
Authors: Savanov I. S.
Published: October 2023

The results of the analysis of the activity of a solar type star G2V TOI-1422 are presented and estimates of the loss of atmospheric matter of the planet TOI-1422b are made. The planet can be attributed to the type of hot Neptunes. Compared to other exoplanets of a similar mass range, it is expected that the planet has an extensive gas envelope. According to the long-term photometric survey of Kamogata Wide-field Survey (KWS) the TOI-1422 activity was analyzed and the existence of possible activity cycles of 1650–1680 days and 2450 days was suggested. The probable value of the rotation period P of the star lies in the range of 27 (+19, –8) days, observations of the KWS survey in the V filter indicate the most possible value for the period P = 32 days. Mass loss of the planet’s atmosphere is determined using an approximation formula corresponding to the model of atmospheric loss with an energy restriction. To estimate the flux of XUV photons analytical dependences were used linking the flux values and the parameter $$\log R_{{{\text{HK}}}}^{'}$$. Calculations have shown that the atmosphere matter loss of TOI-1422b is $$\dot {M} = 9.4 \times {{10}^{8}}$$ g/s; considering the existing errors in determining the parameters of the atmosphere it lies in the range from $$6.8 \times {{10}^{8}}$$ to $$1.4 \times {{10}^{9}}$$ g/s, and considering the uncertainty in the value of the chromospheric activity index—from $$8.3 \times {{10}^{8}}$$ to $$1.1 \times {{10}^{9}}$$ g/s.
OCP-driven hypertriglyceridaemia and recurrent acute pancreatitis
Authors: Thapa Samriddha , Allakky Akhil , Turaga Anjani
Published: October 2023

Recurrent acute pancreatitis poses a significant challenge in clinical management. In this case, a young, obese woman with metabolic syndrome presented with her third episode of acute pancreatitis within a span of 4 months. Due to unavailability, plasmapheresis could not be performed, and the patient was managed solely with pharmacological therapy. Initial evaluation revealed abdominal pain, tenderness and elevated laboratory markers. CT scan findings indicated pancreatic and peripancreatic oedema. Further investigations highlighted the presence of hypertriglyceridaemia and hypocalcaemia. As the patient was using oral contraceptive pills (OCP), it was crucial to consider their potential role in causing hypertriglyceridaemia. Consequently, the patient was advised to discontinue OCP use. Despite the lack of plasmapheresis, intensive medical management, including medication and lifestyle modifications, showed positive results. This case underscores the importance of recognising the association between OCP, hypertriglyceridaemia and recurrent pancreatitis in patients with metabolic syndrome.
Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis
Authors: Liu Cong , Chen Renjie , Sera Francesco , Vicedo-Cabrera Ana Maria , Guo Yuming , Tong Shilu , Lavigne Eric , Correa Patricia Matus , Ortega Nicolás Valdés , Achilleos Souzana , Roye Dominic , Jaakkola Jouni JK , Ryti Niilo , Pascal Mathilde , Schneider Alexandra , Breitner Susanne , Entezari Alireza , Mayvaneh Fatemeh , Raz Raanan , Honda Yasushi , Hashizume Masahiro , Ng Chris Fook Sheng , Gaio Vânia , Madureira Joana , Holobaca Iulian-Horia , Tobias Aurelio , Íñiguez Carmen , Guo Yue Leon , Pan Shih-Chun , Masselot Pierre , Bell Michelle L , Zanobetti Antonella , Schwartz Joel , Gasparrini Antonio , Kan Haidong
Published: October 2023

Objective

To investigate potential interactive effects of fine particulate matter (PM
2.5
) and ozone (O
3
) on daily mortality at global level.

Design

Two stage time series analysis.

Setting

372 cities across 19 countries and regions.

Population

Daily counts of deaths from all causes, cardiovascular disease, and respiratory disease.

Main outcome measure

Daily mortality data during 1994-2020. Stratified analyses by co-pollutant exposures and synergy index (>1 denotes the combined effect of pollutants is greater than individual effects) were applied to explore the interaction between PM
2.5
and O
3
in association with mortality.

Results

During the study period across the 372 cities, 19.3 million deaths were attributable to all causes, 5.3 million to cardiovascular disease, and 1.9 million to respiratory disease. The risk of total mortality for a 10 μg/m
3
increment in PM
2.5
(lag 0-1 days) ranged from 0.47% (95% confidence interval 0.26% to 0.67%) to 1.25% (1.02% to 1.48%) from the lowest to highest fourths of O
3
concentration; and for a 10 μg/m
3
increase in O
3
ranged from 0.04% (−0.09% to 0.16%) to 0.29% (0.18% to 0.39%) from the lowest to highest fourths of PM
2.5
concentration, with significant differences between strata (P for interaction <0.001). A significant synergistic interaction was also identified between PM
2.5
and O
3
for total mortality, with a synergy index of 1.93 (95% confidence interval 1.47 to 3.34). Subgroup analyses showed that interactions between PM
2.5
and O
3
on all three mortality endpoints were more prominent in high latitude regions and during cold seasons.

Conclusion

The findings of this study suggest a synergistic effect of PM
2.5
and O
3
on total, cardiovascular, and respiratory mortality, indicating the benefit of coordinated control strategies for both pollutants.
PM2.5exposure, glycemic markers and incidence of type 2 diabetes in two large Indian cities
Authors: Mandal Siddhartha , Jaganathan Suganthi , Kondal Dimple , Schwartz Joel D , Tandon Nikhil , Mohan Viswanathan , Prabhakaran Dorairaj , Narayan K M Venkat
Published: October 2023

Introduction

Exposure to fine particulate matter has been associated with several cardiovascular and cardiometabolic diseases. However, such evidence mostly originates from low-pollution settings or cross-sectional studies, thus necessitating evidence from regions with high air pollution levels, such as India, where the burden of non-communicable diseases is high.

Research design and methods

We studied the associations between ambient PM2.5levels and fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and incident type 2 diabetes mellitus (T2DM) among 12 064 participants in an adult cohort from urban Chennai and Delhi, India. A meta-analytic approach was used to combine estimates, obtained from mixed-effects models and proportional hazards models, from the two cities.

Results

We observed that 10 μg/m3differences in monthly average exposure to PM2.5was associated with a 0.40 mg/dL increase in FPG (95% CI 0.22 to 0.58) and 0.021 unit increase in HbA1c (95% CI 0.009 to 0.032). Further, 10 μg/m3differences in annual average PM2.5was associated with 1.22 (95% CI 1.09 to 1.36) times increased risk of incident T2DM, with non-linear exposure response.

Conclusions

We observed evidence of temporal association between PM2.5exposure, and higher FPG and incident T2DM in two urban environments in India, thus highlighting the potential for population-based mitigation policies to reduce the growing burden of diabetes.